SALL4 is a transcription factor expressed in the human fetal liver and silenced in adults but often re-expressed in HCC patients, which correlates with poor prognosis. There is a demonstrated link between GSPT1 degradation and antitumor activity. GSPT1 is a protein involved in the termination of translation, a process in which ribosomes synthesize proteins after the transcription of DNA to RNA. (WSE:CTX), a biopharmaceutical company focused on the development of targeted protein degradation (TPD) drugs for cancer and autoimmune diseases, today announces the molecular targets of one of its core pipeline projects designated CT-01, which is focused on the development of TPD therapy for hepatocellular carcinoma (HCC).Ĭompelling in-vitro and in-vivo preclinical data demonstrate that CT-01 candidate compounds induce degradation of Eukaryotic peptide chain release factor GTP-binding subunit ERF3A (GSPT1), Sal-like protein 4 (SALL4) and another undisclosed neo-substrate with essential function in tumorigenesis. WROCLAW, Poland, Ap(GLOBE NEWSWIRE) - Captor Therapeutics S.A. CT-01 on track to enter clinical development in 2023.Compelling pre-clinical data generated demonstrating HCC tumor regression.The unique degradation profile supports the strong competitive potential of the program.CT-01 compounds induce degradation of GSPT1, SALL4 and another as yet undisclosed neo-substrate.“ However, we are still learning how to use this scientific potential to generate commercial value. “ The number of biotech companies in Poland is growing, as well as the level of investment in science, ” Sagan said. Other notable Polish biotechs include Warsaw-based OncoArendi and Selvita from Krakow. “ We believe that the way to a successful degrader may depend on the target ,” Sagan said.Ĭaptor Therapeutics is part of the expanding biotech scene in Poland, which includes Pure Biologics, based in the same city as Captor. Rather than investing in one type of degrader drugs like many other companies do, Captor Therapeutics is exploring different classes of degrader drugs. “ We can expect that several degraders will enter clinical trials in the near future ,” Sagan said to me. Other companies are springing up to develop similar drugs, such as the UK biotech Polyprox, which makes PROTACS out of proteins, rather than small molecules. The most advanced PROTACs belong to the US biotech Arvinas, and are currently in phase I. Many companies focus on the development of PROTACS, which are chimeric small molecules designed to trigger the destruction of target proteins. The protein degradation approach is hot at the moment, especially in oncology. This could then allow new classes of drugs to enter the market for difficult-to-treat conditions such as cancer and autoimmune diseases. Protein degradation has the potential to open up the undruggable proteome. The company has raised €33M so far in grants and investments to fuel the development of its cancer treatments. “ In this case, taking the protein down provides a clear advantage over simple inhibition ,” Maria Sagan, biotechnology specialist at Captor Therapeutics, told me.įounded in 2017, Captor Therapeutics is currently in the early preclinical stages, and hasn’t yet disclosed which particular diseases it will be targeting. In contrast, Captor can get access to proteins inside the cell that have more specific roles, an approach that is therefore less likely to result in side effects.Īnother advantage is that proteins can interact with other proteins to contribute to a disease, even if they are being blocked from their main function. For one, many existing drugs cause side effects because they target cell surface proteins that have many other roles besides the one that is causing the disease. This approach has a number of advantages over traditional drugs. This is done by labeling the proteins with a special tag that sends the protein to the ‘trash can’ of the cell, called the proteasome. Instead of designing drugs that either activate or block the target they bind to, the company instructs the cell to degrade the target. This can be a problem, since many of these proteins could be viable targets for treating diseases, such as some transcription factor proteins in cancer.Ĭaptor Therapeutics is developing small molecule drugs capable of targeting these undruggable proteins. The rest of the proteins can’t bind to existing small molecule drugs, making them ‘undruggable’. Small molecule drugs are able to target a small minority of proteins in the cell, such as cell surface proteins. Mission : To develop cancer treatments able to degrade proteins that are normally outside the reach of traditional drugs, called the ‘undruggable proteome’. In the Polish city of Wrocław, Captor Therapeutics is developing cancer treatments that destroy disease-causing proteins.
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