Exelixis, Inc. (Exelixis) operates as an oncology company innovating next-generation medicines and combination regimens at the forefront of cancer care.
The company has produced four marketed pharmaceutical products, two of which are formulations of its flagship molecule, cabozantinib, and it is steadily advancing and evolving its product pipeline portfolio, including its lead investigational asset, zanzalintinib, the focus of an extensive late-stage clinical development program. With a rationa...
Exelixis, Inc. (Exelixis) operates as an oncology company innovating next-generation medicines and combination regimens at the forefront of cancer care.
The company has produced four marketed pharmaceutical products, two of which are formulations of its flagship molecule, cabozantinib, and it is steadily advancing and evolving its product pipeline portfolio, including its lead investigational asset, zanzalintinib, the focus of an extensive late-stage clinical development program. With a rational and disciplined approach to investment, the company is leveraging its internal experience and expertise, and the strength of strategic partnerships, to identify and pursue opportunities across the landscape of scientific modalities, including small molecules, biotherapeutics, and antibody-drug conjugates (ADCs).
Sales related to cabozantinib account for the majority of the company’s revenues. Cabozantinib is an inhibitor of multiple tyrosine kinases, including MET, AXL, VEGF receptors, and RET, and has been approved by the U.S. Food and Drug Administration (FDA) and in 67 other countries: as CABOMETYX (cabozantinib) tablets for advanced renal cell carcinoma (RCC) (both alone and in combination with Bristol-Myers Squibb Company’s (BMS) nivolumab (OPDIVO)), for previously treated hepatocellular carcinoma (HCC), and for previously treated, radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC); and as COMETRIQ (cabozantinib) capsules for progressive, metastatic medullary thyroid cancer (MTC). For physicians treating these types of cancer, cabozantinib has become or is becoming an important medicine in their selection of effective therapies.
The other two products resulting from the company’s discovery efforts are: COTELLIC (cobimetinib), an inhibitor of MEK approved as part of multiple combination regimens to treat specific forms of advanced melanoma and marketed under a collaboration with Genentech, Inc. (a member of the Roche Group) (Genentech); and MINNEBRO (esaxerenone), an oral, non-steroidal, selective blocker of the mineralocorticoid receptor (MR), approved for the treatment of hypertension in Japan and licensed to Daiichi Sankyo Company, Limited (Daiichi Sankyo).
The company’s pipeline is zanzalintinib, a novel, potent, third-generation oral tyrosine kinase inhibitor (TKI) that targets VEGF receptors, MET, and the TAM kinases (TYRO3, AXL, and MER). The zanzalintinib program includes a series of ongoing and planned pivotal trials to explore its therapeutic potential in colorectal cancer (CRC), RCC, non-clear cell (ncc) RCC, squamous cell cancers of the head and neck (SCCHN), and neuroendocrine tumors (NET), as well as earlier-stage trials. The company’s other pipeline programs in phase 1 development each have best-in-class potential and include: XL309, a small molecule inhibitor of USP1, which has emerged as a synthetic lethal target in the context of BRCA-mutated tumors; XB010, an ADC consisting of a monomethyl auristatin E (MMAE) payload conjugated to a monoclonal antibody (mAb) targeting the tumor antigen 5T4; and XL495, a small molecule inhibitor of PKMYT1. The company complements its internal drug discovery and development efforts by in-licensing investigational oncology assets or obtaining options to acquire other investigational oncology assets from third parties if they demonstrate evidence of clinical success. Examples of this approach include XL309 and ADU-1805, a clinical-stage and potentially best-in-class mAb that targets SIRPa.
Exelixis Marketed Products: CABOMETYX and COMETRIQ
CABOMETYX and COMETRIQ have been approved to treat patients with various forms of cancer by the FDA for the U.S. market, the European Medicines Agency (EMA) for the European Union (EU) market, and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) for the Japanese market, as well as by comparable regulatory authorities across other markets worldwide.
Renal Cell Carcinoma - CABOMETYX is a Leading TKI Treatment Option for Patients with Advanced RCC
CABOMETYX has become a standard of care for the treatment of patients with advanced RCC, and a growing number of these patients have been or will be treated with CABOMETYX. In 2024, approximately 33,200 patients with advanced kidney cancer required systemic therapy in the U.S., with over 21,000 patients receiving first-line treatment.
Since CABOMETYX was first approved, the company has deployed its Medical Affairs and Commercial teams to educate physicians about CABOMETYX. CABOMETYX is attributable to the strength of the clinical data reflected in its FDA-approved labeling for advanced RCC. The indications for the treatment of advanced RCC in the CABOMETYX label are based on the results of the METEOR, CABOSUN, and CheckMate -9ER clinical trials. CABOMETYX has also demonstrated positive clinical results in combination with immune checkpoint inhibitors (ICIs), most notably in CheckMate -9ER, an open-label, randomized, multinational phase 3 pivotal trial evaluating CABOMETYX in combination with nivolumab versus sunitinib in patients with previously untreated, advanced or metastatic RCC. Results from CheckMate -9ER demonstrated that the combination of CABOMETYX and nivolumab doubled PFS and ORR and reduced the risk of disease progression or death by 40% compared with sunitinib and formed the basis for FDA approval of the combination in January 2021 as a first-line treatment of patients with advanced RCC. At five years of follow-up, the CheckMate -9ER results continued to show superior PFS and ORR in patients treated with CABOMETYX in combination with nivolumab over sunitinib, regardless of risk classification (as determined by International Metastatic Renal Cell Carcinoma Database Consortium scores). Superior OS was also observed in patients treated with the combination. In addition, the National Comprehensive Cancer Network (NCCN), the nation’s foremost non-profit alliance of leading cancer centers, has included the combination of CABOMETYX with nivolumab in its Clinical Practice Guidelines for Kidney Cancer as a Category 1 preferred option for the first-line treatment of patients with clear cell RCC across all risk groups, and as a Category 2A other recommended option for first-line nccRCC.
In 2024, in markets outside the U.S., the company continued to work closely with its collaboration partner Ipsen in the support of its regulatory strategy and commercialization efforts for CABOMETYX, both as a single agent and in combination with nivolumab, as well as in preparation for submission of applications for potential additional approvals of CABOMETYX, and similarly with its collaboration partner Takeda with respect to the Japanese market. As a result of the approvals of CABOMETYX and/or the combination of CABOMETYX with nivolumab for RCC indications in 67 countries outside of the U.S., including the Member States of the EU, Japan, the U.K., Canada, Brazil, Taiwan, South Korea, Australia, and Hong Kong, CABOMETYX has continued to grow markedly outside the U.S. both in sales revenue and the number of RCC patients benefiting from its clinical effect.
Hepatocellular Carcinoma - CABOMETYX Offers an Important Alternative for Patients with Previously Treated HCC
The FDA approved the HCC indication for CABOMETYX in January 2019 based on the company’s phase 3 pivotal study, CELESTIAL. The CELESTIAL study met its primary endpoint, demonstrating that cabozantinib significantly improved OS compared to placebo. The NCCN has included CABOMETYX in its Clinical Practice Guidelines for Hepatocellular Carcinoma as a Category 1 option for the treatment of patients with HCC as a subsequent-line systemic therapy if disease progression occurs, providing further support for CABOMETYX as an important treatment option for eligible HCC patients.
Outside the U.S., the EMA’s approval of CABOMETYX provided physicians in the EU with a second approved therapy for the second-line treatment of this aggressive and difficult-to-treat cancer, and approvals from Health Canada and the Japanese PMDA brought a much-needed treatment option to HCC patients in those countries. In addition to the Member States of the EU, Japan, the U.K., and Canada, CABOMETYX is also approved for previously treated HCC indications in Brazil, Taiwan, South Korea, Australia, and Hong Kong, among other countries.
Differentiated Thyroid Cancer - An Opportunity for CABOMETYX to Help an Underserved Patient Population
In December 2020, the company announced that COSMIC-311, its phase 3 pivotal trial evaluating cabozantinib in patients with RAI-refractory DTC who have progressed after receiving up to two prior VEGF receptor-targeted therapies, met one of its two primary endpoints, demonstrating a statistically significant improvement in PFS compared with placebo.
Outside the U.S., its collaboration partner Ipsen received approval from the EMA in May 2022 for CABOMETYX as a monotherapy for the treatment of adult patients with locally advanced or metastatic DTC, refractory or not eligible to RAI who have progressed during or after prior systemic therapy, which followed an approval from Health Canada in April 2022 to market CABOMETYX for a similar DTC indication.
Medullary Thyroid Cancer - COMETRIQ, the First Commercial Approval of Cabozantinib
Estimates suggest that there will be approximately 970 MTC cases diagnosed in the U.S. in 2025, and COMETRIQ has served as an important treatment option for these patients since January 2013. The FDA approved COMETRIQ for progressive, metastatic MTC based on the company’s phase 3 trial, EXAM. The EXAM trial met its primary endpoint, demonstrating a statistically significant and clinically meaningful prolongation in PFS for cabozantinib compared with placebo. The company is continuing to market COMETRIQ capsules for MTC patients at the labeled dose of 140 mg.
Development Programs
Cabozantinib Development Program
Cabozantinib inhibits the activity of tyrosine kinases, including MET, AXL, VEGF receptors, and RET. These receptor tyrosine kinases are involved in both normal cellular function and in pathologic processes, such as oncogenesis, metastasis, tumor angiogenesis, drug resistance, and maintenance of the tumor microenvironment. Beyond the established clinical benefits of cabozantinib in its approved indications, objective responses have been observed in patients treated with cabozantinib in additional individual tumor types investigated in early- and late-stage clinical trials, reflecting the medicine’s broad clinical potential. The company is continuing to evaluate cabozantinib in combination with ICIs in late-stage clinical trials that it sponsors, along with its collaboration partners. Independent investigators also conduct trials evaluating cabozantinib through its Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute’s Cancer Therapy Evaluation Program (NCI-CTEP) or its investigator-sponsored trial (IST) program. In addition to facilitating label expansion for the cabozantinib franchise, including its regulatory submissions for cabozantinib to treat NET based on the positive results from the phase 3 CABINET study, data sets from these externally sponsored clinical trials may also prove valuable by informing its development plans for zanzalintinib. Moreover, its collaboration partners Ipsen and Takeda have conducted trials in their respective territories through independently-sponsored programs, as well as co-funding select cabozantinib trials with it.
Combination Studies with BMS
In February 2017, the company entered into a clinical collaboration agreement with BMS for the purpose of conducting clinical studies combining cabozantinib with BMS’s PD-1 ICI, nivolumab, with or without BMS’s CTLA-4 ICI, ipilimumab. Based on the data from CheckMate -9ER, the first clinical trial conducted under this collaboration, the FDA approved CABOMETYX in combination with nivolumab on January 22, 2021, as a first-line treatment of patients with advanced RCC. In May 2019, the company initiated COSMIC-313, a multicenter, randomized, double-blinded, controlled phase 3 pivotal trial evaluating the triplet combination of cabozantinib, nivolumab, and ipilimumab versus the combination of nivolumab and ipilimumab in patients with previously untreated advanced intermediate- or poor-risk RCC. Patients were randomized 1:1 to the experimental arm of the triplet combination or to the control arm of nivolumab and ipilimumab in combination with matched placebo. In August 2024, the company announced the final analysis for the secondary endpoint of OS, which demonstrated that the experimental arm did not demonstrate an OS benefit over the control arm.
Combination Studies with Roche
The company has also entered into collaborations with F. Hoffmann-La Roche Ltd. (Roche) for the purpose of evaluating the combination of cabozantinib and Roche’s anti-PD-L1 ICI, atezolizumab, diversifying its exploration of cabozantinib combinations with ICIs.
COSMIC-021 - Locally Advanced or Metastatic Solid Tumors: In February 2017, the company entered into a master clinical supply agreement with Roche. As part of the clinical supply agreement, in June 2017, it initiated COSMIC-021, a large phase 1b study evaluating the safety and tolerability of cabozantinib in combination with atezolizumab in patients with a wide variety of locally advanced or metastatic solid tumors. The company is the trial sponsor of COSMIC-021, and Roche is providing atezolizumab free of charge. The study is divided into two parts: a dose-escalation phase, which was completed in 2018; and an expansion cohort phase, which completed enrollment in January 2022. Enrollment in the expansion phase of this study included 20 combination therapy tumor expansion cohorts in non-small cell lung cancer (NSCLC), mCRPC, RCC, and various other tumor types.
CONTACT trials: Informed by the encouraging efficacy and safety data that emerged from COSMIC-021, the company entered into a joint clinical research agreement with Roche in December 2019, pursuant to which the parties co-funded and undertook three pivotal phase 3 studies evaluating the combination of cabozantinib and atezolizumab. Two of these trials, CONTACT-01 in advanced NSCLC and CONTACT-03 in RCC (each sponsored by Roche) did not meet their respective primary endpoints. The third trial, CONTACT-02, is sponsored by the company and evaluates the combination in patients with mCRPC.
CONTACT-02 – mCRPC: In June 2020, the company and Roche initiated CONTACT-02, a global, multicenter, randomized, open-label phase 3 pivotal trial evaluating cabozantinib in combination with atezolizumab versus a second novel hormonal therapy (NHT) (either abiraterone and prednisone or enzalutamide) in patients with measurable extra-pelvic mCRPC who have progressed after treatment with one prior NHT. CONTACT-02 is informed by positive early-stage results from an mCRPC cohort of COSMIC-021, as well as by COMET-1, the company’s earlier phase 3 trial that evaluated monotherapy cabozantinib in mCRPC. The CONTACT-02 trial enrolled 575 patients at 275 sites globally, and enrollment was completed in the second half of 2023.
Trials Conducted through its CRADA with NCI-CTEP and its IST Program
Clinical trials conducted with support from external partners have enabled further expansion of the cabozantinib development program with less burden on its internal development resources. In October 2011, the company entered into a CRADA with NCI-CTEP for the clinical development of cabozantinib and has extended its term through October 2026. The CRADA reflects a commitment by NCI-CTEP to provide funding for the broad exploration of cabozantinib’s potential in a wide variety of cancers, each representing a substantial unmet medical need. Investigational New Drug (IND) applications for trials under the CRADA are held by NCI-CTEP. NCI-CTEP also retains rights to any inventions made in whole or in part by NCI-CTEP investigators.
CABINET – NET: The Alliance led the CABINET phase 3 pivotal study under the CRADA that evaluated cabozantinib versus placebo in patients who experienced progression after prior systemic therapy in two independently powered cohorts: one for advanced pancreatic NET (pNET) that enrolled 93 patients; and another for extra-pancreatic NET (epNET), historically referred to as carcinoid tumors, that enrolled 193 patients. Patients in both cohorts were randomized 2:1 to either the experimental arm of 60 mg cabozantinib daily or placebo, respectively. The primary endpoint for both studies was PFS per RECIST v. 1.1. In August 2023, enrollment into the study was stopped, patients were unblinded, and those on placebo were offered treatment with cabozantinib due to dramatic improvements in PFS observed at interim analyses and based upon local investigator assessment. In August 2024, the company announced that the FDA had accepted its sNDA seeking approval for cabozantinib to treat adult patients with previously treated, locally advanced/unresectable or metastatic, well- or moderately differentiated pNET or epNET, granted standard review in the U.S., and assigned a Prescription Drug User Fee Act (PDUFA) target action date of April 3, 2025. The FDA also granted orphan drug designation to cabozantinib for the treatment of pNET. In November 2024, the company announced that its sNDA would be discussed at an Oncologic Drugs Advisory Committee (ODAC) meeting in March 2025; however, in January 2025, it announced that the FDA had notified it that its sNDA would no longer be the subject of discussion at an ODAC.
Pipeline Development Programs - Advancing Exelixis’ Future Cancer Therapy Candidates
To continue growing its pipeline, the company is investing heavily in the identification, exploration, and advancement of new molecules that are clinically differentiated with the potential to improve the standard of care for cancer patients.
Zanzalintinib Development Program
Zanzalintinib is a novel, potent, third-generation oral TKI that targets VEGF receptors, MET, and the TAM kinases (TYRO3, AXL, and MER) implicated in cancer’s growth and spread, and is the company's first in-house compound to enter the clinic following its re-initiation of drug discovery activities in 2017. Zanzalintinib has a pharmacokinetic half-life of approximately one day, supporting once-daily dosing, which could translate into more effective management of adverse events and a potentially favorable safety profile compared with other VEGF-receptor TKIs. Taken together with the promising anti-tumor activity, zanzalintinib is positioned to be a VEGF-receptor TKI in a wide range of solid tumors when used as a monotherapy, as well as in combination regimens. Accordingly, the company is evaluating zanzalintinib in a growing development program that builds on its prior experience with cabozantinib and targets indications with high unmet need.
STELLAR-001 - Advanced Solid Tumors: Initiated in 2019, STELLAR-001 is a multicenter phase 1b/2 clinical trial evaluating the pharmacokinetics, safety, tolerability, and preliminary anti-tumor activity of zanzalintinib and is divided into dose-escalation and expansion phases designed to evaluate zanzalintinib both as a monotherapy and in combination with atezolizumab in a variety of solid tumors. The company previously presented data from STELLAR-001 during poster sessions at the 2022 ESMO Congress, which demonstrated preliminary clinical activity similar to that observed with cabozantinib, across a range of solid tumors and dose levels, with a manageable safety profile. The phase 2 recommended dose for both monotherapy zanzalintinib and zanzalintinib in combination with atezolizumab was determined to be 100 mg once daily. Enrollment into the STELLAR-001 expansion cohorts for clear cell RCC, nccRCC, hormone-receptor positive breast cancer, mCRPC, and CRC is complete, and the company presented initial results evaluating monotherapy zanzalintinib in patients with previously treated clear cell RCC during the Oral Abstracts session at the International Kidney Cancer Symposium (IKCS) in November 2023.
STELLAR-002 - Advanced Solid Tumors: In December 2021, the company initiated STELLAR-002, a multicenter phase 1b/2 clinical trial evaluating the safety, tolerability, and efficacy of zanzalintinib in combination with either nivolumab, nivolumab and ipilimumab, or a fixed-dose combination of nivolumab and relatlimab, a lymphocyte activation gene-3-blocking (LAG-3) antibody developed by BMS. STELLAR-002 is divided into dose-escalation and expansion phases. The company has established recommended doses of zanzalintinib for these combination regimens and is exploring them in a diverse array of solid tumor expansion cohorts, including clear cell RCC, nccRCC, HCC, mCRPC, and CRC. The key efficacy endpoints are investigator-assessed ORR per RECIST v. 1.1, PFS, and OS. Monotherapy zanzalintinib may also be evaluated to support regulatory requirements for dosing and contribution of components. The company anticipates initial clinical data readouts from STELLAR-002 in the first half of 2025.
STELLAR-009 - Advanced Clear Cell RCC and Other Solid Tumors: In December 2023, the company initiated STELLAR-009, a targeted phase 1b/2 trial evaluating the safety, tolerability, and pharmacokinetics of zanzalintinib in combination with AB521, an inhibitor of hypoxia-inducible factor-2 alpha (HIF-2?) developed by Arcus Biosciences, Inc. (Arcus). In September 2024, the company halted enrollment following the joint decision between it and Arcus to wind down the study and end its clinical collaboration given the two companies’ differing strategies with respect to potential TKI-HIF combination regimens to treat RCC.
STELLAR-303 – CRC: In June 2022, the company initiated STELLAR-303, a global, multicenter, randomized, open-label phase 3 pivotal trial evaluating zanzalintinib in combination with atezolizumab versus regorafenib in patients with metastatic, refractory non-microsatellite instability-high or non-mismatch repair-deficient CRC. The company announced the completion of enrollment into STELLAR-303 in August 2024, and preliminary results are expected in the second half of 2025, dependent on study event rates. Patients are randomized 1:1 to the experimental arm of zanzalintinib in combination with atezolizumab or to the control arm of regorafenib. Under the amended trial protocol, the primary efficacy endpoint for STELLAR-303 is OS in those patients without liver metastases, followed by OS in the full intent-to-treat population. Additional key endpoints include investigator-assessed PFS, ORR, and DOR per RECIST v. 1.1 in each population.
TELLAR-304 - Non-Clear Cell RCC: In December 2022, the company initiated STELLAR-304, a global, multicenter, randomized, open-label phase 3 pivotal trial evaluating zanzalintinib in combination with nivolumab versus sunitinib in previously untreated patients with advanced nccRCC. The trial aims to enroll approximately 291 patients at approximately 173 sites globally by mid-2025. Patients are being randomized 2:1 to the experimental arm of zanzalintinib in combination with nivolumab or to the control arm of sunitinib, respectively. The primary efficacy endpoints for STELLAR-304 are BIRC-assessed PFS and ORR per RECIST v. 1.1. The secondary efficacy endpoint is OS. Based on current enrollment status in the trial, the primary endpoint of PFS is expected to be available in the second half of 2025, dependent on study event rates.
STELLAR-305 - Squamous Cell Cancers of the Head and Neck (SCCHN): In December 2023, the company initiated STELLAR-305, a global, multicenter, randomized, double-blinded phase 2/3 pivotal trial evaluating zanzalintinib in combination with pembrolizumab, an anti-PD-1 ICI developed by Merck & Co., Inc. (Merck & Co.), versus monotherapy pembrolizumab in patients with previously untreated PD-L1-positive recurrent or metastatic SCCHN. The trial aims to enroll approximately 600 patients at approximately 215 sites globally, and enrollment is ongoing. Patients will be randomized 1:1 to receive zanzalintinib in combination with pembrolizumab or placebo in combination with pembrolizumab. The primary efficacy endpoints for STELLAR-305 are BIRC-assessed PFS per RECIST v. 1.1 and OS. Secondary endpoints include investigator-assessed PFS per RECIST v. 1.1 and ORR and DOR per RECIST v. 1.1 as assessed by both BIRC and the investigator.
Beyond STELLAR-303, STELLAR-304, and STELLAR-305, the company intends to initiate additional early-stage and pivotal trials evaluating zanzalintinib across a broad array of future potential indications.
XL309 Development Program
In September 2023, the company entered into an exclusive global license agreement with Insilico Medicine US, Inc. and its affiliate, Insilico Medicine Hong Kong Limited, along with their parent company and certain other affiliated entities (individually and collectively referred to as Insilico). The agreement with Insilico grants the company global rights to develop and commercialize XL309, a potentially best-in-class small molecule inhibitor of USP1, a synthetic lethal target in the context of BRCA-mutated tumors. XL309 is being evaluated in a phase 1 clinical trial to explore its pharmacokinetics, safety, tolerability, and preliminary anti-tumor activity in patients with advanced solid tumors as a monotherapy and in combination with olaparib, a PARP1/2 inhibitor, and enrollment is ongoing. XL309 has potential in patients whose tumors are no longer responsive to PARP inhibitors (PARPi), including ovarian, breast, and prostate cancers. XL309 also has potential in combination with PARPi agents to deepen and prolong the response seen to PARPi, as well as to broaden the activity beyond that observed in patients with tumors that harbor a BRCA1/2 mutation.
ADU-1805 Development Program
In November 2022, the company executed an exclusive option and license agreement and clinical development collaboration with Sairopa B.V. (Sairopa), providing the company with the right to exclusively in-license ADU-1805, a clinical-stage and potentially best-in-class mAb developed by Sairopa that targets SIRPa. In February 2023, the FDA cleared the initial IND for ADU-1805 to evaluate the safety and pharmacokinetics of ADU-1805 in adults with advanced solid tumors. ADU-1805 is being evaluated in a phase 1 clinical trial to explore its pharmacokinetics, safety, tolerability, and preliminary anti-tumor activity in patients with advanced or metastatic refractory solid tumors, and enrollment is ongoing.
Termination of CBX-12 and XB002 Development Programs
In January 2024, the company elected to terminate its collaboration agreement, executed in November 2022 with Cybrexa Therapeutics, LLC (Cybrexa), and relinquish all rights with respect to CBX-12 (alphalex exatecan), a clinical-stage, peptide-drug conjugate that utilizes Cybrexa’s proprietary alphalex technology to enhance delivery of exatecan to tumor cells. In August 2024, the company announced that it will discontinue the development of XB002, its tissue factor (TF) targeting ADC, as part of its portfolio prioritization efforts. Based on available data, the compound is unlikely to improve upon tisotumab vedotin or other competitor TF-targeting ADCs in development. The company plans to disclose data from the phase 1 JEWEL-101 study, evaluating XB002 in advanced solid tumors, at a later date. The company plans to reallocate resources to new pivotal trials with zanzalintinib, advancing XL309, and its growing pipeline.
Expansion of the Exelixis Pipeline
The company is working to expand its oncology product pipeline through drug discovery efforts, which encompass its diverse biotherapeutics and small molecule programs exploring multiple modalities and mechanisms of action.
Biotherapeutics Programs
The company is advancing a variety of biotherapeutics that have the potential to become anti-cancer therapies, including bispecific antibodies and ADCs. ADCs, in particular, present a unique opportunity for new cancer treatments, given their capabilities to deliver anti-cancer drug payloads to targets with increased precision while minimizing impact on healthy tissues. The company has established multiple research collaborations and in-licensing arrangements, and entered into other strategic transactions, aimed at conserving capital and managing risks, that provide it with access to antibodies, binders, payloads, and conjugation technologies, which are the components employed to generate next-generation ADCs or multispecific antibodies. In addition to the option deal with Sairopa, some of the company’s active research collaborations for biotherapeutics programs include collaborations with:
Adagene Inc. (Adagene), which is focused on using Adagene’s SAFEbody technology to develop novel masked ADCs or other innovative biotherapeutics with potential for improved therapeutic index;
Catalent, Inc. (Catalent), which is focused on the discovery and development of multiple ADCs using Catalent’s proprietary SMARTag site-specific bioconjugation technology; and
Invenra, Inc. (Invenra), which is focused on the discovery and development of novel binders and multispecific antibodies for the treatment of cancer.
XB064 is a high-affinity mAb that targets immunoglobulin-like transcript 2 (ILT2), which is associated with resistance to PD-1 pathway inhibitors, with potential to combine broadly with the company's internal pipeline and approved immunotherapy agents, and was discovered, in part, in collaboration with Invenra: XB033 is an ADC targeting the tumor antigen IL13Ra2, and was discovered, in part, in collaboration with Invenra and Catalent.
Small Molecule Programs
Since its formation in 2000, the company's drug discovery group has advanced over 25 compounds to the IND stage, either independently or with collaboration partners, and today it deploys its drug discovery expertise to advance small molecule programs toward and through preclinical development.
Collaborations and Business Development Activities
Cabozantinib Commercial Collaborations
Ipsen Collaboration
In February 2016, the company entered into a collaboration and license agreement with Ipsen for the commercialization and further development of cabozantinib. Under the collaboration agreement, Ipsen received exclusive commercialization rights for current and potential future cabozantinib indications outside of the U.S., Canada, and Japan. The collaboration agreement has been subsequently amended on multiple occasions, including in December 2016 to include commercialization rights in Canada. The company has also agreed to collaborate with Ipsen on the development of cabozantinib for current and potential future indications.
Takeda Collaboration
In January 2017, the company entered into a collaboration and license agreement with Takeda, as subsequently amended to, among other things, modify the amount of reimbursements it receives for costs associated with its required pharmacovigilance activities and milestones it is eligible to receive, as well as modify certain cost-sharing obligations related to the Japan-specific development costs associated with CONTACT-01 and CONTACT-02. Under the collaboration agreement, Takeda has exclusive commercialization rights for current and potential future cabozantinib indications in Japan, and the parties have agreed to collaborate on the clinical development of cabozantinib in Japan. The operation and strategic direction of the parties’ collaboration is governed through a joint executive committee and appropriate subcommittees.
Cabozantinib Development Collaborations
BMS Collaboration
In February 2017, the company entered into a clinical trial collaboration agreement with BMS for the purpose of exploring the therapeutic potential of cabozantinib in combination with BMS’s ICIs, nivolumab and/or ipilimumab, to treat a variety of types of cancer.
Roche Collaboration
In February 2017, the company entered into a master clinical supply agreement with Roche for the purpose of evaluating cabozantinib and Roche’s ICI, atezolizumab, in locally advanced or metastatic solid tumors. Under this agreement, in June 2017, the company initiated COSMIC-021 and in December 2018, it initiated COSMIC-312.
Zanzalintinib Clinical Collaborations
The company has also entered into multiple collaboration and supply agreements to evaluate zanzalintinib in various combination trials, including with Roche’s atezolizumab, BMS’s nivolumab, ipilimumab, and relatlimab, and Merck’s pembrolizumab and belzutifan. These agreements facilitate the efficient exploration of the tolerability and activity of zanzalintinib in combinations with a variety of established cancer therapies as the company continues to build a broad development program for zanzalintinib.
Research Collaborations and In-licensing Arrangements
Sairopa: In November 2022, the company entered into an exclusive option and license agreement and clinical development collaboration with Sairopa to develop ADU-1805. Under the agreement, the company made an upfront payment to Sairopa, including additional payments for near-term milestones, in exchange for an option to obtain an exclusive, worldwide license to develop and commercialize ADU-1805 and other anti-SIRPa antibodies, and for certain expenses to be incurred by Sairopa in conducting prespecified phase 1 clinical studies of ADU-1805 during the option period.
Insilico: In September 2023, the company entered into an exclusive global license agreement with Insilico. Under the agreement, Insilico granted the company global rights to develop and commercialize XL309 in exchange for an upfront payment to Insilico of $80 million. Insilico is also eligible to receive future development, commercial, and sales-based milestone payments, as well as tiered royalties on net sales. In the fourth quarter of 2023, the company completed the transfer of stewardship of the ongoing phase 1 clinical trial evaluating XL309 from Insilico to it.
The company continues to make progress on its various research collaborations and in-licensing arrangements focused on its early-stage pipeline with the intention of advancing new candidates toward the clinic, including the following:
Catalent: In September 2020, the company entered into a collaboration and license agreement with Catalent to develop multiple ADCs using Catalent’s proprietary SMARTag site-specific bioconjugation technology.
Adagene: In February 2021, the company entered into a collaboration and license agreement with Adagene to utilize Adagene’s SAFEbody technology platform to generate masked versions of mAbs from its growing preclinical pipeline for the development of ADCs or other innovative biotherapeutics against Exelixis-nominated targets.
Iconic: In May 2019, the company entered into an exclusive option and license agreement with Iconic to advance an innovative next-generation ADC program for cancer, leveraging Iconic’s expertise in targeting TF in solid tumors. The company later amended this agreement to obtain broad rights to develop the in-licensed anti-TF antibodies, allowing it to advance preclinical development of XB371, an ADC consisting of a topoisomerase payload conjugated to a TF-targeting monoclonal antibody.
Invenra: In May 2018, the company entered into a collaboration and license agreement with Invenra to discover and develop multispecific antibodies for the treatment of cancer. Invenra is responsible for antibody lead discovery and generation while the company will lead IND-enabling studies, manufacturing, clinical development in single-agent and combination therapy regimens, and future regulatory and commercialization activities.
In order to prioritize the advancement of the company's pipeline of clinical and near-clinical programs, the company rebalanced its investment priorities and research and development resources toward its product development activities. Accordingly, in April 2024, the company terminated its arrangements with Aurigene, BioInvent International AB, Cybrexa, and STORM Therapeutics LTD.
Other Collaborations
Prior to the commercialization of the company's first product, COMETRIQ, the company's primary business strategy was focused on the development and out-licensing of innovative drug candidate compounds to pharmaceutical and biotechnology companies under collaboration agreements that allowed it to retain economic participation in the asset and support additional development of its proprietary products. The company's collaboration agreements with Genentech and Daiichi Sankyo are representative of this historical strategy. Under its collaboration agreement with Genentech, the company out-licensed the further development and commercialization of COTELLIC, and under its collaboration agreement with Daiichi Sankyo, the company granted Daiichi Sankyo an exclusive, worldwide license to certain intellectual property, including MINNEBRO.
Marketing and Sales
The company has a fully integrated commercial team consisting of sales, marketing, market access, and commercial operations functions. The company's sales team promotes CABOMETYX and COMETRIQ in the U.S. The company markets its products in the U.S. and concentrates its efforts on oncologists, oncology nurses, pharmacists, and other healthcare professionals. In addition to using customary in-person pharmaceutical company practices, the company also utilizes digital marketing technologies to expand its engagement opportunities with customers.
The company's commercial products, CABOMETYX and COMETRIQ, are sold initially through wholesale distribution and specialty pharmacy channels and then, if applicable, resold to hospitals and other organizations that provide CABOMETYX and COMETRIQ to end-user patients. To facilitate its commercial activities in the U.S., the company also employs various third parties, such as advertising agencies, market research firms, and vendors providing other sales-support related services as needed, including digital marketing and other non-personal promotion.
In addition, the company relies on Ipsen and Takeda for ongoing and further commercialization and distribution of CABOMETYX in territories outside of the U.S., as well as for access and distribution activities for the approved products, including named patient use programs or similar programs, and the company also relies on Ipsen for these same activities with respect to the commercialization and distribution of COMETRIQ outside of the U.S.
Government Regulation
The FDA and comparable regulatory agencies in state and local jurisdictions and in foreign countries impose substantial requirements upon the clinical development, manufacture, and marketing of pharmaceutical products. These agencies and other federal, state, and local entities regulate, among other things, research and development activities and the testing, marketing approval, manufacture, quality control, safety, effectiveness, labeling, storage, distribution, post-marketing safety reporting, export, import, record keeping, advertising, and promotion of the company's products.
The company and its third-party contract manufacturing organizations are subject to periodic unannounced inspections by the FDA and certain state agencies, as well as inspectors from other jurisdictions in which the company's products are approved, for compliance with GMP, which impose certain manufacturing requirements (including procedural and documentation requirements) upon the company and its third-party contract manufacturing organizations.
Patents and Proprietary Rights
Cabozantinib
Cabozantinib is covered by more than 15 issued patents in the U.S., building from U.S. Patent No. 7,579,473, for the composition of matter of cabozantinib and pharmaceutical compositions thereof. This composition of matter patent, with patent term extension, will expire in August 2026.
In the EU, cabozantinib is protected by issued patents covering the composition of matter until 2029, with Supplementary Protection Certificates. In addition to the composition of matter patent, Exelixis owns certain later-expiring patents directed to the commercial product, including particular salts, polymorphs, formulations, or use of the compound in the treatment of specified diseases or conditions.
Similarly, in Japan, cabozantinib is protected by issued patents covering the composition of matter, and salts thereof, as well as pharmaceutical compositions and related methods of use. Takeda has applied for patent term extension in Japan to extend the term of the composition of matter patent to 2029. The company has other filed patent applications and issued patents in the U.S. and other selected countries covering certain synthetic methods, salts, polymorphs, formulations, prodrugs, metabolites, and/or combinations of cabozantinib that, if issued, are anticipated to expire as late as 2037. Outside the U.S. and Japan, cabozantinib is licensed to Ipsen, and in Japan, cabozantinib is licensed to Takeda, each in accordance with the respective collaboration agreements.
Zanzalintinib and Other Product Candidates
The company also has issued patents and pending patent applications, and will continue to file new patent applications, in the U.S., the EU, and other selected countries covering zanzalintinib and its other product candidates in clinical and/or preclinical development. Zanzalintinib is covered by U.S. Patent No. 11,542,259, and the company has pending patent applications in the U.S. and other selected countries covering the composition of matter, certain synthetic methods, salts, polymorphs, formulations, and combinations of zanzalintinib that, if issued, are anticipated to expire between 2039 and 2044, excluding any potential patent term adjustments and/or extensions.
Research and Development
The company’s research and development expenses for 2024 were $910.4 million.
History
The company was founded in 1994. It was incorporated in Delaware in 1994. The company was formerly known as Exelixis Pharmaceuticals, Inc. and changed its name to Exelixis, Inc. in 2000.
