Astellas and Cullgen to develop small molecule protein degraders

Japan-based Astellas Pharma has entered a partnership with Cullgen to discover and develop multiple targeted protein degraders through the latter’s proprietary uSMITE targeted protein degradation platform, in a deal potentially worth $1.9bn.

Under the agreement, Astellas will give an upfront payment of $35m to the San Diego-based biotech, Cullgen. The deal gives Astellas the option to exclusively license its rights for clinical development and commercialisation for any protein degrader compounds developed within the lead programme. Astellas could pay Cullgen up to $85m upon using its license option regarding the deal. Thus, Cullgen’s total compensation could surpass $1.9bn if Astellas uses all of its exclusive licensing rights and all predicted milestones for the programme are met. Astellas may also give Cullgen royalty payments based on potential sales.

In the earlier clinical development stages, Cullgen will co-promote new therapies from the lead programme in the US and partake equally in costs, profits and losses. The lead program will focus on producing cell cycle protein degraders for the treatment of breast cancer and other solid tumours.

Cullgen’s uSMITE platform, otherwise known as ubiquitin-mediated, small molecule-induced target elimination technology, targets the ubiquitin-proteasome system, which controls nearly all cellular processes such as cell growth, death and proliferation. Dysfunction in this system is the cause of many disease conditions. Small molecule products developed using the uSMITE platform degrade disease-related proteins in this system. The company claims this method allows for increased target specificity and reduced systemic drug exposure. This method can target enzymes, transcription factors, scaffold proteins and more.

The deal marks Cullgen’s first publicly disclosed collaboration. Since 2019, the company has raised $106m in three financing rounds to push the development of its uSMITE platform.

The partnership follows a series of pharmaceutical deals from Astellas. In June 2023, the Japan-based company signed a licence deal with Kate Therapeutics to develop and commercialise its X-linked myotubular myopathy (XLMTM) gene therapy, KT430. In April 2023, the biotech also entered a research agreement with Veneno Technologies to develop drugs that target G protein-coupled receptors (GPCRs).