Exelixis Announces Initiation of First-In-Human Phase 1 Trial Evaluating XL114 Monotherapy in Patients with Non-Hodgkin’s Lymphoma

– XL114 is a CARD11-BCL10-MALT1 pathway inhibitor with demonstrated activity in lymphoma models that are resistant to Bruton's tyrosine kinase inhibitors –

Exelixis, Inc. (Nasdaq: EXEL) today announced initiation of the dose-escalation stage of the first-in-human phase 1 trial of XL114, a novel anti-cancer compound that inhibits the CARD11-BCL10-MALT1 complex, as a monotherapy in patients with non-Hodgkin’s lymphoma (NHL) who have received prior standard therapies. The objectives of the study are to determine the recommended dose and/or the maximum tolerated dose of XL114 and to evaluate the safety and preliminary efficacy of XL114 in patients with NHL.

“The initiation of the dose-escalation stage of our first-in-human phase 1 trial of XL114 marks an important milestone in our early efforts to identify treatments for people with blood cancers, such as non-Hodgkin’s lymphoma, who have exhausted known life-prolonging treatment options and are thus facing poor prognoses,” said Vicki L. Goodman, M.D., Executive Vice President, Product Development and Medical Affairs, and Chief Medical Officer, Exelixis. “Based on preclinical data demonstrating activity in lymphoma cell lines that are resistant to therapies that inhibit Bruton's tyrosine kinase, we are encouraged by the potential XL114 holds and look forward to advancing to the expansion stage once the appropriate dose is identified.”

The dose-escalation stage will determine the recommended dose of XL114 in patients with advanced B- and T-cell NHL. In the cohort-expansion stage, the safety and preliminary efficacy of XL114 will be further evaluated in B-cell NHL-specific expansion cohorts, including patients with activated B-cell-like diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma. The primary endpoint of the expansion stage will be objective response rate based on lymphoma-specific response criteria as assessed by the investigator.

As announced last year, Exelixis in-licensed XL114 from Aurigene Discovery Technologies Limited under the companies’ July 2019 collaboration, option and license agreement. Exelixis assumed responsibility for the future clinical development, commercialization and global manufacturing of XL114.

More information about this trial is available at ClinicalTrials.gov.

About NHL

According to the American Cancer Society, more than 80,000 people will be diagnosed with NHL in 2022, making it the seventh most common cancer in the U.S.¹ Age is one of the strongest risk factors for NHL, meaning cases are expected to rise as the American population ages.^1,2 NHL comprises more than 60 subtypes, with DLBCL as the most common.³ About 85% of NHL cases in the U.S. affect B cells, and the remainder affect T cells or Nature Killer (NK) cells.^3,4 NHL can also be classified by how quickly the cancer grows; about 40% of cases, including chronic lymphocytic leukemia, are “indolent,” or slow-growing, whereas 60%, including DLBCL, are “aggressive,” or rapidly progressing.^3,5 Although standard of care first-line therapy can be curative, up to 50% of patients with DLBCL may be refractory to treatment or relapse.⁶ The overall five-year survival rate for NHL is 73%.⁷

About XL114

XL114 is a novel anti-cancer compound that inhibits the CARD11-BCL10-MALT1 complex, a key component of signaling downstream of B- and T-cell receptors, which promotes B- and T-cell lymphoma survival and proliferation. In preclinical studies, the compound was shown to have activity in lymphoma models that are resistant to Bruton's tyrosine kinase inhibitor therapy, and in subsets of B-cell lymphomas in which Bruton's tyrosine kinase inhibitors are not active. XL114 is currently being developed for NHL.

About Exelixis

Founded in 1994, Exelixis, Inc. (Nasdaq: EXEL) is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model system genetics, we established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need. Our discovery efforts have resulted in four commercially available products, CABOMETYX^® (cabozantinib), COMETRIQ^® (cabozantinib), COTELLIC^® (cobimetinib) and MINNEBRO^® (esaxerenone), and we have entered into partnerships with leading pharmaceutical companies to bring these important medicines to patients worldwide. Supported by revenues from our marketed products and collaborations, we are committed to prudently reinvesting in our business to maximize the potential of our pipeline. We are supplementing our existing therapeutic assets with targeted business development activities and internal drug discovery – all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. Exelixis is a member of the Standard & Poor’s (S&P) MidCap 400 index, which measures the performance of profitable mid-sized companies. For more information about Exelixis, please visit www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook.

Forward-looking Statements

This press release contains forward-looking statements, including, without limitation, statements related to: the clinical and therapeutic potential of XL114 as a monotherapy for patients with NHL; and Exelixis’ plans to reinvest in its business to maximize the potential of the company’s pipeline, including through targeted business development activities and internal drug discovery. 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 potential failure of to demonstrate safety and/or efficacy in the phase 1 trial and in future trials; uncertainties inherent in the product development process; 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; the continuing COVID-19 pandemic and its impact on Exelixis’ research and development operations, including Exelixis’ ability to initiate new clinical trials and clinical trial sites, enroll clinical trial patients, conduct trials per protocol, and conduct drug research and discovery operations and related activities; the costs of conducting clinical trials; Exelixis’ dependence on third-party vendors for the development, manufacture and supply of XL114; Exelixis’ ability to protect its intellectual property rights; market competition; changes in economic and business conditions; and other factors affecting Exelixis and its development programs discussed under the caption “Risk Factors” in Exelixis’ Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on February 18, 2022, and in Exelixis’ future filings with the SEC. 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 U.S. trademarks of Exelixis.

COTELLIC is a registered trademark of Genentech, Inc.

MINNEBRO is a registered trademark of Daiichi Sankyo Company, Limited.

¹ Cancer Facts & Figures 2022. American Cancer Society website. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2022/2022-cancer-facts-and-figures.pdf. Accessed April 2022.

² Non-Hodgkin Lymphoma Risk Factors. American Cancer Society website. Available at: https://www.cancer.org/cancer/non-hodgkin-lymphoma/causes-risks-prevention/risk-factors.html. Accessed April 2022.

³ Lymphoma – Non-Hodgkin: Subtypes. Cancer.Net website. Available at: https://www.cancer.net/cancer-types/lymphoma-non-hodgkin/subtypes. Accessed April 2022.

⁴ Types of B-cell Lymphoma. American Cancer Society website. Available at: https://www.cancer.org/cancer/non-hodgkin-lymphoma/about/b-cell-lymphoma.html. Accessed April 2022.

⁵ NHL Subtypes. Leukemia & Lymphoma Society website. Available at: https://www.lls.org/lymphoma/non-hodgkin-lymphoma/nhl-subtypes. Accessed April 2022.

⁶ Crump, M., Neelapu, S.S., Farooq, U., et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. October 2017; 130(16):1800-1808.

⁷ Lymphoma – Non-Hodgkin: Statistics. Cancer.Net website. Available at: https://www.cancer.net/cancer-types/lymphoma-non-hodgkin/statistics. Accessed April 2022.

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