RemeGen, Innovent Biologics to collaborate on clinical trials for combination therapies with ADCs

RemeGen, a commercial-stage Chinese biotechnology firm, and Innovent Biologics have announced their collaboration in a clinical research and supply agreement.

This partnership focuses on conducting clinical trials that explore combination therapies involving novel antibody-drug conjugates (ADCs), specifically, RC88 and RC108, and the PD-1 inhibitor sintilimab injection, TYVYT.

As per the agreement, Innovent Biologics will supply the clinical drug sintilimab during the trial period, while RemeGen will spearhead Phase I/IIa clinical studies in China. The purpose of these trials is to evaluate the safety, tolerability, and preliminary effectiveness of RC88 or RC108 combined with sintilimab in Chinese cancer patients.

Dr Zhou Hui — Innovent Biologics Senior Vice President said: “Preclinical studies have suggested that combining ADCs with an anti-PD-1 monoclonal antibody may improve patient outcomes and overcome drug resistance.

“As immunotherapy advanced into the 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.”

RemeGen has independently developed the ADC, RC88, targeting mesothelin (MSLN), with preliminary results from Phase I clinical trials initiated in November 2018 showcasing RC88 monotherapy’s potential anti-tumor activity against MSLN-expressing solid tumors. These trials have also revealed manageable safety concerns.

Combining RC88 with immune checkpoint inhibitors (ICIs) such as PD-1/PD-L1 can potentially stimulate immunogenic cell death (ICD), release signaling molecules, and amplify the tumor immune response.

RC108, another ADC independently produced by RemeGen that targets c-MET, was approved for Phase I clinical trials in November 2020. Ongoing trials indicate the possibility of RC108 monotherapy against c-MET-expressing solid tumors, maintaining manageable safety standards. Preclinical research hints at RC108 inducing tumor-specific adaptive immunity and increasing T cell infiltration, which, combined with PD-1 monoclonal antibodies, can enhance the anti-tumor immune response.

TYVYT, a PD-1 inhibitor developed by Innovent Biologics and Eli Lilly and Company, has been approved for seven indications and has been included in China’s National Reimbursement Drug List (NRDL) for six of these. It is unique as it is the only PD-1 inhibitor included for first-line treatment for five major high-incidence solid tumors, and the only immunotherapy drug in the field of gastric cancer included in the NRDL.

Su Na — RemeGen Senior Vice President said: “The alliance with Innovent is a critical step forward in the research and commercialization strategy of combination therapies with RC88 and RC108.

“By combining these therapies with sintilimab, we offer innovative treatment plans that target two pathways. These mechanisms are complementary, potentially helping to overcome or delay treatment resistance and provide an effective solution to unmet clinical needs.”