Synbio GRObio Startup Secures $ 25 Million to Work with New Building Blocks for Protein Drugs

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Many of the protein therapies available today, as well as many others in development, got their start on computers. The software identifies the protein forms best suited for therapeutic applications and these designs are tested in the laboratory. While computer techniques have advanced the design and development of new therapeutic proteins, even the most advanced of them are limited to 20 standard amino acids found in nature which are the building blocks of all proteins. Harvard University spin-off company GRO Biosciences aims to improve protein therapies by expanding this alphabet of amino acids.

GRObio has been quietly developing its technology for several years. The company has progressed in its preclinical research and is now positioning itself to advance its own therapies and forge partnerships with pharmaceutical companies interested in working with the startup’s technology. To support these efforts, GRObio announced on Wednesday a $ 25 million Series A 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 led to the founding of many life science startups. Dan Mandell, co-founder and CEO of GRObio, was a genetics researcher at Harvard, where he worked with Church on the computational design of new proteins whose folding and function depend on this new alphabet of amino acids, made up of non-standard amino acids (NSAA).

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 basic 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 a E. coli-based organism. But the company went further than what nature offers by recoding the E. coli genome so that these bacteria are able to produce proteins using NSAIDs. GRObio calls these bacteria “genetically recoded organisms”, or GRO.

“What’s special about these organisms is that they can make proteins made up of amino acids beyond the standard 20 amino acids,” Mandell said. “Only these organisms can produce these NSAA proteins with high efficiency and on a large scale. “

So why would anyone want a protein produced by GRO from NSAA? Mandell said therapeutic proteins made with standard amino acids still have limitations ranging from safety concerns to the durability of treatment. Working with NSAIDs allows for the production of personalized proteins whose shape and chemical properties provide benefits for a biologic drug.

GRObio has so far worked with two families of NSAA chemicals. The first, which the company calls DuraLogic, makes a more stable protein and improves its half-life. Currently available biologic drugs dosed as frequent injections are bothersome or undesirable (or both), leading many patients to miss doses, Mandell said. By making a more stable protein, GRObio could produce a drug whose therapeutic effect lasts longer, which means protein therapy requiring less frequent injections.

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

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

Without specifying a disease target, Mandell said he expects GRObio to begin its first human testing of a therapeutic protein grown by GRO in 2024. The new funding will support preclinical research leading to these tests. GRObio is also looking for partners from the pharmaceutical industry. These partners could license GRObio therapeutic candidates, supporting the 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 cannot because they do not have access to a production platform capable of producing NSAA-based proteins on a large scale. Mandell said GRObio has been approached by companies that have already designed their own new molecules and are considering GROs as a way to produce them.

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

Photo by Flickr user Eduprints Plus via a Creative Commons Licence


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