G-protein-coupled receptors (GPCRs) are a popular drug target because they have a hand in numerous functions of the human body. Despite its popularity, this group of proteins remains largely untapped; small molecules aren’t the best way to engage many of them, and researchers have faced hurdles trying to discover other kinds of drugs against them. Tectonic Therapeutic is trying to change that.
The Boston-based biotech launches with $80 million in series A funding and technology based on the work of Andrew Kruse, Ph.D., a professor of biological chemistry and molecular pharmacology at Harvard Medical School. It will use the platform, dubbed GEODe, to go after GPCRs that are unexplored or thought to be “undruggable” and create a pipeline of biologics against them.
“Almost all of the drugs on the market, except for two, against GPCRs are small molecules. Some of the GPCR targets would be more amenable to biologics and yet, the discovery of biologics against GPCRs has been incredibly challenging,” said Tectonic CEO Alise Reicin, M.D.
The company will use the funding to expand the GEODe platform, build out its team and pursue some early targets, Reicin said. It hopes the capital will fund it through some early development candidates and push a lead compound into the clinic.
Because GPCRs bind to a variety of ligands and play a role in so many different processes, there are lots of disease areas Tectonic could go into. For now, the company is making a conscious effort to look broadly and land on targets that have the highest probability of success in areas that are in serious need of new treatments, Reicin said.
“Certainly, over time, we would start to focus more. That will then drive what our strategy will be for partnerships versus internal discovery, but at this early stage, we really are agnostic to disease area,” she added.
Researchers estimate about one-third of approved drugs work by targeting GPCRs, but these drugs are only hitting the tip of the iceberg.
"Despite the rich pipeline of approved drugs, these target less than 15% of the GPCR class,” said Timothy Springer, Ph.D, who co-founded Tectonic alongside Kruse in 2019. Springer is a professor of biological chemistry and molecular pharmacology and a professor of medicine at Harvard Medical School, as well as a major investor in Tectonic’s series A. Vida Ventures, Polaris Partners and EcoR1 Capital also participated in the round.
Small molecules just aren’t specific enough for some GPCR targets, and they’re not ideal for binding to GPCR targets with large binding sites meant for long peptide or protein chains, Reicin said. And on the biologics side, researchers have run into issues expressing large enough amounts of GPCRs to develop antibodies against or purifying them without destroying their natural structure. The company developed the GEODe technology to surmount these hurdles.
The challenge is one of the reasons Reicin joined the company. A physician by training, Reicin held many positions over a long career at Merck & Co. before moving onto Merck KGaA’s EMD Serono and then to Celgene, where she served as president of clinical development.
“There’s a lot of interest in going into protein degraders and ‘undruggable’ targets within a cell. This is an opportunity—and not a lot of people have the expertise to do this—to go after hard-to-target, ‘undruggable’ proteins on the cell surface,” she said. “We think the platform could go beyond GPCRs to other difficult-to-target cell surface proteins.”