FHD-609

FHD-609 showed dose-dependent increases in systemic FHD-609 exposure and pharmacodynamic response profiles. The MTDs were identified (40 mg BIW/80 mg QW) and preliminary clinical activity was observed. Future studies of BRD9 degraders will require strict cardiac monitoring given the QTc prolongation observed in this study.

P1, N=55, Terminated, Foghorn Therapeutics Inc. | N=104 --> 55 | Trial completion date: May 2025 --> Dec 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2024 --> Dec 2023; Sponsor decision

In this Phase 1 dose escalation study, treatment with FHD-609 drove robust degradation of BRD9 in synovial sarcoma patient tumors. Complete degradation was observed in samples from QW and BIW cohorts, including several collected multiple days post-dose. BRD9 degradation was associated with histological treatment effects, and decreased markers of proliferation.

P1, N=104, Active, not recruiting, Foghorn Therapeutics Inc. | Recruiting --> Active, not recruiting

P1, N=104, Recruiting, Foghorn Therapeutics Inc. | N=70 --> 104

Here we report the first use of IHC and flow cytometry to measure target engagement with a BRD9 protein degrader in clinically relevant tissues. Using these methods, we found that higher doses of FHD-609 led to more prolonged suppression of BRD9 in tumors and PBMCs. Our results also suggest that certain PBMC populations are effective surrogates for tumor PD, which may enable longitudinal assessment of target engagement through serial blood collection in the clinic.

We identified TP53-modulating drugs to be possibly effective in 20-26% of patients, followed by the Wnt signaling pathway inhibitors (15%), Telomelysin and INO5401 (13%), FHD-609 (13%), etc. According to our data, 67% of ACC patients exhibited genomic alterations that might be targeted by FDA-approved drugs or drugs being tested in current clinical trials. Although there are not many current therapy options directly targeting reported ACC alterations, this study identifies emerging options that could be tested in clinical trials.

P1, N=70, Recruiting, Foghorn Therapeutics Inc.