Developing a Novel Pipeline of Cancer Therapies

As we seek to improve treatments for cancer, we are pursuing development of a diverse array of molecules with important therapeutic potential. Agnostic as to drug type or target, we have flexibility to advance a pipeline of products based on rigorous scientific and clinical evidence, with addressing unmet patient need as our guiding principle for continued development.

Building on our legacy of small molecule oncology drug discovery, we have a diverse portfolio of oral kinase inhibitors in various stages of development. Cabozantinib has been successfully commercialized in multiple cancer indications and is the focus of 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. XL102, our small molecule inhibitor of cyclin-dependent kinase 7 (CDK7) and a promising target in multiple cancer indications, entered in-human trials in January 2020. Cobimetinib, an Exelixis-discovered compound approved in multiple countries, is being developed under our collaboration agreement with Genentech/Roche.

We have broadened our pipeline to include biologic therapies as well. XB002, an antibody-drug conjugate (ADC) targeting tissue factor, is our first clinical-stage biologic therapy, and we expect to add additional biologics to our pipeline as we move forward. Our strategy to establish a broad and deep biologics pipeline is supported by multiple partnerships and licensing agreements that provide access to a wide variety of biologics platforms including novel monoclonal antibodies, bispecifics, linkers, payloads and related technologies. For more information, visit our Collaborations page.

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. 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 2020, Exelixis in-licensed XL102 (formerly AUR102) from Aurigene. Exelixis has assumed responsibility for the future clinical development, manufacturing and commercialization of XL102.

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 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 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.

Exelixis 2021 Pipeline Graphic Design

For more information, please visit www.clinicaltrials.gov.

Forward-looking statements

This publication contains forward-looking statements, including, without limitation, statements related to: the therapeutic potential of Exelixis’ pipeline; Exelixis’ future clinical development plans for cabozantinib, XL092 and other product candidates; Exelixis’ expectation to add additional biologics to its pipeline; 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’ Annual Report on Form 10-K submitted to the Securities and Exchange Commission (SEC) on February 10, 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 May 6, 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.

Cabozantinib Pipeline

Explore the diverse development program for our flagship molecule