- Potential to target GPRC5D in multiple myeloma patients relapsed after BCMA-targeted therapy
EMERYVILLE, CA, USA I March 27, 2019 I Eureka Therapeutics, Inc., a clinical stage biotechnology company developing novel T-cell therapies that harness the evolutionary power of the immune system, today announced the publication of a proof-of-concept study in Science Translational Medicine entitled “GPRC5D is a target for the immunotherapy of multiple myeloma with rationally designed CAR-T cells.” The study was led by researchers from Eureka, Memorial Sloan Kettering Cancer Center (MSK) and Juno Therapeutics (Juno).
Antibody-based therapies, including bi-specific antibodies and chimeric antigen receptor (CAR) T-cell therapies targeting B cell maturation antigen (BCMA) for multiple myeloma, have shown promising clinical results, but relapses associated with low-to-negative expression of BCMA have been reported, necessitating additional targets for multiple myeloma.
The orphan G protein-coupled receptor GPRC5D has been previously identified in bone marrow cells in patients with multiple myeloma. However, the protein expression profile of GPRC5D remained elusive. Through immunohistochemical analyses, the study demonstrated that GPRC5D is expressed on malignant bone marrow plasma cells, while normal tissue expression is limited to the hair follicle, an immune-privileged site.
In 83 evaluated primary myeloma marrow samples, 65% of samples have GPRC5D expression above a 50% antigen expression cutoff on CD138+ cells. More importantly, GPRC5D expression on CD138 multiple myeloma cells was independent of BCMA expression, suggesting GPRC5D as an ideal clinical target.
In collaboration with MSK, Eureka developed antibodies targeting GPRC5D using Eureka’s proprietary E-ALPHA® discovery platform. These antibodies, together with antibodies targeting BCMA and another undisclosed multiple myeloma target, were licensed by Eureka and MSK to Juno (now Celgene) in 2016 for use in CARs.
In a head-to-head comparison with BCMA-targeted CARs with an identical backbone, GPRC5-targeted CAR-T cells demonstrated efficient antigen-specific cytotoxicity in vitro, as well as comparable effect in inducing tumor regression and extending survival at different dose levels in vivo. The study further showed that tumor escape can be rescued by GPRC5D-targeted CAR T-cells in a model of BCMA-antigen loss mediated relapse.
“The study confirms GPRC5D as a viable target in multiple myeloma,” said Eric Smith, M.D., Ph.D., a medical oncologist and the Director of Clinical Translation within the Cellular Therapeutics Center at MSK. “We look forward to moving this study into the clinic, including in relapsed patients after BCMA-targeted therapy.”
“Targeting GPRC5D has the potential to improve the durability of response from current bi-specific and T-cell therapies that target only BCMA,” said Dr. Cheng Liu, President and Chief Executive Officer at Eureka Therapeutics. “This study reflects our commitment to increasing the long-term clinical benefit for patients with multiple myeloma and other cancers, and we look forward to leveraging our E-ALPHA® and ARTEMIS™ platforms to develop transformational new T-cell therapies that are potentially safer and more effective.”
ABOUT EUREKA THERAPEUTICS, INC.
Eureka Therapeutics, Inc. is a privately held clinical stage biotechnology company developing antibody-TCR (AbTCR) T-Cell Therapies for solid and hematological malignancies. Its core technology centers around its proprietary ARTEMIS™ AbTCR T-cell receptor platform and E-ALPHA® antibody discovery platform for the discovery and development of potentially safer and more effective T-cell therapies for the treatment of multiple solid and hematologic tumors. The E-ALPHA platform comprises a highly diverse human-derived antibody phage library, containing over 100 billion clones with unique antibody sequences, and a robust workflow to develop highly specific antibodies against target antigens.
Eureka’s lead asset, ET140202, utilizes Eureka’s proprietary ARTEMIS™ T-cell receptor platform engineered with a proprietary human TCR-mimic (TCRm) antibody to target an AFP-peptide/HLA-A2 complex on HCC cancer cells. Data presented in September 2018 from Eureka’s ongoing first-in-human study of ET140202 in China demonstrated a favorable safety profile with no observed cytokine release syndrome or drug-related neurotoxicity. The Company plans to initiate its Phase 1/2 US multicenter clinical trial in the first half of 2019.
Eureka Therapeutics, Inc. is headquartered in the San Francisco Bay Area. For more information, please visit www.eurekatherapeutics.com.
SOURCE: Eureka Therapeutics
Post Views: 10
- Potential to target GPRC5D in multiple myeloma patients relapsed after BCMA-targeted therapy
EMERYVILLE, CA, USA I March 27, 2019 I Eureka Therapeutics, Inc., a clinical stage biotechnology company developing novel T-cell therapies that harness the evolutionary power of the immune system, today announced the publication of a proof-of-concept study in Science Translational Medicine entitled “GPRC5D is a target for the immunotherapy of multiple myeloma with rationally designed CAR-T cells.” The study was led by researchers from Eureka, Memorial Sloan Kettering Cancer Center (MSK) and Juno Therapeutics (Juno).
Antibody-based therapies, including bi-specific antibodies and chimeric antigen receptor (CAR) T-cell therapies targeting B cell maturation antigen (BCMA) for multiple myeloma, have shown promising clinical results, but relapses associated with low-to-negative expression of BCMA have been reported, necessitating additional targets for multiple myeloma.
The orphan G protein-coupled receptor GPRC5D has been previously identified in bone marrow cells in patients with multiple myeloma. However, the protein expression profile of GPRC5D remained elusive. Through immunohistochemical analyses, the study demonstrated that GPRC5D is expressed on malignant bone marrow plasma cells, while normal tissue expression is limited to the hair follicle, an immune-privileged site.
In 83 evaluated primary myeloma marrow samples, 65% of samples have GPRC5D expression above a 50% antigen expression cutoff on CD138+ cells. More importantly, GPRC5D expression on CD138 multiple myeloma cells was independent of BCMA expression, suggesting GPRC5D as an ideal clinical target.
In collaboration with MSK, Eureka developed antibodies targeting GPRC5D using Eureka’s proprietary E-ALPHA® discovery platform. These antibodies, together with antibodies targeting BCMA and another undisclosed multiple myeloma target, were licensed by Eureka and MSK to Juno (now Celgene) in 2016 for use in CARs.
In a head-to-head comparison with BCMA-targeted CARs with an identical backbone, GPRC5-targeted CAR-T cells demonstrated efficient antigen-specific cytotoxicity in vitro, as well as comparable effect in inducing tumor regression and extending survival at different dose levels in vivo. The study further showed that tumor escape can be rescued by GPRC5D-targeted CAR T-cells in a model of BCMA-antigen loss mediated relapse.
“The study confirms GPRC5D as a viable target in multiple myeloma,” said Eric Smith, M.D., Ph.D., a medical oncologist and the Director of Clinical Translation within the Cellular Therapeutics Center at MSK. “We look forward to moving this study into the clinic, including in relapsed patients after BCMA-targeted therapy.”
“Targeting GPRC5D has the potential to improve the durability of response from current bi-specific and T-cell therapies that target only BCMA,” said Dr. Cheng Liu, President and Chief Executive Officer at Eureka Therapeutics. “This study reflects our commitment to increasing the long-term clinical benefit for patients with multiple myeloma and other cancers, and we look forward to leveraging our E-ALPHA® and ARTEMIS™ platforms to develop transformational new T-cell therapies that are potentially safer and more effective.”
ABOUT EUREKA THERAPEUTICS, INC.
Eureka Therapeutics, Inc. is a privately held clinical stage biotechnology company developing antibody-TCR (AbTCR) T-Cell Therapies for solid and hematological malignancies. Its core technology centers around its proprietary ARTEMIS™ AbTCR T-cell receptor platform and E-ALPHA® antibody discovery platform for the discovery and development of potentially safer and more effective T-cell therapies for the treatment of multiple solid and hematologic tumors. The E-ALPHA platform comprises a highly diverse human-derived antibody phage library, containing over 100 billion clones with unique antibody sequences, and a robust workflow to develop highly specific antibodies against target antigens.
Eureka’s lead asset, ET140202, utilizes Eureka’s proprietary ARTEMIS™ T-cell receptor platform engineered with a proprietary human TCR-mimic (TCRm) antibody to target an AFP-peptide/HLA-A2 complex on HCC cancer cells. Data presented in September 2018 from Eureka’s ongoing first-in-human study of ET140202 in China demonstrated a favorable safety profile with no observed cytokine release syndrome or drug-related neurotoxicity. The Company plans to initiate its Phase 1/2 US multicenter clinical trial in the first half of 2019.
Eureka Therapeutics, Inc. is headquartered in the San Francisco Bay Area. For more information, please visit www.eurekatherapeutics.com.
SOURCE: Eureka Therapeutics
Post Views: 10
