Preclinical studies show epigenetic silencer CRMA-1001 achieves durable HBV antigen loss and DNA silencing across multiple models
Company preparing to initiate first-in-human Phase 1 study of CRMA-1001 in early 2026
BOSTON–(BUSINESS WIRE)–#AASLD25–nChroma Bio, a genetic medicines company advancing in vivo delivery of innovative cargoes to overcome the limitations of existing therapies, today announced new preclinical data presented at The Liver Meeting® 2025 of the American Association for the Study of Liver Diseases (AASLD). The results, including a Poster of Distinction, highlight the potential of the company’s lead candidate, CRMA-1001, to deliver a functional cure for chronic hepatitis B virus (HBV) through a novel epigenetic silencing approach.
Chronic HBV affects nearly 300 million people worldwide and current antiviral treatments rarely achieve functional cure, resulting in patients enduring lifelong viral suppression regimens. nChroma’s epigenetic silencer CRMA-1001 leverages DNA methylation to suppress viral antigens and, therefore, antigen production replication at the transcriptional level without cutting or nicking DNA, targeting both covalently closed circular DNA (cccDNA) and integrated HBV DNA (intDNA).
Data was featured in three accepted abstracts at The Liver Meeting® 2025, highlighting both the preclinical pharmacology and safety of CRMA-1001 and its demonstrated ability to achieve HBV surface antigen loss across multiple models. Sarah Voytek, PhD, Vice President of Translational Medicine & Global Program Lead at nChroma Bio, will participate in the Hepatitis B Special Interest Group (SIG) session, which features the top high-impact abstracts showcasing the latest advances in HBV research. She will deliver an in-person presentation spotlighting nChroma’s work on CRMA-1001 on Sunday, November 9 from 3:45-4:15 pm in the SIG Abstract Highlights Theater (Exhibit Hall).
Key Findings Presented at AASLD:
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Robust suppression of HBV biomarkers in multiple models
In transgenic and AAV-HBV mouse models, CRMA-1001 led to >3 log reduction in hepatitis B surface antigen (HBsAg) and demonstrated durability for 6 months at the time of analysis. Treatment at the highest dose resulted in undetectable HBsAg (from both cccDNA and intDNA) and undetectable HBV DNA in 90% of treated mice.
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Compatibility as combination therapy
CRMA-1001 was compatible with the standard-of-care nucleoside analogue entecavir. Combination therapy led to greater depth and durability of HBV DNA suppression compared with single-agent treatment.
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Durability and safety supported by preclinical studies in non-human primates
PCSK9 is used as a surrogate target to demonstrate target engagement and safety using the same epigenetic effector and LNP delivery vehicle utilized in CRMA-1001. Data from non-human primate studies demonstrated durable PCSK9 silencing sustained for over one year with a single dose. CRMA-1001 also exhibited an acceptable safety, specificity, and biodistribution profile.
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Robust assay confirms the specificity of CRMA-1001
Gene expression and DNA methylation profiling assays were implemented to assess the specificity of CRMA-1001 and did not identify any unverified targets in liver, spleen or adrenal cells.
“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. “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.”
The company 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.
“Epigenetic silencing represents a fundamental shift in how we think about treating chronic diseases,” said Jeff Walsh, Chief Executive Officer of nChroma Bio. “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.”
Our Approach
Leveraging complementary scientific approaches to pair potential best-in-class cargo with target-appropriate in vivo delivery methods, nChroma Bio is taking a disease-first approach to design customized genetic medicines. nChroma’s lead program is a best-in-class epigenetic editor in development as a potential functional cure for chronic hepatitis B.
About nChroma Bio
nChroma Bio is a genetic medicines company committed to addressing the limitations of existing therapies through a disease-first approach. By combining programmable in vivo delivery and gene-regulating technologies, nChroma is designing optimal solutions to deliver precise, potent and durable treatments for patients with high unmet needs. nChroma’s lead candidate, CRMA-1001, is a near clinical-stage, liver-directed epigenetic therapy in development as a potential functional cure for chronic hepatitis B. Guided by a world-class team at the forefront of genetic medicine, founded by renowned pioneers in the field, and supported by top-tier investors, nChroma is redefining targeted in vivo genetic medicine with the initial goal of treating diseases affecting the liver, blood, and central nervous system. For more information, visit nChromaBio.com and follow us on LinkedIn and X.
Contacts
Media Contact
Michelle Linn
Linnden Communications
michelle@linndencom.com