Creating Time

You want to wake up each morning, more capable than you were the day before. But regardless of genetics, and physical or mental self-care, a human existence has inevitably become constrained by time. Days become filled with hospital visits, and simple tasks like walking up stairs or hugging your grandkids become a struggle. Gordian Biotechnology envisions a life limited only by our imagination rather than by our physiology, one where we continue growing wiser and stronger, one that gets better each day, both mentally and physically. We produce medicines that allow each of us to look forward to getting old. We are creating what all of us are running out of: time.

Drug discovery is hard, especially for age-related disease

Animal testing is currently the bottleneck in drug discovery. Until now, animal testing meant we could only make one guess at a curative therapy at a time, and testing those guesses was very expensive. Moreover, age-related disease is incredibly complex, so our guesses have been incredibly poor. Together, this has led to the stream of clinical failures we have experienced for nearly all age-related disorders. 

To solve this, we must be able to make thousands of guesses, each guess needs to be cheap, and we must test them rapidly.

Mosaic Screening

The concept is simple: rather than experiment with perturbations to cells in a dish then move best guesses into animals one at a time, perturb cells directly in a living animal. A dish makes things easy: cells are accessible and plentiful, different perturbations are separated by walls of plastic, and the system is compact and highly reproducible. But a dish doesn’t replicate the living system. It lacks an immune system, blood, hormones, and the full suite of cells in the 3D structure of living tissue…a dish lacks nearly all of the things that make up an aged environment.

At Gordian Biotechnology, we experiment on cells directly inside a living, aged animal with the disease of interest. A pooled library of gene therapies is introduced into the target tissue, turning it into a “mosaic.” Various cells receive different individual therapies, each with a unique barcode, separated not by walls of plastic but by diseased tissue unperturbed by any treatment.

We single-cell sequence the treated tissue and use the library’s unique barcodes to identify the specific treatment given to each cell. The single-cell transcriptome allows us to explore various aspects of disease biology simultaneously in an environment very similar to where a clinical drug would need to be effective. 

In this way, we run the most patient-predictive in vivo experiments, at a scale previously thought impossible.

Link to video

80% Predictive Power

Mosaic screening is operational across three diseases: osteoarthritis (OA), metabolic dysfunction-associated steatohepatitis (MASH), and heart failure with preserved ejection fraction (HFpEF), with applications to pulmonary fibrosis under development. The list of areas we can tackle next is long: neurodegenerative, neuromuscular, ophthalmologic, renal, intestinal, etc. 

Our screens take advantage of advanced animal models we call Patient Avatars, and have each explored up- and down-regulation of hundreds of gene targets and target combinations:

Our OA screens are done in horses with naturally occurring diseases. Using our AI-powered analysis, Pythia, we’ve validated screen hits by measuring cartilage regeneration capacity in patient-derived human cells and discovered three novel therapeutics that exceeded the performance of FGF18, a drug that demonstrated cartilage regenerative properties in phase 2 clinical trials. Notably, both horses and human samples capture some individual differences in response to therapy, which is an important complication in clinical trials.

The predictive power of this experiment was demonstrated to be 80%. While these results are early in the preclinical validation and development process, we couldn’t be more excited about the potential as we move these discoveries forward.

An Asset Discovery Factory

Mosaic Screening has already produced the largest in vivo perturbation dataset on the planet, and we are just getting started.

We are building a vertically integrated pharmaceutical company, with the intention of bringing dozens of blockbuster therapeutics for prevalent age-related disorders into and through clinical trials. We are sitting on more therapeutic data than we can push into development ourselves. We use this data to engage the broader pharma community, leveraging discovery and asset partnerships to cause as many therapies to enter the clinic as possible.

We have developed the world’s first in vivo asset discovery factory, allowing us to generate preclinical revenue while pushing internal development programs into the clinic. In this way, we achieve our mission: curing age-related disease.

Who says money can’t buy time?

We are always looking for excellent team members, mission-aligned investors, and world-class advisors to join us in our journey. Please reach out to us.