Eureka Therapeutics Announces Publication of Preclinical Study Demonstrating GPRC5D as a Promising Target for Antibody-Based Therapies in Multiple Myeloma

  • Potential to target GPRC5D in multiple myeloma patients relapsed after
    BCMA-targeted therapy

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

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

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

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.”


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.


Eureka Therapeutics, Inc.
Natalie Liu
[email protected]

Kimberly Ha
[email protected]

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