Studies will assess ST-067 in acute myeloid leukemia or myelodysplastic syndrome and in multiple myeloma

Preclinical data to be presented at the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition support the potential therapeutic use of ST-067 in hematologic cancers

South San Francisco, Calif., and New Haven, Conn. – December 5, 2024 – Simcha Therapeutics (“Simcha”), a clinical-stage immunobiology company pioneering first-in-class cytokine treatments in cancer, today announced the opening of two clinical studies assessing the use of ST-067, Simcha’s decoy-resistant IL-18, in hematological indications. One study (ClinicalTrials.gov ID NCT06492707) will assess ST-067 in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), while the other study (ClinicalTrials.gov ID NCT06588660) will test ST-067 in combination with teclistamab (TECVAYLI®) in patients with multiple myeloma.

“These two studies, both of which may rapidly generate clinical proof-of-concept data in indications where there is significant need for better therapies, represent a very exciting opportunity for us to explore additional therapeutic areas that have great potential to respond well to treatment with IL-18,” said Sanuj Ravindran, M.D., chief executive officer of Simcha. “Emerging data, including those included in our preclinical poster to be presented at ASH, are generating signals that serve as proof-of-concept and point to the therapeutic potential of IL-18 across various hematological cancers, so we are pleased to partner with leading hematologic cancer experts on these trials.”

The AML/MDS study, under principal investigator Elizabeth Krakow, M.D., of Fred Hutch Cancer Center, is enrolling patients over 18 years of age who have persistent or recurrent AML or MDS after hematopoietic cell transplantation (HCT), also known as a bone marrow transplant. While HCT is the only curative therapy for most forms of AML or MDS, relapse occurs in approximately one-third of patients and is the most common cause of death following HCT.

The Phase 1, open-label, dose-escalation study will primarily assess dose limiting toxicities and the number of clinical trial subjects who complete four consecutive weeks of treatment with ST-067. Secondary endpoints will assess response rates, overall survival and whether graft-versus-leukemia effects can be elicited without the accompanying graft-versus-host disease.

The study assessing ST-067 in combination with teclistamab, a bi-specific antibody with T cell engagement activity, in patients 18 years of age or older with relapsed or refractory multiple myeloma is occurring under the direction of Rahul Banerjee, M.D., of the University of Washington and Fred Hutch Cancer Center. This open-label Phase 1b study will primarily assess dose-limiting toxicities of ST-067 alone and in combination with teclistamab, as well as optimal dosing and the incidence of adverse events. Secondary endpoints will include overall response rate, duration of response, progression-free survival, overall survival and measurable residual disease negativity.

T-cell directed therapeutics, like teclistamab, other bi-specific antibodies or CAR Ts, have become standards of care for the treatment of relapsed/refractory multiple myeloma. However, they are not curative, as not all patients respond to teclistamab, and relapse can occur in those that do. The multiple myeloma study is based on the hypothesis that ST-067 in combination with teclistamab will promote T-cell fitness and persistence, which could increase the number of patients who respond to teclistamab and lengthen durations of response.

Data to be highlighted at ASH in a poster presentation demonstrate the therapeutic activity of decoy-resistant IL-18 in multiple mouse models of hematological tumors including B-cell lymphoma, acute myeloid leukemia and plasma cell myeloma. The poster, entitled “Preclinical Efficacy of Decoy-Resistant IL-18 in Hematological Malignancies” will be presented during poster session 802 on Monday, December 9 from 6:00 PM to 8:00 PM.

In addition, a trials in progress poster describing the AML/MDS study will be presented at ASH. The poster, entitled “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 be presented Monday, December 9 from 6:00 PM to 8:00 PM in poster session 701.

About Simcha Therapeutics
Simcha Therapeutics is a clinical-stage immunobiology company pioneering the development of first-in-class engineered cytokine therapeutics with transformational promise for patients. The company is built on a foundation of scientific rigor to overcome biological challenges in clinically translatable pathways, exemplified by the first decoy-resistant interleukin-18 (IL-18). By unlocking the potential of IL-18, Simcha is developing its lead program (ST-067) as monotherapy and in combination with other anticancer agents. ST-067 is currently being studied both as a monotherapy and in combination with KEYTRUDA® (pembrolizumab) in Phase 1/2 clinical trials, in patients with solid tumors and who have progressed on other immunotherapeutic agents. Simcha is exploring additional modalities for IL-18-based therapeutics to capture the full potential of this best-in-class cytokine. For more information, please visit www.simchatherapeutics.com.

Media contact:
Carolyn Hawley
Inizio Evoke Comms
Carolyn.hawley@inizioevoke.com  

South San Francisco, Calif., and New Haven, Conn. – January 8, 2024 – Simcha Therapeutics (“Simcha”), a clinical-stage immunobiology company pioneering first-in-class cytokine treatments in cancer, today announced that it has entered into a license and option agreement with Janssen Biotech, Inc. (“Janssen”), a Johnson & Johnson company, where Janssen will work to armor select CAR T-based cell therapy candidates with Simcha’s novel proprietary decoy-resistant IL-18 (DR-18). The agreement was facilitated by Johnson & Johnson Innovation.

Under the terms of the agreement, Janssen will develop, manufacture, and commercialize DR-18 armored cell therapies for a set number of programs. In exchange, Simcha will receive an undisclosed upfront fee, potential option exercise fees and development and commercialization milestone payments.

“Interest in developing IL-18 therapeutic approaches for cancer has continued to increase in recent years, tying back to findings published by our scientific founder that reinvigorated therapeutic interest in this cytokine. Armoring CAR T cells to secrete IL-18 is one of the most exciting areas of research, and we are proud to move the research forward with Janssen,” said Sanuj Ravindran, M.D., chief executive officer of Simcha. “We will continue to expand our focus on IL-18 and the range of modalities that have potential to significantly improve outcomes for cancer patients, including through our internal development programs and additional strategic partnerships in the future.”

About Simcha Therapeutics

Simcha Therapeutics is a clinical-stage immunobiology company pioneering the development of first-in-class engineered cytokine therapeutics with transformational promise for patients. The company is built on a foundation of scientific rigor to overcome biological challenges in clinically translatable pathways, exemplified by the first decoy-resistant interleukin-18 (IL-18). By unlocking the potential of IL-18, Simcha is developing its lead program (ST-067) as monotherapy and in combination with other anticancer agents. ST-067 is currently being studied both as a monotherapy and in combination with KEYTRUDA® (pembrolizumab) in Phase 1/2 clinical trials, in patients with solid tumors and who have progressed on other immunotherapeutic agents. Simcha is exploring additional modalities for IL-18-based therapeutics to capture the full potential of this potentially transformational cytokine. For more information, please visit www.simchatherapeutics.com.

SOUTH SAN FRANCISCO, Calif., and NEW HAVEN, Conn., – August 22, 2023 – Simcha Therapeutics (“Simcha”), a clinical-stage immunobiology company pioneering first-in-class cytokine treatments in cancer, today announced the formation of a scientific advisory board that will support the company’s efforts to realize the potential of IL-18-focused therapeutic approaches.

“IL-18 has a significant range of potential therapeutic uses across multiple modalities, and Simcha is eager to identify and evaluate the applications with the most promise for yielding transformational outcomes for patients,” said Sanuj Ravindran, M.D., CEO of Simcha. “Our scientific advisory board of experts in immunology and cancer will help guide our efforts to broaden the applications for decoy-resistant IL-18, and drive explorations in new directions.”

The members of the advisory board are:

W. Nicholas Haining, BM, BCh, is chief scientific officer and co-founder of ArsenalBio. He is a physician-scientist, and prior to co-founding ArsenalBio, he was the vice president of discovery oncology and immunology at Merck Research Laboratories. Dr. Haining received his undergraduate and medical degree from Oxford University and completed his medical training in pediatrics at Boston Children’s Hospital, and subsequently in pediatric hematology/oncology at Dana-Farber Cancer Institute. As an associate professor of pediatrics at Harvard Medical School and an associate member of the Broad Institute of MIT and Harvard, his lab defined some of the key transcriptional and epigenetic regulators of T cell exhaustion and used in vivo genetic screens to identify immune vulnerabilities of cancer cells in mouse models. He also led a multi-disciplinary organization at Merck that focused on using innovative approaches to identify new therapeutic strategies for cancer and immunological disease.

Susan Kaech, Ph.D., is professor and director of the NOMIS Center for Immunobiology & Microbial Pathogenesis and holds the NOMIS Chair at the Salk Institute. Her work focuses on understanding how memory T cells are produced during infection and vaccination to provide long-term immunity and sometimes fail to do so. She is also a leader in field of cancer immunology and elucidating metabolic control of immune cells in cancer. She was previously a Waldemar Von Zedwitz Professor in the Department of Immunology at Yale University. She holds a Ph.D. in developmental biology from Stanford University and completed her postdoctoral fellowship in the department of microbiology and immunology at Emory University.

Jeffrey Miller, M.D., is professor of medicine, University of Minnesota and deputy director, Masonic Cancer Center and the Roger L. and Lynn C. Headrick Chair in cancer therapeutics. Dr. Miller has more than 25 years of experience studying the biology of natural killer (NK) cells and other immune effector cells and their use in clinical immunotherapy with over 300 peer-reviewed publications. After completing a post-doctoral fellowship in hematology, oncology and transplantation at the University of Minnesota, he joined the faculty in 1991. Previously, he completed an internship and residency in Internal Medicine at the University of Iowa in Iowa City. Dr. Miller received a BSc degree from Northwestern University in Evanston, Illinois and received his M.D. from Northwestern University School of Medicine.

Aaron Ring, M.D., Ph.D., is the founder of Simcha Therapeutics and currently serves as associate professor and Anderson Family Chair for Immunotherapy at Fred Hutchinson Cancer Center. Prior to this, he was associate professor of immunobiology at Yale University. His research is focused on understanding and manipulating the communication circuitry of the immune system using precision immunopharmacology and systems immunology. His seminal work identifying the “jamming signal” called IL-18BP produced by tumors that prevents IL-18 binding and activation is the foundation of Simcha’s therapeutic approach. He holds M.D. and Ph.D. degrees from Stanford University.

Emmett Schmidt, M.D., Ph.D., is vice president of early oncology development for Merck Research Labs where he oversees more than 46 company collaborations involving more than 95 clinical studies. He joined Merck in 2010 as a senior principal scientist and has continued to take on additional responsibilities in the development of oncology therapies. Prior to joining Merck, Dr. Schmidt was a professor of pediatrics at Harvard Medical School and Massachusetts General Hospital. Dr. Schmidt holds M.D. and Ph.D. degrees from Duke University and earned a M.A in biology from Harvard University.

Mario Sznol, M.D., professor of medicine and clinical research leader in the melanoma program and co-leader, cancer immunology program at Yale Cancer Center. Dr. Sznol conducts clinical research for melanoma and kidney cancer patients with a major focus on immunotherapies. Before joining Yale in 2004, Dr. Sznol served as vice president, clinical affairs of Vion Pharmaceuticals where he oversaw development of the company’s anticancer drug candidates. Prior to that, he served as head of the Biologics Evaluation Section, Investigational Drug Branch at the National Cancer Institute. Dr. Sznol earned a M.D. from Baylor College of Medicine and a B.S. in biochemistry from Rice University.

About Simcha Therapeutics

Simcha Therapeutics is a clinical-stage immunobiology company pioneering the development of first-in-class engineered cytokine therapeutics with transformational promise for patients. The company is built on a foundation of scientific rigor to overcome biological challenges in clinically translatable pathways, exemplified by the first decoy-resistant interleukin-18 (IL-18). By unlocking the potential of IL-18, Simcha is developing its lead program (ST-067) as monotherapy and in combination with potentially several other anticancer agents. ST-067 is currently being studied both as a monotherapy and in combination with KEYTRUDA® (pembrolizumab) in Phase 1/2 clinical trials, in patients with solid tumors and who have progressed on other immunotherapeutic agents. Simcha is seeking to explore additional modalities for IL-18-based therapeutics and capture the full potential of this potentially transformational cytokine. For more information, please visit www.simchatherapeutics.com.

Media Contact

Carolyn Hawley
Evoke Canale
Carolyn.hawley@evokegroup.com
619.849.5382

NEW HAVEN, Conn., and SOUTH SAN FRANCISCO, Calif. – July 6, 2023 – Simcha Therapeutics (“Simcha”), a clinical-stage immunobiology company pioneering first-in-class cytokine treatments in cancer, today announced that the first patient has been dosed in a Phase 1/2 clinical trial of ST-067, Simcha’s decoy resistant IL-18 agent, in combination with Merck’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab), in patients with advanced solid tumors.

The Phase 1/2 open-label, dose-escalation study is evaluating ST-067 in combination with pembrolizumab in a variety of solid tumors (NCT04787042). The objective of the study is to determine the maximum tolerated dose (MTD), the recommended Phase 2 dose (R2PD) and preliminary activity of ST-067 in combination with pembrolizumab. Secondary endpoints include assessment of safety, pharmacokinetics, pharmacodynamics and immunogenicity.

“We have observed encouraging anti-tumor activity in preclinical studies combining our decoy-resistant IL-18 with PD-1 inhibitors, and we look forward to now studying this combination in the clinic,” said Sanuj Ravindran, M.D., CEO of Simcha Therapeutics. “KEYTRUDA has become the standard of care for many cancer patients, and we believe adding ST-067 could further improve clinical outcomes. This combination has the potential to become a powerful new therapeutic option for patients and physicians.”

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About ST-067

ST-067 is the first “decoy-resistant” variant of IL-18, designed to be impervious to the decoy receptor IL-18BP, which blocks IL-18 from interacting with its receptor. ST-067 has been shown in preclinical studies to maintain strong immune stimulation in the tumor microenvironment and is currently in Phase 1/2 clinical development as both a monotherapy and in combination with KEYTRUDA® (pembrolizumab).

About Simcha Therapeutics

Simcha Therapeutics is a clinical-stage immunobiology company pioneering the development of first-in-class engineered cytokine therapeutics with transformational promise for patients. The company is built on a foundation of scientific rigor to overcome biological challenges in clinically translatable pathways, exemplified by the first decoy-resistant interleukin-18 (IL-18). By unlocking the potential of IL-18, Simcha is developing its lead program (ST-067) as monotherapy and in combination with potentially several other anticancer agents. ST-067 is currently being studied both as a monotherapy and in combination with KEYTRUDA® (pembrolizumab) in a Phase 1/2 clinical trials, in patients with solid tumors and who have progressed on other immunotherapeutic agents. Simcha is seeking to explore additional modalities for IL-18-based therapeutics and capture the full potential of this potentially transformational cytokine. For more information, please visit www.simchatherapeutics.com.

Media Contact

Carolyn Hawley
Evoke Canale
Carolyn.hawley@evokegroup.com
619.849.5382

Dr. Emmett Schmidt, Merck Vice President of Early Oncology Development, to Join the Simcha Scientific Advisory Board

NEW HAVEN, Conn., and SOUTH SAN FRANCISCO, Calif. – April 5, 2023 – Simcha Therapeutics (“Simcha”), a clinical-stage immunobiology company pioneering first-in-class cytokine treatments in cancer, today announced a clinical trial collaboration with Merck (known as MSD outside the US and Canada) to evaluate clinical safety and benefits of ST-067, Simcha’s decoy resistant IL-18 agent, in combination with Merck’s anti-PD-1 therapy, KEYTRUDA^® (pembrolizumab), in patients with solid tumors. In conjunction with this collaboration, Dr. Emmett Schmidt, vice president of early oncology development for Merck, will join Simcha’s scientific advisory board.

“ST-067, with its ability to stimulate both adaptive and innate immunity, has potential in a broad range of tumor types, and preclinical experiments combining ST-067 with immuno-oncology agents such as Keytruda have generated encouraging results,” said Sanuj Ravindran, M.D., CEO of Simcha Therapeutics. “I’m excited to work with Dr. Schmidt, and we are eager to leverage Merck’s expertise to evaluate the clinical benefits of ST-067 in combination with Keytruda in hopes of bringing transformational medicines for cancer patients.”

“I am delighted to join the Scientific Advisory Board at Simcha,” commented Dr. Schmidt. “I look forward to directly contributing to the development of agents with the potential to benefit patients receiving Keytruda in combination with emerging combination agents.”

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About ST-067

ST-067 is the first “decoy-resistant” variant of IL-18, designed to be impervious to the decoy receptor IL-18BP, which blocks IL-18 from interacting with its receptor, thereby blocking the cytokine’s immunostimulatory activity. ST-067 has been shown in preclinical studies to maintain strong immune stimulation in the tumor microenvironment and is currently in Phase 1a/2 clinical development as a monotherapy in solid tumors. Additional clinical studies of ST-067 as both a monotherapy and in combination with other therapies such as Keytruda (pembrolizumab) are planned.

About Simcha Therapeutics

Simcha Therapeutics is a clinical-stage immunobiology company pioneering the development of first-in-class engineered cytokine therapeutics with transformational promise for patients. The company is built on a foundation of scientific rigor to overcome biological challenges in clinically translatable pathways, exemplified by the first decoy-resistant interleukin-18 (IL-18). By unlocking the potential of IL-18, Simcha is developing its lead program (ST-067) as monotherapy and in combination with potentially several other anticancer agents. ST-067 is currently being studied in a Phase 1a/2 clinical trial, in patients with solid tumors and who have progressed on other immunotherapeutic agents. Simcha is seeking to explore additional modalities for IL-18-based therapeutics and capture the full potential of this potentially transformational cytokine.  For more information, please visit www.simchatherapeutics.com.

Media Contact

Carolyn Hawley
Evoke Canale
Carolyn.hawley@evokegroup.com
619.849.5382