MTX652 has advanced through preclinical regulatory toxicology studies and is ready for a phase 1 trial

Mission Therapeutics has been granted approval to take its lead USP30 deubiquitinating enzyme (DUB) inhibitor – MTX652 – into a clinical study.

The mitochondrial-associated DUB removes ubiquitin, which is what damaged mitochondria are labelled with. This inhibits the degradation of mitochondria, which can affect cell health. Mission has developed MTX652 to inhibit USP30, with the aim to enable appropriate degradation of dysfunctional mitochondria to preserve and improve cellular health.

Specific kidney cells are rich in mitochondria, making them highly vulnerable to injury if those mitochondria are not working properly. Mitochondrial dysfunction is strongly implicated in kidney injury and chronic kidney disease (CKD), while its quality is implicated in various other poorly treated conditions, such as idiopathic pulmonary fibrosis, muscular dystrophy and primary mitochondrial disease.

MTX652 has successfully advanced through preclinical regulatory toxicology studies, following candidate nomination last year. It is now ready to be progressed into the clinic and the phase 1 trial will evaluate the safety, tolerability and pharmacokinetics of MTX652 in over 60 participants given either a single or multiple doses.

Dr Suhail Nurbhai, chief medical officer of Mission Therapeutics, commented: “We are delighted that our lead programme is entering the clinic. Mission has built a groundbreaking platform for the discovery and development of first-in-class small molecule drugs that selectively target DUBs. MTX652 entering the clinic is a major milestone for the company and a tremendous achievement. We are excited to be taking this important next step.”

CKD affects an estimated 780 million people around the world. The NHS costs in 2009/10 were around £1.5bn, and are likely to be much more now, while estimated US Medicare costs for CKD are greater than $87bn.