This Is Not The 90's Neuroscience
By Amy Mahery
Neuroscience is making a comeback. From the 90’s flush of Big Pharma investment to the present day with advancements in disease biology, technology, and a variety of game-changing digital tools, neuroscience is this decade’s comeback kid. This renewed interest, backed by crucial VC investment and Big Pharma deal-making, is for good reason.
Since my college days, when I first fell in love with neuroscience, to working in a central nervous system (CNS) specialty division at my first biopharma company, and subsequently across a variety of experiences in immunology and oncology, neuroscience always has been a passion of mine and an area that I return to again and again. Over my 20-plus years in the industry, I have witnessed incredible growth in many therapeutic areas, and I’m excited to see neuroscience taking center stage once again.
The (Recent-ish) History of Neuroscience
Remember when the 1990s was deemed the “Decade of the Brain?”
This was more of an effort to raise awareness rather than direct funding, but some critical advancements were made - in the fields of neurodevelopment and plasticity, the neuropharmacology of addiction, and brain imaging to name a few.
It also was a period of great achievement in biopharma as the first blockbuster antidepressants came to market. Investments flooded into neuroscience programs, as everyone rushed to participate in the boom.
In the 2000s, we saw that pay off with the next generation of antipsychotics. But while neuropsychiatry was racking up breakthroughs, other conditions continued to languish, particularly neurodegenerative diseases. With the high development costs and low probability of success, frustrated biopharma companies facing the patent cliff of initial innovation decided to direct their R&D dollars elsewhere. By 2019, big biopharma players like Amgen, Eli Lilly, and Pfizer had largely exited the field.
The Challenge of Neuroscience
Development in neuroscience is notoriously difficult. The success rate for CNS therapies is about half of that for other categories with the road to regulatory approval being approximately 40% longer.
While the blood-brain barrier provides a physical challenge to CNS drug development, the knowledge gap in this space is the bigger issue. There are over 600 diseases of the CNS but relatively few genetic drivers and molecular pathways clearly identified. This context makes it difficult to identify the patients most likely to respond to a given therapy and select the right endpoints to show meaningful and statistically significant benefits.
With relatively few biomarkers identified in progressive diseases of the CNS, clinical trials are often designed for the full clinical outcome, which might take years to manifest. For companies that have large, multi-therapeutic area portfolios, it becomes increasingly difficult to prioritize the investment.
The Promise of Advancements
While it is true that neuroscience has had more than its fair share of spectacular failures, the pattern that has plagued this category is finally changing, which is why we’re seeing renewed interest. With advancements in diagnostics, biomarkers, and technology, we can better grasp the causes of diseases, how to measure them, and then predict impacts that help us better target individual patients, as well as better understand larger populations.
While the path to market has been rocky and met with a high degree of scrutiny, we have finally seen disease-modifying therapies come to the neurodegenerative disease space.
The approval of Amylyx’s Relyvrio for amyotrophic lateral sclerosis (ALS) heralded the first treatment that showed a significant slowing in both disease progression and functional decline, as well as extended survival. And Biogen and Eisai have secured the first approved drugs that attempt to treat a possible cause of Alzheimer’s disease, rather than just the symptoms. It’s worth noting the role that surrogate endpoints have played in these approvals, enabling a fast-to-market approach for a patient population with incredible unmet needs.
Success in the clinic is creating a positive feedback loop to drive increased deal-making across discovery and late-stage opportunities. Second, only to oncology, CNS deals topped the 2022 M&A landscape signally increasing interest that seems to be continuing into 2023. The largest was Pfizer’s acquisition of Biohaven and its calcitonin gene-related peptide (CGRP) receptor antagonist portfolio at $11 billion.
In the back half of 2021, Eli Lilly struck a deal with Verge and Roche/Genentech with Recursion, both with hundreds of millions of dollars in potential. In March of 2022, AbbVie purchased Syndesi Therapeutics, a company focused on SV2A modulators. Others have recently announced new collaborations including Schrödinger with BMS and Neurocrine Biosciences with Voyager, in a deal worth up to $1 billion.
Seeing the opportunity alongside the need, new companies and new approaches are emerging. NeuroX1, is entirely focused on using machine learning (ML) to identify novel drivers of neurodegenerative disease. Companies undertaking artificial intelligence (AI) and ML initiatives are also flexing their muscles – anchoring their discovery focus squarely on CNS and pharma and is placing big bets on discovering novel targets; Insilico Medicine’s AI uncovered 28 potential new drug targets for ALS, and Alto Neuroscience is using AI-derived biomarkers to deliver precision psychiatry.
Where We Find Ourselves
A crop of CNS biotechs have sprung up giving fuel to this resurgence. They each have their unique approach and area of concentration. Some are working at the intersection of neurology and immunology, such as Vigil Neuroscience, focused on restoring the vigilance of microglia, and Escient Pharmaceuticals, aiming to provide targeted therapeutic intervention at the interface of the neurosensory and immune systems.
Other industry players like Sage and Karuna are dedicated to delivering the next innovation in neuropsychiatry. Others are centering their efforts on generic drivers of disease, like AviadoBio, Cajal Neuroscience, and Alcyone Therapeutics. Will these companies be headlined in the deals of tomorrow? (It is worth noting that as I write this, Alcylone announced a license and collaboration agreement with Biogen centered on an implantable medical device in development for intrathecal drug delivery.)
The goal of CNS therapies has been to slow the progression of disease. With increased understanding, more advanced tools, and the commitment of the biopharma ecosystem, we are now moving past that goal to reversing disease and offering patients -- not just a slower and less severe decline but hope for real improvement.
From there, our sights are on finding a cure and then ensuring prevention. The comeback of neuroscience gives us firmer ground on which to build and increased hope for the innovation to come. Nevertheless, we know that this area remains one of the most challenging in biopharma and that setbacks are inevitable, but these perceived setbacks are an integral part of the forward momentum that is continually increasing – offering new hope for the future and new opportunities for people to live longer, healthier lives.
Amy Mahery is Chief Commercial Officer at Roivant Science