Developing a Novel Pipeline of Cancer Therapies

As we seek to improve the treatment of cancer, we are addressing a broad array of targets selected based on rigorous scientific and clinical evidence with the aim of developing a diverse pipeline with meaningful clinical potential. We are building a discovery and development capability that allows us to advance multiple therapeutic modalities, including both small molecules and biologics, to pursue an optimal approach for each individual target.

Small Molecule Drug Discovery: Strong Legacy and Future Potential

Building on our legacy of small molecule oncology drug discovery, we have a diverse portfolio of programs in various stages of development. Cabozantinib has been successfully commercialized in multiple cancer indications and is the focus of a broad development program, including multiple ongoing pivotal phase 3 clinical trials designed to support additional label expansions. XL092, our next-generation oral tyrosine kinase inhibitor (TKI), is currently in phase 1b clinical testing and could enter pivotal studies later in 2021. With a significant expansion underway, including additional laboratory space that opened in mid-2021, we anticipate a steady flow of internally discovered compounds advancing into preclinical development over the next few years.

We’ve supplemented our drug discovery efforts with collaborations that provide complementary expertise and approaches, including an agreement with Aurigene that has yielded XL102, our small molecule inhibitor of cyclin-dependent kinase 7 (CDK7), which entered in-human trials in January 2021. We are working with Aurigene on a number of earlier-stage programs for exciting targets and pathways. Separately, our collaboration with StemSynergy focuses on a novel approach to inhibiting the beta catenin pathway, one of the major undrugged pathways in human cancer.

Biotherapeutics: A New Dimension of Our Pipeline

As our small molecule programs move forward, we’re broadening our pipeline to encompass biologics that cover a broad range of targets and therapeutic modalities. XB002, the tissue factor-targeting antibody-drug conjugate (ADC) program under our research collaboration with Iconic Therapeutics, is our first clinical-stage biologic therapy and the subject of an ongoing phase 1 trial that was initiated in the second quarter of 2021.

In building out our biologics capabilities, we’ve established a network of collaborations and partnerships that allow us to discover and advance novel therapies by gaining access to the building blocks necessary to assemble effective therapies for potential use in different tumor indications. Our agreements with Invenra, WuXi Biologics, and GamaMabs give us access to various novel antibodies and bispecifics. Collaboration and license agreements with Catalent and NBE-Therapeutics provide us with highly compelling ADC platforms. Through our work with Adagene, we can utilize a conditional antibody-masking technology with the potential for an improved therapeutic index through reduction of on-target toxicity.

For more information on the technologies that underpin our fast-moving biotherapeutics development efforts, visit our Collaborations page.

Please see our early compound pipeline chart, here. For additional information on our clinical trials, please visit www.clinicaltrials.gov.

Pipeline Overview

Cabozantinib

Exelixis’ flagship compound cabozantinib is a targeted agent that inhibits the activity of receptor 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, and resistance to multiple therapies, including immune checkpoint inhibitors (ICIs). Exelixis discovered cabozantinib internally and maintains exclusive rights to commercialize the product in the United States. Outside of the United States, Ipsen has exclusive commercialization and development rights for current and future cabozantinib indications, except in Japan, where Exelixis has granted exclusive rights to Takeda. Exelixis and its partners are collaborating on the global development plan for cabozantinib and Ipsen and Takeda are responsible for the cabozantinib development work specific to their respective regions.

For information on approved uses of cabozantinib, please visit Our Medicines page.

XL092

XL092 is a next-generation oral TKI that builds on our extensive experience with cabozantinib. XL092 also targets VEGF receptors, MET, TAM kinases and other kinases implicated in cancer’s growth and spread. In preclinical tumor models, XL092 showed excellent activity as a single agent and in combination with ICIs. XL092 also has an optimized pharmacokinetic profile aimed at facilitating adverse event management in the clinic. XL092 is the first new Exelixis-discovered compound to come out of the company’s reinitiated drug discovery activities, which entered phase 1 clinical development in 2019 and could enter pivotal studies later in 2021.

In March 2021, the ongoing phase 1b STELLAR-001 trial was expanded to include dose-escalation and 15 expansion cohorts for XL092 in combination with atezolizumab. In June 2021, Exelixis announced a clinical trial collaboration and supply agreement with Bristol Myers Squibb for STELLAR-002, a phase 1b trial that will evaluate XL092 in combination with immuno-oncology therapies in advanced solid tumors. Based upon our experience with cabozantinib, the clinical profile of XL092 and initial data of the phase 1 dose escalation trial evaluating XL092, we are also pursuing additional combination trials evaluating XL092 with multiple therapeutic agents across various tumor types.

XL102

XL102 is a potent, selective and orally bioavailable covalent inhibitor of CDK7, which is an important regulator of the cellular transcriptional and cell cycle machinery. CDK7 helps regulate cell cycle progression, with overexpression observed in multiple cancers, such as breast, prostate and ovarian cancers. In preclinical studies, XL102 revealed potent anti-proliferative activity, induced cell death in a large panel of cancer cell lines and caused tumor growth inhibition and regression in xenograft models, demonstrating its potential as a targeted antitumor agent.

In late 2020, Exelixis exercised its option to in-license XL102 (formerly AUR102) from Aurigene per the companies’ July 2019 collaboration, option and license agreement. Exelixis has assumed responsibility for the future clinical development, manufacturing and commercialization of XL102. Aurigene retains limited development and commercial rights for India and Russia.

XB002

XB002 is a next-generation ADC composed of a human monoclonal antibody against tissue factor that is conjugated to a cytotoxic agent. After binding to tissue factor on tumor cells, XB002 is internalized, and the cytotoxic agent is released, resulting in targeted tumor cell death. This rationally designed next-generation ADC leverages Zymeworks’ proprietary ZymeLink™ linker-payload.

Preclinical data demonstrated that XB002 binds to tissue factor without affecting the blood coagulation cascade, in contrast with prior therapies in this class. The data also demonstrated encouraging activity of XB002 in multiple solid tumor models and improved tolerability compared with other tissue factor-targeting ADCs. XB002 has shown significant tumor growth inhibition and, in some cases, complete regression.

In late 2020, Exelixis exercised its exclusive option for XB002 (formerly ICON-2) per its May 2019 agreement with Iconic Therapeutics. Exelixis has assumed responsibility for the future clinical development, manufacturing and commercialization of XB002.

Forward-looking statements

This publication contains forward-looking statements, including, without limitation, statements related to: the clinical potential of Exelixis’ pipeline; Exelixis’ future clinical development plans for cabozantinib, XL092 and other product candidates; Exelixis’ expectation to advance internally discovered compounds and partnered programs into preclinical and/or clinical development within the next few years, as well as expand into additional laboratory space in mid-2021; Exelixis’ potential future financial and other obligations under its various collaboration agreements; and other statements relating to Exelixis’ goals, efforts and objectives. Any statements that refer to expectations, projections or other characterizations of future events or circumstance 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 level of costs associated with Exelixis’ research and development, in-licensing or acquisition of product candidates, and other activities; the potential failure of cabozantinib 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 adherence to their obligations under relevant collaboration agreements and the level of their investment in the resources necessary to complete clinical trials 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 products; 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; changes in economic and business conditions, including as a result of the COVID-19 pandemic; and other factors affecting Exelixis and its drug discovery and clinical development programs discussed under the caption “Risk Factors” in Exelixis’ Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on May 6, 2021, and in Exelixis’ future filings with the SEC. All forward-looking statements in this publication are based on information available to Exelixis as of June 17, 2021, the date of this publication, and Exelixis undertakes no obligation to update or revise any forward-looking statements contained herein, except as required by law.

Our Early-Stage Compounds

View the pipeline chart for our small molecules and biologics