eFFECTOR Therapeutics, Inc. provided an update on its ongoing clinical development programs for both zotatifin, in Phase 2 expansion cohorts for the treatment of estrogen receptor positive breast cancer (ER+ BC) and KRAS non-small cell lung cancer (KRAS NSCLC) as well as Phase 1 development for SARS-CoV-2 (COVID-19), and tomivosertib, in a Phase 2b trial for the treatment of non-small cell lung cancer (NSCLC) in combination with pembrolizumab, an established anti-immune checkpoint inhibitor used to treat various types of cancer. Zotatifin program update as of December 15, 2022: In the cohort (n=7) receiving zotatifin, fulvestrant and abemaciclib (ECBF+A), two patients experienced confirmed PRs, and a third patient had stable disease continuing beyond 24 weeks, for an objective response rate (ORR) of 29% (2/7) and a clinical benefit rate (CBR) of 43% (3/7). Zotatifin was generally safe and well-tolerated in this triplet combination.

ORR and CBR data for the remaining 11 patients is anticipated to be available in the first half of 2023. In the ECBF cohort (n=18) receiving zotatifin and fulvestrant, one patient experienced a confirmed PR and one patient had stable disease continuing beyond 24 weeks. Zotatifin was generally safe and well-tolerated in this doublet combination.

Dose-dependent target engagement was observed by two independent methods, without obvious signs of target saturation. Therefore, the company has resumed dose escalation with topline data anticipated in the second half of 2023. The company is deferring initiation of the Cyclin D1 amplified cohort in ER+ BC and pausing enrollment in the KRAS G12C lung cancer cohort until completion of dose escalation.

Enrollment has completed in the third and final cohort in the Phase 1b COVID study. Tomivosertib Program Update: Enrollment challenges have persisted across both cohorts resulting from staffing issues across clinical sites and competition from other trials, and topline data from the frontline PD-L1>50% cohort is now anticipated to readout in the second half of 2023. The company is discontinuing further enrollment of the PD-L1>1% maintenance cohort.