• 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, UK – 02 July 2024 – 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).

– ENDS –

For further information, please contact:

Mission Therapeutics Ltd: Anker Lundemose MD PhD Chief Executive Officer Tel: +44 (0)1223 607 340

Optimum Strategic Communications: Mary Clark, Stephen Adams, Vici Rabbetts Email: mission@optimumcomms.com Tel: +44 (0) 208 078 4357

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

• Developing novel therapeutics which enhance the removal of dysfunctional mitochondria, promoting cell health and function
• MTX325 is a potentially disease-modifying treatment for Parkinson’s Disease with clinical trial due to start imminently
• Backed by blue chip international investors

Cambridge, UK – March 14, 2024 – Mission Therapeutics (“Mission” or the “Company”), a clinical-stage biotech developing first-in-class therapeutics that enhance mitophagy to promote cell/organ health, today announces it has raised £25.2 million to progress the clinical development of its drug candidates. The financing was jointly led by existing investors Pfizer Venture Investments, Sofinnova Partners, Roche Venture Fund, SR One, IP Group, and Rosetta Capital.

Mission plans to use the funds to accelerate development of its lead drug candidates, MTX325 and MTX652, through clinical trials. MTX325 and MTX652 both inhibit USP30, a mitochondrial de-ubiquitylating enzyme (DUB), increasing damage-associated mitochondrial ubiquitylation to promote mitophagy – the essential 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 Parkinson’s Disease (PD), Kidney Disease, Heart Failure, and Duchenne’s Muscular Dystrophy (DMD).

MTX325, a CNS penetrant which is a potential disease-modifying treatment for Parkinson’s Disease, is about to enter Phase I trials; while peripherally-restricted MTX652 is currently in Phase II investigating acute kidney injury (AKI) associated with cardiac surgery.

Dr Anker Lundemose, Chief Executive Officer of Mission Therapeutics, said: “Mission Therapeutics has made huge strides in developing its pipeline, first progressing MTX652 into Phase II, then obtaining robust preclinical proof-of-concept data for its Parkinson’s candidate MTX325 – published in Nature Communications – followed by regulatory approval for MTX325 clinical trials in the UK. Thanks to this additional £25.2m from our investors, we can now make the next vital steps, progressing with essential clinical trials.”

Dr James B. Summers, Acting Chairman of Mission Therapeutics, said: “Mission’s laser focus on mitophagy has resulted in a promising suite of drugs that tackle a range of hard-to-treat diseases in a unique and novel way. This latest financing round is a sign of our investors’ confidence in the Company and the enormous potential of our clinical assets.”

The Nature Communications paper, published last November by scientists at Cambridge University, Harvard University and Mission Therapeutics, provided key experimental evidence to support the thesis that MTX325 can modify the course of Parkinson’s by targeting USP30. By first using a USP30 knockout mouse model, and then a pharmacological strategy deploying MTX325, they found USP30 inhibition led to protection against loss of dopamine and dopaminergic neurons induced by alpha-synuclein in vivo. USP30 inhibition also reduced potential biomarkers of PD including phosphorylated alpha-synuclein and glial cell activation.

In December, the sister publication Nature Reviews Drug Discovery commented that restoring mitophagy to accelerate the removal of damaged mitochondria was “an appealing disease-modifying therapeutic strategy” for Parkinson’s Disease.

The same month, Mission gained clearance from the US FDA to commence a Phase II trial of MTX652, after the Company received official approval of its Investigational New Drug (IND) application for the candidate drug.

ENDS 

For further information, please contact:

Mission Therapeutics Ltd: Anker Lundemose MD PhD Chief Executive Officer Tel: +44 (0)1223 607 340

Optimum Strategic Communications: Mary Clark, Stephen Adams, Vici Rabbetts Email: mission@optimumcomms.com Tel: +44 (0) 208 078 4357

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.

• 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, UK – 5 December 2023 – 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 modelsi – 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

– ENDS –

For further information, please contact:

 

Mission Therapeutics Ltd

Anker Lundemose MD PhD

Chief Executive Officer

Tel: +44 (0) 122 360 7340

 

Optimum Strategic Communications:

Mary Clark, Stephen Adams, Vici Rabbetts, Vareen Outhonesack

Tel: +44 (0) 208 078 4357

E-mail: mission@optimumcomms.com

 

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://www.nature.com/articles/s41467-023-42876-1

[ii]USP30 inhibition protects dopaminergic neurons (nature.com)

CAMBRIDGE, UK, 2 November 2023 – Mission Therapeutics (“Mission”), a clinical-stage biotech company developing first-in-class therapeutics targeting mitophagy, today announces that it will present an oral abstract on its experimental drug candidate MTX652 at the American Society of Nephrology’s Kidney Week in Philadelphia, from 2-5 November 2023.

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. MTX652 targets USP30, 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. Mitophagy is a quality control system that ensures dysfunctional mitochondria are removed.

Pau Aceves, MS, MSc, PharmD., Head of Clinical Pharmacology and Pharmacometrics, Mission Therapeutics, commented: We look forward to presenting our latest Phase 1 and Modelling & Simulation results on MTX652 for the treatment of acute kidney injury (AKI). The American Society of Nephrology is a major organization working toward a goal of a world without kidney diseases and we are excited to have the opportunity to share our progress at this important conference.

Details of the presentation are as follow:

Presentation Title: MTX652, a Novel Selective USP30 Inhibitor for the Treatment of AKI: Phase 1 Results in Healthy Subjects and Model-Driven Human Efficacious Dose Projections

Session Name: Onconephrology and Precision Pharmacology
Session Date: Thursday, November 2^nd, 2023
Presentation Time: 4:48 PM – 4:57 PM

Presenter: Pau Aceves, MS, MSc, PharmD., Head of Clinical Pharmacology and Pharmacometrics

Location: Room 107, Pennsylvania Convention Center

Mission has completed its first Phase I clinical study with MTX652, in which it demonstrated 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.

– ENDS –

For further information, please contact:

Mission Therapeutics Ltd: Anker Lundemose MD PhD Chief Executive Officer Tel: +44 (0)1223 607 340

Optimum Strategic Communications: Mary Clark, Stephen Adams, Vici Rabbetts Email: mission@optimumcomms.com Tel: +44 (0) 208 078 4357

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.

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.

Professor Steve Jackson earns KBE for services to innovation and research

CAMBRIDGE, UK – 17 June 2023 – Mission Therapeutics (“Mission”), a drug discovery and development company focused on protein homeostasis by selectively inhibiting deubiquitylating enzymes (DUBs), sends its congratulations to the company’s founder, Professor Steve Jackson, who has been made a Knight Bachelor as part of His Majesty The King’s Birthday Honours List.

Buckingham Palace confirmed the award was for services to innovation and research when the full list was announced on 17 June 2023.

Professor Jackson was appointed Frederick James Quick Professor of Biology at the University of Cambridge in 1995. He founded Mission Therapeutics in 2011 in order to advance and explore new therapeutic opportunities through his research in protein ubiquitylation and deubiquitylation. He has served as Chairman of the Scientific Advisory Board since the Company’s founding.

Professor Jackson also serves as Senior Group leader at Cancer Research UK Cambridge Institute, having previously been Head of Laboratories at the University’s Gurdon Institute. His team was responsible for the discovery of the mechanism that led to the creation of Olaparib, the world’s first marketed DNA-repair enzyme inhibitor, which has now been administered to over 60,000 patients globally.

Anker Lundemose, CEO of Mission Therapeutics, said: “The team at Mission are delighted for Steve and wish him many congratulations. His pioneering research and discoveries in the DUB field are the inspiration for Mission. His continued guidance on the Company’s development has been invaluable. The team at Mission are very proud of his achievements and this recognition in the Birthday Honours list is richly deserved.”

– ENDS –

FOR MORE INFORMATION PLEASE CONTACT:

Mission Therapeutics Ltd Anker Lundemose MD PhD Chief Executive Officer Tel: +44 (0)1223 607 340

Instinctif Partners Melanie Toyne-Sewell / Adam Loudon Tel: +44 (0) 20 7457 2013 missiontherapeutics@instinctif.com

 NOTES TO EDITORS:

About Mission Therapeutics

Mission Therapeutics is a clinical-stage drug development company targeting the ubiquitin pathway for the treatment of kidney disease, heart disease and neurodegenerative disease. The Company has built a leading platform for the discovery and development of first-in-class, small molecule drugs that selectively target deubiquitylating enzymes (DUBs) – an emerging drug class that is attracting significant commercial interest in the area of protein homeostasis.

Mission has strong links with key academic and research centers, including Prof. Steve Jackson’s Cancer Research UK Laboratories at the University of Cambridge Gurdon Institute, and leading UK centres in neurodegenerative diseases. The Company also has secured major industry partnerships, including its collaboration with AbbVie in November 2018, for the research and preclinical development of specified DUB inhibitors for the treatment of Alzheimer’s Disease and Parkinson’s Disease. The Company is managed by a team with broad international, commercial and clinical-science experience.

To date the Company has received $112 million in funding and its investors comprise blue chip institutional and corporate investors including: Pfizer Venture Investments, Sofinnova Partners, Roche Venture Fund, SR One, IP Group and Rosetta Capital. Mission Therapeutics was founded in 2011 and is based at the Babraham Research Campus, Cambridge, UK.

For more information, please visit our website, www.missiontherapeutics.com, or follow us on Twitter or LinkedIn.