Montara Therapeutics, a preclinical-stage biotech company focused on brain-selective therapies, has secured a $3.3 million non-dilutive grant from The Michael J. Fox Foundation for Parkinson's Research (MJFF) to develop a novel treatment for Parkinson's disease. The funding will support the application of Montara's innovative BrainOnly™ platform to create a brain-selective LRRK2 inhibitor that could overcome significant challenges that have plagued previous development efforts targeting this protein.
LRRK2 (leucine-rich repeat kinase 2) is recognized as the most common genetic cause of inherited Parkinson's disease. Despite its strong genetic validation as a therapeutic target, no LRRK2-targeting therapy has successfully completed late-stage clinical trials, largely due to toxicity issues when the protein is inhibited in peripheral tissues.
Innovative Approach to CNS Drug Delivery
Montara's BrainOnly™ platform represents a novel approach to increasing the therapeutic index of CNS drugs. Each BrainOnly™ product consists of a two-molecule combination: a brain-penetrant drug paired with a universal peripheral blocker designed to prevent the drug's activity outside the brain.
"MJFF's network and expertise make them a wonderful partner to our mission of developing BrainOnly™ therapies that selectively target the CNS while blocking harmful peripheral effects—in this case, enabling and accelerating the development of new therapies for Parkinson's," said Nicholas T. Hertz, Ph.D., Founder and CEO of Montara.
The company's approach could potentially solve a critical problem in LRRK2 inhibitor development. When LRRK2 is inhibited in peripheral tissues and organs, particularly the lungs and kidneys, significant adverse effects can occur. By restricting the inhibitor's activity to the brain, Montara aims to maintain therapeutic efficacy while avoiding these toxicities.
Joining the LITE Program
As part of this collaboration, Montara will also join MJFF's LRRK2 Investigative Therapeutics Exchange (LITE) program, which was launched in 2024 to accelerate the development of LRRK2-targeted therapies and advance progress toward new LRRK2-relevant clinical biomarkers.
Dario Alessi, PhD, Director of the MRC Protein Phosphorylation Unit at the University of Dundee and LITE principal investigator, expressed enthusiasm about the collaboration: "The LITE initiative seeks to provide opportunities for better understanding Parkinson's and treating it. We welcome Montara to the initiative and are excited to explore how the Company's BrainOnly platform could unlock the enormous potential of LRRK2-targeted therapies in a way that mitigates adverse effects."
The LITE program fosters international collaboration across more than 30 academic and clinical centers and more than a dozen companies. It is governed by a steering committee consisting of MJFF staff and field leaders and is implemented by the University of Dundee in the United Kingdom.
Building on Previous Success
Miratul Muqit, Professor of Experimental Neurology at Dundee and a member of Montara's Scientific Advisory Board, highlighted the company's track record: "This team has an impressive track record in the Parkinson's space, having advanced a potentially disease-modifying treatment at Mitokinin, and is really well positioned to replicate this success with the BrainOnly™ platform and its promise for LRRK2-targeted therapy."
The grant from MJFF aligns with the foundation's strategic research agenda to help drug developers validate new findings in Parkinson's biology and enable novel therapeutic approaches. The funding will specifically support Montara's development of a wholly-owned next-generation BrainOnly™ LRRK2 inhibitor drug candidate.
Broader Implications for CNS Drug Development
Montara believes its BrainOnly™ platform has potential applications beyond Parkinson's disease. The technology could address major safety and tolerability challenges in the treatment of various neurological diseases by enabling higher, more effective dosing of CNS-targeted therapies while minimizing peripheral side effects.
The platform may also make it possible to target proteins previously considered "undruggable," potentially expanding therapeutic options for patients with neurological conditions that currently have limited treatment options.
Montara Therapeutics is backed by several prominent investors, including SV Health Investors' Dementia Discovery Fund, Two Bear Capital, KdT Ventures, Dolby Family Ventures, and BEVC.
