Benzinga | Oct 7, 2021 07:07AM EDT

Forma Therapeutics' FT-7051 Is Well-tolerated And Demonstrates Evidence If Activity In Initial Results From Ongoing Phase 1 Courage Study In Men With Metastatic Castration-resistant Prostate Cancer

Forma Therapeutics Holdings, Inc. (NASDAQ:FMTX), a clinical-stage biopharmaceutical company focused on sickle cell disease, prostate cancer and other rare hematologic diseases and cancers, today announced positive initial results from a Phase 1 trial of its novel CBP/p300 inhibitor, the oral small molecule FT-7051, in men with metastatic castration-resistant prostate cancer (mCRPC). Initial clinical data from the Courage Study, an ongoing first-in-human Phase 1 trial presented at the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics, showed an encouraging safety profile of FT-7051, as well as high specificity to the CBP/p300 pathway.

"Preliminary data from the Courage Study are promising," said Andrew J. Armstrong, M.D., principal investigator of the Courage Study, and Professor of Medicine, Pharmacology and Cancer Biology, and Director of Research at the Duke Cancer Institute Center for Prostate and Urologic Cancers. "Managing the balance between safety, tolerability and efficacy is a key element of targeting this pathway, and thus far the doses studied are achieving pharmacodynamic target engagement with acceptable tolerability."

Preliminary results reported today include data as of Sept. 1, 2021, from eight men enrolled in the trial. FT-7051 was administered in 28-day cycles, with 21 days of dosing followed by seven days of no dosing. Three patients remain on study; five patients left the study (four due to disease progression and one withdrawal of consent). The adaptive trial design is intended to efficiently explore safe and efficacious doses of FT-7051. Prior to enrollment, all of the men had received diagnoses of mCRPC, castration-levels of serum testosterone and rising levels of the biomarker prostate specific antigen (PSA) after the failure of at least two lines of therapy with an approved androgen-receptor pathway inhibitor.

The initial pharmacokinetic (PK) analysis of FT-7051 documented rapid absorption, which produced maximum blood concentrations within two hours. The 150 mg dose achieved drug concentrations that approached the predicted efficacious dose based on modeling with preclinical results. Skin biopsies of the men participating in the study demonstrated a reduction in H3K27AC, a marker of activity in the CBP/p300 pathway, the target of FT-7051.

The majority of the treatment-emergent adverse events (TEAEs) were mild or moderate, at Grade 2 or lower, with no events leading to treatment discontinuation. One patient experienced Grade 3 hyperglycemia, which was medically managed. Following a dose reduction, this patient remained on treatment and experienced an ongoing PSA decline of greater than 50% at 12 weeks and greater than 80% at 16 weeks. Based upon these safety results, dose escalation is ongoing. The trial is continuing according to its adaptive design to further understand the safety and tolerability of FT-7051, gather data on clinical response including PSA and radiographic tumor response, as well as the assessment of secondary endpoints of clinical response.

"There is substantial need for new therapies to treat those with mCRPC as they progress while on existing lines of anti-androgen or chemotherapy," said David N. Cook, Ph.D., senior vice president, Forma Therapeutics' chief scientific officer. "Thanks to the eight patients who participated in the Courage Study to date, we have made progress in understanding the potential of CBP/p300 inhibition in prostate cancer and look forward to continuing our dose escalation study."