Poster Presentation Highlights MDL-001’s Pan-Viral Activity Across HBV, HCV, and HDV, Including Co-Infection; A Novel Therapeutic Backbone for WHO 2030 Elimination Goals.
San Diego, Calif. — December 8, 2025 — Model Medicines, a leading generative AI biotech, today announced that preclinical data for its lead antiviral candidate, MDL-001, will be presented at HEPDART 2025, which celebrates its 30th year advancing therapeutics for viral liver disease. The 2025 meeting, themed “New Therapeutics for Chronic Hepatitis and Viral Liver Disease: Discovery, Translation, and Clinical Application,” will be held in Honolulu, Hawaii, from December 7–11, 2025. The presentation, titled "Oral Thumb-1 polymerase inhibitor MDL-001 achieves preclinical HCV and HBV proof-of-concept, including HCV/HBV co-infection and equivalence to sofosbuvir", will be delivered by Virgil Woods Jr., Ph.D., and will showcase MDL-001's equivalence to sofosbuvir in HCV, activity against HBV and HDV, and dual activity in HCV/HBV and HDV/HBV coinfections, as well as differentiated safety and resistance profile. The data include findings from humanized mouse models, suppression of co-infection, liver PK far exceeding EC90s, and resistance mapping confirming Thumb-1 polymerase targeting.
The full preclinical data package for MDL-001 is available on Model Medicines’ website.
MDL-001 is a first-in-class, oral, direct-acting broad-spectrum antiviral that targets the conserved Thumb-1 domain of the viral RNA-dependent RNA polymerase (RdRp). The molecule has demonstrated preclinical efficacy across six viral families, including the hepatitis viruses HBV, HCV, and HDV. The data underscore its potential as a foundational agent in finite-duration, curative regimens for hepatitis.
Preventing Complications in HCV/HBV Co-Infection
Dual infection with hepatitis C and hepatitis B is clinically complex and poses serious treatment risks. When HCV is cleared using standard direct-acting antivirals, HBV reactivation can occur, sometimes leading to fulminant hepatitis and liver failure. MDL-001’s dual antiviral activity across HCV and HBV offers a potential direct solution by suppressing both viruses simultaneously. This feature may reduce the risk of reactivation and simplifies treatment by eliminating the need for additional prophylactic HBV therapy during HCV treatment, improving safety and efficacy for co-infected patients.
Standard HCV therapies like sofosbuvir carry an FDA boxed warning for HBV reactivation. MDL-001’s dual activity against HCV and HBV addresses this clinical risk directly by concurrently suppressing both viruses, potentially eliminating the need for prophylactic HBV therapy. This represents a major advance in simplifying safe, single-regimen treatment for co-infected patients.
Addressing the Cure Gap in Hepatitis B and D
MDL-001 has the potential to address the key shortcomings of current hepatitis B therapy, which relies on lifelong suppressive nucleos(t)ide analogs (NAs). These regimens rarely achieve a functional cure and have limited patient uptake. By targeting a novel viral mechanism, MDL-001 offers a complementary path to viral suppression and potentially to sustained antigen clearance, positioning it as a critical component in multi-drug cure strategies. Unlike injectable HDV treatments such as bulevirtide, MDL-001 is orally bioavailable and broadly active, which may drive significantly improved patient access and adherence.
Positioning MDL-001 for Elimination Campaigns
The World Health Organization and United Nations have committed to eliminating viral hepatitis as a major public health threat by 2030, including a 65% reduction in related mortality. This effort targets not just hepatitis C, but also hepatitis B and the particularly deadly hepatitis D virus. MDL-001’s pan-hepatic activity across HCV, HBV, and HDV aligns directly with this mission. Its potency, oral formulation, and differentiated pharmacology support the potential for ultra-short treatment durations and cost-efficient regimens, making it a strong candidate for integration into national and global elimination campaigns. With the ability to simplify care in co-infected patients and address viral suppression across hepatitis B, C, and D, MDL-001 offers a strategic, cross-cutting platform well suited to national and international hepatitis elimination efforts.
Expanding Protection for Immunocompromised and Fibrotic Patients
Chronic liver disease, particularly advanced fibrosis and cirrhosis, heightens vulnerability to systemic complications when respiratory infections are superimposed. Co-infection with viruses like SARS-CoV-2 or influenza can trigger acute-on-chronic liver failure (ACLF), a condition with high mortality, especially in immunocompromised patients. Additionally, cytokine storms induced by severe respiratory infections may further destabilize hepatic function in patients with chronic hepatitis B, C, or D.
MDL-001’s unique ability to concurrently suppress both hepatic and respiratory viruses offers a new clinical paradigm for protecting this vulnerable population. By addressing both the underlying viral hepatitis and the acute triggers of systemic decompensation, MDL-001 could reduce the incidence of ACLF and mitigate immune overactivation scenarios in cirrhotic or immunocompromised patients. This cross-coverage simplifies care, reduces pharmacologic burden, and supports safer management during seasonal or pandemic respiratory outbreaks.
Presentation Details
Session: Poster Session
Presenter: Virgil Woods Jr., Ph.D.
Title: Oral Thumb-1 polymerase inhibitor MDL-001 achieves preclinical HCV and HBV proof-of-concept, including HCV/HBV co-infection and equivalence to sofosbuvir.
Conference: HEPDART 2025 | December 7–11, 2025 | Honolulu, Hawai‘i |
Hepatic Indications: MDL-001 and 50mg/kg sofosbuvir (Gilead) were both found to reduce plasma viral load by 3.3 log10, relative to vehicle, in a head-to-head 28-day in vivo study of HCV infection conducted at Scripps Research. On day 28 the viral load in both groups was within the limit of detection of the experiment, indicating viral clearance.
"The equivalence we've observed between MDL-001 and sofosbuvir in HCV models is remarkable," said Philippe Gallay, Ph.D., Professor of Immunology at Scripps Research. "Importantly, MDL-001's dual activity against both HCV and HBV offers a compelling advantage to sofosbuvir in co-infected patients, potentially reducing the risk of HBV reactivation after sofosbuvir therapy, a clinically significant concern with current regimens."
Commercial Potential
Sofosbuvir is an established standard of care in HCV and a commercial blockbuster, with multi-billion-dollar annual revenues. The drug generated over $1.5 billion in 2024 revenues per Gilead’s 2024 10-K (Epclusa (sofosbuvir/velpatasvir) $1.596 billion). The data reported here position MDL-001 as a next-generation, cornerstone chronic hepatitis therapy that could either replace or complement existing standards of care.
MDL-001 is currently completing IND-enabling studies with a regulatory submission targeted for 2026.
About Model Medicines
Model Medicines is a biotechnology company engineering
first-in-class small molecules that target the biological linchpins underlying
disease. The company’s research spans virology, oncology, and inflammation,
with programs designed around conserved biological choke points that drive
multiple pathologies. Model Medicines had discovered a direct-acting,
non-nucleoside, broad-spectrum antiviral and a BRD4 inhibitor with no
measurable activity against BRD2/3. Its work demonstrates how large-scale
computation can uncover entirely new classes of drugs once thought unreachable.
Model Medicines is advancing a new generation of therapeutics that redefine
what is possible in modern drug discovery. Learn more at www.modelmedicines.com.
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