Swiss pharmaceutical giant Roche announced Monday a major collaboration with Boston-based biotech Manifold Bio, committing $55 million upfront in a deal potentially worth over $2 billion to develop artificial intelligence-driven technologies for delivering drugs across the blood-brain barrier.
The partnership addresses one of medicine's most persistent challenges: the blood-brain barrier (BBB), a tightly locked layer of cells that protects the brain from harmful substances but also blocks beneficial therapies from reaching neurological disease targets. This barrier has historically thwarted numerous attempts at treating brain disorders, prompting the emergence of specialized companies focused on overcoming this obstacle.
AI-Powered Drug Discovery Platform
Manifold Bio, co-founded by renowned geneticist George Church alongside CEO Gleb Kuznetsov and CTO Pierce Ogden, has developed a unique approach that combines AI with in vivo testing capabilities. The company's platform can measure thousands of biological "shuttles" that may successfully cross the blood-brain barrier, evaluating these candidates in living organisms rather than traditional petri dish methods.
"It's always felt like going into clinical trials with your hands tied behind your back, because you never could really engineer a molecule that could successfully, fully get into the brain," Kuznetsov explained. "That's why there's been such a strong push into these brain-shuttling technologies."
The company's approach differs significantly from conventional drug discovery methods. As Kuznetsov describes it using an automotive analogy: "If we could just take diseased cells out of a human body — like we could take engine out of car — repair them and put them back in, we will have cured many diseases. Of course, it is very hard to do that. And so a big part of drug design and drug engineering is effectively bringing the mechanic to the broken cells in the body."
Strategic Value for Roche's Neuroscience Portfolio
For Roche, this collaboration represents a strategic investment in its substantial neuroscience pipeline. The company currently maintains 21 neuroscience programs in human trials, including more than a dozen for not-yet-approved drugs targeting rare illnesses, multiple sclerosis, and neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's disease.
Roche's neuroscience division generated significant revenue growth last year, with sales increasing 13% to 9.3 billion Swiss francs (approximately $10.6 billion), accounting for 20% of the company's overall pharmaceutical sales. The company has established itself as a leader in BBB shuttle technology over the past 15 years, with its closely watched Alzheimer's candidate trontinemab built using shuttle technology.
"We are excited about our partnership with Manifold to identify the next generation of highly specific [brain-blood-barrier] shuttles," said Boris Zaïtra, head of corporate business development at Roche. "To tackle some of the most important neurological and neurodegenerative diseases."
Deal Structure and Future Implications
Under the agreement, Manifold will lead activities related to discovering and advancing novel shuttles tailored to Roche-selected therapeutic payloads, while Roche will handle preclinical and human testing along with commercialization. The partnership allows Manifold to receive tiered royalties on resulting products and maintains the right to opt-in and co-fund development of one product candidate.
Importantly, Manifold retains ownership of its shuttle technology and can apply it to create other drugs for the same or different diseases. "This alliance provides Manifold with a foundational partnership that contains key structural elements that will enable [Manifold] to grow as an independent biopharmaceutical company," said Steven Holtzman, Manifold's executive chairman.
The collaboration targets what Kuznetsov describes as "massive" diseases that are "in many ways, diseases of aging," though specific therapeutic targets remain undisclosed. If successful, the technology could enable medicines that are effective at lower, safer doses and administered in more convenient ways.
Broader Industry Context
This partnership reflects Roche's broader strategy of pursuing collaborations and licensing agreements in neuroscience rather than outright acquisitions. Recent deals include a $60 million agreement with Ionis Pharmaceuticals in 2023 for RNA medicines targeting Alzheimer's and Huntington's diseases, and partnerships with Sangamo Therapeutics and RNA editing specialists.
The deal also represents Roche's continued investment in AI-driven drug discovery, following previous collaborations with Dyno Therapeutics for gene therapies, chipmaker Nvidia, and Recursion Pharmaceuticals through its Genentech division.
Founded in 2020, Manifold has grown to 46 employees and plans to use the $55 million upfront payment to expand operations and workforce from its Fenway-area headquarters. The company's leadership emphasizes that their competitive advantage lies not just in AI capabilities, but in the quality and relevance of their data.
"AI, in and of itself, is really no longer an edge," noted Pierce Ogden, Manifold's CTO. "It has to be paired with quality and relevant data. And that's really what makes Manifold unique."
