Plexium Bags $102 Million for Targeted Protein Degraders

Plexium sees the promise of using small molecules to destroy rather than inhibit disease-causing proteins – and now it has $102 million to bring candidates into clinical trials. 

Lining its pipeline is a molecular glue that degrades the IKZF2 transcription factor, which helps regulate lymphocyte development. 

Plexium is also assessing selective degraders of CDK2, a cell cycle protein, and SMARCA2, a gene regulator in neuronal development. 

The San Diego, California-based preclinical biotech launched in 2019 with $28 million in Series A financing. To date, it has raised almost $200 million. This includes an oncology-focused drug discovery collab with Amgen that could earn Plexium $500 million in total. 

Related Article: Expanding Deals and Investments Underscore Burgeoning Market of Targeted Protein Degradation

How Do Targeted Protein Degraders Work?

Targeted protein degraders mediate the labeling of a target protein for destruction. 

The degraders, which could be a small molecule, could bring a target protein and a E3 ubiquitin ligase together. Imagine a sort of molecular glue that encourages interactions between two targets that don’t normally interact, and subsequently labels the target for degradation via proteasome. Small molecules with this function are called proteolysis targeting chimeras, or PROTACs. 

Other small molecules called monovalent protein degraders could change the surface of a target protein to make it easier for the cell degradation machinery to recognize and destroy the target. 

Plexium believes its high-throughput cell-based screening platform could discover new protein degraders from molecular glues to monovalent degraders, while also identifying new E3 ligases. This could open opportunities to address undruggable targets, the company said. 

Protein Degraders in the Clinic

As Plexium hopes to go clinical, several companies are already taking their products through human trials. Ranok Therapeutics was recently cleared by the US FDA to conduct a Phase 1/2 trial for its BRD4-selective degrader in advanced solid tumors and lymphomas. 

Meanwhile, Arvinas Therapeutics has reported that its androgen receptor degrader is showing responses in prostate cancer patients with a specific mutation. Arvinas is hoping to get accelerated approval once data on 100 patients with the mutation comes out. In 2019, the company was the first to take a protein degrader into a clinical trial.  

Related Article: Eli Lilly, Lycia Partnership Signifies the Growing Targeted Protein Degradation Market

Details of the $102 Million Funding Round 

The oversubscribed round was led by BVF Partners, L.P. and TCG X, with participation from four new investors Softbank Vision Fund 2, RA Capital Management, Surveyor Capital (a Citadel company), and Pappas Capital. Seven existing investors including Lux Capital and Pivotal bioVenture Partners also took part. 

In connection with the financing, Cariad Chester, a partner at TCG X, has joined Plexium’s board.

Author

Joy Lin

Without knowledge, there is no imagination. Without imagination, knowledge is meaningless

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