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, 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

Mission Therapeutics commences landmark trial of MTX325, a potential disease-modifying treatment for Parkinson’s Disease

    • 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:

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

Mission Therapeutics raises £25.2 million to progress clinical candidates in the area of mitophagy

  • 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.

Mission Therapeutics announces US FDA approval to initiate Phase II clinical trial of its lead asset MTX652 in Acute Kidney Injury

  • 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:

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.

[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/

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, 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)

Mission Therapeutics announces publication in Nature Communications outlining potential of experimental drug MTX325 as a disease-modifying therapy for Parkinson’s Disease

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 titledKnockout 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:

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 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.

Mission Therapeutics to Present Abstract at American Society of Nephrology (ASN) Kidney Week 2023

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 2nd, 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.

Mission Therapeutics to Present at Michael J. Fox Foundation’s 15th Annual Parkinson’s Disease Therapeutics Conference

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 15th 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:

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 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.

 

 

Mission Therapeutics founder to receive Knighthood in Birthday Honours List

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.

Mission Therapeutics to Present at the Targeted Protein Degradation Europe Conference 2023

Presentation at 9am Thursday, March 30th 2023

CAMBRIDGE, UK– 6 March 2023 – Mission Therapeutics (“Mission”), a drug discovery and development company focused on protein homeostasis by selectively inhibiting deubiquitylating enzymes (DUBs), announces that Dr Nick Edmunds, Chief Technology Officer at Mission, will be presenting at the Targeted Protein Degradation Europe conference 2023.

Mission Therapeutics’ presentation will take place 9am Thursday, March 30th, 2023, at The Tower Hotel, St Katharine’s Way, London, E1W 1LD. The presentation will cover the Development of a DUB Inhibitor Platform & Emerging Data from a USP30 Inhibitor, based on Mission’s recent research. It has been highlighted as one of 5 key talks not to miss by the conference organisers.

The event, which will take place in London, 28th-30th March, is the Leading Forum Showcasing Key Stakeholders & Expert Minds from the European Degradation Community. The conference is returning to London for its third year to discuss key topics in what is expected to be a landmark year for the degradation community.

Prospective attendees can register for the event here: https://tpd-europe.com/

If you would like to meet with Nick and the team at TPD Europe, please contact info@missiontherapeutics.com.

– ENDS –

FOR MORE INFORMATION:

Mission Therapeutics Ltd

Anker Lundemose MD PhD

Chief Executive Officer

Tel: +44 (0)1223 607 340

Instinctif Partners

Melanie Toyne-Sewell / Agnes Stephens

Tel: +44 (0) 20 7457 2013

missiontherapeutics@instinctif.com

NOTES TO EDITORS:

About Mission Therapeutics

Mission Therapeutics is an early-stage drug development company targeting the ubiquitin pathway for the treatment of kidney disease, neurodegenerative disease, rare mitochondrial diseases and fibrosis. 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 $103 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.