On December 22, 2020 Sosei Group Corporation, a world leader in GPCR-focused structure-based drug design and development, and Captor Therapeutics, a European leader in targeted protein degradation, have entered a strategic technology collaboration focused on the discovery and development of novel small molecules that target the degradation of disease-associated G protein-coupled receptors (GPCRs) (Press release, Captor Therapeutics, DEC 22, 2020, View Source [SID1234623171]).
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Targeted protein degradation (TPD) is an approach whereby the body’s natural process for degrading proteins is diverted using small molecule drugs to eliminate disease-causing proteins. The selective destruction of such proteins is expected to have multiple advantages over classical drugs such as inhibitors and antibodies for the development of novel therapeutics against a broad range of diseases.
Sosei Heptares and Captor initially will focus on identifying small molecules targeting a GPCR with a key role in a strongly validated signalling pathway implicated in gastrointestinal disorders. A further aim of the collaboration is to generate high resolution structural information around the GPCR-E3 ligase complex to enhance drug discovery efforts as well as provide proof of concept for targeted degradation discovery approaches with other GPCRs and other target classes.
The collaboration combines Sosei Heptares’ structure-based drug design (SBDD) platform, including its structural insights around the target, and its deep understanding of GPCR pharmacology, together with Captor’s proprietary TPD Optigrade, platform and extensive know-how and expertise in protein degradation.
Since 2017, Captor has raised approximately €40 million from private investors and non-dilutive funding sources, allowing it to create an advanced TPD platform and establish five pipeline programs in cancer and autoimmune diseases.
Captor’s Optigrade platform is focused on improving the selectivity and performance of first-generation degrader drugs. The principle of TPD is to use small molecules to commit the target protein into the E3 ligase-mediated degradation pathway thereby eliminating or reducing its activity. Molecular glues and bifunctional degraders are two different approaches to promote the direct binding of a specific E3 ligase to the target protein, and in each case, Captor has developed molecules with improved selectivity. These approaches can also be coupled with Captor’s novel E3 Ligase ligands (Lilis) which take advantage of Captor’s extensive library of E3 Ligase enzymes to create a new generation of degrader drugs.
Promising leads will be progressed using the partners’ complementary discovery skills, resources and development capabilities for subsequent development and commercialization.
Under the agreement, the companies will jointly conduct the discovery and development program and will co-own any resulting products, with Sosei Heptares supporting initial R&D costs. No further financial details are disclosed.
Miles Congreve, Chief Scientific Officer of Sosei Heptares, commented: "Targeted protein degradation is a promising approach to drug discovery that is gaining strong interest in the pharmaceutical industry. However, there has so far been limited progress in applying this exciting approach to membrane-associated proteins such as GPCRs. We can see a real opportunity to expand the reach of our SBDD and GPCR pharmacology expertise into this area; GPCRs themselves play key roles in disease yet are often difficult to drug. We are delighted to enter this collaboration with Captor, which has developed multiple novel approaches to identify small molecules that promote TPD. We are excited to explore the potential of this unique combination of technologies to develop a novel GPCR degraders platform, opening up so far intractable drug targets for us to address."
Michal J. Walczak, Chief Scientific Officer of Captor Therapeutics, added: "This is an important partnership for both Captor and Sosei Heptares. We believe that the successful application of targeted protein degradation to G Protein-Coupled Receptors will open new avenues in medicine and will maximize treatment opportunities for patients. Working with Sosei Heptares, a global leader in targeting GPCRs, is an exciting opportunity to create truly novel medicines and unlock TPD for GPCR targets, which will constitute another cornerstone validating the potential of TPD as an emerging drug discovery technology."