Manifold Bio is commercializing an end-to-end drug discovery and development platform to improve the efficiency of protein therapeutic creation.
Proteins have great potential as therapeutics, but identifying, testing, and engineering candidate protein drugs is expensive and slow. Proteins that are engineered to perform well in vitro often fail when they are moved to in vivo studies, which are also low-throughput: only about five molecules can be tested in one study.
The Wyss Institute has created a novel platform that combines protein binder identification with protein barcoding technology to enable rapid, multiplexed testing of potential protein drugs in vitro and in vivo, creating an end-to-end solution for drug development.
Gleb Kuznetsov and Pierce Ogden met on their first day of graduate school at Harvard University. They had come from different backgrounds – Kuznetsov was a software engineer and Ogden was a molecular biologist – but were both intrigued by the work being done at the intersection of biology and computation in Wyss Core Faculty member George Church’s lab. They were particularly interested in the power of DNA sequencing and synthesis, and how they could use these technologies to drive positive impact in the world. They decided to focus on reducing the time and money required to produce protein-based therapeutics, and together they created a protein binder discovery platform at the Wyss Institute. The platform uses DNA sequencing to identify proteins that bind to a target of interest, indicating that the protein has the potential to be used as a therapeutic.
Kuznetsov and Ogden were awarded Validation Project funding from the Wyss Institute to de-risk and develop their platform into a commercializable product in 2019. As they started having conversations with potential customers in the pharmaceutical industry, they discovered that while their platform used new, cutting-edge technology, other methods to identify early-stage protein binders already existed. What was more sorely needed in the drug development space was a solution to the bottleneck that occurred when drug candidates moved from in vitro to animal studies. In vivo experiments are much more expensive to run, and it is difficult to test more than one protein drug candidate at a time using current technologies.
To address this unmet need, Kuznetsov and Ogden pivoted from their original idea and developed a protein barcoding system that could allow multiple proteins to be tagged and tracked in pooled and in vivo experiments. When added to their protein binding platform, they created a workflow that could both generate protein drug candidates and test them quickly through high-throughput in vivo screening, providing an end-to-end drug development platform. Confident that this updated system would provide real value to pharmaceutical customers, they co-founded Manifold Bio in May 2020 and moved from the Wyss Institute to Harvard’s Pagliuca Life Lab for the next stage of commercialization.
Manifold Bio is initially focusing on oncology applications for its technology, and aims to help solve the problem of specifically delivering protein drugs to cancer cells while sparing healthy cells. Its ability to do pooled, in-context testing opens the door to engineering drugs that bind to multiple targets to help improve delivery of the drug to the site of disease. The startup hopes to partner with companies along every step of drug development through preclinical studies, and make the engineering and manufacturing process less daunting using Kuznetsov and Ogden’s combined expertise in DNA sequencing, DNA synthesis, and computation. Since spinning out, Manifold Bio has raised a $5.4 million seed investment round and a $40 million Series A round.