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In 2012, Domain Therapeutics has granted Prexton Therapeutics (Geneva – Switzerland) an exclusive option to license and develop metabotropic glutamate receptor 4 (mGluR4) Positive Allosteric Modulator (PAM) drugs targeting Parkinson’s disease. The chemical series was previously developed through a licensing and collaboration agreement signed between Domain and Merck Serono, a division of Merck (Darmstadt – Germany) in January 2011. Under the terms of the initial agreement between Domain Therapeutics and Prexton Therapeutics – a spin-off company of Merck Serono – Prexton benefited from an exclusive license option to progress the mGluR4 PAM drug candidates into clinical development.

After having exercised the exclusive option, Prexton entered into license agreement with Domain Therapeutics, selected an mGluR4 PAM candidate, PXT002331, and conducted regulatory preclinical development and Phase I. In September 2016, Prexton announced the successful completion of the Phase I clinical trial.

In 2017, Prexton initiated a Phase II to assess the safety and efficacy in reducing motor complications of Levodopa therapy in subjects with PD experiencing end-of-dose wearing off and Levodopa-Induced dyskinesia. The company was acquired early in March 2018 by Lundbeck (see press release).

Program description

mGluR4 PAM (Foliglurax-exit)

  • Discovery
  • Candidate
  • Preclinical
  • Clinical

Recent studies have demonstrated that a promising alternative to dopaminergic treatments for Parkinson’s disease (PD) resides in the correction of excessive glutamate transmission in the basal ganglia in particular through the activation of presynaptic metabotropic glutamate type 4 receptors (mGluR4)

We discovered a novel chemical family of mGluR4 PAMs. This series was licensed to Prexton Therapeutics, which together with Domain’s team identified PXT002331 (foliglurax) as the most promising compound of the series with robust validation in the golden MPTP-non-human primate model of PD (Charvin et al, 2018). This study has been performed with the support of the Michael J. Fox Foundation.

Prexton was the first company to initiate a clinical phase II with a mGluR4 PAM, across six countries in Europe (study NCT03162874, AMBLED) before being acquired by Lundbeck in March 2018.

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