Celgene, Evotec ink $65M oncology deal

HAMBURG, Germany—Evotec AG and Celgene Corporation have teamed up in their second large collaboration, having announced a long-term strategic drug discovery and development partnership for the identification of new oncology therapeutics. Per the terms of the agreement, Celgene gains exclusive opt-in rights to license worldwide rights to all programs developed under the auspices of this deal, for which it will make an upfront payment to Evotec of $65 million. Evotec also stands to receive significant milestone payments and tiered royalties on each licensed program.

Celgene has an established history in the field of cancer, and Evotec brings with it “an industry-leading phenotypic screening platform with unique compound libraries and associated target deconvolution capabilities,” the company noted in a press release. The initial target for this deal will be solid tumors.

“We are extremely pleased and encouraged about the opportunity to enter into a second major alliance with our colleagues at Celgene. Our first alliance in neurodegenerative diseases has already proven that both companies and teams are united by the same spirit and objectives bringing new and better treatment to patients,” Dr. Cord Dohrmann, chief scientific officer of Evotec, said in a press release.

The companies' first partnership was announced in December 2016 as a five-year collaboration to discover disease-modifying therapeutics for neurodegenerative diseases, including Alzheimer's disease, Parkinson’s disease and amyotrophic lateral sclerosis, among others. The agreement netted Evotec $45 million up front, for which Celgene gained exclusive options to in-license worldwide rights to Evotec programs developed from its compound library. The deal also includes up to $250 million in milestone payments for Evotec, as well as up to low double-digit royalties. Celgene also can choose to screen compounds from its CELMoD library using Evotec's iPSC platform to determine their potential in neurodegenerative disease models.

This is the second cancer collaboration for Evotec this month, as the company announced on May 8 that it would be working with Carna Biosciences Inc.—though with the target of blood cancers, rather than solid tumors. The deal stipulates that Carna will leverage Evotec's INDiGO platform to speed the advancement of CB-1763, Carna's program for the treatment of blood cancer, through to the submission of an Investigational New Drug application. That filing is expected in the first half of 2019.

“We are excited to initiate IND-enabling studies for our next-generation non-covalent BTK inhibitor, CB-1763, in collaboration with Evotec,” remarked Dr. Masaaki Sawa, chief scientific officer at Carna Biosciences. “We’ve been working with Evotec from last year and found they are a really reliable partner. We believe Evotec’s INDiGO program and their team will help us to accelerate the development of our CB-1763, and we are confident that we will achieve our goal to reach IND-filing in the first half of 2019.”

The compound, as noted on Carna's website, is “a highly selective, orally bioavailable, non-covalent inhibitor of both wild type and C481S-mutant Bruton’s tyrosine kinase (BTK).” The company notes that ibrutinib, the first FDA-approved BTK inhibitor, is a promising approach for treating B-cell malignancies, though it is not without drawbacks.

“Ibrutinib covalently binds to the Cysteine 481 residue (C481) of BTK to inhibit BTK enzymatic activity, but recent studies indicated that about some of patients discontinued ibrutinib therapy at a median follow-up of 20 months due to drug resistance,” Carna's website explains. “The primary resistance mechanism for ibrutinib is thought to be via C481 mutations. Mutation of C481 prevents covalent binding of ibrutinib and other second-generation covalent BTK inhibitors, and diminishes inhibitory activities. In addition, several adverse effects such as bleeding, rash, atrial fibrillation have been reported, which were mostly associated with the off-target effects by inhibiting other kinases. Therefore, a selective and non-covalent BTK inhibitor is highly demanded to overcome ibrutinib resistance. CB1763 was designed to inhibit both wild type and C481S mutant BTKs in a highly selective and reversible manner.”

Dr. Mario Polywka, chief operating officer of Evotec, noted that: “This development of Carna’s key project directly reflects the success of our comprehensive and industry-unique INDiGO service. We are delighted to support Carna’s CB-1763 inhibitor program, an innovative approach to blood cancer, through to the clinic. Additionally, working with Carna also highlights our increasing presence in the Japanese market.”

INDiGO helps to speed drug candidates' development by “reducing time from nomination to regulatory submission in 52 weeks, and under circumstances, even less,” Evotec reports on its website, adding that “We achieve accelerated development by tightly integrating traditional drug silos into a single project managed under one roof.”