A phase 2 clinical trial of Calithera Biosciences’ telaglenastat in renal cell carcinoma has missed its primary endpoint. The failure of the glutaminase inhibitor to improve progression-free survival (PFS) prompted Calithera to lay off 35% of its staff to stretch its cash reserves beyond future readouts.
Telaglenastat is designed to stop cancer cells from consuming the glutamine they need to survive and grow. Calithera tested the hypothesis by randomizing 444 metastatic renal cell carcinoma patients to receive telaglenastat or placebo orally twice a day, in addition to Exelixis’ Cabometyx, and assessing the effect of the experimental drug on PFS.
The drug flunked the test. Median PFS in the telaglenastat arm was 9.2 months, compared to 9.3 months in the control cohort. Almost two-thirds of patients had previously been treated with PD(L)-1 therapies. Calithera said the arms were well balanced.
Calithera responded to the setback in the CANTATA clinical trial by outlining plans to lay off 35% of its employees. With Calithera having 90 full-time employees at the last publicly disclosed count, the proposal suggests around 30 positions are at risk. The cuts are intended to stretch the $115 million Calithera had in the bank at the end of 2020 past data drops from two clinical trials.
One of the studies, KEAPSAKE, is assessing telaglenastat in KEAP1/NRF2 mutant non-small cell lung cancer (NSCLC) patients. Calithera is continuing the NSCLC trial despite the clear failure of CANTATA in the belief that there is a strong, distinct rationale for targeting the patient population.
The KEAP1/NRF2 pathway’s regulation of reactive oxygen species is implicated in the development of some cases of NSCLC. As the process results in cells that depend on glutaminase activity, Calithera sees reasons to think telaglenastat can succeed in a genetic subset of NSCLC patients despite failing in renal cell carcinoma.
Laying off the staff is intended to enable Calithera to keep going into 2022, by which time it will have delivered interim results from the NSCLC clinical trial. The extended cash runway also takes Calithera past the completion of a phase 1 clinical trial of arginase inhibitor CB-280 in cystic fibrosis patients.
The readouts could revitalize Calithera, but, for now, the company is at a low point. Shares in the West Coast biotech fell more than 50% in premarket trading, sinking to their lowest point since its 2014 IPO.