USP30

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, England, March 14, 2024 /PRNewswire/ -- 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. 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. SOURCE Mission Therapeutics

Mission Therapeutics’ strategy of boosting a natural cellular recycling process, called mitophagy, to treat neurodegenerative and mitochondria-related diseases has attracted £25.2 million ($32.1 million) in fresh funding. The biotech, which also boasts a pair of pharma partnerships, is focused on developing small molecule inhibitors of de-ubiquitylating enzymes (DUBs) – the brakes on the garbage disposal system.  Since its founding in 2011, Mission has raised a total of £117 million. Thursday’s series D financing was jointly led by a syndicate of existing investors, including Pfizer Venture Investments. The pharma giant’s first investment in Mission was over a decade ago, and in 2020, Pfizer led a £12 million financing and also staked a claim on its DUB platform. Under the deal, Pfizer has the option to negotiate target exclusivity for certain, prespecified DUB inhibitors. The Cambridge-based biotech also has a 2018 tie-up with AbbVie for two DUB programmes to treat Alzheimer’s disease. Other backers of the round include Sofinnova Partners, Roche Venture Fund, SR One, IP Group, and Rosetta Capital.DUB developmentWhile DUBs’ role in mitophagy-associated diseases is well established, they have been historically difficult to selectively and specifically target with small molecules, as they comprise a large family of proteins. Mission’s lead candidate, MTX652, is in Phase II testing for acute kidney injury (AKI) associated with cardiac surgery. Thursday’s round will help progress the company’s second candidate, MTX325, which has been cleared to start a Phase I trial for Parkinson’s disease (PD) in the UK. Both programmes target USP30, a key DUB in the regulation of mitophagy. According to Mission, USP30 inhibition can promote the degradation of disease-associated proteins and impaired mitochondria, potentially improving cellular health and longevity. If cells don’t routinely recycle their mitochondria, an accumulation of the dysfunctional organelles can lead to cellular degeneration, particularly of neurons. Mitochondrial dysfunction is a key driver of PD mechanisms, Mission CEO Anker Lundemose told FirstWord. Inhibiting USP30 to promote mitophagy is “likely to have a positive impact on dopaminergic neurons undergoing chronic degenerative processes, as such degeneration results in functional impairment,” Lundermose added.Mission has shown that, in a mouse model of PD, USP30 inhibition can help protect against loss of dopamine and dopaminergic neurons induced by alpha-synuclein.

Mission gains clearance from US FDA for Phase II trial of MTX562 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, England, Dec. 14, 2023 /PRNewswire/ -- 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, which will take place at 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 MTX562 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. 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] [ii] SOURCE Mission Therapeutics