Model Medicines, an AI/ML pharmaceutical company, today announced preclinical data from a study of their orally available MDL-001 small molecule therapeutic against SARS-CoV-2, the virus that causes COVID-19 disease. In a live virus preclinical mouse study, once daily oral dosing of MDL-001 protected mice against COVID-19 mediated weight loss, a primary endpoint for COVID-19 in mice, in a statistically significant manner relative to vehicle (two-way ANOVA, P < 0.05). Furthermore, once daily, oral dosing of MDL-001 was found to be non-inferior to twice daily, subcutaneous dosing of remdesivir relative to the primary endpoint. MDL-001 was evaluated at the human equivalent dose previously shown to be safe and well tolerated, with no grade three or grade four adverse events, in a Phase 1 clinical trial in human subjects.

MDL-001 is an orally available compound with an extended half life. These features, along with its clinical safety profile, are prerequisites of any therapeutic which intends to treat mild/moderate COVID-19 disease patients, who currently have no FDA approved therapeutic options. The Model Medicines CHEMprint? platform discovered that MDL-001 was expected to inhibit SARS-CoV-2 replication via a broad spectrum antiviral target, indicating that MDL-001 may be effective against a broad array of RNA based viruses beyond SARS-CoV-2 and including SARS-CoV-2 variants.

"A broad spectrum, orally available antiviral therapeutic with an extended half-life and a well documented safety and toxicity profile that can be administered on an outpatient basis is an extreme and urgent unmet medical need, which would be a game-changer in the global fight against COVID-19." – Adolfo Garcia-Sastre, PhD, Director of the Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai

Model Medicines leveraged its CHEMprint? AI/ML drug discovery platform to discover MDL-001 and a number of additional small molecule compounds active against COVID-19. The company selected a small number of broad spectrum targets known to be conserved across SARS-CoV-2, corona viruses and RNA viruses, and developed target specific iterations of their cheminformatic AI/ML platform, CHEMprint?, to discover small molecule inhibitors in silico. The platform screened over 16,000 compounds and identified priority ranked compounds for each target. Priority ranked compounds were evaluated in vitro, in a HeLa2-ACE2 live virus assay to identify compounds potent against SARS-CoV-2 replication in partnership with Scripps Research, ranked the most influential institution in the world for innovation by Nature Index, as part of a drug discovery partnership announced last year.

The Model Medicines-Scripps Research Partnership led by Dr. Arnab Chatterjee, PhD, VP of Medicinal Chemistry for Calibr at Scripps Research, demonstrated that the CHEMprint? AI drug discovery platform had a 14.3% success rate for identifying active compounds and a 5.7% success rate for discovering compounds potent and selective against SARS-CoV-2, yielding multiple candidates for preclinical development. Recent publications by Dittmar et al, Yang et al and Chen et al using a traditional screening approach to discover small molecule therapeutics active against SARS-CoV-2 have recently reported hit rates ranging from 0.76% to 2.60% for active compounds. These results demonstrate that CHEMprint? was approximately 6-19x more effective than traditional screening methods for discovering compounds active against SARS-CoV-2.

"The Model Medicines-Scripps partnership has demonstrated that integrating artificial intelligence and machine learning models into the traditional High Throughput Screening drug discovery process can significantly improve the efficacy of drug discovery and accelerate the process of identifying treatments for urgent medical needs, while also reducing risk, time and investment for future drug development." – Dr.Arnab Chatterjee, PhD, VP of Medicinal Chemistry for Calibr at Scripps Research

To confirm these in silico and in vitro findings, Model Medicines partnered with Kris White, PhD, Assistant Professor of Microbiology, and Adolfo Garcia-Sastre, PhD, Director of the Global Health and Emerging Pathogens Institute, at the Icahn School of Medicine at Mount Sinai, a world leader in infectious disease research, whose laboratory has helped develop the global standard for COVID-19 mouse models for vaccine and therapeutic development. The Model Medicines funded study at Icahn Mount Sinai found that MDL-001 protected mice against the primary endpoint of COVID-19 relative to vehicle, and once daily, oral dosing of MDL-001 was non-inferior to twice daily, subcutaneous dosing of remdesivir.

Model Medicines has now developed a pipeline of broad spectrum antiviral drug candidates. MDL-001 is now completing IND enabling and dose optimization studies. Additional pipeline candidates are being advanced from in vitro to preclinical testing.

"I cannot say enough about the Model Medicines team and our partners at Scripps Research and Mount Sinai. Our antiviral program developed from hypothesis to animal model efficacy data in under 12 months, yielding multiple preclinical candidates including MDL-001, an orally available COVID-19 therapeutic that may finally bring a therapeutic option to mild/moderate COVID-19 disease patients who currently have none. This program demonstrates that the pharmaceutical industry is entering a new phase of AI/ML-drug discovery, enabled by fundamental, first-principles chemistry. " – Daniel Haders II, PhD, CEO Model Medicines

About Calibr and Scripps

Calibr is a first-of-its kind non-profit translational research Institute dedicated to creating the next generation of medicines. Part of Scripps Research and situated in the heart of San Diego's Torrey Pines Mesa biomedical research hub, Calibr is uniquely positioned to create and proliferate innovative partnerships. Calibr has created a broad therapeutic pipeline extending from early stage discovery through clinic-ready programs, including candidate medicines ranging from small molecules and peptides to biotherapeutics and cell-based therapies.

Scripps Research is ranked the most influential scientific institution in the world for its impact on innovation. A nonprofit research organization, Scripps expands basic knowledge in the biosciences and uses these fundamental advancements to develop profound innovations that improve well-being. Scripps researchers lead breakthrough studies that address the world's most pressing health concerns, accelerating the creation and delivery of medical breakthroughs to better human health across the globe. Our educational and training programs mold talented and committed students and postdocs into the next generation of leading scientists.

About The Mount Sinai Health System

The Mount Sinai Health System is New York City's largest academic medical system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. We advance medicine and health through unrivaled education and translational research and discovery to deliver care that is the safest, highest-quality, most accessible and equitable, and the best value of any health system in the nation. The Health System includes approximately 7,300 primary and specialty care physicians; 13 free-standing joint-venture centers; more than 410 ambulatory practices throughout the five boroughs of New York City, Westchester, and Long Island; and more than 30 affiliated community health centers. The Mount Sinai Hospital is ranked in U.S. News & World Report's "Honor Roll" of the top 20 U.S. hospitals and among the top in the nation by specialty: No. 1 in Geriatrics and top 20 in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Neurology/Neurosurgery, Orthopedics, Pulmonology/Lung Surgery, Urology, and Rehabilitation. Mount Sinai Kravis Children's Hospital is ranked in U.S. News & World Report's "Best Children's Hospitals" among the country's best in four out of 10 pediatric specialties. New York Eye and Ear Infirmary of Mount Sinai is ranked among the Top 20 nationally for ophthalmology. The Icahn School of Medicine at Mount Sinai is one of three medical schools that have earned distinction by multiple indicators: ranked in the top 20 by U.S. News & World Report's "Best Medical Schools," aligned with a U.S. News & World Report"Honor Roll" Hospital, and No. 14 in the nation for National Institutes of Health funding. Newsweek's "The World's Best Smart Hospitals" ranks The Mount Sinai Hospital as No. 1 in New York and top five globally, and Mount Sinai Morningside as top 20 globally, and "The World's Best Specialized Hospitals" ranks Mount Sinai Heart as No. 1 in New York and No. 5 globally and the Division of Gastroenterology as No. 5 globally. For more information, visit https://www.mountsinai.org or find Mount Sinai on Facebook, Twitter and YouTube.

About Model Medicines

Model Medicines is an AI/ML Drug Discovery company that reduces the time to bring a drug to market by 10+ years and the cost to bring a drug to market by $1B+. Model Medicines is transforming drug discovery by leveraging the historical compendium of drug development data, a drug and disease agnostic discovery platform, and unbiased AI to create Phase II/III ready drug candidates in months rather than years. The company has developed a robust pipeline of patent-pending therapeutics for infectious diseases, gastric disorders, neurological disorders, weight disorders and oncology. The company is based in San Diego, CA.

SOURCE Model Medicines