MTX652 / Mission Therap - LARVOL DELTA

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

Discovery of potent and selective activity-based probes (ABPs) for the deubiquitinating enzyme USP30. (PubMed, RSC Chem Biol) - "A USP30 inhibitor, MTX652, has recently entered clinical trials as a potential treatment for mitochondrial dysfunction...Target engagement studies demonstrate that IMP-2587 and IMP-2586 engage active USP30 at nanomolar concentration after only 10 min incubation time in intact cells, dependent on the presence of the USP30 catalytic cysteine. Interestingly, proteomics analyses revealed that DESI1 and DESI2, small ubiquitin-related modifier (SUMO) proteases, can also be engaged by these probes, further suggesting a novel approach to develop DESI ABPs."

Journal • Metabolic Disorders • Oncology • Targeted Protein Degradation

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

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 Successfully Completes First Clinical Assessment for Lead DUB Program, MTX652 (Businesswire) - "Mission Therapeutics...announced the successful completion of its first Phase I clinical assessment for lead USP30 DUB inhibitor, MTX652....The trial successfully achieved its key goals of demonstrating the safety, tolerability and pharmacokinetics of MTX652, given as single- and multiple-ascending doses of oral solution or suspension to the healthy subjects. MTX652 was shown to be well tolerated and safe up to a single dose of 200mg and multiple doses of 100mg once daily for 14 days. It also demonstrated an excellent pharmacokinetic profile with dose proportionality, and time independent exposure....'We are now in the process of planning for our next stage of clinical development and are looking forward to MTX652 entering further clinical trials later this year.'"

New trial • P1 data • Trial status • Idiopathic Pulmonary Fibrosis • Interstitial Lung Disease