DUB

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.

Agreement leverages Ubiquigent’s DUB-focused drug discovery platform to support the development of novel therapeutic candidates for multiple disease targets selected by Nanna Therapeutics DUNDEE, Scotland--(BUSINESS WIRE)-- Ubiquigent Limited (Ubiquigent), a drug discovery and development company harnessing novel deubiquitinase (DUB) modulators as new therapeutics for areas of high unmet medical need, today announced an agreement with Nanna Therapeutics (Nanna). Under the terms of the agreement, Ubiquigent will provide Nanna with access to its deubiquitylase (DUB) focused drug discovery platform to support the development of novel therapeutics for human disease targets selected by Nanna. The DUB enzymes regulate ubiquitination in the ubiquitin-proteasome system (UPS). Dysregulation of DUB activity is implicated in many human diseases, highlighting their importance and promise for the development of novel therapeutics. Ubiquigent is the partner chosen by many leading industry and academic organisations for their drug discovery programmes in the fields of protein degradation, stabilisation and cellular signalling. Ubiquigent has an established specialised drug discovery platform and long-standing expertise in the exploitation of the DUBs for therapeutic benefit. The platform can be applied to support the development of DUB inhibitors, DUB-targeting PROTACs, and DUBTACs across any therapeutic area. Jason Mundin, CEO of Ubiquigent, commented: “We are delighted to enter this latest agreement and look forward to supporting the team at Nanna Therapeutics. Our platform was established to support those seeking to modulate DUB activity for therapeutic benefit and has been used by a long list of global partners which we are very pleased to add Nanna Therapeutics to.” To learn more about Ubiquigent’s discovery and development platform, please visit . View source version on businesswire.com: Contacts Esmé Walters Zyme Communications E-mail: esme.walters@zymecommunications.com Phone: +44 (0) 7377 543244 Source: Ubiquigent View this news release online at:

CAMBRIDGE, England, Oct. 10, 2023 /PRNewswire/ -- 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 Science 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. 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. SOURCE Mission Therapeutics