Oral MDL-001 Demonstrated Equivalence to Remdesivir and Sofosbuvir in Head-to-Head Animal Model Studies Performed at The Icahn School of Medicine at Mount Sinai and Scripps Research, and Superiority to Nirmatrelvir in a Literature Comparison of Equivalent Animal Models. The Potential First-in-Category, Direct-Acting, Broad-Spectrum Antiviral Targets A Novel Conserved Site on The Viral Polymerase Across Six Viral Families.
San Diego, Calif. — December 4, 2025 — Model Medicines, a leading generative AI biotech, today announced a major milestone in antiviral drug development, pandemic preparedness and biodefense: its lead candidate, MDL-001, has demonstrated in vivo superiority or equivalence to three current standards of care (Nirmatrelvir, Remdesivir and Sofosbuvir) in both acute respiratory and chronic hepatic viral infections.
MDL-001, an oral direct-acting broad-spectrum antiviral, achieved equivalency to both subcutaneously administered remdesivir (Gilead) in SARS-CoV-2 and oral sofosbuvir (Gilead) in Hepatitis C (HCV) in head-to-head preclinical studies. MDL-001 also achieved superiority to Nirmatrelvir (Pfizer) in a literature comparison of equivalent animal models. The drug has also demonstrated nanomolar EC90 potency against RSV, Influenza A/B, Hepatitis B (HBV), and Hepatitis D (HDV).
This is the first time a single oral small molecule has demonstrated efficacy across such a breadth of human viral infections and superiority or equivalency to multiple current standards of care (SoC), setting the stage for a new class of direct-acting, broad-spectrum antivirals targeting the Thumb-1 domain of viral RNA polymerases.
The full preclinical data package for MDL-001 is available on Model Medicines’ website.
Novel Broad-Spectrum Mechanism of Action (MoA)
Mechanistic studies conducted at Scripps Research validated that MDL-001 is a non-nucleoside, direct-acting inhibitor of the viral RNA-dependent RNA polymerase (RdRp), targeting a novel cryptic allosteric site (Thumb-1) conserved across multiple viral families. Preclinical data demonstrate in vitro and/or in vivo activity across:
● Respiratory viruses: SARS-CoV-2 (and variants), Influenza A/B, RSV
● Liver viruses: HCV, HBV, HDV
Superiority or Equivalence to Current Standards of Care
Respiratory Indications: Orally administered MDL-001 inhibited SARS-CoV-2 symptomatic progression equivalent to 100mg/kg subcutaneously administered remdesivir (Gilead) in a head-to-head in vivo study conducted at the Icahn School of Medicine at Mount Sinai. MDL-001 was also found to reduce SARS-CoV-2 lung viral loads by 2.7 log10 relative to vehicle on Day 3 post-infection as compared to nirmatrelvir (Pfizer), which reported a 1.9 log10 reduction on Day 4 post-infection for a 1000mg/kg BID oral dose in a study authored by Pfizer Worldwide Research and published in Science. Both studies were conducted in mouse-adapted models.
"A broad-spectrum, orally available antiviral therapeutic with a long half-life and favorable safety profile, deployable in outpatient settings, is an urgent unmet need," said Adolfo Garcia-Sastre, Ph.D., Director, Global Health and Emerging Pathogens Institute at the Icahn School of Medicine at Mount Sinai.
"This is an exciting next-generation oral SARS-CoV-2 and broad-spectrum antiviral candidate," added Kris White, Ph.D., Assistant Professor at Mount Sinai and NIH AViDD/ASAP Center Co-Investigator.
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."
Clinical Impact Potential
"MDL-001 has first-line treatment potential across multiple viral diseases," said Davey Smith, M.D., MAS, FIDSA, Assistant Vice Chancellor of Clinical and Translational Research at UC San Diego. "Physicians urgently need a safe, oral, broad-spectrum antiviral. Today, clinicians often must delay treatment decisions until diagnostic confirmation is available. A broadly active antiviral like MDL-001 would allow physicians to treat presenting patients immediately, before virus-specific testing results are available, helping avoid disease progression and complications. This would represent a meaningful shift in clinical practice and a long-overdue advance in antiviral care."
Commercial Potential
Nirmatrelvir, remdesivir, and sofosbuvir are established standards of care and commercial blockbusters, with multi-billion-dollar annual revenues. Nirmatrelvir’s global revenues for 2024 were $5.716 billion, per Pfizer’s 2024 10-K (Paxlovid (nirmatrelvir/ritonavir)). Remdesivir and Sofosbuvir collectively generated over $3.4 billion in 2024 revenues per Gilead’s 2024 10-K (Veklury (remdesivir) $1.799 billion and Epclusa (sofosbuvir/velpatasvir) $1.596 billion). The data reported here position MDL-001 as a next-generation, cornerstone antiviral therapy that could either replace or complement existing standards of care. Potential global revenues for a safe, oral, broad-spectrum antiviral like MDL-001 could exceed $10–$15 billion annually when the combined global burden of HCV, HBV, HDV, Influenza, COVID-19, and RSV is considered.
MDL-001 is currently completing IND-enabling studies with a regulatory submission targeted for 2026.
Biodefense and Pandemic Preparedness
A direct-acting, broad-spectrum antiviral has generally been considered to be unattainable.
MDL-001 has now demonstrated direct-acting antiviral activity across six major viral pathogens: HCV, HBV, HDV, Influenza, COVID-19, and RSV. This breadth of efficacy enables MDL-001 to treat known pathogens today and likely treat the unknown pathogens of tomorrow. The breadth of activity also enables a new antiviral treatment model where therapy can begin immediately upon exposure or presentation of symptoms, reducing treatment delays tied to diagnostics and supporting early intervention. MDL-001’s ability to inhibit complex co-infections further adds to its utility, along with its safety, tolerability, and oral dosing profile.
As a result, MDL-001 is well-suited for government stockpiling, pandemic preparedness, and frontline biodefense applications, including front-line deployment for the warfighter. Its cross-family mechanism positions it as a proactive medical countermeasure against known threats and potential future pathogens, including the BARDA-defined “Disease X.”
In 2025, Model Medicines was selected for the BARDA VANGUARD Hub for emerging technologies. The VANGUARD Hub supports the development of innovations in drug discovery and development, biomanufacturing innovations to increase speed, capacity, portability, and scalability, and innovations to improve clinical research and clinical care coordination.
About Model Medicines
Media Contact
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.
Patrick O’Neill
Head of Partnerships and Investor Relations
press@modelmedicines.com
