Exhibit 10.1

CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “ *** ”

January 2, 2009

Dear Mark:

The purpose of this Letter Amendment (“ LA ”), effective January 2, 2009, (the “ LA Effective Date ”) is to amend (a) the License and Development Agreement (the “ EU License ”), entered into as of August 2, 2006 by and among BioDelivery Sciences International, Inc., a Delaware corporation with offices at 801 Corporate Center Drive, Suite 210, Raleigh, North Carolina 27607 (“ Parent ”), its wholly-owned subsidiary Arius Pharmaceutical, Inc., a Delaware corporation with offices at the same address (“ Arius ”, and together with Parent, “ BDSI ”), and Meda AB (“ Meda ”), a Swedish corporation located at Pipers väg 2 A, SE-170 09, Solna, Sweden (“ Meda ”) and (b) the BEMA Fentanyl Supply Agreement (the “ Supply Agreement ”), entered into August 2, 2006 by and between BDSI and Meda in conjunction with the EU License. Any capitalized terms not defined in this LA shall have the meaning ascribed to such terms in the EU License or the Supply Agreement, as applicable.

In consideration of the mutual covenants herein, and intending to be legally bound hereby, BDSI and Meda agree as follows:

1. EU License Amendments . The EU License is hereby amended as follows:

““ European Countries ” means the countries specified in Exhibit E attached hereto.”

““ Licensed Patent Rights ” means all Patent Rights in the Territory that claim the same subject matter claimed in the patents and patent applications listed on Exhibit C, claiming BEMA or any Improvement, or which are necessary or appropriate to develop, manufacture and commercialize the Licensed Product in the Territory, and that are under the Control of BDSI or Arius Two as of the Effective Date or that come under BDSI’s or Arius Two’s Control during the Term.”

CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

“ *** ”

“ *** ”

““ Territory ” means all countries of the world other than the United States, Canada, Mexico, Taiwan and the Republic of Korea.”

“In addition to and without limiting Sections 3.02(e) and 11.03, Meda shall use Commercially Reasonable Efforts to pursue Product Development for the Licensed Product in the Territory.”

“Notwithstanding the exclusivity of Section 3.02(a), (i) if Meda fails to use Commercially Reasonable Efforts to pursue Product Development in the European Countries in accordance with this Section 2.01(a), *** .”

“However, if, following expiration of the last to expire of the Licensed Patent Rights in the European Countries, *** .”

“Subject to the directions, instruction, and oversight of the ESC, Meda shall prepare and file with each of the applicable Competent Authorities the appropriate applications and related documents necessary to obtain Governmental Approval to market and sell the Licensed Product in each country in the Territory in which Meda decides to market the Licensed Product.”

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CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

“upon receipt of Governmental Approval to market and sell the Licensed Product in a country in the Territory (including but not limited to Pricing and Reimbursement Approvals, if and as necessary), Meda shall commence the marketing and sale of the Licensed Product in such country within *** of receipt of such Governmental Approval or, if such country is not listed on Exhibit E, *** .”

“Meda agrees to use Commercially Reasonable Efforts to promote the sale, marketing, and distribution of the Licensed Product in each of the European Countries and in such other countries of the Territory in which Meda decides to market the Licensed Product.”

“Meda agrees that (i) during the *** after launch of the Licensed Product in the European Countries, *** and (ii) after launch of the Licensed Product in any country(ies) of the Territory *** .”

“Meda will maintain a pharmacovigilance database for the Licensed Product in the Territory, and BDSI shall use (or use commercially reasonable efforts to

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CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

ensure that its sublicensees use) commercially reasonable efforts to materially comply with any comparable obligations or requirements of any applicable laws in the United States.”

“BDSI shall maintain and protect the Licensed Patent Rights in the Territory, including but not limited to the use of commercially reasonable efforts to defend any interference actions initiated by or in any jurisdiction’s patent office with respect to the Licensed Patent Rights in the Territory. Notwithstanding the foregoing, upon written request by BDSI, Meda shall provide such assistance as may be necessary to enable BDSI to prosecute and obtain new patents related to any Improvements, with the cost and expense of such assistance to be borne by BDSI (except Meda shall bear such costs to the extent relating to Patent Rights in the European Countries and such other countries in the Territory that Meda designates upon request by BDSI reasonably in advance of incurring any material costs with respect to the patenting of a particular Improvement in any country(ies) that are not European Countries). BDSI shall be free to pursue and maintain, at its expense, patent protection of any particular Improvement in any country(ies), other than European Countries, that are not designated by Meda in accordance with the foregoing and, in the event BDSI does pursue patent protection of such Improvement in such country(ies) at its own expense, any resulting Patent Rights in such country(ies) shall, notwithstanding to the contrary, be excluded from Licensed Patent Rights.”

“BDSI, following the earliest of (i) the expiration of the Initial Term *** , (ii) the expiration of all Patent Rights owned or exclusively in-licensed by BDSI claiming the Licensed Product in the United States, or (iii)  *** , shall have the right, in its sole discretion, to terminate this Agreement upon thirty (30) days’ notice.”

“13.06 Limitation and Effects of Termination with respect to non-European Countries in the Territory . Notwithstanding anything to the contrary in this Agreement, the rights of BDSI to terminate this Agreement or render Meda’s rights hereunder nonexclusive upon an uncured breach of any provision of this Agreement by Meda with respect to a country of the Territory, other than the European Countries, shall be limited to such country, except in such cases where such breach materially and adversely affects the Licensed Product, or its development or commercialization, in any country(ies) other than such country, in which case, such remedy shall apply to such affected country(ies) outside the

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CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

European Countries and not any European Countries. For the avoidance of doubt, such remedy for a breach by Meda in any country outside the European Countries shall not apply to any European Countries, provided that the foregoing shall not be construed as limiting any remedies of BDSI hereunder with respect to any breach by Meda in any European Country. In the event of any termination of this Agreement or Meda’s rights hereunder with respect to any particular country(ies), the provisions of Section 13.05 (and the Parties’ rights and obligations thereunder) that would, if the Agreement were being terminated with respect to the entire Territory, apply to the entire Territory shall, notwithstanding anything to the contrary, apply with respect to the country(ies) subject to such termination.”

2. Amendment to Supply Agreement . The Supply Agreement is hereby amended as follows:

“1.5 “GMP” means, as relevant to the Products, the principles and guidelines of good manufacturing practice as contained in either directive 91/356/EEC (medicinal products for human use) or directive 91/412/EEC (medicinal products for veterinary use), as such principles and guidelines are interpreted and expanded in “The Rules Governing Medicinal Products in the European Community, Volume IV. Good Manufacturing Practice for medicinal Products” or, with respect to Products explicitly ordered for distribution or sale in jurisdictions not subject to the foregoing, good manufacturing practices reasonably sufficient to satisfy the corresponding requirements of Competent Authorities in such jurisdictions.”

“This Agreement shall be effective for a period beginning on the Effective Date and continue until the earlier of (i) any termination of the License Agreement other than a termination by BDSI under Section 13.03A thereof, (ii) an Arius Two Termination Event (as defined in that certain Sublicensing Consent between Arius Two, Inc. (“Arius Two”), Arius, and Meda dated August 2, 2006), (iii) a CDC Termination Event (as defined in that certain Sublicensing Consent and Amendment between Parent, Arius, and CDC dated August 2, 2006) (termination of this Agreement resulting from the occurrence of the events described in clause (ii) above or this clause (iii), a “Licensor Termination”), (iv)  *** .”

3. Fee . Meda shall pay to BDSI, upon execution of this LA, a non-refundable, non-creditable payment of US$3,000,000 in United States dollars by wire-transfer of immediately available funds to an account designated by BDSI.

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CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

Except as expressly set forth herein, the terms and conditions of the EU License or the Supply Agreement, as the case may be, shall remain in full force and effect. In the event of any conflict between the terms and conditions of this LA and the EU License or this LA and the Supply Agreement, the terms and conditions set forth in this LA shall control with respect to the subject matter hereof.

Please indicate your acceptance of the terms above by countersigning this letter where indicated below.

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1. For PCT application US97/18605: it has issued in the following European countries with the expiration date of 16 Oct 2017: Austria, Belgium, Switzerland, Germany, Denmark, Spain, France, United Kingdom, Greece, Ireland, Italy, Netherlands, and Sweden.

2. For PCT application US99/0378: it has issued in the following European countries with the expiration date of 16 Oct 2017: Austria, Belgium, Switzerland/Liechtenstein, Germany, Denmark, Spain, Finland, France, United Kingdom, Greece, Ireland, Italy, Luxembourg, , Netherlands, Portugal and Sweden.

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Exhibit 10.2

CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

AMENDMENT TO

LICENSE AND DEVELOPMENT AGREEMENT

This AMENDMENT TO LICENSE AND DEVELOPMENT AGREEMENT (the “Amendment”) is entered this January 2, 2008 (the “Amendment Date”), by BioDelivery Sciences International, Inc., a Delaware corporation with offices at 801 Corporate Center Drive, Suite 210, Raleigh, North Carolina 27607 (“Parent”), its wholly-owned subsidiary Arius Pharmaceuticals, Inc., a Delaware corporation with offices at the same address (“Arius”, and together with Parent, “BDSI”) and Meda AB, a Swedish corporation located at Pipers väg 2 A, SE-170 09, Solna, Sweden (“Meda”),

RECITALS

WHEREAS, BDSI entered into a License and Development Agreement, dated September 5, 2007, with Meda (the “License Agreement”) concerning the development, marketing and sale of BDSI’s BEMA fentanyl product in the United States, Canada and Mexico; and

WHEREAS, BDSI and Meda desire to amend the License Agreement as set forth in this Amendment.

NOW THEREFORE, in consideration of the mutual covenants herein, and intending to be legally bound hereby, BDSI and Meda agree as follows:

1. Definitions . Any capitalized terms not separately defined in this Amendment shall have the meaning provided in the License Agreement.

2. Advance Fee .

3. Amendments . The License Agreement is hereby amended as follows:

CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

“US Approval Milestone” means (i) US$11,900,000 if FDA approval of an NDA filed with respect to the Fentanyl Product occurs on or before June 30, 2009, (ii) US$11,800,000 if FDA approval of an NDA filed with respect to the Fentanyl Product occurs after June 30, 2009 and on or before December 1, 2009, or (iii) US$15,000,000 if FDA Approval of an NDA filed with respect to the Fentanyl Product occurs after December 1, 2009.”.

“the US Approval Milestone upon FDA approval of an NDA filed with respect to the Fentanyl Product;”.

4. Governing Law . This Amendment shall be governed by, and construed and enforced in accordance with, the laws of the State of New York, without regard to its conflict of law rules.

5. Counterparts . This Amendment may be executed in two or more counterparts, each of which shall be deemed an original, but all of which together shall constitute one and the same instrument. Signature to this Amendment may be transmitted via facsimile, e-mail or other electronic means and such signature shall be deemed to be originals.

6. Headings . The captions contained in this Amendment are not a part of this Amendment, but are merely guides or labels to assist in locating and reading the several Sections hereof.

7. Effect . To the extent that the terms of the License Agreement are varied by this Amendment, such variations shall be deemed to be lawfully made amendments to the License Agreement. Except as it may be modified by this Amendment, the License Agreement shall remain unchanged and in full force and effect.

[ Signature page to follow .]

CONFIDENTIAL TREATMENT REQUESTED

WITH RESPECT TO CERTAIN PORTIONS HEREOF

DENOTED WITH “***”

IN WITNESS HEREOF, each party hereto has caused this Amendment to be executed in its name effective as of the date first written above.

Exhibit 10.3

CONSENT AGREEMENT

This CONSENT AGREEMENT (the “Consent”) is entered this January 2, 2009, by BioDelivery Sciences International, Inc., with offices at 801 Corporate Center Drive, Suite 210, Raleigh, North Carolina 27607, its wholly-owned subsidiary Arius Pharmaceuticals, Inc., with offices at the same address (“Arius”; with Parent, “BDSI”), and CDC IV, LLC, with offices at 47 Hulfish Street, Suite 310, Princeton, New Jersey 08542 (“CDC”).

RECITALS

WHEREAS, CDC and BDSI are parties to that certain Clinical Development and License Agreement, dated July 14, 2005, as amended (the “CDLA”), and that certain Royalty Purchase and Amendment Agreement, dated September 5, 2007 (the “RPAA”),

WHEREAS, BDSI entered into a License and Development Agreement, dated August 2, 2006, with Meda AB, a Swedish corporation located at Pipers väg 2 A, SE-170 09, Solna, Sweden (“Meda”), concerning the development, marketing and sale of BDSI’s BEMA fentanyl product in Europe (the “EU License”), and a BEMA Fentanyl Supply Agreement, dated August 2, 2006, with Meda, concerning the manufacture and supply of BDSI’s BEMA Fentanyl Product for Europe (the “EU Supply Agreement”),

WHEREAS, BDSI has entered into a License and Development Agreement, dated September 5, 2007, with Meda concerning the development, marketing and sale of BDSI’s BEMA fentanyl product in the United States, Mexico and Canada (the “NA License”),

WHEREAS, CDC is a third-party beneficiary to each of the (i) BEMA License Agreement, dated as of August 2, 2006, by and between Arius and Arius Two, Inc. (“Arius Two”), as amended by the First Amendment, dated August 6, 2006 (the “Arius EU License”); and (ii) the BEMA License Agreement, dated as of September 5, 2007, by and between Arius and Arius Two (the “Arius NA License”),

WHEREAS, BDSI, CDC, and Meda are parties to a Sublicensing Consent and Amendment, dated August 2, 2006, enabling BDSI and Meda to enter into the EU License (the “EU Consent”) and a Sublicensing Consent and Amendment, dated September 5, 2007, enabling BDSI and Meda to enter into the NA License (the “NA Consent”), and

WHEREAS, BDSI and Meda wish to amend the EU License and NA License, respectively, pursuant to the forms of amendment attached hereto as Exhibit A and Exhibit B , respectively (the “EU Amendment” and “NA Amendment”, respectively; collectively, the “Amendments”), and CDC wishes BDSI and Meda to enter into the Amendments.

NOW THEREFORE, in consideration of the mutual covenants herein, and intending to be legally bound hereby, BDSI and CDC agree as follows:

1. Consents .

a. Pursuant to the CDLA and the EU Consent, and as a third party beneficiary to the Arius EU License and Arius NA License, CDC hereby consents to BDSI and Meda entering into the EU Amendment without, in any case, breach of the CDLA, EU Consent, or any other documents executed by CDC in conjunction with the EU License, which consents shall include, if necessary, but not be limited to, a consent under Section 4 of the EU Consent. CDC hereby agrees that all references to the EU License, EU Supply Agreement, and the defined terms thereof contained in the EU Consent and any other documents executed by CDC in conjunction with the EU License and EU Supply Agreement shall hereafter apply to the EU License, EU Supply Agreement, and their defined terms as amended, in each case, by the EU Amendment.

b. Pursuant to the CDLA and NA Consent and as a third party beneficiary to the Arius EU License and Arius NA License, CDC hereby consents to BDSI and Meda entering into the NA Amendment without, in any case, breach of the CDLA, RPAA, NA Consent, or any other documents executed by CDC in conjunction with the NA License, which consents shall include, if necessary, but not be limited to a consent under Section 4 of the NA Consent and waiver of all rights of Section 6 of the RPAA with respect to the matters contemplated by the NA Amendment. CDC hereby agrees that all references to the NA License and the defined terms thereof contained in the NA Consent and any other documents executed by CDC in conjunction with the NA License shall hereafter apply to the NA License and its defined terms as amended, in each case, by the NA Amendment.

2. Governing Law . This Consent shall be governed by, and construed and enforced in accordance with, the laws of the State of New York, without regard to its conflict of law rules.

3. Counterparts . This Consent may be executed in two or more counterparts, each of which shall be deemed an original, but all of which together shall constitute one and the same instrument. Signature to the Consent may be transmitted via facsimile, e-mail or other electronic means and such signature shall be deemed to be originals.

4. Headings . The captions contained in this Agreement are not a part of this Agreement, but are merely guides or labels to assist in locating and reading the Sections hereof.

5. Effect . To the extent that the terms of the CDLA, RPAA, EU Consent, NA Consent, and other documents executed by CDC in conjunction with the EU License or NA License are varied by this Consent, such variations shall be deemed to be lawfully made amendments to the CDLA, RPAA, EU Consent, NA Consent, and such other documents. Except as it may be modified by this Consent, the CDLA, RPAA, EU Consent, NA Consent, and such other documents shall remain unchanged and in full force and effect.

[ Signature page to follow .]

IN WITNESS HEREOF, each party hereto has caused this Agreement to be executed in its name effective as of the date first written above.

Exhibit 10.4

AMENDMENT CONSENT

This AMENDMENT CONSENT (the “Consent”) is entered this January 2, 2009 (the “Consent Date”) by Arius Pharmaceuticals, Inc. (“Arius”) and Arius Two, Inc. (“Arius Two”).

WHEREAS, Arius and Arius Two are parties to that certain BEMA License Agreement, dated August 2, 2006, as amended (the “Ex-NA Arius Two License”);

WHEREAS, Arius and BioDelivery Sciences International, Inc. (“Parent”; with Arius, “BDSI”) granted Meda AB (“Meda”) rights to develop and commercialize certain Products in Europe pursuant to that certain License and Development Agreement between BDSI and Meda dated August 2, 2006 (the “EU Meda License”);

WHEREAS, Section 3.01(b) of the Ex-NA Arius Two License requires Arius Two’s approval of any sublicense granted by Arius under the Ex-NA Arius Two License;

WHEREAS, Arius Two and Arius entered into that certain Sublicensing Consent, dated August 2, 2006 (the “EU License Consent”), enabling Arius to enter into the EU Meda License;

WHEREAS, BDSI and Meda wish to amend the EU Meda License as described in the amendment attached hereto as Exhibit A (the “EU Amendment”), and Arius Two wishes to enable Arius to enter into the EU Amendment by executing this Consent.

NOW THEREFORE, in consideration of the foregoing premises and for other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the parties to this Consent agree as follows:

1. Definitions . Any capitalized terms not separately defined in this Consent or by reference to the EU Meda License shall have the meaning provided in the EU Arius Two License.

2. Consent and Approval . Arius Two hereby approves of and consents to the amendment of the EU Meda License as described in the EU Amendment and Arius’ execution thereof pursuant to Section 3.01(b) of the Ex-NA Arius Two License, and agrees that its consents, approvals, waivers, and agreements provided in the EU License Consent and other documents executed by Arius Two in conjunction with the EU Meda License shall hereafter apply to the EU Meda License as amended by the EU Amendment. Arius Two hereby agrees that all references to the EU Meda License and the defined terms thereof contained in the EU License Consent and any other documents executed by Arius Two in conjunction with the EU Meda License shall hereafter apply to the EU Meda License and its defined terms as amended, in each case, by the EU Amendment.

3. License to Continue in Full Force and Effect. To the extent that the terms of the Ex-NA Arius Two License are varied by Section 2 of this Consent with respect to the EU Meda License, as amended by the EU Amendment, or Arius’ performance as it relates thereto, such variations shall be deemed to be lawfully made amendments to the Ex-NA Arius Two License pursuant to Section 14.11 thereof with respect to the EU Meda License, as amended by the EU Amendment. Except as it may be modified by Section 2 of this Consent with respect solely to the EU Meda License, as

amended by the EU Amendment, or Arius’ performance as it relates thereto, the Ex-NA Arius Two License shall remain unchanged and in full force and effect. Nothing in this Consent shall operate as or be deemed to be an amendment of the EU Meda License, as amended by the EU Amendment.

4. Governing Law . This Consent shall be governed by, and construed and enforced in accordance with, the laws of the State of North Carolina, without regard to its conflicts of laws rules.

5. Counterparts . This Consent may be executed in two or more counterparts, each of which shall be deemed and original, but all of which together shall constitute one and the same instrument. Signatures to the Consent may be transmitted via facsimile and such signatures shall be deemed to be originals.

[Signature page to follow]

IN WITNESS WHEREOF, the parties have executed and delivered this Consent as of the Consent Date.

Exhibit 10.5

AMENDMENT CONSENT

This AMENDMENT CONSENT (the “Consent”) is entered this January 2, 2009 (the “Consent Date”) by Arius Pharmaceuticals, Inc. (“Arius”) and Arius Two, Inc. (“Arius Two”).

WHEREAS, Arius and Arius Two are parties to that certain BEMA License Agreement, dated September 5, 2007, as amended (the “NA Arius Two License”);

WHEREAS, Arius and BioDelivery Sciences International, Inc. (“Parent”; with Arius, “BDSI”) granted Meda AB (“Meda”) rights to develop and commercialize certain Products in the United States, Canada, and Mexico in that certain License and Development Agreement between BDSI and Meda dated September 5, 2007 (the “NA Meda License”);

WHEREAS, Arius Two and Arius entered into that certain Sublicensing Consent, dated September 5, 2007 (the “NA License Consent”), enabling Arius to enter into the NA Meda License;

WHEREAS, Section 3.02(b) of the NA Arius Two License requires Arius Two’s approval of any sublicense granted by Arius under the NA Arius Two License;

WHEREAS, BDSI and Meda wish to amend the NA Meda License as described in the amendment attached hereto as Exhibit A (the “NA Amendment”), and Arius Two wishes to enable Arius to enter into the NA Amendment by executing this Consent.

NOW THEREFORE, in consideration of the foregoing premises and for other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the parties to this Consent agree as follows:

1. Definitions . Any capitalized terms not separately defined in this Consent or by reference to the NA Meda License shall have the meaning provided in the NA Arius Two License.

2. Consent and Approval . Arius Two hereby approves of and consents to the amendment of the NA Meda License as described in the NA Amendment and Arius’ execution thereof pursuant to Section 3.02(b) of the NA Arius Two License, and agrees that its consents, approvals, waivers, and agreements provided in the NA License Consent and other documents executed by Arius Two in conjunction with the NA Meda License shall hereafter apply to the NA Meda License as amended by the NA Amendment. Arius Two hereby agrees that all references to the NA Meda License and the defined terms thereof contained in the NA License Consent and any other documents executed by Arius Two in conjunction with the NA Meda License shall hereafter apply to the NA Meda License and its defined terms as amended, in each case, by the NA Amendment.

3. License to Continue in Full Force and Effect . To the extent that the terms of the NA Arius Two License are varied by Section 2 of this Consent with respect to the NA Meda License, as amended by the NA Amendment, or Arius’ performance as it relates thereto, such variations shall be deemed to be lawfully made amendments to the NA Arius Two License pursuant to Section 15.11 thereof with respect to the NA Meda License, as amended by the NA Amendment. Except as it may be modified by Section 2 of this Consent with respect solely to the NA Meda License, as

amended by the NA Amendment, or Arius’ performance as it relates thereto, the NA Arius Two License shall remain unchanged and in full force and effect. Nothing in this Consent shall operate as or be deemed to be an amendment of the NA Meda License, as amended by the NA Amendment.

4. Governing Law . This Consent shall be governed by, and construed and enforced in accordance with, the laws of the State of North Carolina, without regard to its conflicts of laws rules.

5. Counterparts . This Consent may be executed in two or more counterparts, each of which shall be deemed and original, but all of which together shall constitute one and the same instrument. Signatures to the Consent may be transmitted via facsimile and such signatures shall be deemed to be originals.

[Signature page to follow]

IN WITNESS WHEREOF, the parties have executed and delivered this Consent as of the Consent Date.