Innovent and RemeGen Enter into Clinical Trial Collaboration Investigating Combination Therapy of TYVYT (sintilimab injection) and Novel ADC Candidates for Advanced Solid Tumors in China

Innovent Biologics, Inc. and RemeGen Co., Ltd. announced that they entered into a clinical trial collaboration and supply agreement with for the combination therapies of TYVYT (sintilimab injection) with RC88, a novel mesothelin(MSLN)-targeting antibody-drug conjugate (ADC), or RC108, a novel c-Met-targeting ADC, respectively, as potential treatment options for advanced solid tumors in China.

Under the agreement, Innovent will provide clinical drug supplies of TYVYT (sintilimab injection) during the clinical trial collaboration. RemeGen will conduct Phase 1/2a clinical studies to evaluate the anti-tumor activity and safety of the combination therapy of TYVYT (sintilimab injection) with RC88 or RC108 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, sintilimab has been approved for seven indications and included in the National Reimbursement Drug List (NRDL) for six indications. TYVYT (sintilimab injection) is the only PD-1 inhibitor for the first-line treatment of five high-incidence cancer types in the NRDL – including non-squamous NSCLC, squamous NSCLC, hepatocellular carcinoma, esophageal squamous cell carcinoma, and gastric cancer, as well as the first and the only immunotherapy medicine for gastric cancer in the NRDL.

RC88 is a novel MSLN-targeting ADC independently developed by RemeGen. RC88 is currently being investigated in an ongoing Phase 1 clinical trial, which was approved by the NMPA in November 2018. The preliminary results demonstrated anti-tumor activity and a manageable safety profile of RC88 monotherapy in MSLN-positive advanced solid tumors. Preclinical studies also showed that RC88 can selectively delivers a potent cytotoxic payload to MSLN-expressing cells through internalization, thus inducing G2/M arrest and apoptosis. When combined with PD-1/PD-L1 or other immune checkpoint inhibitors (ICIs), RC88 can induce immunogenic cell death (ICD), releasing a series of signaling molecules to further activate T cells, enhance tumor immune response, and synergistically exert a stronger anti-tumor effect.

RC108 is a novel c-Met targeting ADC independently developed by RemeGen. RC108 is currently being investigated in an ongoing Phase 1 clinical trial, which was approved by the NMPA in November 2020. The preliminary results demonstrated anti-tumor activity and a manageable safety profile of RC108 monotherapy in c-Met-positive advanced solid tumors. Preclinical studies also showed that RC108 can induce tumor-specific adaptive immunity and increase the infiltration of T cells into the tumor microenvironment, while anti-PD-1 monoclonal antibody can activate T cells to enhance anti-tumor killing effect. Therefore, it is expected that the combination therapy of RC108 and sintilimab can not only improve antigen presenting by dendritic cells , but also boost the tumor killing of T cells, therefore bringing in synergistic tumor inhibition effect.

Dr. Hui Zhou, Senior Vice President of Innovent, stated: “We are pleased to collaborate with RemeGen to further explore the combination therapy potential of sintilimab injection and novel ADC candidates. Preclinical studies has suggested the synergistic anti-tumor effects, which supports the investigation of combining ADCs with an anti-PD-1 monoclonal antibody to improve patient outcomes and overcome drug-resistance. As immunotherapy advanced into next era of development, we hope to strengthen the leading position of sintilimab as a backbone immunotherapy as well as investigate the new opportunities of combination therapies, and provide better treatment options for more cancer patients. ”

Ms. Na Su, Senior Vice President of RemeGen, stated “Collaborating with Innovent is an important advancement in the research and commercialization strategy for the combination therapy of RC88 and RC108. The combination of RC88 and RC108 with sintilimab provides an innovative treatment approach that targets two different targets simultaneously. The mechanisms are complementary and synergistic, helping to overcome or delay resistance, achieve multi-pathway targeting of tumors, and provide an efficient solution for unmet clinical needs.”