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Simcere Zaiming Enrolls First Patient in Phase 1 Trial of SIM0237, an anti-PD-L1/IL-15 Bi-functional Fusion Protein

Release time:2023-03-10

-       SIM0237 offers a unique mechanism of action that targets both IL-15 and PD-1/PD-L1

-       The Phase 1 Trial of SIM0237 will examine the safety, tolerability, pharmacokinetics and preliminary antitumor activity of SIM0237 in adult participants with advanced solid tumors

On March 08, 2023, Simcere Zaiming, an innovative oncology-focused biopharmaceutical company and a subsidiary of Simcere Pharmaceutical Group, (the “Company”) announced today that a Phase 1 clinical study of the Company’s anti-PD-L1/IL-15 bi-functional antibody SIM0237 has dosed the first patient (FPI) with advanced solid tumors in Hunan Cancer Hospital in China.


This global multicenter, open-label, Phase 1 study(SIM0237-101), led by Professor Jing Wang, Director of Early Clinical Research Center of Hunan Cancer Hospital, aims to enroll approximately 192 adult patients with advanced solid tumors to evaluate the safety, efficacy, and pharmacokinetic/pharmacodynamics profile of SIM0237. The study has obtained IND approval both from China NMPA and The US FDA.


SIM0237 is an anti-PD-L1/IL-15 bi-functional fusion protein developed by Simcere Zaiming. IL-15 is an immune-activating cytokine that promotes the expansion and activation of NK cells and CD8 + T cells. Previous research has revealed that IL-15 when combined with anti-PD-L1/PD-1 antibodies showed good clinical benefits in patients with advanced malignancies including patients who have either not responded to or have relapsed after immune checkpoint inhibitor treatment. Therefore, this bi-functional fusion protein, targeting both IL-15 and PD-1/PD-L1, may have the potential for antitumor efficacy in relapsed/refractory patients after immunotherapy.


“This is Simcere Zaiming’s first bi-functional antibody candidate that has dosed cancer patients in a clinical study.” said Dr. Renhong Tang, Chairman and CEO of Simcere Zaiming, “By targeting both mutated IL-15 and PD-1/PD-L1 pathways, Simcere Zaiming is taking an innovative pathway that is focused on differentiated clinical value. We look forward to working closely with clinical experts to promote development of this project and bring more effective medicines to cancer patients in China and globally.”


About SIM0237

SIM0237 is an anti-PD-L1 monoclonal antibody fused with potency-reduced IL-15/IL-15Rα sushi domain developed in-house by utilizing Simcere Zaiming’s protein engineering platform. The compound can block the PD-1/PD-L1 immunosuppressive pathway via binding to PD-L1 and activate the immune system through its IL-15 part, thus playing a synergistic role of relieving immunosuppression and boosting the immune activation to exhibit antitumor effect. The attenuated IL-15 part of SIM0237 increases MTD and avoids overstimulation and accompanied anergy of NK and CD8+ T cells. In the meantime, fusion of attenuated IL-15 to full anti-PD-L1 mAb further enhances the half-life of attenuated IL-15 and delivers IL-15 directly to the tumor microenvironment avoiding notorious CRS toxicity induced by systemic IL-15 exposure. Moreover, SIM0237 is able to bridge CD8+ T and NK cells to PD-L1+ APC/tumor cells, which fosters immune synapse formation to further boost the activation of effective cells and promote tumor cell lysis. Preclinical studies showed that SIM0237 is more effective than PD-L1 or IL-15 mono treatment in mouse tumor models, suggesting a high potential for clinical development.


About the SIM0237-101 Clinical Trial


SIM0237-101 is a phase 1, first-in-human, open-label, multicenter study to investigate the safety, tolerability, pharmacokinetics and preliminary antitumor activity of SIM0237 in adult participants with advanced solid tumors. The dose escalation phase of the study will evaluate the pharmacokinetics and pharmacodynamics and identify the maximum tolerated dose (MTD) or the recommended dose for expansion (RDE) of SIM0237. The dose expansion phase of the study will assess safety, and activity of SIM0237 at the RDE.


About Simcere Zaiming

Simcere Zaiming is an oncology-focused biopharmaceutical company and a subsidiary of Simcere Pharmaceutical Group Limited. Founded in 2023, the Company is committed to developing disruptive therapies that have the potential to address unmet clinical needs for cancer patients around the world . Simcere Zaiming has built an innovative R&D pipeline, with differentiated clinical values. Several products of Zaiming are commercially available in China, which include COSELA®, Endostar®, and Envafolimab. Simcere Zaiming strives to bring potentially breakthrough treatments options to cancer patients worldwide through in-house R&D, manufacturing and commercialization, as well as collaborations with global partners of innovative cancer therapeutics.


About Simcere

Simcere Pharmaceutical Group Limited (2096.HK) is an innovation and R&D-driven pharmaceutical company. The company focuses on three therapeutic areas, oncology, central nervous system and autoimmune diseases, with a forward-looking vision toward disease areas that may have significant clinical needs in the future, aiming to achieve the mission of "providing today's patients with medicines of the future." Leveraging its R&D capability and commercialization excellence, Simcere has built a market-leading product portfolio in China. Its vigorous in-house R&D efforts and extensive R&D collaborations have made it a strategic cooperation partner with world leading innovative companies and research institutes.


Media contact:  simcere.mediarelations@simcere.com