Submission of application for approval of a phase 1 clinical trial in patients with hepatocellular carcinoma

Current report No. 31/2024

Date of preparation: 22.08.2024

Subject: Submission of application for approval of a phase 1 clinical trial in patients with hepatocellular carcinoma

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

The Management Board of Captor Therapeutics S.A., headquartered in Wroclaw, Poland (the "Company"), announces that on  22 August 2024 the Company submitted an application for permission to conduct a first-in-human Phase 1 clinical trial of the compound CT-01 to the European Medical Agency (EMA).

A multi-center, open-label, phase 1 study, dose-escalation and dose-expansion Phase 1 study is planned to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of CT-01 as monotherapy and in combination with everolimus in patients with intermediate or advanced hepatocellular carcinoma (BCLC grade B or C) with preserved liver function (Child-Pugh grade A).

The multi-center clinical trial will be conducted at leading European centers for the treatment of this cancer in Spain, Germany and France. Patients will receive ascending doses of CT-01 orally. The primary objective of the study is to evaluate the safety and tolerability of the drug in patients diagnosed with primary liver cancer and to determine the maximum tolerated dose and/or recommended dose for further clinical phases, both as monotherapy and in combination treatment. In addition, the study will evaluate the anti-tumor activity using radiological imaging techniques and serum tumor markers, as well as the pharmacokinetic and pharmacodynamic profile of the drug candidate after monotherapy and in combination treatment.

CT-01 is a low-molecular-weight protein degrader of GSPT1, NEK7 and SALL4, which has demonstrated anti-tumor efficacy in several preclinical liver cancer models (in cells and animals). In addition, the combination of CT-01 with everolimus (an inhibitor of the mTOR pathway, which is severely impaired in tumor-bearing cells) has shown improved in-vitro and in-vivo anti-tumor efficacy compared to CT-01 or everolimus as monotherapy.

Despite significant advances in the treatment of advanced liver cancer in recent years, treatment options for this cancer remain limited. Available systemic therapies have a moderate response rate and impact on survival, and most patients experience disease progression despite available treatments. The average survival time for patients with metastatic disease is estimated to be about 20 months. Therefore, the treatment of patients with advanced hepatocellular carcinoma remains an unmet medical need.

The potential anti-tumor efficacy of CT-01 is based on a novel mechanism of action, involving the removal of factors that affect tumor cell viability (GSPT1) and potentially stabilize the tumor microenvironment (NEK7). Unlike current therapies that rely on inhibiting angiogenesis or activating the immune system, CT-01 works by directly preventing efficient protein synthesis by tumor cells, a mechanism that is also independent of the presence of the poorly prognostic TP53 protein mutation.

The application to the EMA has been submitted through the central procedure. The organization of the study, under the supervision of the Sponsor (Captor), will be carried out by ICON Clinical Research Limited (The company announced the conclusion of an agreement with this entity in current report No. 46/2023 dated October 13, 2023).

The Company will report to further proceedings as required by law.