Well-known for its oncology efforts and making recent headlines for a rumored mega merger with AstraZeneca, Bristol Myers Squibb is also dedicating considerable resources to neurological and psychiatric diseases, with a “continuum of care” mindset.
When it comes to neuroscience, Bristol Myers Squibb watchers are laser-focused on the upcoming readouts for Cobenfy—the schizophrenia drug the pharma acquired in the $14 billion purchase of Karuna Therapeutics—in Alzheimer’s disease psychosis. But BMS has a deeper neuro pipeline, built upon a much larger transaction—the $74 billion mega-merger with Celgene in 2019.
Readouts for Cobenfy—approved in 2024 as the first new schizophrenia treatment in decades—in Alzheimer’s disease psychosis have been repeatedly delayed by clinical trial challenges and are now expected in 2027, with a possible interim analysis later this year. But BMS touts a growing pipeline of neuroscience assets in Alzheimer’s, multiple sclerosis and other neuropsychiatric diseases.
BMS stepped away from neuro in 2013, instead throwing its primary capital and resources behind immuno-oncology and other priority focuses. Ken Rhodes, vice president of neuroscience, told BioSpace he joined BMS in July 2023 “out of excitement about what the company was doing as it re-entered [the space].”
The company’s neuroscience renaissance began with its $74 billion mega-merger with Celgene in 2019, Rhodes continued. “Through the acquisition and looking at the portfolio that the Celgene crew had put together, I think BMS realized the value in that portfolio and chose to sort of re-enter the therapeutic area in earnest.”
In March 2020, BMS won approval for Celgene’s ozanimod—now Zeposia—in multiple sclerosis in March 2020. A S1P receptor modulator, Zeposia blocks the capacity of immune cells to enter the central nervous system, reducing inflammation. Based on that foundation, BMS continued to build out neuroimmunology and neuroinflammation drug development programs and capabilities to study new approaches to treating diseases like multiple sclerosis (MS) and Alzheimer’s, Rhodes said.
One of these programs, a dual FAAH/MAGL inhibitor called irafamdastat, is currently in Phase 2 trials for MS spasticity and agitation associated with Alzheimer’s. Another is the Prothena Biosciences–partnered anti-MTBR-tau antibody moponetug. The asset is being tested in Phase 2 development as a disease-modifying therapy intended to slow or halt the progression of Alzheimer’s. Like Rhodes, Laura Gault said she came to BMS to help oversee this collection of assets.
“Really, what brought me here is the promise of our pipeline and the opportunity to really build a world-class team to deliver on this very promising pipeline,” the senior vice president and head of neuroscience development told BioSpace.
As for BMS’ business development efforts, deals “may be done to expand core TAs [therapeutic areas] (e.g., neuroscience) but doesn’t appear to be [a] primary focus,” Truist wrote in April after speaking with Chief Medical Officer Cristian Massacesi and Commercialization Head of CV & Immunology Al Reba.
A neuroscience renaissance
Neuroscience overall has experienced a comeback recently, with several companies—including BMS, AbbVie and Sanofi—returning after the complexity of the brain and high clinical trial failure rates drove many away.
“What really has changed the probability of success, what’s demonstrated success now in disease-modifying therapies in Alzheimer’s disease, is all the investments that academia and industry have made . . . in biomarkers and in genetics,” Rhodes said. “The genetics have taught us what the most valuable targets are likely to be. The biomarkers have taught us how to make sure that we have the right patients in our clinical trials and how to monitor the response to therapy.”
As for psychiatric diseases—where the clinical failure rate is especially high—Rhodes acknowledged that the science is further behind. “In psychiatric disease, our understanding of the causal biology is not quite as mature as it is in neurologic diseases,” he said. However, he added, “I think there’s been some important advances there as well, and hopefully, the lessons we learned about how to succeed in Alzheimer’s disease will be replicated in other indications, including psychiatric disease, although that may be a little further off.”
BMS is currently evaluating Cobenfy in bipolar-1 mania, Alzheimer’s disease agitation, Alzheimer’s cognition and pediatric autism irritability. The company also has evifacotrep, a TRPC4/5 inhibitor, in Phase 1 testing for mood and anxiety disorders, among other programs.
“Cobenfy is viewed as an anchor asset in a broader neuroscience portfolio,” Truist wrote in the April note, adding that two of the ADEPT trials in Alzheimer’s psychosis “need to hit for label expansion and mgmt has indicated that any stat sig result would be positive.”
While agreeing that the underlying pathobiology is less understood in psychiatric disease than in other neurologic indications, Gault said the field has “really invested a lot in terms of identifying potential biomarkers that could be used to define subtypes within a disease category or predict treatment response to certain agents.” She specifically noted EEG and functional MRI as diagnostic tools researchers are gaining experience with.
A continuum of care
What sets BMS apart from some of its peer companies in Alzheimer’s disease, Rhodes said, is a focus on a continuum of care strategy.
“We’re interested in developing both disease-modifying therapies and treatments like Cobenfy to treat some of the debilitating symptoms that affect patients with Alzheimer’s disease,” he explained, adding that this is an approach BMS looks to replicate in in other disease areas.
Gault agreed, saying that beyond Alzheimer’s, BMS is thinking about how to develop treatments “in other areas that are symptomatic” that have a different profile of risk, cost and time than is involved in a trial for a disease-modifying asset.
Elsewhere in the pipeline, Rhodes is also “really excited” about discovery and early development work around brain shuttle technologies and the possibility of delivering different therapeutic modalities across the blood-brain barrier [BBB] to interact with targets inside the central nervous system.
In December 2024, BMS inked a global license agreement with Swedish biotech BioArctic to leverage the company’s BrainTransporter technology against Alzheimer’s. One preclinical program, BAN2803, is an antibody that uses the transferrin receptor protein to facilitate transport across the BBB.
“It actually binds to the pyroglutamate form of amyloid, which is the same target, or same form of amyloid, that’s targeted by Eli Lilly’s drug Kisunla,” Rhodes said. “So it’s a clinically validated approach to modifying amyloid pathology and improving or offering disease modification in Alzheimer’s disease.”
In addition to this BioArctic-targeted program, BMS has earlier-stage programs that “incorporate various types of shuttle technologies” that the company has not yet disclosed, Rhodes said. “We and perhaps others see [this technology] as an important area for future innovation in the neuroscience space.”
Certainly, BMS is far from alone in advancing BBB-crossing platforms. Roche’s Alzheimer’s next-gen candidate trontinemab is an intravenously delivered Brainshuttle Aβ antibody engineered to provide enhanced access to the brain to rapidly reduce amyloid. The asset succeeded in a mid-phase trial in December 2025. A month earlier, Roche put $2 billion-plus on the line to work with Manifold Bio on BBB shuttles for multiple targeted neurological and neurodegenerative disease therapies.
Rhodes discussed the evolution of the anti-amyloid space, and where brain shuttle tech could fit within it.
“I think data are suggesting that the earlier you begin to treat, the greater the benefit with anti-amyloid therapies,” he said. The results so far “beg the question as to whether [BBB-crossing technologies] will offer a really compelling opportunity with subcutaneous or a more convenient route of administration for patients.”
Such technology also enables the delivery of therapeutic modalities besides antibodies, Rhodes added, opening the door to targets that have historically “been very difficult to drug.”
Antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs), for example, are also being investigated for neuro indications. “There’s good clinical support now in a couple of programs suggesting that shuttle technology can deliver those types of medicines into muscle, into heart, into other tissues, including the nervous system,” Rhodes said.
No comments:
Post a Comment
Note: Only a member of this blog may post a comment.