Precision Protein Design Start-Up Gains $40M in Early Funds

(Fernando Zhiminaicela, Pixabay. https://pixabay.com/illustrations/chemical-molecular-atom-medicine-3086130/)

14 July 2022. A start-up company designing and testing precise proteins within live animals to speed creation of new therapeutics is raising $40 million in its first venture round. Manifold Bio, in Boston, is spun-off from the lab of geneticist and serial entrepreneur George Church at Harvard Medical School and the university’s Wyss Institute for Biologically Inspired Engineering.

The two year-old enterprise seeks to create more highly targeted protein therapeutics, which today, says the company, are hampered by imprecise targeting, requiring higher drug doses resulting in more adverse effects. Drug development is making some improvements in targeting, says Manifold Bio, with cell engager and antibody drug conjugates in immunotherapies, but progress so far is limited to treating blood-related cancers. And, says the company, advances in targeting have not yet reached most solid tumor cancers and other diseases.

To achieve more precise targeting, the Manifold Bio technology designs synthetic proteins with a built-in unique identifier it calls an M-code. The company says these unique M-codes, integrated into the chemistry like bar codes, enable tracking of individual proteins, even when combined and active in complex environments. In addition, says Manifold, the design process takes place in vivo, or inside live animals, which makes possible large-scale simultaneous testing of proteins in more realistic environments. The company says it already built a working drug discovery engine for custom-designed proteins.

“Decoupled from the complex mammalian environment”

“Despite a growing understanding of surface targets of diseased cells and the promise of new complex antibody formats,” says Manifold Bio co-founder and CEO Gleb Kuznetsov in a company statement released through BusinessWire, “drug programs continue to face significant clinical challenges, including major dose limiting toxicities caused by imprecise targeting.” Kuznetsov adds, “This comes from fundamental limitations of the current paradigm of protein therapeutics development, where engineering of these targeted drugs is largely decoupled from the complex mammalian environment they are meant to navigate.”

The Manifold Bio technology is derived from research by company co-founder and chief scientist Pierce Ogden, while a doctoral candidate in Church’s lab at Harvard. In a paper in the journal Science in Nov. 2019, Ogden and colleagues described their process of identifying many unique mutations in proteins making up the capsid or outer shell of an adeno-associated virus, and testing for those unique chemistries inside a living lab mouse.

Manifold Bio is raising $40 million in it first venture funding round, led by technology and life science investor Triatomic Capital in Lake Tahoe, Nevada with participation by current investors Playground Global, Fifty Years, and FAST by GETTYLAB, and new investors Section 32, FPV Ventures, Horizons Ventures, and Tencent. The company raised $5.4 million in seed funds in Sept. 2020.

The company plans to apply proceeds from the round to design of its own cancer therapy candidates, while scaling up the technology. “We are using our in vivo design engine in several internal programs while continuing to invest in scaling our platform,” says Ogden. “By making it possible to eventually test thousands of designs simultaneously, we can generate unprecedented data on the in vivo targeting behavior of our drug candidates and significantly change the clinical risk equation.”

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