On December 27, 2023 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases, and Xuanzhu Biopharma, reported that they entered into a clinical trial collaboration and supply agreement for the combination therapies of sintilimab injection (brand name: TYVYT) with KM-501, a novel HER-2 bispecific ADC, as potential treatment options for advanced solid tumors in China (Press release, Innovent Biologics, DEC 27, 2023, View Source [SID1234638806]).

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Under the agreement, Innovent will supply sintilimab for the collaborated clinical trial. Xuanzhu Biopharma will conduct a Phase 1b clinical study to evaluate the anti-tumor activity and safety of the combination therapy of sintilimab with KM-501 in Chinese patients with advanced solid tumors.

TYVYT (sintilimab injection) is an innovative PD-1 inhibitor co-developed by Innovent and Eli Lilly and Company in China. It has been approved and included in the national reimbursement drug list (NRDL) for seven indications. It is also the only PD-1 inhibitor for the first-line treatment of five high-incidence cancer types in the NRDL.

KM-501 is designed by Mebs-Ig (antibody-edited bispecific antibody) platform with independent intellectual property rights to target dual-antibody ADC with two different domains of HER2. It is suitable for the treatment of locally advanced/metastatic solid tumors with HER2 positive / expression, amplification or mutation, including related advanced tumors with low HER2 expression. The IND was approved by the NMPA in March this year, and it is currently in the phase I dose escalation study. Pre-clinical studies showed that KM-501 was better than control-drugs DS-8201 and Herceptin in terms of endocytosis rate, internalization rate and in vitro inhibitory activity; KM-501 was better than DS-8201 in tumor models with high and low expression of HER2.

Combining a PD-1 inhibitor and an ADC candidate represents a new direction for the development of cancer therapy in terms of potentially improving the effect of immunotherapy and overcoming potential drug resistance. The PD-1 immunotherapy can release the suppressed state of T cells while the ADC drug can achieve the anti-tumor killing effect through cytotoxic payload, thus bringing in synergistic tumor inhibition effect.

Dr. Hui Zhou, Senior Vice President of Innovent, stated: "We are pleased to collaborate with Xuanzhu Biopharma to explore the synergistic anti-tumor effects of the combination therapy of sintilimab and a novel ADC candidate. The leading position and clinical value of sintilimab as a backbone immunotherapy are further strengthened. In light of the synergistic mechanism of two novel medicines, we hope to bring new treatment options for cancer patients in the future. "

Dr. Xiaodong Zhu, General Manager of Xuanzhu Bio, stated: " The collaboration with Innovent is an important milestone for KM-501 in the development and commercialization strategy. We look forward to new opportunities for KM-501 in combo with sintilimab so as to potentially improve patient benefit and overcome tumor resistance."

About KM-501

KM-501 is designed by Mebs-Ig (antibody-edited bispecific antibody) platform with independent intellectual property rights to target dual-antibody ADC with two different domains of HER2. It is suitable for the treatment of locally advanced/metastatic solid tumors with HER2 positive / expression, amplification or mutation, including related advanced tumors with low HER2 expression. The IND was approved by the NMPA in March this year, and it is currently in the phase I dose escalation study. Pre-clinical studies showed that KM-501 was better than control-drugs DS-8201 and Herceptin in terms of endocytosis rate, internalization rate and in vitro inhibitory activity; KM-501 was better than DS-8201 in tumor models with high and low expression of HER2.

About Sintilimab

Sintilimab, marketed as TYVYT (sintilimab injection) in China, is a PD-1 immunoglobulin G4 monoclonal antibody co-developed by Innovent and Eli Lilly and Company. Sintilimab is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells[i].

In China, sintilimab has been approved and included in the National Reimbursement Drug List (NRDL) for seven indications. The updated NRDL reimbursement scope of TYVYT (sintilimab injection) include:

For the treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy;
For the first-line treatment of unresectable locally advanced or metastatic non-squamous non-small cell lung cancer lacking EGFR or ALK driver gene mutations;
For the treatment of patients with EGFR-mutated locally advanced or metastatic non-squamous non-small cell lung cancer who progressed after EGFR-TKI therapy;
For the first-line treatment of unresectable locally advanced or metastatic squamous non-small cell lung cancer;
For the first-line treatment of unresectable or metastatic hepatocellular carcinoma with no prior systematic treatment;
For the first-line treatment of unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma;
For the first-line treatment of unresectable locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma.
Besides, two clinical studies of sintilimab have met their primary endpoints:

Phase 2 study of sintilimab monotherapy as second-line treatment of esophageal squamous cell carcinoma;
Phase 3 study of sintilimab monotherapy as second-line treatment for squamous NSCLC with disease progression following platinum-based chemotherapy.