Data Presented At IDWeek 2025 To Demonstrate Broad-Spectrum Antiviral Activity And In Vivo Proof-of-Concept Across Both Respiratory And Liver Viruses
San Diego, CA — October 15, 2025 — Model Medicines, an AI-first biotechnology company developing first-in-class small-molecule therapeutics, today announced that it will present new preclinical data for MDL-001, a direct-acting, oral, well-tolerated, broad-spectrum antiviral targeting the Thumb-1 domain of viral RNA-dependent RNA polymerases (RdRp), during IDWeek 2025 in Atlanta, Georgia, October 19–22, 2025.
A link to the IDWeek 2025 presentation can be found here.
This forthcoming data represents a significant step forward in addressing the clinical need for safe, direct-acting, orally available antivirals that act across multiple viral families. By introducing a novel mechanism of action and unprecedented broad-spectrum activity, MDL‑001 may expand therapeutic options for patients facing both acute respiratory and chronic hepatic viral infections.
Details of the presentations are as follows:
Title: “MDL-001:
A Broad-Spectrum Antiviral Targeting the Thumb-1 Domain of Viral Polymerases”
Date: Monday, October 20, 2025
Time: 3:39 PM - 3:51 PM US ET
Presentation Number: 232
Session: New Anti-Infective Agents
Location: B213-B214
Presenter: Virgil Woods, Ph.D., Senior Scientist at Model Medicines
“We look forward to sharing new data demonstrating how MDL-001 targets a previously undiscovered, conserved, broad-spectrum viral target,” said Virgil Woods, PhD, Senior Scientist at Model Medicines and presenting author. “Its unique mechanism of action offers a definitive path to the creation of oral, well-tolerated, broad-spectrum, direct-acting, non-nucleoside, antivirals for the first time in medical history.”
Key Findings of Preclinical Data Readout
The upcoming presentation will demonstrate comprehensive preclinical validation of MDL-001’s direct-acting mechanism of action, in vitro and in vivo broad-spectrum antiviral activity, oral pharmacokinetics, and safety profile. Key highlights will include:
● Broad-spectrum activity: Activity in both respiratory and liver viral disease - across six viral families, including SARS-CoV-2, Influenza A/B, RSV, Hepatitis B, Hepatitis C, and Hepatitis D.
● In vivo efficacy across three viral indications:
○ HCV: Viral load reduced by 3.1‑log₁₀ following oral dosing.
○ HBV: Viral load reduced by 1.8‑log₁₀ following oral dosing.
○ SARS‑CoV‑2: Oral MDL‑001 achieved non‑inferior inhibition of symptomatic progression versus subcutaneous remdesivir.
● Mechanism: Direct-acting, non‑nucleoside inhibitor targeting the Thumb‑1 domain of viral RNA‑dependent RNA polymerase (RdRp).
● Mechanism Validation: 8 weeks of HCV passaging produced an MDL‑001‑resistant NS5B Thumb‑1 site mutation (P495S). Substitutions at P495 consistently and uniquely confer resistance to Thumb‑1 inhibitors, while P495S variants exhibit two‑fold lower replicative capacity than wild‑type NS5B.
● Oral Pharmacokinetics: Tissue concentrations in the lung and liver exceed EC90 values by large margins.
● Safety: Evaluated in 400+ animals with no observed adverse events.
● IND readiness: pivotal efficacy and safety studies completed; AMES, hERG, and Micronucleus tests passed. CMC scale‑up has been initiated.
MDL‑001 is a first-in-class oral, well-tolerated, direct-acting antiviral with unprecedented broad-spectrum activity, representing a significant advancement in antiviral drug development.
Rapid Discovery and Expert Collaboration
Model Medicines’ virology program moved from program concept to the discovery of both the novel broad-spectrum Thumb-1 site and MDL-001 in under 100 days. The company then validated the program in consultation with a global coalition of leading Key Opinion Leaders (KOLs). This collaborative effort united expertise in virology, pharmacology, and translational medicine to accelerate program validation.
The KOL research consortium includes:
● David “Davey” Smith, MD, MAS, FACP, FIDSA – UC San Diego; Co-Chair, ACTIV-2
● Philippe Gallay, PhD – Scripps Research
● Adolfo García-Sastre, PhD and Kris White, PhD – Icahn School of Medicine at Mount Sinai
This expert collaboration enabled the validation of the conserved Thumb-1 domain as a novel, broad-spectrum antiviral target and the validation of MDL‑001 as the first direct-acting, orally available, broad-spectrum drug to exploit this novel mechanism.
“The presentation at IDWeek 2025 will highlight MDL-001’s potential to redefine antiviral therapy,” said David “Davey” Smith, MD, MAS, FACP, FIDSA, Assistant Vice Chancellor of Clinical and Translational Research and Director, Altman Clinical and Translational Research Institute at UCSD, and co-author of the study. “Its well-tolerated, broad-spectrum, direct-acting profile could offer physicians a much-needed oral option for both respiratory and hepatic viral infections.”
MDL-001 Clinical Plan
MDL‑001 has established robust in vivo efficacy, superior pharmacokinetics, and exceptional safety across multiple viral families. Pivotal preclinical studies are complete, and IND‑enabling work is in its final phase. Model Medicines plans regulatory submission in 2026, with clinical trial initiation to follow immediately upon clearance.
“MDL‑001 represents the next generation antiviral therapy - direct-acting, oral, well-tolerated and broad-spectrum,” said Daniel Haders II, PhD, Founder and CEO of Model Medicines. “Its reproducible, multi‑family efficacy, excellent safety, and strong translational potential make it a compelling first‑in‑class therapeutic candidate.”
About MDL-001
MDL-001 is an orally available, direct-acting antiviral that targets the Thumb-1 subdomain of viral RNA-dependent RNA polymerase (RdRp), a conserved, previously unrecognized druggable site across numerous RNA viruses. Its non-nucleoside, non-protease mechanism of action and unprecedented broad-spectrum activity differentiates it from existing direct-acting antivirals in preclinical and early clinical studies. MDL-001 is advancing toward regulatory submission.
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 infectious disease, oncology, and inflammation, with programs designed around conserved molecular 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.
