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Human-Centric Drug Discovery is a new Oxford University spinout company from Professor Zameel Cader's lab.

Caleb Webber and Zameel Cader standing outside the ScienceOxford Centre
Professors Caleb Webber and Zameel Cader

The company

Human-Centric is a new company founded by Zameel Cader, Caleb Webber and James Peach. They have received seed funding from Oxford Science Enterprises and are establishing their purpose-built facilities at the Wood Centre for Innovation, Headington, Oxford. They are looking for talented post-doctoral researchers to join the team and further develop the human stem cell disease models as well as bio-informaticians to advance the informatics.

The approach

Finding drug targets typically is a bottom-up process – ideally starting with a genetic association for a disease and then working out how a candidate gene might drive disease processes which in turn reveal druggable targets. For many common and disabling neurological disorders it continues to be very challenging to get to a target this way because the genetic associations in common disorders do not easily illuminate the relevant mechanisms, and positive signals in preclinical models do not translate into safe or effective drugs in humans.

Neurological disorders are among the most disabling disorders world-wide and as a clinician-scientist, I am always looking for ways to accelerate the drug discovery process. Human-Centric is a really exciting opportunity to take our latest lab research to the clinic. - Professor Zameel Cader

Human-Centric uses an alternative and complementary top-down approach. Many clinically approved drugs will modulate multiple targets in addition to the main intended target. Mainly this causes unwanted side-effects but in some cases, it can also lead to unexpected benefits. Take a drug like candesartan – developed for high blood pressure by targeting the angiotensin receptor. It turns out candesartan is very effective for migraine prevention unrelated to its effects on blood pressure. This is the well-known process of re-purposing, however in re-purposing the original target then becomes a side-effect, and the original patent may prevent further commercial development. Human-Centric works instead to isolate and identify the alternative target that the existing drug is binding. This alternative target then represents a de-risked and possibly novel target for a new drug discovery programme. The advantage is that the drug discovery process is starting from a place where it is known that a drug against that target is clinically effective and safe.

Human-Centric has developed a unique platform to be able to undertake this drug-discovery approach at scale. This involves integrating clinical health record informatics, disease- and therapy-relevant human cellular assays and genomics to ensure that the nominated targets have robust validation. The Cader lab applied this approach to headache and migraine as proof of concept and this has now been licensed by Oxford University Innovation to Human-Centric.

The approach can be applied to any common disorder from Parkinson's Disease to diabetes. The company will focus on neurological disorders and intends to work with pharmaceutical companies to provide de-risked targets as well as develop in-house assets. Drug-discovery programmes cost several billions of dollars and have a very high failure rate. Human-Centric's platform will significantly increase the chances of success.

James Peach (Human-Centric's CEO) commented: 'I'm delighted to have founded Human Centric with Professors Cader and Webber to bring their ground-breaking cell and data work a step closer to patients. We're absolutely focused on using more human data to develop better treatments, and we're looking forward to building the scientific team and external partnerships in 2022.'

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