Partnership leverages Manifold's AI-guided direct-to-vivo platform for Roche to create multiple novel brain-targeted therapeutic products 

• Collaboration to utilize Manifold’s mDesign direct-to-vivo AI-guided drug discovery engine and tissue-targeting shuttle portfolio to create blood-brain barrier (BBB) shuttles for multiple brain-targeted therapeutic modalities
• Manifold to receive $55 million upfront, with potential for over $2 billion in total research, preclinical, clinical development and commercial milestones, plus tiered royalties, and the right to opt-in to co-fund development of one product candidate in exchange for enhanced royalty participation
• Manifold retains full rights to apply its BBB shuttles to non-licensed targets in internally developed and future partnered programs

Manifold Bio, a platform therapeutics company pioneering AI-guided drug discovery coupled with direct-to-vivo measurement, today announced a strategic research collaboration and license agreement with Roche (SIX: RO, ROG; OTCQX: RHHBY). The partnership will apply Manifold's proprietary tissue-targeting shuttle portfolio and mDesign AI-driven in vivo discovery engine to create multiple next-generation BBB shuttles for the treatment of neurological and neurodegenerative diseases.

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Pierce Ogden, CTO (left) and Gleb Kuznetsov, CEO (right) of Manifold Bio (photo by Marissa Fiorucci)

“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 Chief Executive Officer 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. 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.”

Unlike traditional approaches that rely heavily on in vitro assays, Manifold’s mDesign platform can be used to measure thousands to millions of biologic variants directly in vivo, providing physiologically relevant data at unprecedented scale. This allows for rapid translation of biologics to patients, spanning antibodies, oligonucleotides, and other modalities. The company is using its platform to pursue the broad opportunity in tissue-targeted medicines, including delivery of medicines to the brain using antibody-based BBB shuttles - the focus of the collaboration.

“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,” said Pierce Ogden, Ph.D., Co-Founder and Chief Technology Officer of Manifold Bio. “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.”

The first generation of BBB shuttles has improved the efficacy of certain therapeutic payloads. Manifold’s proprietary platform systematically measures thousands of prospective BBB shuttles that transit medicines to the brain through multiple “portals” (receptors) directly in vivo. The resulting BBB shuttles are then fused with antibodies or conjugated to siRNAs, ASOs, or other therapeutic molecules to facilitate crossing the BBB, expanding the breadth, efficacy, and safety of product candidates that can be created.

“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, Roche. “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.”

Under the agreement, Manifold will lead research and discovery activities to identify and develop novel BBB shuttles tailored to select Roche therapeutic payloads. Roche will then lead preclinical, clinical, and commercialization efforts. Roche will pay Manifold an upfront fee of $55 million (USD). In addition, Manifold is eligible to receive significant research, discovery, and preclinical milestones as well as clinical and sales milestones totaling over $2 billion, along with tiered royalties. Manifold also retains the right to co-fund development of one program in exchange for enhanced royalties, as well as the right to apply its BBB shuttles to therapeutic payloads outside of Roche’s licensed targets.

“Manifold is delighted to have the opportunity to collaborate with Roche’s team of talented research and translational neuroscientists,” said Steven Holtzman, Executive Chair of Manifold Bio. “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.”

About Manifold Bio

Manifold Bio is a platform therapeutics company building the first AI-guided direct-to-vivo discovery platform to accelerate the development of tissue-targeted medicines. By testing thousands of molecules simultaneously in vivo, Manifold uncovers delivery strategies that unlock new therapeutic possibilities across neurodegenerative, metabolic, and other major diseases. Its mDesign engine integrates AI-guided protein design with multiplexed in vivo data, creating a virtuous cycle of design and translation. In addition to developing its internal pipeline of novel medicines, Manifold collaborates with leading pharmaceutical partners worldwide.

Learn more at www.manifold.bio.

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Manifold Bio announces strategic collaboration with Roche to develop multiple next-generation brain shuttles for neurological diseases. Manifold to receive $55 million upfront, with potential for over $2 billion in milestones.