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Eureka Therapeutics Announces Publication of Armored T-Cell Proof-of-Concept Study in Nature Biotechnology

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Eureka Therapeutics, Inc., a clinical stage biopharmaceutical company
with the goal of curing cancer by 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 Nature Biotechnology
entitled "Targeted
delivery of a PD-1-blocking scFv by CAR-T cells enhances anti-tumor
efficacy in vivo
." The publication details the approach of combining
CAR and PD-1 checkpoint inhibitor antibodies on the same engineered
T-cell, creating what is often described as an "armored T-cell" or
"armored CAR". This approach was developed in collaboration with Renier
J. Brentjens, M.D., Ph.D., Director of the Cellular Therapeutics Center
at Memorial Sloan Kettering Cancer Center (MSKCC).

Engineered T-cell therapy, and in particular CAR T-cells, have shown
efficacy in CD-19+ blood cancer such as lymphomas and leukemias.
However, to date, T-cell therapies have found little success in solid
tumors – in part due to the immunosuppressive tumor microenvironment.
Checkpoint inhibitors, on the other hand, have been proven effective at
empowering the immune system to fight a variety of solid tumors. The
checkpoint inhibitor antibody binds to a protein called PD-1 and shields
the T-cell from the immunosuppressive response generated by the cancer
cell, thus activating the potential of the T-cell to kill the cancer
cell. However, checkpoint inhibitors can unbalance the immune system and
induce toxicity and severe immune-related adverse event (irAEs).

The study analyzed two versions of the armored CAR in mouse models – one
against CD-19 positive targets, and the second against MUC-16 positive
targets. CD-19 antigens are found on B-Cell malignancies, while MUC-16
antigens are found on some ovarian and pancreatic cancers. The study
showed that by co-expressing a PD-1 inhibiting antibody on a CAR-T cell,
the CAR-T cells tend to stay locally around the tumor site, therefore
potentially avoiding toxicities associated with systematic checkpoint
inhibition. In addition, since the checkpoint drugs were released
directly into the tumor, they activated nearby T-cells, creating a
positive bystander effect. In both mouse models, the armored CARs
persisted longer than standard CARs.

"These data, together with in vivo models, suggest that this is
an early step toward exploring how we can make the first iterations of
CAR-T-cell therapies even better," said Dr. Brentjens, corresponding
author.

The PD-1 antibody used in this study was developed using Eureka's
proprietary E-ALPHA® phage display library for the discovery and
engineering of human antibodies. The publication is the result of a
joint collaboration initiated in 2013 between Eureka and MSKCC to
develop T-cell therapies.

"We are encouraged by the observed safety and anti-tumor activity
profile of PD-1 antibodies expressed on engineered T-cells," said Dr.
Cheng Liu, President and Chief Executive Officer of Eureka Therapeutics
and co-author on the paper. "Armoring an engineered T-cell against an
antigen target with a PD-1 checkpoint inhibitor antibody is an
innovative and novel approach to make T-cell therapies more effective,
in particular, against solid tumors. We are excited about the
possibility of applying this approach to our proprietary ARTEMIS™ T-cell
receptor platform."

Eureka's proprietary ARTEMIS™ T-cell receptor platform was designed to
create potentially safer and more effective T-cell therapies. In
proof-of-concept clinical studies against CD19+ malignancies, Eureka's
ARTEMIS™ T-cells demonstrated robust cancer-killing potency but with a
dramatic reduction in the levels of inflammatory cytokines released when
compared to currently approved CAR-T therapies. Cytokine release
syndrome (CRS) and neurotoxicity are other forms of serious side effects
associated with CAR-T therapies.

About Eureka Therapeutics, Inc.

Eureka Therapeutics, Inc. is a privately held clinical stage
biopharmaceutical company focused on developing novel T-cell therapies
that harness the evolutionary power of the immune system. Its core
technology platforms center around its proprietary ARTEMIS™ 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 hematologic and solid tumors.

Eureka Therapeutics, Inc. is headquartered in the San Francisco Bay
Area. For more information on Eureka Therapeutics, please visit www.eurekatherapeutics.com.

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