OTX-2002 / Omega Therap - LARVOL DELTA

MYCHELANGELO I: A Phase 1/2 Study to Evaluate OTX-2002 in Patients with Hepatocellular Carcinoma and Other Solid Tumor Types Known for Association with the MYC Oncogene (clinicaltrials.gov) - P1/2 | N=24 | Terminated | Sponsor: Omega Therapeutics | N=190 ➔ 24 | Trial completion date: Dec 2028 ➔ Nov 2024 | Recruiting ➔ Terminated | Trial primary completion date: Jun 2025 ➔ Nov 2024; Sponsor decision to terminate after monotherapy dose escalation.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

First-in-human phase 1/2 study (MYCHELANGELO I) of first-in-class epigenomic controller OTX-2002 targeting MYC oncogene in patients with hepatocellular carcinoma (HCC) and other solid tumors. (ASCO-GI 2025) - P1/2 | "OTX-2002 is well-tolerated and induces rapid and durable epigenomic changes to the MYC locus. These results provide clinical proof of mechanism of the epigenomic controller platform and support continued development of OTX-2002."

Clinical • P1/2 data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • MYC

Topline Data from Completed Phase 1 MYCHELANGELO Trial (GlobeNewswire) - P1/2 | N=190 | MYCHELANGELO I (NCT05497453) | Sponsor: Omega Therapeutics | "Topline data from the completed Phase 1 trial showed:...(i) Safety and tolerability: At the recommended dose for expansion (0.12 mg/kg), 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; (ii) Preliminary clinical activity in HCC: The observed disease control rate (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 (29-65%)."

P1 data • Hepatocellular Cancer

Omega Therapeutics Announces Successful Completion of Phase 1 Trial for Novel Epigenomic Controller, Prioritized Pipeline, Leadership Changes, and Third Quarter 2024 Financial Results (GlobeNewswire) - "The Phase 1 MYCHELANGELO trial of OTX-2002 has been completed and the Company is engaged in discussions with potential partners to further advance clinical development into Phase 2 or may choose to resume development through internal efforts with additional funding. The OTX-2101 and CXCL1-8 programs have been deprioritized in order to focus resources and capital on the three selected programs....The Company is pursuing strategic partnership opportunities to advance these programs or may choose to resume development through internal efforts with additional funding."

Pipeline update • Trial status • Solid Tumor

Omega Therapeutics Announces Publication of Epigenomic Controller OTX-2002 Preclinical Data in Nature Communications (GlobeNewswire) - "Omega Therapeutics, Inc...announced the publication of preclinical data from studies of OTX-2002 in Nature Communications....Rapid reduction in both MYC mRNA and protein levels; Decreased viability of multiple HCC cell lines; Dose-dependent reduction in tumor size and growth rate in preclinical models of HCC; Antitumor activity and mechanism of action that is synergistic when combined with either tyrosine kinase inhibitors or immune checkpoint inhibitor agents; Beneficial impact on the tumor microenvironment in immune-competent mice bearing HCC tumors as evidenced by a decrease in inhibitory regulatory T cells."

Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Omega Therapeutics Reports Second Quarter 2024 Financial Results and Highlights Recent Company Progress (GlobeNewswire) - Progressed dose escalation portion of Phase 1/2 MYCHELANGELO I clinical trial evaluating OTX-2002 in patients with hepatocellular carcinoma (HCC): Made steady progress towards identifying the recommended dose for expansion (RDE) of OTX-2002, with patient enrollment ongoing in Cohort 6 at the 0.2 mg/kg dose level across sites in the U.S. and Asia. The Company expects to report updated clinical data and is planning for expansion into monotherapy and combination settings in the fourth quarter of 2024."

P1/2 data • Trial status • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Detection and quantification of site-specific DNA methylation from liquid biopsies as a pharmacodynamic biomarker of OTX-2002, a novel MYC-targeting epigenomic mRNA therapeutic (AACR 2024) - P1/2 | "This degree of sensitivity translated to successful preclinical detection of on-target methylation by OTX-2002 from DNA extracted from plasma samples collected from mice-bearing human HCC xenografts. Overall, we present a non-invasive and exquisitely sensitive method of assessing target engagement and site-specific pharmacodynamic activity of a novel epigenomic medicine that can be directly translated to the clinical setting."

Biomarker • Biopsy • Epigenetic controller • Liquid biopsy • PK/PD data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Omega Therapeutics Presents New Preclinical Data at AACR 2024 Supporting the Potential of Precision Epigenomic Control (GlobeNewswire) - "The Company also presented preclinical data validating a novel pharmacodynamic biomarker assay for monitoring on-target engagement and activity of its clinical-stage EC candidate, OTX-2002....Development of a new DNA methylation assay consisting of a minimal hybridization capture panel to evaluate CpG methylation events across a ~50 kilobase target region; Ultra-sensitive detection of methylation events at the MYC locus down to the theoretical limit of 1 in 104 copies of MYC; Demonstration of highly specific on-target engagement and methylation by OTX-2002 in liquid biopsies from mice bearing human hepatocellular carcinoma (HCC) xenografts."

Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Omega Therapeutics Reports Fourth Quarter and Full Year 2023 Financial Results and Provides Strategic Update (GlobeNewswire) - P1/2 | N=190 | MYCHELANGELO I (NCT05497453) | Sponsor: Omega Therapeutics | "The interim disease control rate (DCR) for the target population of HCC patients was 80%, reflecting 4 out of 5 efficacy-evaluable patients having a best overall response of stable disease...The DCR for patients with non-HCC solid tumors in the trial (n=5) was 40%, indicating the potential specificity of OTX-2002 for HCC....Advanced the Phase 1/2 MYCHELANGELO I clinical trial evaluating OTX-2002 in patients with hepatocellular carcinoma (HCC): Omega expects to report additional updated clinical data from monotherapy dose escalation in mid-2024; The Company plans for expansion into monotherapy and combination settings in mid-2024."

P1/2 data • Trial status • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Omega Therapeutics Announces Two Poster Presentations at the American Association for Cancer Research Annual Meeting 2024 (GlobeNewswire) - "Omega Therapeutics, Inc...announced that it will present two posters at the American Association for Cancer Research (AACR) Annual Meeting 2024, taking place in San Diego, California, April 5 – 10, 2024. The first poster will feature preclinical data validating a novel method for evaluating epigenomic controller (EC) target engagement using noninvasive liquid biopsies. Additionally, the Company will present new preclinical data supporting a MYC-targeting EC approach in models of non-small cell lung cancer (NSCLC) resistant to EGFR inhibitors."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Omega Therapeutics Reports Third Quarter 2023 Financial Results and Highlights Recent Company Progress (GlobeNewswire) - "Omega expects to report updated clinical data from monotherapy dose escalation in the first half of 2024; The Company is planning to initiate expansion cohorts in monotherapy and in combination settings with standard of care agents mid-2024."

P1/2 data • Trial status • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

A POSITIVE FEEDBACK BETWEEN CHOLESTEROL SYNTHESIS AND THE PENTOSE PHOSPHATE PATHWAY RATHER THAN GLYCOLYSIS PROMOTES HEPATOCELLULAR CARCINOMA (AASLD 2023) - " Activation of cholesterol synthesis, glycolysis and the pentose phosphate pathway (PPP) was observed in HCC patients and c-Myc HCC mouse model... This study identified a previously undescribed positive feedback loop between cholesterol synthesis and the PPP, which drives HCC development by providing substrate of DNA synthesis and energy for hepatocyte proliferation, while microRNA-206 prevents HCC by disrupting this loop. Cholesterol synthesis as a process rather than cholesterol itself is the major contributor of HCC, which at least in part explains the controversial findings of cholesterol-lowering drugs for the treatment of HCC."

Dyslipidemia • Gastrointestinal Cancer • Hepatocellular Cancer • Metabolic Disorders • Oncology • Solid Tumor • MIR206 • MYC

Omega Therapeutics Announces Promising Preliminary Clinical Data for OTX-2002 from Ongoing MYCHELANGELO I Trial (GlobeNewswire) - P1/2 | N=190 | MYCHELANGELO I (NCT05497453) | Sponsor: Omega Therapeutics | "Omega Therapeutics, Inc...announced encouraging preliminary safety, tolerability, pharmacokinetic and translational data from the initial two dose level cohorts (n=8) from Part 1 of its ongoing Phase 1/2 MYCHELANGELO™ I study evaluating OTX-2002 in patients with hepatocellular carcinoma (HCC) and other solid tumors associated with the c-MYC (MYC) gene....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....Consistent pharmacokinetic (PK) data across both dose levels with rapid clearance and minimal variability observed within and between patients."

P1/2 data • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Omega Therapeutics to Host Conference Call to Discuss Preliminary Clinical Data for OTX-2002 from Ongoing MYCHELANGELO I Trial on September 26 (GlobeNewswire) - "Omega Therapeutics...announced that management will host a conference call and webcast to discuss preliminary clinical data from the ongoing Phase 1/2 MYCHELANGELO™ I trial of OTX-2002 on Tuesday, September 26, 2023, at 8:00 a.m. ET."

P1/2 data • Hepatocellular Cancer

Omega Therapeutics Reports Second Quarter 2023 Financial Results and Highlights Recent Company Progress (GlobeNewswire) - "Advanced the MYCHELANGELO I Clinical Trial Evaluating OTX-2002: The Phase 1/2 trial is evaluating OTX-2002, the Company’s lead OEC, as a monotherapy (Part 1) and in combination with standard of care therapies (Part 2) in patients with relapsed or refractory hepatocellular carcinoma (HCC) and other solid tumor types known for association with the c-Myc (MYC) oncogene. Trial enrollment continues to progress as planned at clinical sites across the U.S. and Asia. Preliminary data from the Phase 1 monotherapy dose escalation portion of the study, including initial safety, tolerability, pharmacologic and translational data, are expected in the fourth quarter of 2023."

P1 data • Trial status • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Galactoside 2-alpha-L-fucosyltransferase 2 (FUT2) as a novel stemness driver and therapeutic target in hepatocellular carcinoma driven by PTEN suppression (EACR 2023) - "As a prove of concept, AAV8-mediated liver-directed therapy of FUT2 suppression was introduced into mice with Pten-KO HCC as a therapeutic approach.Results and DiscussionsRNA-sequencing revealed glycosphingolipid biosynthesis to be activated in mice organoids derived from Pten-KO/c-Myc HCC, compared to control organoids...Meanwhile, shRNA-mediated suppression of Fut2 was able to prolong survival of mice in HCC driven by Pten-KO.ConclusionBy introducing clean driver mutation into mice and coupling that with organoid system, we were able to identify and study, in detail, the molecular features specific to HCC driven by PTEN suppression. As an essential player in glycoprotein fucosylation, FUT2 may shed light on unique post-translational modification promoting HCC, which can be exploited for novel therapy."

IO biomarker • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • ELF3 • MYC • PTEN

Effect of MYC-targeting programmable epigenetic mRNA therapeutics on TME and immunotherapy responses. (ASCO 2023) - "These efficacy and tolerability data support the combination of MYC-OEC and CBI treatment in patients with solid tumors. OTX-2002 is currently being evaluated in a Phase 1/2 clinical trial as a monotherapy and in combination with SoC (i.e., TKI and CBIs) for patients with HCC and other solid tumor types known for an association with MYC."

IO biomarker • Burkitt Lymphoma • Gastrointestinal Cancer • Hematological Malignancies • Hepatocellular Cancer • Hepatology • Liver Cancer • Lung Cancer • Lymphoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • MYC

Omega Therapeutics Presents New Preclinical Data Demonstrating the Potential of Omega Epigenomic Controllers to Synergize with Immunotherapies at the ASCO 2023 Annual Meeting (GlobeNewswire) - "'We continue to advance OTX-2101 through IND-enabling studies and look forward to announcing preliminary OTX-2002 monotherapy data from our Phase 1 clinical trial this year while progressing toward initiation of the combination portion of the study'....Consistent with our previous preclinical studies, MYC OECs resulted in the downregulation of MYC mRNA and protein expression, as well as decreased cell viability in Hepa1-6 mouse liver cancer cells. MYC OECs downregulated expression of PD-L1 protein on the surface of HCC and NSCLC tumor cells in vitro. The combination of MYC OEC and anti-PD-1 or anti-PD-L1 blockade significantly reduced tumor growth in a mouse xenograft liver tumor model compared to single agent treatment."

P1 data • Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Gefapixant Is Effective Over Long-Term for Refractory/Unexplained Chronic Cough (BioSpace) - "Continued Enrollment into the MYCHELANGELO I Clinical Trial Evaluating OTX-2002: The Phase 1/2 study is evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of OTX-2002, the Company’s lead Omega Epigenomic Controller™ (OEC) designed to downregulate MYC expression pre-transcriptionally, 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 the association with the MYC oncogene. Trial enrollment continues to progress as planned at clinical sites across the U.S. and Asia. Preliminary data from the Phase 1 monotherapy dose escalation portion of the study, including initial safety, tolerability, pharmacologic and translational data, is expected in 2023."

P1/2 data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Omega Therapeutics Announces Clinical Supply Agreement to Evaluate the Combination of OTX-2002 and Atezolizumab in Hepatocellular Carcinoma (GlobeNewswire) - "Omega Therapeutics, Inc...announced a clinical supply agreement with Roche to evaluate OTX-2002, its lead candidate in development for the treatment of MYC-driven hepatocellular carcinoma (HCC), in combination with Roche’s anti-PD-L1 therapy, atezolizumab, as part of Omega’s Phase 1/2 MYCHELANGELO™ I clinical trial....Preliminary data from the Phase 1 monotherapy dose escalation portion of the study are anticipated in 2023. Under the terms of this agreement, Roche will supply atezolizumab and Omega will evaluate the combination as part of the overall conduct of the trial."

Licensing / partnership • P1 data • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology

Omega Therapeutics to Present New Preclinical Data at the American Society of Clinical Oncology 2023 Annual Meeting (GlobeNewswire) - "Omega Therapeutics, Inc...announced that it will present new preclinical data related to its MYC-HCC and MYC-NSCLC programs at the upcoming American Society of Clinical Oncology (ASCO) Annual Meeting taking place in Chicago, Illinois, June 2 – 6, 2023."

Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

A phase 1/2 open-label study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of OTX-2002 as a single agent and in combination with standard of care in patients with hepatocellular carcinoma and other solid tumor types known for association with the MYC oncogene (MYCHELANGELO I). (ASCO-GI 2023) - P1/2 | "2022; 33: S355. Clinical trial information: NCT05497453."

Clinical • Combination therapy • IO biomarker • P1/2 data • PK/PD data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • MYC

Omega Therapeutics Reports Fourth Quarter and Full Year 2022 Financial Results and Provides Corporate Update (GlobeNewswire) - "Advanced MYCHELANGELO I Clinical Trial for OTX-2002, the Company’s Lead Omega Epigenomic Controller™ (OEC): Enrollment continues in the Phase 1/2 trial evaluating OTX-2002 as a monotherapy (Part I) and in combination with standard of care therapies (Part 2) in patients with relapsed or refractory hepatocellular carcinoma (HCC) and other solid tumor types known for association with the c-Myc (MYC) oncogene. Trial enrollment is progressing as planned with multiple clinical sites initiated across the U.S. and Asia; additional sites are expected to activate in these regions. Preliminary data from the Phase 1 monotherapy dose escalation portion of the study are anticipated in 2023."

P1/2 data • Trial status • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology

Omega Therapeutics to Present Trial-in-Progress Poster for Phase 1/2 MYCHELANGELO I Study at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (GlobeNewswire) - "Omega Therapeutics...announced that it will present a trial-in-progress poster at the upcoming American Society for Clinical Oncology 2023 Gastrointestinal Cancers Symposium (ASCO-GI), taking place in San Francisco, Calif., and virtually, January 19–21, 2023. The poster will highlight the design of the ongoing MYCHELANGELO™ I study, a Phase 1/2 open-label trial evaluating OTX-2002, a first-in-class Omega Epigenomic Controller™ (OEC) candidate, for the treatment of hepatocellular carcinoma (HCC) and other solid tumor types known for association with the c-Myc (MYC) oncogene."

Clinical protocol • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Omega Therapeutics Receives Orphan Drug Designation for OTX-2002 for the Treatment of Hepatocellular Carcinoma (PRNewswire) - "Omega Therapeutics, Inc...announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation for OTX-2002, the company's first-in-class epigenomic controller engineered to downregulate c-Myc (MYC), for the treatment of hepatocellular carcinoma (HCC)....'We look forward to continuing to work with clinical investigators, patients and the FDA as we advance our MYCHELANGELO clinical program and evaluate the potential of OTX-2002 to bring a new treatment option to the liver cancer patient community'."

Orphan drug • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor