On December 28, 2023, Xuanzhu Biotechnology Co., Ltd. (hereinafter referred to as "Xuanzhu Biopharma") and Innovent Biologics Group jointly announced that they have entered into a clinical research and drug supply cooperation agreement to carry out a clinical research cooperation on the combination of Xuanzhu Biopharma's novel bispecific antibody conjugate KM-501 (targeting HER2-HER2 biepitope antigen ADC) and sinlidicimab injection (PD-1 inhibitor, trade name: Tyvyt).
Under the terms of the agreement, Xuanzhu will lead the Phase Ib clinical study in China, and Innovent will provide investigational use of sintilimab to evaluate the safety, tolerability and preliminary efficacy of KM-501 in combination with sintilizumab in patients with multiple solid tumors.
KM-501 is a bispecific antibody ADC targeting two different domains of HER2 independently developed by Xuanzhu Biopharma, which is suitable for locally advanced metastatic solid tumors with HER2-positive expression, amplification or mutation, including related advanced tumors with low HER2 expression. The drug candidate was approved by the National Medical Products Administration of China for clinical trials in March this year and is currently in the phase I clinical phase of single-agent ramp-up. Preclinical studies have shown that KM-501 is superior to DS-8201 and Herceptin in terms of intracellular endocytosis rate, internalization rate and in vitro inhibitory activityKM-501 has better antitumor activity than DS-8201 in tumor models with high and low HER2 expression.
Jointly developed by Innovent Biologics and Eli Lilly, Tyvyt (sintilimab injection) has been approved for a total of seven indications, covering non-squamous non-small cell lung cancer, squamous non-small cell lung cancer, EGFR mutant lung cancer, liver cancer, gastric cancer, esophageal cancer, and Hodgkin lymphoma, all of which are included in the National Medical Insurance Catalog, and is the only PD-1 inhibitor that has included all five first-line high-incidence tumor types** in the National Medical Insurance Catalog.
With the advent and continuous evolution of the era of ADC drugs, the combination of immune checkpoint PD-1 inhibitors and ADC drugs** has become a hot spot in the current research and development, showing bright prospects in improving the effect of immunity** and overcoming potential drug resistance. On the one hand, the combination can relieve the suppressive state of T cells through immune checkpoint inhibitors, and on the other hand, it can kill tumor cells through ADC drugs carrying cytotoxic loads, thus producing a synergistic effect.
Dr. Xiaodong Zhu, Head of Macromolecule Segment at Xuanzhu Biologics, said, "The collaboration with Innovent Biologics is an important development in the R&D and commercialization strategy of KM-501 and Synergy**. We look forward to the new opportunities for the combination of KM-501 and sintilimab** to potentially improve patient benefits and overcome tumor resistance." ”
Hui Zhou, Senior Vice President of Innovent Biologics, said, "We are pleased to establish a clinical research collaboration with Xuanzhu Biologics. Sintilimab's leading position and clinical value in the first-line oncology** have also been further recognized. We look forward to the potential synergy between PD-1 immunization** and new ADC drugs, which can bring new potential methods to the majority of cancer patients." ”