Simcha Therapeutics Launches Two Clinical Studies on ST-067 in Hematological Conditions

SOUTH SAN FRANCISCO, Calif. & NEW HAVEN, Conn.--Simcha Therapeutics, a clinical-stage company at the forefront of immunobiology, has announced the commencement of two significant clinical trials aimed at exploring the efficacy of ST-067, their innovative decoy-resistant IL-18, in various hematological conditions. One of the studies (ClinicalTrials.gov ID NCT06492707) will focus on patients suffering from acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The other study (ClinicalTrials.gov ID NCT06588660) will investigate the use of ST-067 in combination with teclistamab (TECVAYLI®) for treating patients with multiple myeloma.

According to Sanuj Ravindran, M.D., CEO of Simcha, these trials hold significant promise for providing clinical evidence of ST-067's potential in treating hematological cancers. The preclinical data being presented at an upcoming ASH conference supports this potential, indicating encouraging therapeutic possibilities for IL-18 in various blood cancers. Simcha is collaborating with leading experts in the field of hematologic cancers to undertake these trials.

The trial focusing on AML and MDS, led by principal investigator Elizabeth Krakow, M.D., at Fred Hutch Cancer Center, is currently enrolling patients over 18 who have experienced persistent or recurrent AML or MDS following hematopoietic cell transplantation (HCT), commonly known as bone marrow transplantation. While HCT remains the only curative treatment for most AML or MDS cases, approximately one-third of patients relapse, which is the leading cause of mortality post-transplant.

This Phase 1 trial is open-label and designed to escalate the dose, primarily assessing the toxicities that limit dosing and the number of participants who successfully complete four weeks of consecutive ST-067 treatment. Secondary objectives include evaluating response rates, overall survival, and the possibility of inducing graft-versus-leukemia effects without triggering graft-versus-host disease.

In the study examining ST-067 combined with teclistamab, led by Rahul Banerjee, M.D., from the University of Washington and Fred Hutch Cancer Center, patients aged 18 and older with relapsed or refractory multiple myeloma are being enrolled. This Phase 1b open-label study will primarily assess the dose-limiting toxicities of ST-067 both alone and in combination with teclistamab. The study will also determine optimal dosing and the frequency of adverse events. Secondary measures will include overall response rate, duration of response, progression-free survival, overall survival, and the absence of measurable residual disease.

Teclistamab, a bi-specific antibody that engages T cells, along with other bi-specific antibodies and CAR T-cell therapies, have become standard treatments for relapsed or refractory multiple myeloma. However, these therapies are not curative, as not all patients respond, and relapses are common even among responders. The hypothesis driving the multiple myeloma study is that combining ST-067 with teclistamab can enhance T-cell fitness and persistence, potentially increasing the response rate and prolonging the duration of the response.

Simcha’s data to be highlighted at ASH includes a poster presentation showcasing the therapeutic activity of decoy-resistant IL-18 in various mouse models of hematological tumors, including B-cell lymphoma, acute myeloid leukemia, and plasma cell myeloma. The poster titled “Preclinical Efficacy of Decoy-Resistant IL-18 in Hematological Malignancies” will be presented during a session on Monday, December 9.

Additionally, a poster detailing the AML/MDS study, titled “Trials in Progress: Decoy-Resistant Interleukin-18 (DR-18) for Relapse or Pre-Emptive Treatment of Measurable Residual Disease after Allogeneic Hematopoietic Cell Transplantation in Patients with AML and MDS: DR. DREAM, a Phase I Trial (NCT06492707)” will also be presented on the same day.

Simcha Therapeutics is dedicated to pioneering the development of first-in-class engineered cytokine therapies that promise to transform patient care. The company emphasizes rigorous scientific research to tackle biological challenges and translates them into clinical applications. Their flagship program, ST-067, is being evaluated both as a standalone therapy and in combination with other anticancer agents, including KEYTRUDA® (pembrolizumab), in ongoing Phase 1/2 clinical trials for patients with solid tumors who have not responded to other immunotherapies. Simcha is also exploring additional applications for IL-18-based therapies to fully harness this cytokine's potential.