Thomas McCauley, PhD, on Potential Advantages of Epigenetic Therapy Over Small Molecule, Gene Therapy

This is the third part of an interview with Thomas McCauley, PhD. For the second part, click here.

“A number of really important disease genes are very auto regulated. So, if they're important to the cell, the cell is going to have many redundant layers of control to keep it at a certain level. If you try to tamp it down, for example, an oncogene, the harder you squeeze it, the more it's going to create of itself... It's very difficult to get every single molecule and unless you do that, this transcriptional sort of spigot keeps churning out more and more of the molecule you're trying to soak up. You end up having to put in more and more drug, and ultimately, you run into some kind of dose-limiting toxicity. Whereas targeting pretranscriptionally, you avoid all of those considerations.”

Omega Therapeutics is developing MYC-targeted Omega Epigenomic Controller (OEC) therapy to target MYC-expressing tumors. Preclinical data presented at the 2023 American Society of Clinical Oncology (ASCO) meeting, held June 2-6, 2023, held both virtually and in Chicago, Illinois, demonstrated antitumor activity in mouse models treated with the OEC therapy in combination with checkpoint blockade immunotherapy.

The preclinical data were presented by Thomas McCauley, PhD, chief scientific officer, Omega Therapeutics. Omega’s lead, MYC-targeted OEC candidate, OTX-2002, is currently being evaluated in a phase 1/2 clinical trial (NCT05497453) as a monotherapy and in combination with standard of care for patients with hepatocellular carcinoma and other MYC-expressing solid tumor types. CGTLive spoke with McCauley to learn more about the advantages of epigenetic modes of therapy compared with small molecules and gene editing or replacement therapy.

REFERENCE

Moore Y, Senapedis W, Gallagher K, et al. Effect of MYC-targeting programmable epigenetic mRNA therapeutics on TME and immunotherapy responses. Presented at: 2023 ASCO Meeting; June 2-6; Chicago, Illinois. Poster #437