Omega Therapeutics provides updated MYCHELANGELO I data

The Phase 1 monotherapy dose escalation portion of MYCHELANGELO I was designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of OTX-2002 in patients with relapsed or refractory hepatocellular carcinoma, or HCC, and other solid tumor types known for association with the MYC oncogene. Twenty-four patients, including 19 with HCC, were enrolled across six dose cohorts and were treated with OTX-2002 intravenously once every two weeks. Highly specific on-target engagement with intended epigenetic changes at the target genomic loci, as evidenced by a robust increase in cell-free DNA MYC methylation signal following administration of study drug. The signal was dose dependent within the tolerated dose range. Pre-dose levels of MYC methylation were non-detectable. The increased methylation signal persisted throughout the two-week dosing interval and downregulation of MYC expression was observed. Predictable and consistent pharmacokinetics profile with rapid clearance, minimal variability observed within and between patients, and no accumulation observed with repeat administration. At the recommended dose for expansion, OTX-2002 showed a favorable safety profile, with infusion-related reactions being the most common adverse event, generally consistent with the known profile of other FDA-approved LNP-delivered therapeutics. The observed disease control rate, or DCR, for response-evaluable HCC patients was 50%, with a best overall response of stable disease. This DCR is in-line with the historical benchmark range for completed Phase 1 trials for approved TKIs and PD-1 monotherapies in HCC.