BMS-986288

Shares in CytomX fell 21% to just under $2 in premarket trading. Bristol Myers Squibb has checked out of its CytomX Therapeutics checkpoint inhibitor pact, walking away from a potential successor to Yervoy and wiping $300 million off the value of the alliance in the process.  CytomX broke the news after the markets closed Monday. BMS took the candidate, BMS-986288, into a phase 1/2 trial to assess whether changes to the Yervoy antibody and the addition of a Probody mask increase potency and reduce systemic toxicity. The drugmaker is yet to share data but has decided against further trials.  Removing the candidate from the wider pact reduced the potential milestones payable to CytomX from $2.1 billion to $1.8 billion. Shares in CytomX fell 21% to just under $2 in premarket trading Tuesday from a Monday closing price of $2.51. CytomX CEO Sean McCarthy discussed BMS’ decision and next steps on the biotech’s fourth-quarter results earning call postmarket Monday.  “This unexpected decision followed a broad internal portfolio review at BMS. We continue to work with BMS to gain more visibility on the data from this program and the factors that led to this decision,” the CEO said. “The BMS collaboration continues to be very active and will now focus primarily in the field of T-cell engagers where, together, we have initiated several new programs over the last two years.” BMS paid $50 million to enter into a collaboration with CytomX almost 10 years ago. In 2016, the Big Pharma selected a CTLA-4 candidate. The next year, BMS moved its internal potential Yervoy successor, BMS-986218, into the clinic. A second CytomX-partnered CTLA-4 prospect, BMS-986288, entered phase 1 in 2019. By February 2023, BMS had enough data to pick its preferred program, prioritizing BMS-986288 over the older CytomX candidate and its internal candidate. The drugmaker designed its own asset to boost T-cell priming and mitigate suppression in the tumor microenvironment, while CytomX’s first crack at CTLA-4 masked the antibody in Yervoy to minimize systemic toxicity and unlock higher doses.  BMS-986288 brought the ideas behind the two other candidates together, combining tweaks to the antibody seen in BMS’ internal program with the mask CytomX applied to its first CTLA-4 prospect. The goal was to prevent the widespread activation of the immune system that causes recipients of Yervoy to suffer side effects that prevent the administration of the optimal dose. Other groups are continuing to pursue that goal. BioNTech paid $200 million upfront for OncoC4’s CTLA-4 prospect one year ago. Phase 1/2 data soon followed. The candidate is now in a phase 3 lung cancer trial that is assessing its effectiveness as a monotherapy in patients who progress on PD-1/L1 drugs. Other groups are trying to unlock the power of CTLA-4 using bispecific molecules.

Bristol Myers Squibb has decided not to continue the development of BMS-986288, a potential successor to its blockbuster anti-CTLA-4 drug Yervoy (ipilimumab), beyond the current Phase II study.The company was partnered on the next-generation checkpoint inhibitor with CytomX Therapeutics, which made the disclosure during its earnings call after having been notified by Bristol Myers Squibb on March 6."This unexpected decision followed a broad internal portfolio review at BMS. We continue to work with BMS to gain more visibility on the data from this programme and the factors that led to this decision," stated CytomX CEO Sean McCarthy. The news dragged down company shares as much as 19% in after-hours trading Monday, and remained down about 15% by mid-day Tuesday.BMS-986288 is a probody composed of a modified version of Yervoy and linked to a proprietary masking peptide that minimises binding to CTLA-4 in normal tissues, potentially resulting in lower systemic toxicity. Bristol Myers Squibb was running a mid-stage trial of BMS-986288 alone and in combination with Opdivo (nivolumab) in close to 500 patients with advanced solid tumours. Primary completion was set for next month, according to the study's entry on ClinicalTrials.gov.