Allogene Therapeutics Presents Preclinical Data for ALLO-329, an Allogeneic CD19/CD70 Dual CAR T for the Treatment of Autoimmune Disease at the American College of Rheumatology (ACR) Convergence
November 18 2024 - 7:30AM
Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage
biotechnology company pioneering the development of allogeneic CAR
T (AlloCAR T™) products for cancer and autoimmune disease, today
announced preclinical data for ALLO-329, an investigational
allogeneic CD19/CD70 dual CAR T cell therapy being evaluated as a
treatment for autoimmune diseases. The data, presented at the
American College of Rheumatology (ACR) Convergence 2024,
demonstrate the potential of ALLO-329 to specifically address key
challenges associated with current autologous CAR T cell therapies
in development for patients with autoimmune disease and highlights
the promise of an allogeneic CAR T to reset the immune system.
ALLO-329 is the first CAR T designed to target both CD19+
B-cells and CD70+ activated T cells. Targeting of B cells has been
shown to induce durable, treatment-free remissions in patients with
certain autoimmune diseases. CD70 is expressed in activated T
cells, which have been implicated in immune responses, including in
autoimmunity. Simultaneous elimination of CD70+ T cells may enhance
the therapeutic benefit and expand the list of addressable
indications.
CD70+ activated T cells also include alloreactive T-cells – the
patient’s cells that would attack and reject an allogeneic CAR-T.
ALLO-329 is designed to effectively eliminate alloreactive T-cells
and render ALLO-329 resistant to rejection. Incorporation of
Dagger® technology into ALLO-329 is intended to reduce or eliminate
lymphodepletion prior to cell infusion.
“The CAR T space for autoimmune disease is highly competitive,
with many approaches focusing only on isolated aspects of
autoimmune pathogenesis,” said Zachary Roberts, M.D., Ph.D., EVP,
Research and Development and Chief Medical Officer of Allogene.
“What sets ALLO-329 apart is its ability to target a greater
spectrum of immune dysfunction, addressing both B cells and
activated T-cells involved in the disease process, potentially
improving disease outcomes with reduced or even no lymphodepletion.
Coupled with its “off-the-shelf” accessibility, ALLO-329 has the
potential to meet the substantial needs of a broad patient
population. These preclinical findings reinforce our excitement as
we move this therapy toward clinical development across multiple
autoimmune conditions.”
Key findings from the preclinical evaluation of ALLO-329
include:
- High CAR expression and cytotoxic activity: ALLO-329 produced
through site-specific integration of a dual CAR construct into the
TRAC locus demonstrated robust CAR expression and specific
cytotoxic activity against both CD19+ B cells and CD70+ T cells in
vitro and in vivo.
- Resistance to rejection: In mixed lymphocyte reaction (MLR)
assays, ALLO-329 successfully eliminated CD70+ alloreactive T
cells, demonstrating resistance to rejection and enhanced
persistence compared to CD19 CAR T cells.
- B cell depletion and antibody reduction: ALLO-329 effectively
eradicated B cells derived from healthy donors and patients with
systemic lupus erythematosus (SLE) in vitro and in vivo, leading to
a reduction in IgG and IgM production.
- Potential to eliminate lymphodepletion: In humanized
pre-clinical models, ALLO-329 demonstrated engraftment, B cell
depletion, and expansion even without lymphodepletion.
- Manufacturability: CRISPR-mediated, T-cell receptor alpha
(TRAC) site-specific transgene integration leads to a highly
consistent, dual CAR T-expressing product.
Based on these promising preclinical results, the Company plans
to file an investigational new drug (IND) application with the FDA
in the first quarter of 2025 and expects to have proof-of-concept
by year-end 2025.
About ALLO-329ALLO-329 is a CD19/CD70 dual
AlloCAR T™ investigational product being developed for the
treatment of autoimmune diseases. ALLO-329 utilizes CRISPR-based
site-specific integration for dual CAR expression. This approach
targets both CD19+ B cells and CD70+ T cells, which play a role in
autoimmune disease pathogenesis. Additionally, ALLO-329
incorporates Allogene's clinically validated Dagger® technology,
designed to reduce or eliminate the need for lymphodepletion, a
pre-treatment regimen that may be a significant barrier to CAR T
cell therapy adoption in autoimmune indications.
About Allogene TherapeuticsAllogene
Therapeutics, with headquarters in South San Francisco, is a
clinical-stage biotechnology company pioneering the
development of allogeneic chimeric antigen receptor T cell
(AlloCAR T™) products for cancer and autoimmune disease. Led by a
management team with significant experience in cell therapy,
Allogene is developing a pipeline of “off-the-shelf” CAR T cell
product candidates with the goal of delivering readily
available cell therapy on-demand, more reliably, and
at greater scale to more patients. For more information,
please visit www.allogene.com, and follow @AllogeneTx on X and
LinkedIn.
Cautionary Note on Forward-Looking Statements for
Allogene This press release contains forward-looking
statements for purposes of the safe harbor provisions of the
Private Securities Litigation Reform Act of 1995. The press release
may, in some cases, use terms such as “potential,” “develop,”
“promise,” “designed to,” “explore,” “expects,” “plans,” “intends,”
“may,” “could,” “would,” or other words that convey uncertainty of
future events or outcomes to identify these forward-looking
statements. Forward-looking statements include statements regarding
intentions, beliefs, projections, outlook, analyses or current
expectations concerning, among other things: the timing of filing
Investigational New Drug applications relating to ALLO-329 and the
progress and success of such clinical program; clinical outcomes,
which may materially change as more patient data become available;
the design and potential benefits of ALLO-329 and our Dagger™
technology including the ability overcome rejection and expand the
presence of alloreactive T-cells, to enhance engraftment, expansion
and persistence of AlloCAR T cells, the ability to resist rejection
of AlloCAR T cells by the host immune cells and the expected
benefits therefrom, or the ability to target CD19+ B-cells and
CD70+ activated T-cells that will induce durable, treatment-free
remissions or enhance the therapeutic benefits in autoimmune
disease, and our plans to deploy the Dagger™ technology; the
potential that our dual CAR targeting B- and T-cell components of
autoimmune disease will allow for broader application of CAR T
across multiple autoimmune conditions; the potential benefits of
AlloCAR T products; the ability of our product candidates to treat
autoimmune disease; the potential for off-the-shelf CAR T products;
our ability to deliver cell therapy on-demand, more reliably, and
at greater scale to more patients. Various factors may cause
material differences between Allogene’s expectations and actual
results, including, risks and uncertainties related to: our product
candidates are based on novel technologies, which makes it
difficult to predict the time and cost of product candidate
development and obtaining regulatory approval; the limited nature
of our pre-clinical data and the extent to which such data may or
may not be validated in any future clinical trial; our product
candidates may cause undesirable side effects or have other
properties that could halt their clinical development, prevent
their regulatory approval or limit their commercial potential; the
extent to which the Food and Drug Administration disagrees with our
clinical or regulatory plans or the import of our clinical results,
which could cause future delays to our clinical trials, including
initiation of clinical trials, or require additional clinical
trials; we may encounter difficulties enrolling patients in our
clinical trials; we may not be able to demonstrate the safety and
efficacy of our product candidates in our clinical trials, which
could prevent or delay regulatory approval and commercialization;
and challenges with manufacturing or optimizing manufacturing of
our product candidates. These and other risks are discussed in
greater detail in Allogene’s filings with the SEC, including
without limitation under the “Risk Factors” heading in its
Quarterly Report on Form 10-Q for the quarter ended September
30, 2024. Any forward-looking statements that are made in this
press release speak only as of the date of this press release.
Allogene assumes no obligation to update the forward-looking
statements whether as a result of new information, future events or
otherwise, after the date of this press release.
AlloCAR T™ and Dagger™ are trademarks of Allogene
Therapeutics, Inc.
Allogene Media/Investor Contact:Christine
CassianoEVP, Chief Corporate Affairs & Brand Strategy
OfficerChristine.Cassiano@allogene.com
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