Startup Booster Therapeutics is launching to usher in the next wave of protein-degrading drugs

When proteins cause disease, the body has ways to deal with it. An emerging class of therapies that uses a cell’s built-in systems to eliminate harmful proteins has already reached the clinic through several companies. But there’s more than one way to get cells to break down disease-causing proteins, and Booster Therapeutics is developing drugs that can expand this approach to more proteins and more diseases. Neurodegeneration is Booster’s initial focus, and the startup secretly launched on Thursday, backed by $15 million in funding.

The protein-degrading drugs currently in clinical development target disease-causing proteins to a part of a cell called the proteasome. The drugs themselves are small molecules that recruit a molecular tag that marks a protein for removal by the proteasome. Companies developing targeted protein degraders include Kymera Therapeutics, Arvinas and Nurix Therapeutics. All three have research alliances with major pharmaceutical companies. Most breakdown products currently in development are intended for cancer, but research is also being conducted in this area for immunological disorders.

There are limitations to the current approach to breaking down proteins, says Diogo Feleciano, co-founder and Chief Scientific Officer of Booster. These protein-degrading drugs each target only one disease-causing protein, but some diseases are caused by multiple proteins. Targeted protein degradation also requires a molecular tag. Without this, the proteasome leaves the proteins alone.

Cells have different types of proteasome than the ones that are the focus of targeted protein degradation, and Feleciano says this is where Booster stands out. Berlin-based Booster focuses on the 20S proteasome, which can target multiple proteins without the need for a tag to mark them for degradation. Cells have ways of determining whether proteins are being broken down or not, Feleciano said. The 20S proteasome naturally targets proteins that are misfolded. In some diseases, these problem proteins aggregate and overwhelm the proteasome, which then becomes inactive. The startup develops small molecules that specifically target 20S proteasomes to give them a pharmacological boost.

“What we want to do with our molecules: reboot and reactivate that function to homeostatic levels,” Feleciano said. “By doing that we can improve the breakdown of proteins and alleviate the build-ups that are known to be toxic.”

Drug research has already produced drugs that target the proteasome. For example, proteasome inhibitors treat multiple myeloma by preventing proteasomes from removing proteins that are no longer useful. The resulting protein buildup leads to the death of cancer cells. But scientists have been looking for ways to activate proteasomes to treat disease, a field that Feleciano acknowledges didn’t start with Booster.

Feleciano’s Ph.D. research addressed neurodegeneration, including the role of the proteasome in such diseases. He said his work sparked interest in therapies that could target the proteasome and form the basis of a company. He found promising science in the laboratory of Darci Trader, a professor in the department of pharmaceutical sciences at the University of California, Irvine, whose research focuses on chemically stimulating the 20S proteasome in neurons. Parkinson’s disease is a focus of Trader’s research. Booster founded in 2020 with Trader as scientific co-founder. The startup is incubating within Apollo Health Ventures, the venture capital firm where Feleciano is an entrepreneur in residence.

Booster is based on DGRADX, a platform technology that uses computational techniques to understand the structure of the 20S proteasome. The platform also uses proprietary methods to automate high-throughput screening to identify and optimize small molecule proteasome activators.

For now, Booster isn’t saying much about its pipeline. But in addition to Parkinson’s, Feleciano says his company’s approach also has potential applications in Alzheimer’s disease. Booster’s seed funding announced Thursday was led by Apollo Health Ventures and Novo Holdings. With the capital, Booster will continue to build the company and further the development of its programs, according to Feleciano.

“Not only are we pioneering the activation of the proteasome, we are also pioneering the understanding of what that means,” he said. “We are building up more knowledge of what is there. This is an area that is still unexplored.”

Image: a bit, Getty Images