Omega Therapeutics Announces Promising Preliminary Clinical Data for OTX-2002 from Ongoing MYCHELANGELO I Trial - Seite 2

MYCHELANGELO I (NCT05497453) is an ongoing Phase 1/2 open label trial evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of OTX-2002 as a monotherapy (Part 1) and in combination with standard of care therapies (Part 2) in patients with relapsed or refractory HCC and other solid tumor types known for association with the MYC oncogene. These preliminary data cover the first two dose cohorts from the monotherapy dose escalation portion of the trial, which is currently being conducted at clinical sites across the United States and Asia. Patients were treated intravenously with either 0.02 mg/kg (n=4) or 0.05 mg/kg (n=4) of OTX-2002 once every two weeks. Changes in MYC DNA methylation and mRNA levels were analyzed through measurements of cell-free DNA and exosomal mRNA, respectively. As of the data cut-off date of September 18, 2023, one HCC patient in the 0.05 mg/kg dose level cohort remained on treatment.

Key Highlights:

Translational:

• Highly specific on-target engagement and intended epigenetic changes at the target genomic loci were observed for all eight patients across both dose levels, as evidenced by a robust increase in cell-free DNA MYC methylation signal following administration with OTX-2002. The increased methylation signal persisted throughout the two-week dosing interval.
• Epigenetic modulation of MYC translated to rapid, robust and durable downregulation of MYC expression in all eight patients, with mean reductions across both dose levels of approximately 55% observed 7 days following administration with OTX-2002.
• The increase in methylation and corresponding downregulation of MYC expression observed clinically are within the ranges that led to anti-tumor activity in preclinical xenograft models.
  

Pharmacokinetics:

• Consistent pharmacokinetic (PK) data across both dose levels with rapid clearance and minimal variability observed within and between patients.
• No accumulation was observed following repeat administration, and low, transient levels of immune response were observed with no related adverse events or impact on PK observed.
• Both initial dose levels are below the predicted threshold for anti-tumor activity based on preclinical models.
  

Safety and Tolerability:

• At both dose levels, OTX-2002 was generally well tolerated, with no dose-limiting toxicities.
• The majority of adverse events observed in the trial were grade 1 or 2.
• The most common treatment-related adverse events were infusion-related reactions (26%) including fever and chills, generally consistent with the known profile of other FDA-approved LNP-delivered therapeutics.