Gordian Biotechnology, Inc.

$60 Million in Venture Capital Raised to Date from World-Class Longevity, Biotech, and Technology InvestorsUnprecedented Approach Tests Hundreds of Gene Therapies Simultaneously in Individual Animals that are Highly Representative of Human Patients, Including Horses and MonkeysScreen Results Match Preclinical and Clinical Outcomes of Two Age-Related Indications with 80% Accuracy SAN FRANCISCO, April 26, 2024 /PRNewswire/ -- Gordian Biotechnology, an in vivo drug discovery and development company, today announced its platform that enables patient predictive, in vivo screening of hundreds of gene targets for FDA-recognized diseases of aging at a scale never before possible. The company has raised $60 million to date from investors including The Longevity Fund, Arctica Ventures, Athos Service GmbH, Gigafund, Founders Fund, Fifty Years, and former Novartis CEO Thomas Ebeling. Gordian Biotechnology Gene Therapy Testing Platform Gordian Biotechnology Scientists Process Tissue From a Mosaic Screening in the Company’s South San Francisco Headquarters Gordian Biotechnology Gene Therapy Testing Platform Traditional Drug Discovery Compared to Gordian Biotechnology Gordian Biotechnology In Vitro vs. In Vivo Gene Therapy Testing Gordian Biotechnology Single Gene Therapy Screen Results Gordian's Osteoarthritis (OA) program has screened hundreds of therapies in horses that acquired OA naturally and advanced dozens of therapies into human ex vivo validation studies. The results of these ex vivo studies matched screen predictions with 80% accuracy, and several hits progressed to additional testing and optimization. Gordian presented these findings at the Osteoarthritis Research Society International (OARSI) World Congress last week. In proof of concept experiments during initial development, Gordian introduced a pooled library of 50 gene therapies into a mouse model of metabolic-associated steatohepatitis (MASH). The therapies were evaluated using the company's proprietary in vivo screening platform, which successfully recapitulated 13 out of 16 clinical outcomes for targets where clinical data exists. Today, Gordian is completing in vivo screens of thousands of novel single and multi-target therapies across four indications in highly representative animal models across multiple species. "Gordian leverages recent advancements in single-cell sequencing and gene therapy to discover and predict what drugs will be successful in a way that would have been inconceivable just five years ago," said co-founder and CEO Francisco LePort. "Our ultimate goal is to help people wake up every day, more capable than the one before." The first and only platform of its kind Screening in vivo lets Gordian run the equivalent of hundreds of preclinical experiments in a matter of months and at a small fraction of the cost of traditional preclinical studies. Thus, enormous amounts of in vivo data are obtained at the beginning of the discovery process in animal models that would otherwise be impractical to use, allowing only the most efficacious therapeutics to move into development and clinical trials. The Gordian platform consists of three proprietary components working in concert: Patient Avatars™ are animal models with biology more representative of human patients than those typically used, such as horses for OA and monkeys for MASH. Because few animals are required for screening, Gordian can use large or advanced animal models that would otherwise be impractical for extensive preclinical studies. Often these animal models acquire the disease naturally and therefore have other conditions associated with biological aging, as a human would. Mosaic Screening™ is pooled in vivo screening that tests hundreds of therapies simultaneously in a single sick animal, the Patient Avatar. The diseased tissue becomes a "mosaic," where different cells receive different barcoded therapies. The therapies are introduced at a low dose, such that each perturbed cell is separated by diseased tissue unperturbed by any treatment, minimizing interactions between treatments. Each of these cells is sequenced, revealing the effect of each therapy in the full diseased in vivo context. Pythia™ is an analysis methodology that uses artificial intelligence to interpret single-cell data from hundreds of cellular experiments and measure the effect of each therapy in vivo. By analyzing this data alongside existing human pathology data, Gordian determines which therapies are most likely to succeed in preclinical development and clinical trials. "Our most severe unmet medical needs are the result of aging. This is due to the complexities of the aging body, often involving multiple comorbidities at once, making research and development especially challenging and expensive," said Martin Borch Jensen, Gordian co-founder and chief scientific officer. "Gordian is creating a future in which age-related ailments are treated and cured as effectively as infectious diseases today." Aging is the ultimate risk factor for humans, the most expensive, yet research is under-funded. "Age-related diseases are incredibly complex, and a living animal, ideally one that is aged and acquired the disease naturally, is the only experimental system that can capture this complexity," said Laura Deming, a partner at The Longevity Fund and Gordian investor. "Our ability to understand these diseases is bottlenecked by the rate we can run tests in these living systems. Scaling that rate by over 100 fold is really exciting and is a huge leap toward curing age-related disease." In addition to MASH and OA, Gordian's current focus indications include heart failure with preserved ejection fraction and pulmonary fibrosis. The platform is capable of discovering therapies for a long list of complex diseases. The company seeks to partner with pharmaceutical companies to develop drugs as well as move therapeutics into the clinic internally. LePort and Borch Jensen studied and worked in separate scientific fields in different parts of the world before meeting in early 2018 as a result of their shared interest in longevity entrepreneurship. They founded Gordian in October of that year. Follow Gordian on LinkedIn and X and visit for more information. Photos and video available at Media Contact [email protected] About Gordian Biotechnology Founded in 2018 and headquartered in San Francisco, Gordian is an in vivo drug discovery and development company whose mission is to cure age-related diseases. Named for solving intractable problems by changing the rules, the company has developed an innovative in vivo screening platform that tests thousands of gene therapies and predicts clinical outcomes with unprecedented accuracy and efficiency. The Gordian Platform comprises three proprietary components working in concert to drive predictive ability. Mosaic Screening is the Gordian method of pooled in vivo screening, Patient Avatars are animals most representative of humans, and Pythia is an analysis methodology that combines Gordian screening data with existing human data and uses machine learning to maximize predictive power. The company is funded by world-renowned investors including The Longevity Fund, Athos Service GmbH, Gigafund, Founders Fund, and former Novartis CEO Thomas Ebeling. Gordian: Creating Time. SOURCE Gordian Biotechnology

Using the latest technologies --i ncluding both single-nuclear sequencing of mice and human liver tissue and advanced 3D glass imaging of mice to characterize key scar-producing liver cells -- researchers have uncovered novel candidate drug targets for non-alcoholic fatty liver disease (NAFLD). Using the latest technologies -- including both single-nuclear sequencing of mice and human liver tissue and advanced 3D glass imaging of mice to characterize key scar-producing liver cells -- researchers have uncovered novel candidate drug targets for non-alcoholic fatty liver disease (NAFLD). The research was led by investigators at the Icahn School of Medicine at Mount Sinai. Utilizing these innovative methods, the investigators discovered a network of cell-to-cell communication driving scarring as liver disease advances. The findings, published online on January 4 in Science Translational Medicine, could lead to new treatments. Characterized by fat in the liver and often associated with type 2 diabetes, hypertension, and elevated blood lipids, NAFLD is a worldwide threat. In the United States, 30 to 40 percent of adults are estimated to be affected, with about 20 percent of these patients having a more advanced stage called non-alcoholic steatohepatitis, or NASH, which is marked by liver inflammation and may progress to advanced scarring (cirrhosis) and liver failure. NASH is also the fastest-rising cause of liver cancer worldwide. Since advanced stages of NASH are caused by the accumulation of fibrosis or scarring, attempts to block fibrosis are at the center of efforts to treat NASH, yet no drugs are currently approved for this purpose, say the investigators. As part of the experiments, the researchers performed single-nuclear sequencing in parallel studies of both mouse models of NASH and human liver tissue from nine subjects with NASH and two controls. They identified a shared number of 68 pairs of potential drug targets across the two species. Furthermore, the investigators pursued one of these pairs by testing an existing cancer drug in mice as a proof of concept. "We aimed to understand the basis of this fibrotic scarring and identify drug targets that could lead to new treatments for advanced NASH by studying hepatic stellate cells, which are the key scar-producing cells in the liver," said senior study author Scott L. Friedman, MD, Irene and Dr. Arthur M. Fishberg Professor of Medicine, Dean for Therapeutic Discovery, and Chief of Liver Diseases at Icahn Mount Sinai. "In combining this new glass liver imaging approach -- an advanced tissue clearing method that enables deep insight -- along with gene expression analysis in individual stellate cells, we have unveiled an entirely new understanding of how these cells generate scarring as NASH advances to late stages." The researchers discovered that in advanced disease, stellate cells develop a dense network, or meshwork, of interactions among themselves that facilitate these 68 unique interaction pairs not previously identified in this disease. "We confirmed the importance of one such pair of proteins, NTF3-NTRK3, using a molecule already developed to block NTRK3 in human cancers and repurposed it to establish its potential as a new drug to fight NASH fibrosis," said first author Shuang (Sammi) Wang, PhD, an instructor in the Division of Liver Diseases. "This new understanding of fibrosis development suggests that advanced fibrosis may have a unique repertoire of signals that accelerate scarring, which represent a previously unrecognized set of drug targets." The researchers hypothesize that the circuitry of how cells communicate with each other evolves as the disease progresses, so some drugs may be more effective earlier and others at more advanced stages. And the same drug may not work for all stages of disease. The investigators are currently working with Icahn Mount Sinai chemists to further optimize NTRK3 inhibitors for the treatment of liver fibrosis. Next, the investigators plan to functionally screen all candidate interactors in a cell-culture system, followed by testing in preclinical models of liver disease, as they have done for NTRK3. In addition, they hope to extend their efforts to determine if similar interactions among fibrogenic cells underlie fibrosis of other tissues including heart, lung, and kidneys. The paper is titled "An autocrine signaling circuit in hepatic stellate cells underlies advanced fibrosis in non-alcoholic steatohepatitis." Additional co-authors are: Kenneth Li (Icahn Mount Sinai); Eliana Pickholz Li (Icahn Mount Sinai); Ross Dobie (University of Edinburgh, UK); Kylie P. Matchett (University of Edinburgh, UK); Neil C. Henderson (University of Edinburgh, UK); Chris Carrico (Gordian Biotechnology, CA); Ian Driver (Gordian Biotechnology, CA); Martin Borch Jensen (Gordian Biotechnology, CA); Li Chen PharmaNest, Inc., NJ); Mathieu Petitjean (PharmaNest, Inc.,NJ); Dipankar Bhattacharya (Icahn Mount Sinai); Maria I. Fiel (Icahn Mount Sinai); Xiao Liu (University of California); Tatiana Kisseleva (University of California); Uri Alon (Weizmann Institute of Science, Israel); Miri Adler (Yale University School of Medicine, CT); Ruslan Medzhitov (Yale University School of Medicine, CT). The work was supported, in part, by funds from the National Institutes of Health grant numbers R01DK56621, R01DK128289, TR004419, P30CA196521, R01DK101737, R01DK099205, R01DK111866, R01AA028550, P50AA011999, P30 DK120515, and U01AA029019.

LEXINGTON, Mass.--(BUSINESS WIRE)-- Cognesy Therapeutics, a recently established company developing a platform for the discovery of neuroplasticity-inducing drugs to treat a wide range of neuropsychiatric disorders, announced appointments of its senior leadership team, the company said today. This press release features multimedia. View the full release here: Thomas C. Wessel, MD, PhD, CEO, Cognesy Therapeutics (Photo: Business Wire) The company seeks to address the worldwide medical need for novel therapeutics to treat central nervous system diseases, such as depression, anxiety, schizophrenia and dementia, as well as acquired brain disorders, such as stroke and traumatic brain injury. Collectively, these conditions affect one in eight people worldwide, and many of these patients are not adequately treated with current drugs. Cognesy’s initial investor is Gordian Ventures, an incubation fund investing in and building global life science companies. A growing body of evidence points to neuroplasticity as a shared neurobiological response underlying the clinical efficacy of different compounds, including ketamine and esketamine as well as various psychedelic agents such as psilocybin, for treating depression, post-traumatic stress disorder, and other conditions. Although these compounds have significant activity and act rapidly, their consciousness-altering, hallucinatory and other side effects present significant challenges to broader clinical use. “Our neuroplasticity-first approach has immense potential to rapidly generate compounds with promise across a broad range of psychiatric and cognitive disorders, stroke and traumatic brain disorders, substance abuse conditions and pain,” commented Tom Wessel, CEO at Cognesy Therapeutics. “Cognesy has established an outstanding team with deep experience in CNS drug discovery and development.” CSO Pete Distefano added: “Our team is building a cutting-edge neuroplasticity drug discovery platform that integrates advanced medicinal chemistry, proprietary screens for neuroplasticity, and in vivo models to assess efficacy and safety of novel compounds. We believe this approach will lead to new insights and important new agents to trigger neuroplasticity in different clinical settings.” The senior leadership team at Cognesy Therapeutics includes: Thomas C. Wessel, MD, PhD, Chief Executive Officer, is a board-certified neurologist with more than 25 years of drug development experience, including as medical lead for three CNS products approved in the United States: Razadyne® (galantamine), Lunesta® (eszopiclone) and Ampyra® (dalfampridine). Previously, Dr. Wessel served in research leadership roles at Relmada Therapeutics, Asceneuron, Flex Pharma, Acorda Therapeutics, Sepracor and Janssen Pharmaceuticals. Peter S. DiStefano, PhD, Co-founder and Chief Scientific Officer, who has more than 35 years’ drug discovery and development experience in the pharmaceutical and biotech industries. Dr. DiStefano joined Cognesy from Zebra Biologics, where he was Chief Scientific Officer. Prior to that he served as Senior Vice President of Research and Development at Second Genome, as Chief Scientific Officer, and Senior Vice President of Research and Development at Elixir Pharmaceuticals, Earlier in his career, Dr. DiStefano served in research leadership and research positions in neurology and neurobiology at Millennium Pharmaceuticals, Regeneron and Abbott Laboratories. Danny Talati, PharmD, MBA, Senior Vice President, Corporate Strategy, has spent more than 20 years in the pharmaceutical industry in a variety of roles, including sales, medical and business development. Prior to joining Cognesy, Dr. Talati was Head of Business Development at atai Life Sciences. Previously, he held roles at a number of companies, including ten years at Eli Lilly, primarily in the Neuroscience Medical division. Neuroplasticity is the process by which the brain changes through nerve cell growth, reorganization and communication to alter its function. The process is fundamental to growth, from infancy to adulthood, to learning and memory, and to recovery from brain injury. Neuroplasticity involves changes at the molecular level (e.g., expression of brain growth factors), cellular level (e.g., increases in synapses between neurons), and system levels (e.g., increased synaptic connectivity among brain regions). Cognesy’s platform is focused on the discovery of first-in-class neuroplasticity-inducing drugs with potential to treat multiple neuropsychiatric disorders. The company’s goal is to design compounds with improved therapeutic profiles – enhanced activity without side effect liabilities of existing drugs. The company’s platform integrates advanced medicinal chemistry with screens for neuroplastic activity, including neurite outgrowth and synaptogenesis, as well as assays to determine a compound’s mechanism of action and the pathway in which it acts. These assays are coupled with in vivo disease models as well as predictive models for human hallucinogenic potential. About Gordian Ventures Gordian is a global life science venture fund focused on the incubation of companies with high technical barriers to entry. Gordian’s team is comprised of successful entrepreneurs who focus on being a co-founder to each of the ventures it incubates. Gordian has offices in Lexington, Massachusetts and Shanghai, China. Learn more at . About Cognesy Therapeutics Cognesy Therapeutics is building a best-in-class platform technology to discovery of novel drugs that induce neuroplasticity for the treatment of neuropsychiatric diseases. Learn more at: .