▎WuXi AppTec Content Team Report

On August 23, the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) announced that three Class 1 cancer investigational new drugs developed by Hansoh Pharma have been approved for clinical trials.

• HS-10502 Tablets,In combination with enzalutamide or in combination with reviluramide or in combination with abiraterone acetate tablets (II), or in combination with apatinib or in combination with albumin paclitaxel or in combination with docetaxel or in combination with irinotecan liposome or in combination with HS-20093 or in combination with HS-20089 or in combination with HS-20089 + bevacizumab for the treatment of patients with advanced solid tumors;

• HS-20089 for Injection, in combination with HS-10502 tablets, is intended for the treatment of patients with advanced solid tumors;

• HS-20093 for Injection, in combination with HS-10502 tablets, is intended for the treatment of patients with advanced solid tumors.

Screenshot source: CDE official website

Public information shows that HS-10502 is aPARP1-Specific Selective Inhibitor。HS-20089 for Injection andHS-20093 are respectivelyTargeting B7-H4AndTargetedB7-H3Antibody-drug conjugates (ADCs): GlaxoSmithKline (GSK) has obtained exclusive global rights outside of Greater China (mainland China, Hong Kong, Macao, and Taiwan regions) for these two ADC products through authorization from Hansoh Pharma.

HS-10502: A PARP1-Specific Selective Inhibitor

PARP inhibitors are targeted therapies developed by exploiting the DNA damage response (DDR) defects in tumors. They have already received regulatory approval for treating various cancer types with DDR defects, including breast cancer, ovarian cancer, and prostate cancer. Researchers are currently developing multiple next-generation PARP1-specific inhibitors that are specifically designed to target PARP1.Due to its non-inhibition of PARP2 activity, it has lower toxicity compared to other PARP inhibitors, thereby offering better tolerability, target binding affinity, and efficacy.

According toClinicalTrialsOfficial Website,Hansoh Pharma has already launched in June 2023HS-10502Phase 1 Clinical Study for the Treatment of Solid Tumors, Aiming to Evaluate HS-10502 inHomologous Recombination Repair (HRR) Gene mutations or homologous recombination deficiency (HRD) positive advanced solid tumorsSafety, tolerability, pharmacokinetics (PK), and efficacy in patients. The study plans to enroll 318 subjects and is expected to conclude in 2026.

HS-20089 for Injection: B7-H4 Targeted ADC

B7H4 is one of the newly discovered members of the B7 family, and is aCell surface proteins that are overexpressed in a variety of tumors,Can help tumor cells evade the monitoring of the immune system.Studies have shown that,B7H4 in Triple-Negative Breast Cancer (74%), Ovarian Cancer (77%), endometrial cancer (94%), and gallTube cancer (89%) is the most common, whileLimited expression in normal tissues. In addition,B7H4 is independent of PD-L1 expression,Usually highly expressed in PD-L1 negative tumors, demonstrating an immune escape mechanism distinct from PD-1/L1.This suggests that therapies targeting the B7H7 pathway have the potential to be effective in PD-L1-negative/refractory patients.

According toClinicalTrialsOn the official website, researchers are conducting a Phase 2 clinical study of HS-20089, targetingOvarian cancer and endometrial cancer,and multiple phase 1 clinical studies on solid tumors. According to the public data from Hansoh Pharma, the phase 1 clinical trial results showed that this product demonstrated good tolerability and anti-tumor activity in advanced solid tumors, andShows encouraging efficacy in triple-negative breast cancer。

HS-20093 for Injection:B7-H3 Targeting ADC

B7-H3: A New and Promising Target in Cancer TherapyAs a transmembrane protein of the B7 family, B7-H3 is frequently overexpressed in various types of cancer. Studies have shown that inhibitors targeting B7-H3, including antibodies, ADCs, and radioimmunotherapy, represent a new class of anti-tumor drugs.According to public information, currently multiple products fromB7-H3 isNew drugs targeting have entered phase 2 or phase 3 clinical research stages globally, including those from Hansoh Pharma.HS-20093 is one of the products with faster progress.

For InjectionHS-20093 is composed of a fully humanized B7-H3 monoclonal antibody covalently linked to a topoisomerase inhibitor (TOPOi) payload, and this product has currently entered clinical trials targeting...Recurrent Small Cell Lung CancerThe international multi-center Phase 3 clinical study (ARTEMIS-008), andMultiple phase 1 and phase 2 clinical studies for the treatment of lung cancer, sarcoma, head and neck cancer, and other solid tumors are currently being conducted in China.. Recently, the product also received approval from the U.S. FDABreakthrough Therapy Designation, for the treatment of patients with extensive-stage small cell lung cancer (ES-SCLC) that has progressed during or after platinum-based chemotherapy (recurrent or refractory).

Hansoh Pharma's recent approval for a new clinical trial by implication means it is about to embark on new clinical explorations involving a PARP1 inhibitor combined with B7-H4 targeted ADC, as well as in combination with B7-H3 targeted ADC. We look forward to these new explorations achieving breakthroughs soon, bringing new options for disease treatment.

[1] Official website of the Center for Drug Evaluation, National Medical Products Administration of China. Retrieved Aug 23, 2024, from https://www.cde.org.cn/main/xxgk/listpage/da6efd086c099b7fc949121166f0130c

[2]PARP1 inhibitor HS-10502, from https://www.cancer.gov/publications/dictionaries/cancer-drug/def/parp1-inhibitor-hs-10502

[3]ClinicalTrials Official Website. From https://clinicaltrials.gov/study/NCT05740956?term=HS-10502&rank=1