Epigenetic inhibitors have a reputation problem. The science is solid. The targets are real. But the drugs keep making patients too sick to stay on them. That’s been the story with BET inhibitors, HDAC inhibitors, and most of the EP300/CBP programs that have come before.
Opna Bio thinks the issue isn’t the target. It’s the pharmacokinetics. Their compounds are designed with high Cmax and short half-life, creating a pulsatile dosing profile that hits the target hard and clears fast. The idea is that you get effective engagement without the prolonged exposure that causes the GI and hematologic toxicities that have killed other programs in this class.
The FDA apparently sees enough promise to grant Fast Track designation to OPN-6602, an oral dual inhibitor of EP300 and CBP, for relapsed/refractory multiple myeloma in patients with at least four prior lines of therapy.
Opna Bio clinical pipeline
OPN-6602
Small molecule · EP300/CBP dual inhibitor · Relapsed/refractory multiple myeloma
OPN-2853 (zavabresib)
Small molecule · BET inhibitor · Myelofibrosis (combo w/ ruxolitinib)
OPN-6602 dose escalation expected to complete 2026
The mechanism goes after IRF4 and MYC, two transcription factors that drive myeloma cell survival. In preclinical data presented at ASH 2024, OPN-6602 showed 71% tumor suppression as monotherapy in myeloma xenograft models and complete tumor regression when combined with dexamethasone, pomalidomide, or mezigdomide. The Phase 1 trial is currently recruiting up to 130 patients at U.S. sites.
Opna has a second clinical asset too. OPN-2853 (zavabresib), a BET inhibitor, is in Phase 2 for myelofibrosis in combination with ruxolitinib, with early data showing spleens no longer palpable in 50% of evaluable patients.
The founding team matters here. Dr. Gideon Bollag, Dr. Douglas Hanahan, and Dr. Joseph Schlessinger have collectively been involved in multiple FDA-approved oncology drugs. The $38 million Series A from Longitude Capital and Northpond Ventures in 2022 launched the company, and the pipeline they acquired from Plexxikon gave them a head start.
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Fast Track won’t make or break OPN-6602. But it signals FDA engagement on a drug class that has historically frustrated developers and patients alike. If pulsatile dosing is the answer to the tolerability problem, Opna could be the company that finally makes epigenetic inhibitors work.
