Bristol-Myers Squibb (BMS) has pulled the trigger on two deals designed to bolster its immune-oncology portfolio, acquiring Flexus Biosciences for up-to-$1.25 billion, as well as launching an R&D collaboration with Rigel Pharmaceuticals that could net that company more than $339 million-plus.

In acquiring privately held Flexus, BMS will gain full rights to F001287, Flexus’ lead preclinical small molecule IDO1-inhibitor targeted for IND filing in the second half of 2015. BMS will also acquire Flexus’ indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) discovery programs, which include its IDO-selective, IDO/TDO dual, and TDO-selective compound libraries.

The combined company plans to explore combination regimens with immunotherapies based on the inhibition of IDO and TDO, with the goal of reducing kynurenine production, which BMS and Flexus reason will enable the immune system to attack tumors more effectively. IDO and TDO are enzymes expressed by many tumor cells and surrounding cells that inhibit the immune system from identifying and destroying certain types of tumors by suppressing T-cell function through the production of kynurenine.

“With the addition of a potentially best-in-class IDO1 inhibitor and the broad IDO/TDO programs, Bristol-Myers Squibb will accelerate its ability to explore numerous immunotherapeutic approaches across tumor types, including combinations with our biologic checkpoint and co-stimulatory agents that target different and complementary pathways,” Francis Cuss, BMS’ evp and CSO, said in a statement.

A newly formed entity established by current Flexus shareholders will retain all non-IDO/TDO assets of Flexus, including those related to Flexus’ Phase I FLT3 and CDK4/6 inhibitor, its earlier stage small molecule Treg cancer immunotherapy programs, and its current personnel and facilities.

That spin-off company will house Flexus’ oncology and immuno-oncology pipeline of Agents for Reversal of Tumor Immunosuppression (ARTIS). The development of ARTIS was the stated goal of Flexus closing a Series B financing that swelled its coffers to $38 million, led by venture capital firm Kleiner Perkins Caufield & Byers (KPCB), The Column Group, and Celgene.

BMS agreed to pay Flexus $800 million upfront and up to $450 million in payments tied to development milestones. The deal is set to close later in the first quarter of this year.

Separately, BMS said it will launch a collaboration with Rigel to discover, develop, and commercialize cancer immunotherapies based on Rigel’s extensive portfolio of small molecule Transforming Growth Factor (TGF) beta receptor kinase inhibitors.

According to the collaboration partners, 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.

The companies believe they can counteract a key mechanism used by cancers to escape immuno-surveillance by developing drugs that inhibit TGF beta signaling in cancer patients. The collaboration will focus on developing a new class of treatments aimed at increasing the immune system’s activity against various cancers—either as monotherapy or in combination with immune checkpoint inhibitors that include BMS’ already-marketed drugs Opdivo (nivolumab) and Yervoy (ipilimumab).

Under the collaboration, BMS 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.

In return, BMS agreed to pay Rigel $30 million upfront, and potentially more than $309 million in payments tied to development and regulatory milestones for a successful compound approved in multiple indications. Rigel will also be eligible for tiered royalties on net sales of any products developed through the collaboration.

“Together, we believe TGF beta inhibition may offer novel therapeutic opportunities in oncology treatments,” Raul Rodriguez, Rigel’s president and CEO, said in a statement.

Rodriguez said the collaboration with BMS was Rigel’s first in immuno-oncology and is one of the company’s several programs in this area.”

Immuno-oncology is among BMS’ therapeutic areas of focus, along with oncology, immunoscience, cardiovascular, virology, fibrotic diseases, genetically defined diseases, and metabolics—where BMS says its focus is advancing early-development assets, with later-stage assets transferred to AstraZeneca. Last year, BMS sold its share of the diabetes busienss owned jointly with AstraZeneca for $2.7 billion, plus up-to-$1.4 billion tied to milestones and royalties until 2025, including $600 million related to the approval of Farxiga in the U.S.

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