Oral presentation unifies the respiratory and hepatic programs. The first-in-class, direct-acting, broad-spectrum, Thumb-1 polymerase inhibitor demonstrates single-agent activity against influenza, RSV, SARS-CoV-2, HCV, HBV, and HDV, including activity against oseltamivir-resistant influenza and oral in vivo proof-of-concept.
SAN DIEGO —
Model Medicines
,
an AI-first biotechnology company developing first-in-class therapeutics
against multi-indication biological choke points, today announced that it will
present new preclinical data at the 45th Annual Meeting of the American Society
for Virology (
ASV
2026
), to be held July 27–30, 2026, on the University of Minnesota
Twin Cities campus in Minneapolis, MN. The event is being supported by Gilead
Sciences Foundation, Elanco, GSK, Roche, Moderna, and Cocrystal Pharma, among
others.
The oral presentation will be delivered by
Daniel Haders, PhD, Founder and CEO of Model Medicines. The data advance
MDL-001 toward two first-in-class therapeutic goals: a universal direct-acting
antiviral for influenza-like illness (influenza, RSV, and coronaviruses) and a
universal direct-acting antiviral for chronic hepatitis (hepatitis C, hepatitis
B, and hepatitis D). The ASV presentation is the first to report both goals as
a single cross-family dataset.
ASV 2026 Oral Presentation
Presenter:
Daniel Haders, PhD, Founder and CEO, Model Medicines
Title:
MDL-001, an oral Thumb-1 polymerase inhibitor, demonstrates
broad-spectrum antiviral activity across six viral families with oral in vivo
proof-of-concept
Workshop:
W44 — Antiviral Therapies II
Program Number:
W44-3
Abstract ID:
4518354
Date:
July 29, 2026
Time:
7:00–7:15 PM CT (workshop session: 6:30–8:00 PM CT)
Location:
Room PWB 2-470, Phillips-Wangensteen Building
Authors:
Daniel Haders, Virgil Woods, Tyler Umansky, Sean Russell, Asha Goodman,
Michael Bobardt, Briana McGovern, Kris M. White, Adolfo García-Sastre, William
Brubaker, Philippe Gallay, Davey Smith
Affiliations: Model Medicines; Scripps Research; Icahn
School of Medicine at Mount Sinai; Farmington Pharma Development; University of
California, San Diego.
Each winter, clinicians face a recurring
tripledemic of influenza, RSV, and SARS-CoV-2 that imposes hundreds of millions
of infections and hundreds of thousands of deaths worldwide every year.
[1]
In a non-pandemic year in the U.S. alone, adults experience two to six of these
respiratory viral illnesses and children approximately six to eight, at an
economic cost exceeding $100 billion.
[2]
,
[3]
Despite this recurring toll, no single-agent antiviral is approved to treat the
annual convergence of the tripledemic, and the world is no better prepared for
the next respiratory pandemic than it was for the last.
Chronic viral hepatitis is a health crisis of
comparable scale. Hepatitis B and C infections persist in 254 million and 58
million people worldwide, respectively.
[4]
An estimated 5–15 million carry both viruses at once, yet most will never be
diagnosed. Only 13% of HBV infections and 36% of HCV infections are identified
globally, and fewer than 1% of co-infected patients know their status.
Co-infection is not merely additive. Patients carrying both viruses are over
100-fold more likely to develop hepatocellular carcinoma than uninfected
individuals.
[5]
Compounding the danger, every FDA-approved HCV direct-acting antiviral (DAA)
carries a boxed warning for the risk of hepatitis B virus (HBV) reactivation in
patients with current or prior HBV infection. This reactivation can lead to
fulminant hepatitis, liver failure, or death. This FDA-mandated warning, added
in 2016, applies to all DAA regimens, such as Epclusa, Harvoni, Mavyret, and
others.
Together, these gaps point to a single,
persistent, and largely unaddressed need: one oral agent with broad-spectrum,
direct-acting activity across the RNA viruses that drive both crises. For forty
years, that molecule has been considered impossible to build.
MDL-001 is designed to meet that need. It is
the first direct-acting, non-nucleoside antiviral shown to be potent across
multiple RNA virus families, and the first therapeutic of any mechanism to
match or exceed multiple approved standards of care across RNA virus families
in preclinical models. Its activity across both acute respiratory and chronic
hepatic infection, combined with oral bioavailability, favorable
pharmacokinetics, and a clean preclinical safety profile, positions the
compound as a potential first-in-class therapy that could collapse multiple
fragmented treatment paradigms into one.
Model Medicines has reported the respiratory
and hepatic arms of the MDL-001 program separately over the past year at IDWeek
2025
[6]
,
AASLD 2025
[7]
,
HepDART 2025
[8]
,
CROI 2026
[9]
,
ESCMID Global 2026
[10]
,
SERVC 2026
[11]
and EASL 2026
[12]
.
“MDL-001 is
the first Thumb-1 inhibitor to demonstrate antiviral activity across six viral
families,” said Daniel Haders, PhD, Founder and CEO of Model Medicines. “The
field held that allosteric pockets on viral polymerases diverge too rapidly to
support cross-family targeting. Our work shows the RdRp Thumb-1 pocket is
conserved and cryptic, and that the right chemistry engages it across families.
ASV convenes the virologists best equipped to interrogate that claim, and we
look forward to the discussion in Minneapolis.”
The American Society for Virology is the
largest virology society in the world. ASV meetings are among the largest and
most important virology conferences globally, providing a forum for discussion
and collaboration among scientists working across all aspects of virology, from
basic research to vaccines and antiviral therapeutics. Program details are
available at
.
About the Target: RdRp Thumb-1, A Conserved and Druggable Allosteric
Target
Conventional scientific wisdom holds that
allosteric sites on viral polymerases diverge too rapidly to enable
broad-spectrum direct-acting antiviral (DAA) development. Model Medicines
overturned this assumption by demonstrating the structural conservation of the
RNA-dependent RNA polymerase (RdRp) Thumb-1 allosteric pocket across viral
families. The Thumb-1 site governs an essential mechanism for viral
replication. The Thumb-1 pocket interacts with the viral Λ1-loop to control an
indispensable conformational change required for polymerase initiation. Viruses
cannot abandon this mechanism without sacrificing their replicative fitness.
This target discovery is the biological foundation for Model Medicines’
Virology Program.
Data on RdRp Thumb-1 can be found
here
. The corresponding preprint can be found
here
.
About MDL-001: Discovery and Preclinical Profile
Model Medicines utilized its AI-driven
GALILEO™ platform to discover novel broad-spectrum inhibitor chemistry for this
target within a multi-scaffold Markush structure. The research team trained
GALILEO™ on a proprietary dataset spanning multiple viral families. This
training enabled the model to learn the structural and chemical features
required for broad-spectrum Thumb-1 inhibition.
A library of potent inhibitors has been
discovered, reduced to practice, and validated. Specifically, MDL-001 is the
first DAA shown to be potent against multiple viral families in vitro:
Orthomyxoviridae,
Pneumoviridae, Coronaviridae, Flaviviridae, Kolmioviridae, and Hepadnaviridae.
MDL-001 has demonstrated multi-log antiviral efficacy against influenza,
SARS-CoV-2, HCV, and HBV in animal models. Furthermore, in vivo results
demonstrate superiority or equivalence to multiple standards of care, including
sofosbuvir, oseltamivir, remdesivir, and nirmatrelvir. Model Medicines plans to
Investigational New Drug (IND) application with the FDA for MDL-001 in
2027.
The full preclinical data readout can be found
here
. The corresponding preprint can be found
here
.
About
GALILEO™
GALILEO™ is Model Medicines’ proprietary,
peer-reviewed, end-to-end multimodal generative AI drug discovery platform
designed to discover and de-risk therapeutics against challenging and
"undruggable" biological targets. Powered by Built-for-Purpose
datasets and an ensemble of generative AI and zero-shot models, GALILEO™
integrates target discovery, tera-scale ultra-large virtual screening, ADMET
prediction, compound synthesis, and automated lead optimization. By leveraging
3D protein structure data and strict chemical novelty metrics, the platform
enables early, high-confidence compound prioritization with industry-leading
prospective hit rates and exceptional chemical novelty. GALILEO™ powers Model
Medicines' internal pipeline, including lead candidates MDL-001 and MDL-4102.
The platform was validated through peer-reviewed publication in the American
Chemical Society (ACS) journal Chemical Research in Toxicology.
About Model Medicines
Model Medicines is an AI-first 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 has discovered a
direct-acting, non-nucleoside, broad-spectrum antiviral (MDL-001) and a potent,
selective, and novel BRD4 inhibitor (MDL-4102). 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
.
Media Contact
Patrick O’Neill
Head of
Partnerships & Investor Relations
media@modelmedicines.com
[1]
Luong QXT, Hoang PT, Ho PT, Ayun RQ, Lee TK,
Lee S. Potential broad-spectrum antiviral agents: a key arsenal against newly
emerging and reemerging respiratory RNA viruses. Int J Mol Sci. 2025;26:1481.
[2]
Rossignol JF. Rethinking methods used to
evaluate effectiveness of therapeutics for COVID-19 and other viral respiratory
illnesses. Future Virol. 2022;17:67-69.
[3]
Hanage, W. P., & Schaffner, W. (2025).
Burden of Acute Respiratory Infections Caused by Influenza Virus, Respiratory
Syncytial Virus, and SARS-CoV-2 with Consideration of Older Adults: A Narrative
Review. Infectious diseases and therapy, 14(Suppl 1), 5–37.
[4]
World Health Organization. Global hepatitis
report 2024: action for access in low- and middle-income countries. Geneva:
WHO; 2024.
[5]
Mavilia MG, Wu GY. HBV-HCV coinfection: viral
interactions, management, and viral reactivation. J Clin Transl Hepatol.
2018;6:296-305.
[6]
MDL-001: A Broad-Spectrum Antiviral Targeting
the Thumb-1 Domain of Viral Polymerases, Open Forum Infectious Diseases, Volume
13, Issue Supplement_1, January 2026, ofaf695.084,
[7]
MDL-001 As A Next Generation HCV Thumb-1
inhibitor With Clinical-Stage Safety, The Liver Meeting: 2025 Abstracts.
(2025). Hepatology (Baltimore, Md.), 82(S1), S1–S2308. Abstract 0088.
[8]
Oral Thumb-1 polymerase inhibitor MDL-001
achieves preclinical HCV and HBV proof-of-concept, including HCV/HBV
co-infection and equivalence to sofosbuvir. Paper presented at: HEPDART 2025;
December 7–11, 2025
.
[9]
MDL-001, a novel oral thumb-1 polymerase
inhibitor, shows efficacy in HCV/HBV in vitro and in vivo. Paper presented at:
Conference on Retroviruses and Opportunistic Infections (CROI); February 22–25,
2026; Denver, CO. Abstract 589.
[10]
MDL-001, an oral direct-acting Thumb-1
polymerase inhibitor, demonstrates broad-spectrum activity against influenza
viruses, respiratory syncytial virus, and SARS-CoV-2 with oral proof-of-concept
in mice. Abstract presented at: ESCMID Global 2026; April 18, 2026; Munich,
Germany. Abstract 5803
.
MDL-001, an oral direct-acting Thumb-1 polymerase inhibitor, demonstrates
single-agent efficacy against HCV/HBV co-infection in vitro, and achieves HCV
and HBV preclinical proof-of-concept. Abstract presented at: ESCMID Global
2026; April 18, 2026; Munich, Germany. Abstract 5778.
[11]
MDL-001, an oral direct-acting Thumb-1
polymerase inhibitor, demonstrates broad-spectrum activity against influenza
viruses, respiratory syncytial virus, and SARS-CoV-2 with oral proof-of-concept
in mice. Paper presented at: The 18th Southeastern Regional Virology Conference
(SERVC 2026), April 24–26, 2026
[12]
MDL-001, an oral direct-acting Thumb-1
polymerase inhibitor, demonstrates efficacy against HCV/HBV co-infection in
vitro, and achieves HCV and HBV preclinical proof-of-concept, including
equivalence to sofosbuvir, Journal of Hepatology, Volume 84, Supplement 1, May
2026, Pages S877-S878, THU-580.
(26)02352-4/abstract
