In Vivo Biologics Design for Next-Generation Targeting

July 2022

When we founded Manifold Bio, we set out to build a transformational drug discovery company to unlock the next generation of protein therapeutics. Our goal was not only to create new drugs, but to redefine the paradigm of how protein therapeutics are discovered. We’ve pursued a bold approach from the beginning: rapid technological innovation to bring massively parallel measurement to every stage of drug development, including and especially in vivo testing.

Today, we’re excited to announce that we have closed a $40M Series A to advance Manifold Bio’s in vivo biologics design platform. Since raising our seed in 2020, we’ve brought to life an approach to drug discovery where molecules are tested in vivo as soon as they are designed. In vivo data drives design updates, uniquely empowering us to optimize our drugs to navigate complex mammalian environments. We’ve leveraged the platform to initiate several ambitious drug programs. With the new round of funding, we accelerate our journey by expanding the team and continuing to advance our programs while further investing in the platform.

Using the platform, we stand to unlock the full potential of targeted effectors—drugs like cell engagers and ADCs (antibody drug conjugates) where a powerful effect is driven to a precise location by an engineered targeting domain. The promise of this class was first exemplified by monoclonal antibodies like Rituximab, which took a big step beyond chemotherapies, paving a shift from the legacy of indiscriminate killing of all dividing cells to just those cells, mostly cancerous, that expressed its target. A desire to increase potency subsequently drove a proliferation of effector strategies from ADCs to BiTEs to CAR-Ts and beyond. 

But engineering the precise targeting to leverage these effectors hasn’t kept up. While effective for blood cancers with high specificity targets, most targeted effectors have failed in solid tumors. In many cases these failures were driven by imprecise targeting, leading to dose-limiting, on-target / off-tumor toxicities that prevent the drug from being given in sufficient quantity to drive therapeutic benefit. Beyond oncology, the promise of targeted effectors is barely tapped. There are many well-established effector strategies but high precision targeting to diseased tissues and cells has lagged behind.

Enter in vivo biologics design: Rather than attempting to tune targeting in artificial in vitro assays and hoping for adequate in vivo performance, Manifold Bio’s platform makes biodistribution a core step of the design loop. We can optimize for maximal therapeutic window from the beginning of discovery, by designing drugs that go where they should and not where they shouldn’t. In our programs, we have already taken an order of magnitude step in the number of drugs that we test in vivo at every cycle—and we’re continuing to push this capability. The innovation that enables this is a Manifold-developed technology we call “M-Codes,” a protein barcoding approach that allows quantitative tracking of mixtures of new protein designs through complex environments. It’s protein multiplexing custom-built for drug discovery.

We have already built a working drug discovery engine. We’re now hiring drug hunters to use it, and we’re looking for synthetic biologists and engineers to continue to improve it and unlock other innovations just around the corner. Drug hunters will be empowered to leverage unprecedented amounts of in vivo data to achieve precision targeting that previous technologies could not. Synthetic biologists will recognize that we've unlocked multiplexing in protein space. Both will work together in a company culture that combines scientific audacity with a team-centric approach, all united toward a common mission of creating previously intractable therapeutics.

We’re excited to have Triatomic Capital lead our Series A with Jeff Huber joining our board. Triatomic is joined by a supportive group of investors who believe in the power of Manifold’s technology to realize agency over human health: Section32, FPV, Horizons, and Tencent. And we are grateful for the continued support of our partners since the beginning Playground Global, Fifty Years, and FAST from GETTYLAB.

If you are excited about the power of a technological-driven drug discovery platform and are excited about working with our team, we invite you to join us in unlocking the next generation of protein therapeutics.

Gleb Kuznetsov (Co-founder & CEO)

Pierce Ogden (Co-founder & CSO)

Shane Lofgren (Co-founder & Head of Business Development)

George Church (Co-founder)