2020 will be remembered as the year of RNA blockbusters, including both COVID-19 vaccines and Novartis’ Leqvio. While the traditional view of RNA, developed by Francis Crick in the 1950’s, was merely as a messenger between DNA and protein, further research has since demonstrated the critical role of RNA as a commander within the cell.
Drug makers have been constrained by their limited understanding of how proteins function, or more specifically dysfunction within cells, but targeting RNA allows them to move upstream of proteins, creating new, functional proteins and ‘turning off’ dysfunctional ones. The Covid-19 vaccines alerted the world to the power of RNA therapies, and RNA-based treatments are now in development for Alzheimer’s, heart disease and cancer.
RNA Therapy: A Programmable Medicine
Through their interaction with the genetic makeup of a cell, RNA therapies modify the ribonucleic acid (RNA) within cells and can therefore target specific functions in that cell, making their impact both more specific and potentially more effective than traditional therapies. RNA medicines are inherently programmable; the sequence of the RNA medicine can be tweaked to create a new ‘program’ that can be ‘plugged into’ the human body in order to change function and fight disease. By making small changes to the RNA sequence, we are able to optimise an existing medicine, or create an entirely new one with a different, novel therapeutic target.
Despite the programmability of RNA therapeutics, the speed and success of drug discovery is still limited by it’s assumptions and models, including laboratory animals, microorganisms, cell and tissue based systems to ensure therapeutics efficacy and safety. In many cases, animal models have failed to predict therapeutic efficacy in humans, and so begs the question, what is the model system for drug development? Perhaps Nobel Prize Winner, Sydney Brenner, sums up this difficult challenge best:
“There are many aspects of humanity that we still need to understand for which there are no useful models. Perhaps we should pretend that morality is known only to the gods and that if we treat humans as model organisms for the gods, then in studying ourselves we may come to understand the gods as well”.
In liver disease specifically, clinical trials to develop cures are exceptionally high risk and require large patient numbers because liver disease is silent until it is too late.
Breaking Disease Silence With Phenomics
Ochre Bio leverages deep phenotyping (‘phenomics’) to digitize liver biology at scale, from healthy livers through to advanced liver disease. Through this, Ochre Bio have uncovered hundreds of novel liver therapeutic targets at the cellular and genetic level. By 2022, Ochre will have built a complete in silico human liver atlas of over 10¹¹ measurements. Ochre Bio then uses machine learning to spot patterns in gene causality and make predictions.
This deeper level of understanding is used to develop new therapies for chronic liver diseases. Once convinced that a gene’s change in expression is causal, Ochre develops and optimises synthetic RNAs to knock down expression. After in vitro validation, the next stage is to test these RNA therapies on discarded donor livers, which gives Ochre Bio high conviction on the likelihood of success in clinical trials.
In essence, Ochre Bio is a computational drug discovery company, with an ability to validate liver targets and move safe and effective medicines into the clinic at unparalleled speed. It is their target selection expertise that positions Ochre Bio so well in the exploding field of RNA therapeutics. Ochre Bio is able to rapidly identify, develop and test RNA therapies, bringing them from bench to human liver validation in months rather than years.
Ochre Bio’s founders have over 15 years’ experience in liver genomics and bringing advanced therapies, including gene therapies, to the market. Ochre Bio brings together an expert team of wet- and dry-lab scientists as well as advisors who are world leaders in liver research and biopharma strategy. Of particular note, Peter Friend, Director of the Oxford Transplant Center brings exceptional insights into transplant medicine, while Scott Friedman, Chief of Liver Diseases at Mount Sinai advises Ochre brings years of NASH expertise to the table, and Peter Hutt, former FDA Chief Counsel from 1971–1975, brings unparalleled Regulatory Affairs expertise to further bolster the Ochre team.
Changing the Future of Liver Disease
With no existing cure for end-stage liver disease except for transplants, and with chronic liver disease representing a top 10 global cause of death, Ochre Bio is positioning itself as the expert in liver, hoping to address this real unmet medical need. Ochre Bio’s starting point is to rejuvenate marginal donor livers to improve outcomes for patients. Not only is excess liver fat fast becoming the main reason for needing a liver transplant, but it is also the primary reason for a shortage in healthy, high-quality, donor livers. Solving this important problem first, begins our journey toward tackling some of the most difficult health conditions of our time.
Learn more: Ochre-Bio.com