Medicxi will invest up to €9m ($10m) in the asset-centric company to show clinical efficacy of Mavalon’s GDNF-inducer drug candidate, an mGluR3 PAM molecule discovered by Domain Therapeutics.

Domain Therapeutics, a biopharmaceutical company that specializes in the discovery and development of G protein-coupled receptor (GPCR) drugs, today announces the creation of Mavalon Therapeutics, a company focused on stopping the progression of Parkinson’s disease. Medicxi, a venture fund dedicated to financing asset-centric companies, has committed up to €9m ($10m) in Mavalon.

Over the past two decades, biotech companies and clinicians have tried to develop a cure for Parkinson’s disease based on Glial cell line-Derived Neurotrophic Factor (GDNF), a naturally occurring factor promoting the growth of dopamine neurons. Some clinical results were stunning, with patients experiencing a spectacular improvement in their symptoms and a return to 'normal' life. However, delivery of GDNF has been a major challenge. As it cannot be absorbed orally, a variety of delivery methods have been tested including direct pumping into the brain, intranasal delivery and gene therapy. Newly formed Mavalon Therapeutics is developing the first orally available small molecule able to induce GDNF production within the brain of Parkinson’s patients, a treatment that will bring benefits to a larger population than the current intra-brain delivery of GDNF.

The drug candidate, a positive allosteric modulator of the metabotropic glutamate receptor type 3 (mGluR3 PAM), was discovered and initially developed by Domain Therapeutics with the support of the Michael J. Fox Foundation. This program is the third Parkinson’s disease drug candidate discovered by Domain Therapeutics and further developed by an asset-centric company. An mGluR4 PAM is ready to enter Phase II at Prexton Therapeutics and a dual adenosine A2A/A1 receptor antagonist is in preclinical development at Kaldi Pharma. Both treatments address Parkinson’s symptoms while Mavalon’s drug is aimed at stopping the progression of the disease and at reversing its effects.

“Mavalon’s asset clearly fits with Medicxi’s investment strategy supporting biopharma companies at the forefront of innovation,” said Michèle Ollier, partner at Medicxi Ventures. “The mGluR3 PAM-mediated GDNF induction certainly represents a very promising approach with strong market potential.”

“We are very proud to have Medicxi as investor partner in Mavalon. This investment highlights Domain Therapeutics’ expertise in the GPCR area and its ability to repeatedly select first-in-class drug candidates for major therapeutic indications,” said Pascal Neuville, CEO of Domain Therapeutics. “We are confident in the capacity of the Mavalon team to rapidly move this asset forward towards the clinical stage and make this promising treatment available to the Parkinson’s disease patient population.”

About Parkinson’s disease and mGluR3 PAM program

Parkinson's disease is a chronic and progressive neurological disorder characterized by a number of symptoms including tremors, limb stiffness, slowness of movements and difficulties with posture and balance. It is estimated that more than 10 million people worldwide live with the disease. As Parkinson's disease is more prevalent in people over 60 the incidence of the disease is expected to increase along with the average age of the population.

The Glial cell line-Derived Neurotropic Factor (GDNF) is a growth factor promoting neuronal survival and growth that focused the attention of the pharma industry as the basis of a disease-modifying therapy. The main challenge remains the delivery of this growth factor. Several ongoing trials use different routes and modes of direct administration of GDNF (either invasive based on surgery or via viral particles) with limited results due to delivery heterogeneity.

mGluR3 receptor has been shown - by Ferdinando Nicoletti’s group in Italy - to promote GDNF production when activated by glutamate release. The glutamate is released by degenerating neurons in the brain of Parkinson’s patients. The mGluR3 PAM drug candidate that Mavalon is developing will further induce a physiological GDNF production at the site of neuron degeneration.

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