Ventus raises $100M to pursue NLRP3, crack undruggable targets

Ventus Therapeutics has raised a $100 million series B to take small molecules against traditionally undruggable targets into clinical trials. The pipeline features NLRP3 inhibitors that Ventus is pitching as best-in-class candidates in the competitive inflammasome space.

Last year, Ventus broke cover with $60 million from Versant Ventures, its founding investor, and GV. The series A positioned Ventus to build on the early progress it had made against inflammasome- and nucleic-acid-sensing targets with the help of scientific founders who are at the forefront of structural biology and immunology.

Now, Ventus has expanded its investor syndicate to raise a further $100 million. The round, which was led by RA Capital Management, equips Ventus to start finding out how its candidates perform in people.   

“The series B funding allows us to advance our five compounds, two of them into the clinic in the more near-term, without trade-offs or further fundraising. We anticipate having our lead program enter the clinic … in late 2022 or early 2023,” Marcelo Bigal, president and CEO of Ventus Therapeutics, said. 

Ventus is yet to disclose the target of its lead candidate, an innate immunity prospect that is in lead optimization, but has shared details of its next most advanced asset. The second drug in the pipeline targets NLRP3, an inflammasome protein complex that has attracted a lot of attention.

Multiple large and small drug developers are going after the target. Roche paid €380 million ($451 million) upfront to buy Inflazome in September after seeing clinical data on its brain-penetrant and peripherally restricted NLRP3 inhibitors. Bristol Myers Squibb and Novartis have also bought their way into the space, and a clutch of biotechs are pursuing the target independently. Bigal is bullish on Ventus’ prospects of coming from behind in the crowded field to claim a sizable slice of the market.

“Currently, development-stage NLRP3 inhibitors are derived from MCC950, a compound discovered by Pfizer 20 years ago that, while active on NLRP3, failed in the clinic due to safety issues that are believed to be compound/scaffold based. The current competitor compounds are first-generation NLRP3 inhibitors and they appear to be very similar in structure to each other and to MCC950 and thus lack meaningful differentiation. Importantly, the active forms of these competitor compounds demonstrate no obvious brain penetration levels when dosed in preclinical species.” the CEO said. 

Bigal expects Ventus’ NLRP3 inhibitors to have “a unique pharmacological and safety profile” as they were discovered in a novel way that rendered them “completely structurally distinct from all other competitor compounds.” Notably, Ventus’ inhibitors lack “chemically pro-fibrotic areas of MCC0950 which resulted [in] its discontinuation,” Bigal said. 

Ventus’ inhibitors include brain-penetrant and peripherally restricted molecules. Bigal said both sets of molecules have best-in-class submicromolar levels of potency. “Our novel NLRP3 inhibitors that demonstrate full brain penetration are unique in the field and have a strong likelihood to have a best-in-class profile from indications of the CNS,” the CEO said. 

Across sites in Boston and Montreal, Ventus is “fully resourced” to take compounds into early clinical development, Bigal said. Ventus currently employs 39 full-time equivalents and plans to grow its staff by 20% in the next year.

The expanded team will advance the existing programs, which span innate immunity, oncology and neurology, while using Ventus’ two platforms to uncover high-value drug targets. The leading innate immunity programs stem from a platform that enables structure-based drug discovery for critical targets. Ventus has paired that platform with a system for finding novel druggable sites.

RA Capital sees promise in the drug candidates and platforms, leading the series B with assists from BVF Partners, Casdin Capital, Cormorant Asset Management, Fonds de solidarité FTQ and Alexandria Venture Investments, as well as Ventus’ existing backers. “It provides the balance sheet to explore a range of options for the evolution of the company, including an IPO if this is the desired path for the company,” Bigal said.