Prexton Therapeutics has brought its mGluR4-positive allosteric modulator through a first-in-human trial. And, with the Merck Serono spinout viewing safety data from the trial of 64 healthy volunteers favorably, it is set to advance into a Phase II study in Parkinson’s disease patients in the first half of next year.
Geneva, Switzerland-based Prexton initiated the single and multiple ascending-dose trial to assess the safety, tolerability and pharmacokinetics of PXT002331 in healthy volunteers. Prexton is yet to post a proper look at the data. But, in its view, the mGluR4-positive allosteric modulator was safe and well tolerated at doses in excess of those that have been efficacious in animal models of Parkinson’s, giving it the confidence to commit to a Phase II trial in patients with the condition.
"We are very happy with the completion of the first clinical trial with our lead compound PXT002331, which is the first mGluR4 PAM ever to enter a clinical phase. This achievement ensures Prexton is in a solid position for a successful clinical development of PXT002331,” Prexton CEO Francois Conquet said in a statement.
The readout marks a step forward for Prexton, which emerged from the shuttering of Merck Serono’s Geneva R&D center with €2.1 million ($2.3 million) in seed funding and intellectual property its parent company was working on with Domain Therapeutics. Merck Serono, through the €30 million biotech-creation program it created to mitigate the Geneva cuts, helped Prexton get up and running, before Sunstone Capital and Ysios Capital took it to the next level with an €8.7 million Series A last year.
Talking to FierceBiotech at the time of the Series A, Conquet said the €8.7 million would take Prexton up to a readout from the Phase I trial, suggesting the company will need fresh funds or financial support to execute the next stage of development.
For Conquet, the Phase II trial represents another chapter in a multidecade drive to realize the potential of metabotropic glutamate receptors (mGluR). Conquet’s interest in the potential of mGluR spans a decade-long spell at GlaxoSmithKline ($GSK), the founding and running of Addex Therapeutics (SIX:ADXN) and now time at the helm of Prexton. Over that period, overall interest in mGluR has waxed and waned--Merck ($MRK) dropped Addex’s mGluR4 Parkinson’s drug in 2011--but Conquet has kept the faith.
The CEO’s interest in the receptor is underpinned by a belief that it represents a better target than dopaminergic pathways. While the impact of drugs that target dopaminergic pathways is hamstrung by the deaths of dopamine-producing nerve cell that characterize Parkinson’s, mGluR4 is free from this progressively-intensifying brake on efficacy, potentially enabling drugs that target it to achieve longer-term symptom control.