Mission Therapeutics awarded $5.2m from The Michael J. Fox Foundation and Parkinson's UK to advance potential disease-modifying treatment MTX325

• Investment will support investigation of Mission's small molecule drug MTX325 in patients with early-stage Parkinson's disease
• Marks latest step in Mission's relationship with The Michael J. Fox Foundation (MJFF), after MJFF awarded Mission preclinical research grants in 2017 and 2021, and first with Parkinson's UK
• Comes as promising early data from healthy volunteers show MTX325 has a good safety profile, pharmacokinetics and CNS penetration

CAMBRIDGE, England, July 2, 2024 /PRNewswire/ -- Mission Therapeutics ("Mission" or the "Company"), a clinical-stage biotech developing first-in-class therapeutics targeting mitophagy, has been awarded $5.2 million from The Michael J. Fox Foundation for Parkinson's Research (MJFF) and Parkinson's UK. The funding will help advance Mission's potential disease-modifying treatment for Parkinson's, MTX325.

MTX325 is a potent, selective, small molecule brain-penetrant USP30 inhibitor, which is designed to protect dopamine-producing neurons by improving mitochondrial quality and function. The funding will support a 28-day dosing of MTX325 in patients with early-stage Parkinson's disease (PD), as part of Mission's ongoing MTX325 Phase I program. Patient dosing is expected to start early in 2025. The aims are to understand MTX325's safety, tolerability, pharmacokinetic profile and CNS penetration in PD patients, as well as observing effects on relevant mechanisms and disease biology biomarkers.

Mission started its multi-part, adaptive Phase I first-in-human clinical trial of MTX325 in March, beginning with a single ascending dose stage in healthy volunteers. Initial investigations of MTX325's CNS penetration ability in these healthy volunteers have yielded positive results. The multiple ascending dose stage of the study was initiated last month (June).

Anker Lundemose, Chief Executive Officer, Mission Therapeutics, said: "This significant grant, from two of the world's leading Parkinson's disease organisations, underlines the huge potential of MTX325 as a disease-modifying treatment for this terrible neurodegenerative illness. It also represents a major endorsement of our mitophagy strategy in human diseases including PD."

Dr Paul Thompson, Chief Scientific Officer, Mission Therapeutics, said: "We have already made excellent progress in healthy volunteers with preliminary data from the ongoing clinical trial showing that MTX325 has a good single dose safety profile, pharmacokinetics and CNS penetration. We look forward to starting the PD patient part of the trial in the new year, which this generous funding from MJFF and Parkinson's UK is helping to support."

Katharina Klapper, director of clinical research at MJJF, said: "Mission Therapeutics has made great advances in the understanding of how mitochondrial health can play a pivotal role in the development of Parkinson's disease in recent years. We look forward to seeing the results of the MTX325 trial."

Dr Arthur Roach, Director of the Parkinson's Virtual Biotech at Parkinson's UK, said: "We are delighted to be working with Mission Therapeutics to help fund this vital, UK-based clinical trial. Disease-modifying treatments are one of the great hopes of people with Parkinson's. We now know that mitochondria play a crucial role in the development of Parkinson's, so addressing mitochondrial problems could have far-reaching benefits for those living with the condition."

Parkinson's is a neurodegenerative disease which affects around 10 million people globally. It is characterised by low levels of the neurotransmitter dopamine and there are currently no approved disease-modifying treatments for the condition.

MTX325 protects dopamine-producing neurons by enhancing a cellular quality control process called mitophagy, in which faulty mitochondria are tagged and then removed. MTX325 does this by inhibiting USP30, a deubiquitylating enzyme (DUB) which impedes normal mitophagy.

Last December scientists at Cambridge University, Harvard University and Mission Therapeutics published a key academic paper outlining preclinical research on USP30 and MTX325 in the journal Nature Communications. The paper detailed knockout mouse model data which, the authors said, provided strong experimental evidence supporting the thesis that MTX325 can modify the course of PD by targeting USP30.

A growing body of scientific evidence has linked a build-up of dysfunctional mitochondria in cells to a range of diseases including Parkinson's, 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

About Parkinson's UK and the Parkinson's Virtual Biotech

We are Parkinson's UK. Here for everyone affected by the condition. Funding research into the most promising treatments, taking us closer to a cure every day. Fighting for fair treatment and better services.
In 2017, we founded the Parkinson's Virtual Biotech. A groundbreaking global movement to deliver life-changing new treatments in years not decades. It uses cutting edge biological and chemical research to come up with new treatments. Driven by people with Parkinson's, not profit, it adapts successful methods from the biotech and business worlds to deliver new treatments faster.
The Parkinson's Virtual Biotech is now an international programme in partnership with the Parkinson's Foundation. We believe we'll get a cure faster by collaborating, not competing. The innovative approach is working. The next treatment is closer than ever.

Further information, advice and support is available on our website, www.parkinsons.org.uk