• MYC-targeting Omega Epigenomic Controllers (OECs) Demonstrated Consistent Anti-Tumor Activity Across Multiple Tumor Types, Including Hepatocellular Carcinoma and Non-Small Cell Lung Cancer, in Preclinical Models

• MYC OECs Modulate Tumor Microenvironment, Enhanced Response to Checkpoint Blockade Immunotherapies and Conferred Immune Memory in Preclinical Models

• Data Support Clinical Strategy and Planned Combination with Standard of Care, Including Anti-PD-1 and Anti-PD-L1 Therapies, in Ongoing Phase 1/2 MYCHELANGELO™ I Clinical Trial

CAMBRIDGE, Mass., May 31, 2023 (GLOBE NEWSWIRE) -- Omega Therapeutics, Inc. (Nasdaq: OMGA) (“Omega”), a clinical-stage biotechnology company pioneering the development of a new class of programmable epigenomic mRNA medicines, today announced that it will present new preclinical data demonstrating the effect of MYC-targeting Omega Epigenomic Controllers™ (OECs) on the tumor microenvironment (TME) and immunotherapy responses in hepatocellular carcinoma (HCC) and non-small cell lung cancer (NSCLC) models in a poster presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting taking place in Chicago, Illinois, June 2 – 6, 2023.

“As a master oncogene, MYC plays multiple roles in promoting tumor growth, including regulating the tumor microenvironment, yet a direct MYC-targeting anti-cancer agent has remained elusive,” said Thomas McCauley, Ph.D., Omega's Chief Scientific Officer. “The enhanced anti-tumor activity demonstrated in these preclinical data strongly support further investigation of MYC-targeting OECs in combination with clinically-validated approaches such as checkpoint blockade immunotherapies. We are excited by these results, which further validate our clinical trial strategy to evaluate our lead clinical candidate OTX-2002 in combination with anti-PD-1/PD-L1 agents in our landmark Phase 1/2 MYCHELANGELO™ I trial, as well as our rationale to pursue OTX-2101, our second OEC development candidate, for the treatment of NSCLC. 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.”

Details for the poster presentation:

Title: Effect of MYC-targeting Programmable Epigenomic mRNA Therapeutics on TME and Immunotherapy Responses
Abstract #: 4116
Poster #: 437
Session Information: Gastrointestinal Cancers – Gastroesophageal, Pancreatic, and Hepatobiliary
Date and Time: June 5, 2023, from 8:00 a.m. to 11:00 a.m. CDT

Key findings:

• 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.
• As a single agent or in combination with checkpoint blockade immunotherapy (CBI), MYC OECs reduced the levels of immune-suppressive regulatory T cells and increased levels of activated CD8 T cells in the TME of mouse xenograft liver tumors, potentially enhancing the adaptive antitumor immune response.
• In immune-competent mouse allograft tumor models MYC OEC alone or in combination with CBI conferred anti-tumor immune memory.

The poster will be made available on the Omega website at the time of the presentation at https://omegatherapeutics.com/our-science/#publications-research.

About Omega Therapeutics

Omega Therapeutics is a clinical-stage biotechnology company pioneering the development of a new class of programmable epigenomic mRNA medicines to treat or cure a broad range of diseases. By pre-transcriptionally modulating gene expression, Omega’s approach enables precision epigenomic control of nearly all human genes, including historically undruggable and difficult-to-treat targets, without altering native nucleic acid sequences. Founded in 2017 by Flagship Pioneering following breakthrough research by world-renowned experts in the field of epigenetics, Omega is led by a seasoned and accomplished leadership team with a track record of innovation and operational excellence. The Company is committed to revolutionizing genomic medicine and has a diverse pipeline of therapeutic candidates derived from its OMEGA platform spanning oncology, regenerative medicine, multigenic diseases including immunology, and select monogenic diseases.

For more information, visit omegatherapeutics.com, or follow us on Twitter and LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding the timing, progress and design of our Phase 1/2 MYCHELANGELO™ I clinical trial and our preclinical studies, as well as the timing of announcements of data related thereto; expectations surrounding the potential of our product candidates, including OTX-2002 and OTX-2101; and upcoming events and presentations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: the novel technology on which our product candidates are based makes it difficult to predict the time and cost of preclinical and clinical development and subsequently obtaining regulatory approval, if at all; the substantial development and regulatory risks associated with epigenomic controllers due to the novel and unprecedented nature of this new category of medicines; our limited operating history; the incurrence of significant losses and the fact that we expect to continue to incur significant additional losses for the foreseeable future; our need for substantial additional financing; our investments in research and development efforts that further enhance the OMEGA platform, and their impact on our results; uncertainty regarding preclinical development, especially for a new class of medicines such as epigenomic controllers; potential delays in and unforeseen costs arising from our clinical trials; the fact that our product candidates may be associated with serious adverse events, undesirable side effects or have other properties that could halt their regulatory development, prevent their regulatory approval, limit their commercial potential, or result in significant negative consequences; the impact of increased demand for the manufacture of mRNA and LNP based vaccines to treat COVID-19 on our development plans; difficulties manufacturing the novel technology on which our OEC candidates are based; our ability to adapt to rapid and significant technological change; our reliance on third parties for the manufacture of materials; our ability to successfully acquire and establish our own manufacturing facilities and infrastructure; our reliance on a limited number of suppliers for lipid excipients used in our product candidates; our ability to advance our product candidates to clinical development; and our ability to obtain, maintain, enforce and adequately protect our intellectual property rights. These and other important factors discussed under the caption "Risk Factors" in our Quarterly Report on Form 10-Q for the quarter ended March 31, 2023, and our other filings with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management's estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change.