Manifold Bio, a platform therapeutics company pioneering AI-guided drug discovery using direct-to-vivo measurement, announced a major research collaboration and license agreement with Roche to develop multiple next-generation blood-brain barrier (BBB) shuttles for neurological and neurodegenerative diseases.
The collaboration combines Manifold’s proprietary mDesign AI-guided in vivo discovery engine and tissue-targeting shuttle portfolio with Roche’s extensive expertise in brain-targeted therapeutics. The partnership aims to enable the development of advanced medicines capable of safely and efficiently crossing the BBB—a long-standing challenge in neuroscience drug development.
Under the terms of the agreement, Manifold will receive $55 million upfront and may earn over $2 billion in research, preclinical, clinical, and commercial milestone payments, as well as tiered royalties. Manifold will lead the discovery of novel BBB shuttles tailored to Roche’s therapeutic payloads, while Roche will oversee preclinical, clinical, and commercialization efforts. Manifold also retains the right to co-fund the development of one program for enhanced royalties and can apply its BBB shuttles to non-licensed targets in other internal or partnered programs.
Unlike traditional in vitro methods, Manifold’s mDesign platform directly measures thousands to millions of biologic variants in vivo, generating physiologically relevant data at a scale that enables faster and more predictive drug design. This approach accelerates the discovery of tissue-targeted medicines across modalities such as antibodies, oligonucleotides, and other biologics.
The company’s proprietary platform systematically identifies BBB shuttles capable of transporting therapeutic molecules across the blood-brain barrier through multiple receptor “portals.” These shuttles can be fused with antibodies or conjugated to siRNAs, ASOs, or other therapeutic payloads to enhance delivery, efficacy, and safety. Roche, which has been at the forefront of BBB shuttle technology for more than 15 years, will leverage Manifold’s technology to expand its pipeline of brain-targeted therapies.
This partnership marks a significant validation of Manifold Bio’s approach to AI-guided, direct-to-vivo drug design. It represents one of the most significant AI-driven collaborations in neuroscience to date.
KEY QUOTES:
“Manifold’s mission is to unlock the full potential of AI-guided drug design with drastically increased experimental throughput in living systems to overcome the translational barrier holding back the creation of critical new medicines. Engineering molecules to safely cross the blood-brain barrier has been a grand challenge for decades, and it’s exactly the kind of problem where Manifold’s direct-to-vivo approach provides a decisive edge. We look forward to working with Roche, already a world-leader in technology to enable medicines to cross the BBB, to bring our approach and novel shuttle technologies to expand the breadth of brain-shuttled medicines.”
Gleb Kuznetsov, Ph.D., Co-Founder and Chief Executive Officer, Manifold Bio
“We founded Manifold on the idea that leveraging large-scale in vivo data generation to power AI models would result in a generative drug design engine that learns directly from living systems. Today we’ve built the world’s first AI system for the design of tissue-targeted biologics. With the resulting data, we are already building the world’s first virtual organism model. The collaboration with Roche validates our vision that the future of biomedicine lies in data-driven, generative design directly informed by living biology.”
Pierce Ogden, Ph.D., Co-Founder and Chief Technology Officer, Manifold Bio
“Roche has worked in the field of BBB shuttles for over 15 years and has demonstrated the significant impact BBB shuttles can have on improving antibody pharmacology. We are excited about our partnership with Manifold to identify the next generation of highly specific BBB shuttles, applicable across multiple therapeutic modalities, to tackle some of the most important neurological and neurodegenerative diseases.”
Boris Zaïtra, Head of Corporate Business Development, Roche
“Manifold is delighted to have the opportunity to collaborate with Roche’s team of talented research and translational neuroscientists. This alliance provides Manifold with a foundational partnership that contains key structural elements that will enable the Company to grow as an independent biopharmaceutical company, thereby enabling us to create significant value for patients, caregivers, employees, and shareholders.”
Steven Holtzman, Executive Chair, Manifold Bio
