SALL4

Captor Therapeutics, a biopharmaceutical company developing drugs based on Targeted Protein Degradation (TPD), has applied for approval to conduct a first-in-human Phase 1 clinical trial with CT-01, a compound developed as part of a FENG-funded project entitled: "Discovery and development of a drug candidate for the treatment of hepatocellular carcinoma to eliminate cancer stem cells by induced degradation of an oncogenic transcription factor". The trial will be conducted by ICON PLC under the supervision of Captor Therapeutics. - We have been preparing for many months to make the most important announcement in the CT-01 project, the start of clinical trials. We do so with great satisfaction and a sense of responsibility for the next steps that could bring new treatment options to many patients around the world. Despite significant progress in recent years, treatment options for advanced HCC remain limited. Available systemic treatments are characterized by a moderate response rate and impact on survival, and most patients experience disease progression despite available treatments. As a result, the median survival for patients with metastatic disease is approximately 20 months. Therefore, the treatment of patients with advanced hepatocellular carcinoma remains an unmet medical need," commented Dr. Tom Shepherd, CEO of Captor Therapeutics. The Company's submission is for a planned multi-center, open-label, dose escalation and expansion Phase 1 study. The study is designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of CT-01, both as monotherapy and in combination with everolimus, in patients with moderately to highly advanced HCC (BCLC grade B or C) and preserved liver function (Child-Pugh grade A). The multicenter clinical trial will be conducted at leading European liver cancer centers in Spain, Germany and France. Patients will receive escalating doses of CT-01 orally. The primary objective of the study is to evaluate safety and tolerability following experimental treatment with the drug candidate in patients diagnosed with primary liver cancer and to determine the maximum tolerated dose and/or recommended dose for further phases of clinical trials in monotherapy and combination treatment. In addition, the anti-tumor activity using radiological imaging and serum tumor markers as well as the pharmacokinetic and pharmacodynamic profile of the drug candidate after monotherapy and in combination treatment will be evaluated. - CT-01 is a small molecule protein degrader of GSPT1, NEK7 and SALL4 that has demonstrated anti-tumor activity in several liver cancer models in preclinical studies. In combination with everolimus (an inhibitor of the mTOR pathway, which is often dysregulated in cancer cells), CT-01 demonstrated greater anti-tumor efficacy than CT-01 alone or everolimus as monotherapy. The potential anti-tumor efficacy of CT-01 is based on its novel mechanism of action, which involves 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 directly by preventing efficient protein synthesis by cancer cells. This is also important in a mechanism that is independent of the presence of an unfavorable mutation of the TP53 protein," said Michal Walczak, Board Member and CSO of Captor Therapeutics. The goal of the CT-01 project is to develop a drug candidate using targeted protein degradation technology that will halt the progression of hepatocellular carcinoma and provide significant clinical benefit to patients. Primary liver cancer is the sixth most common cancer and the fourth leading cause of cancer-related deaths worldwide. The majority (80-90%) of liver cancers are hepatocellular carcinomas (HCC) that arise from chronic liver disease.

Captor Therapeutics has signed an agreement for the implementation and funding of the Stage II of the CT-01 Project Captor Therapeutics, a biopharmaceutical company specialized in the development of drugs based on Targeted Protein Degradation ("TPD"), on 12.06.2024 signed an agreement for the implementation and funding of the second stage of its most advanced project, CT-01: "Discovery and development of a new clinical drug candidate for the eradication of cancer stem cel in the treatment of hepatocellular carcinoma, through degradation of oncofetal transcription factor. - Stage II". The agreement approves the extension of the project until March 31, 2026. The decision received is in response to a protest filed in November 2023 by the Company against the originally negative evaluation of the project application. Further Cofinancing in the amount of PLN 6,766,157.95 will be used by the Company for ongoing work on the final formulation of the drug candidate and the start of multi-center clinical trials, still scheduled to begin in 2024. CT-01 is the Company's second implemented in phases Project next to CT-03. The basis of both projects is the application of an innovative approach, i.e. targeted protein degradation (TPD) to fight cancer. In the case of CT-01, the Company has developed a molecule - a triple degrader against proteins: GSPT-1, NEK7 and SALL4 with high anti-cancer activity in xenogeneic models of HCC (Hepatocellular carcinoma), the most common liver cancer worldwide. The therapy being developed by the Company is a response to the very limited treatment options for patients diagnosed with Hepatocellular carcinoma, Currently, the only methods that offer the possibility of a complete cure for this type of cancer are surgery or liver transplantation for which the eligibility criteria are very restrictive. We are confident in the success of Project CT-01 and look forward to the first positive results after administration of our drug. We will keep you informed about the results of the ongoing research

CT-01 targets 3 well suited proteins including NEK7 with poor prognosis in key liver cancer Strong preclinical data generated with CT-02 against NEK7 CT-05 potential best-in-class pro high potential / partially de-risked PKCӨ protein pathway Webcast to take place on Thursday 30th March at 4 pm CET / 10 am ET – Registration link below WROCŁAW, Poland, March 28, 2023 (GLOBE NEWSWIRE) -- Captor Therapeutics S.A. (“Captor”) (WSE:CTX), a leader in the development of Targeted Protein Degradation (TPD)-based drugs, today discloses the identity of the drug targets as well as associated supporting data, and provides an update on the progress in the research and development of its pipeline lead programs CT-01, CT-02 and CT-05. Dr Michal Walczak, Chief Scientific Officer and Co-founder of Captor, will present the scientific rational for these targets as well as the market potential of each of Captor’s lead programs and will answer questions during a webcast on March 30th 2023. Webcast invitation to discuss scientific rational and market potential of new targets Date: March 30th 2023 at 4pm CET / 10 am ET Please register by following this link. CT-01 / CPT-6281 targeting GSPT1, SALL4 and (new disclosure) NEK7 CT-01 / CPT-6281 is currently undergoing IND/CTA-enabling studies with the first clinical trial expected to start at the end of 2023. The first indication will be in Hepatocellular Carcinoma (HCC). CPT-6281 is a first-in-class degrader of GSPT1, SALL4, and NEK7. GSPT1 is a protein involved in the termination of translation, SALL4 is a transcription factor often over-expressed in HCC patients and correlating with poor prognosis, and NEK7 is a protein in which degradation leads to a reduction in IL-1b production, a well-known pro-carcinogenic factor. Moreover, CPT-6281 is particularly well suited for liver, lung, and neuroendocrine tumors since it is a prodrug1 activated by an enzyme present in high concentration in the liver, the lungs, and some gastrointestinal tumors. CT-02 targeting (new disclosure) NEK7 In addition to the potential benefits of NEK7 degradation combined with the degradation of GSPT1 and SALL4 in cancer, as mentioned above for the CT- 01 Project, the selective degradation of NEK7 alone in the CT-02 Project has many potential benefits as a treatment of several autoimmune diseases. Such NEK7 degradation allows the modulation of the inflammasome, a complex that plays a critical role in the regulation of the inflammatory response. Captor believes that selective NEK7 degraders have the potential to overcome the limitations shown in the past of NLRP3 inhibitor drugs related to increased susceptibility to infection. Importantly, it is established that NEK7 pro-inflammatory activity is largely driven by its scaffolding function, and because of that, classical inhibition of NEK7’s kinase function doesn’t provide therapeutic benefit. It is therefore expected that selective degradation of NEK7 would also remove the NEK7 scaffolding function leading to potent inflammatory inhibition. Pre-clinical studies have revealed the following benefits of CT-02: Effective NEK7 degradation 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 Compounds with the ability to cross the blood-brain-barrier have been identified and provide opportunity for further development in the area of neurodegeneration CT-05 targeting (new disclosure) PKCӨ (PKC theta) CT-05 targets the PKCӨ protein, a protein highly relevant in both autoimmune diseases and cancer. Indeed, PKCӨ plays an important role in the modulation of T cells by limiting the suppressive function of T cells. It is therefore expected that degrading the PKCӨ protein would lead to an increased T cell suppressive function. PKCӨ is a high-value target with opportunities in certain autoimmune diseases, such as allergy, psoriasis, and inflammatory bowel disease, as well as certain malignancies, such as breast and gastrointestinal cancer. Importantly, the approach behind CT-05 is partially de-risked thanks to: the PKCӨ protein acts via the CD3/CD28 – IL-2/IL-17 pathway. The IL-17 pathway is a clinically validated pathway in autoimmune diseases such as psoriasis with established modulators2 the potential of the PKCӨ protein pathway is underpinned by BMS’s latest in-licensing of Exscientia’s PKCӨ inhibitor EXC4318 In preclinical studies, CT-05 has demonstrated attractive features that differentiate CT-05 from inhibitors that failed in clinical trials due to side effects: Potent degradation and first-in-class selectivity pro the molecular target PKCӨ in immune cells in vitro Desired effect on ex vivo immune cells No effect on non-immune cells AboutCaptorTherapeutics Captor Therapeutics is a drug discovery and development company applying targeted protein degradation (TPD) technology to discover and develop breakthrough drugs for diseases with significant unmet medical need. TPD is a revolutionary approach to developing new drugs that can target new molecular targets considered undruggable" using classical drug modalities and provide additional treatment options for diseases where existing drugs do not provide optimal treatment. Captor is currently developing treatments for undertreated serious conditions, including cancer and autoimmune diseases. For more information on Captor Therapeutics, visit: LinkedIn: @CaptorTherapeutics Twitter: @CaptorTherapeu1 Mediaandinvestor contacts: PolishMediaandInvestorRelations: Point of View Bartosz Sawulski +48 694 400 787 captortherapeutics@pov.pl International InvestorRelations: LifeSci Advisors Guillaume van Renterghem +41 (0)76 735 01 31 gvanrenterghem@lifesciadvisors.com 1 A prodrug is a biologically inactive compound which can be metabolized in the body to produce a drug which is pharmacological active. 2 Ixekizumab, Secukinumab, Brodalumab