Mission Therapeutics commences landmark trial of MTX325, a potential disease-modifying treatment for Parkinson's Disease

• Builds on preclinical proof-of-concept that MTX325 protects dopamine-producing brain cells by enhancing mitophagy – the process cells use to remove dysfunctional mitochondria 

CAMBRIDGE, England, March 21, 2024 /PRNewswire/ -- Mission Therapeutics ("Mission" or the "Company"), a clinical-stage biotech developing first-in-class therapeutics targeting mitophagy, today announces the start of a Phase I first-in-human clinical trial of MTX325, its potential disease-modifying treatment for Parkinson's Disease (PD).

Around 10 million people suffer from Parkinson's Disease worldwide, including almost one million in the US and around 1.2 million in Europe – numbers that are set to increase as populations age.

Mission Therapeutics has now completed dosing the first cohort of healthy volunteers in a multi-part, adaptive Phase I study evaluating safety, tolerability, pharmacokinetics and brain penetration of MTX325. Single ascending, multiple dose ascending and elderly healthy volunteer cohorts are planned in 2024, whereas Parkinson's Disease patients will be the focus of the trial in 2025.

Dr Paul Thompson, PhD, Chief Scientific Officer, Mission Therapeutics, said: "The launch of this first-in-human trial is a significant step forward for Mission Therapeutics, as we look to assess the potential of MTX325 as a disease-modifying treatment for Parkinson's Disease. While existing treatments for Parkinson's can help control symptoms such as tremors, slowness of movement, and cognitive problems, none address the underlying neuronal loss which causes this devastating condition."

Dr Suhail Nurbhai, Chief Medical Officer, Mission Therapeutics, said: "We are delighted to have brought this second USP30 inhibitor into clinical development. The overall objectives of this Phase I trial are to confirm the safety, tolerability and CNS penetration of MTX325, in both healthy volunteers and patients with Parkinson's Disease, and help us determine appropriate doses for future efficacy testing. We look forward to progressing this compound rapidly through initial clinical testing and aim to demonstrate its potentially beneficial clinical profile later this year."

The start of the trial follows the publication of a key academic paper in the journal Nature Communications last December by scientists at Cambridge University, Harvard University and Mission Therapeutics. The paper outlined their preclinical research in mouse models, which provided strong experimental evidence supporting the thesis that MTX325 can modify the course of PD by targeting USP30.

USP30 is a deubiquitylating enzyme (DUB) known to inhibit mitophagy, the process cells use to rid themselves of dysfunctional mitochondria. A growing body of scientific evidence has linked a build-up of dysfunctional mitochondria in cells to a range of diseases, including PD, Kidney Disease, Heart Failure, idiopathic pulmonary fibrosis (IPF) and Duchenne's Muscular Dystrophy (DMD).

About Mission Therapeutics

Mission Therapeutics is a world leader in discovering and developing novel therapeutics which promote the removal of dysfunctional mitochondria, promoting cell health and function. Mitochondria are energy producing organelles which require lifetime quality control through a ubiquitin-mediated clearance mechanism known as mitophagy. In certain situations, such as cellular stress, cell injury, and/or defects of the mitophagy process, the mitochondria can become dysfunctional and damaging to the cell, leading to reduced energy production, oxidative stress, inflammation and potentially cell death. Dysfunctional mitochondria are significant drivers of disease pathophysiology in acute kidney injury (AKI), Parkinson's Disease (PD), heart failure, Duchenne's Muscular Dystrophy, IPF, mitochondrial diseases and Alzheimer's.

USP30 is a deubiquitylating enzyme that constantly removes ubiquitin from mitochondria, providing a potential brake on clearance of dysfunctional mitochondria. Mission is currently developing two small molecule drugs, MTX652 (peripheral) and MTX325 (targeting the CNS) which, through inhibition of the mitochondrial DUB enzyme USP30, will promote clearance of dysfunctional mitochondria – consequently improving overall cellular health. Mission's USP30 inhibitors MTX652 and MTX325 could potentially be used to treat any disease or condition driven by mitochondrial dysfunction.

Mission is backed by blue chip investors including Pfizer Venture Investments, Sofinnova Partners, Roche Venture Fund, SR One, IP Group and Rosetta Capital.

About MTX325 and USP30

MTX325 is a potent selective central nervous system-penetrant compound designed to improve mitochondrial quality and function by enhancing mitophagy. MTX325 inhibits USP30, a deubiquitylating enzyme localised to mitochondria which is a negative regulator of mitophagy. Data from an in vivo model of Parkinson's, where USP30 was deleted through gene knockout, validate USP30 as a potential target in PD. Researchers found MTX325 produced a similar effect to gene knockout of USP30 in the same PD mouse model, further validating the approach of USP30 inhibition in PD. See the paper in Nature Communications here: https://www.nature.com/articles/s41467-023-42876-1