Senhwa?s CX-5461 with Astrazeneca/Daiichi Sankyo?s ADC, Trastuzumab Deruxtecan in Phase 1b HER2+ and Breast Cancer Trial; NCI Submits FDA Application

Senhwa Biosciences, Inc. announced that Senhwa's novel drug Pidnarulex (CX-5461) has been selected under the U.S. National Cancer Institute?s (NCI) anticancer program. To date, three clinical trials have successfully received IND clearance and some commenced patient enrollment: CX-5461 monotherapy in advanced solid tumors, CX-5461 monotherapy in MYC-aberrant B-cell lymphoma, CX-5461 in combination with Sanofi/Regeneron?s marketed PD-1 inhibitor Cemiplimab for refractory microsatellite stable colorectal cancer. The fourth trial, for which a new protocol has now been submitted as Protocol Amendment: New Protocol under existing IND, marks the first clinical trial of CX-5461 combined with an ADC, Trastuzumab Deruxtecan (T-DXd, brand name Enhertu), in a Phase 1b trial for the treatment of HER2-positive solid tumors and HER2-low or HR-positive HER2-ultralow breast cancer.

T-DXd is the first ADC therapy approved for HER2-low metastatic breast cancer, a newly defined subtype of the disease. This ADC utilizes the monoclonal antibody trastuzumab to selectively target HER2-expressing tumor cells and delivers the cytotoxic payload deruxtecan directly into the tumor, thereby enhancing antitumor activity while minimizing damage to healthy tissues. CX-5461 has previously demonstrated promising antitumor activities in breast cancer and other solid tumors in the clinical trial sponsored by SU2C-CCTG in Canada.

This combination of CX-5461 with T-DXd aims to enhance therapeutic efficacy in patients with low HER2 expression and offer new treatment options for these patients. Trial Design: a.Title: Phase 1b study of Pidnarulex and Trastuzumab Deruxtecan in patients with HER2 expressing Solid Tumors b.Enrollment: Dose Escalation: up to 24 patients Dose Expansion: 12 patients c.Treatment Regimen: This is a dose-escalation and dose-expansion trial. Patients will receive intravenous T-DXd on Day 1 and intravenous CX-5461 on Day 8 of each 21-day cycle.

Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. d.Trial Objectives: To evaluate the safety, tolerability, and preliminary efficacy of CX-5461 combined with T-DXd in patients with metastatic, unresectable, or locally advanced HER2-low or HR-positive HER2-ultralow breast cancer, and other HER2-positive solid tumors. Primary Endpoints: Dose Escalation: Determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of CX-5461 in combination with T-DXd in patients HER2-low breast cancer, hormone receptor (HR)-positive HER2-ultralow breast cancer or HER2-positive solid tumors 2.Dose Expansion: Evaluate safety and tolerability of CX-5461 combined with T-DXd at the RP2D in HER2-low and HR-positive HER2-ultralow breast cancer patients.

Secondary Endpoints: 1.Observe and record anti-tumor activity. 2.Evaluate the plasma pharmacokinetic (PK) profiles of CX-5461 and T-DXd when administered in combination. 3.Determine markers of deoxyribonucleic acid (DNA) damage response (DDR) in tumor specimens at baseline and on-treatment in patients with HER2-low and ultralow breast cancer in the dose expansion cohort (pharmacodynamic [PD] objective).

(3)Market Outlook: The global Antibody-Drug Conjugate (ADC) market is experiencing rapid growth. According to the latest market research by BCC Research, the global ADC market surpassed USD 10.8 billion in 2023 and is projected to reach USD 47 billion by 2029, with a compound annual growth rate (CAGR) of 28.4%. By the end of 2022, 15 ADC drugs had received regulatory approvals worldwide, with over 140 ADCs in clinical development, reflecting robust R&D momentum.

HER2 has been recognized as a key oncogenic driver across multiple tumor types, including breast, gastric, cholangiocarcinoma, colorectal, bladder, salivary gland, and non-small cell lung cancers. HER2-targeted therapies have significantly improved survival outcomes particularly in breast and gastric cancer, and HER2 remains one of the most impactful targets in ongoing ADC development pipelines. Nevertheless, further breakthroughs in other solid tumors are still needed.

As ADCs emerge as a pivotal area in oncology drug development, Senhwa aims to expand HER2-targeted treatment into broader solid tumor indications. By combining CX-5461 with next-generation ADC Enhertu, the company strives to pioneer transformative therapies, capture opportunities in the rapidly growing global ADC market, and strengthen its leadership in precision oncology. (4)A single clinical trial result does not reflect the success or failure of new drug development and launch in the future.

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