While many pharmaceutical companies are chasing targeted and immunotherapy therapeutic drugs, protein degradation therapy has also attracted the attention of more and more companies and has become another new direction in the field of new drug R&D. Recently, Plexium, an emerging biotechnology company, announced the completion of financing US$ 102 million to develop a new generation of targeted protein degradation (TPD) therapies. This round was led by BVF Partners and TCG X, with participation from new investors Softbank Vision Fund 2, RA Capital Management, Surveyor Capital (a subsidiary of Citadel), Pappas Capital and other existing investors.
The funds generated this time will enable Plexium to accelerate its R&D projects toward the clinic practices, including a molecular glue that selectively degrades the IKZF2 transcription factor, as well as selective protein degradation agents for CDK2, SMARCA2 and other undisclosed high-value targets.
PROTAC & small-molecule monovalent degradation agent
In the human body, the overexpression of pathogenic proteins has become an important reason for the occurrence and development of diseases. Can we use special means to send these pathogenic proteins to the proteasomes for degradation, so as to treat diseases? The answer is yes, and the key point is how to make disease-causing proteins ubiquitinated. This series of processes all involve the well-known PROTAC technology.
PROTAC (Proteolysis Targeting Chimera) is a bifunctional small molecule, which is composed of target protein ligands and E3 ubiquitin ligase ligands connected by Linker. It uses the ubiquitin-protease system to recognize, bind and degrade disease-related target proteins. One of the greatest advantages of PROTAC technology is that it changes the target from "undruggable" to "druggable". It has made progress in the fields of tumors and autoimmune diseases, and has shown great potential in overcoming the drug resistance. From the birth of the world's first PROTAC molecule in 2001 to the clinical trial of the first PROTAC drug ARV-110 in 2019, targeted protein degradation therapy has attracted high attention from academia, pharmaceutical and biotechnological industries.
Compared with PROTAC technology, Plexium focuses on the development of single-functional molecules. Through the DELPhe platform, a series of small molecule monovalent protein degradants are identified. These small molecules can bind to target protein or E3 ubiquitin ligase alone, resulting in conformational deformation of the protein through adjusting the selective ubiquitination of E3 ligase, and will ultimately induce the degradation of pathogenic target proteins.
At present, there are less than 20 small-molecule degradation agent companies entering the clinical research stage worldwide, and there is no approved small-molecule degradation agent drug on the market. In this emerging track, Plexium as a pipeline has not yet entered the clinical research stage. What is it that attracts the investment?
Plexium's unique DELPhe platform
Plexium focuses on the development of monovalent degradation agents. Its DELPhe platform is named after the DNA Encoding Library (DEL) and Phenotypic Screening (Phe). The key factor of the platform is miniaturization. It combines the screening breadth of the DEL with the screening depth in cell-based deep multiplexed phenotype, enabling high-throughput screening of DEL of small molecules ranging from picoliter to nanoliter volumes to identify novel small molecules that bind to E3 ubiquitin ligases. The small molecules can bind to the target protein or E3 ubiquitin ligase alone, resulting in a change in protein conformation and ultimately degrading the target protein.
As a unique drug discovery engine, its advantage lies in the use of the DEL technology to rapidly synthesize and screen the DNA codes at a low cost, and extend the screening of the DEL to the cell-based functional detection. In addition, the platform is very suitable for the research of E3 ubiquitin ligase and adjusting the effec...
(All Rights Reserved)