Information on progress in research and development related to the CT-01, CT-02 and CT-05 projects and information on the molecular targets of these projects

Current Report No. 12/2023

Date of preparation: 27 March 2023

Subject: Information on progress in research and development related to the CT-01, CT-02 and CT-05 projects and information on the molecular targets of these projects

Legal basis: Article 17(1) MAR - confidential information

The Management Board of Captor Therapeutics S.A. based in Wrocław ("the Company") announces the progress of research and development and discloses the molecular targets of the following projects

1. CT-01 “Discovery and development of a new clinical candidate for the eradication of cancer stem cell in the treatment of hepatocellular carcinoma, through degradation of oncofetal transcription factor” ("Project CT-01");
2.  CT-02 "Design and development of non-toxic ligands of ligases and their application in the treatment of autoimmune diseases" ("Project CT-02"); and
3. CT-05 “Application of targeted protein degradation technology for the treatment of psoriasis and rheumatoid arthritis” (“Project CT-05”);

In the CT-01 Project, the Company previously announced in current report no 11/2022 dated 11 April 2022, two of the three molecular targets of the CT-01 Project, namely the proteins GSPT1 and SALL4. Approaching the clinical phase, Captor can now reveal that the clinical candidate compound in CT-01 also effectively degrades the NEK7 protein, thus providing a unique protein degradation profile of three proteins that is well suited to the treatment of hepatocellular carcinoma (HCC) and certain other cancers. Degradation of NEK7 leads to a reduction in IL-1b - a well-established pro-carcinogenic factor. IL-1b is elevated in inflammation, observed in 80% of HCC patients. A reduction in IL-1b levels enables the activation of the immune response against the tumor. We also wish to disclose that clinical candidate CPT-6282 is a pro-drug activated by an enzyme present in high levels in the liver, lungs and certain gastrointestinal tumours, which confers additional potential benefits for the treatment of liver, lung and neuroendocrine tumors.

The Company also discloses the NEK7 protein as a molecular target of Project CT-02. In addition to the anticancer benefits of degrading the NEK7 protein, in combination with the degradation of the GSPT1 and SALL4 proteins in Project CT-01, the selective degradation of NEK7 itself in Project CT-02 is also of significant value in the treatment of several autoimmune diseases, by providing a balance between the realization of a therapeutic role and the preservation of the immune function of the IL-1b-dependent pathway.

The NEK7 protein is involved in modulating the activity of the inflammasome complex, which plays key roles in the induction of the inflammatory response. Activation of the inflammasome complex, is not fully dependent on the kinase activity of the NEK7 protein - its structural (scaffolding) function plays a key role. Therefore, classical inhibition of the kinase activity of the NEK7 protein, will not provide a therapeutic benefit in contrast to its degradation.

The results of the Company's Project CT-02 studies demonstrate the desired activity in the form of:

• Effective degradation of the NEK7 at low concentrations in vitro (high potency) and ex vivo
• Degradation of NEK7 is correlated with the desired in-vitro biological effects on the inflammatory response
• Optimised compounds with good pharmacokinetics in animals have been developed
• Chemical series with capacity to cross the blood-brain-barrier has been identified and provides a framework for further development of drugs in the area of neurodegeneration

In Project CT-05, small-molecule compounds that induce selective degradation of PKCӨ can be used to treat a range of both autoimmune and oncological diseases. The degradation of PKCӨ kinase represents a high therapeutic value, and previous approaches based on classical inhibitors have been characterized by good efficacy in patients, but numerous side effects due to inhibition of other PKC protein isoforms, as well as other unidentified molecular targets. The application of TPD technology, particularly the use of bifunctional degraders, has enabled the development of molecules with the highest selectivity in the class. This is particularly promising especially as the target is of unwavering interest to the pharmaceutical industry, as evidenced by the recent deal to license the inhibitor of this protein to BMS by Exscientia.

The results of the Company's Project CT-05 studies demonstrate the desired activity in the form of:

• Potent degradation and first-in-class selectivity profile of the molecular target PKCӨ in immune cells in vitro
• Desired effect on ex vivo immune cells, but no effect on non-immune cells
• First-in-class selectivity differentiates Captor’s compounds from the earlier inhibitor approaches that were unsuccessful in clinical trials due to side effects

The PKCӨ proteins an established modulator of the IL-17 pathway, which is a clinically-validated target in autoimmune diseases such as psoriasis. 

The Company will report further progress on the Projects CT-01, CT-02 and CT-05 as required by law.