Atara Biotherapeutics Presents New Preclinical Data on ATA3271, a Next-Generation Allogeneic Mesothelin-Targeted CAR T to Tre...
November 12 2020 - 8:30AM
Business Wire
Atara’s allogeneic CAR T therapy leverages the
combination of cell intrinsic PD1DNR checkpoint inhibition and 1XX
CAR signaling technologies built on the Company’s novel EBV T-cell
platform
Preclinical findings demonstrate potent
antitumor activity, persistence and low toxicity profile of
ATA3271, supporting further clinical investigation
Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a pioneer in T-cell
immunotherapy, leveraging its novel allogeneic EBV T-cell platform
to develop transformative therapies for patients with serious
diseases including solid tumors, hematologic cancers and autoimmune
disease, today announced the presentation of the first preclinical
evaluation of ATA3271, a next-generation, off-the-shelf, allogeneic
EBV CAR T-cell therapy targeting mesothelin designed for the
treatment of solid tumors. These data are being featured in a
poster presentation at the 35th Society for Immunotherapy of Cancer
Annual Meeting (SITC 2020), November 11-14, 2020.
“We have made meaningful progress advancing IND-enabling studies
for ATA3271, an allogeneic mesothelin CAR T, which leverages our
differentiated EBV T-cell platform and utilizes the PD1DNR and 1XX
technologies to improve efficacy, persistence, and durability of
response. Such innovative CAR T design addresses key hurdles for
realizing the potential for CAR T therapies in solid tumor
settings,” said Jakob Dupont, Global Head of Research and
Development at Atara. “Mesothelin, an antigen associated with
aggressive solid tumors, is a promising target for tumor-specific
therapy and combined with our EBV T-cell platform and the PD1DNR
and 1XX technologies has led to the potent preclinical antitumor
activity of ATA3271 that functionally persists after multiple tumor
cell challenges.”
Results presented at SITC detail findings from in vitro and in
vivo evaluation of ATA3271. Specifically, in vitro functional
studies show potent antitumor activity of ATA3271 against
mesothelin-expressing cell lines, with potency maintained in the
presence of high tumor PD-L1 expression. These data support the
design of ATA3271, which expresses a dominant negative version of
PD-1 receptor, to maintain function in the presence of suppressive
checkpoint ligands commonly associated with solid tumor
microenvironments. In addition, results further support the
combined functional design of ATA3271’s 1XX costimulatory domain
technology in maintaining memory phenotype while limiting cell
exhaustion in the context of repeated tumor cell challenges.
Furthermore, ATA3271 retains reduced allocytotoxic function
against HLA mismatched targets, a characteristic that is associated
with Atara’s allogeneic EBV T-cell platform that leverages
enrichment of endogenous EBV-TCR function to decrease clinical
risks for GvHD. We also believe that our allogeneic EBV CAR T-cell
platform may prevent cellular exhaustion and augment in vivo
expansion.
In vivo, ATA3271 exhibited potent antitumor activity and
significant survival benefit in mice implanted with MGM-PDL1 cells
that highly express both mesothelin as well as PD-L1. This in vivo
potency was demonstrated without evident toxicities. All mice
treated with ATA3271 (n=10) survived through the study duration,
while control mice (n=10) all died within a median duration of 25
days (15- to 35-day survival range), post tumor implantation.
Evidence in six of ten mice also showed that ATA3271 persisted in
vivo by day 51. Ex vivo analysis of a subset of these persistent
cell populations (n=4) demonstrated maintenance of phenotypic
memory markers over the duration of the in vivo activity.
Mesothelin is a tumor-specific antigen that is commonly
expressed at high levels on the cell surface in many aggressive
solid tumors including mesothelioma, triple-negative breast cancer,
esophageal cancer, ovarian cancer, pancreatic cancer and non-small
cell lung cancer and is an attractive target for immune-based
therapies. Both in vitro and in vivo results for ATA3271 suggest
that allogeneic mesothelin-CAR-engineered EBV T cells are a
promising approach for the treatment of mesothelin-positive
cancers.
“The results presented today further support the continued
development of our allogeneic mesothelin-targeted next-generation
CAR T program,” said AJ Joshi, M.D., Senior Vice President and
Chief Medical Officer at Atara. “We look forward to building upon
these foundational preclinical studies to advance ATA3271 in the
clinic with the goal of bringing a potentially transformative
therapeutic option to treat aggressive solid tumors including
mesothelioma.”
Atara’s next generation CAR T immunotherapy franchise for
mesothelin also includes autologous ATA2271. The U.S. Food and Drug
Administration (FDA) recently accepted an Investigational New Drug
(IND) application to initiate a Phase 1 clinical study of ATA2271
for the treatment of advanced mesothelioma.
About Atara Biotherapeutics, Inc.
Atara Biotherapeutics, Inc. (@Atarabio) is a pioneer in T-cell
immunotherapy leveraging its novel allogeneic EBV T-cell platform
to develop transformative therapies for patients with serious
diseases including solid tumors, hematologic cancers and autoimmune
disease. With our lead program in Phase 3 clinical development,
Atara is the most advanced allogeneic T-cell immunotherapy company
and intends to rapidly deliver off-the-shelf treatments to patients
with high unmet medical need. Our platform leverages the unique
biology of EBV T cells and has the capability to treat a wide range
of EBV-associated diseases, or other serious diseases through
incorporation of engineered CARs (chimeric antigen receptors) or
TCRs (T-cell receptors). Atara is applying this one platform to
create a robust pipeline including: tab-cel® (tabelecleucel) in
Phase 3 development for Epstein-Barr virus-driven post-transplant
lymphoproliferative disease (EBV+ PTLD); ATA188, a T-cell
immunotherapy targeting EBV antigens as a potential treatment for
multiple sclerosis; and multiple next-generation chimeric antigen
receptor T-cell (CAR-T) immunotherapies for both solid tumors and
hematologic malignancies. Improving patients’ lives is our mission
and we will never stop working to bring transformative therapies to
those in need. Atara is headquartered in South San Francisco and
our leading-edge research, development and manufacturing facility
is based in Thousand Oaks, California. For additional information
about the company, please visit atarabio.com and follow us on
Twitter and LinkedIn.
Forward-Looking Statements
This press release contains or may imply "forward-looking
statements" within the meaning of Section 27A of the Securities Act
of 1933 and Section 21E of the Securities Exchange Act of 1934. For
example, forward-looking statements include statements regarding:
preclinical results and data from the IND-enabling studies for
ATA3271; the timing and progress of ATA3271 and ATA2271, and
Atara’s ability to successfully advance the development of its CAR
T programs. Because such statements deal with future events and are
based on Atara Biotherapeutics' current expectations, they are
subject to various risks and uncertainties and actual results,
performance or achievements of Atara Biotherapeutics could differ
materially from those described in or implied by the statements in
this press release. These forward-looking statements are subject to
risks and uncertainties, including, without limitation, risks and
uncertainties associated with the costly and time-consuming
pharmaceutical product development process and the uncertainty of
clinical success; the COVID-19 pandemic, which may significantly
impact (i) our business, research, clinical development plans and
operations, including our operations in South San Francisco and
Southern California and at our clinical trial sites, as well as the
business or operations of our third-party manufacturer, contract
research organizations or other third parties with whom we conduct
business, (ii) our ability to access capital, and (iii) the value
of our common stock; the sufficiency of Atara’s cash resources and
need for additional capital; and other risks and uncertainties
affecting Atara’s and its development programs, including those
discussed in Atara Biotherapeutics' filings with the Securities and
Exchange Commission (SEC), including in the “Risk Factors” and
“Management’s Discussion and Analysis of Financial Condition and
Results of Operations” sections of the Company’s most recently
filed periodic reports on Form 10-K and Form 10-Q and subsequent
filings and in the documents incorporated by reference therein.
Except as otherwise required by law, Atara Biotherapeutics
disclaims any intention or obligation to update or revise any
forward-looking statements, which speak only as of the date hereof,
whether as a result of new information, future events or
circumstances or otherwise.
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version on businesswire.com: https://www.businesswire.com/news/home/20201112005385/en/
INVESTOR & MEDIA: Media Kerry Beth Daly Head,
Corporate Communications Atara Biotherapeutics 516-982-9328
kdaly@atarabio.com
Investors Eric Hyllengren Vice President, Investor
Relations & Finance Atara Biotherapeutics 805-395-9669
ehyllengren@atarabio.com
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