Risen Pharma, a clinical stage biotech company focusing on developing treatments that address mechanisms of therapeutic resistance, today announced poster presentations on two therapeutic candidates: (1) RP04340, a potent and orally available PROTAC compound targeting KRAS G12C/D/V mutants in cancers, and (2) RP05129, a small-molecule inhibitor of ADAR1 for cancer immunotherapy, at the American Association for Cancer Research (AACR) Annual Meeting 2025.
Title: Preclinical studies of RP04340: an orally available and potent PROTAC compound targeting KRAS G12C/D/V mutant tumors
Session Category: Experimental and Molecular Therapeutics
Session Title: Degraders and Glues 2
Abstract Number: 1662
Key findings in the presentation:
1. RP04340, a potent and orally bioavailable PROTAC, degrades KRAS G12C/D/V mutant proteins with low nanomolar DC50 values in KRAS-mutant cell lines and >80% of target protein degradation. RP04340 suppresses downstream signaling (pERK, DUSP6) and significantly inhibits tumor cell proliferation.
2. In vivo studies using mouse xenograft models (Miapaca-2, PK-59, and NCI-H727) demonstrated significant tumor growth inhibition following daily oral administration of RP04340 at doses of 25, 50, and 100 mg/kg, with a clear dose-response relationship.
3. Pharmacokinetic analyses revealed that RP04340 accumulated preferentially in tumor tissues, achieving high intratumoral concentrations after repeated dosing.
4. Tissue distribution studies in mouse showed significant accumulation of RP04340 in the lungs and pancreas after 15 days of consecutive dosing, supporting its potential application for treating cancers in these organs.
Full Texts of the Abstracts:
https://www.abstractsonline.com/pp8/#!/20273/presentation/5361
Title: Discovery of a Small-Molecule Inhibitor of ADAR1 for Cancer Immunotherapy
Session Title: Novel Cancer Therapeutic Targets 1
Abstract Number: 4288
1. Risen has screened a 265K compound library against ADAR1 deaminase domain and compound RP05129 was identified as an ADAR1 inhibitor.
2. RP05129 demonstrated the ability to downregulate ADAR1 editing activity and trigger downstream interferon-β activation in an ADAR1 dependent manner.
3. High-resolution co-crystal structures of ADAR1 with inhibitor RP05129 or its analogs were solved in-house to guide SAR study.
4. RP05129 and its analogs hold promise for enhancing the efficacy of immune-based therapies in cancers that are dependent on ADAR1.
https://www.abstractsonline.com/pp8/#!/20273/presentation/3747
About Risen (Shanghai) Pharma Tech Co., Ltd.
Risen Pharma is an internationally competitive clinical-stage biotech company focusing on developing and commercializing highly-needed, patient-accessible therapeutics. The company’s integrated capabilities cover all stages of drug development, including lead identification and optimization, preclinical evaluation, clinical development, and commercialization. Risen specializes in neurodegenerative diseases like Alzheimer’s, leveraging small molecules, PROTACs, and siRNA technologies to develop a comprehensive therapeutic platform encompassing prevention through treatment. Based on strong in-house R&D capabilities, the company has advanced over 20 innovative drug candidates and built a differentiated pipeline in degenerative, metabolic, autoimmune, cancers, and infectious diseases.
Media ContactCompany Name: Risen (Shanghai) Pharma Tech Co., Ltd.Contact Person: Wenbing YuEmail: Send EmailCountry: ChinaWebsite: http://www.risen-pharma.com/
