ATA2271 targets difficult-to-treat solid tumors
using proprietary 1XX CAR signaling and intrinsic PD-1 checkpoint
inhibition technology
Ongoing Phase 1 dose-escalation trial in
advanced mesothelioma shows promising early safety and persistence
of armored CAR T cells in patients
Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leader in T-cell
immunotherapy, leveraging its novel allogeneic Epstein-Barr virus
(EBV) T-cell platform to develop transformative therapies for
patients with cancer and autoimmune diseases, today announced new
preclinical and preliminary clinical results for ATA2271, a
next-generation autologous chimeric antigen receptor (CAR) T-cell
therapy targeting mesothelin (MSLN). These promising early safety
and functional persistence data were presented by collaborators at
Memorial Sloan Kettering Cancer Center as a mini-oral session at
the European Society for Medical Oncology Immuno-Oncology (ESMO
I‑O) Congress 2021, in Geneva, Switzerland.
ATA2271 is an investigational, autologous, second-generation
CAR-T immunotherapy that is designed to treat certain aggressive
solid tumors, including malignant pleural mesothelioma (MPM). Even
with successful completion of a combination of chemotherapy,
aggressive surgical resection and radiation therapy, the median
survival of treated patients in this report is only 9-17 months.
ATA2271 incorporates Atara’s novel inclusion of armoring, in the
form of a PD-1 DNR construct, to overcome checkpoint inhibition and
a 1XX costimulatory domain on the CAR to enhance expansion and
functional persistence of the CAR T-cells.
“CAR T-cell therapies have made incredible in-roads in the
treatment of hematological malignancies, but new technology and
targeting approaches are needed to apply these gains to aggressive
solid tumors,” said Cokey Nguyen, Senior Vice President and Chief
Scientific Officer at Atara. “We are extremely encouraged by these
early data assessing ATA2271 in advanced mesothelioma from a
first-in-human (FIH) Phase 1 study. Early findings represent the
first report of CAR T cells persisting over four weeks in a solid
tumor microenvironment without need for additional agents, such as
checkpoint inhibitors.”
As reported in the full abstract available on the ESMO website,
results from the evaluation of ATA2271 demonstrate the safety,
functional persistence and activation of the CAR T cells. These
studies, led by Prasad S. Adusumilli, MD, and collaborators at MSK
provide both in vitro and in vivo evidence of the preclinical
safety, improved functional characteristics and enhanced anti-tumor
efficacy of ATA2271 and promising preliminary safety and
persistence data in patients with MPM.
Specifically, in vitro functional studies show potent antitumor
activity of ATA2271 following repeat antigen stimulation, with
enhanced expansion observed in cells equipped with a PD-1 dominant
negative receptor (PD1DNR) that provides T-cell intrinsic
checkpoint blockade compared to CAR T-cells with a modified CD3z
(1XX) alone. These data support the design of ATA2271, 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 combination of next-gen CAR design (1XX) plus
PD1 DNR armoring technology in differential enrichment of cytokine
production involving cytokine signaling, effector immune responses,
leukocyte activation and differentiation. Furthermore, in vivo,
intrapleural administration of ATA2271 CAR T-cells in mice (n=8)
eradicated mesothelioma and prolonged survival. Functional
persistence of ATA2271 in vivo was evident by resistance to tumor
reestablishment following 10 rechallenges.
In the ongoing Phase 1 dose finding study (NCT04577326),
intrapleural administration of ATA2271 was found to be
well-tolerated at lowest dose levels with no CAR T-cell related
adverse events (AEs) of Grade >2 observed and no AEs of Grade
>3 to date in the study. All four patients had received at least
four prior lines of therapy. Importantly, ATA2271 CAR T-cells
persisted in patients’ peripheral blood for greater than four weeks
and was associated with upregulated effector cytokines.
Mini-Oral Presentation
Details:
Title: Promoting Functional Persistence in Solid Tumor
CAR T-cell Therapy: Mesothelin-targeted CAR (M28z1XXPD1DNR) with
T-cell Intrinsic PD1 Dominant Negative Receptor
- Presenting Author: Prasad S. Adusumilli, MD, FACS,
Memorial Sloan Kettering Cancer Center, New York, NY
- Date & Time: Thursday, December 9, 2021, at 11:05
a.m. CET / 5:05 a.m. EST / 2:05 a.m. PST
- Abstract Number: 46MO
- Session: Mini Oral Session
- Location: Palexpo Congress Centre, Room C
About Atara’s Mesothelin CAR T Franchise
Atara’s preclinical pipeline is rapidly expanding with novel
technologies and next-generation, multi-targeted CAR T
immunotherapies through collaborations with Moffitt Cancer Center
and Memorial Sloan Kettering Cancer Center.
In December 2020, Bayer and Atara announced an exclusive
worldwide license agreement for next-generation,
mesothelin-directed CAR T-cell therapies for the treatment of solid
tumors. The agreement includes the development candidate ATA3271,
an armored next generation allogeneic T-cell immunotherapy, and an
autologous version, ATA2271, for the treatment of high
mesothelin-expressing tumors such as malignant pleural mesothelioma
and non-small cell lung cancer.
Both ATA2271 and ATA3271 incorporate Atara’s novel inclusion of
armoring in the form of a PD-1 DNR construct to overcome checkpoint
inhibition and a 1XX costimulatory domain on the CAR to enhance
expansion and functional persistence of the CAR T-cells. ATA3271
leverages Atara’s EBV T-cell platform and is currently in
IND-enabling studies.
MSK Disclosures: Dr. Prasad S. Adusumilli has intellectual
property interests and other financial interests related to Atara.
MSK has intellectual property rights and associated interests by
virtue of licensing agreements between MSK and Atara.
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, which
does not require TCR or HLA gene editing, to create a robust
pipeline including: tab-cel® in Phase 3 development for
Epstein-Barr virus-driven post-transplant lymphoproliferative
disease (EBV+ PTLD) and other EBV-driven diseases; 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:
the timing and progress of its CAR T programs, including (i) the
ATA2271 clinical trial, and preliminary clinical data (ii) ATA2271
preclinical development and preclinical data, (iii) the timing and
progress of ATA3271; (iv) the strategic collaboration with Bayer
for ATA2271 and ATA3271, and (v) Atara’s ability to successfully
advance the development of its CAR T programs; and (vi) Atara’s
ability to advance development of its programs. Because such
statements deal with future events and are based on Atara’s current
expectations, they are subject to various risks and uncertainties
and actual results, performance or achievements of Atara 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 ongoing 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’s 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 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/20211209005155/en/
INVESTORS & MEDIA: Investors Eric Hyllengren
805-395-9669 ehyllengren@atarabio.com
Media Alex Chapman 805-456-4772 achapman@atarabio.com
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