Many of the protein therapies available now, as well as many more still in development, got their start on computers. Software identifies the protein shapes best suited for therapeutic applications and those designs are tested in a lab. While computational techniques have advanced the design and development of new therapeutic proteins, even the most advanced of these are limited to 20 standard amino acids found in nature that are building blocks of all proteins. Harvard University spinout GRO Biosciences aims to improve protein therapies by expanding this amino acid alphabet.

GRObio has been quietly developing its technology for the past several years. The company has made progress in its preclinical research and it’s now positioning itself to advance its own therapies, and to strike up partnerships with pharmaceutical companies interested in working with the startup’s technology. To support those efforts, GRObio announced on Wednesday a $25 million Series A round of funding co-led by Leaps by Bayer and Redmile Group.

The science behind GRObio comes from the lab of George Church, a Harvard scientist whose discoveries have led to the founding of many life sciences startups. Dan Mandell, GRObio’s co-founder and CEO, was a research fellow in genetics at Harvard, where he worked with Church on computational design of new proteins whose folding and function depends on this new amino acids alphabet, comprised of non-standard amino acids (NSAAs).

Therapeutic proteins are produced by harnessing the protein-translation machinery of bacteria. Companies such as Ginkgo Biosciences, Synlogic, and Absci work with E. coli to produce their commodity chemicals and proteins. For many synthetic biology companies, E. coli are the bacteria of choice because they are inexpensive and easy to use, Mandell said. GRObio also works with an E. coli-based organism. But the company has gone further than what nature provides by recoding the E. coli genome so that these bacteria are able to produce proteins by using NSAAs. GRObio calls these bacteria “genetically recoded organisms,” or GROs.

“What’s special about these organisms is they can make proteins comprised of amino acids beyond the 20 standard amino acids,” Mandell said. “These organisms are the only organisms that can produce these NSAA proteins at high efficiency, and at scale.”

So why would anyone want a GRO-produced protein made from NSAAs? Mandell said that therapeutic proteins made with standard amino acids still have limitations ranging from safety issues to the durability of the treatment. Working with NSAAs enables the production of customized proteins whose shape and chemical properties offer advantages for a biologic drug.

GRObio is working with two families of NSAA chemistries so far. The first, which the company calls DuraLogic, makes a protein that is more stable and improves its half-life. Currently available biologic drugs dosed as frequent injections are inconvenient or undesirable (or both), which leads many patients to miss doses, Mandell said. By making a more stable protein, GRObio could produce a drug whose therapeutic effect lasts for a longer period of time, which means a protein therapy that requires less frequent injections.

The second NSAA family, which GRObio has dubbed ProGly, enables the biotech to directly modulate the immune system, offering a new way to address autoimmune diseases. The way the immune system distinguishes a foreign protein from one that is part of the body is by detecting sugar molecules called glycans on the protein’s surface, Mandell said. GRObio aims to express proteins decorated with human glycans, which would reeducate the immune system to recognize them as belonging to the body.

GRObio hasn’t disclosed what diseases it aims to address, other than to say the technology has applications in autoimmune and metabolic disorders. One of the company’s early projects was a form of insulin modified in a way to enable weekly dosing. The company was awarded a Phase I Small Business Innovation Research grant in 2019 for that research, followed by a Phase II grant in 2020. Mandell acknowledged that GRObio has worked on insulin, and said the company has received about $1.5 million in non-dilutive capital to support that work.

Without specifying a disease target, Mandell said he expects GRObio could begin its first human tests of a GRO-grown therapeutic protein in 2024. The new financing will support the preclinical research leading up to those tests. GRObio is also looking for pharmaceutical industry partners. Those partners could license GRObio therapeutic candidates, taking on the responsibility of clinical development and potential commercialization of new protein therapies.

Mandell said GRObio is also considering alliances with companies that want to work with NSAAs but can’t because they don’t have access to a production platform that can produce NSAA-based proteins at scale. Mandell said GRObio has been approached by companies that have already designed their own new molecules and are looking at GROs as a way to produce them.

Prior to Wednesday’s funding announcement, GRObio had raised $2.1 million in a 2017 seed financing led by Digitalis Ventures and Innovation Endeavors. Those firms also joined the Series A round, bringing the startup’s total investment to $31.2 million to date.

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