Omega Therapeutics (OMGA) Jefferies 2024 Global Healthcare Conference summary

Platform and clinical progress

• Epigenetic controller platform enables precise, durable gene modulation, targeting over 50 genes with both upregulation and downregulation demonstrated in preclinical and clinical settings.

• Achieved robust, durable downregulation of MYC gene in hepatocellular carcinoma, with specificity and measurable epigenetic changes at all dose levels.

• Dose escalation in phase I trial reached 0.3 mg/kg (dose 5), exceeding the recommended dose, prompting de-escalation to 0.2 mg/kg (dose 6), now enrolling patients.

• Safety signals at higher doses were transient and attributed to lipid nanoparticle delivery, not the epigenomic controller.

• Expansion and combination therapy phases are planned, with comprehensive data updates expected in the second half of the year.

Clinical trial design and future plans

• Dose-finding study in later-line HCC patients, with expansion planned for true second-line patients to improve clinical benefit and statistical power.

• Expansion cohorts will enroll 15–25 patients, aiming to detect efficacy signals; combination with checkpoint inhibitors will follow after establishing the recommended dose.

• Preclinical data show strong synergy with standard-of-care agents, and a supply agreement is in place for atezolizumab.

• Mouse studies indicate potential for both direct tumor killing and immune-mediated effects, supporting the dual mechanism hypothesis.

• Monotherapy and combination expansion cohorts will proceed in a staggered, parallel manner after dose selection.

Pipeline and external validation

• Preclinical lung program data show activity in EGFR inhibitor-resistant tumor cells and synergy against osimertinib resistance.

• Platform demonstrated highly sensitive detection of methylation and durable gene upregulation (10- to 1,000-fold) across multiple genes, maintained for over a month.

• Recent conference presentations highlighted both downregulation and upregulation capabilities, expanding the platform's therapeutic potential.