MTX325 / Mission Therap - LARVOL DELTA

Mission Therapeutics raises $13.3 million to progress first-in-class Parkinson's disease candidate MTX325 through clinical trials (PRNewswire) - "Financing will support the full execution of Phase Ib proof-of-mechanism study of MTX325 in patients with Parkinson's disease (PD)....Phase Ib study due to start in H1 2026."

Financing • New P1 trial • Parkinson's Disease

Targeting mitophagy in neurodegenerative diseases. (PubMed, Nat Rev Drug Discov) - "Accumulating genetic, molecular and preclinical model-based evidence now supports targeting mitophagy in neurodegenerative diseases. Despite clinical development challenges, small-molecule-based approaches for selective mitophagy enhancement - namely, USP30 inhibitors and PINK1 activators - are entering phase I clinical trials for the first time."

Journal • Review • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Genetic Disorders • Huntington's Disease • Metabolic Disorders • Movement Disorders • Parkinson's Disease

The Ubiquitin-Specific Protease 30 Inhibitor, MTX652, Attenuates Cardiac Dysfunction And Remodelling In a Murine Model Of Transverse Aortic Constriction (AHA 2024) - "Captopril (30 mg/kg/d, n=13) was also included as a positive control. The USP30 inhibitor, MTX652 significantly protected mice from TAC induced cardiac hypertrophy and LV dysfunction. Furthermore, MTX652 potentiates ubiquitylation of TOM20 as a mechanism to promote mitophagy. These data suggest our clinical stage molecule could provide a novel therapeutic approach for the treatment of cardiac hypertrophy and heart failure."

Preclinical • Cardiovascular • Congestive Heart Failure • Heart Failure • Targeted Protein Degradation

Mission Therapeutics awarded $5.2m from The Michael J. Fox Foundation and Parkinson’s UK to advance potential disease-modifying treatment MTX325 (PRNewswire) - "Mission Therapeutics...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...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."

Financing • Trial status • CNS Disorders • Parkinson's Disease

Mission Therapeutics raises £25.2 million to progress clinical candidates in the area of mitophagy (PRNewswire) - "Mission Therapeutics...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."

Financing • CNS Disorders • Idiopathic Pulmonary Fibrosis • Parkinson's Disease • Respiratory Diseases

Mission Therapeutics granted MHRA Clinical Trial Authorisation (CTA) for MTX325 for the treatment of Parkinson's Disease (PRNewswire) - "Mission Therapeutics...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)....'We look forward to starting the trial in the coming months, and providing preliminary first-in-human data later in 2024.'"

New P1 trial • CNS Disorders • Parkinson's Disease

Knockout or inhibition of USP30 protects dopaminergic neurons in a Parkinson's disease mouse model. (PubMed, Nat Commun) - "These observations were recapitulated with a potent, selective, brain-penetrant USP30 inhibitor, MTX115325, with good drug-like properties. These data strongly support further study of USP30 inhibition as a potential disease-modifying therapy for PD."

Journal • Preclinical • CNS Disorders • Metabolic Disorders • Movement Disorders • Parkinson's Disease • SNCA

Mission Therapeutics announces publication in Nature Communications outlining potential of experimental drug MTX325 as a disease-modifying therapy for Parkinson's Disease (PRNewswire) - "Mission Therapeutics...today announces the publication of a peer-reviewed article...in the journal Nature Communications, which can be viewed here. The research was the result of collaborative work between Cambridge University, Harvard Medical School, and Mission Therapeutics....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."

Preclinical • CNS Disorders • Parkinson's Disease

MTX652, a Novel Selective USP30 Inhibitor for the Treatment of AKI: Phase 1 Results in Healthy Subjects and Model-Driven Human Efficacious Dose Projections (KIDNEY WEEK 2023) - "This is the first report of clinical data with a USP30 inhibitor. MTX652 presented an acceptable safety/PK profile in healthy subjects. PK/PD modelling enabled the selection of a safe and well tolerated dose predicted to have renal protective effects in humans."

Clinical • P1 data • Cardiovascular • Fibrosis • Immunology • Nephrology • Renal Disease • Reperfusion Injury • Targeted Protein Degradation

Mission Therapeutics to Present at Michael J. Fox Foundation's 15th Annual Parkinson's Disease Therapeutics Conference (PRNewswire) - "Mission Therapeutics...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)."

Preclinical • CNS Disorders • Parkinson's Disease

Mission Therapeutics Awarded Follow-On Therapeutic Pipeline Program Grant from The Michael J. Fox Foundation (Businesswire) - "Mission Therapeutics...announced today that it has been awarded a Therapeutic Pipeline Program grant of approximately 0.5M USD from The Michael J. Fox Foundation for Parkinson’s Research (MJFF)....This research grant will support testing of Mission’s lead CNS-penetrant USP30 DUB inhibitors in an in vivo model of Familial Parkinson’s Disease (PD), as well as ongoing preclinical development towards candidate selection."

Financing • CNS Disorders • Parkinson's Disease

Mission Therapeutics raises £12m and deepens Pfizer relationship (Cambridge Independent) - "Mission Therapeutics has raised $15m (£12m) in equity investment and expanded its relationship with Pfizer....Capital would support the development of its world-leading DUB platform, and growth in its pipeline of DUB inhibitor programmes....Mission and Pfizer Inc have expanded their relationship by entering into an evaluation and option agreement for DUB target validation....The new agreement will enable Pfizer to access specific DUB inhibitors from Mission’s platform....Pfizer will have the option to negotiate target exclusivity for each of the DUBs of interest, but the deal does not include any of Mission’s own lead DUB programs, such as USP30."

Financing • Licensing / partnership • CNS Disorders • Parkinson's Disease