On October 27, 2022 Omega Therapeutics, Inc. (NASDAQ: OMGA) ("Omega"), a clinical-stage biotechnology company pioneering the first systematic approach to use mRNA therapeutics as programmable epigenetic medicines, reported dosing of the first patient in its Phase 1/2 MYCHELANGELO I trial evaluating OTX-2002 for the treatment of relapsed or refractory hepatocellular carcinoma (HCC) and other solid tumor types associated with c-Myc (MYC) oncogene overexpression (Press release, Omega Therapeutics, OCT 27, 2022, View Source [SID1234622536]). OTX-2002, a novel epigenomic controller, is an mRNA therapeutic designed to downregulate MYC expression pre-transcriptionally through epigenetic modulation while potentially overcoming MYC autoregulation.

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"Today’s announcement marks a new era of therapeutic development utilizing precision genomic control intended to treat and cure serious diseases. As the first-ever Omega Epigenomic Controller (OEC) to be dosed in a patient, this milestone for OTX-2002 and the MYCHELANGELO clinical program represents a significant step forward on our mission to deliver a new approach to bringing engineered, programmable mRNA therapeutics to patients," said Mahesh Karande, President and Chief Executive Officer of Omega Therapeutics. "OTX-2002 leverages our proprietary Omega Epigenomic Programming platform and is designed for precise and durable tuning of MYC expression. We look forward to evaluating OTX-2002 for the treatment of HCC, and believe it has the potential to meaningfully transform the treatment landscape for patients in need."

Yan Moore, M.D., Chief Medical Officer of Omega Therapeutics added, "MYC has been a long sought-after target for cancer therapeutics given its critical role in disease progression, however properties of the MYC gene and protein have made it a historically undruggable target. Omega’s unique approach has the potential to downregulate expression through epigenetic modulation by acting pre-transcriptionally to target MYC dysregulation at its source, a mechanism of action that could potentially lead to an enhanced efficacy and improved safety profile, for patients in need, compared to currently available treatments."

"HCC is one of the most rapidly increasing causes of cancer deaths worldwide, and MYC overexpression is associated with aggressive disease in up to 70% of these cases. Preclinical results of OTX-2002 showed downregulation of MYC in target cancer cells while sparing healthy cells and demonstrate the potential of this approach using Omega’s unique epigenomic modulation technology," added Ildefonso Ismael Rodriguez, M.D., Medical Oncologist and Clinical Investigator at Next Oncology and principal investigator of the site. "I look forward to evaluating OTX-2002 in the clinical setting and building on the potential of this first-in-class therapy."

The Phase 1/2 MYCHELANGELO I trial (NCT05497453) will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor 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. The study is expected to enroll approximately 190 patients at clinical trial sites in the United States, Asia, and Europe.

Omega has previously announced preclinical data supporting OTX-2002’s mechanism of action and antitumor activity in multiple in vitro and in vivo models. The Company demonstrated OTX-2002’s ability to modulate the epigenetic profile of MYC and control its expression pre-transcriptionally in multiple in vitro studies. Preclinical studies also showed that OTX-2002 induced robust antitumor activity alone and in combination with standard of care therapies in multiple in vivo HCC models. Additionally, treatment with OTX-2002 resulted in successful pre-transcriptional downregulation of hepatocyte MYC expression in non-human primates. Cumulatively, these preclinical data support the clinical potential of OTX-2002 to provide a novel treatment strategy for patients with HCC.

About Hepatocellular Carcinoma and MYC
Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths worldwide and represents an unmet clinical need with few therapeutic options. Tyrosine kinase inhibitors (TKIs) have been used as a systemic therapy for HCC, but patients frequently develop resistance with oncogenic MYC identified as a correlating prognostic factor. The MYC oncogene is associated with aggressive disease in up to 70% of patients with HCC.

About OTX-2002
OTX-2002 is a first-in-class Omega Epigenomic Controller in development for the treatment of hepatocellular carcinoma (HCC). OTX-2002 is an mRNA therapeutic delivered via lipid nanoparticles (LNPs) and is designed to downregulate MYC expression pre-transcriptionally through epigenetic modulation while potentially overcoming MYC autoregulation. MYC is a master transcription factor that regulates cell proliferation, differentiation and apoptosis and plays a significant role in more than 50% of all human cancers. OTX-2002 is currently being evaluated in the Phase 1/2 MYCHELANGELO I trial in patients with relapsed or refractory HCC and other solid tumor types known for association with the MYC oncogene; visit clinicaltrials.gov (NCT05497453) for more details.