Mission Therapeutics commences landmark trial of MTX325, a potential disease-modifying treatment for Parkinson’s Disease
May 21, 2024 – Clinical Trials, Drug Discovery, Pharmaceutical – Mission Therapeutics, Parkinson's disease, clinical trials
Builds on preclinical proof-of-concept that MTX325 protects dopamine-producing brain cells by enhancing mitophagy – the process cells use to remove dysfunctional mitochondria
21 March 2024 — Cambridge, UK — Mission Therapeutics, 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 PD 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 PD 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 PD. While existing treatments for Parkinson’s can help control symptoms such as tremours, 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 PD, 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 disease. 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. Visit: missiontherapeutics.com.
