Notice of Publication of Article Related to the Development of RS5614, a PAI-1 Inhibitor for the Treatment of Non-Small Cell Lung Cancer

Renascience, in collaboration with Hiroshima University and other medical and research institutions, has been conducting a phase II investigator-initiated clinical trial of RS5614, a PAI-1 inhibitor, for the treatment of non-small cell lung cancer (NSCLC). We are pleased to announce that an interview with Dr. Takeshi Masuda, Lecturer & Head, Hospitalized Patient Treatment, at the Department of Respiratory Medicine, Hiroshima University Hospital, one of the physicians who play central roles in promoting this investigator-initiated clinical trial, was published in the January 19, 2024 issue of Kagaku Shimbun.

(Background of the interview article)

Renascience conducted a phase II study to confirm the efficacy and safety of the PAI-1 inhibitor RS5614 in combination with nivolumab^*1 for the treatment for malignant melanoma and obtained a Proof-of-Concept (POC)^*2 for RS5614 as an immune checkpoint inhibitor^*3 . Specifically, the combination of RS5614 in patients with malignant melanoma who were 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^*4 (13.5% response rate). In addition, the combination of nivolumab and RS5614 resulted in two adverse events (5.9%) of liver dysfunction, both of which were potentially causally related to the study drug, and both of which were resolved, demonstrating a higher safety profile than the combination of nivolumab and ipilimumab (announced on August 16, 2023).

Based on the immune checkpoint inhibitor mechanism, a phase II investigator-initiated clinical trial to investigate the efficacy and safety of RS5614 in combination with nivolumab in 39 patients with unresectable advanced or recurrent non-small cell lung cancer who have received multiple prior anticancer treatments (third-line treatment patients) is being conducted in collaboration with six hospitals: Hiroshima University Hospital, Okayama University Hospital, Shimane University Hospital, Tottori University Hospital, National Hospital Organization Shikoku Cancer Center, and Hiroshima City Hiroshima Citizens Hospital (announced on September 26, 2023). Dr. Masuda is one of the physicians who play central roles in promoting this phase II investigator-initiated clinical trial, and his thoughts on this investigator-initiated clinical trial are described in Kagaku Shimbun. Please see the following link for the article in the Kagaku Shimbun.

*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 Proof-of-Concept (POC)

When the efficacy of a new drug candidate is confirmed in non-clinical and/or clinical studies, the POC is said to have been obtained.

*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.

*4 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.