On February 23, 2015 Rigel Pharmaceuticals, Inc. (Nasdaq:RIGL) and Bristol-Myers Squibb Company (NYSE:BMY) reported that they have entered into a collaboration agreement for the discovery, development and commercialization of cancer immunotherapies based on Rigel’s extensive portfolio of small molecule TGF beta receptor kinase inhibitors (Press release Bristol-Myers Squibb, FEB 23, 2015, http://news.bms.com/press-release/rd-news/rigel-and-bristol-myers-squibb-announce-research-and-development-collaboration [SID:1234501827]). TGF beta can promote tumor growth, broadly suppress the immune system and increase the ability of tumors to spread in the body. The collaboration will focus on developing a new class of therapeutics aimed at increasing the immune system’s activity against various cancers either as monotherapy or in combination with immune checkpoint inhibitors, including Bristol-Myers Squibb’s Opdivo (nivolumab) and Yervoy (ipilimumab).
Under the terms of the agreement, Bristol-Myers Squibb will obtain exclusive, worldwide rights to develop and commercialize small molecule therapeutics derived from Rigel’s TGF beta library, including, but not limited to, those approved to treat cancer. Bristol-Myers Squibb will pay $30 million upfront and Rigel will be eligible to receive development and regulatory milestones that could total more than $309 million for a successful compound approved in multiple indications. Rigel will also be eligible to receive tiered royalties on the net sales of any products from the collaboration.
“As a company dedicated to leading scientific advances in immuno-oncology, we are committed to exploring the utility of TGF beta inhibition as a potential therapeutic to fight certain cancers,” said Carl Decicco, Ph.D., Head of Discovery, R&D, Bristol-Myers Squibb. “Working with Rigel and having access to their TGF beta receptor kinase inhibitors extends our existing portfolio of immunotherapeutic approaches to include this key mediator of immunosuppression in the tumor microenvironment.”
“This collaboration places our TGF beta receptor kinase inhibitor program into the hands of Bristol-Myers Squibb, a premier immuno-oncology company. Together, we believe TGF beta inhibition may offer novel therapeutic opportunities in oncology treatments,” said Raul Rodriguez, president and chief executive officer of Rigel. “Rigel has focused on immunology, and oncology via numerous partnerships. This collaboration is Rigel’s first in immuno-oncology and is one of the Company’s several programs in this area.”
TGF beta Inhibition
Within the immune system, TGF beta often plays an immunosuppressive role by potently suppressing effector cell proliferation and function while simultaneously promoting differentiation of certain suppressive T-cells. This master regulator is often present within tumor microenvironments and can significantly dampen anti-tumor host immune responses. Current evidence suggests that TGF beta can arise from many sources, including the cancer itself, surrounding cells and infiltrating macrophages.
Developing a drug that inhibits TGF beta signaling in cancer patients has the potential to counteract an important mechanism used by cancers to escape immuno-surveillance, thereby making this signaling pathway an appealing therapeutic target for immuno-oncology related applications.
Rigel has identified a large number of orally bioavailable, potent and selective small molecule inhibitors of TGF beta receptor kinases that have demonstrated in vivo efficacy, in preclinical animal models of cancer, consistent with an immune-mediated mechanism of action.