Notice of Publication of Article Related to the Development of RS5614, a PAI-1 Inhibitor, for the Treatment of Malignant Melanoma

Renascience has been developing RS5614, a PAI-1 inhibitor, as a treatment for malignant melanoma in collaboration with Tohoku University, Tokai University, and other medical and research institutions. We are pleased to announce that an interview with our collaborators, Associate Professor Taku Fujimura, Department of Dermatology, Tohoku University Graduate School of Medicine, and Professor Takashi Yawata, Department of Innovative Medical Science, Tokai University School of Medicine, was published in Kagaku Shimbun (September 29, 2023).

(Background of the interview article)

Renascience conducted a phase II study as an investigator-initiated clinical trial to confirm the efficacy and safety of the combination of RS5614, a PAI-1 inhibitor, and nivolumab^*1 for the treatment of malignant melanoma, and the results showed that the combination of RS5614 with nivolumab for 8 weeks in patients with malignant melanoma who was refractory to nivolumab resulted in a response rate of 24.1%, which was higher than the response rate of the combination of nivolumab and ipilimumab^*2 (13.5%). In addition, the combination of nivolumab and RS5614 resulted in two adverse events (5.9%) of liver dysfunction that may have been causally related to the study drug, but both events were mild and resolved, indicating that the combination of nivolumab and RS5614 was safer than the combination of nivolumab and ipilimumab.

As demonstrated with the novel discovery and the successful clinical study, Professor Takashi Yawata, who led the basic research on the PAI-1 inhibitor as an immune checkpoint inhibitor^*3 , and Associate Professor Taku Fujimura, who served as the coordinating investigator for the phase II investigator-initiated clinical trial for advanced malignant melanoma, explained the importance of drug discovery from academia in an interview with Kagaku Shinbun. Please refer to the following link for the Kagaku Shimbun article.

As for the future development, we plan to compile the results of the phase II study into a clinical study report and proceed with discussions with the regulatory authorities, including the next phase study required for regulatory approval. In addition, based on the immune checkpoint inhibitory activity of RS5614, we will conduct phase II investigator-initiated clinical trials for other solid tumors such as non-small cell lung cancer and cutaneous hemangiosarcoma.

*1 Nivolumab

It is an antibody therapeutic (human monoclonal anti-human PD-1 antibody) that targets an immune checkpoint molecule called programmed cell death-1 (PD-1) and is intended to have anti-cancer effects by releasing the suppression of the immune system. It is a typical immune checkpoint inhibitor.

*2 Ipilimumab

It is an antibody therapeutic (a human monoclonal anti-human CTLA-4 antibody) that targets an immune checkpoint molecule called cytotoxic T-lymphocyte antigen-4 (CTLA-4). It is an immune checkpoint inhibitor targeting a molecule different from nivolumab.

*3 Immune checkpoint inhibitors The molecules that inhibit the immune system from over-activating and attacking self are called immune checkpoint molecules. However, cancer cells abuse these immune checkpoint molecules to evade attacks from the immune system. Immune checkpoint inhibitors are drugs that activate the immune system against cancer by blocking the action of immune checkpoint molecules. All drugs currently used as therapeutics are antibodies that directly bind to immune checkpoint molecules and inhibit them.