DURECT CORP (Form: 10-Q, Received: 05/02/2014 17:00:59)

Large accelerated filer

Accelerated filer

Non-accelerated filer

Smaller reporting company

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 10-Q

x	QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the quarterly period ended March 31, 2014

¨	TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the transition period from to

Commission file number 000-31615

DURECT CORPORATION

(Exact name of registrant as specified in its charter)

Delaware

94-3297098

(State or other jurisdiction of

incorporation or organization)

(I.R.S. Employer

Identification No.)

10260 Bubb Road

Cupertino, California 95014

(Address of principal executive offices, including zip code)

(408) 777-1417

(Registrant’s telephone number, including area code)

Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. Yes x No ¨

Indicate by check mark whether the registrant has submitted electronically and posted on its corporate Web site, if any, every Interactive Data File required to be submitted and posted pursuant to Rule 405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit and post such files). Yes x No ¨

Indicate by a check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, or a smaller reporting company. See definition of “large accelerated filer,” “accelerated filer” and “smaller reporting company” in Rule 12b-2 of the Exchange Act. (Check one):

Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes ¨ No x

As of April 24, 2014, there were 110,522,882 shares of the registrant’s Common Stock outstanding.

INDEX


		Page
PART I. FINANCIAL INFORMATION

Item 1.	Financial Statements		3

	Condensed Balance Sheets as of March 31, 2014 and December 31, 2013		3

	Condensed Statements of Comprehensive Loss for the three months ended March 31, 2014 and 2013		4

	Condensed Statements of Cash Flows for the three months ended March 31, 2014 and 2013		5

	Notes to Condensed Financial Statements		6

Item 2.	Management’s Discussion and Analysis of Financial Condition and Results of Operations		13

Item 3.	Quantitative and Qualitative Disclosures about Market Risk		24

Item 4.	Controls and Procedures		24

PART II. OTHER INFORMATION

Item 1.	Legal Proceedings		25

Item 1A.	Risk Factors		25

Item 2.	Unregistered Sales of Equity Securities and Use of Proceeds		45

Item 3.	Defaults Upon Senior Securities		45

Item 4.	Mine Safety Disclosures		45

Item 5.	Other Information		45

Item 6.	Exhibits		45

Signatures			46

PART I. FINANCIAL INFORMATION

Item 1.

Financial Statements

DURECT CORPORATION

CONDENSED BALANCE SHEETS

(in thousands)


	March 31, 2014			December 31, 2013
	(unaudited)			(Note 1)
A S S E T S
Current assets:
Cash and cash equivalents	$	1,970		$	7,836
Short-term investments		15,838			12,753
Accounts receivable (net of allowances of $197 at March 31, 2014 and $144 at December 31, 2013)		2,108			2,349
Inventories		3,510			3,502
Prepaid expenses and other current assets		2,064			1,888

Total current assets		25,490			28,328
Property and equipment (net of accumulated depreciation of $20,638 and $20,488 at March 31, 2014 and December 31, 2013, respectively)		1,837			1,985
Goodwill		6,399			6,399
Intangible assets, net		13			18
Long-term investments		3,611			3,352
Long-term restricted investments		350			450
Other long-term assets		288			288

Total assets	$	37,988		$	40,820

L I A B I L I T I E S A N D S T O C K H O L D E R S’ E Q U I T Y
Current liabilities:
Accounts payable	$	1,161		$	736
Accrued liabilities		3,869			5,865
Contract research liabilities		202			329
Deferred revenue, current portion		255			255

Total current liabilities		5,487			7,185
Deferred revenue, non-current portion		1,232			1,296
Other long-term liabilities		1,604			1,618
Commitments and contingencies
Stockholders’ equity:
Preferred stock		—			—
Common stock		11			11
Additional paid-in capital		394,044			391,504
Accumulated other comprehensive income		5			1
Accumulated deficit		(364,395	)		(360,795	)

Stockholders’ equity		29,665			30,721

Total liabilities and stockholders’ equity	$	37,988		$	40,820

The accompanying notes are an integral part of these financial statements.

DURECT CORPORATION

CONDENSED STATEMENTS OF COMPREHENSIVE LOSS

(in thousands, except per share amounts)

(unaudited)


	Three months ended March 31,
	2014			2013
Collaborative research and development and other revenue (see Note 2)	$	3,512		$	913
Product revenue, net		2,781			3,240

Total revenues		6,293			4,153
Operating expenses:
Cost of product revenues		1,063			1,658
Research and development		5,469			4,789
Selling, general and administrative		3,363			2,901

Total operating expenses		9,895			9,348

Loss from operations		(3,602	)		(5,195	)
Other income (expense):
Interest and other income (expenses)		3			14
Interest expense		(1	)		(2	)

Net other income (expense)		2			12

Net loss	$	(3,600	)	$	(5,183	)

Net loss per share
Basic	$	(0.03	)	$	(0.05	)

Diluted	$	(0.03	)	$	(0.05	)

Weighted-average shares used in computing net loss per share
Basic		110,468			101,881

Diluted		110,468			101,881

Total comprehensive loss	$	(3,596	)	$	(5,181	)

The accompanying notes are an integral part of these financial statements.

DURECT CORPORATION

CONDENSED STATEMENTS OF CASH FLOWS

(in thousands)

(unaudited)


	Three months ended March 31,
	2014			2013
Cash flows from operating activities
Net loss	$	(3,600	)	$	(5,183	)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation and amortization		155			258
Stock-based compensation		726			945
Changes in assets and liabilities:
Accounts receivable		241			599
Inventories		(9	)		341
Prepaid expenses and other assets		(176	)		449
Accounts payable		425			(952	)
Accrued and other liabilities		(285	)		626
Contract research liabilities		(127	)		(60	)
Deferred revenue		(64	)		(400	)

Total adjustments		886			1,806

Net cash used in operating activities		(2,714	)		(3,377	)

Cash flows from investing activities
Purchases of property and equipment		(2	)		(26	)
Purchases of available-for-sale securities		(6,060	)		(5,382	)
Proceeds from maturities of available-for-sale securities		2,820			5,840

Net cash (used in) provided by investing activities		(3,242	)		432

Cash flows from financing activities
Payments on equipment financing obligations		(2	)		(2	)
Net proceeds from issuances of common stock		92			2

Net cash provided by financing activities		90			—

Net decrease in cash and cash equivalents		(5,866	)		(2,945	)
Cash and cash equivalents, beginning of the period		7,836			11,195

Cash and cash equivalents, end of the period	$	1,970		$	8,250

The accompanying notes are an integral part of these financial statements.

DURECT CORPORATION

NOTES TO UNAUDITED CONDENSED FINANCIAL STATEMENTS

Note 1. Summary of Significant Accounting Policies

Nature of Operations

DURECT Corporation (the Company) was incorporated in the state of Delaware on February 6, 1998. The Company is a pharmaceutical company developing therapies based on its proprietary drug formulations and delivery platform technologies. The Company has several products under development by itself and with third party collaborators. The Company also manufactures and sells osmotic pumps used in laboratory research, and designs, develops and manufactures a wide range of standard and custom biodegradable polymers and excipients for pharmaceutical and medical device clients for use as raw materials in their products. In addition, the Company conducts research and development of pharmaceutical products in collaboration with third party pharmaceutical and biotechnology companies.

Basis of Presentation

The accompanying unaudited financial statements include the accounts of the Company. These financial statements have been prepared in accordance with the rules and regulations of the Securities and Exchange Commission (SEC), and therefore do not include all the information and footnotes necessary for a complete presentation of the Company’s results of operations, financial position and cash flows in conformity with U.S. generally accepted accounting principles (U.S. GAAP). The unaudited financial statements reflect all adjustments (consisting only of normal recurring adjustments) which are, in the opinion of management, necessary for a fair presentation of the financial position at March 31, 2014, the operating results and comprehensive loss for the three months ended March 31, 2014 and 2013, and cash flows for the three months ended March 31, 2014 and 2013. The balance sheet as of December 31, 2013 has been derived from audited financial statements at that date but does not include all of the information and footnotes required by U.S. GAAP for complete financial statements. These financial statements and notes should be read in conjunction with the Company’s audited financial statements and notes thereto, included in the Company’s annual report on Form 10-K for the fiscal year ended December 31, 2013 filed with the SEC.

The results of operations for the interim periods presented are not necessarily indicative of results that may be expected for any other interim period or for the full fiscal year.

Inventories

Inventories are stated at the lower of cost or market, with cost determined on a first-in, first-out basis. The Company’s inventories consisted of the following (in thousands):


	March 31, 2014		December 31, 2013
	(unaudited)
Raw materials	$	1,348	$	1,404
Work in process		1,371		1,063
Finished goods		791		1,035

Total inventories	$	3,510	$	3,502

Revenue Recognition

Revenue from the sale of products is recognized when there is persuasive evidence that an arrangement exists, the product is shipped and title transfers to customers, provided no continuing obligation on the Company’s part exists, the price is fixed or determinable and the collectability of the amounts owed is reasonably assured. The Company enters into license and collaboration agreements under which it may receive upfront license fees, research funding and contingent milestone payments and royalties. The Company’s deliverables under these arrangements typically consist of granting licenses to intellectual property rights and providing research and development services. The accounting standards contain a presumption that separate contracts entered into at or near the same time with the same entity or related parties were negotiated as a package and should be evaluated as a single agreement.

Revenue on cost-plus-fee contracts, such as under contracts to perform research and development for others, is recognized as the related services are rendered as determined by the extent of reimbursable costs incurred plus estimated fees thereon.

Comprehensive Income (Loss)

Components of other comprehensive income (loss) are comprised entirely of unrealized gains and losses on the Company’s available-for-sale securities for all periods presented and are included in total comprehensive income (loss) as follows (in thousands).


	Three months ended March 31,
	2014			2013
Net loss	$	(3,600	)	$	(5,183	)
Net change in unrealized gain on available-for-sale investments, net of tax		4			2

Comprehensive loss	$	(3,596	)	$	(5,181	)

The tax effect of the changes in accumulated other comprehensive income (loss) was immaterial for the periods presented. Accumulated other comprehensive income as of March 31, 2014 and December 31, 2013 is entirely comprised of net unrealized gains on available-for-sale securities.

Net Income (Loss) Per Share

Basic net income (loss) per share is calculated by dividing the net income (loss) by the weighted-average number of common shares outstanding. Diluted net income (loss) per share is computed using the weighted-average number of common shares outstanding and common stock equivalents (i.e., options to purchase common stock) outstanding during the period, if dilutive, using the treasury stock method for options and warrants.

Options to purchase approximately 19.0 million and 21.0 million shares of common stock were excluded from the denominator in the calculation of diluted net loss per share for the three months ended March 31, 2014 and 2013, respectively, as the effect would be anti-dilutive.

Note 2. Strategic Agreements

The collaborative research and development and other revenues associated with the Company’s major third-party collaborators are as follows (in thousands):


	Three months ended March 31,
	2014		2013
Collaborator
Impax Laboratories, Inc. (Impax) (1)	$	2,090	$	—
Zogenix, Inc. (Zogenix) (2)		782		253
Pain Therapeutics, Inc. (Pain Therapeutics)		451		—
Pfizer Inc. (Pfizer)		14		13
Others		175		647

Total collaborative research and development and other revenue	$	3,512	$	913

(1)	Amounts related to recognition of upfront fees were $2.0 million and zero for three months ended March 31, 2014 and 2013, respectively; the Company and Impax signed a license agreement effective January 3, 2014.

(2)

Amounts related to ratable recognition of upfront fees were $64,000 and $50,000 for three months ended March 31, 2014 and 2013, respectively; the Company and Zogenix had previously been working together under a feasibility agreement pursuant to which the Company’s research and development costs were reimbursed by Zogenix.

Agreement with Impax Laboratories, Inc.

On January 3, 2014, the Company and Impax Laboratories, Inc. (Impax) entered into a definitive agreement (the Impax Agreement). Pursuant to the Agreement, the Company has granted Impax an exclusive worldwide license to the Company’s proprietary TRANSDUR transdermal delivery technology and other intellectual property to develop and commercialize ELADUR, the Company’s investigational transdermal bupivacaine patch for the treatment of pain associated with post-herpetic neuralgia (PHN), in addition to selling certain assets and rights in and related to the product. Impax will control and fund the development and commercialization programs, and the parties will establish a joint management committee to oversee, review and coordinate the development and commercialization activities of the parties under the Impax Agreement. Impax will reimburse the Company for certain future research and development it may be requested to conduct on the product.

In connection with the Agreement, Impax paid a non-refundable upfront fee to the Company of $2.0 million in January 2014. The Company’s technology transfer activities were considered integral to utilizing the licensed intellectual property and, accordingly, the deliverables were accounted for as a single unit of accounting. The $2.0 million upfront fee was recognized as collaborative research and development revenue in the first quarter of 2014 when the license to the intellectual property right was delivered and the technology transfer with respect to this product candidate was completed. Impax agreed to make contingent cash payments to the Company of up to $61.0 million payable based upon the achievement of predefined milestones, of which $31.0 million are development-based milestones and $30.0 million are sales-based milestones (none of which has been achieved as of March 31, 2014). Since the milestones are expected to be achieved at a point in time when there are no performance obligations or remaining deliverables of the Company, the milestones are expected to be recognized in full upon achievement. Upon the first commercialization of ELADUR by Impax, the Company would also receive a tiered mid single-digit to low double-digit royalty on annual net product sales determined on a country-by-country basis. Impax is also required to pay to the Company a percentage of fees received in connection with any sublicense of the licensed rights. Impax may terminate the Impax Agreement without cause at any time upon prior written notice, and either party may terminate the Impax Agreement upon certain circumstances including written notice of a material uncured breach.

The following table provides a summary of collaborative research and development revenue recognized under the Impax Agreement (in thousands). The cumulative aggregate payments received by the Company as of March 31, 2014 were $2.1 million under the agreement.


	Three months ended March 31,
	2014		2013
Recognition of upfront payment	$	2,000	$	—
Research and development expenses reimbursable by Impax		90		—

Total collaborative research and development revenue	$	2,090	$	—

Agreement with Pain Therapeutics, Inc.

In December 2002, the Company entered into an exclusive agreement with Pain Therapeutics, Inc. (Pain Therapeutics) to develop and commercialize on a worldwide basis REMOXY and other oral sustained release, abuse deterrent opioid products incorporating four specified opioid drugs, using the ORADUR technology. Total collaborative research and development revenue recognized under the agreements with Pain Therapeutics was $451,000 and zero for the three months ended March 31, 2014 and 2013, respectively. The cumulative aggregate payments received by the Company from Pain Therapeutics as of March 31, 2014 were $35.2 million under this agreement.

Under the terms of this agreement, Pain Therapeutics paid the Company an upfront license fee of $1.0 million, with the potential for an additional $9.3 million in performance milestone payments based on the successful development and approval of the four ORADUR-based opioids. Of these potential milestones, $9.3 million are development-based milestones (of which $1.7 million have been achieved as of March 31, 2014). There are no sales-based milestones under the agreement.

In March 2009, King Pharmaceuticals (King) assumed the responsibility for further development of REMOXY from Pain Therapeutics. As a result of this change, the Company continues to perform REMOXY-related activities in accordance with the terms and conditions set forth in the license agreement between the Company and Pain Therapeutics. King was substituted in lieu of Pain Therapeutics with respect to interactions with the Company in its performance of those activities including the obligation to pay the Company with respect to all REMOXY-related costs incurred by the Company. In February 2011, Pfizer acquired King and thereby assumed the rights and obligations of King with respect to REMOXY; accordingly, amounts attributed to King are now shown as Pfizer figures.

Total collaborative research and development revenue recognized for REMOXY-related work performed by the Company for Pfizer was $14,000 and $13,000 for the three months ended March 31, 2014 and 2013, respectively. Prior to March 2009, the Company recognized collaborative research and development revenue for REMOXY-related work under the agreements with Pain Therapeutics. The cumulative aggregate payments received by the Company from Pfizer as of March 31, 2014 were $7.1 million under this agreement.

Long Term Supply Agreement with King (now Pfizer)

In August 2009, the Company signed an exclusive long term excipient supply agreement with respect to REMOXY with King. In February 2011, Pfizer acquired King and thereby assumed the rights and obligations of King with respect to this long term supply agreement. This agreement stipulates the terms and conditions under which the Company will supply to King, based on the Company’s manufacturing cost plus a specified percentage mark-up, two key excipients used in the manufacture of REMOXY.

Total revenues recognized related to these excipients were zero and $273,000 in the three months ended March 31, 2014 and 2013, respectively. The associated cost of goods sold was zero and $219,000 in the three months ended March 31, 2014 and 2013, respectively.

Agreement with Zogenix, Inc.

On July 11, 2011, the Company and Zogenix, Inc., (Zogenix), entered into a Development and License Agreement (the Zogenix Agreement). The Company and Zogenix had previously been working together under a feasibility agreement pursuant to which the Company’s research and development costs were reimbursed by Zogenix. Under the Zogenix Agreement, Zogenix will be responsible for the clinical development and commercialization of a proprietary, long-acting injectable formulation of risperidone using the Company’s SABER controlled-release formulation technology in combination with Zogenix’s DosePro ^® needle-free, subcutaneous drug delivery system. DURECT will be responsible for non-clinical, formulation and CMC development activities. The Company will be reimbursed by Zogenix for its research and development efforts on the product.

Zogenix paid a non-refundable upfront fee to the Company of $2.25 million in July 2011. The Company’s research and development services are considered integral to utilizing the licensed intellectual property and, accordingly, the deliverables are accounted for as a single unit of accounting. The $2.25 million upfront fee will be recognized as collaborative research and development revenue ratably over the term of the Company’s continuing research and development involvement with Zogenix with respect to this product candidate. Zogenix is obligated to pay the Company up to $103 million in total future milestone payments with respect to the product subject to and upon the achievement of various developments, regulatory and sales milestones. Of these potential milestones, $28 million are development-based milestones (none of which has been achieved as of March 31, 2014), and $75 million are sales-based milestones (none of which has been achieved as of March 31, 2014). Zogenix is also required to pay a mid single-digit to low double-digit percentage patent royalty on annual net sales of the product determined on a jurisdiction-by-jurisdiction basis. The patent royalty term is equal to the later of the expiration of all DURECT technology patents or joint patent rights in a particular jurisdiction, the expiration of marketing exclusivity rights in such jurisdiction, or 15 years from first commercial sale in such jurisdiction. After the patent royalty term, Zogenix will continue to pay royalties on annual net sales of the product at a reduced rate for so long as Zogenix continues to sell the product in the jurisdiction. Zogenix is also required to pay to the Company a tiered percentage of fees received in connection with any sublicense of the licensed rights.

The Company granted to Zogenix an exclusive worldwide license, with sub-license rights, to the Company’s intellectual property rights related to the Company’s proprietary polymeric and non-polymeric controlled-release formulation technology to make and have made, use, offer for sale, sell and import risperidone products, where risperidone is the sole active agent, for administration by injection in the treatment of schizophrenia, bipolar disorder or other psychiatric related disorders in humans. The Company retains the right to supply Zogenix’s Phase III clinical trial and commercial product requirements on the terms set forth in the Zogenix Agreement.

The Company retains the right to terminate the Zogenix Agreement with respect to specific countries if Zogenix fails to advance the development of the product in such country, either directly or through a sublicensee. In addition, either party may terminate the Zogenix Agreement upon insolvency or bankruptcy of the other party, upon written notice of a material uncured breach or if the other party takes any act impairing such other party’s relevant intellectual property rights. Zogenix may terminate the Zogenix Agreement upon written notice if during the development or commercialization of the product, the product becomes subject to one or more serious adverse drug experiences or if either party receives notice from a regulatory authority, independent review committee, data safety monitory board or other similar body alleging significant concern regarding a patient safety issue. Zogenix may also terminate the Zogenix Agreement with or without cause, at any time upon prior written notice.

The following table provides a summary of collaborative research and development revenue recognized under the agreements with Zogenix (in thousands). The cumulative aggregate payments received by the Company as of March 31, 2014 were $11.0 million under these agreements.


	Three months ended March 31,
	2014		2013
Ratable recognition of upfront payment	$	64	$	50
Research and development expenses reimbursable by Zogenix		718		203

Total collaborative research and development revenue	$	782	$	253

Note 3. Financial Instruments

Fair value is defined as the exchange price that would be received for an asset or paid to transfer a liability (an exit price) in the principal or most advantageous market for the asset or liability in an orderly transaction between market participants on the measurement date. The Company’s valuation techniques used to measure fair value maximize the use of observable inputs and minimize the use of unobservable inputs. The Company follows a fair value hierarchy based on three levels of inputs, of which the first two are considered observable and the last unobservable, that may be used to measure fair value. These levels of inputs are the following:

•

Level 1—Quoted prices in active markets for identical assets or liabilities.

•

Level 2—Inputs other than Level 1 that are observable, either directly or indirectly, such as quoted prices for similar assets or liabilities; quoted prices in markets that are not active; or other inputs that are observable or can be corroborated by observable market data for substantially the full term of the assets or liabilities.

•

Level 3—Unobservable inputs that are supported by little or no market activity and that are significant to the fair value of the assets or liabilities.

The Company’s financial instruments are valued using quoted prices in active markets or based upon other observable inputs. Money market funds are classified as Level 1 financial assets. Certificates of deposit, commercial paper, corporate debt securities, and U.S. Government agency securities are classified as Level 2 financial assets. The fair value of the Level 2 assets is estimated using pricing models using current observable market information for similar securities. The Company’s Level 2 investments include U.S. government-backed securities and corporate securities that are valued based upon observable inputs that may include benchmark yields, reported trades, broker/dealer quotes, issuer spreads, two-sided markets, benchmark securities, bids, offers and reference data including market research publications. The fair value of the Company’s commercial paper is based upon the time to maturity and discounted using the three-month treasury bill rate. The average remaining maturity of the Company’s Level 2 investments as of March 31, 2014 is less than twelve months and these investments are rated by S&P and Moody’s at AAA or AA- for securities and A1 or P1 for commercial paper.

The following is a summary of available-for-sale securities as of March 31, 2014 and December 31, 2013 (in thousands):


	March 31, 2014
	Amortized Cost		Unrealized Gain		Unrealized Loss			Estimated Fair Value
Money market funds	$	11	$	—	$	—		$	11
Certificates of deposit		350		—		—			350
Commercial paper		500		—		—			500
Corporate debt		4,893		1		—			4,894
U.S. Government agencies		14,451		4		—			14,455

	$	20,205	$	5	$	—		$	20,210

Reported as:
Cash and cash equivalents	$	411	$	—	$	—		$	411
Short-term investments		15,835		3		—			15,838
Long-term investments		3,609		2		—			3,611
Long-term restricted investments		350		—		—			350

	$	20,205	$	5	$	—		$	20,210


	December 31, 2013
	Amortized Cost		Unrealized Gain		Unrealized Loss			Estimated Fair Value
Money market funds	$	34	$	—	$	—		$	34
Certificates of deposit		450		—		—			450
Commercial paper		1,249		—		—			1,249
Corporate debt		3,257		1		—			3,258
U.S. Government agencies		16,898		1		(1	)		16,898

	$	21,888	$	2	$	(1	)	$	21,889

Reported as:
Cash and cash equivalents	$	5,334	$	—	$	—		$	5,334
Short-term investments		12,752		2		(1	)		12,753
Long-term investments		3,352		—		—			3,352
Long-term restricted investments		450		—		—			450

	$	21,888	$	2	$	(1	)	$	21,889

The following is a summary of the cost and estimated fair value of available-for-sale securities at March 31, 2014, by contractual maturity (in thousands):


	March 31, 2014
	Amortized Cost		Estimated Fair Value
Mature in one year or less	$	16,585	$	16,588
Mature after one year through five years		3,609		3,611

	$	20,194	$	20,199

There were no securities that have had an unrealized loss for more than 12 months as of March 31, 2014.

As of December 31, 2013, unrealized losses on available-for-sale investments are not attributed to credit risk and are considered to be temporary. The Company believes that it is more-likely-than-not that investments in an unrealized loss position will be held until maturity or the recovery of the cost basis of the investment. To date, the Company has not recorded any impairment charges on marketable securities related to other-than-temporary declines in market value.

Note 4. Stock-Based Compensation

As of March 31, 2014, the Company has three stock-based compensation plans. The stock-based compensation cost that has been included in the statements of comprehensive loss is shown as below (in thousands):


	Three months ended March 31,
	2014		2013
Cost of product revenues	$	37	$	49
Research and development		415		570
Selling, general and administrative		274		326

Total stock-based compensation	$	726	$	945

As of March 31, 2014 and December 31, 2013, $13,000 of stock-based compensation cost was capitalized in inventory on the Company’s balance sheets.

The Company uses the Black-Scholes option pricing model to value its stock options. The expected life computation is based on historical exercise patterns and post-vesting termination behavior. The Company considered its historical volatility in developing its estimate of expected volatility.

The Company used the following assumptions to estimate the fair value of stock options granted (including fully vested options issued in January 2014 and February 2013) and shares purchased under its employee stock purchase plan for the three months ended March 31, 2014 and 2013:


	Stock Options						Employee Stock Purchase Plan
	Three months ended March 31,						Three months ended March 31,
	2014			2013			2014			2013
Risk-free rate		2.0-2.8	%		0.8-1.5	%		0.1	%		0.2	%
Expected dividend yield		—			—			—			—
Expected life of option (in years)		6.5-9.3			5.3-7.8			0.5			1.3
Volatility		77-84	%		77-86	%		81	%		69	%
Forfeiture rate		7.2	%		8.4	%		—			—

Item 2.

Management’s Discussion and Analysis of Financial Condition and Results of Operations

This Management’s Discussion and Analysis of Financial Condition and Results of Operations for the three months ended March 31, 2014 and 2013 should be read in conjunction with our annual report on Form 10-K for the year ended December 31, 2013 filed with the Securities and Exchange Commission and “Risk Factors” section included elsewhere in this Form 10-Q. This Form 10-Q contains forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended. When used in this report, the words “believe,” “anticipate,” “intend,” “plan,” “estimate,” “expect,” “may,” “will,” “could,” “potentially” and similar expressions are forward-looking statements. Such forward-looking statements are based on current expectations and beliefs. Any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties. Actual events or results may differ materially from those discussed in the forward-looking statements as a result of various factors.

Forward-looking statements made in this report include, for example, statements about:

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potential regulatory filings for or approval of REMOXY, POSIDUR or any of our other product candidates;

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the progress of our third-party collaborations, including estimated milestones;

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our intention to seek, and ability to enter into strategic alliances and collaborations;

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the potential benefits and uses of our products;

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responsibilities of our collaborators, including the responsibility to make cost reimbursement, milestone, royalty and other payments to us, and our expectations regarding our collaborators’ plans with respect to our products;

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our responsibilities to our collaborators, including our responsibilities to conduct research and development, clinical trials and manufacture products;

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our ability to protect intellectual property, including intellectual property licensed to our collaborators;

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market opportunities for products in our product pipeline;

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the progress and results of our research and development programs;

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requirements for us to purchase supplies and raw materials from third parties, and the ability of third parties to provide us with required supplies and raw materials;

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the results and timing of clinical trials and the possible commencement of future clinical trials;

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conditions for obtaining regulatory approval of our product candidates;

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submission and timing of applications for regulatory approval;

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the impact of FDA, DEA, EMEA and other government regulation on our business;

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the impact of potential Risk Evaluation and Mitigation Strategies (REMS) on our business;

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uncertainties associated with obtaining and protecting patents and other intellectual property rights, as well as avoiding the intellectual property rights of others;

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products and companies that will compete with the products we license to third-party collaborators;

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the possibility we may commercialize our own products and build up our commercial, sales and marketing capabilities and other required infrastructure;

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the possibility that we may develop additional manufacturing capabilities;

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our employees, including the number of employees and the continued services of key management, technical and scientific personnel;

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our future performance, including our anticipation that we will not derive meaningful revenues from our pharmaceutical systems for at least the next twelve months and our expectations regarding our ability to achieve profitability;

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sufficiency of our cash resources, anticipated capital requirements and capital expenditures and our need for additional financing;

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our expectations regarding marketing expenses, research and development expenses, and selling, general and administrative expenses;

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the composition of future revenues; and

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accounting policies and estimates, including revenue recognition policies.

Forward-looking statements are not guarantees of future performance and involve risks and uncertainties. Actual events or results may differ materially from those discussed in the forward-looking statements as a result of various factors. For a more detailed discussion of such forward looking statements and the potential risks and uncertainties that may impact upon their accuracy, see the “Risk Factors” section and “Overview” section of this Management’s Discussion and Analysis of Financial Condition and Results of Operations. These forward-looking statements reflect our view only as of the date of this report. We undertake no obligations to update any forward-looking statements. You should also carefully consider the factors set forth in other reports or documents that we file from time to time with the Securities and Exchange Commission.

Overview

We are a specialty pharmaceutical company focused on the development of pharmaceutical products based on our proprietary drug delivery technology platforms. Our product pipeline currently consists of eight investigational drug candidates in clinical development, with one program the subject of a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) for which a Complete Response Letter was received in June 2011, another program the subject of a NDA with the FDA for which a Complete Response Letter was received in February 2014, two programs in Phase II and four programs in Phase I. The more advanced programs are in the field of pain management and we believe that each of these targets large market opportunities with product features that are differentiated from existing therapeutics. We have other programs underway in fields outside of pain management, including central nervous system disorders, metabolic disorders, cardiovascular disease and other chronic diseases.

A central aspect of our business strategy involves advancing multiple product candidates at one time, which is enabled by leveraging our resources with those of corporate collaborators. Thus, certain of our programs are currently licensed to corporate collaborators on terms which typically call for our collaborator to fund all or a substantial portion of future development costs and then pay us milestone payments based on specific development or commercial achievements plus a royalty on product sales. At the same time, we have retained the rights to other programs, which are the basis of future collaborations and which over time may provide a pathway for us to develop our own commercial, sales and marketing organization.

Additional details of these programs and related strategic agreements are contained in our annual report on Form 10-K for the year ended December 31, 2013 and in Note 2 above.

REMOXY ^® and other ORADUR ^® -based opioid products licensed to Pain Therapeutics

In December 2002, we entered into an agreement with Pain Therapeutics, amended in December 2005, under which we granted Pain Therapeutics the exclusive, worldwide right to develop and commercialize selected long-acting oral opioid products using our ORADUR technology incorporating four specified opioid drugs. The first product being developed under the collaboration is REMOXY, a novel long-acting oral formulation of the opioid oxycodone targeted to decrease the potential for oxycodone abuse. REMOXY is intended for patients with chronic pain. In November 2005, Pain Therapeutics and King entered into collaboration and license agreements for the development and commercialization of REMOXY by King. In February 2011, Pfizer acquired King and thereby assumed the rights and obligations of King with respect to REMOXY and to the other ORADUR-based opioids.

An NDA was submitted in June 2008 by Pain Therapeutics, in response to which the FDA provided a Complete Response Letter in December 2008. King took over the NDA from Pain Therapeutics and resubmitted the NDA in December of 2010. On June 23, 2011, a Complete Response Letter from the FDA was received by Pfizer on the resubmission of the NDA for REMOXY. The FDA’s June 2011 Complete Response Letter raised concerns related to, among other matters, the Chemistry, Manufacturing, and Controls section of the NDA for REMOXY. Pfizer has efforts underway to resolve these issues. In October 2013, Pfizer stated that, having achieved technical milestones related to manufacturing, they will continue the development program for REMOXY ^® . Following guidance received from the FDA in March 2013, Pfizer announced that they will proceed with the additional clinical studies and other actions required to address the Complete Response Letter. These new clinical studies will include, in part, a pivotal bioequivalence study with the modified REMOXY formulation to bridge to the clinical data related to the original REMOXY formulation, and an abuse-potential study with the modified formulation. As previously disclosed, the complete response submission is not expected to occur prior to mid-2015.

Phase I clinical trials have been conducted for two of the other ORADUR-based product candidates (hydrocodone and hydromorphone), and an Investigational New Drug (IND) application has been accepted by the FDA for the fourth ORADUR-based opioid (oxymorphone). In October 2013, Pain Therapeutics stated that it had regained all rights from Pfizer with respect to the three other ORADUR-based opioid drug candidates (hydrocodone, hydromorphone and oxymorphone). Pain Therapeutics is now free to develop and commercialize these product candidates on its own or with a licensee. During the first quarter of 2014, we conducted research and development activities on these programs under approved workplans with Pain Therapeutics.

NOTE:

POSIDUR™, SABER ^® , CLOUD™,TRANSDUR ^® , ORADUR ^® , ELADUR ^® , DURIN ^® , ALZET ^® and LACTEL ^® are trademarks of DURECT Corporation. Other trademarks referred to belong to their respective owners.

POSIDUR™ (SABER ^® -Bupivacaine)

Our post-operative pain relief depot, POSIDUR, is a sustained release injectable using our SABER delivery system to deliver bupivacaine, an off-patent anesthetic agent. SABER is a patented controlled drug delivery technology that is administered via the parenteral (i.e., injectable) route to deliver drugs that act systemically or locally. POSIDUR is designed to be administered to a surgical site at the time of surgery for post-operative pain relief and is intended to provide local analgesia for up to 3 days, which we believe coincides with the time period of the greatest need for post-surgical pain control in most patients. We are in discussions with potential partners regarding licensing development and commercialization rights to POSIDUR, for which we hold worldwide rights.

Safety

As bupivacaine is a well known drug with an extensive understanding of its risks and benefits, the safety database in the Integrated Summary of Safety (ISS) is not as large as required for a new chemical entity. A total of 1075 patients are included in the ISS database, 951 of whom have been exposed to POSIDUR or SABER-Placebo in volumes ranging from 2.5 to 10 mL. A total of 683 patients have been exposed to POSIDUR with the dose of bupivacaine ranging from 330 to 990 mg. In addition, a total of 124 patients have been treated with bupivacaine HCl in control groups and 268 patients received SABER-Placebo in control groups.

Overall, the POSIDUR patient groups showed a similar systemic safety profile as the patient groups treated with SABER-Placebo and bupivacaine HCl. Long-term follow-up examinations over 6 to 18 months do not show any adverse effects on wound healing or scar formation from the use of POSIDUR or SABER-Placebo. Local site reactions were observed more frequently in the POSIDUR and SABER-Placebo groups than in the active comparator groups, most frequently in abdominal surgeries; most of these observations were discolorations (e.g., surgical bruising), the majority of which resolved without treatment during the observation period. There was little difference in the incidence of severe or serious adverse events between the POSIDUR, SABER-Placebo and bupivacaine HCl treatment groups. Most of the serious adverse events seen in these trials appear to be due to complications of surgery, anesthesia, analgesics, or co-morbidity and not POSIDUR-related. The clinical history for serious adverse events has been reviewed and no evidence of bupivacaine toxicity was apparent. The adverse event data have been analyzed in a variety of ways to detect any evidence of bupivacaine central nervous system or cardiac toxicity or other unexpected effects. No patients treated with POSIDUR had an instance of a severe central nervous system or cardiac adverse event traditionally associated with bupivacaine toxicity. As discussed in “Current Status” below, in February 2014 we received a Complete Response Letter from the FDA.

Efficacy

In our new drug application filed in April 2013, we presented the results from two efficacy trials that we are positioning as pivotal (inguinal hernia repair and shoulder surgery, primarily subacromial decompression) and an Integrated Summary of Efficacy (ISE) based on 7 randomized, controlled, parallel design surgical trials of POSIDUR using the administration technique and 5 mL (660 mg) dose proposed for marketing.

Hernia pivotal efficacy trial

The hernia pivotal efficacy clinical trial was designed to evaluate the tolerability, activity, dose response and pharmacokinetics of POSIDUR in patients undergoing open inguinal hernia repair. The trial was conducted in Australia and New Zealand as a multi-center, randomized, double blind, placebo-controlled study in 122 patients. Study patients were randomized into three treatment groups: patients that were treated with POSIDUR 2.5 mL (n=43), POSIDUR 5 mL (n=47) and placebo (n=32). The co-primary efficacy endpoints for the study were Mean Pain Intensity on Movement area under the curve (AUC), a measure of pain over a period of 1-72 hours post-surgery, and the proportion of patients requiring supplemental opioid analgesic medication during the study (defined as 0-15 days).

In relation to the co-primary endpoint of pain reduction as measured by Mean Pain Intensity on Movement AUC 1-72 hours post-surgery, the patient group treated with POSIDUR 5 mL reported thirty-one percent (31%) less pain versus placebo and was statistically significant (p=0.0033). Fifty-three percent (53%) of the study patients in the POSIDUR 5 mL group took supplemental opioid analgesic medications versus seventy-two percent (72%) of the placebo patients (p=0.0909). Although this positive trend for this co-primary endpoint in favor of the POSIDUR 5 mL group was not statistically significant, both secondary endpoints measuring opioid analgesic medication consumption were met at a statistically significant level. During the periods of 1-24 hours, 24-48 hours and 48-72 hours after surgery, placebo patients consumed approximately 3.5 (p=0.0009), 2.9 (p=0.0190) and 3.6 (p=0.0172) times more supplemental opioid analgesic medications (mean total daily consumption of opioid analgesic medication in morphine equivalents), respectively, than the POSIDUR 5 mL treatment group. The median decrease in supplemental opioid analgesics taken over the first three days after surgery was 80% (p=0.0085) for the POSIDUR 5 mL group as compared to the placebo group.

Shoulder pivotal efficacy trial

The shoulder pivotal efficacy trial was a multicenter, randomized, double-blind, active- and placebo-controlled, parallel-group, dose-response trial conducted at 9 investigational centers in Europe. Nycomed, DURECT’s collaborator at the time, was responsible for the conduct of the clinical trial. In this study, 107 patients were randomly assigned to one of three treatment groups prior to undergoing elective arthroscopic shoulder surgery: POSIDUR 5 mL (n=53), SABER-Placebo (n=25) or bupivacaine HCl solution (n=29). All patients were given a background pain treatment consisting of a daily dose of two or four grams (depending on the patient’s weight) of paracetamol (acetaminophen). In addition, each patient was provided supplemental opioid rescue medication, if needed. With respect to efficacy, the primary endpoints of the study were to demonstrate: (1) an improvement in terms of pain intensity on movement area under the curve (AUC) during the period 1–72 hours post-surgery, and (2) a decrease in the total use of opioid rescue analgesia 0–72 hours post-surgery.

Results from this study demonstrate that the POSIDUR group experienced a statistically significant reduction in pain intensity of approximately 21% (p=0.0122) versus SABER-Placebo. Applying the appropriate statistical test given the data distribution, the POSIDUR group showed a statistically significant reduction of approximately 67% (p=0.013) in median opioid use in favor of POSIDUR. No statistical differences were found when POSIDUR was compared to bupivacaine HCl.

Phase III trial in abdominal surgical procedures

We also conducted a Phase III U.S. and international, multi-center, randomized, double-blind, controlled trial evaluating the safety, efficacy, effectiveness, and pharmacokinetics of POSIDUR in 305 patients undergoing a variety of general abdominal surgical procedures. The trial included the following three cohorts:

Cohort 1: An active comparator cohort in which patients were randomized to receive either POSIDUR 5 mL or commercially available Bupivacaine HCl solution after laparotomy.

Cohort 2: An active comparator cohort in which patients were randomized to receive either POSIDUR 5 mL or commercially available Bupivacaine HCl solution after laparoscopic cholecystectomy.

Cohort 3: A double blind, placebo controlled cohort in which patients were randomized to receive either POSIDUR 5 mL or SABER-Placebo after laparoscopically-assisted colectomy.

Efficacy evaluation in the Phase III trial encompassed a number of parameters. The two co-primary efficacy endpoints for Cohort 3 were mean pain intensity on movement (normalized) Area Under the Curve (AUC) during the period 0-72 hours post-dose and mean total morphine equivalent opioid dose for supplemental analgesia during the period 0-72 hours post-dose. The purpose of Cohorts 1 and 2 was to give us additional experience with the use of POSIDUR in a broader group of surgeries and patients.

Cohort 3. With respect to the co-primary efficacy endpoint of pain reduction as measured by mean pain intensity on movement (normalized) Area Under the Curve (AUC) during the period 0-72 hours post-dose, the patient group treated with POSIDUR reported a mean pain reduction in pain scores of approximately 7%, although this was not statistically significant (p=0.1466). The statistical analysis plan included pain on movement as recorded at scheduled times through an electronic diary plus pain scores reported whenever supplemental opioids were administered with such scores attributed as if they were pain on movement. In the prespecified sensitivity analysis (which includes only scheduled pain assessment on movement scores as collected on the electronic diary), the patient group treated with POSIDUR reported approximately 10% less pain versus placebo (p=0.0410). In relation to the co-primary efficacy endpoint of median total morphine-equivalent opioid dose for supplemental analgesia during the period 0-72 hours post-dose, the patient group treated with POSIDUR reported approximately 16% less opioids consumed versus the placebo group, although this was not statistically significant (p=0.5897).

Cohorts 1 and 2. Cohorts 1 and 2 were prespecified to be pooled due to their small sample size. For Cohorts 1 and 2 (pooled), the mean reduction in pain on movement was approximately 20% and statistically significant (p=0.0111) for the POSIDUR group compared to the patient group treated with bupivacaine HCl. With respect to the median total morphine-equivalent opioid dose for supplemental analgesia during the period 0-72 hours post-dose for Cohorts 1 and 2 (pooled), the patient group treated with POSIDUR reported approximately 18% less opioids consumed compared to the bupivacaine HCl group, although this was not statistically significant (p=0.5455).

Integrated Summary of Efficacy

The seven controlled trials in the ISE can be separated into two basically different surgical types. The four soft tissue trials involved incisions or laparoscopic portals either in the abdomen or in the inguinal area for hernia repair. In these surgeries, the pain producing tissue was primarily soft tissue such as viscera, fascia, muscle, or skin. However, in the three orthopedic surgeries involving shoulder surgery, a major pain producing tissue is bone that has been resected during the procedure. Given that the responsiveness to treatment of these different surgical types may be different, a pooled analysis has been conducted separately by tissue type.

In the soft tissue pooled analysis group comprised of 410 patients, 253 were treated with POSIDUR and 157 were treated with SABER-Placebo. The mean pain intensity was lower during the period 0-72 hours post-dose in the POSIDUR group than in the SABER-Placebo group and the difference was statistically significant (p=0.0099). The median total morphine-equivalent dose during the period 0-72 hours post-dose was lower in the POSIDUR group than in the SABER-Placebo group, however the difference was not statistically significant.

In the orthopedic pooled analysis group comprised of 187 patients, 114 were treated with POSIDUR and 73 were treated with SABER-Placebo. The mean pain intensity during the period 0-72 hours post-dose was lower in the POSIDUR group than in the SABER-Placebo group and the difference was statistically significant (p=0.0205). The median total morphine-equivalent dose during the period 0-72 hours post-dose was lower in the POSIDUR group than in the SABER-Placebo group and the difference was statistically significant (p=0.0025).

Current Status. In April 2013, we submitted an NDA as a 505(b)(2) application, which relies in part on the FDA’s findings of safety and effectiveness of a reference drug. In February 2014, we received a Complete Response Letter from the FDA. Based on its review, the FDA has determined that they cannot approve the NDA in its present form, stating the NDA does not contain sufficient information to demonstrate that POSIDUR is safe when used in the manner described in the proposed label, and the FDA has indicated that additional clinical safety studies need to be conducted. We are evaluating the issues and recommendations described in the Complete Response Letter and plan to have further discussions with the FDA around them.

ELADUR ^® (TRANSDUR ^® -Bupivacaine)

Our transdermal bupivacaine patch (ELADUR) uses our proprietary TRANSDUR transdermal technology and is intended to provide continuous delivery of bupivacaine for up to three days from a single application, as compared to a wearing time limited to 12 hours with currently available lidocaine patches. In December 2007, we announced positive results from a 60 patient Phase IIa study for post-herpetic neuralgia (PHN or post-shingles pain).

Effective in October 2008, we entered into a development and license agreement with Alpharma granting Alpharma the exclusive worldwide rights to develop and commercialize ELADUR. Alpharma paid us an upfront license fee of $20 million in October 2008. Alpharma was acquired by King in December 2008 and, as a result, the rights and obligations of the agreement were assumed by King. In February 2011, Pfizer acquired King and thereby assumed the rights and obligations of King with respect to ELADUR.

We reported top line data from a Phase II clinical trial conducted by King for ELADUR in April 2011. In this study of 263 patients suffering from chronic low back pain, the primary efficacy endpoint of demonstrating a positive treatment difference for the mean change in pain intensity scores from baseline to the mean of weeks 11 and 12 between ELADUR as compared to placebo was not met.

In February 2012, Pfizer gave notice that its rights with respect to ELADUR were being returned to us. In January 2014, we and Impax Laboratories, Inc. (Impax) entered into a definitive agreement (the Impax Agreement) pursuant to which we have granted Impax an exclusive worldwide license to our proprietary TRANSDUR transdermal delivery technology and other intellectual property to develop and commercialize ELADUR, in addition to selling certain assets and rights in and related to the product. Impax will control and fund the development and commercialization programs, and the parties have established a joint management committee to oversee, review and coordinate the development and commercialization activities of the parties under the Impax Agreement.

TRANSDUR ^® -Sufentanil

Our transdermal sufentanil patch (TRANSDUR-Sufentanil) uses our proprietary TRANSDUR delivery system to deliver sufentanil, an opioid medication. TRANSDUR-Sufentanil is designed to provide extended chronic pain relief for up to seven days, as compared to the two to three days of relief provided with currently available opiate patches. We anticipate that the small size of our sufentanil patch (potentially as small as 1/5 ^th the size of currently marketed transdermal fentanyl patches for a therapeutically equivalent dose) may offer improved convenience and compliance for patients. An end-of-Phase II meeting was conducted with the FDA in February 2009 and we have subsequently had discussions with the FDA and regulatory agencies in several major European countries to better understand development requirements for U.S. and European approval. We are in discussions with potential collaborators regarding licensing development and commercialization rights to this program to which we hold worldwide rights.

ORADUR-ADHD Program

We are developing drug candidates (ORADUR-ADHD) based on DURECT’s ORADUR Technology for the treatment of ADHD. These drug candidates are intended to provide once-a-day dosing with added tamper-resistant characteristics to address common methods of abuse and misuse of these types of drugs.

In August 2009, we entered into a development and license agreement with Orient Pharma Co., Ltd., a diversified multinational pharmaceutical, healthcare and consumer products company with headquarters in Taiwan, under which we granted to Orient Pharma development and commercialization rights in certain defined Asian and South Pacific countries to ORADUR-Methylphenidate. DURECT retains rights to North America, Europe, Japan and all other countries not specifically licensed to Orient Pharma. Since 2010, we and Orient Pharma have conducted several Phase I clinical trials in this program with multiple formulations. In 2013, we and Orient Pharma selected a lead formulation based on its potential for rapid onset of action, long duration for once-a-day dosing and target pharmacokinetic profile as demonstrated in a Phase 1 trial. In addition, this product candidate is expected to utilize a small capsule size relative to the leading existing long-acting products on the market. Orient Pharma has met with the Taiwan Food and Drug Administration (TFDA) to discuss the Phase 3 program in that market and is developing its plans for further development in the defined Asian and South Pacific countries to which it has rights from us. We retain rights to all other territories in the world and are engaged in licensing discussions with other companies.

Relday ™ (risperidone) Program

On July 11, 2011, we and Zogenix, Inc. (Zogenix) entered into a development and license agreement for the purpose of developing and commercializing Relday, a proprietary, long-acting injectable formulation of risperidone using our SABER-controlled release formulation technology in combination with Zogenix’s DosePro ^® needle-free, subcutaneous drug delivery system. Risperidone is one of the most widely prescribed medications used to treat the symptoms of schizophrenia and bipolar I disorder in adults and teenagers 13 years of age and older. Under the agreement, we granted Zogenix worldwide development and commercialization rights to Relday.

On January 3, 2013, Zogenix reported positive single-dose pharmacokinetic (PK) results from the Phase 1 clinical trial of Relday. According to Zogenix, adverse events in the Phase 1 trial in patients diagnosed with schizophrenia were generally mild to moderate and consistent with other risperidone products. The Phase 1 clinical trial for Relday was conducted as a single-center, open-label, safety and PK trial of 30 patients with chronic, stable schizophrenia or schizoaffective disorder. Per Zogenix, based on the favorable safety and PK profile demonstrated with the 25 mg and 50 mg once-monthly doses tested in the Phase 1 trial, Zogenix extended the study to include a 100 mg dose of the same formulation. In May 2013, Zogenix announced positive results with the 100 mg arm, demonstrating dose proportionality across the full dose range that would be anticipated to be used in clinical practice. According to Zogenix, the positive results from this study extension positions Zogenix to begin a multi-dose clinical trial, which would provide the required steady-state pharmacokinetic and safety data prior to initiating Phase 3 development studies, and Zogenix plans to commence this multi-dose clinical trial in the fourth quarter of 2014.

Other Programs

Depot Injectable Programs

The proteins and peptides identified by the biotechnology industry are large, complex, intricate molecules, and many are unsuitable as drugs. If these molecules are given orally, they are often destroyed before they can have an effect; if given by injection, they often require impractical, inconvenient frequent injections that may result in unwanted side effects. As a result, the development of biotechnology molecules for the treatment of human diseases has room for improvement, and advanced depot injectable systems such as we possess are required to realize the full potential of many of these protein and peptide drugs. In addition to biologic drugs, many traditional small molecule drugs have to be given by frequent injections, which is costly, inconvenient and may result in either unwanted side effects or suboptimal efficacy. We have active programs underway to improve our depot injectable systems and to apply those systems to various drugs and drug candidates, and have entered into a number of feasibility studies with biotechnology and pharmaceutical companies to test their products in our systems.

Research and Development Programs in Other Therapeutic Categories

We have underway a number of research programs covering medical diseases and conditions other than pain. Such programs include various diseases and disorders of the central nervous system, cardiovascular disease and metabolic disorders. In conducting our research programs and determining which particular efforts to prioritize for formal development, we employ a rigorous opportunity assessment process that takes into account the unmet medical need, commercial opportunity, technical feasibility, clinical viability, intellectual property considerations, and the development path including costs to achieve various critical milestones.

Product Revenues

We also currently generate product revenue from the sale of three product lines:

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ALZET ^® osmotic pumps for animal research use;

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LACTEL ^® biodegradable polymers which are used by our customers as raw materials in their pharmaceutical and medical products; and

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certain key excipients that are included in REMOXY and one excipient that is included in a currently marketed animal health product.

Because we consider our core business to be developing and commercializing pharmaceuticals, we do not intend to significantly increase our investments in or efforts to sell or market any of our existing product lines. However, we expect that we will continue to make efforts to increase our revenue related to collaborative research and development by entering into additional research and development agreements with third-party collaborators to develop product candidates based on our drug delivery technologies.

Operating Results

Since our inception in 1998, we have had a history of operating losses. At March 31, 2014, we had an accumulated deficit of $364.4 million. Our net losses were $21.5 million and $18.8 million for the years ended December 31, 2013 and 2011, respectively, while we reported net income of $16.2 million for the year ended December 31, 2012 related to the termination of certain of our collaboration agreements, which triggered recognition of $35.4 million of deferred revenue. These losses have resulted primarily from costs incurred to research and develop our product candidates and to a lesser extent, from selling, general and administrative costs associated with our operations and product sales. We expect our research and development expenses to increase modestly in the near future compared to recent quarters. We expect selling, general and administrative expenses to decrease modestly in the near future compared to the first quarter of 2014. We do not anticipate meaningful revenues from our pharmaceutical systems, should they be approved, for at least the next twelve months. Therefore, we expect to incur continuing losses and negative cash flow from operations for the foreseeable future.

Critical Accounting Policies and Estimates

The preparation of financial statements in conformity with generally accepted accounting principles requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the dates of the financial statements and the reported amounts of revenues and expenses during the reporting periods. The most significant estimates and assumptions relate to revenue recognition, the recoverability of our long-lived assets, including goodwill and other intangible assets, accrued liabilities, contract research liabilities, inventories and stock-based compensation. Actual amounts could differ significantly from these estimates. There have been no material changes to our critical accounting policies and estimates as compared to the disclosures in our annual report on Form 10-K for the year ended December 31, 2013.

Results of Operations

Three months ended March 31, 2014 and 2013

Collaborative research and development and other revenue

We recognize revenues from collaborative research and development activities and service contracts. Collaborative research and development revenue primarily represents net reimbursement of qualified expenses related to collaborative agreements with various third parties to research, develop and commercialize potential products using our drug delivery technologies, and revenue recognized from ratable recognition of upfront fees and milestone payments in connection with our collaborative agreements.

We expect our collaborative research and development revenue in the next few quarters to decrease compared to the first quarter of 2014, pending establishment of new collaborations or an increase in activities undertaken by us under existing collaborations. In general, we expect our collaborative research and development revenue to fluctuate in future periods pending our efforts to enter into potential new collaborations and our existing third party collaborators’ commitment to and progress in the research and development programs as well as our role in the workplans for those programs at any point in time. The collaborative research and development and other revenues associated with our major collaborators are as follows (in thousands):


	Three months ended March 31,
	2014		2013
Collaborator
Impax Laboratories, Inc. (Impax) (1)	$	2,090	$	—
Zogenix, Inc. (Zogenix) (2)		782		253
Pain Therapeutics, Inc. (Pain Therapeutics)		451		—
Pfizer Inc. (Pfizer)		14		13
Others		175		647

Total collaborative research and development and other revenue	$	3,512	$	913

(1)	Amounts related to recognition of upfront fees were $2.0 million and zero for the three months ended March 31, 2014 and 2013, respectively; the Company and Impax signed a license agreement effective January 3, 2014.

(2)

Amounts related to ratable recognition of upfront fees were $64,000 and $50,000 for the three months ended March 31, 2014 and 2013, respectively; the Company and Zogenix had previously been working together under a feasibility agreement pursuant to which the Company’s research and development costs were reimbursed by Zogenix.

We recorded $3.5 million and $913,000 of collaborative research and development revenue for the three months ended March 31, 2014 and 2013, respectively. The increase in collaborative research and development revenue in the three months ended March 31, 2014 was primarily due to revenue recognized from our agreement with Impax and higher revenue recognized from our agreements with Zogenix and PTI as our role in the development activities for Relday and select ORADUR-based opioid products increased in the first quarter of 2014, offset by lower collaborative research and development revenue recognized in connection with our feasibility agreements with other companies compared with the corresponding period in 2013.

We received a $2.0 million upfront fee in connection with the license agreement signed with Impax in January 2014 relating to ELADUR. The $2.0 million upfront fee was recognized as collaborative research and development revenue in the first quarter of 2014 as revenue was recognized when the license to the intellectual property right was delivered and the technology transfer was completed.

Product revenue

A portion of our revenues is derived from product sales, which include our ALZET mini pump product line, our LACTEL biodegradable polymer product line and certain excipients that are included in REMOXY and another product. Net product revenues were $2.8 million and $3.2 million in the three months ended March 31, 2014 and 2013, respectively. The decrease in the three months ended March 31, 2014 was primarily attributable to lower product revenue from the sale of certain excipients included in REMOXY and another product as well as lower revenue from our LACTEL polymer product line and ALZET mini pump product line as a result of lower units sold compared to the corresponding period in 2013.

Cost of product revenues. Cost of product revenues were $1.1 million and $1.7 million for the three months ended March 31, 2014 and 2013, respectively. The decrease in the cost of product revenue was primarily the result of lower cost of goods sold related to the sale of certain excipients to Pfizer, lower scrap expense associated with our LACTEL product line and lower cost of goods sold from our ALZET mini pump product line arising from lower manufacturing costs for products sold in the first quarter of 2014 compared to the corresponding period in 2013. Cost of product revenues and gross profit margin will fluctuate from period to period depending upon the product mix in a particular period and unit volumes sold. Stock-based compensation expense recognized related to cost of product revenues was $37,000 and $49,000 for the three months ended March 31, 2014 and 2013, respectively.

As of March 31, 2014, we had 21 manufacturing employees compared with 22 as of March 31, 2013. We expect the number of employees involved in manufacturing will remain comparable in the near future.

Research and development . Research and development expenses are primarily comprised of salaries, benefits, stock-based compensation and other compensation cost associated with research and development personnel, overhead and facility costs, preclinical and non-clinical development costs, clinical trial and related clinical manufacturing costs, contract services, and other outside costs. Research and development expenses were $5.5 million and $4.8 million for the three months ended March 31, 2014 and 2013, respectively. The increase in the three months ended March 31, 2014 was primarily attributable to higher research and development costs associated with Relday, other ORADUR-based opioid products licensed to Pain Therapeutics, ELADUR, REMOXY and other research programs, partially offset by lower research and development costs associated with POSIDUR, Depot injectable programs, ORADUR-ADHD and TRANSDUR-Sufentanil compared to the corresponding period in 2013 as more fully discussed below. Stock-based compensation expense recognized related to research and development personnel was $415,000 and $570,000 for the three months ended March 31, 2014 and 2013, respectively.

Research and development expenses associated with our major development programs approximate the following (in thousands):


	Three months ended March 31,
	2014		2013
POSIDUR	$	1,894	$	2,747
Depot Injectable Programs		770		981
Relday (1)		724		174
Other ORADUR-based opioid products licensed to Pain Therapeutics (1)		330		10
ELADUR (1)		282		5
REMOXY (1)		118		44
ORADUR-ADHD		99		152
TRANSDUR-Sufentanil		4		34
Others		1,248		642

Total research and development expenses	$	5,469	$	4,789

(1)	See Note 2 Strategic Agreements in the condensed financial statements for more details about our agreements with Impax, Pfizer, Pain Therapeutics and Zogenix.

POSIDUR

Our research and development expenses for POSIDUR were $1.9 million and $2.7 million in the three months ended March 31, 2014 and 2013, respectively. The decrease in the three months ended March 31, 2014 was primarily due to lower employee-related costs for POSIDUR compared with the corresponding period in 2013 as we incurred higher costs associated with preparing the NDA in the first quarter of 2013.

Depot Injectable Programs

Our research and development expenses for depot injectable programs were $770,000 and $981,000 in the three months ended March 31, 2014 and 2013, respectively. The decrease in the three months ended March 31, 2014 was primarily due to lower employee-related costs and lower costs related to research supplies for these programs compared with the corresponding period in 2013.

Relday

Our research and development expenses for Relday were $724,000 and $174,000 in the three months ended March 31, 2014 and 2013, respectively. The increase in the three months ended March 31, 2014 was primarily due to increased development activities and higher costs for non-clinical studies associated with Relday compared with the corresponding period in 2013.

Other select ORADUR-based opioid products licensed to Pain Therapeutics

Our research and development expenses for other ORADUR-based opioid products licensed to Pain Therapeutics were $330,000 and $10,000 in the three months ended March 31, 2014 and 2013, respectively. The increase in the three months ended March 31, 2014 was primarily due to higher employee-related costs as well as increased formulation activities associated with these products in the first quarter of 2014 compared with the corresponding period in 2013.

ELADUR

Our research and development expenses for ELADUR were $282,000 and $5,000 in the three months ended March 31, 2014 and 2013, respectively. The increase in the three months ended March 31, 2014 was primarily due to higher employee-related costs associated with the technology transfer related to this product candidate as we signed a license agreement with Impax in the first quarter of 2014 compared with the corresponding period in 2013.

REMOXY

Our research and development expenses for REMOXY were $118,000 and $44,000 in the three months ended March 31, 2014 and 2013, respectively. The increase in the three ended March 31, 2014 was primarily due to higher employee-related costs for REMOXY in the first quarter of 2014 compared with the corresponding period in 2013.

ORADUR-ADHD

Our research and development expenses for ORADUR-ADHD were $99,000 and $152,000 in the three months ended March 31, 2014 and 2013, respectively. The decrease in the three months ended March 31, 2014 was primarily due to lower employee-related costs for these drug candidates in the first quarter of 2014 compared with the corresponding period in 2013.

TRANSDUR-Sufentanil

Our research and development expenses for TRANSDUR-Sufentanil were $4,000 and $34,000 in the three months ended March 31, 2014 and 2013, respectively. The decrease in the three months ended March 31, 2014 was primarily due to decreased employee-related costs for this drug candidate in the first quarter of 2014 compared with the corresponding period in 2013.

Other DURECT research programs

Our research and development expenses for all other programs were $1.2 million and $642,000 in the three months ended March 31, 2014 and 2013, respectively. The increase in the three months ended March 31, 2014 was primarily due to higher employee-related costs and higher external contract manufacturing expenses for these programs.

As of March 31, 2014, we had 53 research and development employees compared with 55 as of March 31, 2013. We expect research and development expenses to increase modestly in the near future compared to recent quarters.

We cannot reasonably estimate the timing and costs of our research and development programs due to the risks and uncertainties associated with developing pharmaceuticals, as outlined in the “Risk Factors” section of this report. The duration of development of our research and development programs may span as many as ten years or more, and estimation of completion dates or costs to complete would be highly speculative and subjective due to the numerous risks and uncertainties associated with developing pharmaceutical products, including significant and changing government regulation, the uncertainties of future preclinical and clinical study results, the uncertainties with our collaborators’ commitment and progress to the programs and the uncertainties associated with process development and manufacturing as well as sales and marketing. In addition, with respect to our development programs subject to third-party collaborations, the timing and expenditures to complete the programs are subject to the control of our collaborators. Therefore, we cannot reasonably estimate the timing and estimated costs of the efforts necessary to complete the research and development programs. For additional information regarding these risks and uncertainties, see “Risk Factors” below.

Selling, general and administrative. Selling, general and administrative expenses are primarily comprised of salaries, benefits, stock-based compensation and other compensation cost associated with finance, legal, business development, sales and marketing and other administrative personnel, overhead and facility costs, and other general and administrative costs. Selling, general and administrative expenses were $3.4 million and $2.9 million for the three months ended March 31, 2014 and 2013, respectively. The increase in selling, general and administrative expenses was primarily due to higher employee related costs and higher outside expense in connection with signing of the Impax agreement in the three months ended March 31, 2014 compared to the corresponding period in 2013. Stock-based compensation expense recognized related to selling, general and administrative personnel was $274,000 and $326,000 for the three months ended March 31, 2014 and 2013, respectively.

As of March 31, 2014, we had 25 selling, general and administrative employees compared with 26 as of March 31, 2013. We expect selling, general and administrative expenses to decrease modestly in the near future compared to the first quarter of 2014.

Other income (expense). Interest and other income (expenses) was $3,000 and $14,000 for the three months ended March 31, 2014 and 2013, respectively. The decrease in interest income was primarily the result of lower average cash and investment balances during the three months ended March 31, 2014 compared to the corresponding periods in 2013. In the first quarter of 2014, other income (expense) also included income tax expense of $9,000 related to the impact of recording a deferred tax liability associated with goodwill related to an asset acquisition in 2000.

Interest expense was $1,000 and $2,000 for the three months ended March 31, 2014 and 2013, respectively.

Liquidity and Capital Resources

We had cash, cash equivalents and investments totaling $21.8 million at March 31, 2014 compared to $24.4 million at December 31, 2013. These balances include $350,000 and $450,000 of interest-bearing marketable securities classified as restricted investments on our balance sheets as of March 31, 2014 and December 31, 2013, respectively. The decrease in cash, cash equivalents and investments during the three months ended March 31, 2014 was primarily the result of ongoing operating expenses, partially offset by payments received from customers.

We used $2.7 million of cash in operating activities for the three months ended March 31, 2014 compared to $3.4 million for the corresponding period in 2013. The cash used for operations was primarily to fund operations as well as our working capital requirements. The decrease in cash used for operations during the three months ended March 31, 2014 was primarily attributable to a receipt of $2.0 million upfront payment from Impax as well as an increase in accounts receivable, partially offset by decreases in accrued liabilities, contract research liabilities and deferred revenue compared to the corresponding period in 2013.

We used $3.2 million of cash in investing activities for the three months ended March 31, 2014 compared to $432,000 of cash received for the corresponding period in 2013. The increase in cash used in investing activities was primarily due to an increase in net purchases of available-for-sale securities for the three months ended March 31, 2014 compared to the corresponding period in 2013. We anticipate incurring capital expenditures of approximately $100,000 in 2014 to purchase research and development and other capital equipment. The amount and timing of these capital expenditures will depend on, among other things, the timing of clinical trials for our products and our collaborative research and development activities.

We received $90,000 of cash from financing activities for the three months ended March 31, 2014 compared to zero cash received for the corresponding period in 2013. The increase in cash received from financing activities was primarily a result of higher proceeds received from exercises of stock options in the three months ended March 31, 2014 compared to the corresponding period in 2013.

We anticipate that cash used in operating and investing activities will remain comparable in the near future, pending our efforts to sign new collaborators or experience an increase in research and development activities under existing collaborations.

During the three months ended March 31, 2014, there have been no significant changes in our commercial commitments and contractual obligations as disclosed in our Annual Report on Form 10-K for the year ended December 31, 2013.

We believe that our existing cash, cash equivalents and investments will be sufficient to fund our planned operations, existing debt and contractual commitments, and planned capital expenditures through at least the next 12 months. We may consume available resources more rapidly than currently anticipated, resulting in the need for additional funding. Additionally, we do not expect to generate meaningful revenues from our pharmaceutical product candidates currently under development for at least the next twelve months, if at all. Depending on whether we enter into additional collaborative agreements in the near term, we may be required to raise additional capital through a variety of sources, including:

•

the public equity markets;

•

private equity financings;

•

collaborative arrangements; and/or

•

public or private debt.

There can be no assurance that we will enter into additional collaborative agreements in the near term or additional capital will be available on favorable terms, if at all. If adequate funds are not available, we may be required to significantly reduce or refocus our operations or to obtain funds through arrangements that may require us to relinquish rights to certain of our products, technologies or potential markets, either of which could have a material adverse effect on our business, financial condition and results of operations. To the extent that additional capital is raised through the sale of equity or convertible debt securities, the issuance of such securities would result in ownership dilution to our existing stockholders.

Our cash and investments policy emphasizes liquidity and preservation of principal over other portfolio considerations. We select investments that maximize interest income to the extent possible given these two constraints. We satisfy liquidity requirements by investing excess cash in securities with different maturities to match projected cash needs and limit concentration of credit risk by diversifying our investments among a variety of high credit-quality issuers.

Off-Balance Sheet Arrangements

As of March 31, 2014, we did not have any off-balance sheet arrangements, as defined under SEC Regulation S-K Item 303(a)(4)(ii).

Item 3.

Quantitative and Qualitative Disclosures about Market Risk

During the three months ended March 31, 2014, there have been no significant changes in market risks as disclosed in our Annual Report on Form 10-K for the year ended December 31, 2013.

Item 4.

Controls and Procedures

Evaluation of Disclosure Controls and Procedures : The Company’s principal executive and financial officers reviewed and evaluated the Company’s disclosure controls and procedures (as defined in Exchange Act Rule 13a-15(e)) as of the end of the period covered by this Form 10-Q. Based on that evaluation, the Company’s principal executive and financial officers concluded that the Company’s disclosure controls and procedures are effective at ensuring that information required to be disclosed by the Company in reports that the Company files or submits under the Exchange Act is recorded, processed, summarized, and reported within the time periods specified in SEC rules and forms, and is accumulated and communicated to management, including the Company’s principal executive officer and principal financial officer, as appropriate, to allow timely decisions regarding required disclosure.

Changes in Internal Control Over Financial Reporting : There were no significant changes in the Company’s internal control over financial reporting (as defined in Exchange Act Rule 13a-15(f)) during the Company’s most recently completed fiscal quarter that has materially affected, or is reasonably likely to materially affect, the Company’s internal control over financial reporting.

PART II—OTHER INFORMATION

Item 1.

Legal Proceedings

We are not a party to any material legal proceedings.

Item 1A.

Risk Factors

In addition to the other information in this Form 10-Q, a number of factors may affect our business and prospects. These factors include but are not limited to the following, which you should consider carefully in evaluating our business and prospects.

Risks Related To Our Business

Pfizer may discontinue development of REMOXY

We rely on Pfizer and its subsidiaries to devote time and resources to the development, manufacturing and commercialization of REMOXY. Pfizer has indicated that they would not expect to resubmit the NDA in response to the Complete Response Letter before mid-2015. There can be no assurance that Pfizer will continue development of REMOXY. Pfizer and its subsidiaries and affiliates may commercialize, develop or acquire drugs or drug candidates that may compete directly or compete for resources with REMOXY. For instance, Pfizer is developing ALO-02 (an extended release abuse resistant formulation of oxycodone that would compete with REMOXY) and owns Embeda ^® (an extended-release oral formulation of morphine sulfate), and Avinza ^® (a once-daily morphine treatment for moderate to severe pain). If Pfizer does not continue development of REMOXY, rights to REMOXY may revert to Pain Therapeutics, which may not continue REMOXY development either. If Pfizer continues development of REMOXY, there can be no assurance that their resubmission of the NDA will be timely, or that it will satisfy the FDA’s requirements. Any discontinuation or delay in the development of REMOXY will significantly harm our prospects and would be likely to have a negative effect on the price of our common stock.

Regulatory approval of POSIDUR has been delayed or may be denied, and regulatory approval of our other product candidates is subject to delay or may be denied, which could harm our business

In February 2014, we received a Complete Response Letter to our NDA for POSIDUR from the FDA. Based on its review, the FDA has determined that they cannot approve the NDA in its present form, stating the NDA does not contain sufficient information to demonstrate that POSIDUR is safe when used in the manner described in the proposed label, and the FDA has indicated that additional clinical safety studies need to be conducted. The failure to adequately demonstrate the safety and effectiveness of a pharmaceutical product candidate under development to the satisfaction of FDA and other regulatory agencies has, with respect to POSIDUR and could with respect to other product candidates delay or prevent regulatory clearance of the potential product candidate, resulting in delays to the commercialization of our product candidate, and could materially harm our business. Clinical trials may not demonstrate the sufficient levels of safety and efficacy necessary to obtain the requisite regulatory approvals for our product candidates, or may require such significant numbers of patients or additional costs to make it impractical to satisfy the FDA’s requirements, and thus our product candidates may not be approved for marketing. During the review process, the FDA may request more information regarding the safety of our product candidates, as they have in their Complete Response Letter for POSIDUR, and answering such questions could require significant additional work and expense, and take a significant amount of time, resulting in a material delay of approval or the failure to obtain approval. During the review process, the FDA may also request more information regarding the chemistry, manufacturing or controls related to our product candidates, as they have in their Complete Response Letter for REMOXY, and answering such questions could require significant additional work and expense, and take a significant amount of time, resulting in a material delay of approval or the failure to obtain approval.

Development of our pharmaceutical product candidates is not complete, and we cannot be certain that our product candidates will be able to be commercialized

To be profitable, we or our third-party collaborators must successfully research, develop, obtain regulatory approval for, manufacture, introduce, market and distribute our pharmaceutical product candidates under development. For each product candidate that we or our third-party collaborators intend to commercialize, we must successfully meet a number of critical developmental milestones for each disease or medical condition targeted, including:

•

selecting and developing a drug delivery technology to deliver the proper dose of drug over the desired period of time;

•

determining the appropriate drug dosage for use in the pharmaceutical product candidate;

•

developing drug compound formulations that will be tolerated, safe and effective and that will be compatible with the system;

•

demonstrating the drug formulation will be stable for commercially reasonable time periods;

•

demonstrating through clinical trials that the drug and system combination is safe and effective in patients for the intended indication; and

•

completing the manufacturing development and scale-up to permit manufacture of the pharmaceutical product candidate in commercial quantities and at acceptable cost.

The time frame necessary to achieve these developmental milestones for any individual product is long and uncertain, and we may not successfully complete these milestones for any of our products in development. We have not yet completed development of POSIDUR, ELADUR, Relday, TRANSDUR-Sufentanil, REMOXY and our other ORADUR-based drug candidates, and we have limited experience in developing such products. We may not be able to finalize the design or formulation of any of these product candidates. In addition, we may select components, solvents, excipients or other ingredients to include in our product candidates that have not been previously approved for use in pharmaceutical products, which may require us or our collaborators to perform additional studies and may delay clinical testing and regulatory approval of our product candidates. Even after we complete the design of a product candidate, the product candidate must still complete required clinical trials and additional safety testing in animals before approval for commercialization. We are continuing testing and development of our product candidates and may explore possible design or formulation changes to address issues of safety, manufacturing efficiency and performance. We or our collaborators may not be able to complete development of any product candidates that will be safe and effective and that will have a commercially reasonable treatment and storage period. If we or our third-party collaborators are unable to complete development of POSIDUR, ELADUR, Relday, TRANSDUR-Sufentanil, REMOXY and our other ORADUR-based drug candidates, or other product candidates, we will not be able to earn revenue from them, which would materially harm our business.

We or our third-party collaborators must show the safety and efficacy of our drug candidates in animal studies and human clinical trials to the satisfaction of regulatory authorities before they can be sold; failure to obtain approvals for REMOXY, POSIDUR or our other product candidates would significantly harm our business, prospects and financial condition

Before we or our third-party collaborators can obtain government approval to sell any of our pharmaceutical product candidates, we or they, as applicable, must demonstrate through laboratory performance studies and safety testing, nonclinical (animal) studies and clinical (human) trials that each system is safe and effective for human use for each targeted indication. The clinical development status of our most advanced publicly announced development programs is as follows:

•

REMOXY—In December 2010, King (now Pfizer) resubmitted the NDA in response to a Complete Response Letter received in December 2008 by Pain Therapeutics. On June 23, 2011, a Complete Response Letter from the FDA was received by Pfizer on the resubmission to the NDA for REMOXY. The issues raised in the Complete Response Letter relate primarily to manufacturing. Pfizer has efforts underway to resolve these issues. In October 2013, Pfizer stated that, having achieved technical milestones related to manufacturing, they will continue the development program for REMOXY ^® . Following guidance received from the FDA earlier in 2013, Pfizer announced that they will proceed with the additional clinical studies and other actions required to address the Complete Response Letter. These new clinical studies will include, in part, a pivotal bioequivalence study with the modified REMOXY formulation to bridge to the clinical data related to the original REMOXY formulation, and an abuse-potential study with the modified formulation. As previously disclosed, the complete response submission is not expected to occur prior to mid-2015.

•

POSIDUR—In April 2013, we submitted a new drug application as a 505(b)(2) application, which relies in part on the FDA’s findings of safety and effectiveness of a reference drug. In June 2013, we announced that our NDA submission had been accepted by the FDA indicating that the application is sufficiently complete to permit a substantive review. In February 2014, we received a Complete Response Letter from the FDA. Based on its review, the FDA has determined that they cannot approve the NDA in its present form, stating the NDA does not contain sufficient information to demonstrate that POSIDUR is safe when used in the manner described in the proposed label, and the FDA has indicated that additional clinical safety studies need to be conducted. We are evaluating the issues and recommendations described in the Complete Response Letter and plan to have further discussions with the FDA around them. There can be no assurance that we will be able to adequately address all of FDA’s concerns regarding the POSIDUR NDA or there could be a delay in addressing such concerns, the FDA may not grant regulatory approval of POSIDUR, adverse effects may arise from additional testing or use of POSIDUR, and the data that we have generated or may generate may not be deemed sufficient by FDA or other regulatory agencies to support regulatory approval of POSIDUR.

•

ELADUR—A Phase IIa clinical trial in post-herpetic neuralgia (PHN or post-shingles pain) was completed and positive efficacy trends were reported in the fourth quarter of 2007. King, which assumed worldwide development and commercialization rights for ELADUR through its acquisition of Alpharma, conducted a Phase II clinical trial to evaluate ELADUR for the treatment of chronic low back pain and reported in April 2011 that the primary efficacy endpoint for the trial was not met. In February 2012, Pfizer, which assumed worldwide development and commercialization rights to ELADUR through its acquisition of King, notified us that they were returning their worldwide development and commercialization rights to ELADUR. In January 2014, we and Impax entered into an agreement, pursuant to which we have granted Impax an exclusive worldwide license to our proprietary TRANSDUR transdermal delivery technology and other intellectual property to develop and commercialize ELADUR. There can be no assurance that Impax will be able to successfully develop ELADUR to obtain marketing approval by the FDA or other regulatory agencies.

•

TRANSDUR-Sufentanil Patch—In February 2009, an end-of-Phase II meeting with the FDA was conducted for this program outlining a potential regulatory pathway for the Phase III program and NDA submission. In 2011, we had discussions with the FDA and regulatory agencies in several major European countries to better understand development requirements for U.S. and European countries. We are in discussions with potential partners regarding licensing development and commercialization rights to this program to which we hold worldwide rights. There can be no assurance that our planned development program for TRANSDUR-Sufentanil will generate data and information that will be deemed sufficient for marketing approval by the FDA or other regulatory agencies or that we will be able to find a collaborator with respect to the development and commercialization of this drug candidate.

•

ORADUR-based opioids—Phase I clinical trials have been conducted for two of these ORADUR-based product candidates (hydrocodone and hydromorphone), and an IND has been accepted by the FDA for the third ORADUR-based opioid (oxymorphone). In October 2013, Pain Therapeutics stated that it had regained all rights from Pfizer with respect to the three ORADUR-based opioid drug candidates (hydrocodone, hydromorphone and oxymorphone). During the first quarter of 2014, we conducted research and development activities on these programs under approved workplans with Pain Therapeutics.There can be no assurance that we or our collaborators will be able to successfully develop ORADUR-based formulations of hydrocodone, hydromorphone or oxymorphone to obtain marketing approval by the FDA or other regulatory agencies.

•

ORADUR-ADHD—Since 2010, we and Orient Pharma have conducted several Phase I studies to evaluate multiple formulations of ORADUR-Methylphenidate. We and Orient Pharma have selected a lead formulation containing the active pharmaceutical ingredient methylphenidate. This formulation was chosen based on its potential for rapid onset of action, long duration for once-a-day dosing and target pharmacokinetic profile as demonstrated in a recent Phase 1 trial. In addition, this product candidate will utilize a small capsule size relative to the leading existing long-acting products on the market. Orient Pharma has met with the Taiwan Food and Drug Administration (TFDA) to discuss the Phase 3 program in that market and is developing its plans for further development in the defined Asian and South Pacific countries to which it has rights from us. DURECT retains rights to all other territories in the world and is engaged in licensing discussions with other companies. There can be no assurance that we will be able to successfully develop ORADUR-methylphenidate to obtain marketing approval by the TFDA or the U.S. FDA or other regulatory agencies, nor is there any assurance that we will be able to find a collaborator with respect to the development and commercialization of this drug candidate for the territories not currently licensed to Orient Pharma.

•

Relday—In January 2013, Zogenix announced positive single-dose pharmacokinetic (PK) results from the Phase 1 clinical trial of Relday. Per Zogenix, based on the favorable safety and PK profile demonstrated with the 25 mg and 50 mg once-monthly doses tested in the Phase 1 trial, Zogenix extended the study to include a 100 mg dose of the same formulation. In May 2013, Zogenix announced positive results with the 100 mg arm, demonstrating dose proportionality across the full dose range that would be anticipated to be used in clinical practice. According to Zogenix, the positive results from this study extension positions Zogenix to begin a multi-dose clinical trial, which would provide the required steady-state pharmacokinetic and safety data prior to initiating Phase 3 development studies, and Zogenix plans to commence this multi-dose clinical trial in the fourth quarter of 2014. There can be no assurance that Zogenix will commence the multi-dose clinical trial in the fourth quarter of 2014 or that the results of such a trial will warrant continued development of Relday.

We are currently in the clinical, preclinical or research stages with respect to all our other product candidates under development. We plan to continue extensive and costly tests, clinical trials and safety studies in animals to assess the safety and effectiveness of our product candidates. These studies include laboratory performance studies and safety testing, clinical trials and animal toxicological studies necessary to support regulatory approval of development products in the United States and other countries of the world. These studies are costly, complex and last for long durations, and may not yield data supportive of the safety or efficacy of our drug candidates or required for regulatory approval.

Early clinical trial results may not predict the results of later trials, and our clinical trials or those of our collaborators for POSIDUR or REMOXY may not satisfy regulatory agencies

While some clinical trials of our product candidates have shown indications of safety and efficacy of our product candidates, there can be no assurance that these results will be confirmed in subsequent clinical trials or provide a sufficient basis for regulatory approval. In addition, side effects observed in clinical trials, or other side effects that appear in later clinical trials, may adversely affect our or our collaborators’ ability to obtain regulatory approval or market our product candidates. For example, in the Phase IIb hysterectomy trial and the BESST Phase III abdominal surgery trial of POSIDUR, transient local hematoma-like discolorations were observed near the surgical site. Side effects such as these, toxicity or other safety issues associated with the use of our drug candidates could require us to perform additional studies or halt development of our drug candidates. We or our collaborators may be required by regulatory agencies to conduct additional animal or human studies regarding the safety and efficacy of our pharmaceutical product candidates which we have not planned or anticipated. For example, the FDA’s Complete Response Letter raised concerns related to, among other matters, the Chemistry, Manufacturing, and Controls section of the NDA for REMOXY. There can be no assurance that Pfizer will resolve these issues to the satisfaction of the FDA in a timely manner or ever, which could harm our business, prospects and financial condition. Further, the FDA’s Complete Response Letter for POSIDUR raised concerns that insufficient safety data had been provided and FDA has indicated that additional clinical safety trials for POSIDUR need to be conducted, which would be expensive and could delay or preclude product approval, harming our business, prospects and financial condition.

Regulatory action or failure to obtain product approvals could delay or limit development and commercialization of our product candidates and result in failure to achieve anticipated revenues

The manufacture and marketing of our pharmaceutical product candidates and our research and development activities are subject to extensive regulation for safety, efficacy and quality by numerous government authorities in the United States and abroad. We or our third-party collaborators must obtain clearance or approval from applicable regulatory authorities before we or they, as applicable, can perform clinical trials, market or sell our products in development in the United States or abroad. Clinical trials, manufacturing and marketing of products are subject to the rigorous testing and approval process of the FDA and equivalent foreign regulatory authorities. In particular, recalls of and reported adverse side effects of marketed drugs have made regulatory agencies, including the FDA, increasingly focus on the safety of drug products. Regulatory agencies are requiring more extensive and ever increasing showings of safety at every stage of drug development and commercialization from initial clinical trials to regulatory approval and beyond. These rigorous and evolving standards may delay and increase the expenses of our development efforts. The FDA or other foreign regulatory agency may, at any time, halt our and our collaborators’ development and commercialization activities due to safety concerns, in which case our business will be harmed. In addition, the FDA or other foreign regulatory agency may refuse or delay approval of our or our collaborators’ drug candidates for failure to collect sufficient clinical or animal safety data, and require us or our collaborators to conduct additional clinical or animal safety studies which may cause lengthy delays and increased costs to our programs.

The Federal Food, Drug and Cosmetic Act and other federal, state and foreign statutes and regulations govern and influence the testing, manufacture, labeling, advertising, distribution and promotion of drugs and medical devices. These laws and regulations are complex and subject to change. Furthermore, these laws and regulations may be subject to varying interpretations, and we may not be able to predict how an applicable regulatory body or agency may choose to interpret or apply any law or regulation to our pharmaceutical product candidates. As a result, clinical trials and regulatory approval can take a number of years to accomplish and require the expenditure of substantial resources. We or our third-party collaborators, as applicable, may encounter delays or rejections based upon administrative action or interpretations of current rules and regulations. We or our third-party collaborators, as applicable, may not be able to timely reach agreement with the FDA on our clinical trials or on the required clinical or animal data we or they must collect to continue with our clinical trials or eventually commercialize our product candidates.

We or our third-party collaborators, as applicable, may also encounter delays or rejections based upon additional government regulation from future legislation, administrative action or changes in FDA policy during the period of product development, clinical trials and FDA regulatory review. We or our third-party collaborators, as applicable, may encounter similar delays in foreign countries. Sales of our pharmaceutical product candidates outside the United States are subject to foreign regulatory standards that vary from country to country.

The time required to obtain approvals from foreign countries may be shorter or longer than that required for FDA approval, and requirements for foreign licensing may differ from FDA requirements. We or our third-party collaborators, as applicable, may be unable to obtain requisite approvals from the FDA and foreign regulatory authorities, and even if obtained, such approvals may not be on a timely basis, or they may not cover the clinical uses that we specify. If we or our third-party collaborators, as applicable, fail to obtain timely clearance or approval for our development products, we or they will not be able to market and sell our pharmaceutical product candidates, which will limit our ability to generate revenue.

Many of our drug candidates under development, including REMOXY, our other ORADUR-based opioids and TRANSDUR-Sufentanil are subject to mandatory Risk Evaluation and Mitigation Strategy (REMS) programs, which could delay the approval of these drug candidates, reduce demand for them, and increase the cost, burden and liability associated with their commercialization

On February 6, 2009, the FDA sent letters to manufacturers of certain opioid drug products, indicating that these drugs will be required to have a Risk Evaluation and Mitigation Strategy (REMS) to ensure that the benefits of the drugs continue to outweigh the risks. The affected opioid drugs include brand name and generic products and are formulated with the active ingredients fentanyl, hydromorphone, methadone, morphine, oxycodone, and oxymorphone.

On April 19, 2011, the Office of National Drug Control Policy (ONDCP) released the Obama Administration’s Epidemic: Responding to America’s Prescription Drug Abuse Crisis —a comprehensive action plan to address the national prescription drug abuse epidemic. This plan includes action in four major areas to reduce prescription drug abuse: education, monitoring, proper disposal, and enforcement. In support of the action plan, the FDA announced the elements of a Risk Evaluation and Mitigation Strategy (REMS) that will require all manufacturers of long-acting and extended-release opioids to ensure that training is provided to prescribers of these medications and to develop information that prescribers can use when counseling patients about the risks and benefits of opioid use. The FDA wants drug makers to work together to develop a single system for implementing the REMS strategies.

On July 9, 2012 the FDA approved a REMS for extended-release (ER) and long-acting (LA) opioids. The REMS is part of a federal initiative to address the prescription drug abuse, misuse, and overdose epidemic. The REMS introduces new safety measures designed to reduce risks and improve the safe use of ER/LA opioids, while ensuring access to needed medications for patients in pain. The new ER/LA opioid REMS will affect more than 20 companies that manufacture these opioid analgesics. Under the new REMS, companies will be required to make education programs available to prescribers based on an FDA Blueprint. It is expected that companies will meet this obligation by providing educational grants to continuing education (CE) providers, who will develop and deliver the training. The REMS also will require companies to make available FDA-approved patient education materials on the safe use of these drugs. The companies will be required to perform periodic assessments of the implementation of the REMS and the success of the program in meeting its goals. The FDA will review these assessments and may require additional elements to achieve the goals of the program.

On September 10, 2013, the FDA announced safety labeling changes and post-market study requirements for extended-release and long-acting opioid analgesics (ER/LA opioids). The updated class-wide labeling changes state that ER/LA opioids are indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. The updated indication further clarifies that, because of the risks of addiction, abuse, and misuse, even at recommended doses, and because of the greater risks of overdose and death, these drugs should be reserved for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain; ER/LA opioid analgesics are not indicated for as-needed pain relief. Recognizing that more information is needed to assess the serious risks associated with long-term use of ER/LA opioids, the FDA is requiring the drug companies that make these products to conduct further post-market studies and clinical trials. These changes may result in a decrease in prescriptions for this class of drugs and will increase the costs borne by manufacturers of ER/LA opioids.

Many of our drug candidates including REMOXY, our other ORADUR-opioid drug candidates and TRANSDUR-Sufentanil are subject to the REMS requirement. The FDA’s REMS requirements have been evolving, and until the contours of required REMS programs are established by the FDA and understood by drug developers and marketers such as ourselves and our collaborators, there may be delays in marketing approvals for these drug candidates. In addition, there may be increased cost, administrative burden and potential liability associated with the marketing and sale of these types of drug candidates subject to the REMS requirement, as well as decreased demand resulting from new labeling requirements, which could negatively impact the commercial benefits to us and our collaborators from the sale of these drug candidates.

We depend to a large extent on third-party collaborators, and we have limited or no control over the development, sales, distribution and disclosure for our pharmaceutical product candidates which are the subject of third-party collaborative or license agreements

Our performance depends to a large extent on the ability of our third-party collaborators to successfully develop and obtain approvals for our pharmaceutical product candidates. We have entered into agreements with Pain Therapeutics, King (now Pfizer), Orient Pharma, Zogenix, Impax and others under which we granted such third parties the right to develop, apply for regulatory approval for, market, promote or distribute REMOXY and other ORADUR-based products, Relday, ELADUR and other product candidates, subject to payments to us in the form of product royalties and other payments. We have limited or no control over the expertise or resources that any collaborator may devote to the development, clinical trial strategy, regulatory approval, marketing or sale of these product candidates, or the timing of their activities. Any of our present or future collaborators may not perform their obligations as expected. These collaborators may breach or terminate their agreement with us or otherwise fail to conduct their collaborative activities successfully and in a timely manner. Enforcing any of these agreements in the event of a breach by the other party could require the expenditure of significant resources and consume a significant amount of management time and attention. Our collaborators may also conduct their activities in a manner that is different from the manner we would have chosen, had we been developing such product candidates ourselves. Further, our collaborators may elect not to develop or commercialize product candidates arising out of our collaborative arrangements or not devote sufficient resources to the development, clinical trials, regulatory approval, manufacture, marketing or sale of these product candidates. If any of these events occur, we may not recognize revenue from the commercialization of our product candidates based on such collaborations. In addition, these third parties may have similar or competitive products to the ones which are the subject of their collaborations with us, or relationships with our competitors, which may reduce their interest in developing or selling our product candidates. We may not be able to control public disclosures made by some of our third-party collaborators, which could negatively impact our stock price.

Cancellation of our collaboration agreements may impact our near-term revenues and adversely affect potential economic benefits

Our collaboration agreements with third parties typically allow the third party to terminate the agreement by providing notice to us. For example, in January 2012, we were notified that Nycomed was terminating the Development and License Agreement between Nycomed and us relating to the development and commercialization of POSIDUR in Europe and their other licensed territories. In February 2012, we were notified that Pfizer was terminating the worldwide Development and License Agreement between Alpharma (acquired by King which subsequently was acquired by Pfizer) and us relating to the development and commercialization of ELADUR. In March 2012, we were notified that Hospira was terminating the Development and License Agreement between Hospira and us relating to the development and commercialization of POSIDUR in the United States and Canada. Termination of such agreements can lead to a near-term increase in our reported revenues resulting from the immediate recognition of payments that would otherwise have been recognized over time. Termination deprives us of potential future economic benefits under such agreements, and may make it more difficult to enter into agreements with other third parties for use of the assets that were subject to the terminated agreement. Termination of our agreements with Pain Therapeutics, Zogenix or Impax, or Pfizer’s agreement with Pain Therapeutics, could have similar effects.

Our revenues depend on collaboration agreements with other companies. These agreements subject us to obligations which must be fulfilled and also make our revenues dependent on the performance of such third parties. If we are unable to meet our obligations or manage our relationships with our collaborators under these agreements or enter into additional collaboration agreements or if our existing collaborations are terminated, our revenues may decrease. Acquisitions of our collaborators can be disruptive

Our revenues are based to a significant extent on collaborative arrangements with third parties, pursuant to which we receive payments based on our performance of research and development activities set forth in these agreements. We may not be able to fulfill our obligations or attain milestones set forth in any specific agreement, which could cause our revenues to fluctuate or be less than anticipated and may expose us to liability for contractual breach. In addition, these agreements may require us to devote significant time and resources to communicating with and managing our relationships with such collaborators and resolving possible issues of contractual interpretation which may detract from time our management would otherwise devote to managing our operations. Such agreements are generally complex and contain provisions that could give rise to legal disputes, including potential disputes concerning ownership of intellectual property under collaborations. Such disputes can delay or prevent the development of potential new product candidates, or can lead to lengthy, expensive litigation or arbitration. In general, our collaboration agreements, including our agreements with Pain Therapeutics and King (now Pfizer) with respect to REMOXY, Pain Therapeutics with respect to the other ORADUR-based products incorporating specified opioids, Orient Pharma with respect to ORADUR-Methylphenidate, Zogenix with respect to Relday, and Impax with respect to ELADUR, may be terminated by the other party at will or upon specified conditions including, for example, if we fail to satisfy specified performance milestones or if we breach the terms of the agreement. From time to time, our licensees may be the subject of an acquisition by another company. For example, Alpharma was acquired by King in December 2008, in February 2011 King was acquired by Pfizer and, in October 2011 Nycomed was acquired by Takeda. Such transactions can lead to turnover of program staff, a review of development programs and strategies by the acquirer, and other events that can disrupt a program, resulting in program delays or discontinuations.

If any of our collaborative agreements are terminated or delayed, our anticipated revenues may be reduced or not materialize, and our products in development related to those agreements may not be commercialized.

Our cash flows are likely to differ from our reported revenues

Our revenues will likely differ from our cash flows from revenue-generating activities. Upfront payments received upon execution of collaborative agreements are recorded as deferred revenue and generally recognized on a straight-line basis over the period of our continuing involvement with the third-party collaborator pursuant to the applicable agreement. The period of continuing involvement may also be revised on a prospective basis. For example, in the first quarter of 2012, we revised the period of continuing involvement related to the termination of our collaborations with Nycomed, Hospira, and Pfizer, resulting in the accelerated recognition of approximately $35.4 million in revenue from upfront payments received in earlier periods; this recognition of revenue in the first quarter of 2012 had no impact on cash flow during the period. As of March 31, 2014, we had $1.5 million of deferred revenue which will be recognized in future periods and may cause our reported revenues to be greater than cash flows from our ongoing revenue-generating activities.

Our revenues also depend on milestone payments based on achievements by our third-party collaborators. Failure of such collaborators to attain such milestones would result in our not receiving additional revenues

In addition to payments based on our performance of research and development activities, our revenues also depend on the attainment of milestones set forth in our collaboration agreements. Such milestones are typically related to development activities or sales accomplishments. While our involvement is necessary to the achievement of development-based milestones, the performance of our third-party collaborators is also required to achieve those milestones. Under our third-party collaborative agreements, our third party collaborators will take the lead in commercialization activities and we are typically not involved in the achievement of sales-based milestones. Therefore, we are even more dependent upon the performance of our third-party collaborators in achieving sales-based milestones. To the extent we and our third-party collaborators do not achieve such development-based milestones or our third-party collaborators do not achieve sales-based milestones, we will not receive the associated revenues, which could harm our financial condition and may cause us to defer or cut-back development activities or forego the exploitation of opportunities in certain geographic territories, any of which could have a material adverse effect on our business.

Our business strategy includes the entry into additional collaborative agreements. We may not be able to enter into additional collaborative agreements or may not be able to negotiate commercially acceptable terms for these agreements

Our current business strategy includes the entry into additional collaborative agreements for the development and commercialization of our pharmaceutical product candidates. The negotiation and consummation of these types of agreements typically involve simultaneous discussions with multiple potential collaborators and require significant time and resources from our officers, business development, legal, and research and development staff. In addition, in attracting the attention of pharmaceutical and biotechnology company collaborators, we compete with numerous other third parties with product opportunities as well the collaborators’ own internal product opportunities. We may not be able to consummate additional collaborative agreements, or we may not be able to negotiate commercially acceptable terms for these agreements. If we do not consummate additional collaborative agreements, we may have to consume money more rapidly on our product development efforts, defer development activities or forego the exploitation of certain geographic territories, any of which could have a material adverse effect on our business.

We will require and may have difficulty raising needed capital in the future

Our business currently does not generate sufficient revenues to meet our capital requirements and we do not expect that it will do so in the near future. We have expended and will continue to expend substantial funds to complete the research, development and clinical testing of our pharmaceutical product candidates. We will require additional funds for these purposes, to establish additional clinical- and commercial-scale manufacturing arrangements and facilities, and to provide for the marketing and distribution of our product candidates. Additional funds may not be available on acceptable terms, if at all. If adequate funds are unavailable from operations or additional sources of financing, we may have to delay, reduce the scope of or eliminate one or more of our research or development programs which would materially harm our business, financial condition and results of operations.

We believe that our cash, cash equivalents and investments, will be adequate to satisfy our capital needs for at least the next 12 months. However, our actual capital requirements will depend on many factors, including:

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regulatory actions with respect to our product candidates;

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continued progress and cost of our research and development programs;

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the continuation of our collaborative agreements that provide financial funding for our activities;

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success in entering into collaboration agreements and meeting milestones under such agreements;

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progress with preclinical studies and clinical trials;

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the time and costs involved in obtaining regulatory clearance;

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costs involved in preparing, filing, prosecuting, maintaining and enforcing patent claims;

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costs of developing sales, marketing and distribution channels and our ability and that of our collaborators to sell our pharmaceutical product candidates;

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costs involved in establishing manufacturing capabilities for clinical and commercial quantities of our product candidates;

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competing technological and market developments;

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market acceptance of our product candidates;

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costs for recruiting and retaining employees and consultants; and

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unexpected legal, accounting and other costs and liabilities related to our business.

We may consume available resources more rapidly than currently anticipated, resulting in the need for additional funding. We may seek to raise any necessary additional funds through equity or debt financings, convertible debt financings, collaborative arrangements with corporate collaborators or other sources, which may be dilutive to existing stockholders and may cause the price of our common stock to decline. In addition, in the event that additional funds are obtained through arrangements with collaborators or other sources, we may have to relinquish rights to some of our technologies or pharmaceutical product candidates that we would otherwise seek to develop or commercialize ourselves. If adequate funds are not available, we may be required to significantly reduce or refocus our product development efforts, resulting in delays in generating future product revenue.

We and our third-party collaborators may not be able to manufacture sufficient quantities of our pharmaceutical product candidates and components to support the clinical and commercial requirements of our collaborators and ourselves at an acceptable cost or in compliance with applicable government regulations, and we have limited manufacturing experience

We or our third-party collaborators to whom we have assigned such responsibility must manufacture our pharmaceutical product candidates and components in clinical and commercial quantities, either directly or through third parties, in compliance with regulatory requirements and at an acceptable cost. The manufacturing processes associated with our product candidates are complex. We and our third-party collaborators, where relevant, have not yet completed development of the manufacturing process for any product candidates or components, including REMOXY and our other ORADUR-based drug candidates, POSIDUR, ELADUR, Relday, and TRANSDUR-Sufentanil. If we and our third-party collaborators, where relevant, fail to timely complete the development of the manufacturing process for our product candidates, we and our third-party collaborators, where relevant, will not be able to timely produce product for clinical trials and commercialization of our product candidates. We have also committed to manufacture and supply product candidates or components under a number of our collaborative agreements with third-party companies. We have limited experience manufacturing pharmaceutical products, and we may not be able to timely accomplish these tasks. If we and our third-party collaborators, where relevant, fail to develop manufacturing processes to permit us to manufacture a product candidate or component at an acceptable cost, then we and our third-party collaborators may not be able to commercialize that product candidate or we may be in breach of our supply obligations to our third-party collaborators.

Our manufacturing facility in Cupertino is a multi-disciplinary site that we have used to manufacture only research and clinical supplies of several of our pharmaceutical product candidates, including POSIDUR, REMOXY and our other ORADUR-based drug candidates, ELADUR, Relday and TRANSDUR-Sufentanil. We have not manufactured commercial quantities of any of our product candidates. In the future, we intend to develop additional manufacturing capabilities for our product candidates and components to meet our demands and those of our third-party collaborators by contracting with third-party manufacturers and by potentially constructing additional manufacturing space at our facilities in California and Alabama. We have limited experience building and validating manufacturing facilities, and we may not be able to accomplish these tasks in a timely or cost effective manner.

If we and our third-party collaborators, where relevant, are unable to manufacture our pharmaceutical product candidates or components in a timely manner or at an acceptable cost, quality or performance level, and are unable to attain and maintain compliance with applicable regulations, the clinical trials and the commercial sale of our product candidates and those of our third-party collaborators could be delayed. Additionally, we may need to alter our facility design or manufacturing processes, install additional equipment or do additional construction or testing in order to meet regulatory requirements, optimize the production process, increase efficiencies or production capacity or for other reasons, which may result in additional cost to us or delay production of product needed for the clinical trials and commercial launch of our product candidates and those of our third-party collaborators.

We have entered into a supply agreement with Hospira Worldwide, Inc. for clinical and commercial supplies of POSIDUR and a supply agreement with Corium International, Inc. for clinical and commercial supplies of ELADUR. These third parties are currently our sole source for drug product required for development and commercialization of these drug candidates. Furthermore, we and our third-party collaborators, where relevant, may also need or choose to subcontract with additional third-party contractors to perform manufacturing steps of our pharmaceutical product candidates or supply required components for our product candidates. Where third party contractors perform manufacturing services for us, we will be subject to the schedule, expertise and performance of third parties as well as incur significant additional costs. Failure of third parties to perform their obligations could adversely affect our operations, development timeline and financial results. We expect to put in place in the future second source supply arrangements, which may be costly and time consuming.

If we or our third-party collaborators cannot manufacture our pharmaceutical product candidates or components in time to meet the clinical or commercial requirements of our collaborators or ourselves or at an acceptable cost, our operating results will be harmed.

Failure to comply with ongoing governmental regulations for our pharmaceutical product candidates could materially harm our business in the future

Marketing or promoting a drug is subject to very strict controls. Furthermore, clearance or approval may entail ongoing requirements for post-marketing studies. The manufacture and marketing of drugs are subject to continuing FDA and foreign regulatory review and requirements that we update our regulatory filings. Later discovery of previously unknown problems with a product, manufacturer or facility, or our failure to update regulatory files, may result in restrictions, including withdrawal of the product from the market. Any of the following or other similar events, if they were to occur, could delay or preclude us from further developing, marketing or realizing full commercial use of our product candidates, which in turn would materially harm our business, financial condition and results of operations:

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failure to obtain or maintain requisite governmental approvals;

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failure to obtain approvals for clinically intended uses of our pharmaceutical product candidates under development; or

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FDA required product withdrawals or warnings arising from identification of serious and unanticipated adverse side effects in our product candidates.

Manufacturers of drugs must comply with the applicable FDA good manufacturing practice regulations, which include production design controls, testing, quality control and quality assurance requirements as well as the corresponding maintenance of records and documentation. Compliance with current good manufacturing practices regulations is difficult and costly. Manufacturing facilities are subject to ongoing periodic inspection by the FDA and corresponding state agencies, including unannounced inspections, and must be licensed before they can be used for the commercial manufacture of our development products. We and/or our present or future suppliers and distributors may be unable to comply with the applicable good manufacturing practice regulations and other FDA regulatory requirements. We have not been subject to a good manufacturing regulation inspection by the FDA relating to our product candidates. If we, our third-party collaborators or our respective suppliers do not achieve compliance for our product candidates we or they manufacture, the FDA may refuse or withdraw marketing clearance or require product recall, which may cause interruptions or delays in the manufacture and sale of our product candidates.

We have a history of operating losses, expect to continue to have losses in the future and may never achieve or maintain profitability

We have incurred significant operating losses since our inception in 1998 and, as of March 31, 2014, had an accumulated deficit of approximately $364.4 million. We expect to continue to incur significant operating losses over the next several years as we continue to incur significant costs for research and development, clinical trials, manufacturing, sales, and general and administrative functions. Our ability to achieve profitability depends upon our ability, alone or with others, to successfully complete the development of our proposed product candidates, obtain the required regulatory clearances, and manufacture and market our proposed product candidates. Development of pharmaceutical product candidates is costly and requires significant investment. In addition, we may choose to license from third parties either additional drug delivery platform technology or rights to particular drugs or other appropriate technology for use in our product candidates. The license fees for these technologies or rights would increase the costs of our product candidates.

To date, we have not generated significant revenue from the commercial sale of our pharmaceutical product candidates and do not expect to do so in the near future. Our current revenues are from the sale of the ALZET product line, the sale of LACTEL biodegradable polymers and certain excipient sales, and from payments under collaborative research and development agreements with third parties. In the year ended December 31, 2012, we had a one-time increase in revenues resulting from the recognition of previously deferred revenues associated with upfront payments from terminated agreements. These revenues represented the recognition of deferred revenue for cash received in earlier periods and we do not expect this to recur. We do not expect our product revenues to increase significantly in the near future, and we do not expect that collaborative research and development revenues will exceed our actual operating expenses. We do not anticipate meaningful revenues to derive from the commercialization and marketing of our product candidates in development in the near future, and therefore do not expect to generate sufficient revenues to cover expenses or achieve profitability in the near future.

We may develop our own sales force and commercial group to market future products but we have limited sales and marketing experience with respect to pharmaceuticals and may not be able to do so effectively

We have a small sales and marketing group focused on our ALZET and LACTEL product lines. We may choose to develop our own sales force and commercial group to market products that we may develop in the future, or to market POSIDUR if we do not enter into an agreement with a third party to commercialize POSIDUR. Developing a sales force and commercial group will require substantial expenditures and the hiring of qualified personnel. We have limited sales and marketing experience, and may not be able to effectively recruit, train or retain sales personnel. If we are not able to put in place an appropriate sales force and commercial group for POSIDUR, we may not be able to effectively launch the product. We may not be able to effectively sell our product candidates, if approved, and our failure to do so could limit or materially harm our business.

We and our third-party collaborators may not sell our product candidates effectively

We and our third-party collaborators compete with many other companies that currently have extensive and well-funded marketing and sales operations. Our marketing and sales efforts and those of our third-party collaborations may be unable to compete successfully against these other companies. We and our third-party collaborators, if relevant, may be unable to establish a sufficient sales and marketing organization on a timely basis, if at all. We and our third-party collaborators, if relevant, may be unable to engage qualified distributors. Even if engaged, these distributors may:

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fail to satisfy financial or contractual obligations to us;

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fail to adequately market our product candidates;

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cease operations with little or no notice to us;

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offer, design, manufacture or promote competing product lines;

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fail to maintain adequate inventory and thereby restrict use of our product candidates; or

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build up inventory in excess of demand thereby limiting future purchases of our product candidates resulting in significant quarter-to-quarter variability in our sales.

The failure of us or our third-party collaborators to effectively develop, gain regulatory approval for, sell, manufacture and market our product candidates will hurt our business, prospects and financial results.

We rely heavily on third parties to support development, clinical testing and manufacturing of our product candidates

We rely on third-party contract research organizations, service providers and suppliers to provide critical services to support development, clinical testing, and manufacturing of our product candidates. For example, we currently depend on third-party vendors to manage and monitor our clinical trials and to perform critical manufacturing steps for our product candidates. These third parties may not execute their responsibilities and tasks competently in compliance with applicable laws and regulations or in a timely fashion. We rely on third-parties to manufacture or perform manufacturing steps relating to our product candidates or components. We anticipate that we will continue to rely on these and other third-party contractors to support development, clinical testing, and manufacturing of our product candidates. Failure of these contractors to provide the required services in a competent or timely manner or on reasonable commercial terms could materially delay the development and approval of our development products, increase our expenses and materially harm our business, financial condition and results of operations.

Key components of our product candidates are provided by limited numbers of suppliers, and supply shortages or loss of these suppliers could result in interruptions in supply or increased costs

Certain components and drug substances used in our product candidates (including POSIDUR, REMOXY, our other ORADUR-based drug candidates, ELADUR, Relday and TRANSDUR-Sufentanil) are currently purchased from a single or a limited number of outside sources. In particular, Eastman Chemical is the sole supplier, pursuant to a supply agreement entered into in December 2005, of our requirements of sucrose acetate isobutyrate, a necessary component of POSIDUR, REMOXY, our other ORADUR-based drug candidates, ELADUR, Relday and certain other pharmaceuticals systems we have under development. The reliance on a sole or limited number of suppliers could result in:

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delays associated with redesigning a pharmaceutical product candidate due to a failure to obtain a single source component;

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an inability to obtain an adequate supply of required components; and

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reduced control over pricing, quality and delivery time.

We have supply agreements in place for certain components of our pharmaceutical product candidates, but do not have in place long term supply agreements with respect to all of the components of any of our product candidates. Therefore the supply of a particular component could be terminated at any time without penalty to the supplier. In addition, we may not be able to procure required components or drugs from third-party suppliers at a quantity, quality and cost acceptable to us. Any interruption in the supply of single source components could cause us to seek alternative sources of supply or manufacture these components internally. Furthermore, in some cases, we are relying on our third-party collaborators to procure supply of necessary components. If the supply of any components for our product candidates is interrupted, components from alternative suppliers may not be available in sufficient volumes or at acceptable quality levels within required timeframes, if at all, to meet our needs or those of our third-party collaborators. This could delay our ability to complete clinical trials and obtain approval for commercialization and marketing of our product candidates, causing us to lose sales, incur additional costs, delay new product introductions and could harm our reputation.

If we are unable to adequately protect, maintain or enforce our intellectual property rights or secure rights to third-party patents, we may lose valuable assets, experience reduced market share or incur costly litigation to protect our rights or our third-party collaborators may choose to terminate their agreements with us

Our ability to commercially exploit our products will depend significantly on our ability to obtain and maintain patents, maintain trade secret protection and operate without infringing the proprietary rights of others.

The patent status of our lead drug candidates, REMOXY and POSIDUR, are as follows:

In the U.S., REMOXY is covered by six patent families. Three patent families include granted patents expiring in at least 2015, 2025, and 2031, respectively. The patent family providing protection until at least 2025 includes six granted patents. The other three patent families include pending patent applications, which if granted, could result in patents expiring in 2028, 2034, and 2034, respectively, plus any eligible patent term adjustments and extensions. We currently have pending U.S. applications for these six patent families. There can be no assurance that the pending patent applications will be granted. In Europe, REMOXY is covered by two granted patents expiring in 2016 and 2023, respectively, plus any eligible patent term extensions.

In the U.S., POSIDUR is covered by two patent families, which include granted patents expiring in at least 2015 and 2025, respectively. In Europe, POSIDUR is covered by two granted patents expiring in 2016 and 2025, respectively, plus any eligible patent term extensions.

As of April 24, 2014, we held over 45 unexpired issued U.S. patents and over 300 unexpired issued foreign patents (which include granted European patent rights that have been validated in various EU member states). In addition, we have over 50 pending U.S. patent applications and over 100 foreign applications pending in Europe, Australia, Japan, Canada and other countries.

The patent positions of pharmaceutical companies, including ours, are uncertain and involve complex legal and factual questions. In addition, the coverage claimed in a patent application can be significantly reduced before the patent is issued. Consequently, our patent applications or those that are licensed to us may not issue into patents, and any issued patents may not provide protection against competitive technologies or may be held invalid if challenged. Our competitors may also independently develop products similar to ours or design around or otherwise circumvent patents issued to us or licensed by us. In addition, the laws of some foreign countries may not protect our proprietary rights to the same extent as U.S. law.

The patent laws of the U.S. have recently undergone changes through court decisions which may have significant impact on us and our industry. Decisions of the U.S. Supreme Court and other courts with respect to the standards of patentability, enforceability, availability of injunctive relief and damages may make it more difficult for us to procure, maintain and enforce patents. In addition, the America Invents Act was signed into law in September 2011, which among other changes to the U.S. patent laws, changes patent priority from “first to invent” to “first to file,” implements a post-grant opposition system for patents and provides a prior user defense to infringement. These judicial and legislative changes have introduced significant uncertainty in the patent law landscape and may potentially negatively impact our ability to procure, maintain and enforce patents to provide exclusivity for our products.

We also rely upon trade secrets, technical know-how and continuing technological innovation to develop and maintain our competitive position. We require our employees, consultants, advisors and collaborators to execute appropriate confidentiality and assignment-of-inventions agreements with us. These agreements typically provide that all materials and confidential information developed or made known to the individual during the course of the individual’s relationship with us is to be kept confidential and not disclosed to third parties except in specific circumstances, and that all inventions arising out of the individual’s relationship with us will be our exclusive property. These agreements may be breached, and in some instances, we may not have an appropriate remedy available for breach of the agreements. Furthermore, our competitors may independently develop substantially equivalent proprietary information and techniques, reverse engineer our information and techniques, or otherwise gain access to our proprietary technology.

We may be unable to meaningfully protect our rights in trade secrets, technical know-how and other non-patented technology. We may have to resort to litigation to protect our intellectual property rights, or to determine their scope, validity or enforceability. In addition, interference, derivation, post-grant oppositions, and similar proceedings may be necessary to determine rights to inventions in our patents and patent applications. Enforcing or defending our proprietary rights is expensive, could cause diversion of our resources and may be unsuccessful. Any failure to enforce or protect our rights could cause us to lose the ability to exclude others from using our technology to develop or sell competing products.

Our collaboration agreements may depend on our intellectual property

We are party to collaborative agreements with Pain Therapeutics, King (now Pfizer), Zogenix and Impax among others. Our third-party collaborators have entered into these agreements based on the exclusivity that our intellectual property rights confer on the products being developed. The loss or diminution of our intellectual property rights could result in a decision by our third-party collaborators to terminate their agreements with us. In addition, these agreements are generally complex and contain provisions that could give rise to legal disputes, including potential disputes concerning ownership of intellectual property and data under collaborations. Such disputes can lead to lengthy, expensive litigation or arbitration requiring us to devote management time and resources to such dispute which we would otherwise spend on our business. To the extent that our agreements call for future royalties to be paid conditional on our having patents covering the royalty-bearing subject matter, the decision by the Supreme Court in the case of MedImmune v. Genentech could encourage our licensees to challenge the validity of our patents and thereby seek to avoid future royalty obligations without losing the benefit of their license. Should they be successful in such a challenge, our ability to collect future royalties could be substantially diminished.

We may be sued by third parties claiming that our product candidates infringe on their intellectual property rights, particularly because there is substantial uncertainty about the validity and breadth of medical patents

We or our collaborators may be exposed to future litigation by third parties based on claims that our product candidates or activities infringe the intellectual property rights of others or that we or our collaborators have misappropriated the trade secrets of others. This risk is exacerbated by the fact that the validity and breadth of claims covered in medical technology patents and the breadth and scope of trade secret protection involve complex legal and factual questions for which important legal principles are unresolved. Any litigation or claims against us or our collaborators, whether or not valid, could result in substantial costs, could place a significant strain on our financial resources and could harm our reputation. We also may not have sufficient funds to litigate against parties with substantially greater resources. In addition, pursuant to our collaborative agreements, we have provided our collaborators with the right, under specified circumstances, to defend against any claims of infringement of the third party intellectual property rights, and such collaborators may not defend against such claims adequately or in the manner that we would do ourselves. Intellectual property litigation or claims could force us or our collaborators to do one or more of the following, any of which could harm our business or financial results:

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cease selling, incorporating or using any of our pharmaceutical product candidates that incorporate the challenged intellectual property, which would adversely affect our revenue;

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obtain a license from the holder of the infringed intellectual property right, which license may be costly or may not be available on reasonable terms, if at all; or

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redesign our product candidates, which would be costly and time-consuming.

Technologies and businesses which we acquire or license may be difficult to integrate, disrupt our business, dilute stockholder value or divert management attention

We may acquire technologies, products or businesses to broaden the scope of our existing and planned product lines and technologies. Future acquisitions expose us to:

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increased costs associated with the acquisition and operation of the new businesses or technologies and the management of geographically dispersed operations;

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the risks associated with the assimilation of new technologies, operations, sites and personnel;

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the diversion of resources from our existing business and technologies;

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the inability to generate revenues to offset associated acquisition costs;

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the requirement to maintain uniform standards, controls, and procedures; and

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the impairment of relationships with employees and customers or third party collaborators as a result of any integration of new management personnel.

Acquisitions may also result in the issuance of dilutive equity securities, the incurrence or assumption of debt or additional expenses associated with the amortization of acquired intangible assets or potential businesses. Past acquisitions, such as our acquisitions of IntraEAR, ALZET, SBS and APT, as well as future acquisitions, may not generate any additional revenue or provide any benefit to our business.

Some of our pharmaceutical product candidates contain controlled substances, the making, use, sale, importation and distribution of which are subject to regulation by state, federal and foreign law enforcement and other regulatory agencies

Some of our product candidates currently under development contain, and our products in the future may contain, controlled substances which are subject to state, federal and foreign laws and regulations regarding their manufacture, use, sale, importation and distribution. The TRANSDUR-Sufentanil patch, REMOXY and our other ORADUR-based drug candidates, and certain other product candidates we have under development contain active ingredients which are classified as controlled substances under the regulations of the U.S. Drug Enforcement Agency. For our product candidates containing controlled substances, we and our suppliers, manufacturers, contractors, customers and distributors are required to obtain and maintain applicable registrations from state, federal and foreign law enforcement and regulatory agencies and comply with state, federal and foreign laws and regulations regarding the manufacture, use, sale, importation and distribution of controlled substances. These regulations are extensive and include regulations governing manufacturing, labeling, packaging, testing, dispensing, production and procurement quotas, record keeping, reporting, handling, shipment and disposal. These regulations increase the personnel needs and the expense associated with development and commercialization of drug candidates including controlled substances. Failure to obtain and maintain required registrations or comply with any applicable regulations could delay or preclude us from developing and commercializing our product candidates containing controlled substances and subject us to enforcement action. In addition, because of their restrictive nature, these regulations could limit our commercialization of our product candidates containing controlled substances. In particular, among other things, there is a risk that these regulations may interfere with the supply of the drugs used in our clinical trials, and in the future, our ability to produce and distribute our products in the volume needed to meet commercial demand.

Write-offs related to the impairment of long-lived assets, inventories and other non-cash charges, as well as stock-based compensation expenses may adversely impact or delay our profitability

We may incur significant non-cash charges related to impairment write-downs of our long-lived assets, including goodwill and other intangible assets. We will continue to incur non-cash charges related to amortization of other intangible assets. For example, we had a $13.5 million non-cash write-down of deferred royalties and commercial rights related to CHRONOGESIC in the fourth quarter of 2008. We are required to perform periodic impairment reviews of our goodwill at least annually. The carrying value of goodwill on our balance sheet was $6.4 million at March 31, 2014. To the extent these reviews conclude that the expected future cash flows generated from our business activities are not sufficient to recover the cost of our long-lived assets, we will be required to measure and record an impairment charge to write-down these assets to their realizable values. We completed our last review during the fourth quarter of 2013 and determined that goodwill was not impaired as of December 31, 2013. However, there can be no assurance that upon completion of subsequent reviews a material impairment charge will not be recorded. If future periodic reviews determine that our assets are impaired and a write-down is required, it will adversely impact or delay our profitability.

Inventories include certain excipients that are sold to a customer and included in products awaiting regulatory approval. These inventories are capitalized based on management’s judgment of probable sale prior to their expiration date which in turn is based on non-binding forecasts from our customer. The valuation of inventory requires us to estimate the value of inventory that may become expired prior to use. We may be required to expense previously capitalized inventory costs upon a change in our judgment, due to, among other potential factors, a denial or delay of approval of our customer’s product by the necessary regulatory bodies, or new information that suggests that the inventory will not be saleable. In addition, these circumstances may cause us to record a liability related to minimum purchase agreements that we have in place for raw materials.

Global credit and financial market conditions could negatively impact the value of our current portfolio of cash equivalents, short-term investments or long-term investments and our ability to meet our financing objectives

Our cash and cash equivalents are maintained in highly liquid investments with remaining maturities of 90 days or less at the time of purchase. Our short-term investments consist primarily of readily marketable debt securities with original maturities of greater than 90 days from the date of purchase but remaining maturities of less than one year from the balance sheet date. Our long-term investments consist primarily of readily marketable debt securities with maturities in one year or beyond from the balance sheet date. While, as of the date of this filing, we are not aware of any downgrades, material losses, or other significant deterioration in the fair value of our cash equivalents, short-term investments or long-term investments since March 31, 2014, no assurance can be given that deterioration in conditions of the global credit and financial markets would not negatively impact our current portfolio of cash equivalents, short-term investments or long-term investments or our ability to meet our financing objectives.

We depend upon key personnel who may terminate their employment with us at any time, and we may need to hire additional qualified personnel

Our success will depend to a significant degree upon the continued services of key management, technical and scientific personnel, including Felix Theeuwes, our Chairman and Chief Scientific Officer, and James E. Brown, our President and Chief Executive Officer. In addition, our success will depend on our ability to attract and retain other highly skilled personnel. Competition for qualified personnel is intense, and the process of hiring and integrating such qualified personnel is often lengthy. We may be unable to recruit such personnel on a timely basis, if at all. Our management and other employees may voluntarily terminate their employment with us at any time. The loss of the services of key personnel, or the inability to attract and retain additional qualified personnel, could result in delays to product development or approval, loss of sales and diversion of management resources.

We may not successfully manage our company through varying business cycles

Our success will depend on properly sizing our company through growth and contraction cycles caused in part by changing business conditions, which places a significant strain on our management and on our administrative, operational and financial resources. To manage through such cycles, we must expand or contract our facilities, our operational, financial and management systems and our personnel. If we were unable to manage growth and contractions effectively our business would be harmed.

Our business involves environmental risks and risks related to handling regulated substances

In connection with our research and development activities and our manufacture of materials and pharmaceutical product candidates, we are subject to federal, state and local laws, rules, regulations and policies governing the use, generation, manufacture, storage, air emission, effluent discharge, handling and disposal of certain materials, biological specimens and wastes. Although we believe that we have complied with the applicable laws, regulations and policies in all material respects and have not been required to correct any material noncompliance, we may be required to incur significant costs to comply with environmental and health and safety regulations in the future. Our research and development involves the use, generation and disposal of hazardous materials, including but not limited to certain hazardous chemicals, solvents, agents and biohazardous materials. The extent of our use, generation and disposal of such substances has increased substantially since we started manufacturing and selling biodegradable polymers. Although we believe that our safety procedures for storing, handling and disposing of such materials comply with the standards prescribed by state and federal regulations, we cannot completely eliminate the risk of accidental contamination or injury from these materials. We currently contract with third parties to dispose of these substances generated by us, and we rely on these third parties to properly dispose of these substances in compliance with applicable laws and regulations. If these third parties do not properly dispose of these substances in compliance with applicable laws and regulations, we may be subject to legal action by governmental agencies or private parties for improper disposal of these substances. The costs of defending such actions and the potential liability resulting from such actions are often very large. In the event we are subject to such legal action or we otherwise fail to comply with applicable laws and regulations governing the use, generation and disposal of hazardous materials and chemicals, we could be held liable for any damages that result, and any such liability could exceed our resources.

Our corporate headquarters, manufacturing facilities and personnel are located in a geographical area that is seismically active

Our corporate headquarters, primary manufacturing facilities and personnel are located in a geographical area that is known to be seismically active and prone to earthquakes. Should such a natural disaster occur, our ability to conduct our business could be severely restricted, and our business and assets, including the results of our research, development and manufacturing efforts, could be destroyed.

Risks Related To Our Industry

The market for our pharmaceutical product candidates is rapidly changing and competitive, and new products or technologies developed by others could impair our ability to grow our business and remain competitive

The pharmaceutical industry is subject to rapid and substantial technological change. Developments by others may render our product candidates under development or technologies noncompetitive or obsolete, or we may be unable to keep pace with technological developments or other market factors. Technological competition in the industry from pharmaceutical and biotechnology companies, universities, governmental entities and others diversifying into the field is intense and is expected to increase.

We may face competition from other companies in numerous industries including pharmaceuticals, medical devices and drug delivery. POSIDUR, TRANSDUR-Sufentanil, ELADUR, Relday, REMOXY and other ORADUR-based drug candidates, if approved, will compete with currently marketed oral opioids, transdermal opioids, local anesthetic patches, anti-psychotics, stimulants, implantable and external infusion pumps which can be used for infusion of opioids and local anesthetics. Products of these types are marketed by Purdue Pharma, Knoll, Janssen, Medtronic, Endo, AstraZeneca, Arrow International, Tricumed, Kimberly-Clark, Cumberland Pharmaceuticals, Pacira, Acorda Therapeutics, Mallinckrodt, Shire, Johnson & Johnson, Eli Lilly, Pfizer, Novartis and others. Our ORADUR-ADHD product candidates, if approved, will compete with currently marketed or approved products by Shire, Johnson & Johnson, UCB, Novartis, Noven, Celgene, Eli Lilly, Pfizer and others. Relday, if approved, will compete with currently marketed products by Johnson & Johnson, Eli Lilly, Astra Zeneca, Pfizer, Bristol-Myers Squibb and others. Numerous companies are applying significant resources and expertise to the problems of drug delivery and several of these are focusing or may focus on delivery of drugs to the intended site of action, including Alkermes, Pacira, Immune Pharmaceuticals, Innocoll, Nektar, Kimberly-Clark, Acorda Therapeutics, Flamel, Alexza, Hospira, Cumberland Pharmaceuticals, Egalet, Acura, Elite Pharmaceuticals, Phosphagenics, Intellipharmaceutics, Collegium Pharmaceutical, Heron Therapeutics and others. Some of these competitors may be addressing the same therapeutic areas or indications as we are. Our current and potential competitors may succeed in obtaining patent protection or commercializing products before us. Many of these entities have significantly greater research and development capabilities than we do, as well as substantially more marketing, manufacturing, financial and managerial resources. These entities represent significant competition for us. Acquisitions of, or investments in, competing pharmaceutical or biotechnology companies by large corporations could increase such competitors’ research and development, financial, marketing, manufacturing and other resources.

We are engaged in the development of novel therapeutic technologies. Our resources are limited and we may experience technical challenges inherent in such novel technologies. Competitors have developed or are in the process of developing technologies that are, or in the future may be, the basis for competitive products. Some of these products may have an entirely different approach or means of accomplishing similar therapeutic effects than our product candidates. Our competitors may develop products that are safer, more effective or less costly than our product candidates and, therefore, present a serious competitive threat to our product offerings.

The widespread acceptance of therapies that are alternatives to ours may limit market acceptance of our product candidates even if commercialized. Chronic and post-operative pain are currently being treated by oral medication, transdermal drug delivery systems, such as drug patches, injectable products and implantable drug delivery devices which will be competitive with our product candidates. These treatments are widely accepted in the medical community and have a long history of use. The established use of these competitive products may limit the potential for our product candidates to receive widespread acceptance if commercialized.

Our relationships with customers and third-party payors will be subject to applicable anti-kickback, fraud and abuse and other healthcare laws and regulations, which could expose us to criminal sanctions, civil penalties, contractual damages, reputational harm and diminished profits and future earnings

Healthcare providers, physicians and third-party payors will play a primary role in the recommendation and prescription of any product candidates for which we obtain marketing approval. Our future arrangements with third-party payors and customers may expose us to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we would market, sell and distribute our products. As a biotechnology company, even though we do not and will not control referrals of healthcare services or bill directly to Medicare, Medicaid or other third-party payors, federal and state healthcare laws and regulations pertaining to fraud and abuse and patients’ rights are and will be applicable to our business. The Federal healthcare Anti-Kickback Statute will constrain our marketing practices, educational programs, pricing policies, and relationships with healthcare providers or other entities, by prohibiting, among other things, persons from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, order or recommendation of, any good or service, for which payment may be made under a federal healthcare program such as Medicare and Medicaid. Federal civil and criminal false claims laws and civil monetary penalty laws impose criminal and civil penalties, including through civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting, or causing to be presented, to the federal government, including the Medicare and Medicaid programs, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government. The federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program and also created federal criminal laws that prohibit knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statements in connection with the delivery of or payment for healthcare benefits, items or services. HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, or HITECH, also imposes obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information. The federal physician sunshine requirements under the Affordable Care Act requires manufacturers of drugs, devices, biologics and medical supplies to report annually to HHS information related to payments and other transfers of value to physicians, other healthcare providers, and teaching hospitals, and ownership and investment interests held by physicians and other healthcare providers and their immediate family members and applicable group purchasing organizations. Analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws, may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers; some state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government and may require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures. State and foreign laws also govern the privacy and security of health information in specified circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts. Efforts to ensure that our business arrangements with third parties will comply with applicable healthcare laws and regulations will involve substantial costs. It is possible that governmental authorities will conclude that our business practices may not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations. If our operations are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, damages, fines, imprisonment, exclusion from government funded healthcare programs, such as Medicare and Medicaid, and the curtailment or restructuring of our operations. If any physicians or other healthcare providers or entities with whom we expect to do business are found to not be in compliance with applicable laws, they may be subject to criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs.

Healthcare reform measures could hinder or prevent our product candidates’ commercial success.

In the United States, there have been, and we expect there will continue to be, a number of legislative and regulatory changes to the healthcare system that could affect our future revenue and profitability and the future revenue and profitability of our collaborators or potential collaborators. Federal and state lawmakers regularly propose and, at times, enact legislation that results in significant changes to the healthcare system, some of which is intended to contain or reduce the costs of medical products and services. For example, in March 2010, the President signed one of the most significant healthcare reform measures in decades, the Affordable Care Act. It contains a number of provisions, including those governing enrollment in federal healthcare programs, reimbursement changes and fraud and abuse measures, all of which will impact existing government healthcare programs and will result in the development of new programs. The Affordable Care Act, among other things:

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imposes a non-deductible annual fee on pharmaceutical manufacturers or importers who sell “branded prescription drugs”;

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increases the minimum level of Medicaid rebates payable by manufacturers of brand-name drugs from 15.1% to 23.1%;

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requires collection of rebates for drugs paid by Medicaid managed care organizations;

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addresses new methodologies by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected, and for drugs that are line extension products;

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requires manufacturers to participate in a coverage gap discount program, under which they must agree to offer 50% point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D; and

•

mandates a further shift in the burden of Medicaid payments to the states.

Other legislative changes have been proposed and adopted since the Affordable Care Act was enacted. For example, automatic reductions to several government programs were enacted during “sequestration”. These reductions included aggregate reductions to Medicare payments to providers of up to 2% per fiscal year, which went into effect on April 1, 2013. On January 2, 2013, President Obama signed into law the American Taxpayer Relief Act of 2012, or the ATRA, which, among other things, further reduced Medicare payments to several providers, including hospitals, imaging centers and cancer treatment centers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years. Additional state and federal healthcare reform measures may be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could result in reduced demand for our product candidates once approved or additional pricing pressures.

We could be exposed to significant product liability claims which could be time consuming and costly to defend, divert management attention and adversely impact our ability to obtain and maintain insurance coverage

The testing, manufacture, marketing and sale of our product candidates involve an inherent risk that product liability claims will be asserted against us. Although we are insured against such risks up to an annual aggregate limit in connection with clinical trials and commercial sales of our product candidates, our present product liability insurance may be inadequate and may not fully cover the costs of any claim or any ultimate damages we might be required to pay. Product liability claims or other claims related to our product candidates, regardless of their outcome, could require us to spend significant time and money in litigation or to pay significant damages. Any successful product liability claim may prevent us from obtaining adequate product liability insurance in the future on commercially desirable or reasonable terms. In addition, product liability coverage may cease to be available in sufficient amounts or at an acceptable cost. An inability to obtain sufficient insurance coverage at an acceptable cost or otherwise to protect against potential product liability claims could prevent or inhibit the commercialization of our product candidates. A product liability claim could also significantly harm our reputation and delay market acceptance of our product candidates.

Acceptance of our pharmaceutical product candidates in the marketplace is uncertain, and failure to achieve market acceptance will delay our ability to generate or grow revenues

Our future financial performance will depend upon the successful introduction and customer acceptance of our products in research and development, including REMOXY and other ORADUR-based drug candidates, POSIDUR, ELADUR, Relday and TRANSDUR-Sufentanil. Even if approved for marketing, our product candidates may not achieve market acceptance. The degree of market acceptance will depend upon a number of factors, including:

•

the receipt of regulatory clearance of marketing claims for the uses that we are developing;

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the establishment and demonstration in the medical community of the safety and clinical efficacy of our products and their potential advantages over existing therapeutic products, including oral medication, transdermal drug delivery products such as drug patches, or external or implantable drug delivery products; and

•

pricing and reimbursement policies of government and third-party payors such as insurance companies, health maintenance organizations, hospital formularies and other health plan administrators.

Physicians, patients, payors or the medical community in general may be unwilling to accept, utilize or recommend any of our products. If we are unable to obtain regulatory approval, commercialize and market our future products when planned and achieve market acceptance, we will not achieve anticipated revenues.

If users of our products are unable to obtain adequate reimbursement from third-party payors, or if new restrictive legislation is adopted, market acceptance of our products may be limited and we may not achieve anticipated revenues

The continuing efforts of government and insurance companies, health maintenance organizations and other payors of healthcare costs to contain or reduce costs of health care may affect our future revenues and profitability, and the future revenues and profitability of our potential customers, suppliers and third-party collaborators and the availability of capital. For example, in certain foreign markets, pricing or profitability of prescription pharmaceuticals is subject to government control. In the United States, recent federal and state government initiatives have been directed at lowering the total cost of health care, and the U.S. Congress and state legislatures will likely continue to focus on health care reform, the cost of prescription pharmaceuticals and on the reform of the Medicare and Medicaid systems. While we cannot predict whether any such legislative or regulatory proposals will be adopted, the announcement or adoption of such proposals could materially harm our business, financial condition and results of operations.

The successful commercialization of our product candidates will depend in part on the extent to which appropriate reimbursement levels for the cost of our product candidates and related treatment are obtained by governmental authorities, private health insurers and other organizations, such as HMOs. Third-party payors are increasingly limiting payments or reimbursement for medical products and services. Also, the trend toward managed health care in the United States and the concurrent growth of organizations such as HMOs, which could control or significantly influence the purchase of health care services and products, as well as legislative proposals to reform health care or reduce government insurance programs, may limit reimbursement or payment for our products. The cost containment measures that health care payors and providers are instituting and the effect of any health care reform could materially harm our ability to operate profitably.

If we or our third-party collaborators are unable to train physicians to use our pharmaceutical product candidates to treat patients’ diseases or medical conditions, we may incur delays in market acceptance of our products

Broad use of our product candidates will require extensive training of numerous physicians on the proper and safe use of our product candidates. The time required to begin and complete training of physicians could delay introduction of our products and adversely affect market acceptance of our products. We or third parties selling our product candidates may be unable to rapidly train physicians in numbers sufficient to generate adequate demand for our product candidates. Any delay in training would materially delay the demand for our product candidates and harm our business and financial results. In addition, we may expend significant funds towards such training before any orders are placed for our products, which would increase our expenses and harm our financial results.

Potential new accounting pronouncements and legislative actions are likely to impact our future financial position or results of operations

Future changes in financial accounting standards may cause adverse, unexpected fluctuations in the timing of the recognition of revenues or expenses and may affect our financial position or results of operations. New pronouncements and varying interpretations of pronouncements have occurred with frequency and may occur in the future and we may make changes in our accounting policies in the future. Compliance with changing regulation of corporate governance and public disclosure may result in additional expenses. Changing laws, regulations and standards relating to corporate governance and public disclosure, including the Sarbanes-Oxley Act of 2002, new SEC regulations, PCAOB pronouncements and NASDAQ rules, are creating uncertainty for companies such as ours and insurance, accounting and auditing costs are high as a result of this uncertainty and other factors. We are committed to maintaining high standards of corporate governance and public disclosure. As a result, we intend to invest all reasonably necessary resources to comply with evolving standards, and this investment may result in increased general and administrative expenses and a diversion of management time and attention from revenue-generating activities to compliance activities.

Risks Related To Our Common Stock

Our stock price has in the past and may in the future not meet the minimum bid price for continued listing on the Nasdaq Global Market. Our ability to publicly or privately sell equity securities and the liquidity of our common stock could be adversely affected if we are delisted from The Nasdaq Global Market or if we are unable to transfer our listing to another stock market

On January 16, 2013, we received written notification from Nasdaq informing us that because the closing bid price of our common stock was below $1.00 for 30 consecutive trading days, our shares no longer complied with the minimum closing bid price requirement for continued listing on the Nasdaq Global Market under Nasdaq Marketplace Rule 5450(a)(1). We were given a 180-day period, until July 15, 2013, to regain compliance with Nasdaq’s listing requirements by having the closing bid price of our common stock listed on Nasdaq be at least $1.00 for at least 10 consecutive trading days.

While we regained compliance within the applicable time period as of February 1, 2013, if our shares again no longer comply with the minimum closing bid price requirement for continued listing on the Nasdaq Global Market under Nasdaq Marketplace Rule 5450(a)(1) and we do not regain compliance within the applicable 180-day time period, we may transfer our common stock listing to The Nasdaq Capital Market, provided that the Company (i) meets the applicable market value of publicly held shares requirement for continued listing and all other applicable requirements for initial listing on The Nasdaq Capital Market (except for the closing bid price requirement) based on the Company’s most recent public filings and market information and (ii) notifies Nasdaq of its intent to cure this deficiency. Following a transfer to The Nasdaq Capital Market, the Company would be afforded the remainder of an additional 180 calendar day grace period in order to regain compliance with the minimum closing bid price requirement of $1.00 per share under The Nasdaq Capital Market, unless it does not appear to NASDAQ that it would be possible for the Company to cure the deficiency.

If compliance is not demonstrated within the applicable compliance period, Nasdaq will notify the Company that its securities will be subject to delisting. The Company may appeal Nasdaq’s determination to delist its securities to a Hearings Panel. During any appeal process, shares of the Company’s common stock would continue to trade on the Nasdaq Global Market or Nasdaq Capital Market, as applicable.

There can be no assurance that we will maintain or regain compliance with the requirements for listing our common stock on the Nasdaq Global Market or that our common stock would be eligible for transfer to the Nasdaq Capital Market and remain in compliance with the requirements for listing on that market. Delisting from Nasdaq could adversely affect our ability to raise additional financing through the public or private sale of equity securities, would significantly affect the ability of investors to trade our securities and would negatively affect the value and liquidity of our common stock. Delisting could also have other negative results, including the potential loss of confidence by employees, the loss of institutional investor interest and fewer business development opportunities.

Our operating history makes evaluating our stock difficult

Our quarterly and annual results of operations have historically fluctuated and we expect will continue to fluctuate for the foreseeable future. We believe that period-to-period comparisons of our operating results should not be relied upon as predictive of future performance. Our prospects must be considered in light of the risks, expenses and difficulties encountered by companies with no approved pharmaceutical products, particularly companies in new and rapidly evolving markets such as pharmaceuticals, drug delivery and biotechnology. To address these risks, we must, among other things, obtain regulatory approval for and commercialize our product candidates, which may not occur. We may not be successful in addressing these risks and difficulties. We may require additional funds to complete the development of our product candidates and to fund operating losses to be incurred in the next several years.

Investors may experience substantial dilution of their investment

Investors may experience dilution of their investment if we raise capital through the sale of additional equity securities or convertible debt securities or grant additional stock options to employees and consultants. In December 2013, we filed a new shelf registration statement on Form S-3 with the SEC, which upon being declared effective in January 2014, allowed us to offer up to $100.9 million of securities from time to time in one or more public offerings of our common stock. In addition, we entered into a Controlled Equity Offering ^SM sales agreement with Cantor Fitzgerald & Co., (Cantor Fitzgerald), under which we may sell, subject to certain limitations, up to $25 million of common stock through Cantor Fitzgerald, acting as agent. Any sales in the public market of the common stock issuable upon such conversion could adversely affect prevailing market prices for our common stock.

The price of our common stock may be volatile

The stock markets in general, and the markets for pharmaceutical stocks in particular, have experienced extreme volatility that has often been unrelated to the operating performance of particular companies. These broad market fluctuations may adversely affect the trading price of our common stock.

Price declines in our common stock could result from general market and economic conditions and a variety of other factors, including:

•

failure of our third-party collaborators to successfully develop and commercialize the respective product candidates they are developing;

•

adverse results (including adverse events or failure to demonstrate safety or efficacy) or delays in our clinical and non-clinical trials of POSIDUR, REMOXY or our other ORADUR-based drug candidates, ELADUR, Relday, TRANSDUR-Sufentanil or other product candidates;

•

announcements of FDA non-approval of our product candidates, or delays in the FDA or other foreign regulatory agency review process;

•

adverse actions taken by regulatory agencies or law enforcement agencies with respect to our product candidates, clinical trials, manufacturing processes or sales and marketing activities, or those of our third party collaborators;

•

announcements of technological innovations, patents, product approvals or new products by our competitors;

•

regulatory, judicial and patent developments in the United States and foreign countries;

•

any lawsuit involving us or our product candidates including intellectual property infringement or product liability suits;

•

announcements concerning our competitors, or the biotechnology or pharmaceutical industries in general;

•

developments concerning our strategic alliances or acquisitions;

•

actual or anticipated variations in our operating results;

•

changes in recommendations by securities analysts or lack of analyst coverage;

•

deviations in our operating results from the estimates of analysts;

•

sales of our common stock by our executive officers or directors or sales of substantial amounts of common stock by others;

•

potential failure to meet continuing listing standards from The NASDAQ Global Market;

•

loss or disruption of facilities due to natural disasters;

•

changes in accounting principles; or

•

loss of any of our key scientific or management personnel.

The market price of our common stock may fluctuate significantly in response to factors which are beyond our control. The stock market in general has recently experienced extreme price and volume fluctuations. In addition, the market prices of securities of technology and pharmaceutical companies have also been extremely volatile, and have experienced fluctuations that often have been unrelated or disproportionate to the operating performance of these companies. These broad market fluctuations could result in extreme fluctuations in the price of our common stock, which could cause a decline in the value of our common stock.

In the past, following periods of volatility in the market price of a particular company’s securities, litigation has often been brought against that company. If litigation of this type is brought against us, it could be extremely expensive and divert management’s attention and our company’s resources.

We have broad discretion over the use of our cash and investments, and their investment may not always yield a favorable return

Our management has broad discretion over how our cash and investments are used and may from time to time invest in ways with which our stockholders may not agree and that do not yield favorable returns.

Executive officers, directors and principal stockholders have substantial control over us, which could delay or prevent a change in our corporate control favored by our other stockholders

Our directors, executive officers and principal stockholders, together with their affiliates, have substantial control over us. The interests of these stockholders may differ from the interests of other stockholders. As a result, these stockholders, if acting together, could have the ability to exercise control over all corporate actions requiring stockholder approval irrespective of how our other stockholders may vote, including:

•

the election of directors;

•

the amendment of charter documents;

•

the approval of certain mergers and other significant corporate transactions, including a sale of substantially all of our assets; or

•

the defeat of any non-negotiated takeover attempt that might otherwise benefit the public stockholders.

Our certificate of incorporation, our bylaws and Delaware law contain provisions that could discourage another company from acquiring us

Provisions of Delaware law, our certificate of incorporation and bylaws may discourage, delay or prevent a merger or acquisition that stockholders may consider favorable, including transactions in which you might otherwise receive a premium for your shares. These provisions include:

•

authorizing the issuance of “blank check” preferred stock without any need for action by stockholders;

•

providing for a classified board of directors with staggered terms;

•

requiring supermajority stockholder voting to effect certain amendments to our certificate of incorporation and bylaws;

•

eliminating the ability of stockholders to call special meetings of stockholders;

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prohibiting stockholder action by written consent; and

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establishing advance notice requirements for nominations for election to the board of directors or for proposing matters that can be acted on by stockholders at stockholder meetings.

Item 2.

Unregistered Sales of Equity Securities and Use of Proceeds

None

Item 3.

Defaults Upon Senior Securities

None

Item 4.

Mine Safety Disclosures

None

Item 5.

Other Information

None

Item 6.

Exhibits



10.75*		Asset Transfer and License Agreement between the Company and Impax Laboratories, Inc effective January 3, 2014.

31.1		Rule 13a-14(a) Section 302 Certification of James E. Brown.

31.2		Rule 13a-14(a) Section 302 Certification of Matthew J. Hogan.

32.1		Certificate pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002 of James E. Brown.

32.2		Certificate pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002 of Matthew J. Hogan.

101.INS		XBRL Instance Document

101.SCH		XBRL Taxonomy Extension Schema Document

101.CAL		XBRL Taxonomy Extension Calculation Linkbase Document

101.DEF		XBRL Taxonomy Extension Definition Linkbase Document

101.LAB		XBRL Taxonomy Extension Labels Linkbase Document

101.PRE		XBRL Taxonomy Extension Presentation Linkbase Document

*	Confidential treatment requested with respect to certain portions of this Exhibit.

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the Registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.


DURECT CORPORATION

By:		/s/ J AMES E. B ROWN
		James E. Brown Chief Executive Officer

Date: May 2, 2014

By:

/s/ M ATTHEW J. H OGAN

Matthew J. Hogan

Chief Financial Officer and Principal

Accounting Officer

Date: May 2, 2014

EXHIBIT INDEX



10.75*		Asset Transfer and License Agreement between the Company and Impax Laboratories, Inc effective January 3, 2014.

31.1		Rule 13a-14(a) Section 302 Certification of James E. Brown.

31.2		Rule 13a-14(a) Section 302 Certification of Matthew J. Hogan.

32.1		Certificate pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002 of James E. Brown.

32.2		Certificate pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002 of Matthew J. Hogan.

101.INS		XBRL Instance Document+

101.SCH		XBRL Taxonomy Extension Schema Document

101.CAL		XBRL Taxonomy Extension Calculation Linkbase Document

101.DEF		XBRL Taxonomy Extension Definition Linkbase Document

101.LAB		XBRL Taxonomy Extension Labels Linkbase Document

101.PRE		XBRL Taxonomy Extension Presentation Linkbase Document

*	Confidential treatment requested with respect to certain portions of this Exhibit.

Exhibit 10.75

Confidential treatment has been sought for portions of this Agreement. The copy filed herewith omits the information subject to the confidential treatment request. Omissions are designated as * * *. A complete version of this exhibit has been filed separately with the Securities and Exchange Commission.

EXECUTION VERSION

CONFIDENTIAL

ASSET TRANSFER AND LICENSE AGREEMENT

This ASSET TRANSFER AND LICENSE AGREEMENT (the “ Agreement ”) is effective as of January 3, 2014 (the “ Effective Date ”) by and between Durect Corporation, a Delaware company having offices located at 10260 Bubb Road, Cupertino, CA 95014 (“ Durect ”) and Impax Laboratories, Inc., a Delaware company having offices at 30831 Huntwood Avenue, Hayward, CA 94544 (“ Impax ”). Impax and Durect are each referred to herein by name or, individually, as a “ Party ” or, collectively, as “ Parties .”

BACKGROUND

A. Durect owns and controls rights in and to its product known as Eladur®, which is a transdermal bupivacaine patch based on Durect’s proprietary TRANSDUR® transdermal delivery technology.

B. Impax desires to acquire certain assets and rights pertaining to Eladur® and obtain a license to Durect’s proprietary TRANSDUR® transdermal delivery technology and other intellectual property to develop and commercialize Eladur®, and Durect desires to transfer such assets and grant such a license to Impax.

NOW, THEREFORE, in consideration of the mutual covenants and agreements provided herein below and other consideration, the receipt and sufficiency of which is hereby acknowledged, Impax and Durect hereby agree as follows:

ARTICLE 1

DEFINITIONS

The following capitalized terms shall have the meanings given in this Article 1 when used in this Agreement:

1.1 “ Acquiring Entity ” shall mean a Third Party that merges or consolidates with or acquires a Party, or to which a Party transfers all or substantially all of its assets to which this Agreement pertains; and any such transaction is referred to herein below as a “ Subject Transaction ”; and any Affiliate of such Third Party other than those Persons which become Affiliates as a result of the Subject Transaction.

1.2 “ Affiliate ” shall mean with respect to a Person, any Person controlling, controlled by or under common control with such Person, for so long as such control exists. For purposes of this Section 1.2 only, “control” shall mean (i) direct or indirect ownership of fifty percent (50%) or more (or, if less than fifty percent (50%), the maximum ownership interest permitted by Applicable Laws) of the stock or shares having the right to vote for the election of directors of such corporate entity or (ii) the possession, directly or indirectly, of the power to direct, or cause the direction of, the management or policies of such entity, whether through the ownership of voting securities, by contract or otherwise.

1.3 “ Annual Net Sales ” shall mean, with respect to a particular calendar year, all Net Sales of Product in the Field in the Territory during such calendar year.

1.4 “ Applicable Laws ” shall mean any and all laws, ordinances, orders, rules, rulings, directives and regulations of any kind whatsoever of any governmental or regulatory authority within the applicable jurisdiction applicable to the Parties’ activities under this Agreement.

1.5 “ Assignment and Assumption Agreement ” means the Assignment and Assumption Agreement in the form attached hereto as Exhibit 1.5 .

1.6 “ Bill of Sale ” means the Bill of Sale in the form attached hereto as Exhibit 1.6 .

1.7 “ Bupivacaine ” shall mean bupivacaine [* * *].

1.8 “ Business Day ” shall mean any day other than a Saturday, Sunday or any other day on which commercial banks in New York, New York, United States are authorized or required by law to remain closed.

1.9 “cGMP” means the then-current standards for the manufacture of pharmaceutical products, pursuant to (a) the FD&C Act (21 U.S.C. 321 et seq.); (b) relevant United States regulations in Title 21 of the United States Code of Federal Regulations (including Parts 11, 210, and 211); (c) EC Directive 2003/94 EC of October 8, 2003; (d) the EC Guide to Good Manufacturing Practice for Medicinal Intermediate Products; (e) International Conference on Harmonization (ICH) ICH Q7A Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients; and (f) all additional Regulatory Authority documents or regulations that replace, amend, modify, supplant or complement any of the foregoing.

1.10 “ Commercialization ” shall mean, with respect to a product, any and all processes and activities conducted to establish and maintain sales for such product (including with respect to reimbursement and patient access), including offering for sale, detailing, selling (including launch), marketing (including education and advertising activities), promoting, storing, transporting, distributing, and importing such product, but shall exclude Development of such product. For clarity, Commercialization shall include the manufacture of a product in support of the foregoing processes and activities, to the extent not included in the definition of Development. “ Commercialize ” and “ Commercializing ” shall have their correlative meanings.

1.11 “ Commercially Reasonable Efforts ” shall mean, with respect to a Party, the efforts and resources normally applied by [* * *].

1.12 “ Competing Product ” shall mean [* * *].

1.13 “ Control ” shall mean, with respect to any particular Know-How or a particular Patent, possession by the Party granting the applicable right, license or sublicense to the other Party as provided herein of the power and authority, whether arising by ownership, license, or other authorization, to disclose and deliver the particular Know-How to the other Party, and to grant and authorize under such Know-How or Patent the right, license or sublicense, as applicable, of the scope granted to such other Party in this Agreement without giving rise to any violation of the terms of any written agreement with any Third Party. “ Controlled ” and “ Controlling ” shall have their correlative meanings. Notwithstanding anything to the contrary in this Agreement, the following shall not be deemed to be Controlled by Durect or its Affiliates for purposes of this Agreement: (i) any Know-How or Patent owned or licensed by any Acquiring Entity immediately prior to the effective date of the Subject Transaction and that was not Controlled by Durect immediately prior to the Subject Transaction and (ii) [* * *].

1.14 “ Cover ” shall mean, with respect to any subject matter, that the manufacture, use, sale, offering for sale, importation, exportation or other exploitation of such subject matter would infringe a claim of a Patent at the time thereof. For clarity with respect to a claim within a patent application, “Cover” includes infringing a claim in such patent application if it was issued as then prosecuted. “ Covered ” or “ Covering ” shall have their correlative meanings.

1.15 “Development ” shall mean, with respect to a product, any and all processes and activities conducted to obtain or maintain Marketing Approvals for such product, including preclinical testing, test method development and stability testing, toxicology, formulation, process development, quality assurance/control development, statistical analysis, clinical studies (including trials for additional indications for a product for which a Marketing Approval has been obtained), quality of life assessments, pharmacoeconomics, post-marketing studies, label expansion studies, regulatory affairs, and further activities relating to development or preparation of such product for Commercialization. For clarity, Development shall include the manufacture of any product in support of the foregoing processes and activities, including, to the extent applicable, any packaging, labeling and other finishing activities, quality control and assurance testing, formulation development and other activities performed in support of the CMC (chemistry, manufacturing and controls, or equivalent) section of any MAA, in each case with respect to such product. “ Develop ” and “ Developing ” shall have their correlative meanings.

1.16 “ EMA ” shall mean the European Medicines Agency, or any successor agency thereto.

1.17 [* * *].

1.18 [* * *].

1.19 “ FDA ” shall mean the United States Food and Drug Administration, or any successor agency thereto.

1.20 “ Field ” shall mean the treatment, management and prevention of all indications.

1.21 “ FTE Rate ” shall mean the hourly rate for Durect’s research and development personnel calculated in accordance with Exhibit 5.2.4 .

1.22 “ GAAP ” shall mean the generally accepted accounting principles of the United States.

1.23 “ Generic Product ” shall mean [* * *].

1.24 “ Know-How ” shall mean any and all nonpublic information and materials comprising (i) ideas, discoveries, inventions (including Patent data or descriptions), improvements or trade secrets, (ii) research and development data, such as medicinal chemistry data, preclinical data, pharmacology data, chemistry data (including analytical, product characterization, manufacturing, and stability data), toxicology data, clinical data (including investigator reports (both preliminary and final), statistical analyses, expert opinions and reports, safety and other electronic databases), analytical and quality control data and stability data, in each case together with supporting data, (iii) databases, practices, methods, techniques, specifications, formulations, formulae and knowledge, (iv) techniques, processes and manufacturing information, and (v) research materials, reagents and compositions of matter.

1.25 “ Liability ” shall mean any debt, obligation, duty or liability of any nature (whether fixed, contingent, potential or otherwise, and whether due or to become due, known or unknown, accrued or unaccrued), whether presently existing, or arising or asserted after the Closing.

1.26 “ Licensed Technology ” shall mean the Licensed Patents and Licensed Know-How.

1.26.1 “ Licensed Know-How ” shall mean any and all Know-How Controlled by Durect or its Affiliates during the Term that is reasonably necessary or useful for the Development or Commercialization of Product within the Field, excluding any Know-How included in the Transferred Assets. For the avoidance of doubt, any and all Know-How transferred by Durect to Impax pursuant to Section 5.1 of this Agreement that is not included in the Transferred Assets shall be deemed Licensed Know-How. Licensed Know-How shall also include Durect’s interest in [* * *] and [* * *] that are reasonably necessary or useful for the Development and Commercialization of a Product within the Field.

1.26.2 “ Licensed Patents ” shall mean any and all Patents Controlled by Durect or its Affiliates during the Term [* * *]. A list of Licensed Patents as of the Effective Date is appended hereto as Exhibit 1.26.2 (collectively with all Licensed Patents issuing therefrom or claiming priority (directly or indirectly) thereto, the “ Existing Licensed Patents ”) and will be updated periodically to reflect changes thereto during the Term. All Licensed Patents filed after the Effective Date that are not Existing Licensed Patents, [* * *], are referred to as the “ New Licensed Patents ”. [* * *].

1.27 [* * *].

1.28 “ MAA ” (Marketing Approval Application) shall mean a new drug application filed with the FDA as more fully defined in 21 C.F.R. §314.50 et. seq., or similar application or submission filed with or submitted to any Regulatory Authority to obtain permission to commence marketing and sales of a product in any particular jurisdiction.

1.29 “Major Market ” shall mean [* * *].

1.30 “ Marketing Approval ” shall mean, with respect to a product in a particular jurisdiction, approval or other permission by the applicable Regulatory Authorities sufficient to initiate marketing and sales of such product, including any applicable pricing and reimbursement approvals. For clarity, the Parties agree that, as of the Effective Date, the Marketing Approval with respect to a product in the United States does not include pricing or reimbursement approvals.

1.31 “ Net Sales ” shall mean gross amounts invoiced by Impax, its Affiliates and Sublicensees (each, a “ Selling Party ”) for sales of Product [* * *], less the following: (i) actual bad debts related to Product; (ii) normal and customary trade, quantity and cash discounts and any other adjustments, including those granted on account of price adjustments, billing errors, rejected goods, damaged or defective goods, recalls, returns, rebates, chargeback rebates, reimbursements or similar payments granted or given to wholesalers or other distributors, buying groups, health care insurance carriers or other institutions, and adjustments arising from consumer discount programs including coupons, in each case actually allowed and taken by the Third Party customer with respect to sales of Product; (iii) any payment in respect of sales of Product to any government (including any agency or department thereof) or with respect to any government-subsidized program or managed care organization; (iv) sales taxes or similar taxes, including duties or other governmental charges imposed on the sale of Product to the Third Party customer (including value added taxes or other governmental charges otherwise measured by the billing amount, but excluding any taxes imposed on or measured by the net income or profits of the Selling Party), to the extent included in the invoice price and not reimbursable, refundable or creditable to the Selling Party; and (v) prepaid freight, insurance and handling fees actually invoiced (to the extent that the Selling Party actually incurs the cost of freight, insurance and handling fees for Product that are not reimbursable, refundable or creditable to the Selling Party), in each case of (i) through (v) as determined from books and records of the Selling Party maintained in accordance with GAAP. Sales of Product between or among Impax, its Affiliates and Sublicensees shall be excluded from the computation of Net Sales if such sales are not intended for end use, but Net Sales shall include the subsequent final sales to Third Party customers by Impax or any such Affiliates or Sublicensees. Net Sales shall not include any disposition or sales of Products supplied (a) for use in clinical trials of Products, (b) under compassionate use or other reduced pricing programs, or (c) for promotional sampling.

1.32 “ Orange Book-Listed Patent ” shall mean, with respect to United States, a Licensed Patent listed for the Product in the FDA publication entitled “Approved Drug Products with Therapeutic Equivalence Evaluations,” or any replacement thereof established or approved by the FDA (the “ Orange Book ”), pursuant to 21 U.S.C. § 355(b)(1) and with respect to a foreign jurisdiction, a Licensed Patent listed in any foreign counterpart of the Orange Book pursuant to Applicable Laws in such foreign jurisdiction.

1.33 “ Patent ” shall mean any of the following, whether existing now or in the future anywhere in the world: (i) any issued patent, including inventor’s certificates, substitutions, extensions, confirmations, reissues, re-examination, renewal or any like governmental grant for protection of inventions; and (ii) any pending application for any of the foregoing, including any continuation, divisional, substitution, continuations-in-part, provisional and converted provisional applications.

1.34 “ Person ” shall mean any individual, corporation, partnership, association, joint-stock company, trust, unincorporated organization, government or political subdivision thereof or any other entity.

1.35 “ Phase Ib Clinical Trial ” shall mean any human clinical trial, typically conducted in healthy volunteers, the primary purpose of which is to characterize pharmacokinetics, pharmacodynamics and mechanism of action of an investigational drug in humans.

1.36 “ Phase III Clinical Trial ” shall mean any human clinical trial conducted in any country on a sufficient number of patients that is designed (a) if the defined end-points are met, to establish efficacy of a pharmaceutical product in patients with the indication being studied for purposes of filing a MAA or (b) to otherwise be a pivotal trial for obtaining a Marketing Approval or label expansion for such pharmaceutical product or (c) to otherwise be generally consistent with 21 C.F.R. §312.21(c).

1.37 “ Product ” shall mean any transdermal patch containing Bupivacaine as the sole active ingredient, including Eladur® as further described in [* * *].

1.38 “ Product-Specific Patents ” shall mean (a) the Licensed Patents listed on Exhibit 1.38 and (b) [* * *].

1.39 “ Prosecution and Maintenance ” shall mean, with respect to a Patent, the preparing, filing, prosecuting and maintenance of such Patent, as well as re-examinations, reissues, requests for Patent term extensions and the like with respect to such Patent, together with the conduct of interferences, the defense of oppositions and other similar proceedings with respect to the particular Patent; and “ Prosecute and Maintain ” shall have the correlative meaning.

1.40 [* * *].

1.41 “ Regulatory Authority ” shall mean any federal, national, multinational, state, provincial or local regulatory agency, department, bureau or other governmental entity with authority over the Development, Commercialization or other use or exploitation (including the granting of Marketing Approvals) of Product in any jurisdiction, including the FDA, EMA, and the Ministry of Health, Labor and Welfare in Japan or successor agency thereto (“ MHLW ”).

1.42 “ Regulatory Filing ” shall mean any filing or application with any Regulatory Authority, including MAAs and authorization, approvals or clearances arising from the foregoing, including Marketing Approvals, and all correspondence with the FDA or other relevant Regulatory Authority, as well as minutes of any material meetings, telephone conferences or discussions with the FDA or other relevant Regulatory Authority, in each case with respect to Product.

1.43 [* * *].

1.44 “ Sublicense Fee ” shall mean [* * *].

1.45 “ Sublicensee ” shall mean any Third Party to whom Impax has granted (directly or through multiple tiers) a sublicense under Licensed Technology in any country to (i) manufacture and sell (or otherwise Commercialize) Product or (ii) sell (or otherwise Commercialize) Product, [* * *]. For clarity, Sublicensee shall exclude distributors, wholesalers and resellers of Product.

1.46 “ Territory ” shall mean all of the countries and territories in the world.

1.47 “ Third Party ” shall mean any Person other than Impax, Durect or their respective Affiliates.

1.48 “ TRANSDUR® Technology ” shall mean Durect’s proprietary transdermal delivery technology as further described in Exhibit 1.48 [* * *].

1.49 “ Transferred Assets ” shall mean those assets listed on Exhibit 1.49 .

1.50 “ Transferred Contract ” shall mean any contract included in the Transferred Assets.

1.51 “ Upstream Agreements ” shall mean all agreements existing as of the Effective Date between Durect and a Third Party under which Durect obtains a license under any Licensed Technology (“ Upstream Licenses ”) or otherwise has any payment obligations with respect to the Development or Commercialization of any Product, excluding any Transferred Contracts. A list of Upstream Licenses is appended hereto as Exhibit 1.51 .

1.52 “ Valid Claim ” shall mean a claim of any issued, unexpired patent or a claim of a pending patent application that is being prosecuted in good faith, which claim does not claim priority to a filing date that is more than [* * *] years earlier than the then-current date, in each case which has not been dedicated to the public, disclaimed, abandoned or held invalid or unenforceable by a court or other government agency of competent jurisdiction in a decision from which no appeal can be taken or is otherwise not taken.

1.53 Additional Definitions . Each of the following definitions shall have the meanings defined in the corresponding sections of this Agreement indicated below:


Definitions		Section
Adverse Drug Reaction		5.4
Agreement		Preamble
ANDA Enforcement Action		7.5.2(a)
Bankrupt Party		12.3
[* * *]		[* * *]
[* * *]		*[ * ]*
Challenge		10.4
Closing		2.4
Commercialization Milestone Event		6.2.2
Commercialization Milestone Payment		6.2.2
Confidential Information		8.1
Defending Party		7.4
Development Milestone Event		6.2.1
Development Milestone Payment		6.2.1
Development Plan		5.2.2
Durect		Preamble
[* * *]		*[ * ]*
Durect Development Responsibilities		5.2.4(a)
Durect Indemnitees		9.4.2
[* * *]		*[ * ]*
Effective Date		Preamble
Enforcement Action		7.5.2(a)
Enforcing Party		7.5.5
*[ * ]*		*[ * ]*
Impax		Preamble


Definitions		Section
[* * *]		[* * *]
[* * *]		*[ * ]*
[* * *]		*[ * ]*
Indemnify		9.4.1
Infringing Product		7.5.1
JMC		3.1.1
[* * *]		*[ * ]*
Licensing Revenue		10.6.1
Losses		9.4.1
Party or Parties		Preamble
[* * *]		[* * *]
Prior CDA		8.3
Product Infringement		7.5.1
Product Trademarks		5.3.4(a)
Royalty Term		6.3.1
Sublicense Payment		6.4
[* * *]		[* * *]
Term		10.1
Third Party Infringement Action		7.4
Third-Party Claim		9.4.1
Transition Period		10.6.6
Upfront Payment		6.1

ARTICLE 2

ASSET PURCHASE

2.1 Transferred Assets . At the Closing, Durect shall convey, assign and transfer (and hereby conveys, assigns and transfers) to Impax, and Impax will (and hereby does) acquire and accept from Durect, all right, title and interest in and to the Transferred Assets.

2.2 Assumption of Liabilities . From and after the Closing, Impax will assume only those Liabilities to the extent related to the Transferred Assets and that arise following the Closing and prior to effectiveness of the assignment of such Transferred Assets back to Durect after termination of this Agreement. Durect will retain [* * *]. Impax will retain [* * *].

2.3 Further Assurances . From and after the Closing, each Party shall, promptly upon the request from time to time of the other Party and at such requesting Party’s expense, do each and every reasonable act, including executing requested documents and providing requested information, as may be necessary or reasonably desirable to effect an orderly transfer to Impax of the Transferred Assets.

2.4 Closing . The closing of the purchase and sale of the Transferred Assets (the “ Closing ”) shall be held in a mutually-agreed manner (in person at a location mutually agreed by the Parties, or by teleconference or email) on the Effective Date.

2.5 Durect Deliverables at Closing .

2.5.1 Ancillary Documents . At the Closing, Durect shall deliver or cause to be delivered to Impax the following documents executed by Durect:

(a) the Bill of Sale; and

(b) the Assignment and Assumption Agreement.

2.5.2 Tangible Materials and Records . Durect shall deliver to Impax within [* * *]. after the Closing, all of the books, data, documents, records, materials, and any other documents, materials and tangible property included in the Transferred Assets.

2.6 Impax Deliverable at Closing : At the Closing, Impax shall deliver to Durect the Assignment and Assumption Agreement executed by Impax and [* * *] as compensation for certain activities conducted by Durect at Impax’s request prior to the Closing.

2.7 Transfers of IND and Orphan Drug Designation . Within [* * *]. Durect shall submit to the FDA (a) a letter transferring sponsorship of [* * *] to Impax in a form substantially in the form of Exhibit 2.7(a) and (b) a letter transferring sponsorship of the orphan drug designation for the Product in post herpetic neuralgia to Impax in a form substantially in the form of Exhibit 2.7(b) . Within [* * *], Impax shall submit to the FDA (c) a letter accepting transfer of sponsorship of [* * *] to Impax in a form substantially in the form of Exhibit 2.7(c) and (d) a letter accepting transfer of sponsorship of the orphan drug designation for the Product in post herpetic neuralgia to Impax in a form substantially in the form of Exhibit 2.7(d) .

2.8 Excluded Assets . Except for the limited license and sublicense granted under Section 4.1, Impax shall not acquire any rights in any assets of Durect or any of its Affiliates other than the assets specifically included in the Transferred Assets.

ARTICLE 3

GOVERNANCE

3.1 Joint Management Committee .

3.1.1 Establishment . Promptly after the Effective Date, Impax and Durect shall establish a joint management committee (the “ JMC ”) to oversee, review and coordinate the activities of the Parties under this Agreement, including the Development and Commercialization of Product in the Territory.

3.1.2 Responsibilities . The JMC shall be responsible for: (i) overseeing, reviewing and monitoring the Parties’ activities under this Agreement; (ii) facilitating access to and the exchange of information between the Parties related to the Development and/or Commercialization of Product; (iii) reviewing and commenting on the Development Plan and any amendment thereto; and (iv) undertaking and/or approving such other matters as are specifically provided for the JMC under this Agreement.

3.1.3 Membership . The JMC shall be comprised of an equal number of representatives from each of Durect and Impax and unless otherwise agreed such number shall be three (3) employees from each Durect and Impax. Either Party may replace its respective JMC representatives at any time with prior notice to the other Party, [* * *]. Unless otherwise agreed by the Parties, the JMC shall have at least one representative with relevant decision-making authority from each Party such that the JMC is able to effectuate all of its decisions within the scope of its responsibilities. [* * *]. The Chairperson of the JMC shall be responsible for calling meetings, preparing and circulating an agenda in advance of each meeting (which agenda will include every matter reasonably requested by either Party), preparing and issuing minutes of each meeting within thirty (30) days thereafter, and resolving disputes under Section 3.3.

3.1.4 Termination . During the term of this Agreement, Durect shall have the right to terminate the JMC by providing thirty (30) days prior written notice to Impax, and Impax will thereafter have the sole right to make all decisions that were previously within the scope of the JMC’s responsibilities.

3.2 Meetings . The JMC shall hold meetings (either in person or by teleconference) at such times and places as the Parties may mutually agree, provided that, unless the Parties agree otherwise, the JMC shall meet at least [* * *] prior to the initiation of the first Phase III Clinical Trial of a Product, and thereafter, the JMC shall meet at least semiannually. Each Party shall bear its own costs associated with attending such meetings. As appropriate, other employees of the Parties may attend JMC meetings as nonvoting observers, but no Third Party personnel may attend unless otherwise agreed by the Parties, in which case such personnel shall be subject to written confidentiality obligations consistent with Article 8. Each Party may also call for special meetings to resolve particular matters requested by such Party.

3.3 Decision Making . Decisions of the JMC shall be made by consensus of the members present in person or by other means (e.g., teleconference) at any meeting, with at least one representative from each Party participating in such vote. The members of the JMC shall at all times use good faith efforts to reach consensus on matters properly referred to the JMC; however, in the event that the JMC is unable to reach consensus with respect to a particular matter despite such good faith efforts, then either Party may, by written notice to the other, refer the matter to the Chief Executive Officer of Durect and the President of Impax Pharmaceuticals for resolution by good faith discussions for a period of [* * *]. In the event such matter cannot be resolved by such good faith discussions within such [* * *], then the Chairperson shall have the final decision-making authority. Notwithstanding anything herein to the contrary, the JMC shall not have any authority to amend, modify or waive compliance with any term or condition of this Agreement or require that Durect incurs any expense or perform any activity not specifically provided for in this Agreement.

3.4 Day-to-Day Responsibilities . Each Party shall: (i) be responsible for day-to-day implementation and operation of the activities hereunder for which it has or is otherwise assigned responsibility under this Agreement, provided that such implementation is not inconsistent with the express terms of this Agreement or the decisions of the JMC within the scope of their authority specified herein; and (ii) keep the other Party informed as to the progress of such activities as reasonably requested by the other Party and as otherwise determined by the JMC.

ARTICLE 4

LICENSES AND EXCLUSIVITY

4.1 License Grant .

4.1.1 License to Product . Subject to the terms and conditions of this Agreement, Durect hereby grants to Impax (i) an exclusive (even as to Durect) license under the Licensed Technology, other than [* * *], solely to make, have made, use, import, sell, offer for sale and otherwise Develop and Commercialize Products in the Field in the Territory, and (ii) subject to the terms of the [* * *], an exclusive (even as to Durect) sublicense under Durect’s license to [* * *] solely to make, have made, use, import, sell, offer for sale and otherwise Develop and Commercialize Products that contain bupivacaine [* * *] in the Field in the Territory; in each case of (i) and (ii) subject only to Durect’s retained rights to conduct its obligations under this Agreement. Impax shall have the right to exercise such license and sublicense through its Affiliates, provided that Impax shall be responsible for the failure by its Affiliates to comply with, and Impax guarantees the compliance by each of its Affiliates with, the terms of this Agreement including all relevant restrictions, limitations and obligations. [* * *].

4.1.2 Sublicenses . The license and sublicense under Section 4.1.1 include the right to grant and authorize sublicenses within the scope thereof, through multiple tiers, to Third Parties [* * *], provided that:

(a) Impax shall promptly notify Durect of the grant of each sublicense, identifying the sublicensee and scope of the license granted, and provide Durect a copy of the final executed sublicense agreement, redacted for information not pertinent to Impax’s obligations under or compliance with this Agreement; and

(b) Subject to Sections 5.3.1 and 10.4, Impax shall be responsible for the failure by its Sublicensees to comply with the terms of this Agreement applicable to such Sublicensees, including all relevant restrictions, limitations and obligations; provided that [* * *].

4.2 No Other Rights . Each Party acknowledges that the rights and licenses granted under this Article 4 and elsewhere in this Agreement are limited to the scope expressly granted. Accordingly, except for the rights expressly granted or otherwise transferred under this Agreement, no right, title, or interest of any nature whatsoever is granted, whether by implication, estoppel, reliance, or otherwise, by either Party to the other Party. All rights with respect to Know-How, Patent or other intellectual property rights that are not specifically granted or otherwise transferred herein are reserved to the owner thereof.

4.3 Exclusivity of Efforts .

4.3.1 [* * *].

4.3.2 [* * *].

4.3.3 [* * *].

4.4 Conflicts of Interest . During the Term, if Impax or its Affiliate or Sublicensee sells Product to a Third Party to whom it also provides other products or services, Impax or such Affiliate or Sublicensee (as applicable) shall not price, discount or otherwise offer (including bundling) Product in any way that benefits such other products or services at the expense of Product or otherwise disadvantage Product.

4.5 [* * *].

ARTICLE 5

DEVELOPMENT AND COMMERCIALIZATION OF PRODUCT

5.1 Technology Transfer . Promptly after the execution of this Agreement, the Parties shall, through the JMC, establish an appropriate exchange process for the transfer of Licensed Know-How from Durect to Impax. Durect shall provide Impax with complete and accurate copies of all Licensed Know-How [* * *] after the Effective Date, and during the term of this Agreement, in the event Impax identifies any Licensed Know-How that has not been transferred by Durect to Impax, Durect shall promptly provide Impax with complete and accurate copies of all such Licensed Know-How that has not been transferred under this Section 5.1, within [* * *]. Each Party shall bear its own costs of conducting the technology transfer activities under this Section 5.1, provided that (i) Impax shall reimburse Durect for reasonable, documented out-of-pocket expenses incurred in connection with such technology transfer activities, and (ii) [* * *].

5.2 Development .

5.2.1 General . As between the Parties, Impax shall take the lead and be responsible for conducting Development activities for Product in the Field in the Territory, including clinical trials and other activities reasonably necessary to obtain Marketing Approvals for Product in the Field in each Major Market in the Territory, all in accordance with the Development Plan. It is understood and agreed that, as between the Parties, all Development efforts for Product in the Field in the Territory shall be at the sole expense of Impax, except as otherwise expressly provided in this Agreement or agreed by the Parties in writing.

5.2.2 Development Plan . [* * *] following the execution of this Agreement, Impax shall prepare a development plan in accordance with the outline attached hereto under Exhibit 5.2.2 , setting forth in reasonable detail the activities to be conducted under this Agreement for the Development of Product [* * *], including timeline therefor (such development plan, as may be updated from time to time, is hereinafter referred to as “ Development Plan ”). The Development Plan will reflect Impax’s reasonable estimate of activities necessary to obtain Marketing Approval, taking into consideration good development principles (including patient safety), based on Impax’s reasonable consideration of the input it receives from the FDA and from the EMA prior to commencing a Phase III Clinical Trial of a Product and, to the extent timely received, in Impax’s judgment, from the MHLW. The Development Plan shall include, among other things, activities related to CMC development, Marketing Approval strategy, validation activities associated with manufacturing of clinical supplies, process development and scale-up for providing clinical and commercial supplies. Impax shall, through the JMC (or directly in the event JMC has terminated), provide Durect an opportunity to review and comment on the Development Plan and any amendments thereto, which comments Impax shall consider in good faith.

5.2.3 Development Due Diligence . Impax (itself or through one or more of its Affiliates or Sublicensees) shall use Commercially Reasonable Efforts to: [* * *]. The Parties acknowledge and agree that Impax shall be deemed to have satisfied its obligations to use Commercially Reasonable Efforts under a particular clause in the preceding sentence if [* * *]. [* * *].

5.2.4 Durect Development Responsibilities .

(a) Durect Development Responsibilities . If requested by Impax and agreed to by Durect [* * *], Durect will perform certain development activities (“ Durect Development Responsibilities ”) on a project-by-project basis in accordance with a mutually agreed work plan, which will include milestones and deliverables for each project. [* * *].

(b) Payment . Impax shall pay Durect for its activities under the Development Plan at [* * *]. On or before [* * *] during the period of time Durect performs any Durect Development Responsibilities, Durect shall invoice Impax for the actual [* * *] incurred by Durect in performing the Durect Development Responsibilities during the preceding month and shall include with such invoice reasonable documentation thereof. To the extent the actual personnel charges incurred by Durect in [* * *] exceed the amount for [* * *], Impax shall pay Durect up to [* * *]

over the total amount for [* * *] but shall not be responsible for any portion over [* * *] of the amount for [* * *] unless such increase is otherwise approved by Impax. The Durect personnel involved in the performance of the Durect Development Responsibilities shall keep time sheets tracking the time each such individual spent working in support of the Durect Development Responsibilities. Additionally, Impax shall reimburse Durect for other [* * *] incurred [* * *]. Except as expressly provided herein, in no event shall Impax be responsible for any [* * *] in excess of the amount budgeted therefor unless such additional amount is otherwise approved in writing by Impax. Subject to this Section 5.2.4(b), Impax shall pay each invoice (except for any portion that is subject to a good-faith dispute) under this Section 5.2.4(b) within [* * *].

5.2.5 Development Data and Regulatory Filings . Impax shall, through the JMC (or directly, if JMC is terminated), keep Durect reasonably and routinely informed regarding progress with respect to the performance of activities pursuant to the Development Plan, including a summary of study results and conclusions generated therefrom, and provide Durect access to and copies of clinical, non-clinical and CMC reports arising from activities under the Development Plan. Upon Durect’s reasonable request, [* * *], Impax shall provide access to and an electronic copy of Regulatory Filings submitted or received by Impax, its Affiliates or Sublicensees with respect to Product. As between the Parties, [* * *].

5.3 Commercialization .

5.3.1 General . Impax agrees to, directly or through one or more of its Affiliates, use Commercially Reasonable Efforts [* * *]. The Parties acknowledge and agree that Impax shall be deemed to have satisfied its obligations in the preceding sentence to use Commercially Reasonable Efforts with respect to [* * *] if [* * *]. [* * *]. It is understood and agreed that, as between the Parties, Impax shall be solely responsible for all Commercialization efforts for Product in the Field in the Territory, at its sole expense.

5.3.2 Sublicensee(s) . To the extent applicable to the territory and scope of the applicable sublicense, Impax shall include in each sublicense agreement with each Sublicensee provisions (i) expressly requiring that such Sublicensee be bound by the specific applicable obligations set forth in Section 5.3.1, and (ii) granting Impax the right to terminate such sublicense agreement and the sublicense granted therein in the event of a material breach by such Sublicensee of such applicable obligations [* * *].

5.3.3 Commercialization Updates . Impax shall, through the JMC (or directly, if JMC is terminated), keep Durect appropriately and routinely informed regarding progress with respect to its Commercialization of the Product in the Territory.

5.3.4 Trademarks .

(a) Product Trademarks . Impax shall have the right to select Product names and all trademarks used in connection with the Commercialization of Product including special promotional or advertising taglines, in each case in the Territory (all such trademarks specific to Product and including all goodwill associated therewith, and all applications, registrations,

extensions and renewals relating thereto, shall be referred to as “ Product Trademarks ”). During the Term, Impax shall be the exclusive owner of Product Trademarks (including Eladur®), and shall be solely responsible for all expenses it incurs to register and maintain such Product Trademarks. Durect shall not challenge Impax’s ownership of, or the validity of “Eladur®” during the term of this Agreement.

(b) Reference to Durect as Licensor . To the extent permitted by Applicable Laws, at Durect’s election, the labels and packaging of Product and all promotional materials for Product shall include text identifying Durect as the licensor of Product and a Durect trademark selected by Durect to be placed in a size and location reasonably agreed to by the Parties, provided that such mark: (i) is used in a consistent and noticeable manner sufficient to constitute trademark usage under Applicable Law, (ii) is clearly identified as a trademark (i.e., through the use of a “®”, “™” or other appropriate identifier), and (iii) is not used as combination marks with other marks or trademarks.

(c) Trademark License . Durect hereby grants to Impax a limited right to use Durect’s trademark “TRANSDUR®” solely in connection with the sale and marketing of Products in the Field within the Territory in accordance with this Agreement. Impax shall consult with Durect as to appearance, placement and display of “TRANSDUR®” and shall follow Durect’s reasonable instructions and guidelines with respect thereto. Impax acknowledges that Durect retains sole ownership of “TRANSDUR ^® ”, including registrations and applications therefor and all the goodwill associated therewith. Impax shall not challenge Durect’s ownership of, or the validity of, “TRANSDUR®” during or after the term of this Agreement. Impax shall execute any documents that are reasonably required by Durect to confirm Durect’s ownership of “TRANSDUR®”, provided that [* * *]. All goodwill arising from any use of “TRANSDUR®” under this Agreement shall inure to the benefit of Durect.

5.4 Regulatory Matters . Except for those activities conducted by Durect in accordance with Section 5.2.4(a), which may include [* * *], Impax, its Affiliates or Sublicensees shall control and be solely responsible for, at its expense, filing, obtaining and maintaining all regulatory approvals (including Marketing Approvals) for Development and Commercialization of Product in the Field in the Territory and for all ongoing communications with the Regulatory Authorities with respect thereto from the Effective Date, including, without limitation: (a) filing, obtaining, maintaining and updating any MAAs and Marketing Approvals for Product; (b) reporting all Adverse Drug Reactions to the applicable Regulatory Authority in the Territory; (c) handling medical and technical complaints and disputes with the applicable Regulatory Authority, patients and physicians in the Territory; and (d) dealing with Product recalls. For purposes of this Agreement, “ Adverse Drug Reaction ” shall have the meaning as defined in the then-current guidelines and regulations promulgated by the ICH (International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use) and shall include any “Adverse Drug Experience” as defined in the then-current 21 C.F.R. §§ 312.32 and 314.80.

5.5 Reporting . Without limiting any other provisions of this Agreement, Impax shall keep Durect reasonably informed, through the JMC (or directly, if JMC is terminated), as to the progress of its activities with respect to the Development and Commercialization of Product or otherwise under this Article 5 and provide such information with respect thereto as designated by the JMC or as may be reasonably requested by Durect, through the JMC (or directly, if JMC is terminated). In addition, Impax shall notify the JMC (or Durect, if JMC is terminated) if it anticipates or there are material deviations from the then-current Development Plan(s), and shall discuss in good faith and keep Durect informed, through the JMC (or directly, if JMC is terminated), as to any actions that it intends or is taking with respect to such deviations.

ARTICLE 6

PAYMENTS

6.1 Upfront Payment . Within [* * *], Impax shall pay to Durect an upfront payment in the amount of Two Million Dollars ($2,000,000) (the “ Upfront Payment ”). The Upfront Payment shall be non-refundable, and shall not be creditable against any other amount due hereunder.

6.2 Milestone Payments .

6.2.1 Development Milestones . Upon [* * *] (each such event, a “ Development Milestone Event ”), Impax shall pay to Durect a payment (each, a “ Development Milestone Payment ”) equal to (a) for Development Milestone Events 2 and 3, the applicable amount set forth in the following table for such Development Milestone Event and (b) for Development Milestone Events 1 and 4, [* * *] on account of the achievement of such Development Milestone Event [* * *].


Development Milestone Event		Development Milestone Payment [* * *]
1. [* * *]		[* * *]
2. [* * *]		[* * *]
3. [* * *]		[* * *]
4. [* * *]		[* * *]

Each Development Milestone Payment will, if achieved, be paid one time only, regardless of [* * *]

6.2.2 Commercialization Milestones . Impax shall pay to Durect the amounts set forth in the following table (each, a “ Commercialization Milestone Payment ”) upon [* * *] (each, a “ Commercialization Milestone Event ”):


Commercialization Milestone Event		Commercialization Milestone Payment
1. [* * *]		[* * *]
2. [* * *]		[* * *]

[* * *].

6.2.3 Payment Terms . Impax shall notify Durect in writing within [* * *] of the achievement of each Development Milestone Event and pay the corresponding Development Milestone Payment [* * *]. Impax shall notify Durect in writing of achievement of each Commercialization Milestone Event within [* * *] and pay the corresponding Commercialization Milestone Payment [* * *]. For clarity, all milestone payments under this Section 6.2 shall be non-refundable and non-creditable.

6.3 Royalty Payments . Impax shall pay to Durect tiered royalties on Annual Net Sales of Products, as calculated by multiplying the applicable royalty rates set forth in the table below by the corresponding amount of incremental Annual Net Sales of Products in the applicable calendar year:


Annual Net Sales of Products		Royalty Rate
[* * *]		[* * *]
[* * *]		[* * *]
[* * *]		[* * *]

6.3.1 Royalty Term . On a country-by-country and Product-by-Product basis, Impax’s royalty obligation shall commence on the first commercial sale of such Product in such country and continue until [* * *] (the “ Royalty Term ”). Notwithstanding the foregoing, upon launch of one Generic Product for a Product in a country during the Royalty Term for such Product and country, the applicable royalty rate for Net Sales of such Product generated in such country shall be reduced by [* * *] of the applicable rate set forth in the table above in this Section 6.3 so long as at least one Generic Product is sold in such country during the remaining Royalty Term.

6.3.2 Royalty Stacking . If Impax or its Affiliates or Sublicensees enters into a license agreement with a Third Party pursuant to which it obtains licenses to Patents necessary for Impax, its Affiliates and/or Sublicensees to exercise Impax’s rights under this Agreement with respect to any Product in any country (including as a result of any patent infringement litigation), then, on a country-by-country and Product-by-Product basis, royalties payable to Durect for such Product in such country under this Section 6.3 during any calendar quarter may be reduced by the amount equal to [* * *] of all amounts payable to such Third Party in connection with the sale of such Product in such country during the same calendar quarter under such license agreement; provided that in no event shall the royalties payable to Durect for any Product in any country be reduced by more than [* * *] during any calendar quarter. [* * *].

6.3.3 Payment/Reports . All payments under this Section 6.3 shall be due and payable within [* * *] of the close of the calendar quarter during which the corresponding Net Sales are recognized. Together with any such payment, Impax shall deliver a report specifying on a country-by-country basis: (i) total gross invoiced amount from sales of Product by Impax and its Affiliates and Sublicensees; (ii) amounts deducted by category (e.g., normal and customary trade, cash and other discounts, allowances and credits actually allowed and taken directly with respect to sales of Product) from gross invoiced amounts to calculate Net Sales; (iii) Net Sales; and (iv) royalties payable. Without limiting the foregoing, upon Durect’s request (which requests shall be limited to the current calendar quarter and shall not be made more than [* * *] per calendar quarter), Impax agrees to provide to Durect, within [* * *] after the close of the applicable calendar quarter, with [* * *] during such calendar quarter and other information necessary for Durect to estimate the royalties payable under this Section 6.3 with respect to such calendar quarter.

6.3.4 Non-Monetary Consideration for Sale . Impax, its Affiliates and Sublicensees shall not accept or solicit any non-monetary consideration for the commercial sale of Product without the prior written consent of Durect, provided that the use by Impax, its Affiliates and Sublicensees of a customary and reasonable amount of Product for research and development, promotional sampling, compassionate use or donations shall not violate this Section 6.3.4.

6.4 Sublicense Payment . Impax shall pay to Durect [* * *] of Sublicense Fee received by Impax or its Affiliates (“ Sublicense Payment ”); provided, however, [* * *]. Impax shall pay to Durect the applicable Sublicense Payment within [* * *], together with a written statement setting forth in reasonable detail the calculation of the Sublicense Fee and Sublicense Payment.

6.5 Payment Method; Withholding Taxes . All payments due under this Agreement to Durect shall be made by bank wire transfer in immediately available funds to an account designated by Durect. All payments hereunder shall be made in the legal currency of the United States of America, and all references to “$” or “Dollars” shall refer to United States dollars. Except as otherwise provided herein, all payments due to Durect under this Agreement shall be due and payable within [* * *]. All amounts referenced hereunder are exclusive of any withholding tax or similar taxes. If any withholding tax or similar tax is due with respect to such a payment, Impax shall deduct such tax from the applicable payment and pay such tax to the applicable taxing authority, and Impax shall furnish to Durect appropriate evidence of payment of any tax or other amount required by Applicable Laws to be deducted from any royalty payment, including any tax or withholding levied by a foreign taxing authority in respect of the payment or accrual of any royalty. Notwithstanding the foregoing, if Impax transfers or assigns its rights under this Agreement or its rights in the Licensed Technology, transfers its domicile, or otherwise transfers its operations, such that the tax laws of a jurisdiction other than United States, or any subdivision thereof, impose any withholding tax or similar taxes with respect to amounts payable under this Agreement for which Durect is unable to recover fully or obtain full credit, then Impax will pay to Durect such amount of withholding

tax or similar taxes that cannot be fully recovered or credited by Durect. For purposes of determining if such amount is recoverable, Durect shall consider the entire carryover period and not only the year in which the withholding or similar tax applies. To the extent that Durect determines that the amounts are not fully recoverable, Durect shall provide reasonable documentation to Impax supporting its conclusion.

6.6 Inspection of Records . Impax shall, and shall cause its Affiliates and Sublicensees to, keep full and accurate books and records setting forth gross sales of Product, Net Sales of Product, itemized deductions from gross sales taken to calculate Net Sales and other amounts payable hereunder to Durect under this Article 6. Durect shall, and shall cause its Affiliates to, keep full and accurate books and records setting forth the [* * *], including hours worked and Third Party expenses incurred by Durect. Each Party shall permit the other Party, by independent qualified public accountants engaged by the auditing Party and reasonably acceptable to the audited Party, to examine such books and records at any reasonable time on reasonable advance notice, but not later than [* * *] following the rendering of any corresponding reports, accountings and payments pursuant to Section 5.2.4(b) or this Article 6. The foregoing right of review may be exercised [* * *] during each [* * *] period and [* * *] with respect to any particular books and records. Such accountants may be required by the audited Party to enter into a reasonably acceptable confidentiality agreement. Disputes over the accuracy of the opinion of said independent accountants will be resolved in accordance with Article 11. The auditing Party shall bear the cost of any such examination and review; provided that if the inspection and audit shows an underpayment or overcharge by the audited Party of more than [* * *] of the amount due for the applicable period, then, [* * *] the audited Party shall promptly reimburse the auditing Party for all reasonable and documented costs of such examination and review. The applicable Party shall promptly pay the other Party the amount of any underpayment, or refund any overpayment, revealed by an examination and review.

6.7 Late Payment . Any payments or portions thereof due hereunder which are not paid when due shall bear interest equal to the lesser of (i) [* * *], or (ii) [* * *]. This Section 6.7 shall in no way limit any other remedies available to Durect.

6.8 Currency Conversion . If any currency conversion shall be required in connection with the calculation of amounts payable hereunder, such conversion shall be made using the same exchange rates used by Impax for its own financial reporting purposes, or if none is used, then the average of the buying and selling rates using [* * *].

6.9 Upstream Agreements . [* * *].

6.10 Third Party In-Licenses . [* * *].

ARTICLE 7

INTELLECTUAL PROPERTY

7.1 Ownership of Inventions . As between the Parties, all right, title and interest in and to inventions and other subject matter made [* * *]. The Parties shall at all times fully cooperate in order to reasonably implement the foregoing ownership provisions. Such cooperation may include the execution of necessary legal documents, and the provision of any other assistance reasonably requested by the other Party. Each Party shall ensure it has appropriate written agreements with its (sub)licensees, employees, consultants or contractors containing confidentiality and invention disclosure and assignment obligations sufficient to enable such Party to comply with its obligations under this Agreement.

7.2 TRANSDUR® Technology Improvements . If any Impax Sole Invention [* * *] constitutes an improvement or modification to the TRANSDUR® Technology, then [* * *].

7.3 Patent Prosecution .

7.3.1 Licensed Patents . As between the Parties, Durect shall control the Prosecution and Maintenance of all Licensed Patents. Durect shall keep Impax reasonably informed on such activities and shall provide Impax reasonable opportunity to review and comment thereon, [* * *]. Durect shall [* * *]. Without limiting the foregoing, [* * *]:

(a) [* * *].

(b) [* * *].

7.3.2 Patents Claiming [* * *] or [* * *] that are not Licensed Patents . During the Term, Patents claiming [* * *] or [* * *] that are reasonably necessary or useful for the Development and Commercialization of any Product shall be deemed Licensed Patents. As between the Parties, [* * *].

7.4 Defense of Third Party Infringement Claims . If Product becomes the subject of a Third Party’s claim or assertion of infringement of a Patent relating to the manufacture, use, sale, offer for sale or importation of Product in the Field in the Territory, the Party first having notice of the claim or assertion shall promptly notify the other Party, and the Parties shall promptly confer to consider the claim or assertion and the appropriate course of action. Subject to Section 9.4, (a) [* * *] shall have the right to defend itself against a suit brought by a Third Party claiming or asserting infringement of [* * *] (“ Third Party Infringement Action ”) that names it as a defendant (the “ Defending Party ”); (b) in the event [* * *] (c) [* * *]; (d) Defending Party shall not enter into any settlement of any claim described in this Section 7.4 that adversely affects the other Party’s rights or interests without such other Party’s written consent, which consent shall not be unreasonably conditioned, withheld or delayed; and (e) in any event, the other Party shall reasonably assist the Defending Party and cooperate in any Third Party Infringement Action [* * *].

7.5 Enforcement .

7.5.1 Notice . Subject to the provisions of this Section 7.5, in the event that either Party reasonably believes that any Licensed Patent is being infringed by a Third Party by (i) the development, manufacture or commercialization of a transdermal patch delivering Bupivacaine as an active ingredient or (ii) the filing of an ANDA under Section 505(j) of the FD&C Act or an application under Section 505(b)(2) of the FD&C Act naming a Product as a reference listed drug and including a patent certification under Section 505(j)(2)(A)(vii)(IV) or 505(b)(2)(A)(IV), respectively, (each of (i) and (ii), a “ Product Infringement ”, and the product described in (i) or subject to any application described in (ii), an “ Infringing Product ”) or is subject to a declaratory judgment action arising from a Product Infringement, such Party shall promptly notify the other Party.

7.5.2 [* * *] .

(a) As between the Parties, [* * *] shall have the initial right (but not the obligation) to initiate and control any enforcement action or defend any declaratory judgment action (each, an “ Enforcement Action ”), at [* * *] expense, with respect to any Product Infringement of any [* * *] in the Territory. [* * *] shall notify [* * *] prior to initiating such Enforcement Action and consider in good faith all comments provided by [* * *], provided that with respect to any Enforcement Action for a Product Infringement described in Section 7.5.1(ii) (an “ ANDA Enforcement Action ”), [* * *] comments are provided within [* * *] following [* * *] receipt of such notice from [* * *] regarding [* * *] intention to initiate such Enforcement Action.

(b) If [* * *] determines not to institute an ANDA Enforcement Action under Section 7.5.2(a), it shall so notify [* * *] at least [* * *] before the expiration of the period within which a patent holder may bring an action for infringement against such Third Party. In such event, or in the event that [* * *] or its designee fails to commence any other Enforcement Action under Section 7.5.2(a) with respect to any Product Infringement within [* * *] of a request by [* * *] to do so, [* * *] shall then have the right, but not the obligation, to initiate and control such Enforcement Action against such Third Party for Product Infringement of the applicable Licensed Patent, [* * *].

7.5.3 [ * * * ]. If following notification under Section 7.5.1 with respect to a Product Infringement of a [* * *], [* * *] notifies [* * *] that [* * *] desires to enforce such [* * *] against such Product Infringement, then within [* * *] after receipt of such notice with respect to an ANDA Enforcement Action, and within [* * *] with respect to any other Enforcement Action, [* * *] shall notify [* * *] whether [* * *] consents to [* * *] initiation of an Enforcement Action. If [* * *] consents to such initiation, then Section 7.5.2 shall apply to the applicable Enforcement Action [* * *]. [* * *].

7.5.4 Restrictions . Notwithstanding anything in this Agreement to the contrary, it is understood that (i) each Party’s right to enforce [* * *] under this Section 7.5 shall be subject to the applicable terms of the [* * *] and (ii) [* * *].

7.5.5 Cooperation . The Party commencing, controlling or defending any Enforcement Action under this Section 7.5 (the “Enforcing Party ”) shall keep the other Party informed of the progress of any such Enforcement Action, and such other Party shall have the right to participate with counsel of its own choice at [* * *]. In any event, the other Party shall reasonably cooperate with the Enforcing Party, including providing information and materials and joining such action as a party plaintiff if required by Applicable Laws to pursue such action, [* * *]. The Enforcing Party shall also have the right to control settlement of such Enforcement Action; provided, however, no settlement shall be entered into without the consent of the other Party if such settlement would materially and adversely affect the interests of the other Party.

7.5.6 Recoveries . Any recovery received as a result of any Enforcement Action to enforce any Licensed Patent pursuant to this Section 7.5 shall be used first to reimburse the Enforcing Party for the costs and expenses (including court, attorneys’ and professional fees) incurred in connection with such Enforcement Action, then the other Party for its costs and expenses (including court, attorneys’ and professional fees) incurred in connection with such Enforcement Action, and the remainder of the recovery shall be shared as follows: [* * *] of such recovery shall be paid to the Enforcing Party and [* * *] of such recovery shall be paid to the other Party, provided that in the event [* * *].

7.5.7 Patents Claiming [* * *]. [* * *].

7.5.8 Patents Claiming [* * *] . [* * *].

7.5.9 Other Infringements of Licensed Patents . [* * *].

7.6 Orange Book Listing . Impax shall have the right to list any Existing Licensed Patent or New Licensed Patent owned jointly by Impax and Durect in the Orange Book (or its foreign counterpart) [* * *] in accordance with Applicable Laws, and will notify Durect upon determining to list any such Licensed Patent. If Durect disputes such listing, then [* * *].

7.7 Durect Personnel Obligations . Prior to beginning any Durect Development Responsibilities or other work under this Agreement, each employee, agent or independent contractor of Durect or its Affiliates shall be bound by written non-disclosure and invention assignment obligations including: (a) promptly reporting any invention, discovery, process or other intellectual property right; (b) assigning to Durect or the applicable Affiliate all of his or her right, title and interest in and to any invention and other subject matter made, and all intellectual property rights therein; (c) cooperating in the preparation, filing, prosecution, maintenance and enforcement of any patent and patent application; (d) performing all acts and signing, executing, acknowledging and delivering any and all documents required for effecting the obligations and purposes of this Agreement; and (e) abiding by the obligations of confidentiality and non-use substantially similar to those set forth in Article 8. It is understood and agreed that such non-disclosure and invention assignment agreement need not reference or be specific to this Agreement.

ARTICLE 8

CONFIDENTIALITY

8.1 Confidentiality; Exceptions . Except to the extent expressly authorized by this Agreement or otherwise agreed by the Parties in writing, the Parties agree that the receiving Party shall keep confidential and shall not publish or otherwise disclose or use for any purpose other than as contemplated by this Agreement any confidential or proprietary information or materials furnished to it by the other Party pursuant to this Agreement (collectively, “ Confidential Information ”); provided that each Transferred Asset and all data generated from Durect’s performance of the Durect Development Responsibilities shall be deemed the Confidential Information of Impax, regardless of whether it satisfies the exclusions in Sections 8.1.1 and 8.1.4. Notwithstanding the foregoing, Confidential Information shall not be deemed to include information or materials to the extent that it can be established by written documentation by the receiving Party that such information or material:

8.1.1 was already known to or possessed by the receiving Party without any obligation of confidentiality, at the time of its disclosure to the receiving Party hereunder;

8.1.2 was generally available to the public or otherwise part of the public domain at the time of its disclosure to the receiving Party hereunder;

8.1.3 became generally available to the public or otherwise part of the public domain after its disclosure hereunder other than through any act or omission of the receiving Party in breach of this Agreement;

8.1.4 was independently developed by the receiving Party without use of or reference to the other Party’s Confidential Information as demonstrated by documented evidence prepared by the receiving Party contemporaneously with such independent development; or

8.1.5 was disclosed to the receiving Party, other than under an obligation of confidentiality, by a Third Party who had no obligation to the disclosing Party not to disclose such information to others.

8.2 Authorized Use and Disclosure . Each Party may use and disclose Confidential Information of the other Party as follows: (i) under appropriate confidentiality provisions substantially equivalent to those in this Agreement in connection with the performance of its obligations or exercise of rights granted to such Party in this Agreement; (ii) to the extent such disclosure is reasonably necessary for any of the following: (a) the Prosecution and Maintenance of Patents (including applications therefor) in accordance with this Agreement, (b) complying with the terms of agreements with Third Parties pursuant to which it Controls Licensed Technology, (c) prosecuting or defending litigation, (d) complying with applicable governmental regulations, (e) conducting preclinical or clinical trials, filing for, obtaining and maintaining regulatory approvals (including Marketing Approvals), or (f) otherwise required by Applicable Laws or the rules of a recognized stock exchange, provided, however, that if a Party is required by Applicable Laws or stock exchange to make any such disclosure of the other

Party’s Confidential Information it will, except where impracticable for necessary disclosures (for example, in the event of medical emergency), give reasonable advance notice to the other Party of such disclosure requirement and will use its reasonable efforts to secure confidential treatment of such Confidential Information required to be disclosed; (iii) in communication with existing and potential investors, acquirers, lenders, consultants, advisors (including financial advisors, lawyers and accountants) and, in the case of Impax, potential and actual licensees, collaborators or service providers on a need to know basis, in each case under appropriate confidentiality provisions substantially equivalent to those of this Agreement; or (iv) to the extent mutually agreed to by the Parties.

8.3 Prior Agreements . The Confidentiality Agreement between Durect and Impax dated [* * *] (the “ Prior CDA ”) is terminated as of the Effective Date and neither Party shall have any obligations thereunder after the Effective Date. All information or materials disclosed or provided by Durect to Impax under the Prior CDA (excluding Transferred Assets) shall be deemed Confidential Information of Durect (subject to the exceptions set forth herein) and shall be subject to Impax’s confidentiality obligations under this Article 8. All information disclosed by Impax to Durect under the Prior CDA shall be deemed Confidential Information of Impax (subject to the exceptions set forth herein) and shall be subject to Durect’s confidentiality obligations under this Article 8.

8.4 Scientific Publications . Durect shall not have the right to publish or otherwise publicly disclose any clinical or scientific results to the extent specifically relating to any Product. Impax shall submit to Durect any proposed publication or public disclosure containing clinical or scientific results relating to Product in the Field at least [* * *] days in advance to allow Durect to review such proposed publication or disclosure. Durect shall notify Impax in writing during such [* * *] reviewing period if Durect wishes to remove its Confidential Information from such proposed publication or presentation, in which event Impax shall remove such Confidential Information from its proposed publication or presentation. In the event Durect notifies Impax within such [* * *] reviewing period that the proposed publication or presentation discloses any patentable invention that is a [* * *] or [* * *], such publication or presentation shall be delayed for a period of no more than [* * *] to allow the filing of patent applications protecting such patentable invention in accordance with Section 7.3. For clarity, if Durect fails to notify Impax during the [* * *] reviewing period as provided under this Section 8.4, Impax shall be free to proceed with the proposed publication or presentation.

8.5 Publicity .

8.5.1 Confidential Terms . Each of the Parties agrees not to disclose to any Third Party the terms and conditions of this Agreement without the prior approval of the other Party, except (a) to advisors (including consultants, financial advisors, attorneys and accountants), potential and existing investors, acquirers and lenders and in the case of Impax, potential and actual licensees, collaborators and service providers, on a need to know basis, in each case under circumstances that reasonably protect the confidentiality thereof, or (b) to the extent required by Applicable Law, including securities laws, provided that it requests confidential treatment of the commercial terms and sensitive technical terms hereof to the extent such confidential treatment is reasonably available

to such Party. In the event of any such filing under clause (b) above, the filing Party will provide the other Party with a copy of this Agreement marked to show provisions for which such Party intends to seek confidential treatment and shall reasonably consider the other Party’s reasonable comments thereon to the extent consistent with the legal requirements, with respect to the filing Party, governing disclosure of material agreements and material information that must be publicly filed. Notwithstanding the foregoing, the Parties agree upon a joint press release to announce the execution of this Agreement, which is attached hereto as Exhibit 8.5.1 ; thereafter, Durect and Impax may each disclose to Third Parties the information contained in such press release without the need for further approval by the other.

8.5.2 Publicity Review . After release of the initial joint press release, if either Party desires to make a public announcement regarding activities under this Agreement, such Party may make such disclosures from time to time with the approval of the other Party, which approval shall not be unreasonably withheld, conditioned or delayed. Such disclosures may include achievement of significant events in the Development (including regulatory process and occurrence of Development Milestone Events) or Commercialization of Product in the Field hereunder. Unless otherwise requested by Durect, Impax shall use reasonable efforts to indicate in each press release disclosing significant Development and Commercialization events for Product in the Field that Durect is the owner and licensor of Product and Licensed Technology, and will consider Durect’s request to so indicate in any other public disclosure issued by Impax regarding Product. When a Party elects to make any such public disclosure under this Section 8.5.2, it will give the other Party reasonable notice, to the extent practicable, to review and comment on such statement, it being understood that if the reviewing Party does not notify the requesting Party in writing within [* * *] or such shorter period if required by Applicable Laws of any reasonable objections, as contemplated in this Section 8.5.2, such disclosure shall be deemed approved, and in any event the reviewing Party shall work diligently and reasonably to agree on the text of any proposed disclosure in an expeditious manner. The principles to be observed in such disclosures shall be accuracy, compliance with Applicable Laws and regulatory guidance documents, reasonable sensitivity to potential negative reactions of applicable Regulatory Authorities and the need to keep investors and others informed regarding the requesting Party’s business, including as required by the rules of a recognized stock exchange. Accordingly, the reviewing Party shall not withhold, condition or delay its approval of a proposed disclosure that complies with such principles.

ARTICLE 9

REPRESENTATIONS, WARRANTIES AND COVENANTS; INDEMNIFICATION

9.1 Impax Representations and Warranties . Impax represents and warrants to Durect that:

9.1.1 it is duly organized and validly existing under the Applicable Laws of the jurisdiction of its incorporation, and has full corporate power and authority to enter into this Agreement and to carry out the provisions hereof;

9.1.2 it is duly authorized to execute and deliver this Agreement and to perform its obligations hereunder, and the person executing this Agreement on its behalf has been duly authorized to do so by all requisite corporate action;

9.1.3 this Agreement is legally binding upon it and enforceable in accordance with its terms and the execution, delivery and performance of this Agreement by it does not conflict with any agreement, instrument or understanding, oral or written, to which it is a party or by which it may be bound, nor violate any material Applicable Law;

9.1.4 it has not granted, and shall not grant during the Term, any right to any Third Party which would conflict with the rights granted to Durect hereunder; and

9.1.5 it is not aware of any action, suit or inquiry or investigation instituted by any Person which questions or threatens the validity of this Agreement.

9.2 Durect’s Representations and Warranties . Durect represents and warrants to Impax that:

9.2.1 it is duly organized and validly existing under the Applicable Laws of the jurisdiction of its incorporation, and has full corporate power and authority to enter into this Agreement and to carry out the provisions hereof;

9.2.2 it is duly authorized to execute and deliver this Agreement and to perform its obligations hereunder, and the person executing this Agreement on its behalf has been duly authorized to do so by all requisite corporate action;

9.2.3 this Agreement is legally binding upon it and enforceable in accordance with its terms and the execution, delivery and performance of this Agreement by it does not conflict with any agreement, instrument or understanding, oral or written, to which it is a party or by which it may be bound, nor violate any material Applicable Law;

9.2.4 [* * *];

9.2.5 it is not aware of any action, suit or inquiry or investigation instituted by any Person which questions or threatens the validity of this Agreement;

9.2.6 as of the Effective Date, [* * *];

9.2.7 as of the Effective Date, [* * *];

9.2.8 [* * *];

9.2.9 Exhibit 1.26.2 is an accurate listing by serial number, filing date, country, and status of all patents and patent applications Controlled by Durect as of the Effective Date that claim the composition, manufacture or use of a Product;

9.2.10 [* * *];

9.2.11 to Durect’s knowledge as of the Effective Date, [* * *];

9.2.12 as of the Effective Date, [* * *];

9.2.13 to Durect’s knowledge as of the Effective Date, [* * *];

9.2.14 [* * *];

9.2.15 to Durect’s knowledge as of the Effective Date, [* * *];

9.2.16 except as set forth in Exhibit 9.2.16 , as of the Effective Date, [* * *];

9.2.17 [* * *];

9.2.18 Durect has delivered or otherwise made available to Impax a true and correct copy of each Transferred Contract; [* * *];

9.2.19 Exhibit 1.51 contains an accurate listing of all Upstream Licenses;

9.2.20 To Durect’s knowledge as of the Effective Date, [* * *];

9.2.21 Durect has provided Impax with true and complete copies of all material Regulatory Filings Controlled by Durect related to any Product; [* * *] has not been terminated or placed on inactive status.

9.2.22 As of the Effective Date, Durect has not received any communication from any Regulatory Authority alleging or asserting material noncompliance with any Applicable Laws in connection with any Product;

9.2.23 Durect has disclosed to Impax [* * *]; and

9.2.24 all Product included in the Transferred Assets has been manufactured, tested and stored in compliance with cGMP and applicable specifications and in material compliance with other Applicable Laws and, to Durect’s knowledge, in compliance with all Applicable Laws.

9.3 Disclaimer of Warranties . EXCEPT AS SET FORTH IN THIS ARTICLE 9, DURECT AND IMPAX EXPRESSLY DISCLAIM ANY WARRANTIES OR CONDITIONS, EXPRESS, IMPLIED, STATUTORY OR OTHERWISE, WITH RESPECT TO THE SUBJECT MATTER OF THIS AGREEMENT (INCLUDING THE LICENSED TECHNOLOGY), INCLUDING ANY WARRANTY OF MERCHANTABILITY, NONINFRINGEMENT, OR FITNESS FOR A PARTICULAR PURPOSE.

9.4 Indemnification .

9.4.1 Indemnification by Durect . Durect hereby agrees to defend, hold harmless and indemnify (collectively, “ Indemnify ”) Impax and its Affiliates, and its and their agents, directors, officers and employees (the “ Impax Indemnitees ”) from and against any liability or expense (including reasonable legal expenses and attorneys’ fees) (collectively, “ Losses ”) resulting from suits, claims, actions and demands, in each case brought by a Third Party (each, a “ Third-Party Claim ”) against any Impax Indemnitee arising out of (a) the research or development of Product by or on behalf of Durect or its Affiliates prior to the Closing, (b) the [* * *], (c) a breach of any of Durect’s obligations, representations and warranties under this Agreement, or (d) the negligence or intentional misconduct of any Durect Indemnitee. Durect’s obligation to Indemnify the Impax Indemnitees pursuant to this Section 9.4 shall not apply to the extent that any such Losses (A) arise from the negligence or intentional misconduct of any Impax Indemnitee; or (B) arise from any breach by Impax of this Agreement.

9.4.2 Indemnification by Impax . Impax hereby agrees to Indemnify Durect and its Affiliates, and its and their agents, directors, officers and employees (the “ Durect Indemnitees ”) from and against any and all Losses resulting from Third-Party Claims against any Durect Indemnitee arising out of: (i) a breach of any of Impax’s obligations, representations and warranties under this Agreement; or (ii) the Development, Commercialization or other exploitation of Product by or on behalf of Impax or its Affiliates or Sublicensees or other exercise of the licenses and rights granted hereunder by or under authority of Impax. Impax’s obligation to Indemnify the Durect Indemnitees pursuant to the foregoing sentence shall not apply to the extent that any such Losses (A) arise from the negligence or intentional misconduct of any Durect Indemnitee; or (B) arise from any breach by Durect of this Agreement.

9.4.3 Procedure . To be eligible to be Indemnified hereunder, the indemnified Party shall provide the indemnifying Party with prompt notice of the Third-Party Claim giving rise to the indemnification obligation pursuant to this Section 9.4 and the exclusive ability to defend (with the reasonable cooperation of the indemnified Party) or settle any such claim; provided, however, that the indemnifying Party shall not enter into any settlement that admits fault or wrongdoing or requires a non-monetary remedy on the part of the indemnified Party without the indemnified Party’s written consent, such consent not to be unreasonably withheld or delayed. The indemnified Party shall have the right to participate, at its own expense and with counsel of its choice, in the defense of any claim or suit that has been assumed by the indemnifying Party, provided that the indemnifying Party shall have no obligations with respect to any Losses resulting from the indemnified Party’s admission, settlement or other communication without the prior written consent of the indemnifying Party.

9.5 Insurance . Each Party shall obtain and maintain, during the Term and, in the case of claims-made policies, for [* * *] thereafter, reasonable insurance, including commercial general liability insurance, workers’ compensation insurance and products liability insurance, at levels consistent with industry standards based upon such Party’s activities hereunder and indemnification obligations hereunder. Each Party shall furnish to the other Party on request certificates issued by the insurance company setting forth the amount of the liability insurance (or evidence of self insurance). Each Party shall ensure that the other Party hereto shall receive

[* * *], written notice prior to termination or material reduction to the level of coverage, if alternative insurance with commensurate coverage is not being obtained. In addition, each Party shall name the other Party as an “additional insured” on all commercial and product liability insurance policies described in this Section 9.5.

9.6 Limitation of Liability . NEITHER PARTY SHALL BE LIABLE TO THE OTHER FOR ANY SPECIAL, CONSEQUENTIAL, INCIDENTAL, PUNITIVE, OR INDIRECT DAMAGES ARISING FROM OR RELATING TO ANY BREACH OF THIS AGREEMENT, REGARDLESS OF ANY NOTICE OF THE POSSIBILITY OF SUCH DAMAGES. NOTWITHSTANDING THE FOREGOING, NOTHING IN THIS SECTION 9.6 IS INTENDED TO OR SHALL LIMIT OR RESTRICT (I) THE INDEMNIFICATION RIGHTS OR OBLIGATIONS OF A PARTY UNDER SECTION 9.4, OR (II) DAMAGES AVAILABLE FOR BREACH OF ARTICLE 8, OR (III) ANY LIABILITIES ARISING FROM EITHER PARTY’S WILLFUL MISCONDUCT.

ARTICLE 10

TERM AND TERMINATION

10.1 Term . This Agreement shall become effective as of the Effective Date and, unless earlier terminated pursuant to the other provisions of this Article 10, shall continue in full force and effect on a country-by-country basis until Impax has no remaining royalty payment obligations in such country (the “ Term ”). Upon such expiration with respect to a country, the license and sublicense granted to Impax in Section 4.1 shall become non-exclusive, fully-paid, royalty-free, perpetual and irrevocable in such country.

10.2 Termination by Impax . Impax shall have the right to terminate this Agreement, in its entirety or on a country-by-country basis, without cause upon [* * *] prior written notice to Durect; provided, however , [* * *].

10.3 Termination for Breach .

10.3.1 Breach . Subject to Sections 4.1.2(b) and 10.3.1, either Party may terminate this Agreement upon written notice to the other Party in the event the other Party materially breaches this Agreement, and such breach shall have continued for [* * *] after notice thereof was provided to the breaching Party by the non-breaching Party; provided that if such breach is not reasonably capable of cure within such [* * *] period, the breaching Party may submit a reasonable cure plan prior to the end of such [* * *] period, in which case the other Party shall not have the right to terminate this Agreement for so long as the breaching Party is using diligent efforts to implement such cure plan, for up to an additional [* * *] (for a total of [* * *]). [* * *].

10.3.2 Disputed Breach . If the alleged breaching Party disputes in good faith the existence or materiality of a breach specified in a notice provided by the other Party in accordance with Section 10.3.1, and such alleged breaching Party provides the other Party notice of such dispute within such [* * *] period, then [* * *].

10.3.3 Setoff Rights . [* * *].

10.4 Termination for Patent Challenge . If Impax or any of its Affiliates or Sublicensees challenges under any court action or proceeding, or before any patent office, the validity, patentability or enforceability of any Licensed Patent, or initiates a reexamination of any Licensed Patent, or assists any Third Party to conduct any of the foregoing activities (each, a “ Challenge ”), Durect will have the right, subject to this Section 10.4, to immediately terminate Impax’s license and sublicense under Section 4.1 with respect to such Licensed Patent. Impax or its Affiliate shall notify Durect at least [* * *] prior to initiating a Challenge. [* * *].

10.5 General Effects of Expiration or Termination .

10.5.1 Accrued Obligations . Expiration or termination of this Agreement for any reason shall not release either Party of any obligation or liability which, at the time of such expiration or termination, has already accrued to the other Party or which is attributable to a period prior to such expiration or termination.

10.5.2 Non-Exclusive Remedy . Notwithstanding anything herein to the contrary, termination of this Agreement by a Party shall be without prejudice to other remedies such Party may have at law or equity.

10.5.3 General Survival . Articles 1, 8, 11 and 12 and Sections 2.1, 2.8, 4.2, 6.5, 6.6, 6.7, 7.1, 7.2, 9.3, 9.4, 9.5, 9.6, 10.1, 10.4, 10.6 and 10.7 shall survive expiration or termination of this Agreement for any reason. Except as otherwise provided in this Article 10, all rights and obligations of the Parties under this Agreement shall terminate upon expiration or termination of this Agreement for any reason.

10.6 Additional Effects of Termination . If this Agreement is terminated pursuant to Sections 10.2, 10.3 or 10.4, then:

10.6.1 Reversion of Rights . All rights and licenses granted by Durect to Impax under this Agreement shall revert back to Durect. Impax shall execute a bill of sale, and the Parties shall execute an assignment and assumption agreement, to effect the assignment of Transferred Assets back to Durect, in each case substantially in the form as the Bill of Sale and Assignment and Assumption Agreement attached to this Agreement, but with the roles of the Parties reversed. In the event this Agreement is terminated pursuant to Sections 10.2 or 10.4, or terminated pursuant to Section 10.3 [* * *], Durect shall not be required to pay any consideration to Impax under Section 10.6 (except as otherwise expressly provided in Section 10.6.6). [* * *].

10.6.2 Ongoing Trials . If there are any ongoing clinical trials with respect to Product being conducted by or on behalf of Impax (or its Affiliate or, subject to Section 10.6.5, its Sublicensee) at the time of notice of termination, Impax agrees to (i) promptly transition to Durect or its designee some or all of such clinical trials and the activities related to or supporting such trials or (ii) terminate such clinical trials (subject to any medically appropriate wind-down); in each case as reasonably requested by Durect. [* * *].

10.6.3 Regulatory Filings . Impax shall promptly assign and transfer to Durect all Regulatory Filings for Product that are held or controlled by or under authority of Impax or its Affiliates or, subject to Section 10.6.5, its Sublicensees, and shall take such actions and execute such other instruments, assignments and documents as may be necessary to effect the transfer of rights under the Regulatory Filings to Durect. Impax shall cause each of its Affiliates and, subject to Section 10.6.5, its Sublicensees to transfer any such Regulatory Filings to Durect if this Agreement terminates. If Applicable Laws prevent or delay the transfer of ownership of a Regulatory Filing to Durect, Impax shall grant, and does hereby grant, to Durect an exclusive and irrevocable right of access and reference to such Regulatory Filing for Product, and shall cooperate fully to make the benefits of such Regulatory Filings available to Durect and/or its designee(s).

10.6.4 Technology and Trademark Licenses . Impax hereby grants Durect a non-exclusive, worldwide, irrevocable, fully paid-up, royalty-free license, with the right to sublicense, under (i) any Patent Controlled by Impax or its Affiliates Covering Product that was Developed or Commercialized by or under authority of Impax; [* * *]. Within [* * *] after effectiveness of termination, Impax shall provide to Durect copies of all such preclinical and clinical data (including raw data, original records, investigator reports, both preliminary and final, statistical analyses, expert opinions and reports, safety and other electronic databases) and other Know-How pertaining to Product, or the manufacture thereof, generated by Impax and not previously provided to Durect.

10.6.5 Sublicensees . Impax’s Sublicensees shall, at the request of Impax, receive license and other rights directly from Durect upon termination of this Agreement so as to maintain their pre-termination rights with respect to Product; provided that (i) each such Sublicensee is in compliance with its obligations under the applicable sublicense as of the date of termination of this Agreement, and (ii) Durect shall receive the same compensation with respect to each such Sublicensee’s activities under the applicable sublicense as if this Agreement had not terminated.

10.6.6 Transition Assistance . Impax agrees to reasonably cooperate with Durect and its designee(s) to facilitate a smooth, orderly and prompt transition of the Development and Commercialization of Product to Durect and/or its designee(s) during the notice period (if terminated pursuant to the first sentence of Section 10.2) and a [* * *] period after the effective date of termination, which may be extended for up to another [* * *] upon Durect’s written request (collectively, the “ Transition Period ”), provided that (i) the Parties shall use reasonable efforts to complete such transition prior to the expiration of the initial [* * *] period without such extension, and (ii) if Durect requests for such extension, [* * *]. Upon request by Durect within [* * *] after the effectiveness of termination, Impax shall transfer to Durect some or all quantities of Product in its or its Affiliates’ Control; provided, however, that Durect shall reimburse Impax for its actual costs to manufacture or otherwise acquire the quantities so provided to Durect. If any Product was manufactured by any Third Party for Impax, or Impax had contracts with vendors which contracts are specific to Product and necessary or useful for Durect to take over responsibility for Product in the Territory, then Impax shall to the extent possible and requested in writing by Durect, assign all of the relevant Third-Party contracts to Durect, and in any case, Impax agrees to cooperate with Durect

to facilitate uninterrupted supply of Product. If Impax or its Affiliate manufactured any Product at the time of termination, then Impax (or its Affiliate) shall continue to provide for manufacturing of such Product for Durect, at its fully-burdened manufacturing cost therefor, from the effectiveness of such termination until such time as Durect is able, using Commercially Reasonable Efforts, to secure an acceptable alternative commercial manufacturing source from which sufficient quantities of Product may be procured and legally sold in the Territory, but no longer than the Transition Period.

10.6.7 Costs and Expenses . Except as expressly provided herein, [* * *].

10.7 Termination Press Releases . In the event of termination of this Agreement for any reason, the Parties shall cooperate in good faith to coordinate public disclosure of such termination and the reasons therefor, and shall not, except to the extent required by Applicable Laws or the rules of a recognized stock exchange, disclose such information without the prior approval of the other Party, such approval not to be unreasonably withheld, conditioned or delayed. To the extent possible under the situation, the terminating Party shall provide the non-terminating Party with a draft of any such public disclosure it intends to issue [* * *] in advance and with the opportunity to review and comment on such statement, it being understood that if the non-terminating Party does not notify the terminating Party in writing within such [* * *] period (or such shorter period if required by Applicable Laws or the rules of a recognized stock exchange) of any reasonable objections, such disclosure shall be deemed approved, and in any event the Parties shall work diligently and reasonably to agree on the text of any such proposed disclosure in an expeditious manner. The principles to be observed in such disclosures shall be accuracy, compliance with Applicable Laws and regulatory guidance documents, reasonable sensitivity to potential negative reactions to such news and the need to keep investors and others informed regarding the Parties’ business and other activities. Accordingly in such situation, the non-terminating Party shall not withhold, condition or delay its approval of a proposed disclosure that complies with such principles.

ARTICLE 11

DISPUTE RESOLUTION

11.1 Disputes . If the Parties are unable to resolve any dispute or other matter arising out of or in connection with this Agreement, either Party may, by written notice to the other, have such dispute referred to the Chief Executive Officer of Durect and the President of Impax Pharmaceuticals for attempted resolution by good faith negotiations within [* * *] after such notice is received. In such event, each Party shall cause its applicable officer to meet (face-to-face or by teleconference) and be available to attempt to resolve such issue. If the Parties should resolve such dispute or claim under this Section 11.1, a memorandum setting forth their agreement will be prepared and signed by both Parties if requested by either Party. The Parties shall cooperate in an effort to limit the issues for consideration in such manner as narrowly as reasonably practicable in order to resolve the dispute.

11.2 Arbitration . In the event that the Parties are unable to resolve any such matter (other than a dispute within the JMC’s decision-making authority, which shall be resolved pursuant to Section 3.3) pursuant to Section 11.1, then such matter shall be resolved by binding arbitration pursuant to this Section 11.2, and either Party may initiate such arbitration. Any arbitration under this Section 11.2 shall be conducted by JAMS in San Francisco, California in accordance with the JAMS Comprehensive Arbitration Rules and Procedures then in effect by a single arbitrator. In such arbitration, the arbitrator shall select an independent expert with significant experience relating to the subject matter of such dispute to advise the arbitrator with respect to the subject matter of the dispute. If the Parties are unable to agree on an arbitrator, the arbitrator shall be selected by the chief executive of the San Francisco office of JAMS. The costs of such arbitration [* * *]. The parties shall use good faith efforts to complete arbitration under this Section 11.2 within [* * *] following the initiation of such arbitration. The arbitrator shall establish reasonable additional procedures to facilitate and complete such arbitration within such [* * *] period. Nothing in this Agreement shall limit the right of either Party to seek to obtain in any court of competent jurisdiction any equitable or interim relief or provisional remedy, including injunctive relief. Each Party agrees to abide by the award rendered in any arbitration conducted pursuant to this Section 11.2, and agrees that, subject to the U.S. Federal Arbitration Act, 9 U.S.C. §§ 1-16, judgment may be entered upon the final award in any court of competent jurisdiction and that other courts may award full faith and credit to such judgment in order to enforce such award. The award shall include interest from the date of any damages incurred for breach of the Agreement, and from the date of the award until paid in full, at a rate fixed by the arbitrator. The arbitration proceeding shall be confidential and the arbitrator shall issue appropriate protective orders to safeguard each Party’s Confidential Information.

ARTICLE 12

MISCELLANEOUS

12.1 Governing Law . This Agreement and any dispute arising from the performance or breach hereof shall be governed by and construed and enforced in accordance with the laws of the State of California without reference to conflicts of laws principles.

12.2 Assignment . This Agreement shall not be assignable by either Party to any Third Party without the written consent of the other Party and any such attempted assignment shall be void. Notwithstanding the foregoing, either Party may assign this Agreement without the written consent of the other Party (a) to an Affiliate of such Party, in its entirety or, in the case of Impax as the assigning Party, to its Affiliate with respect to its rights under this Agreement outside the United States, or (b) in its entirety to an entity that acquires all or substantially all of the business or assets of such Party to which this Agreement pertains (whether by merger, reorganization, acquisition, sale, operation of law or otherwise), and agrees in writing to be bound by the terms and conditions of this Agreement. No assignment or transfer of this Agreement (in whole or in part) shall be valid and effective unless and until the assignee/transferee agrees in writing to be bound by the applicable provisions of this Agreement. The terms and conditions of this Agreement shall be binding on and inure to the benefit of the permitted successors and assigns of the Parties. Except as expressly provided in this Section 12.2, any attempted assignment or transfer of this Agreement shall be null and void.

12.3 Consequences of Bankruptcy . The Parties acknowledge and agree that all rights and licenses now or hereafter granted under or pursuant to any Section of this Agreement are rights to “intellectual property” as defined in Section 101(35A) of Title 11 of the United States Code. In the event that a case under Title 11 is commenced by or against either Party (the “ Bankrupt Party ”), the other Party may elect to retain and may fully exercise all of its rights and elections under Section 365(n) of Title 11 of the United States Code. During the Term, each Party shall create and maintain current copies to the extent practicable of all such intellectual property. Without limiting the Parties’ rights under Section 365(n) of Title 11, if a case under Title 11 is commenced by or against the Bankrupt Party, the other Party shall be entitled to a copy of any and all such intellectual property and all embodiments of such intellectual property, and the same, if not in the possession of such other Party, shall be promptly delivered to it (i) before this Agreement is rejected by or on behalf of the Bankrupt Party, within [* * *] after the other Party’s written request, unless the Bankrupt Party, or its trustee or receiver, elects within [* * *] to continue to perform all of its obligations under this Agreement, or (ii) after any rejection of this Agreement by or on behalf of the Bankrupt Party, if not previously delivered as provided under clause (i) above. All rights of the Parties under this Section 12.3 and under Section 365(n) of Title 11 are in addition to and not in substitution of any and all other rights, powers, and remedies that each party may have under this Agreement, Title 11, and any other Applicable Laws. [* * *].

12.4 Notices . Any notice, request, delivery, approval or consent required or permitted to be given under this Agreement shall be in writing and shall be deemed to have been sufficiently given if delivered in person, transmitted by facsimile (receipt verified) or by express courier service (signature required) or [* * *] after it was sent by registered letter, return receipt requested (or its equivalent), provided that no postal strike or other disruption is then in effect or comes into effect within [* * *] after such mailing, to the Party to which it is directed at its address or facsimile number shown below or such other address or facsimile number as such Party will have last given by notice to the other Party.


		If to Durect, addressed to:		Durect Corporation
				10260 Bubb Road
				Cupertino, CA 95014
				United States
				Attention: General Counsel
				Telephone: (408) 777-3577
				Facsimile: (408) 777-1417


		With a copy to:		Wilson Sonsini Goodrich & Rosati
				Professional Corporation
				650 Page Mill Road
				Palo Alto, CA 94304-1050
				United States
				Attention: Ian B. Edvalson, Esq.
				Telephone: (650) 493-9300
				Facsimile: (650) 493-6811

		If to Impax, addressed to:		Impax Laboratories, Inc.
				30831 Huntwood Avenue
				Hayward, CA 94544
				Attention: General Counsel
				Telephone: (510) 240-6000
				Facsimile: (510) 471-3200

		With a copy to:		Cooley LLP
				3175 Hanover Street
				Palo Alto, CA 94304
				Attention: Marya A. Postner, Ph.D.
				Telephone: (650) 843-5000
				Facsimile: (650) 849-7400

12.5 Waiver . Neither Party may waive or release any of its rights or interests in this Agreement except in writing. The failure of either Party to assert a right hereunder or to insist upon compliance with any term or condition of this Agreement shall not constitute a waiver of that right or excuse a similar subsequent failure to perform any such term or condition. No waiver by either Party of any condition or term in any one or more instances shall be construed as a continuing waiver of such condition or term or of another condition or term.

12.6 Severability . If any provision hereof should be held invalid, illegal or unenforceable in any jurisdiction, the Parties shall negotiate in good faith a valid, legal and enforceable substitute provision that most nearly reflects the original intent of the Parties and all other provisions hereof shall remain in full force and effect in such jurisdiction and shall be liberally construed in order to carry out the intentions of the Parties as nearly as may be possible. Such invalidity, illegality or unenforceability shall not affect the validity, legality or enforceability of such provision in any other jurisdiction.

12.7 Entire Agreement/Modification . This Agreement, including its Exhibits, sets forth all the covenants, promises, agreements, warranties, representations, conditions and understandings between the Parties with respect to the subject matter hereof and supersedes and terminates all prior agreements and understandings between the Parties with respect to such subject matter, including the Prior CDA. No subsequent alteration, amendment, change or addition to this Agreement shall be binding upon the Parties unless reduced to writing and signed by the respective authorized officers of the Parties.

12.8 Relationship of the Parties . The Parties agree that the relationship of Durect and Impax established by this Agreement is that of independent contractors. Furthermore, the Parties agree that this Agreement does not, is not intended to, and shall not be construed to, establish an employment, agency or any other relationship. Except as may be specifically provided herein, neither Party shall have any right, power or authority, nor shall they represent themselves as having any authority to assume, create or incur any expense, liability or obligation, express or implied, on behalf of the other Party, or otherwise act as an agent for the other Party for any purpose.

12.9 Force Majeure . Except with respect to payment of money, neither Party shall be liable to the other for failure or delay in the performance of any of its obligations under this Agreement for the time and to the extent such failure or delay is caused by earthquake, riot, civil commotion, war, terrorist acts, strike, flood, bankruptcy of any Product manufacturer or supplier or governmental acts or restriction, or other cause that is beyond the reasonable control of the respective Party. The Party affected by such force majeure will provide the other Party with full particulars thereof as soon as it becomes aware of the same (including its best estimate of the likely extent and duration of the interference with its activities), and will use commercially reasonable efforts to overcome the difficulties created thereby and to resume performance of its obligations as soon as practicable. If the performance of any such obligation under this Agreement is delayed owing to such a force majeure for any continuous period of more than [* * *], the Parties will consult with respect to an equitable solution.

12.10 Compliance with Laws/Other . Notwithstanding anything to the contrary contained herein, all rights and obligations of Durect and Impax are subject to prior compliance with, and each Party shall comply with, all Applicable Laws, including obtaining all necessary approvals required by the applicable agencies of the governments of the United States and foreign jurisdictions. In addition, each Party shall conduct its activities under this Agreement in accordance with good scientific and business practices.

12.11 Performance by Affiliates . Each Party may discharge any obligations and exercise any right hereunder through any of its Affiliates. Each Party hereby guarantees the performance by its Affiliates of such Party’s obligations under this Agreement, and shall cause its Affiliates to comply with the provisions of this Agreement in connection with such performance. Any breach by a Party’s Affiliate of any of such Party’s obligations under this Agreement shall be deemed a breach by such Party, and the other Party may proceed directly against such Party without any obligation to first proceed against such Party’s Affiliate.

12.12 Interpretation . The captions and headings to this Agreement are for convenience only, and are to be of no force or effect in construing or interpreting any of the provisions of this Agreement. Unless specified to the contrary, references to Articles, Sections or Exhibits mean the particular Articles, Sections or Exhibits to this Agreement and references to this Agreement include all Exhibits hereto. Unless context otherwise clearly requires, whenever used in this Agreement: (i) the words “include” or “including” shall be construed as incorporating, also, “but not limited to” or “without limitation;” (ii) the word “day” or “year” means a calendar day or year unless otherwise specified; (iii) the word “notice” shall mean notice in writing (whether

or not specifically stated) and shall include notices, consents, approvals and other written communications contemplated under this Agreement; (iv) the words “hereof,” “herein,” “hereby” and derivative or similar words refer to this Agreement (including any Exhibits); (v) the word “or” shall be construed as the inclusive meaning identified with the phrase “and/or”; (vi) provisions that require that a Party, the Parties or a committee hereunder “agree,” “consent” or “approve” or the like shall require that such agreement, consent or approval be specific and in writing, whether by written agreement, letter, approved minutes or otherwise; (vii) words of any gender include the other gender; (viii) words using the singular or plural number also include the plural or singular number, respectively; (ix) references to any specific law, rule or regulation, or article, section or other division thereof, shall be deemed to include the then-current amendments thereto or any replacement law, rule or regulation thereof; and (x) neither Party or its Affiliates shall be deemed to be acting “on behalf of” the other Party hereunder.

12.13 Counterparts . This Agreement may be executed in two counterparts, each of which shall be deemed an original, and all of which together, shall constitute one and the same instrument.

[The remainder of this page intentionally left blank; the signature page follows.]

IN WITNESS WHEREOF , the Parties have executed this Agreement in duplicate originals by their duly authorized representatives as of the Effective Date.


DURECT CORPORATION		IMPAX LABORATORIES, INC.

By:	/s/ James E. Brown	By:	/s/ Michael J. Nestor

Name:	James E. Brown	Name:	Michael J. Nestor

Title:	CEO	Title:	President

List of Exhibits


Exhibit 1.5 :		Assignment and Assumption Agreement
Exhibit 1.6 :		Bill of Sale
Exhibit 1.18 :		[* * *]
Exhibit 1.26.2 :		Licensed Patents
Exhibit 1.38 :		Product-Specific Patents
Exhibit 1.40 :		[* * *]
Exhibit 1.43 :		[* * *]
Exhibit 1.48 :		TRANSDUR® Technology
Exhibit 1.49 :		Transferred Assets
Exhibit 1.51 :		Upstream Licenses
Exhibit 2.7(a) :		FDA Letter Transferring IND
Exhibit 2.7(b) :		FDA Letter Transferring Orphan Drug Designation
Exhibit 2.7(c) :		FDA Letter Accepting IND Transfer
Exhibit 2.7(d) :		FDA Letter Accepting Transfer of Orphan Drug Designation
Exhibit 5.2.2 :		Development Plan Outline
Exhibit 5.2.4 :		Calculation of [* * *]
Exhibit 8.5.1 :		Press Release
Exhibit 9.2.16 :		[* * *]

Exhibit 1.5

Assignment and Assumption Agreement

THIS ASSIGNMENT AND ASSUMPTION AGREEMENT (this “ Assignment and Assumption Agreement ”), dated as of January 3, 2014, is made by and between Durect Corporation, a Delaware company having offices located at 10260 Bubb Road, Cupertino, CA 95014 (“ Durect ”) and Impax Laboratories, Inc., a Delaware company having offices at 30831 Huntwood Avenue, Hayward, CA 94544 (“ Impax ”). Capitalized terms used but not defined herein shall have the meanings ascribed to such terms in the Asset Transfer and License Agreement (the “ Asset Transfer Agreement ”), dated as of the date hereof, by and between Durect and Impact.

WHEREAS, pursuant to the terms of the Asset Transfer Agreement, Impax has agreed to assume certain Liabilities from and after the Closing.

NOW, THEREFORE, in consideration of the premises and the mutual representations, warranties, covenants and undertakings contained herein, and for other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the parties, intending to be legally bound, agree as follows:

1. Sale, Transfer and Assignment of Purchased Assets . Durect hereby sells, conveys, transfers and assigns to Impax, on and subject to the terms and conditions set forth in the Asset Transfer Agreement, all of Durect’s right, title and interest in and to the Transferred Assets.

2. Assumption of Assumed Liabilities . Impax hereby assumes and agrees to perform only those Liabilities to the extent related to the Transferred Assets and that arise following the Closing and prior to effectiveness of the assignment of such Transferred Assets back to Durect after termination of the Asset Transfer Agreement, on and subject to the terms of the Asset Transfer Agreement, excluding any [* * *].

3. Further Assurances . Impax and Durect shall, at any time and from time to time after the Closing, upon the request of the other party, execute, acknowledge, seal and deliver all such instruments and documents, and do all such further things, as such other party may reasonably request to accomplish the assumption of the Liabilities described in Section 2 above and the sale, conveyance, transfer, assignment and delivery of the Transferred Assets under the Asset Transfer Agreement.

4. Asset Transfer Agreement . This Assignment and Assumption Agreement does not modify the terms of the Asset Transfer Agreement. The scope, nature and extent of the Transferred Assets and assumed Liabilities are expressly set forth in the Asset Transfer Agreement. Nothing contained herein shall change, amend, extend or alter (nor shall it be deemed or construed as changing, amending, extending or altering) the terms or conditions of the Asset Transfer Agreement in any manner whatsoever. This Agreement does not create or establish liabilities or obligations not otherwise created or existing under or pursuant to the Asset Transfer Agreement. In the event of a conflict or controversy between the terms of this Assignment and Assumption Agreement and the terms of the Asset Transfer Agreement, the terms of the Asset Transfer Agreement shall control. The Miscellaneous provisions contained in Sections 12.1, 12.4, 12.5, 12.6, 12.7 and 12.12 of the Asset Transfer Agreement shall apply to this Assignment and Assumption Agreement.

5. Counterparts; Facsimile . This Assignment and Assumption Agreement may be executed in two or more counterparts and by the different parties hereto on separate counterparts, each of which when so executed and delivered shall be an original, but all of which together shall constitute one and the same instrument. The exchange of signature pages to this Assignment and Assumption Agreement (in counterparts or otherwise) by facsimile transmission or other electronic transmission shall be sufficient to bind the parties to the terms and conditions of this Assignment and Assumption Agreement.

IN WITNESS WHEREOF , the Parties have executed this Assignment and Assumption Agreement in duplicate originals by their duly authorized representatives as of the date first written above.


DURECT CORPORATION		IMPAX LABORATORIES, INC.

By:	/s/ James E. Brown	By:	/s/ Michael J. Nestor

Name:	James E. Brown	Name:	Michael J. Nestor

Title:	CEO	Title:	President

Exhibit 1.6

Bill of Sale

WHEREAS, Durect Corporation, a Delaware company having offices located at 10260 Bubb Road, Cupertino, CA 95014 (“ Durect ”) and Impax Laboratories, Inc., a Delaware company having offices at 30831 Huntwood Avenue, Hayward, CA 94544 (“ Impax ”) are parties to that certain Asset Transfer and License Agreement, dated as of January 3, 2014 (the “ Asset Transfer Agreement ”), providing for, among other things, the transfer and sale of certain assets of Durect constituting the Transferred Assets (as defined in the Asset Transfer Agreement) to Impax, for consideration in the amount and on the terms and conditions provided in the Asset Transfer Agreement; and

WHEREAS, the parties now desire to carry out the purposes of the Asset Transfer Agreement by the execution and delivery of this instrument evidencing the purchase, acquisition, acceptance and vesting in Impax of all of the Transferred Assets.

NOW, THEREFORE, in consideration of the premises and of other valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the parties hereto hereby agree as follows:

All capitalized terms used herein and not defined shall have the meanings ascribed to them in the Asset Transfer Agreement.

1. Sale of Assets . Durect hereby sells, assigns, conveys, transfers and delivers to Impax, its successors and assigns, all of Durect’s right, title and interest in and to all of the Transferred Assets.

2. Further Assurances . On and after the date hereof, Durect shall execute and deliver to Impax, its successors and assigns, such assignments and other instruments as may be reasonably requested by Impax, its successors or assigns to effectuate the transactions contemplated by the Asset Transfer Agreement.

3. Asset Transfer Agreement . This Bill of Sale is entered into pursuant to and is subject in all respects to all of the terms, provisions and conditions of the Asset Transfer Agreement, and nothing herein shall be deemed to modify any of the representations, warranties, covenants and obligations of the parties thereunder.

4. Interpretation . In the event of any conflict or inconsistency between the terms, provisions and conditions of this Bill of Sale and the Asset Transfer Agreement, the terms, provisions and conditions of the Asset Transfer Agreement shall govern.

5. Effective Date . This Bill of Sale shall be effective as of the Closing.

6. Applicable Law . This Bill of Sale, and all disputes, controversies or issues arising with respect to the subject hereof, shall, in each case, be governed exclusively by, and construed and enforced exclusively in accordance with, the internal laws of the State of California without giving effect to the principles of conflicts of laws thereof.

IN WITNESS WHEREOF, this BILL OF SALE is executed and delivered as of the date first written above.


DURECT CORPORATION

By:		/s/ James E. Brown

Name:		James E. Brown

Title:		CEO

Exhibit 1.18

[* * *]

Exhibit 1.26.2

Licensed Patents

[* * *]

Exhibit 1.38

Product-Specific Patents

[* * *]

Exhibit 1.40

[* * *]

Exhibit 1.43

[* * *]

Exhibit 1.48

TRANSDUR ^® Technology

TRANSDUR ^® Technology is defined as [* * *]

Exhibit 1.49

Transferred Assets

[* * *]

Exhibit 1.51

Upstream Licenses

[* * *]

Exhibit 2.7(a)

FDA Letter Transferring IND

[Durect Letterhead]

Sent via Overnight

XX XX 2013

Timothy R. Cote MD, MPH

Director, Office of Orphan Products Development (HF-35)

Food and Drug Administration

5600 Fishers Lane, RM 6A55

Rockville, MD 20857

Re:	Reference Number [* * *]

Orphan-drug Designation Transfer of Sponsorship: [* * *]

Dear Mr. Cote:

This submission is to notify the Agency that, in accordance with 21 CFR 316.27, effective XX XX XX, all ownership rights to the Orphan-drug Designation [* * *] for [* * *] have been transferred to a new sponsor:

Impax Laboratories, Inc.

30831 Huntwood Ave.

Hayward, CA 94544

A complete copy of the request for orphan-drug designation, including any amendments to the request, supplements to the granted request, and correspondence relevant to the orphan-drug designation, has been provided to the new owner (see attached confirmation).

Impax will be submitting a separate letter notifying the Agency of the new contact information for future correspondence relating to this orphan-drug designation.

Sincerely,

Jill H. K. Burns

Senior Director, Regulatory Affairs

DURECT Corporation

Cc: Michael R. Marsman, PharmD, Vice President, Regulatory Affairs, Impax Laboratories, Inc.

Exhibit 2.7(b)

FDA Letter Transferring Orphan Drug Designation

[Durect Letterhead]

Sent via Overnight

XX XX 2013

Central Document Room

Center for Drug Evaluation and Research

Food and Drug Administration

Attention: Bob A. Rappaport, MD, Division Director

Division of Anesthesia, Analgesia and Addiction Products (DAAAP)

5901-B Ammendale Road

Beltsville, MD 20705-1266

Re:

Bupivacaine Transdermal Therapeutic System (TTS)

IND Number: [* * *]

Serial Number: 00XX

General Correspondence: TRANSFER OF IND OWNERSHIP

Dear Dr. Rappaport,

Effective XX XX 2013, all ownership rights of [* * *] has been transferred to the Sponsor listed below.

Impax Laboratories, Inc.

30831 Huntwood Ave.

Hayward, CA 94544

Complete copies of the IND, including all protocol amendments, information amendments, annual reports and FDA correspondence, have been transferred.

Impax will be submitting a separate letter notifying the Agency of the new contact information for future correspondence relating to this IND.

Please don’t hesitate to contact me by phone at 408-777-1829 or by email at jill.burns@durect.com if you have any questions about this submission.

Sincerely,

Jill H. K. Burns

Senior Director, Regulatory Affairs

Cc:	Kimberly Compton, Regulatory Director, DAAAP, CDER, FDA

Michael R. Marsman, PharmD, Vice President, Regulatory Affairs, Impax Pharmaceuticals

Exhibit 2.7(c)

FDA Letter Accepting IND Transfer

[IMPAX LETTERHEAD]

[DATE]

Food and Drug Administration

Center for Drug Evaluation and Research

< FDA Division Name >

Central Document Room

5901-B Ammendale Road

Beltsville, MD 20705

Attention:

< Name of Division Director >

Subject:

[* * *]—Transfer of IND Ownership

Impax Laboratories, Inc. (“Impax”) hereby accepts the transfer of ownership of [* * *] from Durect Corporation having offices located at 10260 Bubb Road, Cupertino, California 95014 effective < date transfer effective >. Additionally, Impax confirms receipt of a complete copy of the approved IND application. In accepting ownership of [* * *], Impax agrees to the commitments and conditions contained in the IND and agrees to maintain the IND in accordance with the requirements of 21 CFR 312.

All future communications regarding [* * *] should be sent to the following contact:

Impax Laboratories, Inc.

[Name]

30831 Huntwood Avenue

Hayward, CA 94544

[Phone number]

[Email address]

Please contact me if you have any or require additional information. Thank you.

Sincerely,

[Name]

[Title]

[Phone number]

cc via email: < FDA Regulatory Project Manager > , < Regulatory Contact at Transferring Company >

Exhibit 2.7(d)

FDA Letter Accepting Transfer of Orphan Drug Designation

[IMPAX LETTERHEAD]

[Date]

Office of Orphan Products Development

Food and Drug Administration

WO 32-5271

10903 New Hampshire Avenue

Silver Spring, MD 20993-0002

Attention:

Gaytari R. Rao M.D., J.D., Director

Subject:

< Orphan-Drug Designation Reference >, [* * *] — Transfer of Orphan-Drug Designation

Impax Laboratories, Inc. (“Impax”) hereby accepts the transfer of ownership of < Orphan Designation Reference No. > from Durect Corporation with offices located at 10260 Bubb Road, Cupertino, California 95014, effective < date transfer effective >. Additionally, Impax hereby confirms receipt of a complete copy of the request for orphan-drug designation, including any amendments, supplements, and relevant correspondence.

The specific rights assigned to Impax and those reserved are listed below.

< List of assigned/reserved rights >

All future communications regarding < Orphan Designation Reference > should be sent to the following contact:

Impax Laboratories, Inc.

[Name]

30831 Huntwood Avenue

Hayward, CA 94544

[Phone number]

[Email address]

Please contact me if you have any questions or require additional information. Thank you.

Sincerely,

[Name]

[Title]

[Phone number]

cc via email: < FDA Orphan Drug Contact > , < Regulatory Contact at Transferring Company >

Exhibit 5.2.2

Development Plan Outline

[* * *]

Exhibit 5.2.4

Calculation of [* * *]

[* * *]

Exhibit 8.5.1

Press Release

Impax and DURECT Sign a $63 Million Agreement to Develop and

Commercialize DURECT’s ELADUR ^® Pain Patch

HAYWARD, CA and CUPERTINO, CA, January 6, 2014 — Impax Laboratories, Inc. (NASDAQ: IPXL) and DURECT Corporation (Nasdaq: DRRX) announced today that they have entered into an agreement granting Impax the exclusive worldwide rights to develop and commercialize ELADUR ^® , DURECT’s investigational transdermal bupivacaine patch for the treatment of pain associated with post-herpetic neuralgia (PHN).

Under the terms of the agreement, Impax will pay DURECT an upfront fee of $2 million, with possible additional payments of up to $61 million upon the achievement of predefined development and commercialization milestones. If ELADUR is commercialized, DURECT would also receive a tiered royalty on product sales. Impax will control and fund the development program.

“We’re pleased to be moving ELADUR back into development through this collaboration with Impax,” stated James E. Brown, president and CEO of DURECT. “Existing patches used to treat PHN pain are limited by their 12 hour duration, followed by a rest period in which the patient is not to wear a patch for 12 hours. Episodes of break-through pain are frequently reported to occur during rest periods for existing patches. We share a vision with Impax to develop a patch that has the potential to reduce these episodes of break-through pain.”

Michael Nestor, president of Impax Pharmaceuticals added, “This agreement is another example of our commitment to building a strong brand pipeline through internal R&D and external business development. We are excited to collaborate with DURECT as this product could, if approved, fit well with the capabilities of our neurology focused specialty sales force.”

ELADUR is an investigational transdermal drug patch intended to deliver bupivacaine for up to three days from a single application. DURECT has previously announced positive results for ELADUR from a 60 patient Phase IIa clinical trial of patients suffering from PHN.

About Impax Laboratories, Inc.

Impax Laboratories, Inc. (Impax) is a technology based specialty pharmaceutical company applying its formulation expertise and drug delivery technology to the development of controlled-release and specialty generics in addition to the development of central nervous system disorder branded products. Impax markets its generic products through its Global Pharmaceuticals division and markets its branded products through the Impax Pharmaceuticals division. Additionally, where strategically appropriate, Impax develops marketing partnerships to fully leverage its technology platform and pursues partnership opportunities that offer alternative dosage form technologies, such as injectables, nasal sprays, inhalers, patches, creams and ointments. For more information, please visit the Company’s Web site at: www.impaxlabs.com.

About DURECT Corporation

DURECT is a specialty pharmaceutical company developing innovative drugs for pain and other chronic diseases, with late-stage development programs including REMOXY ^® , POSIDUR™, ELADUR ^®, and TRANSDUR ^® -Sufentanil. DURECT’s proprietary oral, transdermal and injectable depot delivery technologies enable new indications and superior clinical/commercial attributes such as abuse deterrence, improved convenience, compliance, efficacy and safety for small molecule and biologic drugs. For more information, please visit www.durect.com.

Impax Laboratories Forward-Looking Statement

To the extent any statements made in this news release contain information that is not historical, these statements are forward-looking in nature and express the beliefs and expectations of management. Such statements are based on current expectations and involve a number of known and unknown risks and uncertainties that could cause the Company’s future results, performance or achievements to differ significantly from the results, performance or achievements expressed or implied by such forward-looking statements. Such risks and uncertainties include, but are not limited to, the effect of current economic conditions on the Company’s industry, business, financial position and results of operations, fluctuations in revenues and operating income, the Company’s ability to promptly correct the issues raised in the warning letter and Form 483 observations received from the FDA, the Company’s ability to successfully develop and commercialize pharmaceutical products in a timely manner, reductions or loss of business with any significant customer, the impact of consolidation of the Company’s customer base, the impact of competition, the Company’s ability to sustain profitability and positive cash flows, any delays or unanticipated expenses in connection with the operation of the Company’s Taiwan facility, the effect of foreign economic, political, legal and other risks on the Company’s operations abroad, the uncertainty of patent litigation, the increased government scrutiny on the Company’s agreements with brand pharmaceutical companies, consumer acceptance and demand for new pharmaceutical products, the impact of market perceptions of the Company and the safety and quality of the Company’s products, the difficulty of predicting FDA filings and approvals, the Company’s ability to achieve returns on its investments in research and development activities, the Company’s inexperience in conducting clinical trials and submitting new drug applications, the Company’s ability to successfully conduct clinical trials, the Company’s reliance on third parties to conduct clinical trials and testing, impact of illegal distribution and sale by third parties of counterfeits or stolen products, the availability of raw materials and impact of interruptions in the Company’s supply chain, the use of controlled substances in the Company’s products, disruptions or failures in the Company’s information technology systems and network infrastructure, the Company’s reliance on alliance and collaboration agreements, the Company’s dependence on certain employees, the Company’s ability to comply with legal and regulatory requirements governing the healthcare industry, the regulatory environment, the Company’s ability to protect its intellectual property, exposure to product liability claims, changes in tax regulations, the Company’s ability to manage growth, including through potential acquisitions, the restrictions imposed by the Company’s credit facility, uncertainties involved in the preparation of the Company’s financial statements, the Company’s ability to maintain an effective system of internal control over financial reporting, the effect of terrorist attacks on the Company’s business, the location of the Company’s manufacturing and research and development facilities near earthquake fault lines and other risks described in the Company’s periodic reports filed with the Securities and Exchange Commission. Forward-looking statements speak only as to the date on which they are made, and the Company undertakes no obligation to update publicly or revise any forward-looking statement, regardless of whether new information becomes available, future developments occur or otherwise.

DURECT Forward-Looking Statement

The statements in this press release regarding ELADUR, its anticipated attributes, potential uses and commercial potential, and the milestone and royalty payments that may be potentially paid to DURECT under DURECT’s license agreement with Impax are forward-looking statements involving risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. Potential risks and uncertainties include, but are not limited to, the risk that ELADUR may not receive regulatory approval, Impax’s ability to design, enroll, conduct and complete clinical trials to support regulatory approval, and DURECT and Impax’s ability to complete the design, development, and manufacturing process development of ELADUR, Impax’s ability to manufacture and commercialize ELADUR, marketplace acceptance of the product candidate and the risk that Impax may terminate the agreement under conditions specified in the agreement. Further information regarding these and other risks is included in DURECT’s Form 10-Q dated November 5, 2013 filed with the Securities and Exchange Commission under the heading “Risk Factors.”

NOTE: ORADUR ^® , POSIDUR™, SABER ^® , TRANSDUR ^® , and ELADUR ^® are trademarks of DURECT Corporation. REMOXY, POSIDUR, ELADUR and TRANSDUR-Sufentanil are drug candidates under development and have not been approved for commercialization by the U.S. Food and Drug Administration or other health authorities.


SOURCE:		Impax Laboratories, Inc.
CONTACT:		Mark Donohue, Vice President Investor Relations, 215-558-4526

SOURCE:		DURECT Corporation
CONTACT:		Matthew J. Hogan, Chief Financial Officer, 408-777-4936

# # #

Exhibit 9.2.16

[* * *]

Exhibit 31.1

Rule 13a-14(a) Section 302 Certification

CERTIFICATIONS

I, James E. Brown, certify that:

1.	I have reviewed this quarterly report on Form 10-Q of DURECT Corporation;

2.	Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this report;

3.	Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the financial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report;

The registrant’s other certifying officer(s) and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the registrant and have:

(a)

designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within those entities, particularly during the period in which this report is being prepared;

(b)

designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles;

(c)

evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and

(d)

disclosed in this report any change in the registrant’s internal control over financial reporting that occurred during the registrant’s most recent fiscal quarter (the registrant’s fourth quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially affect, the registrant’s internal control over financial reporting; and

5.	The registrant’s other certifying officer(s) and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to the registrant’s auditors and the audit committee of the registrant’s board of directors (or persons performing the equivalent function):

(a)

all significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonably likely to adversely affect the registrant’s ability to record, process, summarize and report financial information; and

(b)

any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant’s internal control over financial reporting.

May 2, 2014

/s/ JAMES E. BROWN

James E. Brown

Chief Executive Officer

Exhibit 31.2

Rule 13a-14(a) Section 302 Certification

CERTIFICATIONS

I, Matthew J. Hogan, certify that:

1.	I have reviewed this quarterly report on Form 10-Q of DURECT Corporation;

2.	Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this report;

3.	Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the financial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report;

(a)

(b)

(c)

(d)

5.	The registrant’s other certifying officer(s) and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to the registrant’s auditors and the audit committee of the registrant’s board of directors (or persons performing the equivalent function):

(a)

(b)

any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant’s internal control over financial reporting.

May 2, 2014

/s/ MATTHEW J. HOGAN

Matthew J. Hogan

Chief Financial Officer and Principal Accounting Officer

Exhibit 32.1

CERTIFICATION PURSUANT TO

18 U.S.C. SECTION 1350,

AS ADOPTED PURSUANT TO

SECTION 906 OF THE SARBANES-OXLEY ACT OF 2002

In connection with the Quarterly Report of DURECT Corporation (the “Company”) on Form 10-Q for the period ending March 31, 2014 as filed with the Securities and Exchange Commission on the date hereof (the “Report”), I, James E. Brown, Chief Executive Officer of the Company, certify, pursuant to 18 U.S.C. § 1350, as adopted pursuant to § 906 of the Sarbanes-Oxley Act of 2002, that:

(1)

The Report fully complies with the requirements of section 13(a) or 15(d) of the Securities Exchange Act of 1934; and

(2)

The information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of the Company.

May 2, 2014

/ S / J AMES E. B ROWN

James E. Brown

Chief Executive Officer

Exhibit 32.2

CERTIFICATION PURSUANT TO

18 U.S.C. SECTION 1350,

AS ADOPTED PURSUANT TO

SECTION 906 OF THE SARBANES-OXLEY ACT OF 2002

In connection with the Quarterly Report of DURECT Corporation (the “Company”) on Form 10-Q for the period ending March 31, 2014 as filed with the Securities and Exchange Commission on the date hereof (the “Report”), I, Matthew J. Hogan, Chief Financial Officer of the Company, certify, pursuant to 18 U.S.C. § 1350, as adopted pursuant to § 906 of the Sarbanes-Oxley Act of 2002, that:

(1)

The Report fully complies with the requirements of section 13(a) or 15(d) of the Securities Exchange Act of 1934; and

(2)

The information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of the Company.

May 2, 2014

/s/ MATTHEW J. HOGAN

Matthew J. Hogan

Chief Financial Officer and Principal Accounting Officer