nChroma Bio's Epigenetic Therapy CRMA-1001 Shows Promise as Potential Functional Cure for Chronic Hepatitis B
核心洞察
nChroma Bio (搜索) presented preclinical data at AASLD 2025 showing CRMA-1001 achieved >3 log reduction in hepatitis B surface antigen and undetectable HBV DNA in 90% of treated mice.
The epigenetic silencer uses DNA methylation to suppress viral antigens without cutting DNA, targeting both covalently closed circular DNA and integrated HBV DNA.
The company has initiated Clinical Trial Applications and plans to begin Phase 1 first-in-human studies in early 2026.
nChroma Bio (搜索) announced promising preclinical results for CRMA-1001, an epigenetic silencer designed as a potential functional cure for chronic hepatitis B virus (HBV), at The Liver Meeting® 2025 of the American Association for the Study of Liver Diseases (AASLD). The data, which included a Poster of Distinction, demonstrated the therapy's ability to achieve durable HBV antigen loss and DNA silencing across multiple preclinical models.
Chronic HBV affects nearly 300 million people worldwide, with current antiviral treatments rarely achieving functional cure, resulting in patients requiring lifelong viral suppression regimens. CRMA-1001 represents a novel approach that leverages DNA methylation to suppress viral antigens at the transcriptional level without cutting or nicking DNA, targeting both covalently closed circular DNA (cccDNA (搜索)) and integrated HBV DNA (intDNA (搜索)).
Robust Efficacy Across Multiple Models
In transgenic and AAV-HBV mouse models, CRMA-1001 demonstrated significant antiviral activity with >3 log reduction in hepatitis B surface antigen (HBsAg) and sustained durability for 6 months at the time of analysis. Treatment at the highest dose resulted in undetectable HBsAg from both cccDNA (搜索) and intDNA (搜索), along with undetectable HBV DNA in 90% of treated mice.
The therapy also showed compatibility as combination therapy with entecavir, the standard-of-care nucleoside analogue. Combination therapy led to greater depth and durability of HBV DNA suppression compared with single-agent treatment.
Safety and Durability Profile
Preclinical studies in non-human primates supported both the durability and safety of the epigenetic approach. Using PCSK9 as a surrogate target to demonstrate target engagement and safety with the same epigenetic effector and lipid nanoparticle (LNP) delivery vehicle utilized in CRMA-1001, researchers demonstrated durable PCSK9 silencing sustained for over one year with a single dose. CRMA-1001 exhibited an acceptable safety, specificity, and biodistribution profile.
Gene expression and DNA methylation profiling assays implemented to assess the specificity of CRMA-1001 did not identify any unverified targets in liver, spleen or adrenal cells, confirming the therapy's specificity.
Clinical Development Timeline
nChroma Bio (搜索) has initiated submission of Clinical Trial Applications (CTAs) for CRMA-1001. Pending regulatory clearance, the company anticipates initiating a Phase 1 first-in-human study in early 2026.
"For the millions living with HBV, today's therapies offer control, not cure. Our findings showcase how epigenetic silencing could change that paradigm," said Jenny Marlowe, PhD, Chief Development Officer of nChroma Bio (搜索). "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."
Novel Mechanism of Action
The epigenetic silencing approach represents a departure from traditional antiviral strategies. Rather than directly inhibiting viral replication or cutting viral DNA, CRMA-1001 uses DNA methylation to transcriptionally silence viral genes, potentially offering a more durable solution for HBV treatment.
"Epigenetic silencing represents a fundamental shift in how we think about treating chronic diseases," said Jeff Walsh, Chief Executive Officer of nChroma Bio (搜索). "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."
The data was featured in three accepted abstracts at The Liver Meeting® 2025, with Sarah Voytek, PhD, Vice President of Translational Medicine & Global Program Lead at nChroma Bio (搜索), participating in the Hepatitis B Special Interest Group session featuring top high-impact abstracts showcasing the latest advances in HBV research.