DUBLIN – Prexton Therapeutics SA raised €29 million (US$31 million) in a series B round to conduct two phase II trials in Parkinson’s disease of its metabotropic glutamate receptor 4 (mGluR4) agonist, foliglurax (PXT002331).

The transaction reflects the smooth progress the program has made to date. It’s just under two years since Geneva-based Prexton raised $10 million in series A funding to move the compound into clinical development, following positive – but as yet unpublished – data in a macaque model of Parkinson’s. (See BioWorld Today, Feb. 25, 2015.)

The preclinical data, coupled with data from a phase I trial in healthy volunteers, which showed that foliglurax was safe and well-tolerated at doses above those that elicited effects in the preclinical models, were both crucial to raising the new cash. Support from key opinion leaders also helped.

“We knew exactly how we wanted to proceed,” Prexton founder and CEO Francois Conquet told BioWorld Today. “We just had to design the most appropriate phase II clinical trial in patients to show a possible effect of our compound.”

The company will conduct a phase II study in Europe, which will recruit 150 patients with medium- or late-stage disease. “This trial, for the first time, will [simultaneously] measure different aspects of the disease, which are normally considered separately,” Conquet said. Its primary endpoint will assess the effect of foliglurax on symptoms of Parkinson’s disease measured using the Unified Parkinson’s Disease Rating Scale (UPDRS). The secondary endpoint will measure the impact of foliglurax on dyskinesia, or involuntary movement, associated with levodopa (L-dopa), the long-established standard of care in Parkinson’s treatment.

A smaller trial in the U.S., which will recruit 40 participants, will focus specifically on patients with high levels of drug-induced dyskinesia. The problem is particularly pronounced in the U.S. because, Conquet said, it has a different culture of prescribing L-dopa. American patients are highly intolerant, so the drug is administered more aggressively than in Europe. Yet each patient has a finite quantity of what Conquet called “L-dopa capital.” After an initial honeymoon period, when the drug works well, its positive effects decline, and its negative side effects increase.

“Once a physician gives a patient L-dopa, he knows the clock starts ticking,” he said.

Prexton’s approach does not address the core pathophysiology of Parkinson’s disease – the gradual loss of dopaminergic neurons in the substantia nigra pars compacta, the midbrain region associated with movement control, reward and addiction. External administration of L-dopa or dopamine agonists cannot compensate for the problem in the long run. “You can never catch up with the degradation of the neurons,” he said.

Instead, it aims to restore equilibrium to compensatory brain circuits in the basal ganglia, which are also disrupted by the damage to the dopaminergic neuron, leading to increased levels of the excitatory neurotransmitter glutamate. Stimulation of mGluR4 counters that effect. “It’s all a matter of equilibrium between excitation and inhibition,” Conquet said.

Foliglurax is an adjunctive therapy – it will be offered on top of existing therapy. Eventually, it may help to prolong the “honeymoon period” for L-dopa and dopamine agonists, by enabling physicians to reduce the dose of the latter compounds. But that hypothesis will be tested in the future. The upcoming trials will follow standard dosing protocols.

PLENTY OF OPTIONS

The new funding round was co-led by Forbion Capital Partners, of Naarden, the Netherlands, and Seroba Life Sciences, of Dublin. Both funds are in receipt of cash from the European Investment Fund, the European Union’s arm for fostering the growth of small and medium-sized enterprises. To satisfy their investment requirements – and to avail of Dutch R&D and tax incentives – Prexton will establish an operation in the Netherlands while maintaining its existing Swiss base.

Forbion partner Marco Boorsma told BioWorld Today that the fund had encountered Prexton when it was raising its series A round but passed then because it seemed too far from a potential exit. At that point, the company was still in lead optimization, he said. Its swift execution since then, its efficient use of capital and its strong data package all weighed on Forbion’s investment decision this time around.

The upcoming trials will read out in 2019. Positive data will give it plenty of options. “We know there’s keen interest in general in the pharma community for innovative Parkinson’s disease programs,” Boorsma said. New therapeutic modalities and new modes of action are “pretty limited” in Parkinson’s, he said.

Prexton represents the first biotech investment for Seroba’s third life sciences fund, which recently reached a first close at €100 million. (See BioWorld Today, Feb. 6, 2017.)

The company hits two of its sweet spots – central nervous system disease and unmet medical need. “The later stages of Parkinson’s are very poorly controlled from a symptomatic perspective,” Seroba partner Alan O’Connell told BioWorld Today.

O’Connell and Boorsma have both joined Prexton’s board. Other participants in the round included existing investors Merck Ventures, Ysios Capital and Sunstone Capital.