Article | January 1, 2024

Neurvati Maps Path To Neuroscience Approvals

Source: Life Science Leader
wayne koberstein

By Wayne Koberstein, Executive Editor, Life Science Leader
Follow Me On Twitter @WayneKoberstein

Bruce Leuchter
Bruce Leuchter

Getting where you want to go may depend on how you start out. Even if you cannot yet envision the entire path to your goal, you must somehow plot every terrain that may lie ahead. Biopharma is a landscape of boom and bust. A therapeutic space may rest in dormancy for years, then suddenly catch on fire with multiple companies and innovative approaches feeding the flames. That is the challenge facing Neurvati, a relatively young enterprise now in early clinical development to enter the reignited neuroscience (NS) area.

Granted, the metaphor of ignition only works if you’re looking in from the outside. Inside, where Neurvati and others have been active for the better part of two decades, a more accurate simile might be “ebb and flow,” as Neurvati’s president, CEO, and cofounder Bruce Leuchter, M.D., suggests. Drug development programs in the NS space, however large or small, face common challenges such as the need for better definition of disease mechanisms and greater accuracy in target identification, validation, predictive models, biomarkers, and patient stratification for reliable endpoints in clinical trials.

Neurvati Neurosciences, like other companies in the same space, has grown more focused over time as its science led it to explore a range of possibilities. Unlike many other companies in the same field, Neurvati arose out of a broad-based business model that has supported its growth and financial viability. Investment firm Blackstone Life Sciences is creating and supporting divisions, such as Neurvati, to identify and advance a portfolio of promising products. The customized model means that products can be developed by separate business entities or in strategic partnerships with other companies in the neuroscience space.

Blackstone has bet on the multidimensional, nested model that can assure funding for all development programs through hard times and good. Neurvati performs as an NS incubator within Blackstone, and thus it can incubate new companies to develop the assets.

Singular Enterprises

The company’s first operating company, GRIN Therapeutics, is advancing drug candidate radiprodil as a treatment for GRIN-related disorders (and some other indications). GRIN-related disorders are genetic developmental epileptic encephalopathies. Genetic mutations of the GRIN gene, characterized as gain-of-function, lead to hyperactive receptors in the brain. Researchers at GRIN Therapeutics are targeting hyperactivity with radiprodil, a small molecule modulator of the NDMA receptor.

Generally, Neurvati’s strategy is to identify and advance late-stage assets that have been thoroughly studied and de-risked in previous research. Neurvati conducts all of the appropriate diligence around the opportunities in NS.

“Neurvati focuses on clinical-stage neuroscience development programs across the neuroscience waterfront,” says Leuchter. “Unlike other biotechnology companies, even those that may have one or two verticals within neuroscience, we pursue assets that are in the clinic and have sufficient clinical data to allow us to understand how the molecule behaves, the probability of success at the next data card flip, the regulatory path, and the clinical development plan. A lot can be determined relatively early in a development program once an asset is in the clinic and in humans.”

He emphasizes Neurvati’s commitment to fully funding each program it takes on. “We eliminate capital market threats. We eliminate financing overhangs and other problems that can plague development-stage neuroscience companies. We commit to the long haul, which is particularly important in neuroscience given the challenges inherent in developing neuroscience therapeutics,” he says. “Development programs in many areas, including oncology, have a shorter timeline in clinical development. Often in neuroscience a longer and more costly development process is necessary. When you have a long-term commitment by investors, it makes the whole process easier.”

Expanding Space

Neuroscience research seems likely to experience dramatic growth in the new year. The novel schizophrenia drug from Karuna Therapeutics, KarXT, looks likely to be approved, and most industry observers expect the FDA to move on MAPS MDMA-assisted therapy in 2024; MAPS filed its NDA with the agency on December 12, 2023. There may be encouraging new data in Alzheimer’s and Parkinson’s.

As Leuchter noted, however, the advancements may come as isolated and uniquely attractive to people who invest in biopharma. Although investors have shown more interest in neuroscience of late, Leuchter believes a strategy that involves vetting and advancing de-risked later-stage assets makes sense because most of that interest has centered mainly in a few “pockets” in the space. Some consist of products with orphan indications that involve relatively less risk due to shorter development time or less capital outlay. “These products are in therapeutic areas where you typically generate proof-of-concept data in a small Phase 1b/2a study and then you proceed with a confirmatory study and seek approval. This is not true in most areas of neuroscience.”

Leuchter points to the recent enthusiasm for research related to genetically defined NS diseases, and for some of the sexier solutions such as RNAi technology or vectorized therapies that allow for drug developers to function on a faster time horizon with less capital outlay. “But the bigger indications, like the major depressive disorders, schizophrenia, Alzheimer’s, and Parkinson’s, are challenged by investor fatigue. They attract a substantial amount of capital in the early stages of development, but by the mid-stage, many sponsors have rethought their strategies and are not prepared to allocate the necessary additional resources.”

That is the point where the Neurvati approach is especially relevant, according to Leuchter. “If a company has completed a very early clinical-development program that generated good safety and tolerability data, perhaps with some preliminary proof-of-concept, Neurvati, with Blackstone Life Sciences’ financing assistance, can think about licensing an opportunity. Then we can create a new company around it and finance it all the way to approval.”

Neurvati looks at opportunities in, but also beyond, the orphan categories. Orphan-drug development is important in and of itself, but also can play a highly important role by contributing technologies and insights to the creation of more broadly applicable products.

“Investors realize that rare-disease drug development can lead to quite viable and successful businesses. This has continued to drive investor interest in the orphan and rare disease space,” Leuchter says. “And what we’ve determined from many orphan-drug studies is potentially applicable to understanding and treating many intractable diseases of the brain and nervous system.”

Leuchter observes the history of neuroscience long consisted of symptom-driven diagnosis. “But the technologies around neuroscience have vastly improved. Human genetics have been able to more precisely define patients who are optimal candidates for specific treatments, accurately identifying a patient population through human genetics, small molecule strategies, or biomarker strategies, which have all significantly improved. Imaging technologies also have improved to where we can look at actual metabolic function inside the brain, not just the symptoms that the patient manifests.”

It is a trend that spells likely advantage for Neurvati’s open-ended pursuit of new medicines based on data demonstrating safety and effectiveness rather than mechanism. Wherever and whenever biopharma companies venture into brand new or reborn spaces, they will be wise to value models that offer flexibility and planned funding over simple novelty and its companion, volatility. Nesting development within a secure financing structure could be one effective solution to the enduring uncertainty of developing new, optimized therapies to fill a world of need.