(Mark One)
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ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
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For the fiscal year ended December 31, 2017
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or
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☐
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TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
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For the transition period from to
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Delaware
(State or Other Jurisdiction of
Incorporation or Organization)
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26‑1469215
(I.R.S. Employer
Identification No.)
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955 Chesterbrook Blvd., Suite 200, Chesterbrook, PA
(Address of Principal Executive Offices)
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19087
(Zip Code)
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Title of each class
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Name of each exchange on which registered
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Common Stock, par value $0.001 per share
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NASDAQ Global Select Market
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Large accelerated filer ☐
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Accelerated filer ☒
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Non‑accelerated filer ☐
(Do not check if a
smaller reporting company)
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Smaller reporting company ☐
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Emerging growth company ☒
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our plans to develop and potentially commercialize our product candidates;
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our ability to fund future operating expenses and capital expenditures with our current cash resources or to secure additional funding in the future;
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our planned clinical trials and preclinical studies for our product candidates;
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the timing and likelihood of obtaining and maintaining regulatory approvals for our product candidates;
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the extent of clinical trials potentially required by the FDA for our product candidates;
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the clinical utility and potential market acceptance of our product candidates, particularly in light of existing and future competition;
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our sales, marketing and manufacturing capabilities and strategies;
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our intellectual property position; and
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our ability to identify or acquire additional product candidates with significant commercial potential that are consistent with our commercial objectives.
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OLINVO
TM
(oliceridine) Injection:
We are developing OLINVO, a G protein biased ligand of the μ opioid receptor, for the management of moderate-to-severe acute pain where intravenous, or IV, administration is preferred. In February 2017, we announced positive top-line results from our Phase 3 APOLLO-1 and APOLLO-2 pivotal efficacy studies of OLINVO in moderate-to-severe acute pain following bunionectomy and abdominoplasty, respectively. In both studies, all dose regimens achieved their primary endpoint of statistically greater analgesic efficacy than placebo, as measured by responder rate. In July 2017, we announced that we had completed enrollment in the Phase 3 open-label ATHENA safety study to support the new drug application, or NDA, for OLINVO. In the study, 768 patients were administered OLINVO to manage pain associated with a wide range of procedures and diagnoses. In January 2018, we announced that the United States Food and Drug Administration, or FDA, had accepted the NDA we submitted for OLINVO. The FDA also indicated that the Prescription Drug User Fee Act, or PDUFA, review date for the OLINVO NDA is November 2, 2018 and that it plans to hold an advisory committee meeting to discuss the NDA. If OLINVO ultimately receives regulatory approval, we plan to commercialize it in the United States, either on our own or with a commercial partner, for use in acute care settings such as hospitals and ambulatory surgery centers; outside the United States, we plan to commercialize OLINVO in certain countries with a commercial partner. We currently hold all worldwide development and commercialization rights to OLINVO.
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TRV250:
We are developing TRV250, a G protein biased ligand targeting the δ-receptor, as a compound with a potential first-in-class, non-narcotic
mechanism for the treatment of migraine. TRV250 also may have utility in a range of other central nervous system, or CNS, indications. Because TRV250 selectively targets the δ-receptor, we believe it will not have the addiction liability of conventional opioids or other μ opioid related adverse effects like those seen with morphine or oxycodone. In the second quarter of
2017
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All three OLINVO regimens (0.1 mg, 0.35 mg, and 0.5 mg on-demand doses) achieved the primary endpoint with statistically superior responder rates compared to placebo at 48 hours (p<0.0001, adjusted for multiplicity).
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The 0.35 mg and 0.5 mg OLINVO dose regimens demonstrated efficacy comparable to morphine at 48 hours based on responder rate (both doses p<0.005 for non-inferiority to morphine). Both doses were also comparable to morphine for rates of rescue analgesic use.
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Following the 1.5 mg initial loading dose, all OLINVO regimens demonstrated rapid onset with statistically significant efficacy within 5 minutes (p<0.05).
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OLINVO exhibited a dose-related trend of improved respiratory safety burden in all three OLINVO dose regimens (p<0.05 for the 0.1 mg regimen vs. morphine). Consistent with this, in all dose regimens OLINVO showed dose-related trends of reduced respiratory safety events (P<0.05 for 0.1 mg and 0.35 mg regimens vs. morphine), prevalence of oxygen desaturation (O2<90%) and lower prevalence of supplemental oxygen use (p<0.05 for the 0.1 mg regimen vs. morphine for both measures).
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OLINVO exhibited less antiemetic use compared to morphine (p<0.05 for all OLINVO regimens vs. morphine). Consistent with this, OLINVO showed dose related trends of lower prevalence of nausea and vomiting in all three OLINVO regimens (p<0.05 for the 0.1 mg regimen vs. morphine).
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All three OLINVO dose regimens achieved the primary endpoint with statistically superior responder rates compared to placebo at 24 hours (adjusted p<0.05 for the 0.1 mg regimen; adjusted p<0.001 for the 0.35 mg and 0.5 mg regimens).
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The 0.35 mg and 0.5 mg OLINVO dose regimens demonstrated efficacy comparable to morphine at 24 hours based on responder rate (p<0.05 for non-inferiority of the 0.35 mg regimen vs. morphine). Both doses were also comparable to morphine for rates of rescue analgesic use.
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Following the 1.5 mg initial loading dose, all OLINVO regimens demonstrated rapid onset with statistically significant efficacy within 5 to 15 minutes (p<0.05).
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OLINVO showed a dose-related trend of improved respiratory safety burden in all three OLINVO dose regimens (p<0.05 for the 0.1 mg regimen vs. morphine). Consistent with this, for all dose regimens OLINVO showed dose-related trends of reduced respiratory safety events, prevalence of oxygen desaturation (O2<90%) and lower prevalence of supplemental oxygen use (p<0.05 for the 0.1 mg regimen vs. morphine for all measures).
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OLINVO showed a dose-related trend of less antiemetic use than morphine for all three OLINVO regimens (p<0.05 for the 0.1 mg OLINVO regimen vs. morphine). Consistent with this, OLINVO showed dose-related trends of lower prevalence of nausea and vomiting (p<0.05 for the 0.1 mg regimen vs. morphine for both nausea and vomiting; p<0.05 for the 0.35 mg regimen vs. morphine for vomiting).
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completion of preclinical laboratory tests, animal studies and formulation studies in compliance with the FDA’s good laboratory practice, or GLP, regulations;
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submission to the FDA of an IND, which must become effective before human clinical trials may begin;
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approval by an independent institutional review board, or IRB, covering each clinical site before each trial may be initiated;
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performance of human clinical trials, including adequate and well‑controlled clinical trials, in accordance with good clinical practices, or GCP, to establish the safety and efficacy of the proposed drug product for each indication;
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submission of an NDA to the FDA;
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completion of an FDA advisory committee review, if applicable;
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satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the product is produced to assess compliance with current good manufacturing practices, or cGMP, and to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity, as well as satisfactory completion of an FDA inspection of selected clinical sites to determine GCP compliance;
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FDA review and approval of an NDA; and
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in certain cases, DEA review and scheduling activities prior to launch.
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restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls;
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fines, warning letters or holds on post‑approval clinical trials;
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refusal of the FDA to approve pending NDAs or supplements to approved NDAs, or suspension or revocation of product license approvals;
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product seizure or detention, or refusal to permit the import or export of products; or
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injunctions or the imposition of civil or criminal penalties.
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the required patent information has not been filed;
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the listed patent has expired;
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the listed patent has not expired, but will expire on a particular date and approval is sought after patent expiration; or
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the listed patent is invalid, unenforceable or will not be infringed by the new product.
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Name
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Age
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Position
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Maxine Gowen, Ph.D.
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59
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President, Chief Executive Officer and Director
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Carrie L. Bourdow
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Executive Vice President and Chief Operating Officer
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Roberto Cuca
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Senior Vice President and Chief Financial Officer
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David P. Geoghegan
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Senior Vice President, Operations
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Yacoub Habib, Ph.D.
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50
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Senior Vice President, Business Development and Corporate Planning
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John M. Limongelli, Esq.
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Senior Vice President, General Counsel and Chief Administrative Officer
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Jonathan Violin, Ph.D.
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Senior Vice President, Scientific Affairs and Investor Relations Officer
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establish sales, marketing and distribution capabilities and scale up external manufacturing capabilities to commercialize OLINVO, if approved, and any other products that we choose not to license to a third party and for which we may obtain regulatory approval;
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conduct clinical trials for TRV250, our δ‑receptor product candidate, as well as any additional clinical trials of OLINVO that may be required by FDA;
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seek to identify and discover additional product candidates;
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conduct clinical trials and seek regulatory approvals for any product candidates that successfully complete clinical trials;
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maintain, expand, and protect our intellectual property portfolio;
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hire additional sales, marketing, medical, clinical and scientific personnel; and
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add operational, financial, and management information systems and personnel, including personnel to support our product development and planned future commercialization efforts.
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significantly delay, scale back, or discontinue our operations, development programs, and/or any future commercialization efforts;
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relinquish, or license on unfavorable terms, our rights to technologies or product candidates that we otherwise would seek to develop or commercialize ourselves;
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seek collaborators for one or more of our product candidates at an earlier stage than otherwise would be desirable or on terms that are less favorable than might otherwise be available; or
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cease operations altogether.
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the costs, timing, and outcome of regulatory review of the OLINVO NDA or any future product candidates, both in the United States and in territories outside the United States;
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our ability to enter into collaborative agreements for the development and commercialization of our product candidates, including OLINVO;
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the costs and timing of future commercialization activities, including product manufacturing, marketing, sales, and distribution, for any of our product candidates for which we receive marketing approval;
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any product liability or other lawsuits related to our products;
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the scope, progress, results and costs of preclinical development, laboratory testing, and clinical trials for our other product candidates, including TRV250;
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the expenses needed to attract and retain skilled personnel;
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the number and development requirements of other product candidates that we pursue;
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the revenue, if any, received from commercial sales of our product candidates for which we receive marketing approval; and
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the costs involved in preparing, filing, and prosecuting patent applications, maintaining and enforcing our intellectual property rights, and defending any intellectual property-related claims, both in the United States and in territories outside the United States.
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restrictions on such products, manufacturers or manufacturing processes;
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restrictions on the labeling or marketing of a product;
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restrictions on product distribution or use;
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requirements to conduct post‑marketing studies or clinical trials;
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warning letters;
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withdrawal of the products from the market;
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refusal to approve pending applications or supplements to approved applications that we submit;
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recall of products;
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fines, restitution or disgorgement of profits or revenue;
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suspension or withdrawal of marketing approvals;
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refusal to permit the import or export of our products;
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product seizure; or
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injunctions or the imposition of civil or criminal penalties.
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the efficacy, safety and potential advantages compared to alternative treatments;
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the timing of market introduction of the product candidate as well as competitive products;
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our ability to offer the product for sale profitably and at competitive prices;
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the convenience and ease of administration compared to alternative treatments;
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the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies;
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the strength of sales, marketing, and distribution support;
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the availability of third party coverage and adequate reimbursement;
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the prevalence and severity of any side effects;
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the clinical indications for which the product is approved; and
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any restrictions on the use of our products, both on their own and together with other medications.
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our inability to recruit, train and retain adequate numbers of effective sales and marketing personnel or to outsource these tasks to a third party;
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the inability of sales personnel to obtain access to physicians or educate adequate numbers of physicians on the benefit of our future products;
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the lack of complementary or other products to be offered by sales personnel, which may put us at a competitive disadvantage from the perspective of sales efficiency relative to companies with more extensive product lines; and
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unforeseen costs and expenses associated with creating a sales and marketing organization.
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decreased demand for any product candidates or products that we may develop;
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injury to our reputation and significant negative media attention;
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withdrawal of clinical trial participants;
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initiation of investigations by regulators;
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significant costs to defend the related litigation;
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product recalls, withdrawals or labeling, marketing or promotional restrictions;
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substantial monetary awards to trial participants or patients;
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loss of revenue;
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reduced resources of our management to pursue our business strategy; and
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the inability to commercialize any products that we may develop.
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successful completion of preclinical studies and clinical trials;
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receipt of marketing approvals from applicable regulatory authorities;
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obtaining, maintaining, and protecting our intellectual property portfolio, including patents and trade secrets, and regulatory exclusivity for our product candidates;
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making arrangements with third-party manufacturers for, or establishing, commercial manufacturing capabilities;
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launching commercial sales of the products, if and when approved, whether alone or in collaboration with others;
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acceptance of our products, if and when approved, by patients, the medical community, and third party payors;
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effectively competing with other therapies;
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obtaining and maintaining healthcare coverage of our products and adequate reimbursement; and
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maintaining a continued acceptable safety profile of our products following approval.
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regulators or institutional review boards may not authorize us or our investigators to commence a clinical trial or conduct a clinical trial at prospective trial sites;
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we may experience delays in reaching, or fail to reach, agreement on acceptable clinical trial contracts or clinical trial protocols with prospective trial sites;
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clinical trials of our product candidates may produce negative or inconclusive results, and we may decide, or regulators may require us, to conduct additional clinical trials or abandon product development programs;
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the number of patients required for clinical trials of our product candidates may be larger than we anticipate, enrollment in these clinical trials may be slower than we anticipate, or participants may drop out of these clinical trials at a higher rate than we anticipate;
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our third party contractors may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all;
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we may have to suspend or terminate clinical trials of our product candidates for various reasons, including a finding that the participants are being exposed to unacceptable health risks;
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regulators or institutional review boards may require that we or our investigators suspend or terminate clinical research for various reasons, including noncompliance with regulatory requirements or a finding that the participants are being exposed to unacceptable health risks;
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the cost of clinical trials of our product candidates may be greater than we anticipate;
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the supply or quality of our product candidates or other materials necessary to conduct clinical trials of our product candidates may be insufficient or inadequate; and
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our product candidates may have undesirable side effects or other unexpected characteristics, causing us or our investigators, regulators or institutional review boards to suspend or terminate the trials.
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be delayed in obtaining marketing approval for our product candidates;
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not obtain marketing approval at all;
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obtain approval for indications or patient populations that are not as broad as intended or desired;
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obtain approval with labeling that includes significant use or distribution restrictions or safety warnings;
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be subject to additional post‑marketing testing and/or reporting requirements; or
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have the product removed from the market after obtaining marketing approval.
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the severity of the disease under investigation;
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the eligibility criteria for the study in question;
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the perceived risks and benefits of the product candidate under study;
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the efforts to facilitate timely enrollment in clinical trials;
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the patient referral practices of physicians;
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the ability to monitor patients adequately during and after treatment; and
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the proximity and availability of clinical trial sites for prospective patients.
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regulatory authorities may require additional warnings on the label or even withdraw approvals of such product;
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we may be required to create a medication guide outlining the risks of such side effects for distribution to patients, if one is not required in connection with regulatory approval;
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we could be sued and held liable for harm caused to patients; and
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our reputation may suffer.
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collaborators have significant discretion in determining the efforts and resources that they will apply to these collaborations;
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collaborators may not perform their obligations as expected;
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collaborators may elect not to continue development or commercialization programs or may not pursue commercialization of any product candidates that achieve regulatory approval based on clinical trial results, changes in the collaborators’ strategic focus or available funding, or external factors, such as an acquisition, that divert resources or create competing priorities;
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collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a product candidate, repeat or conduct new clinical trials, or require a new formulation of a product candidate for clinical testing;
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collaborators could fail to make timely regulatory submissions for a product candidate;
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collaborators may not comply with all applicable regulatory requirements or may fail to report safety data in accordance with all applicable regulatory requirements;
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collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our products or product candidates if the collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours;
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product candidates discovered in collaboration with us may be viewed by our collaborators as competitive with their own product candidates or products, which may cause collaborators to limit or eliminate efforts and resources to the commercialization of our product candidates;
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a collaborator with marketing and distribution rights to one or more of our product candidates that achieve regulatory approval may not commit sufficient resources to the marketing and distribution of such product or products;
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disagreements with collaborators, including disagreements over proprietary rights, contract interpretation, or the preferred course of development, might cause delays or termination of the research, development or commercialization of product candidates, might lead to additional responsibilities for us with respect to product candidates, or might result in litigation or arbitration, any of which would be time-consuming and expensive;
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collaborators may not properly maintain or defend our intellectual property rights or may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our intellectual property or proprietary information or expose us to potential litigation;
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collaborators may infringe the intellectual property rights of third parties, which may expose us to litigation and potential liability; and
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collaborations may be terminated at the convenience of the collaborator and, if terminated, we could be required to raise additional capital to pursue further development or commercialization of the applicable product candidates.
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reliance on the third party for regulatory compliance and quality assurance;
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the possible breach of the manufacturing agreement by the third party;
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manufacturing delays if our third party manufacturers give greater priority to the supply of other products over our product candidates or otherwise do not satisfactorily perform according to the terms of the agreement between us;
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the possible misappropriation of our proprietary information, including our trade secrets and know-how; and
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the possible termination or nonrenewal of the agreement by the third party at a time that is costly or inconvenient for us.
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the federal Anti‑Kickback Statute, which prohibits, 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 federal and state healthcare programs, such as Medicare and Medicaid;
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federal civil and criminal false claims laws and civil monetary penalty laws, including the federal False Claims Act, which impose criminal and civil penalties, including civil whistleblower or
qui tam
actions, against individuals or entities for, among other things, 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, which imposes, among other things, criminal and civil liability for executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters;
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HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH, and their respective implementing regulations, which impose, among other things, obligations on covered healthcare providers, health plans, and healthcare clearinghouses, as well as their business associates that create, receive, maintain or transmit individually identifiable health information for or on behalf of a covered entity, with respect to safeguarding the privacy, security and transmission of individually identifiable health information;
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the federal Open Payments program, which requires manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to the Centers for Medicare & Medicaid Services, or CMS, information related to “payments or other transfers of value” made to physicians, which is defined to include doctors, dentists, optometrists, podiatrists and chiropractors, and teaching hospitals and applicable manufacturers and applicable group purchasing
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analogous state and foreign laws and regulations, such as state anti‑kickback and false claims laws, which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non‑governmental third party payors, including private insurers; state and foreign laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government or otherwise restrict payments that may be made to healthcare providers; state and foreign laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures; and state and foreign laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.
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an annual, nondeductible fee on any entity that manufactures or imports specified branded prescription drugs and biologic agents, apportioned among these entities according to their market share in certain government healthcare programs;
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an increase in the statutory minimum rebates a manufacturer must pay under the Medicaid Drug Rebate Program to 23.1% and 13.0% of the average manufacturer price for branded and generic drugs, respectively;
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expansion of healthcare fraud and abuse laws, including the False Claims Act and the Anti‑Kickback Statute, new government investigative powers and enhanced penalties for non‑compliance;
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a new Medicare Part D coverage gap discount program, in which manufacturers must agree to offer 50% (and 70% commencing January 1, 2019) point‑of‑sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for a manufacturer’s outpatient drugs to be covered under Medicare Part D;
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extension of a manufacturer’s Medicaid rebate liability to covered drugs dispensed to individuals who are enrolled in Medicaid managed care organizations;
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expansion of eligibility criteria for Medicaid programs by, among other things, allowing states to offer Medicaid coverage to additional individuals and by adding new mandatory eligibility categories for certain individuals with income at or below 133% of the federal poverty level, thereby potentially increasing a manufacturer’s Medicaid rebate liability;
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expansion of the entities eligible for discounts under the Public Health Service pharmaceutical pricing program;
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the new requirements under the federal Open Payments program and its implementing regulations;
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a new requirement to annually report drug samples that manufacturers and distributors provide to physicians; and
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a new Patient‑Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research.
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efforts to develop an international sales, marketing and distribution organization may increase our expenses, divert our management’s attention from the development of product candidates or cause us to forgo profitable licensing opportunities in these geographies;
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changes in a specific country’s or region’s political and cultural climate or economic condition;
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unexpected changes in foreign laws and regulatory requirements;
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difficulty of effective enforcement of contractual provisions in local jurisdictions;
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inadequate intellectual property protection in foreign countries;
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differing payor reimbursement regimes, governmental payors or patient self-pay systems and price controls;
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trade‑protection measures, import or export licensing requirements such as Export Administration Regulations promulgated by the U.S. Department of Commerce and fines, penalties or suspension or revocation of export privileges;
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regulations under the U.S. Foreign Corrupt Practices Act and similar foreign anti‑corruption laws;
|
•
|
the effects of applicable foreign tax structures and potentially adverse tax consequences; and
|
•
|
significant adverse changes in foreign currency exchange rates which could make the cost of our clinical trials, to the extent conducted outside of the United States, more expensive.
|
•
|
actual or anticipated variations in our operating results;
|
•
|
changes in financial estimates by us or by any securities analysts who might cover our stock;
|
•
|
the timing and results of our clinical trials for any of our product candidates;
|
•
|
failure or discontinuation of any of our development programs;
|
|
|
|
•
|
conditions or trends in our industry;
|
•
|
stock market price and volume fluctuations of comparable companies and, in particular, those that operate in the biopharmaceutical industry;
|
•
|
announcements by us or our competitors of significant acquisitions, strategic partnerships or divestitures;
|
•
|
developments or disputes concerning patent applications, issued patents or other proprietary rights;
|
•
|
announcements of investigations or regulatory scrutiny of our operations or lawsuits filed against us;
|
•
|
capital commitments;
|
•
|
investors’ general perception of our company and our business;
|
•
|
recruitment or departure of key personnel;
|
•
|
announcements and expectations of additional financing efforts; and
|
•
|
sales of our common stock, including sales by our directors and officers or specific stockholders.
|
|
|
|
•
|
only one of our three classes of directors will be elected each year;
|
•
|
stockholders are not entitled to remove directors other than by a 66 2/3% vote and only for cause;
|
•
|
stockholders are not permitted to take actions by written consent;
|
•
|
stockholders cannot call a special meeting of stockholders; and
|
•
|
stockholders must give advance notice to nominate directors or submit proposals for consideration at stockholder meetings.
|
|
|
|
|
|
|
|
|
|
|
High
|
|
Low
|
||||
2017
|
|
|
|
||||
First quarter
|
$
|
8.00
|
|
|
$
|
3.26
|
|
Second quarter
|
$
|
3.80
|
|
|
$
|
2.16
|
|
Third quarter
|
$
|
3.10
|
|
|
$
|
2.15
|
|
Fourth quarter
|
$
|
2.64
|
|
|
$
|
1.35
|
|
2016
|
|
|
|
|
|
||
First quarter
|
$
|
10.51
|
|
|
$
|
6.55
|
|
Second quarter
|
$
|
9.49
|
|
|
$
|
5.58
|
|
Third quarter
|
$
|
7.63
|
|
|
$
|
6.13
|
|
Fourth quarter
|
$
|
6.90
|
|
|
$
|
3.76
|
|
|
|
|
Plan Category
|
|
Number of
Securities to be
Issued Upon
Exercise of
Outstanding
Options,
Warrants and
Rights
|
|
Weighted-Average
Exercise Price of
Outstanding
Options, Warrants
and Rights
|
|
Number of
Securities
Remaining
Available
for Issuance
Under Equity
Compensation
Plans (1)(2)(3)
|
||||
Equity compensation plans approved by stockholders
|
|
8,417,223
|
|
|
$
|
5.28
|
|
|
991,613
|
|
Equity compensation plans not approved by stockholders
|
|
207,000
|
|
|
2.62
|
|
|
293,000
|
|
|
Total
|
|
8,624,223
|
|
|
$
|
5.22
|
|
|
1,284,613
|
|
|
|
|
|
Year Ended December 31,
|
||||||||||||||||||
|
2017
|
|
2016
|
|
2015
|
|
2014
|
|
2013
|
||||||||||
Statement of Operations Data:
|
(in thousands, except share and per share data)
|
||||||||||||||||||
Revenue
|
|
|
|
|
|
|
|
|
|
|
|
|
|||||||
Total revenue
|
$
|
—
|
|
|
$
|
3,750
|
|
|
$
|
6,250
|
|
|
$
|
—
|
|
|
$
|
135
|
|
Operating expenses:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|||||
General and administrative
|
19,639
|
|
|
16,077
|
|
|
12,797
|
|
|
9,403
|
|
|
4,718
|
|
|||||
Research and development
|
48,974
|
|
|
89,956
|
|
|
44,074
|
|
|
40,547
|
|
|
18,762
|
|
|||||
Restructuring charges
|
1,774
|
|
|
—
|
|
|
—
|
|
|
—
|
|
|
—
|
|
|||||
Total operating expenses
|
70,387
|
|
|
106,033
|
|
|
56,871
|
|
|
49,950
|
|
|
23,480
|
|
|||||
Loss from operations
|
(70,387
|
)
|
|
(102,283
|
)
|
|
(50,621
|
)
|
|
(49,950
|
)
|
|
(23,345
|
)
|
|||||
Total other income
|
(1,478
|
)
|
|
(711
|
)
|
|
93
|
|
|
249
|
|
|
94
|
|
|||||
Net loss
|
(71,865
|
)
|
|
(102,994
|
)
|
|
(50,528
|
)
|
|
(49,701
|
)
|
|
(23,251
|
)
|
|||||
Accretion of redeemable convertible preferred stock
|
—
|
|
|
—
|
|
|
—
|
|
|
(29
|
)
|
|
(334
|
)
|
|||||
Net loss attributable to common stockholders
|
$
|
(71,865
|
)
|
|
$
|
(102,994
|
)
|
|
$
|
(50,528
|
)
|
|
$
|
(49,730
|
)
|
|
$
|
(23,585
|
)
|
Net loss per share—basic and diluted
|
$
|
(1.21
|
)
|
|
$
|
(1.97
|
)
|
|
$
|
(1.15
|
)
|
|
$
|
(2.02
|
)
|
|
$
|
(29.71
|
)
|
Weighted average shares of common stock outstanding used in computing net loss per share—basic and diluted
|
59,436,649
|
|
|
52,398,521
|
|
|
43,794,276
|
|
|
24,655,603
|
|
|
793,806
|
|
|
As of December 31,
|
||||||||||||||||||
|
2017
|
|
2016
|
|
2015
|
|
2014
|
|
2013
|
||||||||||
|
(in thousands)
|
||||||||||||||||||
Balance Sheet Data:
|
|
|
|
|
|
|
|
|
|
|
|
||||||||
Cash and cash equivalents
|
$
|
16,557
|
|
|
$
|
24,266
|
|
|
$
|
46,774
|
|
|
$
|
36,206
|
|
|
$
|
37,965
|
|
Marketable securities
|
49,543
|
|
|
86,335
|
|
|
125,864
|
|
|
70,699
|
|
|
—
|
|
|||||
Total assets
|
72,722
|
|
|
114,654
|
|
|
175,354
|
|
|
108,337
|
|
|
42,393
|
|
|||||
Total liabilities
|
38,089
|
|
|
36,073
|
|
|
32,223
|
|
|
9,134
|
|
|
3,401
|
|
|||||
Total redeemable convertible preferred stock
|
—
|
|
|
—
|
|
|
—
|
|
|
—
|
|
|
120,562
|
|
|||||
Total stockholders’ equity (deficit)
|
34,633
|
|
|
78,581
|
|
|
143,131
|
|
|
99,204
|
|
|
(81,571
|
)
|
|
|
|
•
|
OLINVO
TM
(oliceridine) Injection:
We are developing OLINVO, a G protein biased ligand of the μ opioid receptor, for the management of moderate-to-severe acute pain where intravenous, or IV, administration is preferred. In February 2017, we announced positive top-line results from our Phase 3 APOLLO-1 and APOLLO-2 pivotal efficacy studies of OLINVO in moderate-to-severe acute pain following bunionectomy and abdominoplasty, respectively. In both studies, all dose regimens achieved their primary endpoint of statistically greater analgesic efficacy than placebo, as measured by responder rate. In July 2017, we announced that we had completed enrollment in the Phase 3 open-label ATHENA safety study to support the new drug application, or NDA, for OLINVO. In the study, 768 patients were administered OLINVO to manage pain associated with a wide range of procedures and diagnoses. In January 2018, we announced that the United States Food and Drug Administration, or FDA, had accepted the NDA we submitted for OLINVO. The FDA also indicated that the Prescription Drug User Fee Act, or PDUFA, review date for the OLINVO NDA is November 2, 2018 and that it plans to hold an advisory committee meeting to discuss the NDA. If OLINVO ultimately receives regulatory approval, we plan to commercialize it in the United States, either on our own or with a commercial partner, for use in acute care settings such as hospitals and ambulatory surgery centers; outside the United States, we plan to commercialize OLINVO in certain countries with a commercial partner. We currently hold all worldwide development and commercialization rights to OLINVO.
|
•
|
TRV250:
We are developing TRV250, a G protein biased ligand targeting the δ-receptor, as a compound with a potential first-in-class, non-narcotic
mechanism for the treatment of migraine. TRV250 also may have utility in a range of other central nervous system, or CNS, indications. Because TRV250 selectively targets the δ-receptor, we believe it will not have the addiction liability of conventional opioids or other μ opioid related adverse effects like those seen with morphine or oxycodone. In the second quarter of
2017
, we began a Phase I study of TRV250 in the United Kingdom in healthy volunteers; we expect to complete dosing in this study by the end of the first quarter of 2018.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Year Ended December 31,
|
|
|
||||||||
|
2017
|
|
2016
|
|
Change
|
||||||
Revenue:
|
|
|
|
|
|
||||||
Collaboration revenue
|
$
|
—
|
|
|
$
|
3,750
|
|
|
$
|
(3,750
|
)
|
Total revenue
|
—
|
|
|
3,750
|
|
|
(3,750
|
)
|
|||
Operating expenses:
|
|
|
|
|
|
||||||
General and administrative
|
19,639
|
|
|
16,077
|
|
|
3,562
|
|
|||
Research and development
|
48,974
|
|
|
89,956
|
|
|
(40,982
|
)
|
|||
Restructuring
|
1,774
|
|
|
—
|
|
|
1,774
|
|
|||
Total operating expenses
|
70,387
|
|
|
106,033
|
|
|
(35,646
|
)
|
|||
Loss from operations
|
(70,387
|
)
|
|
(102,283
|
)
|
|
31,896
|
|
|||
Other income (expense):
|
|
|
|
|
|
||||||
Change in fair value of warrant liability
|
65
|
|
|
78
|
|
|
(13
|
)
|
|||
Miscellaneous income
|
614
|
|
|
222
|
|
|
392
|
|
|||
Net (loss) gain on asset disposals
|
(56
|
)
|
|
(16
|
)
|
|
(40
|
)
|
|||
Interest income
|
679
|
|
|
743
|
|
|
(64
|
)
|
|||
Interest expense
|
(2,780
|
)
|
|
(1,738
|
)
|
|
(1,042
|
)
|
|||
Total other (expense) income
|
(1,478
|
)
|
|
(711
|
)
|
|
(767
|
)
|
|||
Net loss attributable to common stockholders
|
$
|
(71,865
|
)
|
|
$
|
(102,994
|
)
|
|
$
|
31,129
|
|
|
|
|
|
Year Ended December 31,
|
||||||
|
2017
|
|
2016
|
||||
Personnel-related costs
|
$
|
12,115
|
|
|
$
|
12,499
|
|
OLINVO
|
28,688
|
|
|
63,156
|
|
||
TRV027
|
99
|
|
|
6,890
|
|
||
TRV250
|
3,629
|
|
|
2,970
|
|
||
Other research and development
|
4,443
|
|
|
4,441
|
|
||
|
$
|
48,974
|
|
|
$
|
89,956
|
|
|
Year Ended December 31,
|
|
|
||||||||
|
2016
|
|
2015
|
|
Change
|
||||||
Revenue:
|
|
|
|
|
|
||||||
Collaboration revenue
|
$
|
3,750
|
|
|
$
|
6,250
|
|
|
$
|
(2,500
|
)
|
Total revenue
|
3,750
|
|
|
6,250
|
|
|
(2,500
|
)
|
|||
Operating expenses:
|
|
|
|
|
|
||||||
General and administrative
|
16,077
|
|
|
12,797
|
|
|
3,280
|
|
|||
Research and development
|
89,956
|
|
|
44,074
|
|
|
45,882
|
|
|||
Total operating expenses
|
106,033
|
|
|
56,871
|
|
|
49,162
|
|
|||
Loss from operations
|
(102,283
|
)
|
|
(50,621
|
)
|
|
(51,662
|
)
|
|||
Other income (expense):
|
|
|
|
|
|
||||||
Change in fair value of warrant liability
|
78
|
|
|
(70
|
)
|
|
148
|
|
|||
Miscellaneous income
|
222
|
|
|
174
|
|
|
48
|
|
|||
Net (loss) gain on asset disposals
|
(16
|
)
|
|
(8
|
)
|
|
(8
|
)
|
|||
Interest income
|
743
|
|
|
331
|
|
|
412
|
|
|||
Interest expense
|
(1,738
|
)
|
|
(334
|
)
|
|
(1,404
|
)
|
|||
Total other (expense) income
|
(711
|
)
|
|
93
|
|
|
(804
|
)
|
|||
Net loss
|
(102,994
|
)
|
|
(50,528
|
)
|
|
(52,466
|
)
|
|
|
|
|
Year Ended December 31,
|
||||||
|
2016
|
|
2015
|
||||
Personnel-related costs
|
$
|
12,499
|
|
|
$
|
9,646
|
|
OLINVO
|
63,156
|
|
|
16,916
|
|
||
TRV027
|
6,890
|
|
|
11,851
|
|
||
TRV250
|
2,970
|
|
|
1,014
|
|
||
Other research and development
|
4,441
|
|
|
4,647
|
|
||
|
$
|
89,956
|
|
|
$
|
44,074
|
|
|
Year Ended
|
||||||||||
|
December 31,
|
||||||||||
|
2017
|
|
2016
|
|
2015
|
||||||
Net cash (used in) provided by:
|
|
|
|
|
|
||||||
Operating activities
|
$
|
(71,255
|
)
|
|
$
|
(91,554
|
)
|
|
$
|
(40,075
|
)
|
Investing activities
|
32,780
|
|
|
37,798
|
|
|
(56,939
|
)
|
|||
Financing activities
|
30,986
|
|
|
32,329
|
|
|
107,582
|
|
|||
Net (decrease) increase in cash and cash equivalents
|
$
|
(7,489
|
)
|
|
$
|
(21,427
|
)
|
|
$
|
10,568
|
|
|
|
|
•
|
the timing and results of the FDA's review of the NDA submission for OLINVO and related regulatory activities;
|
|
|
|
•
|
our ability to enter into collaborative agreements for the development and/or commercialization of our product candidates, including for OLINVO;
|
•
|
the number and development requirements of any other product candidates that we may pursue;
|
•
|
the scope, progress, results and costs of researching and developing our product candidates or any future product candidates, both in the United States and in territories outside the United States;
|
•
|
the costs, timing and outcome of regulatory review of our product candidates or any future product candidates, both in the United States and in territories outside the United States;
|
•
|
the costs and timing of future commercialization activities, including product manufacturing, marketing, sales and distribution, for any of our product candidates for which we receive marketing approval;
|
•
|
any product liability or other lawsuits related to our products;
|
•
|
the expenses needed to attract and retain skilled personnel;
|
•
|
the revenue, if any, received from commercial sales of our product candidates for which we receive marketing approval; and
|
•
|
the costs involved in preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending our intellectual property-related claims, both in the United States and in territories outside the United States.
|
|
Payments Due By Period
|
||||||||||||||||||
|
|
|
Less than
|
|
|
|
|
|
More than
|
||||||||||
|
Total
|
|
1 year
|
|
1 ‑ 3 years
|
|
3 ‑ 5 years
|
|
5 years
|
||||||||||
Operating lease obligations(1)
|
$
|
14,385
|
|
|
$
|
970
|
|
|
$
|
2,627
|
|
|
$
|
2,777
|
|
|
$
|
8,011
|
|
Loans payable
|
28,500
|
|
|
12,667
|
|
|
15,833
|
|
|
—
|
|
|
—
|
|
|||||
Total
|
$
|
42,885
|
|
|
$
|
13,637
|
|
|
$
|
18,460
|
|
|
$
|
2,777
|
|
|
$
|
8,011
|
|
|
|
|
|
|
|
•
|
pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect our transactions and dispositions of our assets;
|
•
|
provide reasonable assurance that our transactions are recorded as necessary to permit preparation of our financial statements in accordance with accounting principles generally accepted in the United States of America, and that our receipts and expenditures are being made only in accordance with authorization of our management and our directors; and
|
•
|
provide reasonable assurance regarding prevention or timely detection of unauthorized acquisition, use, or disposition of our assets that could have a material effect on our financial statements.
|
|
|
|
|
|
|
|
2017
|
|
2016
|
||||
Assets
|
|
|
|
||||
Current assets:
|
|
|
|
||||
Cash and cash equivalents
|
$
|
16,557
|
|
|
$
|
24,266
|
|
Marketable securities
|
49,543
|
|
|
86,335
|
|
||
Prepaid expenses and other current assets
|
1,393
|
|
|
1,788
|
|
||
Total current assets
|
67,493
|
|
|
112,389
|
|
||
Restricted cash
|
1,413
|
|
|
1,193
|
|
||
Property and equipment, net
|
3,805
|
|
|
1,059
|
|
||
Intangible asset, net
|
11
|
|
|
13
|
|
||
Total assets
|
$
|
72,722
|
|
|
$
|
114,654
|
|
Liabilities and stockholders’ equity
|
|
|
|
||||
Current liabilities:
|
|
|
|
||||
Accounts payable
|
$
|
1,424
|
|
|
$
|
8,749
|
|
Accrued expenses and other current liabilities
|
4,303
|
|
|
8,208
|
|
||
Current portion of loans payable, net
|
12,425
|
|
|
5,039
|
|
||
Deferred rent
|
61
|
|
|
52
|
|
||
Total current liabilities
|
18,213
|
|
|
22,048
|
|
||
Loans payable, net
|
15,725
|
|
|
13,270
|
|
||
Capital leases, net of current portion
|
31
|
|
|
18
|
|
||
Deferred rent, net of current portion
|
3,006
|
|
|
187
|
|
||
Warrant liability
|
10
|
|
|
75
|
|
||
Other long term liabilities
|
1,104
|
|
|
475
|
|
||
Total liabilities
|
38,089
|
|
|
36,073
|
|
||
Commitments and contingencies (Note 8)
|
|
|
|
||||
Stockholders’ equity:
|
|
|
|
||||
Common stock—$0.001 par value; 100,000,000 shares authorized, 62,310,795 and 55,768,414 shares issued and outstanding at December 31, 2017 and December 31, 2016, respectively
|
62
|
|
|
56
|
|
||
Preferred stock—$0.001 par value; 5,000,000 shares authorized, none issued or outstanding at December 31, 2017 and December 31, 2016
|
—
|
|
|
—
|
|
||
Additional paid-in capital
|
392,103
|
|
|
364,148
|
|
||
Accumulated deficit
|
(357,490
|
)
|
|
(285,625
|
)
|
||
Accumulated other comprehensive income (loss)
|
(42
|
)
|
|
2
|
|
||
Total stockholders’ equity
|
34,633
|
|
|
78,581
|
|
||
Total liabilities and stockholders’ equity
|
$
|
72,722
|
|
|
$
|
114,654
|
|
|
|
|
|
Year Ended December 31,
|
||||||||||
|
2017
|
|
2016
|
|
2015
|
||||||
Revenue:
|
|
|
|
|
|
||||||
Collaboration revenue
|
$
|
—
|
|
|
$
|
3,750
|
|
|
$
|
6,250
|
|
Total revenue
|
—
|
|
|
3,750
|
|
|
6,250
|
|
|||
Operating expenses:
|
|
|
|
|
|
||||||
General and administrative
|
19,639
|
|
|
16,077
|
|
|
12,797
|
|
|||
Research and development
|
48,974
|
|
|
89,956
|
|
|
44,074
|
|
|||
Restructuring charges
|
1,774
|
|
|
—
|
|
|
—
|
|
|||
Total operating expenses
|
70,387
|
|
|
106,033
|
|
|
56,871
|
|
|||
Loss from operations
|
(70,387
|
)
|
|
(102,283
|
)
|
|
(50,621
|
)
|
|||
Other income (expense):
|
|
|
|
|
|
||||||
Change in fair value of warrant liability
|
65
|
|
|
78
|
|
|
(70
|
)
|
|||
Miscellaneous income
|
614
|
|
|
222
|
|
|
174
|
|
|||
Net (loss) gain on asset disposals
|
(56
|
)
|
|
(16
|
)
|
|
(8
|
)
|
|||
Interest income
|
679
|
|
|
743
|
|
|
331
|
|
|||
Interest expense
|
(2,780
|
)
|
|
(1,738
|
)
|
|
(334
|
)
|
|||
Total other (expense) income
|
(1,478
|
)
|
|
(711
|
)
|
|
93
|
|
|||
Net loss attributable to common stockholders
|
$
|
(71,865
|
)
|
|
$
|
(102,994
|
)
|
|
$
|
(50,528
|
)
|
Other comprehensive income (loss), net:
|
|
|
|
|
|
|
|
|
|||
Unrealized gain (loss) on marketable securities
|
(44
|
)
|
|
208
|
|
|
(187
|
)
|
|||
Other comprehensive income (loss)
|
(44
|
)
|
|
208
|
|
|
(187
|
)
|
|||
Comprehensive loss
|
$
|
(71,909
|
)
|
|
$
|
(102,786
|
)
|
|
$
|
(50,715
|
)
|
Per share information:
|
|
|
|
|
|
||||||
Net loss per share of common stock, basic and diluted
|
$
|
(1.21
|
)
|
|
$
|
(1.97
|
)
|
|
$
|
(1.15
|
)
|
Weighted average common shares outstanding, basic and diluted
|
59,436,649
|
|
|
52,398,521
|
|
|
43,794,276
|
|
|
|
|
|
|
Stockholders' Equity
|
|||||||||||||||||||||
|
|
Common Stock
|
|
|
|
|
|
|
|
|
|||||||||||||
|
|
|
|
0.001
Par
Value
|
|
Additional
Paid-in
Capital
|
|
|
|
Accumulated
Other
Comprehensive
Income
(Loss)
|
|
Total
Stockholders'
Equity
|
|||||||||||
|
|
Number
of
Shares
|
|
|
|
Accumulated
Deficit
|
|
|
|||||||||||||||
|
|
|
|
|
|
|
|||||||||||||||||
Balance, January 1, 2015
|
|
39,241,173
|
|
|
$
|
39
|
|
|
$
|
231,153
|
|
|
$
|
(131,970
|
)
|
|
$
|
(19
|
)
|
|
$
|
99,203
|
|
Stock-based compensation expense
|
|
—
|
|
|
—
|
|
|
3,427
|
|
|
—
|
|
|
—
|
|
|
3,427
|
|
|||||
Exercise of stock options
|
|
384,033
|
|
|
1
|
|
|
905
|
|
|
—
|
|
|
—
|
|
|
906
|
|
|||||
Net exercise of common stock warrant
|
|
2,397
|
|
|
—
|
|
|
—
|
|
|
—
|
|
|
—
|
|
|
—
|
|
|||||
Issuance of common stock warrants
|
|
—
|
|
|
—
|
|
|
4
|
|
|
—
|
|
|
—
|
|
|
4
|
|
|||||
Issuance of common stock, net of issuance costs
|
|
11,175,000
|
|
|
11
|
|
|
90,295
|
|
|
—
|
|
|
—
|
|
|
90,306
|
|
|||||
Unrealized loss on marketable securities
|
|
—
|
|
|
—
|
|
|
—
|
|
|
—
|
|
|
(187
|
)
|
|
(187
|
)
|
|||||
Net loss
|
|
—
|
|
|
—
|
|
|
—
|
|
|
(50,528
|
)
|
|
—
|
|
|
(50,528
|
)
|
|||||
Balance, December 31, 2015
|
|
50,802,603
|
|
|
$
|
51
|
|
|
$
|
325,784
|
|
|
$
|
(182,498
|
)
|
|
$
|
(206
|
)
|
|
$
|
143,131
|
|
Stock-based compensation expense
|
|
—
|
|
|
—
|
|
|
5,903
|
|
|
—
|
|
|
—
|
|
|
5,903
|
|
|||||
Exercise of stock options
|
|
149,622
|
|
|
—
|
|
|
256
|
|
|
—
|
|
|
—
|
|
|
256
|
|
|||||
Net exercise of common stock warrant
|
|
698
|
|
|
—
|
|
|
—
|
|
|
—
|
|
|
—
|
|
|
—
|
|
|||||
Issuance of common stock, net of issuance costs
|
|
4,815,491
|
|
|
5
|
|
|
32,072
|
|
|
—
|
|
|
—
|
|
|
32,077
|
|
|||||
Unrealized gain on marketable securities
|
|
—
|
|
|
—
|
|
|
—
|
|
|
—
|
|
|
208
|
|
|
208
|
|
|||||
Adjustment to accumulated deficit as a result of adoption of ASU 2016-09
|
|
—
|
|
|
—
|
|
|
133
|
|
|
(133
|
)
|
|
—
|
|
|
—
|
|
|||||
Net loss
|
|
—
|
|
|
—
|
|
|
—
|
|
|
(102,994
|
)
|
|
—
|
|
|
(102,994
|
)
|
|||||
Balance, December 31, 2016
|
|
55,768,414
|
|
|
$
|
56
|
|
|
$
|
364,148
|
|
|
$
|
(285,625
|
)
|
|
$
|
2
|
|
|
$
|
78,581
|
|
Stock-based compensation expense
|
|
—
|
|
|
—
|
|
|
6,387
|
|
|
—
|
|
|
—
|
|
|
6387
|
|
|||||
Exercise of stock options
|
|
293,809
|
|
|
—
|
|
|
361
|
|
|
—
|
|
|
—
|
|
|
361
|
|
|||||
Issuance of common stock warrants
|
|
—
|
|
|
—
|
|
|
501
|
|
|
—
|
|
|
—
|
|
|
501
|
|
|||||
Issuance of common stock, net of issuance costs
|
|
6,248,572
|
|
|
6
|
|
|
20,706
|
|
|
—
|
|
|
—
|
|
|
20,712
|
|
|||||
Unrealized loss on marketable securities
|
|
—
|
|
|
—
|
|
|
—
|
|
|
—
|
|
|
(44
|
)
|
|
(44
|
)
|
|||||
Net loss
|
|
—
|
|
|
—
|
|
|
—
|
|
|
(71,865
|
)
|
|
—
|
|
|
(71,865
|
)
|
|||||
Balance, December 31, 2017
|
|
62,310,795
|
|
|
$
|
62
|
|
|
$
|
392,103
|
|
|
$
|
(357,490
|
)
|
|
$
|
(42
|
)
|
|
$
|
34,633
|
|
|
|
|
|
Year Ended December 31,
|
||||||||||
|
2017
|
|
2016
|
|
2015
|
||||||
Operating activities:
|
(in thousands)
|
||||||||||
Net loss
|
$
|
(71,865
|
)
|
|
$
|
(102,994
|
)
|
|
$
|
(50,528
|
)
|
Adjustments to reconcile net loss to net cash used in operating activities:
|
|
|
|
|
|
||||||
Depreciation and amortization
|
490
|
|
|
246
|
|
|
208
|
|
|||
Stock-based compensation
|
6,387
|
|
|
5,903
|
|
|
3,427
|
|
|||
Noncash interest expense on loans
|
1,050
|
|
|
534
|
|
|
180
|
|
|||
Loss on disposal of assets
|
70
|
|
|
17
|
|
|
11
|
|
|||
Revaluation of warrant liability
|
(65
|
)
|
|
(78
|
)
|
|
70
|
|
|||
Amortization of bond premiums on marketable securities
|
474
|
|
|
1,334
|
|
|
1,210
|
|
|||
Changes in operating assets and liabilities:
|
|
|
|
|
|
|
|
|
|||
Prepaid expenses and other assets
|
612
|
|
|
104
|
|
|
(1,224
|
)
|
|||
Accounts payable and accrued expenses
|
(8,408
|
)
|
|
7,130
|
|
|
2,821
|
|
|||
Deferred revenue
|
—
|
|
|
(3,750
|
)
|
|
3,750
|
|
|||
Net cash used in operating activities
|
(71,255
|
)
|
|
(91,554
|
)
|
|
(40,075
|
)
|
|||
Investing activities:
|
|
|
|
|
|
||||||
Purchases of property and equipment
|
(3,495
|
)
|
|
(605
|
)
|
|
(361
|
)
|
|||
Purchase of intangible asset
|
—
|
|
|
—
|
|
|
(15
|
)
|
|||
Maturities of marketable securities
|
99,018
|
|
|
115,824
|
|
|
69,827
|
|
|||
Purchases of marketable securities
|
(62,743
|
)
|
|
(77,421
|
)
|
|
(126,390
|
)
|
|||
Net cash provided by (used in) investing activities
|
32,780
|
|
|
37,798
|
|
|
(56,939
|
)
|
|||
Financing activities:
|
|
|
|
|
|
||||||
Proceeds from exercise of common stock options
|
361
|
|
|
256
|
|
|
906
|
|
|||
Proceeds from loans payable, net
|
9,921
|
|
|
—
|
|
|
16,368
|
|
|||
Proceeds from issuance of common stock, net
|
20,712
|
|
|
32,077
|
|
|
90,311
|
|
|||
Capital lease payments
|
(8
|
)
|
|
(4
|
)
|
|
(3
|
)
|
|||
Net cash provided by financing activities
|
30,986
|
|
|
32,329
|
|
|
107,582
|
|
|||
Net (decrease) increase in cash and cash equivalents
|
(7,489
|
)
|
|
(21,427
|
)
|
|
10,568
|
|
|||
Cash, cash equivalents, and restricted cash—beginning of period
|
25,459
|
|
|
46,886
|
|
|
36,318
|
|
|||
Cash, cash equivalents, and restricted cash—end of period
|
$
|
17,970
|
|
|
$
|
25,459
|
|
|
$
|
46,886
|
|
Supplemental disclosure of cash flow information:
|
|
|
|
|
|
||||||
Cash paid for interest
|
$
|
1,730
|
|
|
$
|
1,204
|
|
|
$
|
155
|
|
Capital lease additions
|
$
|
27
|
|
|
$
|
18
|
|
|
$
|
—
|
|
Fair value of common stock warrants issued
|
$
|
501
|
|
|
$
|
—
|
|
|
$
|
4
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
December 31, 2017
|
||||||||||||||||||||||||||
|
Adjusted Cost
|
|
Unrealized
Gains
|
|
Unrealized
Losses
|
|
Fair Value
|
|
Cash and Cash
Equivalents
|
|
Restricted
Cash
|
|
Marketable
Securities
|
||||||||||||||
Cash
|
$
|
6,783
|
|
|
$
|
—
|
|
|
$
|
—
|
|
|
$
|
6,783
|
|
|
$
|
5,370
|
|
|
$
|
1,413
|
|
|
$
|
—
|
|
Level 1 (1):
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|||||||
Money market funds
|
11,187
|
|
|
—
|
|
|
—
|
|
|
11,187
|
|
|
11,187
|
|
|
—
|
|
|
—
|
|
|||||||
U.S. treasury securities
|
1,991
|
|
|
—
|
|
|
—
|
|
|
1,991
|
|
|
—
|
|
|
—
|
|
|
1,991
|
|
|||||||
Subtotal
|
13,178
|
|
|
—
|
|
|
—
|
|
|
13,178
|
|
|
11,187
|
|
|
—
|
|
|
1,991
|
|
|||||||
Level 2 (2):
|
|
|
|
|
|
|
|
|
|
|
|
|
|
||||||||||||||
U.S. government agency securities
|
47,594
|
|
|
—
|
|
|
(42
|
)
|
|
47,552
|
|
|
—
|
|
|
—
|
|
|
47,552
|
|
|||||||
Total
|
$
|
67,555
|
|
|
$
|
—
|
|
|
$
|
(42
|
)
|
|
$
|
67,513
|
|
|
$
|
16,557
|
|
|
$
|
1,413
|
|
|
$
|
49,543
|
|
|
December 31, 2016
|
||||||||||||||||||||||||||
|
Adjusted Cost
|
|
Unrealized
Gains
|
|
Unrealized
Losses
|
|
Fair Value
|
|
Cash and Cash
Equivalents
|
|
Restricted
Cash
|
|
Marketable
Securities
|
||||||||||||||
Cash
|
$
|
13,756
|
|
|
$
|
—
|
|
|
$
|
—
|
|
|
$
|
13,756
|
|
|
$
|
12,563
|
|
|
$
|
1,193
|
|
|
$
|
—
|
|
Level 1 (1):
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|||||||
Money market funds
|
10,043
|
|
|
—
|
|
|
—
|
|
|
10,043
|
|
|
10,043
|
|
|
—
|
|
|
—
|
|
|||||||
Level 2 (2):
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|||||||
Repurchase agreements
|
1,660
|
|
|
|
|
|
|
|
|
1,660
|
|
|
1,660
|
|
|
|
|
|
|
|
|||||||
U.S. government agency securities
|
86,333
|
|
|
19
|
|
|
(17
|
)
|
|
86,335
|
|
|
—
|
|
|
—
|
|
|
86,335
|
|
|||||||
Subtotal
|
87,993
|
|
|
19
|
|
|
(17
|
)
|
|
87,995
|
|
|
1,660
|
|
|
—
|
|
|
86,335
|
|
|||||||
Total
|
$
|
111,792
|
|
|
$
|
19
|
|
|
$
|
(17
|
)
|
|
$
|
111,794
|
|
|
$
|
24,266
|
|
|
$
|
1,193
|
|
|
$
|
86,335
|
|
(1)
|
The fair value of Level 1 securities is estimated based on quoted prices in active markets for identical assets or liabilities.
|
(2)
|
The fair value of Level 2 securities is estimated based on observable inputs other than quoted prices in active markets for identical assets and liabilities, quoted prices for identical or similar assets or liabilities in inactive markets, or other inputs that are observable or can be corroborated by observable market data for substantially the full term on the assets or liabilities.
|
|
|
|
|
Warrant Liability
|
||
Balance as of January 1, 2016
|
$
|
153
|
|
Amounts acquired or issued
|
—
|
|
|
Changes in estimated fair value
|
(78
|
)
|
|
Balance as of December 31, 2016
|
75
|
|
|
Amounts acquired or issued
|
—
|
|
|
Changes in estimated fair value
|
(65
|
)
|
|
Balance as of December 31, 2017
|
$
|
10
|
|
|
December 31,
|
||||||
|
2017
|
|
2016
|
||||
Estimated remaining term
|
4.3 years
|
|
|
5.3 years
|
|
||
Risk-free interest rate
|
2.1
|
%
|
|
2.0
|
%
|
||
Volatility
|
77.6
|
%
|
|
77.2
|
%
|
||
Dividend yield
|
—
|
%
|
|
—
|
%
|
||
Fair value of underlying instrument*
|
$
|
1.60
|
|
|
$
|
5.88
|
|
|
|
|
|
Estimated Useful
|
|
December 31,
|
||||||
|
Life in Years
|
|
2017
|
|
2016
|
||||
Laboratory equipment
|
5
|
|
$
|
—
|
|
|
$
|
1,935
|
|
Computers and software
|
3 - 5
|
|
749
|
|
|
521
|
|
||
Office equipment and furniture
|
5
|
|
872
|
|
|
314
|
|
||
Manufacturing equipment
|
5
|
|
242
|
|
|
242
|
|
||
Leasehold improvements
|
5 - 10
|
|
4,824
|
|
|
2,150
|
|
||
Leased assets
|
5
|
|
59
|
|
|
32
|
|
||
Total property and equipment
|
|
|
6,746
|
|
|
5,194
|
|
||
Less accumulated depreciation and amortization
|
|
|
(2,941
|
)
|
|
(4,135
|
)
|
||
Property and equipment, net
|
|
|
$
|
3,805
|
|
|
$
|
1,059
|
|
|
December 31,
|
||||||
|
2017
|
|
2016
|
||||
Compensation and benefits
|
$
|
2,489
|
|
|
$
|
2,680
|
|
Clinical trial expenses
|
—
|
|
|
5,479
|
|
||
Restructuring (severance)
|
1,077
|
|
|
—
|
|
||
Pharmaceutical development expenses
|
444
|
|
|
—
|
|
||
Accrued interest
|
158
|
|
|
—
|
|
||
Other accrued expenses and other current liabilities
|
135
|
|
|
49
|
|
||
Total accrued expenses and other current liabilities
|
$
|
4,303
|
|
|
$
|
8,208
|
|
|
|
|
|
December 31,
2017 |
||
Gross proceeds
|
$
|
28,500
|
|
Debt discount and debt issuance costs
|
(350
|
)
|
|
Carrying value
|
28,150
|
|
|
Current portion of loans payable, net
|
12,425
|
|
|
Loans payable, net
|
$
|
15,725
|
|
|
|
|
2018
|
$
|
12,667
|
|
2019
|
12,667
|
|
|
2020
|
3,166
|
|
|
2021
|
—
|
|
|
2022
|
—
|
|
|
|
$
|
28,500
|
|
Debt Discount and deferred financing costs
|
(350
|
)
|
|
|
$
|
28,150
|
|
|
|
|
|
Year Ended December 31,
|
||||||||||
|
2017
|
|
2016
|
|
2015
|
||||||
Research and development
|
$
|
1,954
|
|
|
$
|
3,511
|
|
|
$
|
1,460
|
|
General and administrative
|
4,433
|
|
|
2,392
|
|
|
1,967
|
|
|||
Total stock-based compensation
|
$
|
6,387
|
|
|
$
|
5,903
|
|
|
$
|
3,427
|
|
|
Options Outstanding
|
|||||||
|
Number of
Shares
|
|
Weighted
Average
Exercise
Price
|
|
Weighted
Average
Remaining
Contractual
Term (in
years)
|
|||
Balance, December 31, 2015
|
4,630,073
|
|
|
$
|
4.98
|
|
|
7.87
|
Granted
|
2,067,500
|
|
|
8.43
|
|
|
|
|
Exercised
|
(149,622
|
)
|
|
1.71
|
|
|
|
|
Forfeitures
|
(177,373
|
)
|
|
(7.47
|
)
|
|
|
|
Balance, December 31, 2016
|
6,370,578
|
|
|
$
|
6.10
|
|
|
7.60
|
Granted
|
4,187,344
|
|
|
3.96
|
|
|
|
|
Exercised
|
(293,809
|
)
|
|
1.23
|
|
|
|
|
Forfeited/canceled
|
(1,639,890
|
)
|
|
(6.18
|
)
|
|
|
|
Balance, December 31, 2017
|
8,624,223
|
|
|
$
|
5.22
|
|
|
7.17
|
Vested or expected to vest at December 31, 2017
|
8,624,223
|
|
|
$
|
5.22
|
|
|
7.17
|
Exercisable at December 31, 2017
|
3,782,652
|
|
|
$
|
5.18
|
|
|
5.04
|
|
|
|
|
Year Ended
|
|||||||
|
December 31,
|
|||||||
|
2017
|
|
2016
|
|
2015
|
|||
Expected term of options (in years)
|
6.2
|
|
|
6.2
|
|
|
6.2
|
|
Risk-free interest rate
|
2.0
|
%
|
|
1.5
|
%
|
|
1.7
|
%
|
Expected volatility
|
75.6
|
%
|
|
68.6
|
%
|
|
68.5
|
%
|
Dividend yield
|
—
|
%
|
|
—
|
%
|
|
—
|
%
|
•
|
Risk‑free interest rate: The Company based the risk‑free interest rate on the interest rate payable on U.S. Treasury securities in effect at the time of grant for a period that is commensurate with the assumed expected option term.
|
•
|
Expected term of options: Due to its lack of sufficient historical data, the Company estimates the expected life of its employee stock options using the “simplified” method, as prescribed in Staff Accounting Bulletin No. 107, whereby the expected life equals the arithmetic average of the vesting term and the original contractual term of the option.
|
•
|
Expected stock price volatility: The Company estimated the expected volatility based on actual historical volatility of the stock price of similar companies with publicly‑traded equity securities. The Company calculated the historical volatility of the selected companies by using daily closing prices over a period of the expected term of the associated award. The companies were selected based on their enterprise value, risk profiles, position within the industry and with historical share price information sufficient to meet the expected term of the associated award. A decrease in the selected volatility would have decreased the fair value of the underlying instrument.
|
•
|
Expected annual dividend yield: The Company estimated the expected dividend yield based on consideration of its historical dividend experience and future dividend expectations. The Company has not historically declared or paid dividends to stockholders. Moreover, it does not intend to pay dividends in the future, but instead expects to retain any earnings to invest in the continued growth of the business. Accordingly, the Company assumed an expected dividend yield of
0.0%
.
|
•
|
Estimated forfeiture rate: In
2016
, upon adoption of ASU 2016-9, the Company elected to record forfeitures upon occurrence, rather than utilizing an estimate.
|
|
|
|
|
2013 Plan
|
|
Inducement Plan
|
||
Available at December 31, 2016
|
1,101,331
|
|
|
500,000
|
|
Authorized
|
2,230,736
|
|
|
—
|
|
Granted
|
(3,966,844
|
)
|
|
(220,500
|
)
|
Forfeited/canceled
|
1,626,390
|
|
|
13,500
|
|
Available at December 31, 2017
|
991,613
|
|
|
293,000
|
|
Stock options outstanding under 2013 Plan
|
8,417,223
|
|
Shares available for future grant under 2013 Plan
|
991,613
|
|
Stock options outstanding under Inducement Plan
|
207,000
|
|
Shares available for future grant under Inducement Plan
|
293,000
|
|
Employee stock purchase plan
|
225,806
|
|
Warrants outstanding
|
123,091
|
|
Total shares of common stock reserved for future issuance
|
10,257,733
|
|
|
|
|
|
Operating
Lease
|
||
2018
|
$
|
970
|
|
2019
|
1,275
|
|
|
2020
|
1,352
|
|
|
2021
|
1,376
|
|
|
2022 and beyond
|
9,412
|
|
|
Total minimum lease payments
|
$
|
14,385
|
|
|
|
|
|
Year Ended December 31,
|
||||||||||
|
2017
|
|
2016
|
|
2015
|
||||||
Basic and diluted net loss per common share calculation:
|
|
|
|
|
|
||||||
Net loss
|
$
|
(71,865
|
)
|
|
$
|
(102,994
|
)
|
|
$
|
(50,528
|
)
|
Net loss attributable to common stockholders
|
$
|
(71,865
|
)
|
|
$
|
(102,994
|
)
|
|
$
|
(50,528
|
)
|
Weighted average common shares outstanding
|
59,436,649
|
|
|
52,398,521
|
|
|
43,794,276
|
|
|||
Net loss per share of common stock - basic and diluted
|
$
|
(1.21
|
)
|
|
$
|
(1.97
|
)
|
|
$
|
(1.15
|
)
|
Balance, January 1, 2016
|
$
|
(206
|
)
|
Net unrealized loss arising during the period
|
208
|
|
|
Balance, December 31, 2016
|
$
|
2
|
|
Net unrealized gains on marketable securities
|
(44
|
)
|
|
Balance, December 31, 2017
|
$
|
(42
|
)
|
|
|
|
|
December 31,
|
||||||
|
2017
|
|
2016
|
||||
Deferred tax assets:
|
|
|
|
||||
Net operating loss carryforwards
|
$
|
16,042
|
|
|
$
|
15,748
|
|
Research and development credits
|
12,239
|
|
|
11,020
|
|
||
Research and development expenses capitalized for tax purposes
|
83,707
|
|
|
97,495
|
|
||
Deferred rent
|
365
|
|
|
97
|
|
||
Depreciation
|
427
|
|
|
553
|
|
||
Other temporary differences
|
3,203
|
|
|
1,895
|
|
||
Total deferred tax assets
|
115,983
|
|
|
126,808
|
|
||
Deferred tax liabilities:
|
|
|
|
||||
Prepaid expenses
|
(65
|
)
|
|
(105
|
)
|
||
Total deferred tax liabilities
|
(65
|
)
|
|
(105
|
)
|
||
Net deferred tax assets
|
115,918
|
|
|
126,703
|
|
||
Less valuation allowance
|
(115,918
|
)
|
|
(126,703
|
)
|
||
Net deferred tax asset
|
$
|
—
|
|
|
$
|
—
|
|
|
December 31,
|
|||||||
|
2017
|
|
2016
|
|
2015
|
|||
Percent of pre-tax income:
|
|
|
|
|
|
|||
U.S. federal statutory income tax rate
|
34.0
|
%
|
|
34.0
|
%
|
|
34.0
|
%
|
Permanent Differences
|
0.1
|
%
|
|
—
|
%
|
|
0.1
|
%
|
State taxes, net of federal benefit
|
6.7
|
%
|
|
6.6
|
%
|
|
6.6
|
%
|
Research and development credit
|
1.7
|
%
|
|
4.0
|
%
|
|
3.9
|
%
|
Rate change due to tax reform
|
(58.5
|
)%
|
|
—
|
|
|
—
|
|
Other
|
1.0
|
%
|
|
—
|
%
|
|
0.3
|
%
|
Change in valuation allowance
|
15.0
|
%
|
|
(44.6
|
)%
|
|
(44.9
|
)%
|
Effective income tax rate
|
—
|
%
|
|
—
|
%
|
|
—
|
%
|
|
|
|
|
First Quarter
|
|
Second Quarter
|
|
Third Quarter
|
|
Fourth Quarter
|
||||||||
|
(in thousands, except share and per share amounts)
|
||||||||||||||
2017
|
|
|
|
|
|
|
|
|
|
||||||
Total revenue
|
$
|
—
|
|
|
$
|
—
|
|
|
$
|
—
|
|
|
$
|
—
|
|
Loss from operations
|
(20,975
|
)
|
|
(19,884
|
)
|
|
(15,413
|
)
|
|
(14,115
|
)
|
||||
Net loss
|
$
|
(20,714
|
)
|
|
$
|
(20,432
|
)
|
|
$
|
(15,999
|
)
|
|
$
|
(14,720
|
)
|
Net loss per share of common, basic and diluted
|
$
|
(0.36
|
)
|
|
$
|
(0.35
|
)
|
|
$
|
(0.27
|
)
|
|
$
|
(0.24
|
)
|
Weighted average shares outstanding, basic and diluted
|
56,894,672
|
|
|
58,381,868
|
|
|
60,113,327
|
|
|
62,290,002
|
|
||||
2016
|
|
|
|
|
|
|
|
|
|
||||||
Total revenue
|
$
|
1,875
|
|
|
$
|
1,875
|
|
|
$
|
—
|
|
|
$
|
—
|
|
Loss from operations
|
(17,749
|
)
|
|
(19,104
|
)
|
|
(29,713
|
)
|
|
(35,717
|
)
|
||||
Net loss
|
$
|
(17,732
|
)
|
|
$
|
(19,295
|
)
|
|
$
|
(29,985
|
)
|
|
$
|
(35,982
|
)
|
Net loss per share of common, basic and diluted
|
$
|
(0.35
|
)
|
|
$
|
(0.37
|
)
|
|
$
|
(0.57
|
)
|
|
$
|
(0.67
|
)
|
Weighted average shares outstanding, basic and diluted
|
51,350,365
|
|
|
52,174,569
|
|
|
52,205,156
|
|
|
53,850,166
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
||
Exhibit
Number
|
|
Description
|
|
|
||
3.1
|
|
|
|
Amended and Restated Certificate of Incorporation of the Registrant (incorporated by reference to
Exhibit 3.1 to the Registrant’s Current Report on Form 8‑K
, filed with the SEC on February 5, 2014).
|
||
3.2
|
|
|
|
Amended and Restated Bylaws of the Registrant (incorporated by reference to
Exhibit 3.2 to the Registrant’s Current Report on Form 8‑K
, filed with the SEC on February 5, 2014).
|
||
4.1
|
|
|
|
|||
4.2
|
|
|
|
Specimen stock certificate evidencing shares of Common Stock of the Registrant (incorporated by reference to
Exhibit 4.2 to the Registrant’s Registration Statement on Form S‑1
, as amended (File No. 333‑191643), originally filed with the SEC on October 9, 2013).
|
||
4.3
|
|
|
|
Form Warrant issued by Trevena, Inc. to Oxford Finance LLC, Pacific Western Bank and Three Point Capital, LLC (incorporated by reference to
Exhibit 4.1 to Registrant’s Current Report on Form 8‑K
, filed with the SEC on December 23, 2015).
|
||
10.1*
|
|
|
|
License Agreement, dated as of May 3, 2013, by and between the Registrant and Forest Laboratories Holdings Limited (now Allergan plc) (incorporated by reference to
Exhibit 10.1 to the Registrant’s Registration Statement on Form S‑1
, as amended (File No. 333‑191643), originally filed with the SEC on October 9, 2013).
|
||
10.2*
|
|
|
|
Option Agreement, dated as of May 3, 2013, by and between the Registrant and Forest Laboratories Holdings Limited (now Allergan plc) (incorporated by reference to
Exhibit 10.2 to the Registrant’s Registration Statement on Form S‑1
, as amended (File No. 333‑191643), originally filed with the SEC on October 9, 2013).
|
||
10.3
|
|
|
|
Letter Agreement dated March 5, 2015 between Trevena, Inc. and Actavis plc (now Allergan plc) (incorporated by reference to
Exhibit 10.1 to the Registrant’s Current Report on Form 8‑K
, filed with the SEC on March 10, 2015).
|
||
10.4
|
|
|
|
Warrant to purchase shares of Series B preferred stock issued to Comerica Bank, dated December 9, 2011 (incorporated by reference to
Exhibit 10.3 to the Registrant’s Registration Statement on Form S‑1
, as amended (File No. 333‑191643), originally filed with the SEC on October 9, 2013).
|
||
10.5
|
|
|
|
Warrant to purchase shares of Common Stock issued to Silicon Valley Bank, dated June 24, 2008 (incorporated by reference to
Exhibit 10.4 to the Registrant’s Registration Statement on Form S‑1
, as amended (File No. 333‑191643), originally filed with the SEC on October 9, 2013).
|
||
10.6
|
|
|
|
Amended and Restated Investor Rights Agreement, dated as of May 3, 2013, by and among the Registrant and certain of its stockholders (incorporated by reference to
Exhibit 10.5 to the Registrant’s Registration Statement on Form S‑1
, as amended (File No. 333‑191643), originally filed with the SEC on October 9, 2013).
|
||
10.7
|
|
|
|
Commercial Lease Agreement, dated as of August 4, 2008, by and between the Registrant and Pios Grande KOP Business Center, L.P. (successor‑in‑interest to KOPBC, Inc.) (incorporated by reference to
Exhibit 10.6 to the Registrant’s Registration Statement on Form S‑1
, as amended (File No. 333‑191643), originally filed with the SEC on October 9, 2013).
|
|
|
|
10.8
|
|
|
|
Amendment No. 1 to Commercial Lease Agreement, dated as of December 8, 2008, by and between the Registrant and Pios Grande KOP Business Center, L.P. (successor‑in‑interest to KOPBC, Inc.) (incorporated by reference to
Exhibit 10.7 to the Registrant’s Registration Statement on Form S‑1
, as amended (File No. 333‑191643), originally filed with the SEC on October 9, 2013).
|
||
10.9
|
|
|
|
Amendment No. 2 to Commercial Lease Agreement, dated as of July 3, 2013, by and between the Registrant and Pios Grande KOP Business Center, L.P. (successor‑in‑interest to KOPBC, Inc.) (incorporated by reference to
Exhibit 10.8 to the Registrant’s Registration Statement on Form S‑1
, as amended (File No. 333‑191643), originally filed with the SEC on October 9, 2013).
|
||
10.10
|
|
|
|
Third Amendment to Commercial Lease Agreement, dated as of February 21, 2014, by and between the Registrant and Pios Grande KOP Business Center, L.P. (successor‑in‑interest to KOPBC, Inc.) (incorporated by reference to
Exhibit 10.9 to the Registrant’s Registration Statement on Form S‑1
, as amended (File No. 333‑200386), originally filed with the SEC on November 20, 2014).
|
||
10.11
|
|
|
|
4
th
Amendment to Commercial Lease Agreement dated as of January 30, 2015, by and between the Registrant and Pios Grande KOP Business Center, L.P. (successor‑in‑interest KOPBC, Inc.) (incorporated by reference to
Exhibit 10.4 to Registrant’s Quarterly Report on Form 10‑Q
, filed with the SEC on May 7, 2015).
|
||
10.12#
|
|
|
|
Agreement of Lease between Chesterbrook Partners, LP and Trevena, Inc. for 955 Chesterbrook Blvd., Suite 200, Wayne, PA, dated as of December 9, 2016 (incorporated by reference to
Exhibit 10.12 to Registrat's Annual Report on Form 10-K
filed with the SEC on March 8, 2017).
|
||
10.13+
|
|
|
|
First Amendment dated June 12, 2017 to Agreement of Lease between Chesterbrook Partners, LP and Trevena, Inc. for 955 Chesterbrook Blvd., Suite 200, Chesterbrook, PA as of December 9, 2016 (incorporated by reference to
Exhibit 10.1 to Registrant's Quarterly Report on Form 10-Q
filed with the SEC on August 3, 2017).
|
||
10.14+
|
|
|
|
2008 Equity Incentive Plan, as amended to date (incorporated by reference to
Exhibit 10.9 to the Registrant’s Registration Statement on Form S 1
, as amended (File No. 333 191643), originally filed with the SEC on October 9, 2013).
|
||
10.15+
|
|
|
|
Form of Stock Option Agreement under 2008 Equity Incentive Plan (incorporated by reference to
Exhibit 10.10 to the Registrant’s Registration Statement on Form S‑1
, as amended (File No. 333‑191643), originally filed with the SEC on October 9, 2013).
|
||
10.16+
|
|
|
|
2013 Equity Incentive Plan (incorporated by reference to
Exhibit 10.11 to the Registrant’s Registration Statement on Form S‑1
, as amended (File No. 333‑191643), originally filed with the SEC on October 9, 2013).
|
||
10.17+
|
|
|
|
Form of Stock Option Grant Notice and Stock Option Agreement under 2013 Equity Incentive Plan (incorporated by reference to
Exhibit 10.12 to the Registrant’s Registration Statement on Form S‑1
, as amended (File No. 333‑191643), originally filed with the SEC on October 9, 2013).
|
|
|
|
10.18+
|
|
|
Form of Stock Option Grant Notice and Stock Option Agreement under 2013 Equity Incentive Plan (incorporated by reference to
Exhibit 10.5 to Registrant’s Quarterly Report on Form 10‑Q
, filed with the SEC on May 7, 2015).
|
||
10.19+
|
|
|
Form of Restricted Stock Grant Notice and Restricted Stock Unit Award Agreement under 2013 Equity Incentive Plan (incorporated by reference to
Exhibit 10.13 to the Registrant’s Registration Statement on Form S‑1
, as amended (File No. 333‑191643), originally filed with the SEC on October 9, 2013).
|
||
10.20+
|
|
|
Trevena, Inc. Inducement Plan, effective January 1, 2017 (incorporated by reference to
Exhibit 10.1 to Registrant’s Current Report on Form 8-K
, filed with the SEC on December 19, 2016).
|
||
10.21+
|
|
|
Form of Stock Option Grant Notice and Stock Option Agreement used in connection with the Trevena, Inc. Inducement Plan (incorporated by referenced to
Exhibit 10.2 to Registrant’s Current Report on Form 8-K
, filed with the SEC on December 19, 2016).
|
||
10.22+
|
|
|
Form of Restricted Stock Unit Grant Notice and Restricted Stock Unit Award Agreement used in connection with Trevena, Inc. Inducement Plan (incorporated by reference to
Exhibit 10.3 to Registrant’s Current Report on Form 8-K
, filed with the SEC on December 19, 2016).
|
||
10.23+
|
|
|
Trevena, Inc. Incentive Compensation Plan, effective as of January 1, 2015 (incorporated by reference to
Exhibit 10.1 to Registrant’s Current Report on Form 8‑K
, filed with the SEC on January 5, 2015).
|
||
10.24+
|
|
|
Non‑Employee Director Compensation Plan (incorporated by reference to
Exhibit 10.1 to the Registrant’s Current Report on Form 8‑K
filed with the SEC on July 1, 2014).
|
||
10.25+
|
|
|
Trevena, Inc. Non‑Employee Director Compensation Policy, effective as of January 1, 2016 (incorporated by reference to
Exhibit 10.1 to Registrant’s Current Report on Form 8‑K
, filed with the SEC on December 11, 2015).
|
10.26+
|
|
|
|
2013 Employee Stock Purchase Plan (incorporated by reference to
Exhibit 10.15 to the Registrant’s Registration Statement on Form S‑1
, as amended (File No. 333‑191643), originally filed with the SEC on October 9, 2013).
|
||
10.27+
|
|
|
|
Form of Indemnity Agreement with executives and directors (incorporated by reference to
Exhibit 10.16 to the Registrant’s Registration Statement on Form S‑1
, as amended (File No. 333‑191643), originally filed with the SEC on October 9, 2013).
|
||
10.28+
|
|
|
|
Employment Agreement, dated as of January 31, 2014, by and between the Registrant and Maxine Gowen (incorporated by reference to
Exhibit 10.17 to the Registrant’s Form 10‑K
filed with the SEC on March 20, 2014).
|
||
10.29+
|
|
|
|
Amendment to Executive Employment Agreement dated as of May 14, 2015 by and between Trevena, Inc. and Maxine Gowen, Ph.D. (incorporated by reference to
Exhibit 10.1 to the Registrant’s Current Report on Form 8‑K
, originally filed with the SEC on May 5, 2015).
|
||
10.30+
|
|
|
|
Second Amendment to Executive Employment Agreement dated as of January 6, 2017 by and between Trevena, Inc. and Maxine Gowen, Ph.D. (incorporated by referenced to
Exhibit 10.1 to Registrant’s Current Report on Form 8-K
, filed with the SEC on January 6, 2017).
|
||
10.31+
|
|
|
|
Employment Agreement, dated as of January 31, 2014, by and between the Registrant and Michael Lark (incorporated by reference to
Exhibit 10.18 to the Registrant’s Form 10‑K
filed with the SEC on March 20, 2014).
|
||
10.32+
|
|
|
|
Employment Agreement, dated as of January 31, 2014, by and between the Registrant and Roberto Cuca (incorporated by reference to
Exhibit 10.19 to the Registrant’s Form 10‑K
filed with the SEC on March 20, 2014).
|
|
|
|
10.33+
|
|
|
|
Employment Agreement, dated as of January 31, 2014, by and between the Registrant and David Soergel (incorporated by reference to
Exhibit 10.20 to the Registrant’s Form 10‑K
filed with the SEC on March 20, 2014).
|
||
10.34+
|
|
|
|
Employment Agreement dated as of May 12, 2014, by and between the Registrant and John M. Limongelli (incorporated by reference to
Exhibit 10.1 to the Registrant’s Form 8‑K
filed with the SEC on May 15, 2014).
|
||
10.35+
|
|
|
|
Omnibus Amendment to Employment Agreements dated as of May 4, 2015 by and between Trevena, Inc. and each of Roberto Cuca, Michael Lark, John M. Limongelli and David Soergel (incorporated by reference to
Exhibit 10.2 to the Registrant’s Current Report on Form 8‑K
, filed with the SEC on May 5, 2015).
|
||
10.36+
|
|
|
|
Omnibus Amendment to Employment Agreements dated January 6, 2017 by and between Trevena, Inc. and each of Carrie L. Bourdow, Roberto Cuca, Yacoub Habib, Michael Lark, John M. Limongelli and David Soergel (incorporated by reference to
Exhibit 10.2 to Registrant’s Current Report on Form 8-K
, filed with the SEC on January 6, 2017).
|
||
10.37+
|
|
|
|
Executive Employment Agreement effective as of May 4, 2015 by Trevena, Inc. and Carrie L. Bourdow (incorporated by reference to
Exhibit 10.3 to Registrant’s Current Report on Form 8‑K
, originally filed with the SEC on May 5, 2015).
|
||
10.38+
|
|
|
|
Executive Employment Agreement effective as of July 20, 2015 by and between Trevena, Inc. and Yacoub Habib (incorporated by reference to
Exhibit 10.1 to the Registrant’s Current Report on Form 8‑K
, originally filed with the SEC on July 21, 2015).
|
||
10.39
|
|
|
|
First Amendment to Executive Employment Agreement effective as of January 1, 2016 by and between Trevena, Inc. and Yacoub Habib (incorporated by reference to
Exhibit 10.33 to the Registrant’s Form 10-K
filed with the SEC on March 9, 2016).
|
||
10.40
|
|
|
|
Loan and Security Agreement, dated September 19, 2014, by and among Trevena, Inc., as borrower, Oxford Finance LLC, as collateral agent and lender, and Square 1 Bank, as lender (incorporated by reference to
Exhibit 10.1 to the Registrant’s Current Report on Form 8‑K
, filed with the SEC on September 22, 2014).
|
|
|
|
10.41
|
|
|
|
First Amendment to Loan and Security Agreement, dated April 13, 2015, by and among Trevena, Inc., as borrower, Oxford Finance LLC, as collateral agent and lender, and Square 1 Bank, as lender (incorporated by reference to
Exhibit 10.1 to Registrant’s Current Report on Form 8‑K
, filed with the SEC on April 13, 2015).
|
||
10.42
|
|
|
|
Second Amendment to Loan and Security Agreement dated December 23, 2015, by and among Trevena, Inc., as borrower, Oxford Finance LLC, as collateral agent and lender, and Pacific Western Bank (as the successor to Square 1 Bank), as lender (incorporated by reference to
Exhibit 10.1 to Registrant’s Current Report on Form 8‑K
, filed with the SEC on December 23, 2015).
|
||
10.43
|
|
|
|
Third Amendment to Loan and Security Agreement dated December 30, 2016, by and between Trevena, Inc., as borrower, Oxford Finance LLC, as collateral agent and lender, and Pacific Western Bank (as successor to Square 1 Bank), as lender (incorporated by reference to
Exhibit 10.1 to Registrant’s Current Report on Form 8-K
, filed with the SEC on January 4, 2017).
|
||
10.44
|
|
|
|
Common Stock Sales Agreement, dated December 14, 2015, by and between Trevena, Inc. and Cowen and Company, LLC (incorporated by reference to
Exhibit 10.1 to Registrant’s Current Report on Form 8‑K
, filed with the SEC on December 14, 2015).
|
||
10.45#*
|
|
|
|
|||
10.46#*
|
|
|
|
|||
12.1#
|
|
|
|
|||
23.1#
|
|
|
|
|||
31.1#
|
|
|
|
|||
31.2#
|
|
|
|
|||
32.1#
|
|
|
|
|||
32.2#
|
|
|
|
|||
101#
|
|
|
|
The following financial information from this Annual Report on Form 10‑K for the periods ended December 31, 2016 and 2015, formatted in XBRL (eXtensible Business Reporting Language): (i) Balance Sheets as of December 31, 2016 and 2015, (ii) Statements of Operations and Comprehensive Loss for the years ended December 31, 2016, 2015 and 2014, (iii) Statement of Redeemable Convertible Preferred Stock and Stockholders’ Equity as of December 31, 2016, 2015 and 2014, (iv) Statements of Cash Flows for the years ended December 31, 2016, 2015 and 2014 and (v) Notes to Financial Statements, tagged as blocks of text.
|
|
|
|
|
TREVENA, INC.
|
|
|
By:
|
/s/ Maxine Gowen
|
|
|
|
|
|
Maxine Gowen
|
|
|
President and Chief Executive Officer
|
Signature
|
|
Title
|
|
Date
|
|
|
|
|
|
/s/ Maxine Gowen
|
|
President and Chief Executive Officer (Principal
Executive Officer) and Director
|
|
March 7, 2018
|
Maxine Gowen
|
|
|
||
|
|
|
|
|
/s/ Roberto Cuca
|
|
Senior Vice President and Chief Financial Officer
(Principal Financial and Accounting Officer)
|
|
March 7, 2018
|
Roberto Cuca
|
|
|
||
|
|
|
|
|
/s/ Leon O. Moulder, Jr.
|
|
Chairman, Board of Directors
|
|
March 7, 2018
|
Leon O. Moulder, Jr
|
|
|
||
|
|
|
|
|
/s/ Michael R. Dougherty
|
|
Director
|
|
March 7, 2018
|
Michael R. Dougherty
|
|
|
||
|
|
|
|
|
/s/ Adam M. Koppel
|
|
Director
|
|
March 7, 2018
|
Adam M. Koppel, M.D., Ph.D.
|
|
|
||
|
|
|
|
|
/s/ Julie H. McHugh
|
|
Director
|
|
March 7, 2018
|
Julie H. McHugh
|
|
|
||
|
|
|
|
|
/s/ Jake R. Nunn
|
|
Director
|
|
March 7, 2018
|
Jake R. Nunn
|
|
|
||
|
|
|
|
|
/s/ Anne M. Phillips
|
|
Director
|
|
March 7, 2018
|
Anne M. Phillips, M.D.
|
|
|
||
|
|
|
|
|
/s/ Barbara Yanni
|
|
Director
|
|
March 7, 2018
|
Barbara Yanni
|
|
|
|
|
|
Exhibit
Number
|
|
Description
|
|||
10.45*
|
|
|
Master Commercial Supply Agreement dated October 20, 2017 by and between Alcami Corporation and Trevena, Inc.
|
||
10.46*
|
|
|
Development and Supply Agreement by and between Pfizer, Inc. and Trevena, Inc. dated as of December 15, 2016.
|
||
12.1
|
|
|
Statement Regarding Computation of Ratios.
|
||
23.1
|
|
|
Consent of Independent Registered Public Accounting Firm.
|
||
24.1
|
|
|
Power of Attorney. Reference is made to the signature page hereto.
|
||
31.1
|
|
|
Certification of the Principal Executive Officer pursuant to Rule 13a‑14(a) or 15d‑14(a) of the Securities Exchange Act of 1934.
|
||
31.2
|
|
|
Certification of the Principal Financial Officer pursuant to Rule 13a‑14(a) or 15d‑14(a) of the Securities Exchange Act of 1934.
|
||
32.1
|
|
|
Certification of the Principal Executive Officer pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes‑Oxley Act of 2002.
|
||
32.2
|
|
|
Certification of the Principal Financial Officer pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes‑Oxley Act of 2002.
|
||
101
|
|
|
The following financial information from this Annual Report on Form 10‑K for the periods ended December 31, 2017 and 2016, formatted in XBRL (eXtensible Business Reporting Language): (i) Balance Sheets as of December 31, 2017 and 2016, (ii) Statements of Operations and Comprehensive Loss for the years ended December 31, 2017, 2016 and 2015, (iii) Statement of Redeemable Convertible Preferred Stock and Stockholders’ Equity as of December 31, 2017, 2016 and 2015, (iv) Statements of Cash Flows for the years ended December 31, 2017, 2016 and 2015 and (v) Notes to Financial Statements, tagged as blocks of text.
|
|
|
|
1.33.1
|
“Drug Product – Bulk”
shall mean Oliceridine in filled, unlabeled vials, packaged in appropriate bulk packaging suitable for shipment to a third party for further processing/packaging.
|
1.33.2
|
“Drug Product – Finished”
shall mean Oliceridine fully packaged for commercial distribution.
|
(i)
|
reviewing business strategy;
|
(ii)
|
ensuring goal alignment by establishing and reviewing agreed upon KPI’s;
|
(iii)
|
assessing and developing risk mitigations and/or redundancies;
|
(iv)
|
discussing market dynamics and impact to supply/demand;
|
(v)
|
reviewing Client’s Long-Term Forecast and Company’s anticipated capacity at least annually; and
|
(vi)
|
implementing procedures for project governance and the resolution of questions or disputes that may arise under this Agreement or a Work Order.
|
i.
|
was not in compliance with the applicable API and Drug Product Specifications or such API and Drug Product’s Certificate of Analysis at the time of [*]; or
|
ii.
|
is recalled by any regulatory authority or by Company due to Company’s negligence, intentional acts or omissions or breach of this
Agreement (collectively, “Nonconforming Product”).
|
a.
|
Products Liability Insurance (including coverage for Clinical Trials) in an amount of not less than [*]; or, if outside the US at compulsory limits (whichever is greater).
|
b.
|
General Liability (Premises Operations) in the amount of not less than [*] per occurrence and in the annual aggregate.
|
c.
|
Automobile Liability in the amount of not less than [*] combined single limit;
|
d.
|
Workers’ Compensation (or equivalent outside the U.S) – Statutory limits;
|
e.
|
Employer’s Liability in an amount not less than:
|
(i)
|
[*] – Each Accident
|
(ii)
|
[*] – Disease Each Employee
|
(iii)
|
[*] – Disease Policy Limit.
|
x.
|
Products Liability/Clinical Trials; and
|
y.
|
Commercial General Liability; and
|
z.
|
Umbrella Liability.
|
a.
|
Products and Professional Liability Insurance (including coverage for Clinical Trials) in an amount of not less than [*].
Such Professional Liability Insurance shall include third-party insurance coverage and shall be at Client’s expense, with a limit of [*], to cover loss or damage to Client supplied Raw Materials, API or Drug Product arising from Company’s negligence in the Manufacturing or handling of any API, CML-474, Client supplied Raw Materials or Drug Product as further provided in Sections 6.2(d), 11.4 and 12.1(b). In the event of an actual loss, Company shall reimburse Client for the premium and pay any applicable deductible attributable to the policy and such policy shall pay covered amounts in excess of the deductible. At Client’s option and expense, Company shall renew the third-party insurance policy annually. |
b.
|
General Liability (Premises Operations) in the amount of not less than [*] and in the annual aggregate.
|
(i)
|
[*] – Each Accident
|
(ii)
|
[*] – Disease Each Employee
|
(iii)
|
[*] – Disease Policy Limit.
|
x.
|
Products Liability/Clinical Trials; and
|
y.
|
Commercial General Liability; and
|
z.
|
Umbrella Liability.
|
Trevena, Inc.
|
Alcami Corporation
|
_______________________________
|
_______________________________
|
Name: _________________________
|
Name: _________________________
|
Title: ___________________________
|
Title: ___________________________
|
Date: ___________________________
|
Date: ___________________________
|
(v)
|
implementing procedures for project governance and the resolution of questions or disputes that may arise under this Agreement or the Project Statement of Work
|
(i)
|
Different fill volume and vial size combinations [*];
|
PFIZER CENTREONE
PFIZER, INC.
|
TREVENA, INC.
|
By:
(Signature)
|
By:
(Signature)
|
Name: Kevin Orfan
|
Name: Michael W. Lark, Ph.D.
|
Title: Vice President
Pfizer CentreOne
Contract Manufacturing Services
|
Title: Senior Vice President, Research and Chief Scientific Officer
|
|
2013
|
|
2014
|
|
2015
|
|
2016
|
|
2017
|
||||||||||
|
(in thousands)
|
||||||||||||||||||
Determination of earnings
|
|
|
|
|
|
|
|
|
|
||||||||||
Income/(loss) before income taxes
|
$
|
(23,251
|
)
|
|
$
|
(49,701
|
)
|
|
$
|
(50,528
|
)
|
|
$
|
(102,994
|
)
|
|
$
|
(71,865
|
)
|
Add:
|
|
|
|
|
|
|
|
|
|
||||||||||
Fixed Charges
|
303
|
|
|
234
|
|
|
531
|
|
|
1,927
|
|
|
3,232
|
|
|||||
Total Earnings/(loss)
|
(22,948
|
)
|
|
(49,467
|
)
|
|
(49,997
|
)
|
|
(101,067
|
)
|
|
(68,633
|
)
|
|||||
Fixed charges:
|
|
|
|
|
|
|
|
|
|
||||||||||
Interest expense and amortization of debt discount and deferred financing costs
|
150
|
|
|
71
|
|
|
334
|
|
|
1,738
|
|
|
2,781
|
|
|||||
Estimated interest component of rent expense
|
153
|
|
|
163
|
|
|
197
|
|
|
189
|
|
|
541
|
|
|||||
Total fixed charges
|
303
|
|
|
234
|
|
|
531
|
|
|
1,927
|
|
|
3,322
|
|
|||||
Ratio of earnings to fixed charges(1)
|
|
|
|
|
|
|
|
|
|
||||||||||
Deficiency of earnings to cover fixed charges
|
$
|
23,251
|
|
|
$
|
49,701
|
|
|
$
|
50,528
|
|
|
$
|
102,994
|
|
|
$
|
71,865
|
|
|
|
|
|
|
|
/s/ Ernst & Young LLP
|
|
|
|
|
|
|
/s/ Maxine Gowen
|
|
|
|
Maxine Gowen
|
|
President and Chief Executive Officer
|
|
(Principal Executive Officer)
|
|
|
|
|
|
|
/s/ Roberto Cuca
|
|
|
|
Roberto Cuca
|
|
Senior Vice President and Chief Financial Officer
|
|
(Principal Financial Officer)
|
|
|
|
|
|
|
|
Date: March 7, 2018
|
/s/ Maxine Gowen
|
|
|
|
President and Chief Executive Officer
|
|
(Principal Executive Officer)
|
|
|
|
|
|
|
|
Date: March 7, 2018
|
/s/ Roberto Cuca
|
|
|
|
Chief Financial Officer and Treasurer
|
|
(Principal Financial Officer)
|
|
|
|
|
|