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

¨	TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from              to

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ITEM 1.	BUSINESS

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CABOMETYX (cabozantinib) was approved by the U.S. Food and Drug Administration, or FDA, on April 25, 2016, for the treatment of patients with advanced renal cell carcinoma, or RCC, who have received prior anti-angiogenic therapy. The European Commission, or EC, approved CABOMETYX on September 9, 2016 similarly for the treatment of advanced RCC in adults following prior vascular endothelial growth factor, or VEGF, targeted therapy. Outside the U.S. and Japan, CABOMETYX is being marketed by our collaboration partner Ipsen Pharma SAS, or Ipsen. Should CABOMETYX be approved in Japan, it will be marketed by our collaboration partner Takeda Pharmaceutical Company Limited, or Takeda. In 2016, we generated $93.5 million in net product revenue from sales of CABOMETYX in the United States.

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COMETRIQ (cabozantinib), our first marketed product, was approved by the FDA on November 29, 2012 for the treatment of patients with progressive, metastatic medullary thyroid carcinoma, or MTC. In March 2014, the EC granted COMETRIQ a similar, conditional marketing authorization for the treatment of adult patients with progressive, unresectable locally advanced or metastatic MTC. COMETRIQ is now commercialized in the European Union by Ipsen. In 2016, we generated $39.4 million in net product revenue from sales of COMETRIQ in the United States and received $2.5 million in product revenue from sales of COMETRIQ by our former distribution partner, Swedish Orphan Biovitrum, or Sobi. Cabozantinib has shown clinical anti-tumor activity in more than 20 forms of

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Cotellic (cobimetinib) was approved by the FDA on November 10, 2015, in combination with vemurafenib for the treatment of patients with BRAF V600E or V600K mutation-positive advanced melanoma in the United States. It has also been approved in combination with vemurafenib in multiple other territories including the European Union, Switzerland, Canada, Australia and Brazil. In 2016, we recognized $2.8 million in collaboration revenue as a result of royalties on ex-U.S. sales of Cotellic and beginning in the fourth quarter of 2016, we also recognized a small net profit for our share of U.S. activities under the collaboration agreement. Genentech has an extensive clinical development program for this compound. For additional information on the cobimetinib development program, see “Cobimetinib Development Program.”

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•	Phase 2 or phase 1/2 clinical trials to help prioritize future pivotal trials of cabozantinib in disease settings where there is substantial unmet medical need and in which cabozantinib has previously demonstrated clinical activity, consisting of randomized phase 2 clinical trials in ocular melanoma, prostate cancer and second/third line EGFR-wt NSCLC;

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Additional phase 2 or phase 1/2 clinical trials to explore cabozantinib’s potential utility in other tumor types, including endometrial cancer, bladder cancer, sarcomas, NSCLC (EGFR-activating mutation positive), differentiated thyroid cancer, triple-negative breast cancer, hormone-receptor-positive breast cancer, cutaneous melanoma (molecularly selected patients), pancreatic neuroendocrine and carcinoid tumors. Positive results in these indications could lead to further study in randomized phase 2 or phase 3 clinical trials; and

•	Additional phase 1 clinical trials to further evaluate cabozantinib, consisting of a combination trial of cabozantinib and immuno-oncology agents (nivolumab with or without ipilumumab) in genitourinary tumors,

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•	The combination of cobimetinib and vemuarfenib in additional melanoma patient populations and settings;

•	A phase 2 trial of cobimetinib in combination with taxanes, with or without atezolizumab in first line triple negative breast cancer (COLET);

•	Phase 1 studies of cobimetinib in combination with atezolizumab in melanoma and NSCLC, in combination with vemurafenib and atezolizumab in melanoma, and in combination with venetoclax in relapsed or refractory acute myeloid leukemia; and

•	A phase 1b study evaluating the safety, tolerability and pharmacokinetics of cobimetinib in combination with atezolizumab and bevacizumab in patients with metastatic CRC.

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•	preclinical laboratory and animal tests that must be conducted in accordance with Good Laboratory Practices;

•	submission of an IND, which must become effective before clinical trials may begin;

•	adequate and well-controlled human clinical trials to establish the safety and efficacy of the proposed drug candidate for its intended use;

•	submission of a New Drug Application, or NDA, to FDA for commercial marketing, or of a sNDA, for approval of a new indication if the product is already approved for another indication;

•	pre-approval inspection of manufacturing facilities and selected clinical investigators for their compliance with Good Manufacturing Practices, or GMP, and Good Clinical Practices, or GCP;

•	if FDA convenes an advisory committee, satisfactory completion of the advisory committee review; and

•	FDA approval of the NDA or sNDA.

•	Phase 1 - Studies, which involve the initial introduction of an IND into humans, are initially conducted in a limited number of subjects to test the product candidate for safety, dosage tolerance, absorption, metabolism, distribution and excretion in healthy humans or patients.

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Phase 2 - Studies are conducted with groups of patients afflicted with a specified disease in order to provide enough data to evaluate the preliminary efficacy, optimal dosages and expanded evidence of safety. Multiple phase 2 clinical trials may be conducted by the sponsor to obtain information prior to beginning larger and more expensive phase 3 clinical trials. Phase 2 studies are typically well controlled, closely monitored, and conducted in a relatively small number of patients, usually involving no more than several hundred subjects. In some cases, a sponsor may decide to run what is referred to as a “phase 2b” evaluation, which is a second, confirmatory phase 2 trial that could, if positive, serve as a pivotal trial in the approval of a product candidate.

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Phase 3 - When phase 2 evaluations demonstrate that a dosage range of the product is effective and has an acceptable safety profile, phase 3 trials are performed to gather the additional information about effectiveness and safety that is needed to evaluate the overall benefit-risk relationship of the drug and to provide an adequate basis for physician labeling. Phase 3 trials are undertaken in large patient populations to further evaluate dosage, to provide replicate statistically significant evidence of clinical efficacy and to further test for safety in an expanded patient population at multiple clinical trial sites.

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•	require the FDA to establish a program to evaluate the potential use of real world evidence to help to support the approval of a new indication for an approved drug and to help to support or satisfy post-approval study requirements;

•	provide that the FDA may rely upon qualified data summaries to support the approval of a supplemental application with respect to a qualified indication for an already approved drug;

•	require FDA to issue guidance for purposes of assisting sponsors in incorporating complex adaptive and other novel trial designs into proposed clinical protocols and applications for new drugs; and

•	require FDA to establish a process for the qualification of drug development tools for use in supporting or obtaining FDA approval for or investigational use of a drug.

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•	efficacy, safety and reliability of cabozantinib;

•	timing and scope of regulatory approval;

•	the speed at which we develop cabozantinib for the treatment of additional tumor types beyond its approved indications;

•	our ability to complete preclinical testing and clinical development and obtain regulatory approvals for cabozantinib;

•	our ability to manufacture and sell commercial quantities of cabozantinib product to the market;

•	our ability to successfully commercialize cabozantinib and secure coverage and adequate reimbursement in approved indications;

•	product acceptance by physicians and other health care providers;

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•	the level of our collaboration partners’ investments in the resources necessary to successfully commercialize cabozantinib in territories where it is approved outside of the United States;

•	skills of our employees and our ability to recruit and retain skilled employees;

•	protection of our intellectual property; and

•	the availability of substantial capital resources to fund development and commercialization activities.

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ITEM 1A.	RISK FACTORS

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•	the effectiveness, or perceived effectiveness, of cabozantinib in comparison to competing products;

•	the safety of cabozantinib, including the existence of serious side effects of cabozantinib and their severity in comparison to those of any competing products;

•	cabozantinib’s relative convenience and ease of administration;

•	unexpected results connected with analysis of data from future or ongoing clinical trials;

•	the timing of cabozantinib label expansions for additional indications, if any, relative to competitive treatments;

•	the price of cabozantinib relative to competitive therapies and any new government initiatives affecting pharmaceutical pricing;

•	the strength of CABOMETYX sales efforts, marketing, medical affairs and distribution support;

•	the sufficiency of commercial and government insurance coverage and reimbursement; and

•	our ability to enforce our intellectual property rights with respect to cabozantinib.

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the federal Anti-Kickback Statute, or AKS, which governs our business activities, including our marketing practices, educational programs, pricing policies, and relationships with healthcare providers or other entities. The AKS prohibits, among other things, persons and entities from knowingly and willfully soliciting, receiving, offering or paying remuneration, directly or indirectly, in exchange for or to induce 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 healthcare programs such as the Medicare and Medicaid programs. Remuneration is not defined in the AKS and has been broadly interpreted to include anything of value, including for example, gifts, discounts, coupons, the furnishing of supplies or equipment, credit arrangements, payments of cash, waivers of payments, ownership interests and providing anything at less than its fair market value. The AKS has been broadly interpreted to apply to manufacturer arrangements with prescribers, purchasers and formulary managers, among others;

•	the FDCA and its regulations which prohibit, among other things, the introduction or delivery for introduction into interstate commerce of any food, drug, device, or cosmetic that is adulterated or misbranded;

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federal civil and criminal false claims laws and civil monetary penalty laws, which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, claims for payment from Medicare, Medicaid, or other third-party payers that are false or fraudulent, or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government;

•	federal criminal laws that prohibit executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters;

•	the Health Insurance Portability and Accountability Act of 1996, or HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, and their implementing regulations, which impose certain requirements relating to the privacy, security and transmission of individually identifiable health information;

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state law equivalents of each of the above federal laws, such as anti-kickback and false claims laws, which may apply to items or services reimbursed by any third-party payer, including commercial insurers, and state laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts;

•	the Foreign Corrupt Practices Act, a U.S. law which regulates certain financial relationships with foreign government officials (which could include, for example, certain medical professionals);

•	federal and state consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers;

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federal and state government price reporting laws that require us to calculate and report complex pricing metrics to government programs, where such reported prices may be used in the calculation of reimbursement and/or discounts on our marketed drugs (participation in these programs and compliance with the applicable requirements may subject us to potentially significant discounts on our products, increased infrastructure costs, and could potentially affect our ability to offer certain marketplace discounts); and

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federal and state financial transparency laws, which generally require certain types of expenditures in the United States to be tracked and reported (compliance with such requirements may require investment in infrastructure to ensure that tracking is performed properly, and some of these laws result in the public disclosure of various types of payments and relationships with healthcare providers and healthcare entities, which could potentially have a negative effect on our business and/or increase enforcement scrutiny of our activities).

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•	lack of efficacy or harmful side effects;

•	negative or inconclusive clinical trial results may require us to conduct further testing or to abandon projects that we had expected to be promising;

•	our competitors may discover or commercialize other compounds or therapies that show significantly improved safety or efficacy compared to our product candidates;

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•	our inability to identify and maintain a sufficient number of trial sites, many of which may already be engaged in other clinical trial programs;

•	patient registration or enrollment in our clinical testing may be lower than we anticipate, resulting in the delay or cancellation of clinical testing;

•	failure of our third-party contract research organization or investigators to satisfy their contractual obligations, including deviating from trial protocol; and

•	regulators or institutional review boards may withhold authorization to commence or conduct clinical trials of a product candidate, or delay, suspend or terminate clinical research for various reasons, including noncompliance with regulatory requirements or their determination that participating patients are being exposed to unacceptable health risks.

•	the number of patients who ultimately participate in the clinical trial;

•	the duration of patient follow-up that is appropriate in view of the results or required by regulatory authorities;

•	the number of clinical sites included in the trials; and

•	the length of time required to enroll suitable patient subjects.

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•	the commercial success of both CABOMETYX and COMETRIQ and the revenues we generate from those approved products;

•	costs associated with maintaining our expanded sales, marketing, medical affairs and distribution capabilities for CABOMETYX in advanced RCC and COMETRIQ in the approved MTC indications;

•	the achievement of stated regulatory and commercial milestones under our collaboration with Ipsen;

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•	the commercial success of Cotellic and the calculation of our share of related profits and losses for the commercialization of Cotellic in the U.S. and royalties from Cotellic sales outside the U.S. under our collaboration with Genentech;

•	the outcome of our arbitration against Genentech in which we have asserted claims related to Genentech’s clinical development, pricing and commercialization of Cotellic, and cost and revenue allocations arising from Cotellic’s commercialization in the United States;

•	the potential regulatory approval of cabozantinib as a treatment for previously untreated advanced RCC and in other indications, both in the United States and abroad;

•	future clinical trial results, notably the results from CELESTIAL, our phase 3 pivotal trial in patients with advanced HCC;

•	our future investments in the expansion of our pipeline through drug discovery and corporate development activities;

•	our repayment and any potential mandatory prepayment of the Secured Convertible Notes due 2018, or the Deerfield Notes, (see “Note 7. Debt” to our “Notes to Consolidated Financial Statements” contained in Part II, Item 8 of this Annual Report on Form 10-K for a description of these notes), which mature on July 1, 2018, and which we intend to repay on or about July 1, 2017;

•	our ability to control costs;

•	our ability to remain in compliance with, or amend or cause to be waived, financial covenants contained in agreements with third parties;

•	the cost of clinical drug supply for our clinical trials;

•	trends and developments in the pricing of oncologic therapeutics in the United States and abroad, especially in the European Union;

•	scientific developments in the market for oncologic therapeutics and the timing of regulatory approvals for competing oncologic therapies; and

•	the filing, maintenance, prosecution, defense and enforcement of patent claims and other intellectual property rights.

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•	increasing our vulnerability to adverse economic and industry conditions;

•	limiting our ability to obtain additional financing;

•	requiring the dedication of a substantial portion of our cash flow from operations to service our indebtedness, thereby reducing the amount of our cash flow available for other purposes, including clinical trials, research and development, capital expenditures, working capital and other general corporate purposes;

•	limiting our flexibility in planning for, or reacting to, changes in our business;

•	dilution experienced by our existing stockholders as a result of a conversion of the Deerfield Notes, at our discretion, into shares of common stock; and

•	placing us at a possible competitive disadvantage with less leveraged competitors and competitors that may have better access to capital resources.

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•	we are not able to control the amount and timing of resources that our collaborators or potential future collaborators will devote to the development or commercialization of drug candidates or to their marketing and distribution;

•	we are not able to control the U.S. commercial resourcing decisions made and resulting costs incurred by Genentech for cobimetinib, which reasonable costs we are obligated to share, in part, under our collaboration agreement with Genentech;

•	collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a drug candidate, repeat or conduct new clinical trials or require a new formulation of a drug candidate for clinical testing;

•	disputes may arise between us and our collaborators that result in the delay or termination of the research, development or commercialization of our drug candidates, or that diminish or delay receipt of the economic benefits we are entitled to receive under the collaboration, or that result in costly litigation or arbitration that diverts management’s attention and resources;

•	collaborators may experience financial difficulties;

•	collaborators may not be successful in their efforts to obtain regulatory approvals in a timely manner, or at all;

•	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 proprietary information or expose us to potential litigation;

•	collaborators may not comply with applicable healthcare regulatory laws;

•	business combinations or significant changes in a collaborator’s business strategy may adversely affect a collaborator’s willingness or ability to complete its obligations under any arrangement;

•	a collaborator could independently move forward with a competing drug candidate developed either independently or in collaboration with others, including our competitors;

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•	we may be precluded from entering into additional collaboration arrangements with other parties in an area or field of exclusivity;

•	future collaborators may require us to relinquish some important rights, such as marketing and distribution rights; and

•	collaborations may be terminated or allowed to expire, which would delay, and may increase the cost of development of our drug candidates.

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•	the commercial success of both CABOMETYX and COMETRIQ and the revenues we generate from those approved products;

•	customer ordering patterns for CABOMETYX and COMETRIQ, which may vary significantly from period to period;

•	the overall level of demand for CABOMETYX and COMETRIQ, including the impact of any competitive products and the duration of therapy for patients receiving CABOMETYX or COMETRIQ;

•	costs associated with maintaining our expanded sales, marketing, medical affairs and distribution capabilities for CABOMETYX, COMETRIQ and Cotellic;

•	our ability to obtain regulatory approval for cabozantinib as a treatment of first-line advanced RCC;

•	the achievement of stated regulatory and commercial milestones, under our collaboration with Ipsen;

•	the outcome of our arbitration against Genentech in which we have asserted claims related to Genentech’s clinical development, pricing and commercialization of Cotellic, and cost and revenue allocations arising from Cotellic’s commercialization in the United States;

•	the progress and scope of other development and commercialization activities for cabozantinib and our other compounds;

•	future clinical trial results, notably the results from CELESTIAL, our phase 3 pivotal trial in patients with advanced HCC;

•	our future investments in the expansion of our pipeline through drug discovery and corporate development activities;

•	the inability to obtain adequate product supply for any approved drug product or inability to do so at acceptable prices;

•	recognition of upfront licensing or other fees or revenues;

•	payments of non-refundable upfront or licensing fees, or payment for cost-sharing expenses, to third parties;

•	the introduction of new technologies or products by our competitors;

•	the timing and willingness of collaborators to further develop or, if approved, commercialize our product candidates out-licensed to them;

•	the termination or non-renewal of existing collaborations or third party vendor relationships;

•	regulatory actions with respect to our product candidates and any approved products or our competitors’ products;

•	disputes or other developments relating to proprietary rights, including patents, litigation matters and our ability to obtain patent protection for our technologies;

•	the timing and amount of expenses incurred for clinical development and manufacturing of cabozantinib;

•	adjustments to expenses accrued in prior periods based on management’s estimates after the actual level of activity relating to such expenses becomes more certain;

•	the impairment of acquired goodwill and other assets;

•	additions and departures of key personnel;

•	general and industry-specific economic conditions that may affect our or our collaborators’ research and development expenditures; and

•	other factors described in this “Risk Factors” section.

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•	adverse results or delays in our or our collaborators’ clinical trials;

•	the announcement of FDA approval or non-approval, or delays in the FDA review process, of cabozantinib or our collaborators’ product candidates or those of our competitors or actions taken by regulatory agencies with respect to our, our collaborators’ or our competitors’ clinical trials;

•	the commercial success of both CABOMETYX and COMETRIQ and the revenues we generate from those approved products;

•	the timing of achievement of our clinical, regulatory, partnering and other milestones, such as the commencement of clinical development, the completion of a clinical trial, the filing for regulatory approval or the establishment of collaborative arrangements for cabozantinib or any of our other programs or compounds;

•	actions taken by regulatory agencies with respect to cabozantinib or our clinical trials for cabozantinib;

•	the announcement of new products by our competitors;

•	quarterly variations in our or our competitors’ results of operations;

•	developments in our relationships with our collaborators, including the termination or modification of our agreements;

•	the announcement of an in-licensed product candidate or strategic acquisition;

•	conflicts or litigation with our collaborators, including the outcome of our arbitration with Genentech regarding Cotellic;

•	litigation, including intellectual property infringement and product liability lawsuits, involving us;

•	failure to achieve operating results projected by securities analysts;

•	changes in earnings estimates or recommendations by securities analysts;

•	the satisfaction of outstanding debt obligations or entry into new financing arrangements;

•	developments in the biotechnology, biopharmaceutical or pharmaceutical industry;

•	sales of large blocks of our common stock or sales of our common stock by our executive officers, directors and significant stockholders;

•	departures of key personnel or board members;

•	FDA or international regulatory actions;

•	third-party coverage and reimbursement policies;

•	disposition of any of our technologies or compounds; and

•	general market, economic and political conditions and other factors, including factors unrelated to our operating performance or the operating performance of our competitors.

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•	a classified Board of Directors;

•	a prohibition on actions by our stockholders by written consent;

•	the inability of our stockholders to call special meetings of stockholders;

•	the ability of our Board of Directors to issue preferred stock without stockholder approval, which could be used to institute a “poison pill” that would work to dilute the stock ownership of a potential hostile acquirer, effectively preventing acquisitions that have not been approved by our Board of Directors;

•	limitations on the removal of directors; and

•	advance notice requirements for director nominations and stockholder proposals.

ITEM 1B.	UNRESOLVED STAFF COMMENTS

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ITEM 2.	PROPERTIES

•	The first two leases cover two buildings for a total of 130,964 square feet and expire in May 2017. We have subleased a total of 93,243 square feet of portions of these buildings to five different subtenants. The terms of the subleases expire at the end of our lease terms.

•	The third lease covers two buildings for a total of 116,063 square feet and expires in June 2018. We have one five-year options to extend the term of the lease prior to expiration.

ITEM 3.	LEGAL PROCEEDINGS

ITEM 4.	MINE SAFETY DISCLOSURES

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ITEM 5.	MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES

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ITEM 6.	SELECTED FINANCIAL DATA

(1)	Prior periods have been revised to reflect the correction of the accounting for non-cash interest expense associated with the 2019 Notes. See “Note 1. Organization and Summary of Significant Accounting Policies - Correction of an Immaterial Error” in the “Notes to the Consolidated Financial Statements” for additional information on the correction.

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ITEM 7.	MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS

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In February 2016, we entered into a collaboration and license agreement with Ipsen for the commercialization and further development of cabozantinib. Pursuant to the terms of the collaboration agreement, Ipsen received exclusive commercialization rights for current and potential future cabozantinib indications outside of the United States, Canada and Japan. The collaboration agreement was subsequently amended in December 2016 to include commercialization rights in Canada.

•	In April 2016, based on results of our phase 3 pivotal trial METEOR, which met its primary endpoint of improving PFS, as well as its secondary endpoints of improving OS and ORR, the FDA approved CABOMETYX for the treatment of patients with advanced RCC who have received prior anti-angiogenic therapy.

•	In May 2016, we announced that CABOSUN met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in PFS compared with sunitinib in patients with advanced intermediate- or poor-risk RCC. Based on these results, we are working towards the submission of a sNDA in the third quarter of 2017 for cabozantinib as a treatment for first-line advanced RCC.

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In June 2016, we presented results from our phase 3 pivotal trial METEOR at the ASCO 2016 Annual Meeting, showing that CABOMETYX demonstrated a statistically significant and clinically meaningful increase in OS. Compared with everolimus, CABOMETYX was associated with a 34% reduction in the rate of death and median OS was 21.4 months for patients receiving CABOMETYX versus 16.5 months for those receiving everolimus (HR=0.66, 95% CI 0.53-0.83, P=0.0003).

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In June 2016, our collaboration partner Genentech announced preliminary results from a phase 1b trial evaluating the safety and clinical activity of the combination of cobimetinib with ateolizumab in patients with metastatic CRC, which included 23 patients with advanced CRC (22 with mutant KRAS and one with wild-type KRAS). The ORR for the combination was 17%, including four confirmed PRs; additionally five patients achieved SD. Responses were seen in tumors with the microsatellite stable, or MSS, phenotype, which comprises 95% of CRC. MSS CRC has historically been refractory to immuno-oncology agents. The median duration of response was not yet reached, with a range of 5.4 months to more than 11.1 months. No dose-limiting toxicities were observed.

•	In September 2016, the EC approved CABOMETYX for the treatment of adult patients with advanced RCC following prior VEGF-targeted therapy and in December 2016, Ipsen recorded its first commercial sales in Europe.

•	In October 2016, we announced positive results from the NCI-CTEP-sponsored phase 1 trial of cabozantinib in combination with nivolumab in patients with previously treated genitourinary tumors.

•	In November 2016, we announced Genentech’s efforts to advance the development program for cobimetinib, through the initiation and announcement of multiple phase 3 pivotal trials exploring the combination of cobimetinib with other targeted and immuno-oncology agents for the treatment of melanoma and CRC.

•	In January 2017, we entered into a collaboration and license agreement with Takeda for the commercialization and further clinical development of cabozantinib in Japan.

•	Our total net product revenue increased by $101.2 million, or 296%, in 2016 compared to 2015, primarily due to the commercial launch of CABOMETYX as a treatment for patients with advanced RCC in April 2016 and, to a lesser extent, an increase in COMETRIQ product sales.

•	Our collaboration revenue increased by $53.1 million in 2016 compared to 2015, primarily due to upfront payments and milestones received as a result of entering into our collaboration and license agreement with Ipsen.

•	Cash and investments increased to $479.6 million at December 31, 2016 as compared to $253.3 million at December 31, 2015.

•	Between August and November 2016, we retired all $287.5 million of the 2019 Notes through privately negotiated exchange transactions and redemption procedures provided for by the 2019 Notes. For additional information on the retirement of the 2019 Notes, see “Note 7. Debt,” to our “Notes to Consolidated Financial Statements contained in Part II, Item 8 of this Annual Report on Form 10-K.

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(1)	Includes amortization of upfront payments.

(2)	Includes milestone payments.

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(1)	Due date is based on our contractual obligations under the Deerfield Notes. We intend to repay the Deerfield Notes on or about July 1, 2017 and as a result, we have classified the Deerfield Notes as a current liability as of December 31, 2016. See “Note 7. Debt” of the Notes to Consolidated Financial Statements regarding the terms of the Deerfield Notes.

(2)	Consists of our obligations under our loan from Silicon Valley Bank. See “Note 7. Debt” of the Notes to Consolidated Financial Statements regarding the terms of our loan from Silicon Valley Bank.

(3)	The operating lease payments do not include $1.2 million to be received in 2017 in connection with the subleases of our South San Francisco buildings.

(4)	At December 31, 2016, we had firm purchase commitments related to manufacturing and maintenance of inventory. These commitments include a portion of our 2017 contractual minimum purchase obligation. Our actual purchases are expected to significantly exceed these amounts.

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ITEM 7A.	QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK

ITEM 8.	FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA

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(1)	Other comprehensive loss consisted solely of unrealized losses, net on available-for-sale securities arising during the periods presented. There were no reclassification adjustments to net loss resulting from realized gains or losses on the sale of securities and there was no income tax expense related to other comprehensive loss during those years.

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(1)	The error did not impact our net cash provided by or used in operating activities, financing activities or investing activities for any of the periods presented.

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(1)	Other restructuring charge from implementation to date for the 2010 Restructurings includes $21.7 million in charges related to employee severance and other benefits for periods ended prior to December 31, 2013. The remainder of Other activity for both restructurings relates primarily to the impairment and sale of property and equipment.

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(1)	As described above, we intend to repay the Deerfield Notes, which have a contractual maturity of July 1, 2018, on or about July 1, 2017. The actual timing of payments may differ materially.

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•	When available, we value investments based on quoted prices for those financial instruments, which is a Level 1 input. Our remaining investments are valued using third-party pricing sources, which use observable market prices, interest rates and yield curves observable at commonly quoted intervals of similar assets as observable inputs for pricing, which is a Level 2 input.

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The 2019 Notes were valued using a third-party pricing model that is based in part on average trading prices, which is a Level 2 input. The 2019 Notes were not marked-to-market and are shown at their initial fair value less the unamortized discount; the portion of the value allocated to the conversion option is included in Stockholders’ equity (deficit) on the accompanying Consolidated Balance Sheets.

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We estimate the fair value of our other debt instruments, where possible, using the net present value of the payments. For the Silicon Valley Bank term loan and line of credit, we use an interest rate that is consistent with money-market rates that would have been earned on our non-interest-bearing compensating balances as our discount rate, which is a Level 2 input. For the Deerfield Notes, we used a discount rate of 9.5%, which we estimate as our current borrowing rate for similar debt as of December 31, 2016, which is a Level 3 input.

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•	The settlement consideration comprises, in part, shares of our Common Stock. The fair value of our Common Stock was determined based on the closing market price of our Common Stock on the various settlement dates of the conversions, which are level 1 inputs;

•	The carrying value of the remaining settlement consideration, which includes cash and the forgiveness of the repayment of certain prior interest payments, approximates fair value;

•	We estimated the fair value of the liability component of the 2019 Notes using the net present value of estimated future cash flows through maturity. We used a discount rate of 9.5%, which we estimated as our current borrowing rate for straight debt as of September 30, 2016, which is a Level 3 input.

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(1)	Minimum payments have not been reduced by minimum sublease rentals of $1.2 million due in the future under noncancelable subleases.

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(1)

Prior period balances reflect revisions due to a correction of an immaterial error with regards to the 2019 Notes. The immaterial error resulted in an overstatement of the discount on the 2019 Notes and therefore overstated the related interest expense. Therefore, net loss was overstated by $2.2 million, $2.1 million, $2.1 million, $2.0 million, $2.0 million, $1.9 million for the quarters ended June 30 2016 and March 31, 2016, December 31, 2015, September 30, 2015, June 30 2015 and March 31, 2015, respectively, and net loss per share, basic and diluted was overstated by $0.01, for each of those quarters. See “Note 1. Organization and Summary of Significant Accounting Policies - Correction of an Immaterial Error” for additional information on the correction of the immaterial error.

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ITEM 9.	CHANGES IN AND DISAGREEMENTS WITH ACCOUNTANTS ON ACCOUNTING AND FINANCIAL DISCLOSURE

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ITEM 9B.	OTHER INFORMATION

ITEM 10.	DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE

ITEM 11.	EXECUTIVE COMPENSATION

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ITEM 12.	SECURITY OWNERSHIP OF CERTAIN BENEFICIAL OWNERS AND MANAGEMENT AND RELATED STOCKHOLDER MATTERS

(1)	The weighted average exercise price does not take into account the shares subject to outstanding restricted stock units, or RSUs, which have no exercise price.

(2)	Represents shares of our common stock issuable pursuant to the 2000 Plan, the 2011 Plan, the 2014 Plan, the Director Plan and the ESPP.

(3)

Represents shares of our common stock issuable pursuant to the 2016 Plan and 401(k) Plan. We sponsor a 401(k) Plan whereby eligible employees may elect to contribute up to the lesser of 50% of their annual compensation or the statutorily prescribed annual limit allowable under Internal Revenue Service regulations. The 401(k) Plan permits us to make matching contributions on behalf of all participants. We match 100% of the first 3% of participant contributions into the 401(k) Plan in the form of our common stock.

ITEM 13.	CERTAIN RELATIONSHIPS AND RELATED TRANSACTIONS, AND DIRECTOR INDEPENDENCE

ITEM 14.	PRINCIPAL ACCOUNTING FEES AND SERVICES

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ITEM 15.	EXHIBITS, FINANCIAL STATEMENT SCHEDULES

(a)	The following documents are being filed as part of this report:

ITEM 16.	FORM 10-K SUMMARY

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(1)	Meeting at which minutes are generated.

(2)	In-person meeting or teleconference at which minutes are generated.

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(b)	information that has been made available by the disclosing Party to others without a confidentiality obligation;

(c)	information that is already known by the receiving Party without obligations of confidentiality, or information that is independently created or compiled by the receiving Party without reference to or use of the information provided under this CRADA; or

(d)	information that is subsequently disclosed to the receiving Party by a third party without obligations of confidentiality.

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3.1

Performance of Research and Development. The research and development activities to be carried out under this CRADA will be performed solely by the Parties identified on the Cover Page, as well as by NCI Investigators as described in the Research Plan. However, NCI Extramural Investigators are not Parties to the CRADA, and this CRADA does not grant to Collaborator any rights to Inventions made by NCI Extramural Investigators. The NIH CRADA Extramural Investigator/Officers and CRADA Collaborator PIs will be responsible for coordinating the scientific and technical conduct of this project on behalf of their employers. Any Collaborator employees who will work at IC facilities will be required to sign a Guest Researcher or Special Volunteer Agreement appropriately modified in view of the terms of this CRADA.

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3.2	Research Plan. The Parties recognize that the Research Plan describes the collaborative research and development activities they will undertake and that interim research goals set forth in the Research Plan are good faith guidelines. Should events occur that require modification of these goals, then by mutual agreement the Parties can modify them through an amendment, according to Paragraph 13.6.

3.3

Use and Disposition of Collaborator Materials and IC Materials. The Parties agree to use Collaborator Materials and IC Materials only in accordance with the Research Plan and Protocol(s), not to transfer these materials to third parties except in accordance with the Research Plan and Protocol(s) or as approved by the owning or providing Party, and, upon expiration or termination of the CRADA, to dispose of these materials as directed by the owning or providing Party.

3.4	Third-Party Rights in Collaborator’s CRADA Subject Inventions. If Collaborator has received (or will receive) support of any kind from a third party in exchange for rights in any of Collaborator’s CRADA Subject Inventions, Collaborator agrees to ensure that its obligations to the third party are both consistent with Articles 6 through 8 and subordinate to Article 7 of this CRADA.

3.5

Disclosures to IC. Prior to execution of this CRADA, Collaborator agrees to disclose to IC all instances in which outstanding royalties are due under a PHS license agreement and in which Collaborator had a PHS license terminated in accordance with 37 C.F.R. § 404.10. These disclosures will be treated as Collaborator Confidential Information upon request by Collaborator in accordance with the definition in Article 2 and Paragraphs 8.3 and 8.4.

3.6

Clinical Investigator Responsibilities. The Clinical Investigator will be required to submit, or to arrange for submission of, each Protocol associated with this CRADA to all appropriate IRBs, and for ensuring that the IRBs are notified of the role of Collaborator in the research. In addition to the Protocol, all associated documents, including informational documents and advertisements, must be reviewed and approved by the appropriate IRB(s) before starting the research at each Clinical Research Site. The research will be done in strict accordance with the Protocol(s) and no substantive changes in a finalized Protocol will be made unless mutually agreed upon, in writing, by the Parties. Research will not commence (or will continue unchanged, if already in progress) until each substantive change to a Protocol, including those required by either the FDA or the IRB, has been integrated in a way acceptable to the Parties, submitted to the FDA (if applicable) and approved by the appropriate IRBs.

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3.7.4

During the term of this CRADA, Collaborator may sponsor its own clinical trials and hold its own IND for studies performed outside the scope of this CRADA. These studies, however, should not adversely affect the ability to accomplish the goal of the Research Plan, for example, by competing for the same study population. All data from those clinical trials are proprietary to Collaborator for purposes of this CRADA. Collaborator will permit DCTD to review and use the summary and safety data from any such trials in its possession solely as necessary for regulatory purposes for DCTD-sponsored clinical trials which are conducted under this CRADA. For clarity, Collaborator is not required to generate any data summaries to provide to DCTD, and is only obligated to provide those summaries that have already been created by or on behalf of Collaborator.

3.7.6

In the event that other international Clinical Research Sites are participating in DCTD-sponsored Protocols, Collaborator will assist such international Clinical Research Sites in the submission of necessary regulatory documents to allow for such participation. The international participant will work directly with the Collaborator to obtain the necessary regulatory documents other than the IB (as defined in Paragraph 3.8.7) or Certificate of Analysis of the Investigational Agent, which may be provided by DCTD with Collaborator’s approval. Notwithstanding the foregoing, no international Clinical Research Sites may participate in any DCTD-sponsored clinical trials without the Collaborator’s consent, which consent may be withheld at Collaborator’s discretion.

3.8.1

Collaborator agrees to provide DCTD without charge and on a schedule that will ensure adequate and timely performance of the research, a sufficient quantity of formulated and acceptably labeled, clinical-grade Investigational Agent (and, if required by the Protocol(s), Placebo) to complete clinical trial(s) under Protocol(s) mutually agreed to and approved under this CRADA. Investigational Agent should be suitable for shipment to all countries and sites participating in DCTD-sponsored clinical trials approved under this CRADA. DCTD does not maintain country-specific Investigational Agent supplies. Collaborator will provide a Certificate of Analysis to DCTD for each lot of the Investigational Agent provided. It is understood that DCTD shall take responsibility for and reasonable steps to maintain appropriate records and assure appropriate supply, handling, storage, distribution and usage of these materials in accordance with the terms of this Agreement, the Protocol(s), the Material Safety Data Sheet provided by Collaborator, and any applicable laws and regulations relating thereto.

3.8.2	DCTD will provide updated forecasts of amounts of Investigational Agent anticipated for ongoing and anticipated clinical studies under mutually agreed upon Protocol(s) and, in any event, will notify Collaborator of the quantity of Investigational Agent required to maintain adequate supply for each

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3.8.3	Collaborator agrees to provide without charge Investigational Agent or unformulated analytical grade Investigational Agent or metabolites, if available, to DCTD to supply to NCI Investigators for the performance of mutually agreed upon Non-Clinical Studies, such as [ * ]. These studies will be approved by the PRC and conducted according to Protocols approved by both Parties.

3.8.4

Collaborator agrees to allow Investigational Agent to be distributed to NCI Investigators for mutually agreeable Non-Clinical Studies [ * ]. These may include non-clinical studies [ * ]. Each such Non-Clinical Study will be proposed by the NCI Investigator and, in order to proceed, must be approved by both NCI and Collaborator. These studies will be conducted according to Non-Clinical Study proposals approved by both Parties.

3.8.5

All NCI Extramural Investigators who will receive Investigational Agent for Non-Clinical Studies as provided in Paragraph 3.8.3 as necessary and appropriate or Paragraph 3.8.4 above must first sign Material Transfer Agreements (MTAs) substantially in the form attached hereto as Appendix C that acknowledge the proprietary nature of the Investigational Agent to Collaborator and include intellectual property and publication provisions. Collaborator acknowledges that the MTA attached hereto as Appendix C is acceptable to Collaborator. NCI will notify Collaborator if an NCI Extramural Investigator wants to make any material changes to such MTA (e.g., modifications to the confidentiality, publication, indemnification or intellectual property provisions), and Collaborator will have the right to approve or reject such changes. Investigational Agent will not be distributed to an NCI Extramural Investigator for Non-Clinical Studies unless and until such investigator signs an MTA that is acceptable to Collaborator.

3.8.6	Collaborator agrees to provide Investigational Agent to DCTD for DCTD to conduct DCTD Clinical Support Assays [ * ]; provided, however, that the total amount of Investigational Agent required to be provided by Collaborator to DCTD and used to conduct DCTD Clinical Support Assays under this Paragraph 3.8.6 will [ * ].

3.8.7

Collaborator agrees to provide to the PMB the Investigator's Brochure (IB) for Investigational Agent and all subsequent revisions/editions. In addition to being filed with the CTEP IND, the IB will be on file in the PMB and will be distributed to all NCI Investigators participating in a clinical trial using the Investigational Agent under this CRADA. Distribution will be accompanied by a statement about the confidentiality of the document and it is anticipated that distribution will be electronic. All electronic distribution will be done using Adobe Acrobat PDF. Any IB received by the PMB that is not in this format will be converted before distribution. Hard copy IBs should be sent to IB Coordinator, Pharmaceutical Management Branch, CTEP, DCTD, NCI, 6130 Executive Blvd, Room 7149, Rockville, MD 20852. Electronic versions should be emailed to the IB Coordinator at IBCoordinator@mail.nih.gov.

3.9

Investigational Agent Delivery and Usage. Collaborator will ship the Investigational Agent and, if required, Placebo for use in mutually agreed Protocol(s) under the Research Plan to NCI or its designee in containers marked in accordance with 21 C.F.R. § 312.6. NCI agrees that the Clinical Investigators will keep appropriate records and take reasonable steps to ensure that the Investigational Agent is used in accordance with the Protocol(s) and applicable FDA regulations. In addition, NCI agrees that the

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3.11

FDA Meetings/Communications. All formal meetings with the FDA concerning any clinical trial within the scope of the Research Plan will be discussed by Collaborator and IC in advance. The Parties acknowledge that day-to-day DCTD communications with the FDA regarding clinical Protocols under the CRADA may not be considered as formal meetings with the FDA. However, DCTD will inform and discuss with Collaborator the outcome of informal communications. Each Party reserves the right to take part in setting the agenda for, to attend, and to participate in these meetings. The Sponsor of a clinical trial conducted under this CRADA will provide the other Party with copies of FDA meeting minutes, all transmittal letters for IND submissions, IND safety reports, formal questions and responses that have been submitted to the FDA, Annual Reports, and official FDA correspondence, pertaining either to the INDs for such clinical trial conducted under this CRADA or to the Clinical Investigators on Protocols performed in accordance with the Research Plan, except to the extent that those documents contain the proprietary information of a third party or dissemination is prohibited by law.

3.12

Steering Committee and CRADA Research. The Parties agree to establish a Steering Committee comprising at least the NIH CRADA Extramural Investigator/Officers and CRADA Collaborator PIs to conduct and monitor the proposed and ongoing clinical studies and non-clinical research of the Investigational Agent in accordance with the CRADA Research Plan. Members of the Steering Committee shall continue to remain employed by their respective employers under their respective terms of employment and, if a member ceases to be employed by a Party, such member shall be replaced with a new member that is an employee of such Party.

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4.1

Interim Research and Development Reports. The NIH CRADA Extramural Investigator/Officers and CRADA Collaborator PIs should exchange information regularly (e.g., at least [ * ], or as appropriate for the stage of the research being conducted under the CRADA), in writing. This exchange may be accomplished through meeting minutes, detailed correspondence, circulation of draft manuscripts, Steering Committee reports, copies of Annual Reports and any other reports updating the progress of the CRADA research. However, the Parties must exchange updated Investigator’s Brochure, safety, formulation and preclinical data, and toxicology findings related to the Investigational Agent as they become available.

4.2

Final Research and Development Reports. IC will provide to Collaborator final reports of the results of all studies conducted under the Research Plan as they become available and, for those final reports that have not been provided by IC during the term of the CRADA, within six (6) months after the expiration or termination of this CRADA. These reports will set forth the technical progress made; any publications arising from the research; and the existence of invention disclosures of potential CRADA Subject Inventions and/or any corresponding Patent Applications. [ * ].

4.3

Fiscal Reports. If Collaborator has agreed to provide funding to IC under this CRADA and upon the request of Collaborator, then concurrent with the provision of final research and development reports according to Paragraph 4.2, IC will submit to Collaborator a statement of all costs incurred by IC for the CRADA. If the CRADA has been terminated, IC will specify any costs incurred before the date of termination for which IC has not received funds from Collaborator in accordance with Paragraph 5.3, as well as for all reasonable termination costs including the cost of returning Collaborator property or removal of abandoned Collaborator property, for which Collaborator will be responsible.

4.4

Safety Reports. DCTD shall report all serious and unexpected possible, probable and definite Adverse Events to the FDA in accordance with the reporting obligations of 21 CFR 312.32 and will, within 24 hours of notification to the FDA, forward a copy of all such reports to Collaborator. All other Adverse Event reports received by DCTD shall be reported to the FDA consistent with 21 CFR 312.32 and 312.33. DCTD will forward a copy of such reports to Collaborator (drugsafety@exelixis.com) within 24 hours of providing such reports to the FDA. In the event that Collaborator informs the FDA or any other regulatory authority of any serious and unexpected Adverse Events, Collaborator must notify the NCI within 24 hours of informing the FDA or any other regulatory authority of such Adverse Events by sending the reports to CTEPSupportAE@tech-res.com. NCI will then notify the Clinical Investigator(s) conducting studies under DCTD-sponsored Protocols, if appropriate.

4.5

Annual Reports. DCTD will provide to Collaborator a copy of the Annual Report concurrently with the submission of the Annual Report to the FDA. Such Annual Reports will be CRADA Data, and will be kept confidential by the Parties in accordance with Article 8. Collaborator will provide DCTD with a copy of its Annual Report to the FDA if Collaborator is sponsoring studies of Investigational Agent under its own IND outside the scope of the Research Plan, which Annual Report will be Collaborator Confidential Information.

5.1	IC and Collaborator Contributions. The contributions of any staff, funds, materials, and equipment by the Parties are set forth in Appendix B. The Federal Technology Transfer Act of 1986, 15 U.S.C. § 3710a(d)(1) prohibits IC from providing funds to Collaborator for any research and development activities under this CRADA.

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5.2

IC Staffing. No IC employees will devote 100% of their effort or time to the research and development activities under this CRADA. IC will not use funds provided by Collaborator under this CRADA for IC personnel to pay the salary of any permanent IC employee. Although personnel hired by IC using CRADA funds will focus principally on CRADA research and development activities, Collaborator acknowledges that these personnel may nonetheless make contributions to other research and development activities, and the activities will be outside the scope of this CRADA. IC personnel will not use the Investigational Agent to perform any research and development activities outside the scope of this CRADA.

5.3

Collaborator Funding. Collaborator acknowledges that Government funds received by Collaborator from an agency of the Department of Health and Human Services may not be used to fund IC under this CRADA. If Collaborator has agreed to provide funds to IC then the payment schedule appears in Appendix B and Collaborator will make payments according to that schedule. If Collaborator fails to make any scheduled payment, IC will not be obligated to perform any of the research and development activities specified herein or to take any other action required by this CRADA until the funds are received. IC will use these funds exclusively for the purposes of this CRADA. IC will maintain separate and distinct current accounts, records, and other evidence supporting its financial obligations under this CRADA and, upon written request, will provide to the Collaborator a Fiscal Report according to Paragraph 4.3, which delineates all payments made and all obligated expenses, along with the Final Research Report described in Paragraph 4.2.

5.4

Capital Equipment. Collaborator’s commitment, if any, to provide IC with capital equipment to enable the research and development activities under the Research Plan appears in Appendix B. If Collaborator transfers to IC the capital equipment or provides funds for IC to purchase it, then IC will own the equipment. If Collaborator loans capital equipment to IC for use during the CRADA, Collaborator will be responsible for paying all costs and fees associated with the transport, installation, maintenance, repair, removal, or disposal of the equipment, and IC will not be liable for any damage to the equipment.

6.1

Ownership of CRADA Subject Inventions, CRADA Data, and CRADA Materials. Subject to the Collaborator option described in Paragraph 7.2, the Government license described in Paragraph 7.5, the sharing requirements and the regulatory filing requirements of Paragraphs 8.1 and 8.2, the producing Party will retain sole ownership of and title to all CRADA Subject Inventions, all copies of CRADA Data, Raw Data and all CRADA Materials, in each case produced solely by its employee(s) or, in the case of Collaborator, produced solely by Collaborator’s employees, contractors or agents. The Parties will own jointly (with each owning an undivided interest) all CRADA Subject Inventions invented jointly by IC employees together with employees, contractors or agents of Collaborator (“Joint CRADA Subject Inventions”) and all CRADA Materials developed jointly by one or more IC employees and one or more of Collaborator’s employees, contractors or agents. The rights of any NCI Extramural Investigator in data it generates will not be affected by this CRADA. The Parties acknowledge that the individuals performing DCTD Clinical Support Assays will be NCI Intramural Investigators or will be IC contractors who are obligated to assign any and all CRADA Subject Inventions and related intellectual property to NIH, in which case such CRADA Subject Inventions and related intellectual property are subject to the Collaborator option described in Paragraph 7.2.

6.2

Reporting. The Parties will promptly report to each other in writing each CRADA Subject Invention reported by their respective personnel, and any Patent Applications filed thereon, resulting from the research and development activities conducted under this CRADA. Each Party will report all CRADA Subject Inventions to the other Party in sufficient detail to determine inventorship, which will be determined in accordance with U.S. patent law. These reports will be treated as Confidential Information in

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6.3

Filing of Patent Applications. Each Party will make timely decisions regarding the filing of Patent Applications on the CRADA Subject Inventions made solely by its employee(s), and will notify the other Party in advance of filing. Collaborator will have the first opportunity to file a Patent Application on Joint CRADA Subject Inventions and will notify PHS of its decision whether to file within [ * ] of the applicable Invention being reported or at least thirty (30) days before any patent filing deadline, whichever occurs sooner. If Collaborator fails to notify PHS of its decision within that time period or notifies PHS of its decision not to file a Patent Application, then PHS has the right to file a Patent Application on the Joint CRADA Subject Invention. Neither Party will be obligated to file a Patent Application. However, if PHS elects not to file a Patent Application on a CRADA Subject Invention made solely by IC employees, PHS may agree to permit Collaborator, at Collaborator’s election and expense, to undertake the preparation, filing, prosecution, and maintenance of such Patent Application and PHS will execute all documents and take such other acts reasonably necessary to enable Collaborator to assume responsibility for filing, prosecuting, and maintaining such Patent Application and any resulting Patents. Such permissions will be at the discretion of the NIH OTT and will not be unreasonably withheld. In the event that PHS elects to file a Patent Application on a CRADA Subject Invention made solely by IC employees, PHS agrees to use reasonable efforts to discuss a patent filing strategy with Collaborator reasonably in advance of filing such Patent Application. Collaborator will place the following statement in any Patent Application it files on a CRADA Subject Invention: “This invention was created in the performance of a Cooperative Research and Development Agreement with the National Institutes of Health, an Agency of the Department of Health and Human Services. The Government of the United States has certain rights in this invention.” If either Party files a Patent Application on a Joint CRADA Subject Invention, then the filing Party will include a statement within the Patent Application that clearly identifies the Parties and states that the Joint CRADA Subject Invention was made under this CRADA.

6.4

Patent Expenses. Unless agreed otherwise, the Party filing a Patent Application will pay all preparation and filing expenses, prosecution fees, issuance fees, post issuance fees, patent maintenance fees, annuities, interference expenses, and attorneys’ fees for that Patent Application and any resulting Patent(s). However, a Party will have the right to elect to cease prosecuting a Patent Application or maintaining any resulting Patent(s) directed to a Joint CRADA Subject Invention, provided that such Party provides at least[ * ] notice to the other Party of such election and, if requested by the other Party, executes all documents and takes such other acts reasonably necessary (e.g., assign its interest) to enable the other Party to assume, at the other Party’s expense, the responsibility for filing, prosecuting, and maintaining the Patent Application and any resulting Patent(s). If a license to any CRADA Subject Invention is granted to Collaborator pursuant to Paragraph 7.2(a)(i), 7.2(a)(ii) or Paragraph 7.2(c), then Collaborator will be responsible for all out-of-pocket expenses and fees, past and future, in connection with the preparation, filing, prosecution, and maintenance of any Patent Applications and Patents claiming exclusively licensed CRADA Subject Inventions and will be responsible for a pro-rated share, divided equally among all licensees, of those out-of-pocket expenses and fees for non-exclusively licensed CRADA Subject Inventions. Collaborator may waive its non-exclusive or exclusive option rights or disclaim its exclusive or non-exclusive license for Patent Application(s) or Patent(s) at any time with respect to one or more countries, and incur no subsequent financial obligation for those Patent Application(s) or Patent(s).

6.5

Prosecution of Patent Applications. Except with respect to CRADA Subject Inventions conceived and reduced to practice solely by Collaborator’s employees, contractors or agents, the Party filing a Patent Application for a CRADA Subject Invention will provide the non-filing Party with a copy of any official communication relating to prosecution of the Patent Application within [ * ] of transmission of the communication. Each Party will also provide the other Party, at the other Party’s request, with copies of material documents retained in the applicable Patent Application or Patent file for such Invention. The

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7.1	Background Inventions. Other than as specifically stated in this Article 7, nothing in this CRADA will be construed to grant any rights in one Party’s Background Invention(s) to the other Party, except to the extent necessary for the Parties to conduct the research and development activities described in the Research Plan during the term of the CRADA.

7.2	Collaborator’s License Option to CRADA Subject Inventions. With respect to Government rights to any CRADA Subject Invention made solely by an IC employee(s) or a Joint CRADA Subject Invention for which a Patent Application has been filed, PHS hereby offers to the Collaborator the following options and grants:

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7.3

Exercise of Collaborator’s License Option. To exercise the option(s) or grant(s) set forth in Paragraph 7.2, Collaborator must submit a written notice to the PHS Patenting and Licensing Contact identified on the Contacts Information Page (and provide a copy to the IC Contact for CRADA Notices) within three (3) months after either (i) Collaborator receives written notice from PHS that a Patent Application has been filed or (ii) the date on which Collaborator files a Patent Application. The written notice exercising the option(s) will include a completed “Application for License to Public Health Service Inventions” and will initiate a negotiation period that expires [ * ] after the date of exercise of the option. If PHS has not responded in writing to the last proposal by Collaborator within this [ * ] period, the negotiation period will be extended to expire one (1) month after PHS so responds, during which month Collaborator may accept in writing the final license proposal of PHS. If PHS and Collaborator fail to reach agreement within [ * ], (or such additional period as described above) on the terms for an exclusive license for a particular Paragraph 7.2(a) Invention, then for a period of [ * ] thereafter PHS agrees not to offer to license the Paragraph 7.2(a) Invention to any third party on materially better terms than those last offered to Collaborator without first offering such terms to Collaborator, in which case Collaborator will have a period of [ * ] in which to accept or reject the offer. In the absence of Collaborator’s exercise of the option with respect to a CRADA Subject Invention, or upon election of a nonexclusive license to such Invention, PHS will be free to license the CRADA Subject Invention to others. These time periods may be extended at the sole discretion of PHS upon good cause shown in writing by Collaborator, provided that [ * ].

7.4

Government License in IC Sole CRADA Subject Inventions and Joint CRADA Subject Inventions. Pursuant to 15 U.S.C. § 3710a(b)(1)(A), for CRADA Subject Inventions owned solely by IC or Joint CRADA Subject Inventions and licensed pursuant to an option in Paragraph 7.2, Collaborator grants to the Government a nonexclusive, nontransferable, irrevocable, paid-up license to practice the CRADA Subject Invention or have the CRADA Subject Invention practiced throughout the world by or on behalf of the Government for research or other Government purposes. In the exercise of this license, the Government will not publicly disclose trade secrets or commercial or financial information that is privileged or confidential within the meaning of 5 U.S.C. § 552(b)(4) or which would be considered privileged or confidential if it had been obtained from a non-federal party.

7.5

Government License in Collaborator Sole CRADA Subject Inventions. Pursuant to 15 U.S.C. § 3710a(b)(2), for CRADA Subject Inventions made solely by an employee of Collaborator, Collaborator grants to the Government a nonexclusive, nontransferable, irrevocable, paid-up license to practice the CRADA Subject Invention or have the CRADA Subject Invention practiced throughout the world by or on behalf of the Government for research or other Government purposes. In the exercise of this license, the Government will not publicly disclose trade secrets or commercial or financial information that is privileged or confidential within the meaning of 5 U.S.C. § 552(b)(4) or which would be considered privileged or confidential if it had been obtained from a non-federal party.

7.6

Third Party License. Pursuant to 15 U.S.C. § 3710a(b)(1)(B), if PHS grants Collaborator an exclusive, or co-exclusive, license to a CRADA Subject Invention made solely by an IC employee or a Joint CRADA Subject Invention, the Government will retain the right to require Collaborator to grant to a responsible applicant a nonexclusive, partially exclusive, or exclusive sublicense to use the CRADA Subject Invention

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7.7

Third-Party Rights In IC Sole CRADA Subject Inventions. For a CRADA Subject Invention conceived prior to the Effective Date solely by an IC employee that is first actually reduced to practice after the Effective Date in the performance of the Research Plan, the option offered to Collaborator in Paragraph 7.2 may be restricted if, prior to the Effective Date, PHS filed a Patent Application and has either offered or granted a license in the CRADA Subject Invention to a third party. Collaborator nonetheless retains the right to apply for a license to any such CRADA Subject Invention in accordance with the terms and procedures of 35 U.S.C. § 209 and 37 C.F.R. Part 404.

7.8

Joint CRADA Subject Inventions Not Exclusively Licensed by Collaborator. If Collaborator does not acquire an exclusive commercialization license to a Joint CRADA Subject Invention in all fields of use then, for those fields of use not exclusively licensed to Collaborator, each Party will have the right to use the Joint CRADA Subject Invention and to license its use to others, and each Party will cooperate with the other, as necessary, to fulfill international licensing requirements. The Parties may agree to a joint licensing approach for any remaining fields of use.

8.1

Right of Access to CRADA Data and CRADA Materials. IC and Collaborator agree to exchange all CRADA Data and to share all CRADA Materials. Both Parties agree that they will not disclose CRADA Data to third parties until it is published in accordance with Paragraph 8.7, except as necessary to perform its obligations under this CRADA or as expressly permitted in Paragraph 8.2. In addition, IC represents that NCI Extramural Investigators are subject to obligations to keep CRADA Data confidential until it is published in accordance with Paragraph 8.7. If the CRADA is terminated, each Party agrees to provide CRADA Materials in quantities needed to complete all active Protocols or Protocols that have commenced or been approved by the PRC and Collaborator in accordance with the procedures set forth in the Research Plan prior to such termination. Such provision will occur before the termination date of the CRADA or sooner, if required by the Research Plan. However, if a Party terminates the CRADA in accordance with Paragraph 10.3 because of the other Party’s material breach, the terminating Party will have no obligation to provide CRADA Materials for the completion of the Research Plan. If Collaborator possesses any human biological specimens from clinical trials under the CRADA, the specimens must be handled as described in the Protocol or as otherwise directed by IC before the termination date of the CRADA.

8.2

Use of CRADA Data and CRADA Materials. The Parties will be free to utilize CRADA Data and CRADA Materials internally for their own purposes, consistent with their obligations under this CRADA. IC may share CRADA Data or CRADA Materials with any NCI Extramural Investigators it has engaged to conduct the CRADA research and development activities, provided the obligations of this Paragraph 8.2 are simultaneously conveyed and such NCI Extramural Investigators agree to comply with such obligations. Collaborator may share CRADA Data or CRADA Materials with any contractors, Affiliates, collaboration/development partners or agents it has engaged to conduct the CRADA research and development activities, as well as with Collaborator’s licensees and contractors, provided the obligations of this Paragraph 8.2 are simultaneously conveyed and such third parties agree to comply with such obligations. In addition,

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8.3

Confidential Information. Each Party agrees to limit its disclosure of Confidential Information to the amount necessary to carry out the Research Plan, and will place a confidentiality notice on all this information. A Party orally disclosing Confidential Information to the other Party will identify the disclosure as confidential at the time of oral disclosure and summarize the disclosure in writing and provide it to the other Party. Each Party receiving Confidential Information agrees to use it only for the purposes described in the Research Plan or as otherwise permitted in this Agreement. Either Party may object to the designation of information as Confidential Information by the other Party. Notwithstanding anything to the contrary in this CRADA, the restrictions on use and disclosure of Confidential Information under this CRADA shall not apply to Collaborator’s use and disclosure of Collaborator Confidential Information or to IC’s use and disclosure of IC Confidential Information.

8.4

Protection of Confidential Information. Confidential Information will not be disclosed, copied, reproduced or otherwise made available by a Party to any other person or entity without the other Party’s consent or as permitted under this CRADA except as required by a court or administrative body of competent jurisdiction, by federal or other applicable law or regulation, or as necessary for Patent filings and/or prosecution in accordance with Article 6. A Party shall be permitted to disclose Confidential

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8.5	Human Subject Protection. The research to be conducted under this CRADA involves Human Subjects or human tissues within the meaning of 45 C.F.R. Part 46, and all research to be performed under this CRADA will conform to applicable federal laws and regulations. Additional information is available from the HHS Office for Human Research Protections (http://www.hhs.gov/ohrp/).

8.6

Duration of Confidentiality Obligation. Collaborator Confidential Information that is a trade secret, or commercial or financial information under the meaning of 5 U.S.C. Section 552(b)(4), shall not be disclosed by IC. The obligation to maintain the confidentiality of all Confidential Information will expire at the earlier of the date when the information is no longer Confidential Information as defined in Article 2 or [ * ] years after the expiration or termination date of this CRADA, except for IPI, for which the obligation to maintain confidentiality will extend indefinitely. Collaborator may request an extension to this term when necessary to protect Confidential Information relating to products not yet commercialized.

8.7

Publication. The Parties are encouraged to make publicly available the results of their research and development activities. [ * ]. Before Collaborator or NCI (including an NCI Investigator) submits a paper or abstract for publication about a CRADA Subject Invention, CRADA Data, or CRADA Materials, the other Party will have thirty (30) days to review proposed manuscripts and three (3) days to review proposed abstracts to assure that Confidential Information is protected. NCI will ensure that Collaborator Confidential Information identified by Collaborator is excised from a proposed publication. Either Party may request in writing that a proposed publication be delayed for up to thirty (30) additional days as necessary to file a Patent Application. If a CRADA Subject Invention disclosed in a proposed publication is solely owned by IC pursuant to Paragraph 6.1, NCI will refrain from publication of such proposed manuscript or presentation until such time as PHS has filed a Patent Application covering such invention. Manuscripts to be submitted for publication by NCI Investigators will be sent to NCI’s Regulatory Affairs Branch NCICTEPpubs@mail.nih.gov for forwarding to Collaborator for review as soon as they are received and in compliance with the timelines outlined above. Abstracts to be presented by NCI Investigators will be sent to NCI’s Regulatory Affairs Branch NCICTEPpubs@mail.nih.gov for forwarding to Collaborator as soon as they are received, preferably no less than [ * ] prior to submission, but prior to presentation or publication, to allow for preservation of U.S. or foreign patent rights. All publications made under this Paragraph 8.7 will contain an appropriate acknowledgement of each Party’s contributions under this CRADA.

8.8

Clinical Investigators’ Research and Non-Clinical Investigators’ Development Activities. In pursuing the development of Investigational Agent pursuant to this CRADA, NCI may utilize NCI Extramural Investigators for part or all of the completion of the Research Plan, which may cover Non-Clinical Studies and clinical studies, through Funding Agreements and MTAs. Participation in DCTD-sponsored clinical trials by NCI Extramural Investigators shall be determined after competitive solicitation and review of Protocol Letters of Intent (LOIs) and Protocols by CTEP, NCI and Collaborator. All Funding Agreements

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8.8.1

With regard to Collaborator Confidential Information, NCI will require the NCI Investigators to agree to confidentiality provisions at least as restrictive as those provided in this CRADA, and to Collaborator’s use of CRADA Data for obtaining regulatory approval for marketing Investigational Agent or pharmaceutical products containing Investigational Agent. In addition, NCI will assure that the NCI Extramural Investigators are aware of their obligations to provide to Collaborator Raw Data or any other data in the possession of NCI Extramural Investigators working with Investigational Agent under a Funding Agreement or MTA as requested by Collaborator in accordance with Paragraph 8.8.2.

8.8.2

If Collaborator wants access to Raw Data or any other data in the possession of the NCI Investigators working with Investigational Agent under a Funding Agreement or other agreements, Collaborator must first contact the Regulatory Affairs Branch (RAB), CTEP, NCI Telephone 301-496-7912; anshers@mail.nih.gov. Subsequent to authorization by RAB, which authorization will not be unreasonably withheld, Collaborator may directly contact the NCI Investigators. Collaborator will bear any costs associated with providing the Raw Data in formats customized for Collaborator, which costs will be paid by Collaborator directly to the NCI Investigators.

8.8.3

If Collaborator abandons development or commercialization of Investigational Agent without the transfer of its development or commercialization efforts to another party within [ * ] of abandonment, NCI has the right to make CRADA Data and Raw Data available to a third party. NCI will notify Collaborator of its intention to provide such data to a third party. For purposes of this Paragraph 8.8.3, Collaborator shall not be deemed to have abandoned development or commercialization of Investigational Agent so long as either (a) Collaborator devotes at least [ * ] to the development or commercialization of Investigational Agent during [ * ], or (b) a third party is actively conducting research relating to Investigational Agent under an agreement with Collaborator.

8.8.4	IC will promptly provide to Collaborator a copy of all Invention disclosures IC receives from NCI Extramural Investigators.

8.8.5	If NCI discovers that an NCI Extramural Investigator that is conducting any portion of the Research Plan breaches any of the provisions of its Funding Agreement or MTA regarding its work with Investigational Agent, NCI will discuss with Collaborator an appropriate resolution to such breach and shall take appropriate action as necessary to rectify such breach.

8.9

Multi-Party Data Rights. For clinical Protocol(s) or Non-Clinical Study(ies) under the Research Plan where Investigational Agent is used in combination with another investigational agent supplied to NCI pursuant to a CTA or CRADA between NCI and an entity not a Party to this CRADA (such entity, hereinafter referred to as a “Third Party”) the access and use of Multi-Party Data by the Collaborator and the Third Party shall be co-exclusive as follows:

8.9.1	NCI will provide both Collaborator and the Third Party with notice regarding the existence and nature of the agreements governing their collaborations with NIH, the design of the proposed combination Protocol(s) or Non-Clinical Study(ies), and the existence of any obligations that

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8.9.2	Collaborator shall agree to permit use of the Multi-Party Data from these trials by the Third Party to the extent necessary to allow the Third Party to develop, obtain regulatory approval for, or commercialize its own investigational agent(s). However, this provision will not apply unless the Third Party also agrees to Collaborator’s reciprocal use of Multi-Party Data.

8.9.3	Collaborator and the Third Party must agree in writing prior to the commencement of the combination Protocol(s) by signing the drug approval form for clinical studies or Non-Clinical Study(ies) that each will use the Multi-Party Data solely for the development, regulatory approval, and commercialization of its own investigational agent(s).

8.10

Access, review and receipt of Identifiable Private Information. Collaborator access to and review of Identifiable Private Information shall be only for on-site quality auditing, or as necessary for purposes of satisfying FDA or other health authorities' reporting requirements, and for internal research purposes, directly related to obtaining regulatory approval of Investigational Agent. Collaborator is prohibited from access, review, receipt, or use of such information for other purposes. All IRB approved Protocols and informed consent documents related to this research project will clearly describe this practice. The Protocol and the informed consent must clearly state (i) the existence of the Collaborator; (ii) the Collaborator's access to and permitted uses of Identifiable Private Information; and (iii) the extent to which confidentiality will be maintained. For clinical Protocol(s) involving a Third Party, the other party's access, review, receipt, or use of Identifiable Private Information shall be subject to the same limitations as described in this Paragraph 8.10.

9.1	Representations of IC. IC hereby represents to Collaborator that:

9.1.1	IC has the requisite power and authority to enter into this CRADA and to perform according to its terms, and that IC’s official signing this CRADA has authority to do so.

9.1.2

To the best of its knowledge and belief, neither IC nor any of its personnel involved in this CRADA is presently subject to debarment or suspension by any agency of the Government. Should IC or any of its personnel involved in this CRADA be debarred or suspended during the term of this CRADA, IC will notify Collaborator within thirty (30) days of receipt of final notice. IC requires all NCI Extramural Investigators performing any part of the Research Plan to assure that they and their respective personnel involved in the performance of the Research Plan are not subject to debarment or suspension by any agency of the Government, and to notify IC if they or any of their personnel involved in the performance of the Research Plan are debarred or suspended during the term of the CRADA. IC will notify Collaborator promptly if it receives notice that any NCI Extramural Investigators performing any part of the Research Plan are debarred or suspended.

9.2	Representations and Warranties of Collaborator. Collaborator hereby represents and warrants to IC that:

9.2.1	Collaborator has the requisite power and authority to enter into this CRADA and to perform according to its terms, and that Collaborator’s official signing this CRADA has authority to do so.

9.2.2	Neither Collaborator nor any of its personnel involved in this CRADA, including Affiliates, agents, and contractors, are presently subject to debarment or suspension by any agency of the

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9.2.3	Subject to Paragraph 12.3, and if and to the extent Collaborator has agreed to provide funding under Appendix B, Collaborator is financially able to satisfy these obligations in a timely manner.

9.2.4	The Investigational Agent provided for use in clinical studies under the Research Plan has been produced in accordance with the FDA’s current Good Manufacturing Practices set out in 21 C.F.R. §§ 210-211, and ICH Q7, and meets the specifications cited in the Certificate of Analysis and Investigator’s Brochure provided.

10.1	Expiration. Unless terminated earlier as permitted in this CRADA, this CRADA will expire on the last date of the term set forth on the Summary Page. In no case will the term of this CRADA extend beyond the term indicated on the Summary Page unless it is extended in writing in accordance with Paragraph 13.6.

10.2	Termination by Mutual Consent. IC and Collaborator may terminate this CRADA at any time by mutual written consent.

10.3

Unilateral Termination. Either IC or Collaborator may unilaterally terminate this CRADA (a) at any time by providing written notice at least sixty (60) days before the desired termination date; or (b) upon written notice in the event of a material breach by the other Party that has not been cured within [ * ] after the breaching Party’s receipt of a written notice of such breach provided in accordance with Paragraph 13.8; or (c) immediately upon written notice for Human Subject safety concerns. IC may, at its option, retain funds transferred to IC before unilateral termination by Collaborator for use in completing the Research Plan. If Collaborator terminates this Agreement under subclause (a) of this Paragraph before the completion of all active Protocol(s) or Protocol(s) that have been approved by the PRC and Collaborator in accordance with the procedures set forth in the Research Plan, then Collaborator will supply enough Investigational Agent (and Placebo, if applicable) to complete these Protocol(s).

10.4

Funding for IC Personnel. If Collaborator has agreed to provide funding for IC personnel and this CRADA is unilaterally terminated by Collaborator before its expiration for any reason other than for an uncured material breach or Human Subject safety concerns, then Collaborator agrees that funds for that purpose will be available to IC for a period of six (6) months after the termination date or until the expiration date of the CRADA, whichever occurs sooner. If there are insufficient funds to cover this expense, Collaborator agrees to pay the difference.

10.5

New Commitments. Neither Party will incur new expenses related to this CRADA after expiration, or mutual termination, or a notice of a unilateral termination and will, to the extent feasible, cancel all outstanding commitments and contracts by the termination date. Collaborator acknowledges that IC will have the authority to retain and expend any funds previously paid by Collaborator for up to two and one-half (2.5) years subsequent to the expiration or termination date to cover any unpaid costs obligated during the term of the CRADA in undertaking the research and development activities set forth in the Research Plan.

11.1	Settlement. Any dispute arising under this CRADA which is not disposed of by agreement of the NIH CRADA Extramural Investigator/Officers and CRADA Collaborator PIs will be submitted jointly to the

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11.2	Continuation of Work. Pending the resolution of any dispute or claim pursuant to this Article 11, the Parties agree that performance of all obligations will be pursued diligently.

12.1

NO WARRANTIES. EXCEPT AS SPECIFICALLY STATED IN ARTICLE 9, THE PARTIES MAKE NO EXPRESS OR IMPLIED WARRANTY AS TO ANY MATTER WHATSOEVER, INCLUDING THE CONDITIONS OF THE RESEARCH OR ANY INVENTION OR MATERIAL, WHETHER TANGIBLE OR INTANGIBLE, MADE OR DEVELOPED UNDER OR OUTSIDE THE SCOPE OF THIS CRADA, OR THE OWNERSHIP, MERCHANTABILITY, OR FITNESS FOR A PARTICULAR PURPOSE OF THE RESEARCH OR ANY INVENTION, MATERIAL OR INVESTIGATIONAL AGENT, OR THAT A TECHNOLOGY OR INVESTIGATIONAL AGENT UTILIZED BY A PARTY IN THE PERFORMANCE OF THE RESEARCH PLAN DOES NOT INFRINGE ANY THIRD-PARTY PATENT RIGHTS.

12.2

Indemnification and Liability. No indemnification for any loss, claim, damage, or liability is intended or provided by any Party under this Agreement. Each Party will be liable for any loss, claim, damage or liability that said Party incurs in connection with or as a result of its activities under this CRADA, except that IC, as an agency of the Government, assumes liability only to the extent provided under the Federal Tort Claims Act , 28 U.S.C. Chapter 171.

12.3

Force Majeure. Neither Party will be liable for any unforeseeable event beyond its reasonable control and not caused by its own fault or negligence, which causes the Party to be unable to perform its obligations under this CRADA, and which it has been unable to overcome by the exercise of due diligence. If a force majeure event occurs, the Party unable to perform will promptly notify the other Party. It will use its diligent efforts to resume performance as quickly as possible and will suspend performance only for such period of time as is necessary as a result of the force majeure event.

13.1	Governing Law. The construction, validity, performance and effect of this CRADA will be governed by U.S. federal law, as applied by the federal courts in the District of Columbia. If any provision in this CRADA conflicts with or is inconsistent with any U.S. federal law or regulation, then the U.S. federal law or regulation will preempt that provision.

13.2

Compliance with Law. IC and Collaborator agree that they will comply with, and advise any individuals they have engaged to conduct the CRADA research and development activities to comply with, all applicable Executive Orders, statutes, and HHS regulations relating to research on human subjects (45 C.F.R. Part 46, 21 C.F.R. Parts 50 and 56) and relating to the appropriate care and use of laboratory animals (7 U.S.C. §§ 2131 et seq.; 9 C.F.R. Part 1, Subchapter A), including all applicable federal regulations for the protection of Human Subjects, which may include the Standards for Privacy of Individually Identifiable Health Information set forth in 45 C.F.R. Part 164. Collaborator agrees to ensure that its employees, contractors, and agents who might have access to a “select agent or toxin” (as that term is defined in 42 C.F.R. §§ 73.4-73.5) transferred from IC is properly licensed to receive the “select agent or toxin.”

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13.3	Waivers. None of the provisions of this CRADA will be considered waived by any Party unless a waiver is given in writing to the other Party. The failure of a Party to insist upon strict performance of any of the terms and conditions hereof, or failure or delay to exercise any rights provided herein or by law, will not be deemed a waiver of any rights of any Party.

13.4	Headings. Titles and headings of the articles and paragraphs of this CRADA are for convenient reference only, do not form a part of this CRADA, and will in no way affect its interpretation.

13.5	Severability. The illegality or invalidity of any provisions of this CRADA will not impair, affect, or invalidate the other provisions of this CRADA.

13.6

Amendments. Minor modifications to the Research Plan may be made by the mutual written consent of the NIH CRADA Extramural Investigator/Officers and CRADA Collaborator PIs. Substantial changes to the CRADA Research Plan, changes to the CRADA including extensions of the term, or any changes to the model template MTA will become effective only upon a written amendment signed by the signatories to this CRADA or by their representatives duly authorized to execute an amendment. A change will be considered substantial if it directly expands the range of the potential CRADA Subject Inventions, alters the scope or field of any license option governed by Article 7, or requires a significant increase in the contribution of resources by either Party.

13.7

Assignment. Neither this CRADA nor any rights or obligations of any Party hereunder shall be assigned or otherwise transferred by either Party without written notification of the other Party in accordance with Paragraph 13.8. The Collaborator acknowledges the applicability of 41 U.S.C. § 15, the Anti Assignment Act, to this Agreement.  The Parties agree that the identity of the Collaborator is material to the performance of this CRADA and that the duties under this CRADA are nondelegable.

13.8

Notices. All notices pertaining to or required by this CRADA will be in writing, signed by an authorized representative of the notifying Party, and delivered by first class registered or certified mail by U.S. Postal Service with return receipt, or by an express/overnight commercial delivery service, prepaid and properly addressed to the other Party at the address designated on the Contacts Information Page, or to any other address designated in writing by the other Party. Notices will be considered timely if received on or before the established deadline date or sent on or before the deadline date as verifiable by U.S. Postal Service postmark or dated receipt from a commercial carrier. Notices regarding the exercise of license options will be made pursuant to Paragraph 7.3. Either Party may change its address by notice given to the other Party in the manner set forth above. All notices will be deemed to have been given on the date received, as evidenced by return receipt of the records of the U.S. Postal Service or other delivery service, as applicable.

13.9

Independent Contractors. The relationship of the Parties to this CRADA is that of independent contractors and not agents of each other or joint venturers or partners. Each Party will maintain sole and exclusive control over its personnel and operations. If Collaborator elects to perform any portion of the Research Plan through contractors or consultants, Collaborator agrees to incorporate into such contract all provisions necessary to ensure that the work of such contractor(s) or consultant(s) is governed by the terms of the CRADA, including, but not limited to a provision for the assignment of inventions of the contractor(s) or consultant(s) to the Collaborator.

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13.10

Use of Name; Press Releases. By entering into this CRADA, the Government does not directly or indirectly endorse any product or service that is or will be provided, whether directly or indirectly related to either this CRADA or to any patent or other intellectual-property license or agreement that implements this CRADA by Collaborator, its successors, assignees, or licensees. Collaborator will not in any way state or imply that the Government or any of its organizational units or employees endorses any product or services. Each Party agrees to provide proposed press releases that reference or rely upon the work under this CRADA to the other Party for review and comment at least five (5) business days before publication. Either Party may disclose the Title and Abstract of the CRADA to the public without the approval of the other Party.

13.11	Reasonable Consent. Unless otherwise expressly provided in this CRADA, whenever a Party’s consent or permission is required under this CRADA, its consent or permission will not be unreasonably withheld or delayed.

13.12

Export Controls. Collaborator agrees to comply with U.S. export law and regulations, including 21 U.S.C. 382 and 21 CFR Part 312.110. If Collaborator has a need to transfer any CRADA Materials made in whole or in part by IC, or IC Materials, or IC Confidential Information to a person located in a country other than the United States, to an Affiliate organized under the laws of a country other than the United States, or to an employee of Collaborator in the United States who is not a citizen or permanent resident of the United States, Collaborator will acquire any and all necessary export licenses and other appropriate authorizations.

13.13

Entire Agreement. This CRADA constitutes the entire agreement between the Parties concerning the subject matter of this CRADA and supersedes any prior understanding or written or oral agreement with respect thereto, including the Confidential Disclosure Agreement entered into between Exelixis and The National Cancer Institute effective March 19, 2010 (the “CDA”). For clarity, this CRADA only supersedes the CDA with respect to Confidential Information (as such term is defined in Section 1 of the CDA) disclosed by or on behalf of Collaborator related to the Investigational Agent and/or drug development programs for Investigational Agent, such that all such Confidential Information disclosed under the CDA shall be deemed Collaborator Confidential Information under this CRADA. The CDA shall remain in effect with respect to all Confidential Information disclosed or to be disclosed by or on behalf of Collaborator related to other Collaborator drug development candidates and/or programs.

13.14	Survivability. The provisions of Paragraphs 3.3, 3.4, 3.7.3, 3.9, 3.10, 3.11, 4.2, 4.3, 4.4, 4.5 (for so long as IC is sponsoring clinical studies of the Investigational Agent under the CRADA), 5.3, 5.4, 6.1-8.10, 10.3-10.5, 11.1, 11.2, 12.1-12.3, 13.1-13.3, 13.5, 13.6, 13.8, 13.9, 13.10 and 13.14 will survive the expiration or early termination of this CRADA.

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For IC:	For Collaborator:

For IC:	For Collaborator (if separate from above):

For IC:	For Collaborator:

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PHS [ * ] Component:	National Cancer Institute

Officer(s):

Collaborator:	Exelixis, Inc.

CRADA Collaborator Principal Investigator:	[ * ]

Term of CRADA:	five (5) years from the Effective Date

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Recipient:	University School of Medicine

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Date	John Doe, Ph.D.

Date	Authorized Signature for Recipient and Title

Date	Sherry Ansher, Ph.D.

________________	_________________________________________

1.	Article 2, Definitions, “Test Article” is hereby amended as follows where underlining denotes addition:

2.	Article 3.8, Investigational Agent Information and Supply is hereby amended as follows where underlining denotes addition:

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1.	Upon final signature, the term of the Agreement is extended for five (5) years from October 5, 2016 to October 5, 2021.

2.	Dr. Jeffrey Abrams is removed as a NCI Principal Investigator. Dr. Margaret Mooney is added as a NCI Principal Investigator.

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4.	MANUFACTURE AND SUPPLY

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EXELIXIS, INC.	GENENTECH, INC.

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o	[ * ]

•	The subject has a histologically confirmed solid tumor that is metastatic or unresectable, and for which standard curative or palliative measures do not exist or are no longer effective, and there are no therapies known to prolong survival.

•	The subject has disease that is assessable by tumor marker, physical, or radiologic means.

•	The subject is ≥18 years old.

•	The subject’s weight is ≥55 kg and ≤120 kg.

•	The subject has an Eastern Cooperative Oncology Group (“ECOG”) performance status ≤2.

•

The subject has organ and marrow function as follows: absolute neutrophil count (“ANC”) ≥1500/mm3, platelets ≥100,000/dL, hemoglobin ≥9 g/dL, bilirubin ≤1.5 mg/dL, serum creatinine ≤1.5 mg/dL or creatinine clearance ≥60 mL/min, and alanine aminotransferase (“ALT”) and aspartate aminotransferase (“AST”) ≤2.5 times the upper limit of normal if no liver involvement, or ≤5 times the upper limit of normal with liver involvement.

•	The subject is capable of understanding and complying with the protocol and has signed the informed consent document.

•	Sexually active subjects (male and female) must use medically acceptable methods of contraception during the course of the study.

•	Female subjects of childbearing potential must have a negative pregnancy test at screening.

•	If a subject has received more than three prior regimens of cytotoxic chemotherapy, more than two biologic regimens, or more than 3000 cGy to >25% of his or her bone marrow, the sponsor must determine subject suitability before enrollment.

•	The subject has had no other diagnosis of malignancy (unless non-melanoma skin cancer or a malignancy diagnosed ³5 years ago, and has had no evidence of disease for 5 years prior to screening for this study).

•	The subject has received anticancer treatment (e.g., chemotherapy, radiotherapy, cytokines, or hormones) within 30 days (6 weeks for nitrosoureas or mitomycin C) before the first dose of study drug.

•	The subject has received radiation to >25% of his or her bone marrow within 30 days of study entry.

•	The subject has not recovered to grade ≤1 from adverse events (“AEs”) or to within 10% of baseline values due to investigational or other agents administered more than 30 days prior to study enrollment.

•	The subject has received another investigational agent within 30 days of the first dose of study drug.

•	The subject has known brain metastases.

•	The subject has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

•	The subject is pregnant or breastfeeding.

•	The subject is known to be positive for the human immunodeficiency virus (“HIV”).

•	The subject has an allergy or hypersensitivity to components of the formulation.

•	The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.

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1.	The following new Sections 1.75 through 1.77 are hereby added to the end of Article 1 of the Agreement:

2.	Section 2.1(d) of the Agreement is hereby amended and restated as follows:

3.	Section 2.2(d) of the Agreement is hereby amended by replacing the phrase [ * ] with [ * ], and by replacing the phrase [ * ] with [ * ].

4.	Section 3.1 of the Agreement is hereby amended and restated as follows:

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5.	Section 3.2(a) of the Agreement is hereby amended and restated as follows:

6.	The second sentence of Section 3.2(d) of the Agreement is hereby amended by: (1) replacing the phrase [ * ] with the phrase [ * ] and (2) replacing the phrase [ * ] with the phrase [ * ].

7.	Section 3.2(d) of the Agreement is amended by adding the following to the end of such section:

8.	Section 3.2(f) of the Agreement is hereby amended and restated as follows:

9.	Section 3.4(a) of the Agreement is hereby amended and restated as follows:

10.	Section 3.4(b)(i) of the Agreement is hereby amended and restated as follows:

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11.

Section 3.4(b)(ii) of the Agreement is hereby amended and restated in its entirety as follows: “If, as of the Initial Opt-In Expiration Date, Genentech notifies Exelixis in writing of its decision to exercise its Opt-In right with respect to such Existing Compound, then: (A) Genentech shall obtain a license, pursuant to Section 7.1, to develop and commercialize such Existing Compound and any other Collaboration Compounds; and (B) all [ * ] Existing Compound will [ * ], but will [ * ]; provided, however, that Exelixis shall [ * ], under this Agreement. The Parties shall conduct further development activities and commercialization activities with respect to such Collaboration Compounds and the associated Licensed Products pursuant to this Agreement, with Genentech being the Party responsible for the further clinical development (after the Transfer Date) of all Collaboration Compound(s) and the commercialization of any Licensed Product(s) containing such Collaboration Compound(s).

12.	Section 3.4(b)(iv) is hereby added to the Agreement to read as follows:

13.	Section 3.5(a) of the Agreement is hereby amended and restated in its entirety as follows:

14.	Section 3.5(c) of the Agreement is amended and restated to read in its entirety as follows:

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15.	Section 3.5(d) is amended and restated to read in its entirely as follows:

16.	Section 4.1(a) of the Agreement is hereby amended and restated as follows:

17.	Section 4.1(b) of the Agreement is hereby amended and restated as follows:

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18.	Section 7.1(e) of the Agreement is hereby amended by inserting the following phrase at the end of subsection (i)(2): “, including without limitation the Initial Phase I Trial (as set forth on Exhibit D)”

19.	Section 8.2(a) of the Agreement is hereby amended and restated in its entirety as follows:

20.	The second sentence of Section 10.1(b) is hereby amended by inserting the phrase “; provided, however, that [ * ] shall have the right to use such Confidential Information of [ * ] to [ * ], under this Agreement.” at the end of such sentence.

21.	Exhibit D is hereby amended and restated in its entirety, as described in the attached Appendix.

22.

Except as expressly and unambiguously stated herein, no other changes are made to the Agreement or Genentech’s rights following an Opt-In, and all other terms and conditions of the Agreement shall remain in full force and effect. In the event of a conflict between the provisions hereof and the Agreement, the provisions of this Amendment shall control. The Agreement and this Amendment contains the entire understanding between the Parties hereto with respect to the subject matter hereof and supersedes and terminates all prior agreements, understandings and arrangements between the Parties, whether written or oral with respect to such subject matter.

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o	[ * ]

•	The subject has a histologically confirmed solid tumor that is metastatic or unresectable, and for which standard curative or palliative measures do not exist or are no longer effective, and there are no therapies known to prolong survival.

•	The subject has disease that is assessable by tumor marker, physical, or radiologic means.

•	The subject is ³18 years old.

•	The subject’s weight is ³55 kg and £120 kg.

•	The subject has an Eastern Cooperative Oncology Group (“ECOG”) performance status £2.

•

The subject has organ and marrow function as follows: absolute neutrophil count (“ANC”) ³1500/mm3, platelets ³100,000/ mm3, hemoglobin ³9 g/dL, bilirubin £1.5 mg/dL, serum creatinine £1.5 mg/dL or creatinine clearance ³60 mL/min, and alanine aminotransferase (“ALT”) and aspartate aminotransferase (“AST”) £2.5 times the upper limit of normal if no liver involvement, or £5 times the upper limit of normal with liver involvement.

•	The subject is capable of understanding and complying with the protocol and has signed the informed consent document.

•	Sexually active subjects (male and female) must use medically acceptable methods of contraception during the course of the study.

•	Female subjects of childbearing potential must have a negative pregnancy test at screening.

•	If a subject has received more than three prior regimens of cytotoxic chemotherapy, more than two biologic regimens, or more than 3000 cGy to ³25% of his or her bone marrow, the sponsor must determine subject suitability before enrollment.

•	The subject has had no other diagnosis of malignancy (unless non-melanoma skin cancer or a malignancy diagnosed ³5 years ago, and has had no evidence of disease for 5 years prior to screening for this study).

•	The subject has received anticancer treatment (e.g., chemotherapy, radiotherapy, cytokines, or hormones) within 30 days (6 weeks for nitrosoureas or mitomycin C) before the first dose of study drug.

•	The subject has received radiation to ³25% of his or her bone marrow within 30 days of study entry.

•	The subject has not recovered to grade £1 from adverse events (“AEs”) or to within 10% of baseline values due to investigational or other agents administered more than 30 days prior to study enrollment.

•	The subject has received another investigational agent within 30 days of the first dose of study drug.

•	The subject has known brain metastases.

•	The subject has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

•	The subject is pregnant or breastfeeding.

•	The subject is known to be positive for the human immunodeficiency virus (“HIV”).

•	The subject has an allergy or hypersensitivity to components of the formulation.

•	The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.

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o	[ * ]