Kelun-Biotech’s HER2 ADC Trastuzumab botidotin (A166) Second NDA Accepted By NMPA

---Jan. 7, 2025, Chengdu, China---

Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (the “Company”) announced that the new drug application (NDA) (the “Application”) for human epidermal growth factor receptor 2 (HER2)-directed antibody-drug conjugate (ADC) trastuzumab botidotin (formerly A166) was accepted by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China for the treatment of adult patients with HER2 positive unresectable or metastatic breast cancer (BC) who have received at least one prior anti-HER2 therapy.

The approval is based on a multi-center, randomized, open-label, controlled, phase III KL166-III-06 study that evaluates the efficacy and safety results of trastuzumab botidotin monotherapy versus T-DM1 in patients with HER2 positive unresectable or metastatic BC who have received prior trastuzumab and Taxane-containing regimens. At a pre-specified interim analysis, trastuzumab botidotin monotherapy demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of progression-free survival (PFS) as assessed by the blinded independent central review (BICR) compared with T-DM1.

Trastuzumab botidotin is an innovative HER2 ADC developed by the Company, which conjugates a novel, MMAF derivative (a highly cytotoxic tubulin inhibitor, Duo-5) via a stable, enzyme-cleavable linker to a HER2 monoclonal antibody with a drug-to-antibody-ratio (DAR) of 2. Trastuzumab botidotin specifically binds to HER2 on the surface of tumor cells and is internalized by tumor cells, releasing the toxin molecule Duo-5 inside the cell. Duo-5 induces tumor cell cycle arrest in the G2/M phase, leading to tumor cell apoptosis. After targeting HER2, trastuzumab botidotin can also inhibit the HER2 signaling pathway; it has antibody-dependent cell-mediated cytotoxicity (ADCC) activity.

Dr. Micheal Ge, CEO of Kelun-Biotech said, “We are pleased that our NDA application for the second indication of trastuzumab botidotin (A166) has been accepted again by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China, which is not only a strong demonstration of the excellent clinical value of our R&D pipeline, but also an affirmation of our tireless efforts. A166 offers differentiated treatment options for patients with high prevalence and urgent medical needs. We are always committed to developing more effective and safer innovative medicines to improve the clinical benefits and quality of life for patients.”

About HER2+ BC
In 2022, there were approximately 357,000 new cases of breast cancer and 75,000 deaths from breast cancer in China [1]. Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is a type of breast cancer, and its gene overexpression is seen in 20%-30% of breast cancer patients, and the prognosis of the patients is closely related to the overexpression of HER2. HER2-positive breast cancer has a high degree of malignancy, is highly invasive, and is prone to recurrence and metastasis in early stage and has a poor prognosis [2]. The existing anti-HER2 targeted therapeutic drugs in China still have insufficient efficacy or cannot be used in some patients due to special adverse events, and the choice of therapeutic drugs for patients is still limited, and there is an urgent need to develop HER2 ADC drugs with different types of payload to further improve the clinical benefits for patients and provide more differentiated therapeutic choices for Chinese patients.

About Kelun-Biotech
Kelun-Biotech（6990.HK）is a holding subsidiary of Kelun Pharmaceutical (002422.SZ), which focuses on the R&D, manufacturing, commercialization and global collaboration of innovative biological drugs and small molecule drugs. The company focuses on major disease areas such as solid tumors, autoimmune, inflammatory, and metabolic diseases, and in establishing a globalized drug development and industrialization platform to address the unmet medical needs in China and the rest of world. The Company is committed to becoming a leading global enterprise in the field of innovative drugs. At present, the Company has more than 30 ongoing key innovative drug projects, of which 1 project has been approved for marketing, 3 projects are in the NDA stage, and more than 10 projects are in the clinical stage. The company has established one of the world’s leading proprietary ADC platforms, OptiDC™, and has 1 ADC project approved for marketing, 1 ADC project in NDA stage, and multiple ADC or novel ADC projects in clinical or preclinical research stage. For more information, please visit https://kelun-biotech.com/.

References
[1] Globocan 2022: China
[2] Pei JH Peak, Zhang Y, Li ZX et al. Mechanisms and research progress of antibody-drug coupling in the treatment of HER-2 positive breast cancer[J]. Clinical Medicine Research and Practice, 2024(15).