Ipsen Pharma SAS

ALAMEDA, Calif.--( BUSINESS WIRE )-- Exelixis, Inc. (Nasdaq: EXEL) today announced updated and final data from CABINET, a phase 3 pivotal trial evaluating cabozantinib (CABOMETYX ® ) versus placebo in two cohorts of patients with previously treated neuroendocrine tumors: one cohort with advanced pancreatic neuroendocrine tumors (pNET) and one cohort with advanced extra-pancreatic NET (epNET). These data are being presented today at the 2024 European Society for Medical Oncology Congress (ESMO 2024) during the Proffered Paper Session: NETs and Endocrine Tumours at 2:45 p.m. CET and were simultaneously published in the New England Journal of Medicine ( NEJM ). “ The phase 3 CABINET study, which was conducted through the National Cancer Institute's National Clinical Trials Network, reflects real-world clinical practice in that it enrolled a wide and heterogeneous range of patients regardless of primary tumor site, grade, somatostatin receptor expression and functional status,” said Jennifer Chan, M.D., M.P.H., study chair for the CABINET trial, Clinical Director of the Gastrointestinal Cancer Center and Director of the Program in Carcinoid and Neuroendocrine Tumors at Dana-Farber Cancer Institute. “ I’m encouraged by these final results showing that cabozantinib provided a clinically meaningful treatment benefit for patients with previously treated advanced neuroendocrine tumors, including across all major clinical subgroups. The findings suggest that cabozantinib has the potential to become a new standard of care for these patients greatly in need of new treatment options.” The final results from the CABINET study presented today at ESMO and published in NEJM demonstrate continued improvement with cabozantinib in the primary endpoint of progression-free survival (PFS) by blinded independent central review (BICR) through the data cutoff of August 24, 2023. In the pNET cohort (n=95), at a median follow-up of 13.8 months, the hazard ratio (HR) was 0.23 (95% confidence interval [CI]: 0.12-0.42; p<0.0001); median PFS was 13.8 months for cabozantinib versus 4.4 months for placebo. In the epNET cohort (n=203), at a median follow-up of 10.2 months, the HR was 0.38 (95% CI: 0.25-0.59; p<0.0001); median PFS was 8.4 months versus 3.9 months, respectively. Upon disease progression, patients were unblinded, and those receiving placebo were permitted to cross over to open-label therapy with cabozantinib. Additional analyses suggest benefits with cabozantinib across all clinical subgroups examined, including primary tumor site, grade and prior systemic anticancer therapy. In the pNET cohort, the objective response rate (ORR) by BICR was 19% with cabozantinib compared with 0% with placebo. In the epNET cohort, the ORR by BICR was 5% with cabozantinib compared with 0% with placebo. Similar interim overall survival (OS) results for cabozantinib compared to placebo were observed in both cohorts; HRs for OS were 0.95 (95% CI: 0.45-2.00) for the pNET cohort and 0.86 (95% CI: 0.56-1.31) for the epNET cohort. “ Patients with advanced neuroendocrine tumors face a poor prognosis with limited treatment options. These updated data reinforce the potential of cabozantinib as a new treatment to significantly delay disease progression,” said Amy Peterson, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. “ We believe the CABINET data indicate that cabozantinib could be practice-changing in NET, and we are working closely with the FDA to bring this differentiated option to patients with advanced NET as quickly as possible.” The safety profile of cabozantinib observed in each cohort was consistent with its known safety profile; no new safety signals were identified. A majority of patients treated with cabozantinib required dose modifications or reductions to manage adverse events. These results were the basis for Exelixis’ supplemental new drug application (sNDA) for cabozantinib for the treatment of adults with advanced NET. The FDA accepted the sNDA in August and assigned a Prescription Drug User Fee Act target action date of April 3, 2025. In August of 2023, CABINET was stopped and unblinded early due to a dramatic improvement in PFS observed at an interim analysis in both of the trial’s cohorts, per a unanimous recommendation of the Alliance for Clinical Trials in Oncology independent Data and Safety Monitoring Board; all patients were unblinded, and those on placebo were given the option to cross over to active treatment with cabozantinib. Cabozantinib demonstrated a statistically significant and clinically meaningful improvement in PFS versus placebo based on results of both local review and available BICR. Initial results by investigator were presented at ESMO 2023. About CABINET (Alliance A021602) CABINET (Randomized, Double-Blinded Phase III Study of CAB ozantinib versus Placebo I n Patients with Advanced NE uroendocrine T umors After Progression on Prior Therapy) is sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and is being led and conducted by the NCI-funded Alliance for Clinical Trials in Oncology with participation from the NCI-funded National Clinical Trials Network as part of Exelixis’ collaboration through a Cooperative Research and Development Agreement with the NCI’s Cancer Therapy Evaluation Program. CABINET is a multicenter, randomized, double-blinded, placebo-controlled phase 3 pivotal trial that had enrolled a total of 298 patients in the U.S at the time of the final analysis. Patients were randomized 2:1 to cabozantinib (60 mg) or placebo in two separately powered cohorts (pNET, n=95; epNET, n=203). The epNET cohort included patients with the following primary tumor sites: gastrointestinal (GI) tract, lung, unknown primary sites and other. Each cohort was randomized separately and had its own statistical analysis plan. Patients must have had measurable disease per RECIST 1.1 criteria and must have experienced disease progression or intolerance after at least one U.S. FDA-approved line of prior therapy other than somatostatin analogs. The primary endpoint in each cohort was PFS per RECIST 1.1 by blinded independent central review. Secondary endpoints included overall survival, radiographic response rate and safety. More information about this trial is available at ClinicalTrials.gov . About NET NET are cancers that begin in the specialized cells of the body’s neuroendocrine system. 1 These cells have traits of both hormone-producing endocrine cells and nerve cells. 1 In the U.S., it is estimated that 161,000 to 192,000 people are living with unresectable, locally advanced or metastatic NET. 2 The number of people diagnosed with NET has been increasing in recent decades. 3 Functional NET release peptide hormones that can cause debilitating symptoms, like diarrhea, hypertension and flushing which may require focused treatment, while symptoms of non-functional NET are related primarily to tumor growth. 4,5 Most NET take years to develop and grow slowly, but eventually all patients with advanced or metastatic NET will develop refractory and progressing disease. 6,7 NET can develop in any part of the body, but most commonly start in the GI tract or in the lungs, where they have historically been referred to as carcinoid tumors and are more recently called epNET. 1 The five-year survival rates for advanced GI and lung NET tumors are 68% and 55%, respectively. 8,9 NET can also start in the pancreas, where they tend to be more aggressive, with a five-year survival rate of only 23% for advanced disease. 1,10 For advanced NET patients, treatment options include somatostatin analogs, chemotherapy, targeted therapy and peptide-receptor radionuclide therapy. 11 About CABOMETYX ® (cabozantinib) In the U.S., CABOMETYX tablets are approved as monotherapy for the treatment of patients with advanced renal cell carcinoma (RCC) and in combination with nivolumab for patients as a first-line treatment for patients with advanced RCC; for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib, and; for adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible. CABOMETYX tablets have also received regulatory approvals in over 65 countries outside the U.S. and Japan, including the European Union. In 2016, Exelixis granted Ipsen Pharma SAS exclusive rights for the commercialization and further clinical development of cabozantinib outside of the U.S. and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the U.S. CABOMETYX is not indicated as a treatment for NET. IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients in RCC, HCC, and DTC studies. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage and prior to surgery as recommended. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena. Perforations and Fistulas: Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Gastrointestinal (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of fistulas and perforations, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a Grade 4 fistula or a GI perforation. Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic events that require medical intervention. Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension was reported in 37% (16% Grade 3 and <1% Grade 4) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume at a reduced dose. Permanently discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis. Diarrhea: Diarrhea occurred in 62% of CABOMETYX patients. Grade 3 diarrhea occurred in 10% of CABOMETYX patients. Monitor and manage patients using antidiarrheals as indicated. Withhold CABOMETYX until improvement to ≤ Grade 1, resume at a reduced dose. Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in 45% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE. Hepatotoxicity: CABOMETYX in combination with nivolumab can cause hepatic toxicity with higher frequencies of Grades 3 and 4 ALT and AST elevations compared to CABOMETYX alone. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes than when the drugs are administered as single agents. For elevated liver enzymes, interrupt CABOMETYX and nivolumab and consider administering corticosteroids. With the combination of CABOMETYX and nivolumab, Grades 3 and 4 increased ALT or AST were seen in 11% of patients. ALT or AST >3 times ULN (Grade ≥2) was reported in 83 patients, of whom 23 (28%) received systemic corticosteroids; ALT or AST resolved to Grades 0-1 in 74 (89%). Among the 44 patients with Grade ≥2 increased ALT or AST who were rechallenged with either CABOMETYX (n=9) or nivolumab (n=11) as a single agent or with both (n=24), recurrence of Grade ≥2 increased ALT or AST was observed in 2 patients receiving CABOMETYX, 2 patients receiving nivolumab, and 7 patients receiving both CABOMETYX and nivolumab. Withhold and resume at a reduced dose based on severity. Adrenal Insufficiency: CABOMETYX in combination with nivolumab can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold CABOMETYX and/or nivolumab and resume CABOMETYX at a reduced dose depending on severity. Adrenal insufficiency occurred in 4.7% (15/320) of patients with RCC who received CABOMETYX with nivolumab, including Grade 3 (2.2%), and Grade 2 (1.9%) adverse reactions. Adrenal insufficiency led to permanent discontinuation of CABOMETYX and nivolumab in 0.9% and withholding of CABOMETYX and nivolumab in 2.8% of patients with RCC. Approximately 80% (12/15) of patients with adrenal insufficiency received hormone replacement therapy, including systemic corticosteroids. Adrenal insufficiency resolved in 27% (n=4) of the 15 patients. Of the 9 patients in whom CABOMETYX with nivolumab was withheld for adrenal insufficiency, 6 reinstated treatment after symptom improvement; of these, all (n=6) received hormone replacement therapy and 2 had recurrence of adrenal insufficiency. Proteinuria: Proteinuria was observed in 8% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. For Grade 2 or 3 proteinuria, withhold CABOMETYX until improvement to ≤ Grade 1 proteinuria; resume CABOMETYX at a reduced dose. Discontinue CABOMETYX in patients who develop nephrotic syndrome. Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures, if possible. Withhold CABOMETYX for development of ONJ until complete resolution, resume at a reduced dose. Impaired Wound Healing: Wound complications occurred with CABOMETYX. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer CABOMETYX for at least 2 weeks after major surgery and until adequate wound healing. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established. Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic findings on MRI, can occur with CABOMETYX. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS. Thyroid Dysfunction: Thyroid dysfunction, primarily hypothyroidism, has been observed with CABOMETYX. Based on the safety population, thyroid dysfunction occurred in 19% of patients treated with CABOMETYX, including Grade 3 in 0.4% of patients. Patients should be assessed for signs of thyroid dysfunction prior to the initiation of CABOMETYX and monitored for signs and symptoms of thyroid dysfunction during CABOMETYX treatment. Thyroid function testing and management of dysfunction should be performed as clinically indicated. Hypocalcemia: CABOMETYX can cause hypocalcemia. Based on the safety population, hypocalcemia occurred in 13% of patients treated with CABOMETYX, including Grade 3 in 2% and Grade 4 in 1% of patients. Laboratory abnormality data were not collected in CABOSUN. In COSMIC-311, hypocalcemia occurred in 36% of patients treated with CABOMETYX, including Grade 3 in 6% and Grade 4 in 3% of patients. Monitor blood calcium levels and replace calcium as necessary during treatment. Withhold and resume at reduced dose upon recovery or permanently discontinue CABOMETYX depending on severity. Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to initiating CABOMETYX and advise them to use effective contraception during treatment and for 4 months after the last dose. ADVERSE REACTIONS The most common (≥20%) adverse reactions are: CABOMETYX as a single agent: diarrhea, fatigue, PPE, decreased appetite, hypertension, nausea, vomiting, weight decreased, and constipation. CABOMETYX in combination with nivolumab: diarrhea, fatigue, hepatotoxicity, PPE, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection. DRUG INTERACTIONS Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice. Strong CYP3A4 Inducers: If coadministration with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John’s wort. USE IN SPECIFIC POPULATIONS Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose. Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. Avoid CABOMETYX in patients with severe hepatic impairment. Please see accompanying full Prescribing Information https://www.cabometyx.com/downloads/CABOMETYXUSPI.pdf . You are encouraged to report negative side effects of prescription drugs to the FDA. Visit http://www.fda.gov/medwatch or call 1-800-FDA-1088. About Exelixis Exelixis is a globally ambitious oncology company innovating next-generation medicines and regimens at the forefront of cancer care. Powered by drug discovery and development excellence, we are rapidly evolving our product portfolio to target an expanding range of tumor types and indications with our clinically differentiated pipeline of small molecules, antibody-drug conjugates and other biotherapeutics. This comprehensive approach harnesses decades of robust investment in our science and partnerships to advance our investigational programs and extend the impact of our flagship commercial product, CABOMETYX ® (cabozantinib). Exelixis is driven by a bold scientific pursuit to create transformational treatments that give more patients hope for the future. For information about the company and its mission to help cancer patients recover stronger and live longer, visit www.exelixis.com , follow @ExelixisInc on X (Twitter), like Exelixis, Inc. on Facebook and follow Exelixis on LinkedIn. Exelixis Forward-Looking Statements This press release contains forward-looking statements, including, without limitation, statements related to: the presentation of final results from the CABINET trial at ESMO 2024; the therapeutic potential of cabozantinib to become a new standard of care for patients with previously treated NET who are greatly in need of new treatment options, and Exelixis’ belief that cabozantinib could be practice-changing and significantly delay disease progression; Exelixis’ plans to work closely with the FDA to bring cabozantinib as a treatment option to patients with advanced NET as quickly as possible, as well as the FDA’s regulatory review process with respect to Exelixis’ sNDA submission, including the Prescription Drug User Fee Act target action date assigned by the FDA; and Exelixis’ scientific pursuit to create transformational treatments that give more patients hope for the future. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements and are based upon Exelixis’ current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: the availability of data at the referenced times; complexities and the unpredictability of the regulatory review and approval processes in the U.S. and elsewhere; Exelixis’ continuing compliance with applicable legal and regulatory requirements; unexpected concerns that may arise as a result of the occurrence of adverse safety events or additional data analyses of clinical trials evaluating cabozantinib; Exelixis’ dependence on its relationships with its cabozantinib commercial collaboration partners, including the level of their investment in the resources necessary to pursue regulatory approvals and successfully commercialize cabozantinib in the territories where approved; Exelixis’ dependence on third-party vendors for the development, manufacture and supply of cabozantinib; Exelixis’ ability to protect its intellectual property rights; market competition, including the potential for competitors to obtain approval for generic versions of CABOMETYX; changes in economic and business conditions; and other factors affecting Exelixis and its development programs detailed from time to time under the caption “Risk Factors” in Exelixis’ most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q, and in Exelixis’ future filings with the Securities and Exchange Commission. All forward-looking statements in this press release are based on information available to Exelixis as of the date of this press release, and Exelixis undertakes no obligation to update or revise any forward-looking statements contained herein, except as required by law. Exelixis, the Exelixis logo and CABOMETYX are registered U.S. trademarks of Exelixis. ___________________________________ 1 Neuroendocrine Tumors. Cleveland Clinic website. Available at: https://my.clevelandclinic.org/health/diseases/22006-neuroendocrine-tumors-net . Accessed September 2024. 2 Population Estimate: Unresectable, Locally Advanced or Metastatic Extra-Pancreatic NET. June 2024 (internal data on file). 3 Pathak, S., Starr, J.S., Halfdanarson T., et al. Understanding the increasing incidence of neuroendocrine tumors. Expert Rev Endocrinol Metab. September 2023;18(5):377-385. 4 Pancreatic Neuroendocrine Tumors (Islet Cell Tumors) Treatment (PDQ ® )–Patient Version. NCI website. Available at: https://www.cancer.gov/types/pancreatic/patient/pnet-treatment-pdq . Accessed September 2024. 5 What Is a Pancreatic Neuroendocrine Tumor? ACS website. Available at: https://www.cancer.org/cancer/types/pancreatic-neuroendocrine-tumor/about/what-is-pnet.html . Accessed September 2024. 6 McClellan, K., Chen. E.Y, Kardosh A., et al. Therapy Resistant Gastroenteropancreatic Neuroendocrine Tumors. Cancers. 2022, 14(19), 4769. 7 What is a Gastrointestinal Carcinoid Tumor? ACS website. Available at: https://www.cancer.org/cancer/types/gastrointestinal-carcinoid-tumor/about/what-is-gastrointestinal-carcinoid.html . Accessed September 2024. 8 Survival Rates for Gastrointestinal Carcinoid Tumors. ACS website. Available at: https://www.cancer.org/cancer/types/gastrointestinal-carcinoid-tumor/detection-diagnosis-staging/survival-rates.html . Accessed September 2024. 9 Survival Rates for Lung Carcinoid Tumors. ACS website. Available at: https://www.cancer.org/cancer/types/lung-carcinoid-tumor/detection-diagnosis-staging/survival-rates.html . Accessed September 2024. 10 Survival Rates for Pancreatic Neuroendocrine Tumor. ACS website. Available at: https://www.cancer.org/cancer/types/pancreatic-neuroendocrine-tumor/detection-diagnosis-staging/survival-rates.html . Accessed September 2024. 11 Neuroendocrine Tumor (NET). NCI website. Available at: https://www.cancer.gov/pediatric-adult-rare-tumor/rare-tumors/rare-endocrine-tumor/carcinoid-tumor . Accessed September 2024.

ALAMEDA, Calif.--( BUSINESS WIRE )-- Exelixis, Inc. (Nasdaq: EXEL) today announced detailed final overall survival (OS) results from CONTACT-02, a phase 3 pivotal study evaluating cabozantinib (CABOMETYX ® ) in combination with atezolizumab (Tecentriq ® ) compared with a second novel hormonal therapy (NHT) in patients with metastatic castration-resistant prostate cancer (mCRPC) and measurable extra-pelvic soft tissue disease who have progressed on one prior NHT. These data are being presented today at the 2024 European Society for Medical Oncology Congress (ESMO 2024) during the Proffered Paper Session: GU Tumours, Prostate at 2:45 p.m. CEST. “ Despite recent advancements, outcomes remain poor for patients with metastatic castration-resistant prostate cancer whose disease progresses after novel hormonal therapy – particularly those with liver metastases,” said Neeraj Agarwal, M.D., FASCO, Senior Director for Clinical Research at Huntsman Cancer Institute at the University of Utah and the global lead investigator of the trial. “ I believe there is a critical need for novel agents with a new mechanism of action that are broadly accessible to patients and can delay disease progression. The positive results from CONTACT-02, especially in the subset of patients with liver metastasis, reinforce the therapeutic potential of cabozantinib in combination with atezolizumab for these patients.” The two primary endpoints for CONTACT-02 were progression-free survival (PFS) and OS. At a median follow-up of 24.0 months, the final analysis of OS showed a numerical but not statistically significant improvement favoring cabozantinib in combination with atezolizumab (hazard ratio: 0.89; 95% confidence interval: 0.72-1.10; P =0.296). An improvement in OS was observed in multiple clinical subgroups, notably in patients with bone or liver metastases, with the latter category representing a population whose disease may be evolving away from androgen receptor signaling. Additional OS efficacy findings are included in Table 1 below. TABLE 1 ITT population Bone metastases Liver metastases Patients, n 575 446 132 HR (95% CI) P-value 0.89 (0.72, 1.10) P =0.30 0.79 (0.63, 1.00) P =0.046 0.68 (0.47, 1.00) P =0.051 Median OS (C+A); months 14.8 (13.4, 16.7) 13.8 (11.9, 16.3) 12.2 (8.8, 13.8) Median OS (NHT); months 15.0 (13.0, 18.5) 11.6 (10.5, 14.1) 7.1 (5.3, 10.4) C+A: cabozantinib + atezolizumab; CI: confidence interval; HR: hazard ratio; ITT: intent-to-treat; NHT: novel hormonal therapy; OS: overall survival “ Within the current treatment landscape, there is a growing population of patients with metastatic castration-resistant prostate cancer with extra-pelvic soft tissue metastases whose disease has progressed after novel hormonal therapy, leaving a high unmet need for effective, widely available treatments for these patients,” said Amy Peterson, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. “ Collectively, the results from the CONTACT-02 trial suggest that there are patients who could benefit from cabozantinib in combination with atezolizumab and that this regimen could be a valuable addition to the treatment landscape for patients with advanced prostate cancer.” Treatment-related grade 3-4 adverse events (AEs) occurred in 40% of patients receiving cabozantinib in combination with atezolizumab and 8% of those receiving NHT. Treatment-related AEs leading to discontinuation of all treatment components were similar (5% for cabozantinib in combination with atezolizumab and 2% of those receiving NHT). The time to clinically meaningful deterioration in quality of life was similar between arms, and the combination of cabozantinib and atezolizumab did not impair quality of life relative to generally well-tolerated NHT. As previously announced, CONTACT-02 met one of its two primary endpoints, demonstrating a statistically significant benefit in PFS in the predefined PFS ITT population (i.e., the first 400 randomized patients). Detailed results were presented at the American Society of Clinical Oncology 2024 Genitourinary Cancers Symposium in January 2024. Exelixis intends to submit a supplemental New Drug Application with the U.S. Food and Drug Administration for cabozantinib in combination with atezolizumab for mCRPC later this year. About CONTACT-02 CONTACT-02 is a global, multicenter, randomized, phase 3, open-label study that randomized 575 patients 1:1 to the experimental arm of cabozantinib in combination with atezolizumab and the control arm of a second NHT (either abiraterone and prednisone or enzalutamide). The two primary endpoints of the trial are PFS and OS. The study included patients with mCRPC who have measurable extra-pelvic soft tissue metastasis and who have progressed on one prior NHT. The secondary endpoint is objective response rate per blinded independent radiology committee. The trial is sponsored by Exelixis and co-funded by Ipsen, Roche and Takeda Pharmaceutical Company Limited (Takeda). Takeda is conducting the trial in Japan. More information about CONTACT-02 is available at ClinicalTrials.gov . About CRPC According to the American Cancer Society, approximately 299,000 new cases of prostate cancer will be diagnosed in the U.S., and over 35,000 people will die from the disease in 2024. 1 Prostate cancer that has spread beyond the prostate and does not respond to androgen-suppression therapies—a common treatment for prostate cancer—is known as mCRPC. 2 Men diagnosed with mCRPC often have a poor prognosis, with an estimated survival of 1-2 years. 3,4 About CABOMETYX ® (cabozantinib) In the U.S., CABOMETYX tablets are approved as monotherapy for the treatment of patients with advanced renal cell carcinoma (RCC) and in combination with nivolumab as a first-line treatment for patients with advanced RCC; for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib; and for adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible. CABOMETYX tablets have also received regulatory approvals in over 65 countries outside the U.S. and Japan, including the European Union. In 2016, Exelixis granted Ipsen Pharma SAS exclusive rights for the commercialization and further clinical development of cabozantinib outside of the U.S. and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the U.S. CABOMETYX is not indicated as a treatment for CRPC. IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients in RCC, HCC, and DTC studies. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage and prior to surgery as recommended. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena. Perforations and Fistulas: Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Gastrointestinal (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of fistulas and perforations, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a Grade 4 fistula or a GI perforation. Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic events that require medical intervention. Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension was reported in 37% (16% Grade 3 and <1% Grade 4) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume at a reduced dose. Permanently discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis. Diarrhea: Diarrhea occurred in 62% of CABOMETYX patients. Grade 3 diarrhea occurred in 10% of CABOMETYX patients. Monitor and manage patients using antidiarrheals as indicated. Withhold CABOMETYX until improvement to ≤ Grade 1, resume at a reduced dose. Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in 45% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE. Hepatotoxicity: CABOMETYX in combination with nivolumab can cause hepatic toxicity with higher frequencies of Grades 3 and 4 ALT and AST elevations compared to CABOMETYX alone. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes than when the drugs are administered as single agents. For elevated liver enzymes, interrupt CABOMETYX and nivolumab and consider administering corticosteroids. With the combination of CABOMETYX and nivolumab, Grades 3 and 4 increased ALT or AST were seen in 11% of patients. ALT or AST >3 times ULN (Grade ≥2) was reported in 83 patients, of whom 23 (28%) received systemic corticosteroids; ALT or AST resolved to Grades 0-1 in 74 (89%). Among the 44 patients with Grade ≥2 increased ALT or AST who were rechallenged with either CABOMETYX (n=9) or nivolumab (n=11) as a single agent or with both (n=24), recurrence of Grade ≥2 increased ALT or AST was observed in 2 patients receiving CABOMETYX, 2 patients receiving nivolumab, and 7 patients receiving both CABOMETYX and nivolumab. Withhold and resume at a reduced dose based on severity. Adrenal Insufficiency: CABOMETYX in combination with nivolumab can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold CABOMETYX and/or nivolumab and resume CABOMETYX at a reduced dose depending on severity. Adrenal insufficiency occurred in 4.7% (15/320) of patients with RCC who received CABOMETYX with nivolumab, including Grade 3 (2.2%), and Grade 2 (1.9%) adverse reactions. Adrenal insufficiency led to permanent discontinuation of CABOMETYX and nivolumab in 0.9% and withholding of CABOMETYX and nivolumab in 2.8% of patients with RCC. Approximately 80% (12/15) of patients with adrenal insufficiency received hormone replacement therapy, including systemic corticosteroids. Adrenal insufficiency resolved in 27% (n=4) of the 15 patients. Of the 9 patients in whom CABOMETYX with nivolumab was withheld for adrenal insufficiency, 6 reinstated treatment after symptom improvement; of these, all (n=6) received hormone replacement therapy and 2 had recurrence of adrenal insufficiency. Proteinuria: Proteinuria was observed in 8% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. For Grade 2 or 3 proteinuria, withhold CABOMETYX until improvement to ≤ Grade 1 proteinuria; resume CABOMETYX at a reduced dose. Discontinue CABOMETYX in patients who develop nephrotic syndrome. Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures, if possible. Withhold CABOMETYX for development of ONJ until complete resolution, resume at a reduced dose. Impaired Wound Healing: Wound complications occurred with CABOMETYX. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer CABOMETYX for at least 2 weeks after major surgery and until adequate wound healing. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established. Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic findings on MRI, can occur with CABOMETYX. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS. Thyroid Dysfunction: Thyroid dysfunction, primarily hypothyroidism, has been observed with CABOMETYX. Based on the safety population, thyroid dysfunction occurred in 19% of patients treated with CABOMETYX, including Grade 3 in 0.4% of patients. Patients should be assessed for signs of thyroid dysfunction prior to the initiation of CABOMETYX and monitored for signs and symptoms of thyroid dysfunction during CABOMETYX treatment. Thyroid function testing and management of dysfunction should be performed as clinically indicated. Hypocalcemia: CABOMETYX can cause hypocalcemia. Based on the safety population, hypocalcemia occurred in 13% of patients treated with CABOMETYX, including Grade 3 in 2% and Grade 4 in 1% of patients. Laboratory abnormality data were not collected in CABOSUN. In COSMIC-311, hypocalcemia occurred in 36% of patients treated with CABOMETYX, including Grade 3 in 6% and Grade 4 in 3% of patients. Monitor blood calcium levels and replace calcium as necessary during treatment. Withhold and resume at reduced dose upon recovery or permanently discontinue CABOMETYX depending on severity. Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to initiating CABOMETYX and advise them to use effective contraception during treatment and for 4 months after the last dose. ADVERSE REACTIONS The most common (≥20%) adverse reactions are: CABOMETYX as a single agent: diarrhea, fatigue, PPE, decreased appetite, hypertension, nausea, vomiting, weight decreased, and constipation. CABOMETYX in combination with nivolumab: diarrhea, fatigue, hepatotoxicity, PPE, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection. DRUG INTERACTIONS Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice. Strong CYP3A4 Inducers: If coadministration with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John’s wort. USE IN SPECIFIC POPULATIONS Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose. Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. Avoid CABOMETYX in patients with severe hepatic impairment. Please see accompanying full Prescribing Information https://www.cabometyx.com/downloads/CABOMETYXUSPI.pdf . You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088. About Exelixis Exelixis is a globally ambitious oncology company innovating next-generation medicines and regimens at the forefront of cancer care. Powered by drug discovery and development excellence, we are rapidly evolving our product portfolio to target an expanding range of tumor types and indications with our clinically differentiated pipeline of small molecules, antibody-drug conjugates and other biotherapeutics. This comprehensive approach harnesses decades of robust investment in our science and partnerships to advance our investigational programs and extend the impact of our flagship commercial product, CABOMETYX ® (cabozantinib). Exelixis is driven by a bold scientific pursuit to create transformational treatments that give more patients hope for the future. For information about the company and its mission to help cancer patients recover stronger and live longer, visit www.exelixis.com , follow @ExelixisInc on X (Twitter), like Exelixis, Inc. on Facebook and follow Exelixis on LinkedIn. Forward-Looking Statements This press release contains forward-looking statements, including, without limitation, statements related to: the presentation of detailed final OS results from the CONTACT-02 trial at ESMO 2024; the therapeutic potential of cabozantinib in combination with atezolizumab to benefit patients with mCRPC and measurable extra-pelvic soft tissue disease who have progressed on one prior NHT, especially in the subset of patients with liver metastasis, and Exelixis’ belief that this combination regimen could be a valuable addition to the treatment landscape for patients with advanced prostate cancer; Exelixis’ plans to submit a supplemental New Drug Application with the U.S. Food and Drug Administration for cabozantinib in combination with atezolizumab for mCRPC later this year; and Exelixis’ scientific pursuit to create transformational treatments that give more patients hope for the future. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements and are based upon Exelixis’ current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: the availability of data at the referenced times; complexities and the unpredictability of the regulatory review and approval processes in the U.S. and elsewhere; Exelixis’ continuing compliance with applicable legal and regulatory requirements; unexpected concerns that may arise as a result of the occurrence of adverse safety events or additional data analyses of clinical trials evaluating cabozantinib; Exelixis’ dependence on its relationships with its cabozantinib commercial collaboration partners, including the level of their investment in the resources necessary to pursue regulatory approvals and successfully commercialize cabozantinib in the territories where approved; Exelixis’ dependence on third-party vendors for the development, manufacture and supply of cabozantinib; Exelixis’ ability to protect its intellectual property rights; market competition, including the potential for competitors to obtain approval for generic versions of CABOMETYX; changes in economic and business conditions; and other factors affecting Exelixis and its development programs detailed from time to time under the caption “Risk Factors” in Exelixis’ most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q, and in Exelixis’ future filings with the Securities and Exchange Commission. All forward-looking statements in this press release are based on information available to Exelixis as of the date of this press release, and Exelixis undertakes no obligation to update or revise any forward-looking statements contained herein, except as required by law. Exelixis, the Exelixis logo and CABOMETYX are registered U.S. trademarks of Exelixis. TECENTRIQ is registered U.S. trademark of Genentech, a member of the Roche Group. 1 Cancer Facts & Figures 2024. ACS. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2024/2024-cancer-facts-and-figures-acs.pdf . Accessed September 2024. 2 Patient education: Treatment for advanced prostate cancer (Beyond the Basics). UpToDate website. Available at: https://www-uptodate-com.libproxy1.nus.edu.sg/contents/treatment-for-advanced-prostate-cancer-beyond-the-basics . Accessed September 2024. 3 Freedland, S. J., et al. Real-world treatment patterns and overall survival among men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) in the US Medicare population. Prostate Cancer Prostatic Dis . 2023. 4 Moreira, D. M., Howard, L. E., Sourbeer, K. N., et al. Predicting Time From Metastasis to Overall Survival in Castration-Resistant Prostate Cancer: Results From SEARCH. Clin Genitourin Cancer . 2017;15:60–66.e2

ALAMEDA, Calif.--( BUSINESS WIRE )--Exelixis, Inc. (Nasdaq: EXEL) today reported financial results for the second quarter of 2024, provided an update on progress toward achieving key corporate objectives, and detailed its recent and anticipated commercial, clinical and pipeline development milestones. “Exelixis is well positioned for an impactful second half of 2024 as we continue to grow the cabozantinib franchise, execute on our regulatory and development objectives, and advance our next-generation pipeline,” said Michael M. Morrissey, Ph.D., President and CEO, Exelixis. “Cabozantinib’s second quarter commercial performance was strong both in the U.S. and globally, with Ipsen’s success prompting a $150 million milestone payment to Exelixis based on sales over the past four quarters. On the regulatory front, the FDA accepted the sNDA for cabozantinib in advanced NET, granted standard review and assigned a target action date of April 3, 2025. We’re actively preparing for launch and excited at the prospect of bringing this new treatment option to previously treated advanced NET patients with high unmet medical need. At the same time, we are prioritizing our clinical pipeline with plans to initiate a new phase 3 pivotal trial for zanzalintinib in NET, advance phase 1 efforts for XL309 and XB010, and discontinue development of XB002. I’d like to thank the entire Exelixis team for their hard work and contributions toward achieving these important milestones for cabozantinib and advancing our broad, differentiated pipeline of oncology therapeutics to help the patients we serve.” Second Quarter 2024 Financial Results Total revenues for the quarter ended June 30, 2024 were $637.2 million, as compared to $469.8 million for the comparable period in 2023. Total revenues for the quarter ended June 30, 2024 included net product revenues of $437.6 million, as compared to $409.6 million for the comparable period in 2023. The increase in net product revenues was primarily due to an increase in sales volume and average net selling price. Collaboration revenues, composed of license revenues and collaboration services revenues, were $199.6 million for the quarter ended June 30, 2024, as compared to $60.2 million for the comparable period in 2023. The increase in collaboration revenues was primarily related to an increase in milestone-related revenues recognized in the quarter and higher royalty revenues for the sales of cabozantinib outside of the U.S. generated by Exelixis’ collaboration partners, Ipsen Pharma SAS (Ipsen) and Takeda Pharmaceutical Company Limited, partially offset by a decrease in development cost reimbursements earned. Research and development expenses for the quarter ended June 30, 2024 were $211.1 million, as compared to $232.6 million for the comparable period in 2023. The decrease in research and development expenses was primarily related to decreases in license and other collaboration costs and clinical trial costs, partially offset by an increase in manufacturing costs to support our development candidates. Selling, general and administrative expenses for the quarter ended June 30, 2024 were $132.0 million, as compared to $141.7 million for the comparable period in 2023. The decrease in selling, general and administrative expenses was primarily related to a decrease in legal and advisory fees related to the proxy contest in the prior year. Provision for income taxes for the quarter ended June 30, 2024 was $66.7 million, as compared to $19.2 million for the comparable period in 2023. GAAP net income for the quarter ended June 30, 2024 was $226.1 million, or $0.78 per share, basic and $0.77 per share, diluted, as compared to GAAP net income of $81.2 million, or $0.25 per share, basic and diluted, for the comparable period in 2023. GAAP net income per share for the quarter ended June 30, 2024 was favorably impacted by lower weighted-average common shares outstanding for the quarter ended June 30, 2024, as compared to the comparable period in 2023, as a result of the stock repurchase programs. Non-GAAP net income for the quarter ended June 30, 2024 was $245.6 million, or $0.85 per share, basic and $0.84 per share, diluted, as compared to non-GAAP net income of $100.3 million, or $0.31 per share, basic and diluted, for the comparable period in 2023. Non-GAAP Financial Measures To supplement Exelixis’ financial results presented in accordance with U.S. Generally Accepted Accounting Principles (GAAP), Exelixis presents non-GAAP net income (and the related per share measures), which excludes from GAAP net income (and the related per share measures) stock-based compensation expense, adjusted for the related income tax effect for all periods presented. Exelixis believes that the presentation of these non-GAAP financial measures provides useful supplementary information to, and facilitates additional analysis by, investors. In particular, Exelixis believes that these non-GAAP financial measures, when considered together with its financial information prepared in accordance with GAAP, can enhance investors’ and analysts’ ability to meaningfully compare Exelixis’ results from period to period, and to identify operating trends in Exelixis’ business. Exelixis has excluded stock-based compensation expense, adjusted for the related income tax effect, because it is a non-cash item that may vary significantly from period to period as a result of changes not directly or immediately related to the operational performance for the periods presented. Exelixis also regularly uses these non-GAAP financial measures internally to understand, manage and evaluate its business and to make operating decisions. These non-GAAP financial measures are in addition to, not a substitute for, or superior to, measures of financial performance prepared in accordance with GAAP. Exelixis encourages investors to carefully consider its results under GAAP, as well as its supplemental non-GAAP financial information and the reconciliation between these presentations, to more fully understand Exelixis’ business. Reconciliations between GAAP and non-GAAP results are presented in the tables of this release. 2024 Financial Guidance Exelixis is providing the following updated financial guidance for fiscal year 2024 (1) : Total revenues $1.975 billion - $2.075 billion Net product revenues (2) $1.650 billion - $1.750 billion Cost of goods sold 4% - 5% of net product revenues Research and development expenses (3) $925 million - $975 million Selling, general and administrative expenses (4) $450 million - $500 million Effective tax rate 20% - 22% ____________________ (1) 2024 financial guidance excludes expenses related to the restructuring plan announced in January 2024. (2) Exelixis’ 2024 net product revenues guidance range includes the impact of a U.S. wholesale acquisition cost increase of 2.2% for both CABOMETYX and COMETRIQ effective on January 1, 2024. (3) Includes $40 million of non-cash stock-based compensation expense. (4) Includes $60 million of non-cash stock-based compensation expense. Cabozantinib and Pipeline Highlights Cabozantinib Franchise Net Product Revenues and Royalties. Net product revenues generated by the cabozantinib franchise in the U.S. were $437.6 million during the second quarter of 2024, with net product revenues of $433.3 million from CABOMETYX ® (cabozantinib) and $4.2 million from COMETRIQ ® (cabozantinib). Based upon cabozantinib-related net product revenues generated by Exelixis’ collaboration partners during the quarter ended June 30, 2024, Exelixis earned $41.2 million in royalty revenues. Achievement of Cabozantinib Sales-Based Milestone from Ipsen. Today, Exelixis announced it earned and recognized in license revenues a $150 million commercial milestone from Ipsen during the second quarter of 2024 based on Ipsen achieving $600 million in cumulative net sales of cabozantinib in its related license territory over four consecutive quarters. Exelixis expects to receive the milestone payment during the third quarter of 2024. FDA Accepts for Standard Review the sNDA for Cabozantinib for Patients with Advanced NET; Updated Results from Phase 3 CABINET Study to be Presented during an Oral Presentation at the European Society for Medical Oncology (ESMO) Congress 2024. Today, Exelixis announced that the FDA accepted its sNDA for cabozantinib for patients with previously treated advanced pancreatic NET (pNET), and for patients with previously treated advanced extra-pancreatic NET (epNET). The FDA assigned a standard review with 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. The application was based on results from the phase 3 CABINET trial, which evaluated cabozantinib compared with placebo in patients with previously treated pNET and epNET. The CABINET study is sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and led by the NCI-funded Alliance for Clinical Trials in Oncology. Updated results from CABINET, including final results on the primary efficacy endpoint of progression-free survival by Blinded Independent Central Review, will be presented during the ESMO Congress 2024 in September. Exelixis Partner Ipsen Opts into Phase 3 CABINET Pivotal Trial in Advanced NET. In July, Ipsen announced it opted into the phase 3 CABINET pivotal trial, expanding the existing collaboration and license agreement with Exelixis and permitting Ipsen to seek potential marketing authorizations for CABOMETYX in advanced pNET and epNET from regulatory authorities outside of the U.S. and Japan. As part of the agreement, Exelixis is eligible to receive a reimbursement of a portion of costs related to the trial, as well as milestone payments for potential future regulatory action by the European Medicines Agency. The decision to expand the existing agreement was based on detailed results from the CABINET trial, which were first presented at the ESMO Congress 2023. Phase 3 CONTACT-02 Metastatic Castration-Resistant Prostate Cancer (mCRPC) Study Update and Intention to Submit sNDA in 2024. Today, Exelixis announced that the final overall survival (OS) analysis for the phase 3 CONTACT-02 trial has been completed. This study is evaluating cabozantinib in combination with atezolizumab compared with a second novel hormonal therapy (NHT) in patients with mCRPC and measurable soft-tissue disease who have progressed after treatment with one prior NHT. As previously reported, the CONTACT-02 study met one of its two primary endpoints, demonstrating a statistically significant benefit in progression-free survival (PFS) (hazard ratio: 0.65; 95% confidence interval: 0.50–0.84; p=0.0007) in the predefined PFS intent-to-treat population (i.e., the first 400 randomized patients). While final OS continued to favor the combination of cabozantinib and atezolizumab, it did not achieve statistical significance. The safety profile of the combination regimen was reflective of the known safety profiles for each single agent and was consistent with the known tolerability profile of approved immune checkpoint inhibitor-tyrosine kinase inhibitor combinations in advanced solid tumors. Exelixis intends to submit an sNDA to the FDA this year and to present these final data at a future medical meeting. Enrollment Completion for Zanzalintinib Phase 3 STELLAR-303 Study and Announcement of New Pivotal Trial for Zanzalintinib in Neuroendocrine Tumors. Today, Exelixis announced that enrollment has been completed in the STELLAR-303 phase 3 pivotal study. STELLAR-303 is evaluating zanzalintinib in combination with atezolizumab compared with regorafenib in patients with metastatic refractory colorectal cancer that is not microsatellite instability-high or mismatch repair-deficient. The primary endpoint in the study is OS in the patients without liver metastases. Exelixis anticipates preliminary results from the study to readout in 2025. Additionally, Exelixis intends to initiate a new phase 3 pivotal trial, STELLAR-311, evaluating zanzalintinib compared with everolimus as a first oral therapy in patients with pNET and epNET, in the first half of 2025. Initiation of Phase 1 Clinical Trial Evaluating XB010 in Patients with Advanced Solid Tumors. Today, Exelixis announced the initiation of the dose-escalation stage of the first-in-human phase 1 clinical trial of XB010 in patients with locally advanced or metastatic solid tumors. XB010, an antibody-drug conjugate (ADC) consisting of a monomethyl auristatin E payload conjugated to a monoclonal antibody targeting the tumor antigen 5T4, is the first custom ADC generated through Exelixis’ biotherapeutics collaboration network. The dose-escalation stage of this phase 1, global, open-label study will evaluate XB010 as a single agent and in combination with pembrolizumab to inform the cohort-expansion stage. The expansion cohorts are designed to further assess the tolerability and activity of monotherapy and of the combination in specific indications. Portfolio Prioritization Update. Today, Exelixis announced it will discontinue the development of XB002, the company’s 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 currently 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. Preclinical development of XB371, its ADC consisting of a topoisomerase payload conjugated to a TF-targeting monoclonal antibody, is ongoing.  Exelixis plans to reallocate resources to new pivotal trials with zanzalintinib, advancing XL309 and its growing pipeline. Corporate Highlights Settlement of CABOMETYX Patent Litigation with Cipla Limited and Cipla USA. In May, Exelixis entered into a Settlement and License Agreement (Agreement) with Cipla Ltd. and Cipla USA, Inc. (individually and collectively referred to as Cipla) resolving two patent litigations brought by Exelixis in response to Cipla’s Abbreviated New Drug Application (ANDA) seeking approval to market generic versions of CABOMETYX tablets (20 mg / 40 mg / 60 mg) prior to the expiration of the applicable patents. Pursuant to the terms of the Agreement, Exelixis will grant Cipla a license to market generic versions of CABOMETYX in the United States beginning on January 1, 2031, if approved by the FDA and subject to conditions and exceptions common to agreements of this type. The U.S. District Court for the District of Delaware dismissed the case without prejudice in July 2024 per the parties’ joint request, effectively terminating all ongoing Hatch-Waxman litigation between Exelixis and Cipla regarding CABOMETYX patents Completion of the $450 million 2024 Stock Repurchase Program. As of June 30, 2024, Exelixis completed the repurchase of 20.3 million shares of the company’s common stock for a total of $450 million, fulfilling its commitment under the stock repurchase program announced in January 2024. With the completion of this 2024 stock repurchase program, the company has returned $1 billion to shareholders since the initial $550 million stock repurchase program was authorized in March 2023. Announcement of Additional Stock Repurchase Program for up to $500 million through the End of 2025. Today, Exelixis announced that the company’s Board of Directors has authorized the repurchase of up to an additional $500 million of the company’s common stock through the end of 2025. The newly authorized stock repurchase program is the third such program undertaken by Exelixis since March 2023. Stock repurchases under the newly authorized program may be made from time to time through a variety of methods, which may include open market purchases, in block trades, accelerated share repurchase transactions, exchange transactions, or any combination of such methods. The timing and amount of any stock repurchases under the stock repurchase program will be based on a variety of factors, including ongoing assessments of the capital needs of the business, alternative investment opportunities, the market price of Exelixis’ common stock and general market conditions. Basis of Presentation Exelixis has adopted a 52- or 53-week fiscal year that generally ends on the Friday closest to December 31. For convenience, references in this press release as of and for the fiscal periods ended June 28, 2024 are indicated as being as of and for the periods ended June 30, 2024. Conference Call and Webcast Exelixis management will discuss the company’s financial results for the second quarter of 2024 and provide a general business update during a conference call beginning at 5:00 p.m. ET / 2:00 p.m. PT today, Tuesday, August 6, 2024. To access the conference call, please register using this link . Upon registration, a dial-in number and unique PIN will be provided to join the call. To access the live webcast link, log onto www.exelixis.com and proceed to the Event Calendar page under the Investors & News heading. A webcast replay of the conference call will also be archived on www.exelixis.com for one year. About Exelixis Exelixis is a globally ambitious oncology company innovating next-generation medicines and regimens at the forefront of cancer care. Powered by drug discovery and development excellence, we are rapidly evolving our product portfolio to target an expanding range of tumor types and indications with our clinically differentiated pipeline of small molecules, antibody-drug conjugates and other biotherapeutics. This comprehensive approach harnesses decades of robust investment in our science and partnerships to advance our investigational programs and extend the impact of our flagship commercial product, CABOMETYX ® (cabozantinib). Exelixis is driven by a bold scientific pursuit to create transformational treatments that give more patients hope for the future. For information about the company and its mission to help cancer patients recover stronger and live longer, visit www.exelixis.com , follow @ExelixisInc on X (Twitter), like Exelixis, Inc. on Facebook and follow Exelixis on LinkedIn. Forward-Looking Statements This press release contains forward-looking statements, including, without limitation, statements related to: Exelixis’ belief that it is well-positioned for an impactful second half of 2024; the regulatory review process with respect to Exelixis’ sNDA for cabozantinib in advanced NET, including the PDUFA target action date assigned by the FDA, and the potential to bring cabozantinib as a new treatment option for these patients with high unmet medical need; Exelixis’ plans to reallocate resources to new pivotal trials in zanzalintinib and to advancing phase 1 efforts for XL309 and XB010, as well as to the rest of the company’s growing pipeline; Exelixis’ updated 2024 financial guidance; the anticipated timing for receipt of a $150 million milestone payment from Ipsen; Exelixis’ plans to present updated results from CABINET, including final results for the primary efficacy endpoint of PFS, at the ESMO Congress 2024 in September; Exelixis’ expectation to receive reimbursement payments from Ipsen relating to CABINET, as well as milestone payments for potential future regulatory actions by the European Medicines Agency; Exelixis’ plans to submit an sNDA for the combination of cabozantinib and atezolizumab in mCRPC to the FDA this year based on the results of CONTACT-02, and to present final data from CONTACT-02 at a future medical meeting; Exelixis’ expectation that preliminary results from STELLAR-303 will readout in 2025; Exelixis’ plans to initiate STELLAR-311 in the first half of 2025; Exelixis’ plans to disclose data from JEWEL-101 at a later date; Exelixis’ future obligations under the Agreement settling the company’s patent litigation with Cipla; Exelixis’ plans to repurchase up to an additional $500 million of its common stock before the end of 2025; and Exelixis’ scientific pursuit to create transformational treatments that give more patients hope for the future. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements and are based upon Exelixis’ current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: the degree of market acceptance of CABOMETYX and other Exelixis products in the indications for which they are approved and in the territories where they are approved, and Exelixis’ and its partners’ ability to obtain or maintain coverage and reimbursement for these products; the effectiveness of CABOMETYX and other Exelixis products in comparison to competing products; the level of costs associated with Exelixis’ commercialization, research and development, in-licensing or acquisition of product candidates, and other activities; Exelixis’ ability to maintain and scale adequate sales, marketing, market access and product distribution capabilities for its products or to enter into and maintain agreements with third parties to do so; the availability of data at the referenced times; the potential failure of cabozantinib, zanzalintinib and other Exelixis product candidates, both alone and in combination with other therapies, to demonstrate safety and/or efficacy in clinical testing; uncertainties inherent in the drug discovery and product development process; Exelixis’ dependence on its relationships with its collaboration partners, including their pursuit of regulatory approvals for partnered compounds in new indications, their adherence to their obligations under relevant collaboration agreements and the level of their investment in the resources necessary to complete clinical trials or successfully commercialize partnered compounds in the territories where they are approved; complexities and the unpredictability of the regulatory review and approval processes in the U.S. and elsewhere; Exelixis’ continuing compliance with applicable legal and regulatory requirements; unexpected concerns that may arise as a result of the occurrence of adverse safety events or additional data analyses of clinical trials evaluating cabozantinib and other Exelixis product candidates; Exelixis’ dependence on third-party vendors for the development, manufacture and supply of its products and product candidates; Exelixis’ ability to protect its intellectual property rights; market competition, including the potential for competitors to obtain approval for generic versions of Exelixis’ marketed products; changes in economic and business conditions; and other factors detailed from time to time under the caption “Risk Factors” in Exelixis’ most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q, and in Exelixis’ other future filings with the Securities and Exchange Commission. All forward-looking statements in this press release are based on information available to Exelixis as of the date of this press release, and Exelixis undertakes no obligation to update or revise any forward-looking statements contained herein, except as required by law. Exelixis, the Exelixis logo, CABOMETYX and COMETRIQ are registered trademarks of Exelixis, Inc. EXELIXIS, INC. CONDENSED CONSOLIDATED STATEMENTS OF INCOME (in thousands, except per share amounts) (unaudited) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 Revenues: Net product revenues $ 437,581 $ 409,646 $ 816,104 $ 773,046 License revenues 194,986 52,747 239,662 91,039 Collaboration services revenues 4,611 7,455 6,638 14,551 Total revenues 637,178 469,848 1,062,404 878,636 Operating expenses: Cost of goods sold 17,667 17,705 38,923 32,020 Research and development 211,147 232,570 438,836 466,816 Selling, general and administrative 132,015 141,723 245,999 273,120 Restructuring 475 — 33,310 — Total operating expenses 361,304 391,998 757,068 771,956 Income from operations 275,874 77,850 305,336 106,680 Interest income 17,258 22,541 37,152 42,043 Other expense, net (287 ) (5 ) (376 ) (59 ) Income before income taxes 292,845 100,386 342,112 148,664 Provision for income taxes 66,729 19,208 78,679 27,458 Net income $ 226,116 $ 81,178 $ 263,433 $ 121,206 Net income per share: Basic $ 0.78 $ 0.25 $ 0.89 $ 0.37 Diluted $ 0.77 $ 0.25 $ 0.88 $ 0.37 Weighted-average common shares outstanding: Basic 289,216 324,205 294,986 324,312 Diluted 293,974 327,305 299,752 326,792 EXELIXIS, INC. RECONCILIATION OF GAAP NET INCOME TO NON-GAAP NET INCOME (in thousands, except per share amounts) (unaudited) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 GAAP net income $ 226,116 $ 81,178 $ 263,433 $ 121,206 Adjustments: Stock-based compensation - research and development expenses (1) 9,178 9,589 13,070 12,841 Stock-based compensation - selling, general and administrative expenses (1) 16,176 15,311 31,397 28,720 Income tax effect of the above adjustments (5,841 ) (5,781 ) (10,289 ) (9,642 ) Non-GAAP net income $ 245,629 $ 100,297 $ 297,611 $ 153,125 GAAP net income per share: Basic $ 0.78 $ 0.25 $ 0.89 $ 0.37 Diluted $ 0.77 $ 0.25 $ 0.88 $ 0.37 Non-GAAP net income per share: Basic $ 0.85 $ 0.31 $ 1.01 $ 0.47 Diluted $ 0.84 $ 0.31 $ 0.99 $ 0.47 Weighted-average common shares outstanding: Basic 289,216 324,205 294,986 324,312 Diluted 293,974 327,305 299,752 326,792 ____________________ (1) Non-cash stock-based compensation expense used for GAAP reporting in accordance with Accounting Standards Codification Topic 718, Compensation—Stock Compensation .