A biotech startup trying to expand the limited palette that nature uses to make proteins has raised funds to test its creations in humans for the first time.
The company, called GRO Biosciences, is based on research from Harvard geneticist George Church’s lab, which created bacteria that can make proteins from 21 different amino acid building blocks instead of the standard 20 found in humans. The startup has long maintained that the genomically recoded organisms, or GROs, could lead to better protein therapies with new properties.
Now, the Cambridge, MA-based startup has a chance to prove it. GRObio announced Friday that it raised a $60 million Series B financing led by Atlas Venture and Access Biotechnology to support a Phase 1 clinical trial.
It’s been a long road for CEO Dan Mandell, who co-founded the company eight years ago near the end of a six-year stint as a postdoc in Church’s lab. In the time since, his startup has turned the new form of life from an academic oddity into a useful tool for making new drugs.
“We invested considerable time and effort industrializing and scaling that organism to build what is now really a plug-and-play solution for installing any non-standard amino acid into any protein,” Mandell told Endpoints News in an interview.
Its first target: improving treatments for gout.
Some people with gout receive infusions of a therapeutic enzyme called uricase that breaks down the painful crystals made of uric acid built up from excess protein. But the drug — marketed by Amgen as Krystexxa — stops working for some patients when their immune system develops antibodies that attack the foreign enzyme, which humans don’t make on their own.
GRObio believes it has built a better uricase whose effectiveness won’t wane over time. The company has incorporated non-standard amino acids into the enzyme to control exactly how the protein is decorated with sugar molecules called glycans.
“It’s a key way to distinguish what’s you and what’s not you,” Mandell said. By controlling these glycosylation patterns, and tricking the immune system into thinking that the protein belongs, the company hopes to shield them from being attacked.
Mandell wouldn’t say when the trial would begin, but monitoring uric acid blood levels in patients receiving the therapy should give the company a quick and easy read on whether its sugar-coated proteins are working. “This is a proof of concept for eliminating anti-drug antibodies,” he said.
GRObio also has earlier-stage work using its programmable sugar-coating to treat autoimmune diseases, including myasthenia gravis, that are caused when antibodies erroneously attack a person’s body. Mandell hopes the approach will “tolerize the patient to their own proteins.”
The original genetically recoded organisms that Church debuted in 2016 added just a single new amino acid to the mix, but Mandell said GRObio has since made organisms that can incorporate multiple new amino acids into the same protein.
He thinks that could be especially useful for making antibody-drug conjugates with multiple hooks for attaching a drug warhead or other molecules that could improve targeting or immune cell recruitment. “We’ll be able to enable scalable production of such products for the first time,” he said.
Editor’s note: This story was corrected to note the announcement was made Friday.