nChroma Bio has presented new preclinical data supporting its lead candidate, CRMA-1001, as a potential functional cure for chronic hepatitis B virus (HBV). The findings were shared at The Liver Meeting 2025 of the American Association for the Study of Liver Diseases (AASLD).

The preclinical data, which earned a Poster of Distinction, demonstrate that CRMA-1001 can achieve durable HBV antigen loss and DNA silencing across several models. The company is now preparing to begin its first-in-human Phase 1 study in early 2026, following regulatory submissions for Clinical Trial Applications.

Chronic HBV affects nearly 300 million people globally, with current antiviral therapies largely focused on controlling the virus rather than achieving a cure. nChroma Bio’s candidate uses an epigenetic silencing mechanism to suppress viral antigens and replication at the transcriptional level without cutting or nicking DNA. The approach targets both covalently closed circular DNA (cccDNA) and integrated HBV DNA (intDNA), aiming to achieve long-term viral silencing.

The preclinical results presented at AASLD showed that in both transgenic and AAV-HBV mouse models, CRMA-1001 led to more than a three-log reduction in hepatitis B surface antigen (HBsAg) levels, with effects sustained for at least six months. At the highest dose, 90% of treated mice showed undetectable HBsAg and HBV DNA.

CRMA-1001 also demonstrated compatibility with standard-of-care nucleoside analogue entecavir, with combination therapy producing greater depth and durability of HBV DNA suppression compared with single-agent use.

Safety and durability were supported by non-human primate data using PCSK9 as a surrogate target to evaluate the same delivery mechanism and epigenetic effector. These studies indicated durable silencing lasting over a year after a single dose, alongside an acceptable safety, specificity and biodistribution profile.

Gene expression and DNA methylation profiling confirmed the specificity of CRMA-1001, identifying no unverified targets in liver, spleen or adrenal tissue.

Jenny Marlowe, chief development officer of nChroma Bio, said: “For the millions living with HBV, today’s therapies offer control, not cure. Our findings showcase how epigenetic silencing could change that paradigm. As we prepare to enter the clinic next year, we see the potential for a single course of treatment with lasting freedom from the virus.”

Jeff Walsh, chief executive officer of nChroma Bio, added: “Epigenetic silencing represents a fundamental shift in how we think about treating chronic diseases. We’re moving beyond incremental advances and aiming for functional cures and see a future where CRMA-1001 can transform the lives of patients living with HBV and set the stage for a new era of genetic medicine.”

nChroma Bio said it expects to begin its first clinical trial of CRMA-1001 in early 2026, subject to regulatory clearance.