• • 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, UK – 21 March 2024 – 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).

ENDS 

For further information, please contact:

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

• Mission gains clearance from US FDA for Phase II trial of MTX652 after it receives official approval of its Investigational New Drug (IND) application
• Phase II trial expected to begin Q1 2024 in up to 160 patients with acute kidney injury (AKI) following cardiac surgery

Cambridge, UK – December 14, 2023 – Mission Therapeutics (“Mission” or the “Company”), a clinical-stage biotech developing first-in-class therapeutics targeting mitophagy, today announces that the US Food and Drug Administration (FDA) has approved its Investigational New Drug (IND) application for its lead asset MTX652, allowing Mission to proceed with its planned Phase II clinical trial in the US.

Up to 160 adults with increased risk for Acute Kidney Injury (AKI) following cardiac surgery are planned to be recruited for the trial from multiple sites in North America and Europe. The double-blind, placebo-controlled trial is expected to begin early next year and is intended to show that MTX652 protects this high-risk group of patients from AKI by assessing standard markers of renal function and renal injury over time.

Dr Anker Lundemose, Chief Executive Officer of Mission Therapeutics, said: “The FDA’s approval of our Phase II clinical study for our lead asset MTX652 marks a major milestone for Mission. We now have two USP30 inhibitors advancing through clinical trials, MTX652 for acute kidney injury and MTX325 for Parkinson’s Disease, validating our unique approach and the breadth of our assets.”

Dr Suhail Nurbhai, Chief Medical Officer of Mission Therapeutics, said: “Recent reports suggest that up to 50% of high-risk patients suffer acute kidney injury following heart surgery[i] [ii]. There are no approved drug treatments and the immediate and longer-term consequences can be very serious, including continued decline of renal function and/or the requirement for renal replacement therapy. We believe MTX652 has the potential to alleviate these outcomes and to meet this serious and important unmet medical need. We are delighted to have received this approval and look forward to starting this trial in 2024.”

Dr Paul Thompson, Chief Scientific Officer of Mission Therapeutics, commented: “In preclinical experiments, MTX652 demonstrated significant protective effects in multiple models of kidney injury, and this breadth of effect is very encouraging in indicating potential clinical benefit. We are very pleased with this strong preclinical foundation, which supports our progress into clinical efficacy trials.”

The FDA’s decision follows completion of a Phase I First Time in Human (FTIH) study of MTX652 earlier in 2023, in which over 80 healthy volunteers received MTX652. The trial successfully demonstrated MTX652 was safe and well tolerated up to a single dose of 200mg a day and multiple doses of 100mg daily for 14 days, with an excellent pharmacokinetic profile.

About MTX652 and USP30

MTX652 is a potent and selective compound designed to improve mitochondrial quality and function by enhancing mitophagy through inhibition of USP30, a deubiquitylating enzyme localised to mitochondria which is a negative regulator of mitophagy. It thereby promotes cellular health by enhancing this key mechanism, which cells use to clear dysfunctional mitochondria. MTX652 has the potential to reduce the impact of impaired mitochondria associated with Ischaemic Reperfusion Injury (IRI) in the heart and kidneys in patients who have undergone heart surgery.

ENDS 

For further information, please contact:

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.

[i] https://guardtherapeutics.com/en/press-releases/guard-therapeutics-reports-robust-efficacy-of-rmc-035-in-phase-2-akita-and-advances-clinical-development-program

[ii] https://pubmed.ncbi.nlm.nih.gov/34474590/

International research collaboration between Harvard Medical School, Cambridge University and Mission Therapeutics

CAMBRIDGE, UK, 13 November, 2023 – Mission Therapeutics (“Mission”), a clinical-stage biotech company developing first-in-class therapeutics targeting mitophagy, today announces the publication of a peer-reviewed article titled ‘Knockout or inhibition of USP30 protects dopaminergic neurons in a Parkinson’s Disease (PD) mouse model’ in the journal Nature Communications, which can be freely accessed here. The research was the result of collaborative work between Cambridge University, Harvard Medical School, and Mission Therapeutics.

Mission Therapeutics is a global leader in discovering and developing innovative therapeutics that promote mitophagy. This quality control process enables the removal of dysfunctional mitochondria, thereby improving cell health and function. Parkinson’s Disease is highly associated with mitochondrial dysfunction, making it a key pathophysiological driver. Mission believes that by improving mitophagy, it can reduce the burden of dysfunctional mitochondria and thus slow or prevent the progression of Parkinson’s Disease, which is a major unmet need for patients with this condition.

Dr Paul Thompson, Chief Scientific Officer at Mission Therapeutics, said: “It is well recognized that mitochondrial dysfunction is a key driver of Parkinson’s Disease mechanisms, in particular, playing an important role in the degeneration of brain cells that produce dopamine. By inhibiting the enzyme USP30, Mission’s experimental drug MTX325 helps promote mitochondrial quality control by increasing the removal of dysfunctional mitochondria. This is likely to have a positive impact on dopaminergic neurons undergoing chronic degenerative processes, which result in functional impairment. This paper strongly supports further study of USP30 inhibition as a potential disease-modifying therapy for Parkinson’s Disease.”

Dr Anker Lundemose, Chief Executive Officer at Mission Therapeutics, said: “The exciting findings of this Nature Communications paper are a tremendous boost to Mission’s Parkinson’s Disease programme. We look forward to starting our first in-human trial of MTX325 early next year.”

The Nature Communications paper outlines how Mission’s drug MTX325 has potential as a novel, disease-modifying treatment for Parkinson’s, by enhancing mitophagy and clearing dysfunctional mitochondria. Dysfunctional mitochondria are usually tagged for removal via mitophagy with a protein ‘flag’ called ubiquitin. However, the enzyme USP30 removes these flags, inhibiting normal mitophagy, leading to a build-up of dysfunctional mitochondria in cells. By inhibiting USP30, MTX325 helps restore normal mitophagy and thus cellular health.

The Nature Comms paper provides key experimental evidence to support USP30 as a valid target in PD through both in vitro mechanisms as well as in vivo PD models. Using both a USP30 knockout mouse model and a pharmacological strategy with Mission’s experimental USP30 inhibitor drug MTX325, we found that USP30 inhibition led to protection against loss of dopamine and dopaminergic neurons induced by alpha-synuclein in vivo and reduced potential biomarkers of disease including phosphorylated alpha-synuclein and glial cell activation.

These new findings suggest that maintaining healthy mitochondrial function by blocking USP30 may slow or even stop the progression of pathology which drives PD.

Prof Gabriel Balmus, Cambridge University, said: “Our study has shown that it is possible to enhance the removal of damaged mitochondria through a process called mitophagy. We demonstrated this by inhibiting the activity of USP30 in both mice and human cells, which resulted in the increased removal of damaged mitochondria and the subsequent protection of dopaminergic neurons against the harmful effects of Parkinson’s Disease, which would typically result in the neurons’ death. This research provides compelling evidence that USP30 is a promising therapeutic target for Parkinson’s disease, where there is a pressing need for disease-modifying treatments.”

Prof David K. Simon, Harvard Medical School, said: “Our study of USP30 KO mice in a synuclein-driven PD model clearly shows an advantage of removing USP30 for dopaminergic neuron protection and maintenance of normal motor function. It has been our pleasure to collaborate with Cambridge and Mission Therapeutics on these studies, and we are keen to see the outcomes of early MTX325 clinical investigations.”

Mission is planning to initiate a MTX325 Phase I trial in humans in early 2024.

ENDS

For further information, please contact:

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 has completed its first Phase I clinical study with MTX652, demonstrating a highly encouraging safety, tolerability and pharmacokinetic profile. A Phase II trial of MTX652 in patients at risk of acute kidney injury following cardiac surgery is planned to start in Q1 2024.

A Phase I trial of MTX325 in healthy volunteers and patients with PD is planned to start in Q1 2024. Mission is backed by blue-chip investors including Pfizer Venture Investments, Sofinnova Partners, Roche Venture Fund, SR One, IP Group and Rosetta Capital.

CAMBRIDGE, UK, 10 October 2023 – Mission Therapeutics (“Mission”), a clinical-stage biotech company developing first-in-class therapeutics targeting mitophagy, today announces that its Chief Scientific Officer, Dr Paul Thompson, will give an oral presentation on its experimental drug candidate MTX325 at the 15^th Annual Michael J. Fox Foundation’s Parkinson’s Disease Therapeutics Conference on October 19, 2023, in New York.

Dr Thompson will participate in the session titled ‘Advances in Emerging Targets and Therapeutic Development’ where he will discuss Mission’s data demonstrating development of USP30 inhibitors for the treatment of Parkinson’s Disease (PD).

As the world’s largest nonprofit funder of Parkinson’s research, The Michael J. Fox Foundation (MJFF) is dedicated to accelerating a cure for Parkinson’s Disease and improved therapies for those living with the condition today. The annual Michael J. Fox Foundation’s Parkinson’s Disease Therapeutics Conference brings together 300 research and business development professionals from both academia and industry and showcases the most exciting and innovative research from MJFF’s research portfolio, and serves as a unique platform for field leaders to share new and unpublished results.

Dr Paul Thompson, Ph.D., Chief Scientific Officer of Mission Therapeutics, commented: “We look forward to presenting our recent findings on USP30 inhibition for the treatment of Parkinson’s Disease at this prestigious conference. The Michael J. Fox Foundation shares our mission of unlocking the complex biology of Parkinson’s Disease to slow disease progression and improve patient lives with the development of the next generation of treatments.”

Mission Therapeutics is a world leader in discovering and developing novel therapeutics which promote the removal of dysfunctional mitochondria to maintain cell health and function. A major unmet need for Parkinson’s Disease patients is a treatment that slows or prevents the progression of disease. Mitochondrial dysfunction is considered a key pathophysiological driver of Parkinson’s Disease (PD) and several disease-associated gene mutations affect proteins involved in a dysfunctional mitochondria ubiquitin-dependent clearance mechanism known as mitophagy, including PINK1 and the ubiquitin E3 ligase, Parkin.

USP30 is a deubiquitylating (DUB) enzyme uniquely localized to the mitochondria that removes ubiquitin groups and is a negative regulator of the PINK1/Parkin pathway and mitophagy. Inhibiting USP30 has therefore been proposed as a therapeutic mechanism for protecting vulnerable dopamine-producing neurons in PD. Mission Therapeutics is currently developing two DUB inhibitors: MTX325 (targeting the CNS) and MTX652 (peripheral) which can potentially be used to treat any disease driven by mitochondrial dysfunction.

– ENDS –

For further information, please contact:

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 has completed its first Phase I clinical study with MTX652, demonstrating a highly encouraging safety, tolerability and pharmacokinetic profile. A Phase II trial of MTX652 in patients at risk of acute kidney injury following cardiac surgery is planned to start in Q1 2024.

A Phase I trial of MTX325 in healthy volunteers and patients with PD is planned to start in Q1 2024.

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