Gordian Biotechnology Introduces High-Throughput In Vivo Screening Platform to Discover Therapies and Better Predict Human Outcomes for Age-Related Diseases

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.

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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