C4 Therapeutics discontinues cancer program, waits for Betta payment

C4 Therapeutics is discontinuing one of its cancer assets after a phase 1/2 trial proved the drug ineffective.   

The small molecule medicines biotech has ended development of CFT8634, an oral BRD9 degrader, in synovial sarcoma—a rare cancer that typically affects large joints—and SMARCB-1 null tumors, according to a Nov. 1 release.

While the drug appeared to be well tolerated, high levels of BRD9 degradation didn’t result in sufficient efficacy for heavily pre-treated patients receiving CFT8634 by itself. C4T has stopped trial enrollment and anticipates the study to be fully shuttered by the end of 2024’s first quarter.

The Massachusetts-based biotech is instead choosing to prioritize its two other ongoing phase 1/2 trials. The company’s lead candidate called 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. 

In 2022, the company posted data revealing early efficacy signals for CFT7455 in five multiple myeloma patients from the trial. Then, this October, the company said it had completed phase 1 dose escalation for CFT7455 as a monotherapy in R/R MM with 22 patients across five dosing groups.

The biotech is expected to share new data from the monotherapy arm at a C4T virtual event Dec. 12. The phase 1 dose escalation assessing CFT7455 as a combo treatment in R/R MM and as a monotherapy in non-Hodgkin’s lymphoma is ongoing.

C4T’s second focus 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 biotech's pipeline also includes CFT8919, a preclinical oral degrader designed to treat EGFR L858R mutations present in patients with NSCLC. The candidate is the center of an exclusive licensing deal with Betta Pharmaceuticals, a China-based biotech that paid $10 million cash for rights to develop and commercialize CFT8919 in the Greater China area. Regulators in the country have accepted Betta’s clinical trial launch request for review.

Under the terms of the deal, C4T is set to receive $35 million, made up of $10 million upfront and a one-time $25 million equity investment. Though both companies have met all the deal’s closing conditions, Betta hasn’t paid out the $25 million equity purchase, citing “business circumstances,” according to the Nov. 1 release. The two companies continue to collaborate on the development of CFT8919.

As of Sept. 30, C4 Therapeutics’ cash, cash equivalents and marketable securities totaled $246.4 million—money that is anticipated to carry the company into the second half of 2025.