Partnering to Expand Therapeutic Boundaries

Exelixis has established multiple partnerships and collaborations with other leading pharmaceutical and biopharmaceutical companies. These partnerships are designed to advance the development of a variety of potential therapies for cancer and other serious diseases.

Esaxerenone (CS-3150)

Esaxerenone (CS-3150) is an oral, non-steroidal, selective blocker of the mineralocorticoid receptor (MR), a nuclear hormone receptor implicated in a variety of cardiovascular and metabolic diseases. MR blockers can be used to treat hypertension and congestive heart failure due to their vascular protective effects. Recent studies have also shown beneficial effects of adding MR blockers to the treatment regimen for patients with type 2 diabetes with nephropathy. As a non-steroidal, selective MR antagonist, esaxerenone may have the potential for the treatment of hypertension and congestive heart failure, and may provide protection from end organ damage due to vascular complications.

Esaxerenone is one of the compounds identified during Exelixis’ research collaboration with Daiichi Sankyo, which the companies entered into in March 2006. Under the terms of the agreement, Exelixis granted Daiichi Sankyo an exclusive, worldwide license to certain intellectual property primarily relating to compounds that modulate MR. In exchange, Exelixis received a $20 million upfront payment, research funding for a joint research period, and the potential for substantial clinical development, regulatory and commercialization milestone payments, as well as double-digit royalties on sales. Since the conclusion of the joint research period in November 2007, Daiichi Sankyo has been responsible for all subsequent preclinical and clinical development, and will also oversee regulatory, manufacturing and commercialization activities for the compound.

In September 2016, Daiichi Sankyo initiated a phase 3 pivotal trial (ESAX-HTN) to evaluate esaxerenone as a treatment for essential hypertension in Japanese patients. In September 2017, Daiichi Sankyo announced positive top-line results from this trial and subsequently submitted a regulatory application to the Japanese Pharmaceutical and Medical Devices Agency in February 2018. In addition to ESAX-HTN, Daiichi Sankyo is sponsoring six smaller phase 3 clinical trials evaluating esaxerenone in specific populations of patients with hypertension, either as monotherapy or in combination with other therapies used to treat the condition, as well as an additional phase 3 clinical trial in patients with diabetic nephropathy. For more information on the clinical trial program for esaxerenone, please visit www.clinicaltrials.gov.

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SAR245408 (XL147)

SAR245408 (XL147) is an orally available inhibitor of phosphoinositide-3-kinase (PI3K). PI3K plays an important role in cell proliferation and survival, and activation of the PI3K pathway is a frequent event in human tumors, promoting cell proliferation, survival, and resistance to chemotherapy and radiotherapy. Exelixis discovered SAR245408 internally and out-licensed the compound to Sanofi. SAR245408 has been evaluated by Sanofi as a single agent and in multiple combination regimens in a variety of cancer indications.

SAR245409 (XL765)

SAR245409 (XL765) is an orally available inhibitor of PI3K and the mammalian target of rapamycin (mTOR), which are frequently activated in human tumors and play central roles in tumor cell proliferation. Exelixis discovered SAR245409 internally and out-licensed the compound to Sanofi. SAR245409 is being evaluated by Sanofi as a single agent and in multiple combination regimens in a variety of cancer indications. Clinical trials have included a single agent phase 2 trial in Non-Hodgkin’s lymphoma, combination phase 1b/2 trials with temozolomide in patients with glioblastoma, with letrozole in hormone receptor positive breast cancer, with bendamustine and/or rituximab in lymphoma or leukemia, and a phase 1 trial in combination with a MEK inhibitor.

LXR Modulators

In December 2005, Exelixis entered into a collaboration with Bristol-Myers Squibb aimed at optimizing and characterizing modulators of LXRs for potential use in a variety of diseases including dyslipidemias and atherosclerosis. Exploratory phase 1 clinical trials have been conducted with candidate compounds and preclinical work is underway to characterize their activity in multiple disease models.

PI3K-δ (XL499) Inhibitor Program

PI3K-δ is a member of the PI3K family of lipid kinases and is primarily expressed in cells of the immune system. PI3Kδ function is required for a variety of immune cell responses and is believed to be associated with auto-immune and inflammatory disorders. Inhibitors of PI3Kδ may have broad potential as anti-inflammatory agents. Exelixis discovered a series of inhibitors of PI3Kδ including XL499, which reached development compound status internally.

The program was out-licensed to Merck (known as MSD outside of the United States and Canada) in December 2011. Characterization of XL499 and related compounds in preclinical models is ongoing at Merck.

ROR Antagonists

RORs are members of the nuclear hormone receptor family and consist of three related family members, RORα, β, and γ. An isoform of RORγ, known as RORγ-t, is required for the development and function of a subset of T-lymphocytes called TH17 cells. These cells secrete pro-inflammatory cytokines such as IL-17 and IL-23 and are thought to be associated with a variety of inflammatory conditions including psoriasis and multiple sclerosis. Small molecule antagonists of RORγ may block TH17 cell development and function and thereby serve as anti-inflammatory agents. In October 2010, Exelixis entered into a joint discovery program with Bristol Myers Squibb to optimize and characterize RORγ antagonists. Since the end of the collaborative research period in July 2013, Bristol-Myers Squibb has had and will continue to have sole responsibility for further research, development, manufacture, and commercialization of products developed under the collaboration.

Clinical Trials

Our lead medicines are involved in a broad clinical trial development program.