Glecaprevir/Pibrentasvir

Atea Pharmaceuticals said Tuesday that its experimental hepatitis C virus (HCV) treatment went toe-to-toe against Gilead Sciences' established therapy Epclusa (sofosbuvir/velpatasvir) in a Phase III trial — and held its own. According to the company, its once-daily combination of bemnifosbuvir, a nucleotide analogue polymerase inhibitor, plus NS5A inhibitor ruzasvir (BEM/RZR) met the primary endpoint of statistical non-inferiority versus Epclusa in the C-BEYOND trial, and could allow for a shorter treatment alternative for many patients.In the 905-patient modified intent-to-treat population, BEM/RZR produced a sustained virologic response (SVR) rate of 93.9% at week 24, compared to 94.8% for Epclusa.Among patients without cirrhosis (n=721) who received an eight-week course of BEM/RZR, the regimen achieved a 93.5% SVR rate versus 94.6% for the 12-week Epclusa regimen. In patients with cirrhosis (n=184), both treatments produced a 95.4% SVR rate after 12 weeks. Atea said safety was comparable between treatment arms, with no drug-related serious adverse events or early treatment discontinuations.The study was conducted in the US and Canada; Atea said its drug showed robust SVR rates across HCV genotypes that predominate in North America.Antiviral market dynamicsStill, Morgan Stanley analysts suggested the commercial prospects for BEM/RZR could be dampened by competition from established HCV therapies. Atea's shares ticked down about 6% on Tuesday. "While comparable efficacy and potential advantages of a shorter treatment duration for most patients, low risk of drug-drug interactions and no food effect reinforce BEM/RZR's profile, we continue to expect focus on antiviral market dynamics for HCV, including Gilead's Epclusa and Abbvie's Mavyret (glecaprevir/pibrentasvir)," they said in a note to clients.That next data point will come from Atea's second Phase III trial, called C-FORWARD, evaluating BEM/RZR outside North America. That study, which has enrolled more than 880 patients across 17 countries, is expected to report topline results in early 2027."Looking ahead, we believe C-FORWARD will provide important additional insight into the regimen's efficacy across HCV genotypes which are less common in the US and Canada," said Janet Hammond, Atea's chief development officer.

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