Roche Holding AG has entered into a strategic research collaboration and licensing agreement with Manifold Bio, a Boston-based biotechnology firm specializing in AI-guided drug discovery and in vivo measurement technologies. The partnership aims to develop next-generation blood-brain barrier (BBB) shuttles to enhance delivery of therapeutics for neurological and neurodegenerative diseases.

Under the terms of the agreement, Manifold will receive an upfront payment of $55 million and is eligible for additional milestone payments exceeding $2 billion, tied to research, clinical development, and commercial success. The company will also receive tiered royalties on future sales. Manifold retains rights to co-fund one program in exchange for enhanced royalties and may apply its BBB shuttle technology to therapeutic payloads outside Roche’s licensed targets.

The collaboration will leverage Manifold’s proprietary mDesign platform, which enables high-throughput, direct-to-vivo screening of biologic variants. Unlike traditional in vitro methods, the platform measures thousands to millions of biologic candidates directly in living systems, generating physiologically relevant data at scale. This approach is designed to accelerate the translation of biologics—including antibodies, oligonucleotides, and other modalities—into clinical candidates.

“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,” said Gleb Kuznetsov, Ph.D., Co-Founder and CEO of Manifold Bio. “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.”

The BBB presents a significant obstacle in the treatment of central nervous system disorders, limiting the effectiveness of many therapeutic agents. Manifold’s platform identifies shuttle molecules that can transport drugs across the BBB via multiple receptor-mediated pathways. These shuttles can be fused with antibodies or conjugated to siRNAs, ASOs, and other payloads to improve delivery, efficacy, and safety.

“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,” said Boris Zaïtra, Head of Corporate Business Development at Roche. “We are excited about our partnership with Manifold to identify the next generation of highly specific BBB shuttles, applicable across multiple therapeutic modalities.”

Manifold’s Chief Technology Officer, Pierce Ogden, Ph.D., added, “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.”