M102 / Aclipse Therap, The University of Sheffield - LARVOL DELTA

M102, a combined NRF2 and HSF1 activator, attenuates motor decline in two transgenic mouse models of amyotrophic lateral sclerosis (ALS) (ALS-MND 2024) - "In the TDP-43Q331K model there was a significant improvement in compound muscle action potential (CMAP) of the hindlimb muscle, weight and gait parameters at 6 months of age in the M102 dose group when compared to vehicle. Tissue analysis showed upregulation of HSF1 targets at 3 and 6 months of age with upregulation of NRF2 targets at 3 months of age. The SOD1G93A mice were dosed orally as this is the intended dose route for humans."

Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders • HSF1

Aclipse Therapeutics Selected to Present M102 ALS Clinical Development Program at Prestigious ALS and Motor Neurone Disease Symposia (Businesswire) - "Aclipse Therapeutics...announced that its M102 drug development program has been selected for presentations at the premier amyotrophic lateral sclerosis (ALS) and motor neurone disease (MND) symposia this fall...Dr. Ira Kalfus will present on M102 at the Industry Day of this symposium on November 14, 2024. Dr. Kalfus’ presentation will highlight the M102 dataset indicating the potential for ALS disease-modification and reversal, our efforts to stratify patients into those with the highest probably of drug response, and our clinical development plans in ALS...At the 35th International Symposium on ALS and Motor Neurone Disease on December 6 to 8, 2024 in Montreal, Canada, Dr. Amy Keerie, a leading SITraN researcher, will report on M102’s ability to significantly improve compound muscle action potential (CMAP), weight, and gait parameters in the TDP-43^Q331K animal model of ALS in a dose dependent manner, correlating with the preservation of motor neurons."

Clinical • Amyotrophic Lateral Sclerosis • CNS Disorders

M102 A multi-target drug suitable for personalised medicine approaches in ALS (ALS-MND 2023) - "As anticipated, by co-culturing these patient-derived astrocytes with healthy motor neurons, we have identified responders and non-responders to M102. Using a combination of immunostaining and immunoblotting techniques, we confirmed that this drug has a modest effect in inducing activation of nuclear factor erythroid 2-related factor 2 (NRF2) and heat shock factor 1 (HSF1) signalling pathways in patient-derived neurons (n = 6), but a much higher effect activating these pathways in patient-derived astrocytes (n = 3). Furthermore, our data suggest M102 can reduce TDP43 proteinopathy in patient-derived astrocytes, by reducing the levels of TDP43 fragments and increasing full length protein (n = 3)."

Proteinopathy • HSF1 • TARDBP

Aclipse Therapeutics Announces $1.475 Million Award from the US Department of Defense (Businesswire) - “Aclipse Therapeutics and its subsidiary Aclipse One Inc…announced that the Company has received a therapeutic development award of $1.475 million from the Congressionally Directed Medical Research Programs (CDMRP) at the United States Department of Defense’s (DOD) U.S. Army Medical Research and Development Command (USAMRDC), as part of its FY21 Amyotrophic Lateral Sclerosis Research Program (ALSRP) Therapeutic Development Award. The award will fund the research by the Company and its collaborator, the Sheffield Institute for Translational Neuroscience (SITraN) at the University of Sheffield in the United Kingdom (UK) entitled, ‘Development of M102 to Investigational New Drug (IND) Stage for Initiation of Phase I Clinical Trials for Treating Amyotrophic Lateral Sclerosis (ALS).’”

Financing • Amyotrophic Lateral Sclerosis • CNS Disorders

£1.6 million grant awarded to advance development of MND drug candidate (News-Medical) - "Researchers from the University of Sheffield's Institute for Translational Neuroscience (SITraN) have been awarded a £1.6 million grant from the Medical Research Council (MRC). The grant will support their partnership with Aclipse Therapeutics to advance the translational development of M102...'The MRC award, coupled with our recent FightMND grant award, accelerates M102's development into its first-in-human clinical studies and validates M102's biology and potential for a precision medicine approach...M102 may have applications in a wide array of conditions associated with impaired neuronal function such as Friedreich's ataxia...Parkinson's disease.'"

Financing • CNS Disorders • Friedreich ataxia • Parkinson's Disease

Aclipse Therapeutics Announces $2.2 Million Grant from UK’s Medical Research Council for Development of M102 (Businesswire) - “Aclipse Therapeutics…announced that the Company and its collaborator, The Sheffield Institute for Translational Neuroscience (SITraN) at the University of Sheffield in the United Kingdom (UK), were awarded a drug development research grant of £1.6 million (approximately US $2.2 million) from the UK’s Medical Research Council (MRC)…to support the translational development of M102. M102 is Aclipse’s drug candidate for the treatment of amyotrophic lateral sclerosis (ALS)…”

Financing • Amyotrophic Lateral Sclerosis • CNS Disorders