Dosing begins in Phase 1 trial of VENT-02 therapy for Parkinson’s

Inhibitor reaches brain, targets NLRP3 protein tied to inflammation

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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Ventus Therapeutics has dosed the first participant in its Phase 1 trial testing VENT-02, a novel oral therapy that features an inhibitor that reaches the brain and targets NLRP3 — a protein that’s linked to brain inflammation in Parkinson’s disease.

The trial aims to assess the safety and tolerability of VENT-02, as well as its effects on the body, through both single and escalating multiple doses. Initial results are anticipated in the first half of 2024, the company said in a press release.

“This trial marks a new chapter for Ventus as we become a clinical-stage organization,” said Marcelo Bigal, MD, PhDthe president and CEO of Ventus.

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The NLRP3 protein is found inside cells, where it works as sensor for danger signals, such as pathogens, or disease-causing agents, and environmental triggers. Once a threat is detected, it triggers the formation of an inflammasome, a molecular complex  involved in inflammatory responses.

While these processes help the immune system respond when there is a problem, in certain situations the NLRP3 protein can become too active and cause more inflammation than needed. That, in turn, can lead to health issues like brain inflammation in conditions like Parkinson’s, Alzheimer’s disease, and amyotrophic lateral sclerosis, more commonly known as ALS.

“NLRP3 is a key driver of many neuroinflammatory diseases,” said Mike Crackower, PhD, Ventus’ chief scientific officer.

The company is developing a number of therapeutic candidates that block the activity of NLRP3. According to Ventus, VENT-02 has shown a strong ability to inhibit NLRP3 in cells and blood from different animals.

[VENT-02] has best-in-class potential based on its unique structure, exceptional brain penetration, and exquisite potency.

VENT-02 also showed an excellent ability in several preclinical models to penetrate the brain — key in treating inflammation — the company noted.

That’s a huge hurdle and a shortcoming for many therapies, which are found to be unable to cross the blood brain barrier, known as the BBB. That barrier is a semi-permeable membrane that shields the central nervous system, comprised of the brain and spinal cord, from general blood circulation and potential threats.

“Our extensive characterization of VENT-02 in multiple disease-relevant preclinical models has de-risked our disease selection process, and we believe VENT-02 has the potential to treat patients across a wide range of neuroinflammatory diseases, including Parkinson’s, Alzheimer’s, and refractory epilepsy, as well as systemic diseases,” Crackower said.

Bigal said VENT-02 “has best-in-class potential based on its unique structure, exceptional brain penetration, and exquisite potency.”

“We are bringing a highly differentiated NLRP3 inhibitor into the clinic with VENT-02,” Bigal said.

“VENT-02 has demonstrated extraordinary safety margins — among the highest I have seen in 20-plus years of developing drugs. These benefits allow us to design an incredibly innovative clinical development plan for VENT-02 and to fully explore the potential impact of NLRP3 inhibition across multiple patient populations suffering from neuroinflammatory diseases,” Bigal added.

The Michael J. Fox Foundation in April awarded Ventus a$150,000 grant to develop a positron emission tomography (PET) tracer for NLRP3. The tracer is expected to help demonstrate NLRP3’s role in nerve-related inflammation, according to the company.