Mission Therapeutics granted MHRA Clinical Trial Authorisation (CTA) for MTX325 for the treatment of Parkinson's Disease

• Company on track to dose first participant in multi-part, adaptive Phase 1, first-in-human study in healthy volunteers and Parkinson's Disease (PD) patients in the first quarter of 2024
• CTA comes as Nature Reviews Drug Discovery hails Mission's mitophagy approach as "an appealing disease-modifying therapeutic strategy" for PD

CAMBRIDGE, England, Dec. 5, 2023 /PRNewswire/ -- Mission Therapeutics ("Mission" or the "Company"), a clinical-stage biotech developing first-in-class therapeutics targeting mitophagy, today announces that the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) has granted clinical trial authorisation (CTA) for Mission to commence its multi-part, adaptive Phase 1, first-in-human study evaluating the safety and tolerability of MTX325, intended for the treatment of Parkinson's Disease (PD).

"The MHRA's authorisation marks a major step forward in our mission to develop MTX325 as a disease-modifying therapy for Parkinson's Disease," said Anker Lundemose, Chief Executive Officer, Mission Therapeutics. "Having recently published data^[i] showing that MTX325 produced a similar beneficial effect to knockout of USP30 in a mouse model of PD, bringing MTX325 into the clinic — with its potential to preserve vital dopamine-producing neurons in the brain — demonstrates our commitment to pushing the boundaries of research in diseases with limited treatment options. Following successful completion of the Phase 1 clinical study with our peripheral compound, MTX652, earlier this year, we now have two compounds targeting mitophagy in clinical phase testing, and this approval represents significant further validation of our unique approach to target unmet medical needs."

Dr Paul Thompson, Chief Scientific Officer, Mission Therapeutics, said: "There are currently no approved treatments for Parkinson's Disease which modify the underlying pathology of this common and devastating degenerative condition. By enhancing mitophagy, MTX325 is designed to address the loss of dopamine-producing neurons resulting from the build-up of dysfunctional mitochondria in these brain cells. Mitophagy is the natural 'quality control system' cells use to clear out dysfunctional mitochondria, and we believe that increasing the removal of these dysfunctional mitochondria will improve the health of dopaminergic neurons and thereby slow the progression of PD."

Dr Suhail Nurbhai, Chief Medical Officer, Mission Therapeutics, commented "We are delighted to have approval to start clinical testing with MTX325. This Phase 1 trial is intended to confirm the safety and tolerability 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 starting the trial in the coming months, and providing preliminary first-in-human data later in 2024."

Up to 160 adults, both healthy people and those with PD, will be recruited for the trial, which is planned to take place at sites across the UK.

The CTA comes as the journal Nature Reviews Drug Discovery identified Mission's recent work with scientists at Cambridge University and Harvard University investigating the potential of MTX325 in PD mouse models^[i] — as a 'Research Highlight'. NRDD commented: "Mitochondrial dysfunction and reduced mitophagy are strongly implicated in the pathogenesis of dopaminergic neurodegeneration in both sporadic and familial Parkinson's Disease (PD). Restoring mitophagy to accelerate the removal of damaged mitochondria is therefore an appealing disease-modifying therapeutic strategy."^[ii]

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 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 the 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.

^[i] https://www.nature.com/articles/s41467-023-42876-1
^[ii] USP30 inhibition protects dopaminergic neurons (nature.com)