Astellas delves deeper into protein degrading drugs with Cullgen deal

2023-06-15

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Dive Brief:

Astellas Pharma has partnered with biotechnology startup Cullgen to develop drugs that break down, rather than block, disease-causing proteins, becoming the latest large pharmaceutical company to team with a biotech working in the emerging field.

Under a deal announced Thursday, the two companies will team up to unearth potential drugs that Astellas will have an exclusive option to license. Cullgen will get the chance during early development to split costs and profits, as well as share U.S. rights.

Astellas will pay Cullgen $35 million upfront and may add another $85 million if it licenses the startup’s lead program, a potential treatment for breast cancer and other solid tumors. Cullgen could receive more than $1.9 billion overall if all deal targets are met, though those payments aren’t guaranteed.

Dive Insight:

Over the last decade, targeted protein degradation — a way of using medicines to rid cells of troublesome proteins — has become one of the more competitive areas of drug research.

The idea behind protein degraders is to use small molecules to forcibly pull two proteins together that normally wouldn’t interact. This “molecular glue,” as it’s known, includes a mechanism that tells a cell’s garbage disposal system to shred the unwanted protein.

The approach could be a way to reach difficult drug targets, and has spawned the creation of a lengthy list of biotech companies in recent years. A few, such as Arvinas Arvinas, Kymera Therapeutics and C4 Therapeutics, are publicly traded. Several have partnered with larger pharmaceutical companies, many of which have built internal research capabilities in the field or looked to biotech startups for help.

Astellas is doing a bit of both. The company has circled protein degraders as a primary area of focus, investing in the drugmaking approach for more than a decade, according to Masahiko Hayakawa, head of the company’s protein degradation research. That effort is one part of a broader plan to change how it conducts research and grow sales despite the loss of patents protecting some of its top products. It’s led to a drug prospect developed in-house — a degrader — that targets the well-known cancer driver KRAS and is now in clinical testing, Hayakawa said.

Protein degraders ”give us an opportunity to create strides in cancer treatment,” he said, as they have the potential ”not only to access targets that have been considered undruggable, but to also reduce the emergence of resistance and toxicity, which has created issues in conventional small molecule drug discovery.”

But Astellas is looking outward as well. Last June, it cut a deal with biotech Generian to develop small molecule drugs that either activate, stabilize or degrade proteins. The new deal with Cullgen adds to those capabilities, giving the company the chance to add several more protein-degrading drugs to its portfolio. The startup has developed proprietary binding molecules that could be useful in making novel degraders, Hayakawa said.

The alliance marks the first disclosed by Cullgen, a San Diego- and China-based biotech that has raised about $106 million in three rounds of funding since 2019. The company is backed by AstraZeneca, Sequoia Capital and other investors.

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