Exelixis will receive $60 million from Bristol-Myers Squibb (BMS) as a combined up-front payment relating to two new deals covering the development of TGR5 agonist and retinoid-related orphan receptor (ROR) antagonist drug candidates. The first deal gives BMS an exclusive license to Exelixis’ small molecule TGR5 agonist program for diabetes, including back-up compounds. The second will initially involve a collaboration to discover, optimize, and characterize small molecule ROR antagonists as potential anti-inflammatory compounds.
The firms say they have in addition made minor amendments to their ongoing XL281 and liver X receptor (LXR) agreements. Exelixis separately also exercised its right to opt out of further co-development of XL139 and will receive an accelerated milestone payment.
Under terms of the two new deals Exelixis could receive potential development and commercialization milestones of $250 million for the TGR5 program and another $255 million for the ROR antagonist program. Sales milestones and royalties will also be due. BMS gets an exclusive, worldwide license to develop and commercialize small molecule TGR5 agonists and ROR antagonists. The firm will have sole responsibility for all activities relating to R&D, manufacturing, and commercialization of TGR5 candidates. It will collaborate with Exelixis on the ROR antagonist programs up to the preclinical transition point. BMS will then take over all R&D, manufacturing, and commercialization activities relating to the ROR candidates.
Exelixis says it is granting BMS rights to the ROR program in exchange for the latter waiving its rights to a third IND candidate that it would have been entitled to under an oncology collaboration signed with Exelixis back in 2006.
“These transactions leverage our discovery expertise with the development expertise of BMS in inflammation and metabolic diseases and provide important additional resources for us to continue our focus on our clinical-stage development pipeline,” comments Michael M. Morrissey, Ph.D., Exelixis president and CEO.
TGR5 is a G-protein coupled bile acid receptor that is highly expressed in the gall bladder and intestine and acts on bile acids to promote the secretion of glucagon-like peptide-1 (GLP-1). The firm suggests stimulating GLP-1 secretion by activating TGR5 could potentially represent a complementary approach to the use of dipeptidyl peptidase-4 inhibitors in the treatment of diabetes.
ROR is a member of the nuclear hormone receptor family that plays a key role in the development and activity of IL17-secreting T cells that are associated with a range of inflammatory disorders. Small molecule antagonists of ROR act to inhibit production of the pro-inflammatory cytokines and could have broad potential as novel anti-inflammatory compounds, Exelixis adds.