C4 lays off 30% of staff in aftermath of BRD9 degrader discontinuation

C4 lays off 30% of staff in aftermath of BRD9 degrader discontinuation

Two months after C4 Therapeutics discontinued one of its cancer assets, the small molecule medicines biotech has revealed that this narrowing of focus will come at the cost of a 30% reduction in headcount.

C4 announced on Nov. 1 that it was halting work on an oral BRD9 degrader called CFT8634 in synovial sarcoma and SMARCB-1 null tumors after the high levels of BRD9 degradation identified in a phase 1/2 trial didn’t result in sufficient efficacy for heavily pre-treated patients receiving CFT8634 by itself.

Instead, the Massachusetts-based biotech said at the time that it would prioritize its two other candidates in phase 1/2 trials. The company’s lead candidate, dubbed CFT7455, is an IKZF1/3 degrader being studied in combination with corticosteroid dexamethasone for patients with relapsed or refractory multiple myeloma (R/R MM), as well as a monotherapy for patients with advanced non-Hodgkin’s lymphoma.

The other asset being prioritized is CFT1946, a BRAF V600 degrader taking aim at solid tumors including non-small cell lung cancer (NSCLC), colorectal cancer and melanoma. The asset is currently being evaluated in a dose escalation phase 1/2 trial to treat solid tumors with BRAF V600 mutations.

The company confirmed in a post-market release yesterday that it would also continue to support the phase 1 development of CFT8919—an oral degrader designed to treat EGFR L858R mutations present in patients with NSCLC—by its China-based partner Betta Pharmaceuticals, as well as “delivering on three discovery collaborations and progressing a streamlined internal discovery effort.”

In the release, C4 explained that restructuring its operations in this way would result in around 30% of its employees being laid off. A total of 45 positions will be impacted, with the changes likely to be completed by the end of the quarter, it added in a related SEC filing.

The biotech entered the new year with $330 million in cash and equivalents. This had been recently topped up by selling off $72 million in shares, as well as a $10 million upfront payment as part of a degrader-antibody conjugate collaboration with Merck & Co. in December and a $25 million equity investment from a subsidiary of Betta as part of the CFT8919 licensing deal.

Combined with savings from the layoffs and restructured operations, C4 said it now expects its cash runway to extend into 2027.

The decision to restructure the company “was not a decision we made lightly,” CEO Andrew Hirsch said in the Jan. 9 release.

“Our sharpened focus on progressing CFT7455 and CFT1946 to critical clinical milestones, along with advancing targeted protein degradation research through our discovery collaborations with Roche, Biogen and Merck and our internal research efforts, will help C4T deliver breakthrough therapies for patients with cancer and other diseases,” Hirsch added.

“Our strengthened balance sheet, coupled with cost savings from our restructuring, provide sufficient runway to execute through and beyond critical milestones across the portfolio.”

Those milestones include updated data from the ongoing phase 1 dose escalation trial of CFT7455 in R/R MM, which is due in the second half of 2024 along with data from a trial in non-Hodgkin’s lymphomas.

The second half of this year is also likely to see a readout from a phase 1 dose escalation trial of CFT1946 in melanoma, colorectal cancer, non-small cell lung cancer and other cancers with BRAF V600X mutations.

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