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 its 2024 Platform Vision that redefines the future of CAR
T by leveraging the unique attributes of allogeneic CAR T products.
“Until now, CAR T development has been defined by how autologous
CAR Ts are made and used. As a management team with extensive
experience in both autologous and allogeneic CAR Ts, and the only
Company with the breadth of data to demonstrate comparability
between the two, we are uniquely positioned to potentially redefine
development and trial design of allogeneic CAR T products that
allows us to do what no autologous CAR T has done before,” said
David Chang, M.D., Ph.D., President, Chief Executive Officer and
Co-Founder of Allogene. “We believe this entirely new approach to
development creates an advantage for our investigational AlloCAR T™
products now and in the future while providing a clinical framework
to generate far more competitive CAR T products and dramatically
expand market opportunity.”
The Foundation: Pivotal ALPHA3 1L Consolidation Trial in
Large B Cell Lymphoma (LBCL)In a commanding pivot for the
CD19 program, the Company will focus development of its
investigational product cemacabtagene ansegedleucel, or cema-cel
(previously known as ALLO-501A) as part of the first line (1L)
treatment plan for newly diagnosed and treated LBCL patients who
are likely to relapse and need further therapy. The groundbreaking
design of the ALPHA3 1L consolidation trial builds upon the results
demonstrated in the Phase 1 ALPHA2 trial and leverages an
investigational cutting-edge diagnostic test developed by Foresight
Diagnostics to identify patients who have minimal residual disease
(MRD) at the completion of 1L chemoimmunotherapy for treatment with
cema-cel.
Although 1L R-CHOP is curative for many with LBCL, approximately
30% of patients who initially respond will relapsei. The standard
of care after 1L treatment has been simply to “watch and wait” for
the disease to relapse. ALPHA3 takes advantage of cema-cel as a
one-time, off-the-shelf treatment that can be administered
immediately upon discovery of MRD following six cycles of R-CHOP,
positioning it to become the standard “7th cycle” of frontline
treatment available to all eligible patients with MRD. ALPHA3
builds on the growing understanding that administration of CAR T
therapies to patients with low disease burden improves both safety
and efficacy outcomes. Cema-cel’s Phase 1 safety profile, with low
rates of cytokine release syndrome (CRS) and immune effector
cell-associated neurotoxicity syndrome (ICANS), already permits its
use in the outpatient setting in relapsed/refractory (r/r) patients
and may further improve in patients with no radiological evidence
of disease.
Start-up activities for the ALPHA3 trial have been initiated.
The study will randomize approximately 230 patients who are MRD
positive at the end of 1L therapy to either consolidation with
cema-cel or the current standard of care (observation). The design,
with a primary endpoint of event free survival (EFS), will
initially include two lymphodepletion arms (one with standard
fludarabine and cyclophosphamide plus ALLO-647 and one without
ALLO-647).
The outcome of this pivotal trial could allow cema-cel to be
embedded in the 1L setting to boost cure rates, potentially
rendering later-line treatment obsolete, and making cema-cel
available in community cancer centers where most earlier line
patients seek care. As a result of this differentiated vision for
cema-cel which competitively places its use ahead of other CAR T
therapies, the Company will focus on quickly advancing this
market-defining ALPHA3 trial and deprioritize the currently
enrolling third line (3L) ALPHA2 and EXPAND trials.
The Higher Bar: ALPHA2 Cema-Cel Trial in Chronic
Lymphocytic Leukemia (CLL)There is a growing need for
effective treatment in CLL post-Bruton tyrosine kinase inhibitors
(BTKis) and B-cell lymphoma 2 inhibitor (BCL2i) therapies. While
recent autologous CD19 CAR T data has been a positive step for
patients with r/r CLL, these therapies are still not meeting the
efficacy bar or expectations set in r/r LBCL. This is likely due in
part to T cell dysfunction and high circulating tumor burden in
CLL, making the isolation of functional T cells for autologous CAR
T manufacturing difficult.
There is strong scientific rationale to believe that an AlloCAR
T™ product derived from healthy donor cells could raise the bar and
potentially create a clinically meaningful advance for these
late-stage patients, with a one-time dose and simpler
administration and logistics.
The new Phase 1 ALPHA2 cohort of 12 patients treated with the
investigational product cema-cel provides the opportunity to set a
higher bar where patients with CLL are not reliant on their own T
cells’ fitness to benefit from the curative potential of CAR T.
This study, driven by investigator enthusiasm, will leverage
currently active ALPHA2 trial sites in the U.S. which should allow
it to advance quickly. It is expected to begin enrolling in Q1 2024
with initial data projected by YE 2024.
The Disruptor: ALLO-329 CD19 Dagger™ in Autoimmune
Disease (AID)The Company is applying its deep
understanding of CAR Ts to design a next-generation allogeneic CAR
T with reduced or chemotherapy-free conditioning that the Company
believes can sustain the scale of the AID market while meeting the
unique requirements for these patients where they seek care.
The risk tolerance of these patients is very different than
those with cancer, in large part because of patient demographics,
wide availability of effective therapies, and rheumatologists’
general lack of experience with chemotherapy, leukapheresis
procedures and cell therapies.
Incorporation of the Dagger technology into an off-the-shelf
CD19 product for use in AID is designed to reduce or eliminate the
need for standard chemotherapy while targeting CD19+ B-cells and
CD70+ activated T-cells, both of which play a role in AID.
Initiation of this Phase 1 trial with ALLO-329 is expected in early
2025.
The Key: TRAVERSE ALLO-316 in Renal Cell Carcinoma
(RCC)A fundamental discovery in early CAR T trials was the
use of tocilizumab and steroids, the “safety key” needed to
mitigate treatment-associated CRS without compromising CAR T
function or efficacy. The Company believes it may have made the
same cornerstone discovery in the TRAVERSE trial in renal cell
carcinoma.
During the careful advancement of the TRAVERSE trial with
ALLO-316, the Company has observed remarkable allogeneic CAR T cell
expansion and persistence driven by its unique CD70 CAR that allows
elimination of alloreactive host lymphocytes. This biology has
brought the potential for clinical efficacy not often seen in
patients with r/r RCC but has also resulted in a hyperinflammatory
response in some patients as CD70 CAR T cells expand and
persist.
Leveraging recent advances in the management of
hyperinflammation following autologous CAR T administration, the
Company has developed a diagnostic and treatment algorithm similar
to what the management team previously helped develop for CRS and
ICANS. Like tocilizumab and steroids, this algorithm may mitigate
the treatment-associated hyperinflammatory response without
compromising the CAR T function needed to eradicate solid tumors.
The Company has recently implemented a protocol amendment to
further maximize the benefit-risk of ALLO-316 in patients with
CD70+ RCC.
The next update from this trial is planned for a medical forum
in Q2 2024 and will discuss the algorithm that is believed to be a
critical advance for both the TRAVERSE trial as well as the
industry at large. A more robust data update from the ongoing trial
with the updated protocol is planned for later in 2024.
The Source: Proprietary Cell Forge 1 Allogeneic CAR T
Manufacturing FacilityCell Forge 1 (CF1), the Company’s
wholly owned and fully integrated manufacturing facility, serves as
a crucial strategic asset given the potential outlook for
allogeneic CAR T product demand. We believe the ability to scale
and control manufacturing will allow the Company to deliver a
consistently high-quality allogeneic CAR T product.
Financial Runway Extended into 2026The refined
approach of the 2024 Platform Vision results in a streamlined trial
footprint as well as a focused pipeline prioritization, allowing
the Company to implement a planned restructuring of resources in Q1
2024. The result will reduce cash burn and is expected to extend
the Company’s financial runway into 2026. Full 2024 guidance will
be provided in the Company’s Q4/YE 2023 quarterly call.
JP Morgan Preview Conference CallThe 2024
Platform Vision Conference Call will be hosted on Thursday, January
4, 2024, at 2:00 p.m. PT/5:00 p.m. ET and include presentations
and/or commentary by:
- David Chang, M.D., Ph.D., President, Chief Executive Officer
and Co-Founder
- Zachary Roberts, M.D., Ph.D., Executive Vice President,
Research & Development and Chief Medical Officer
- Alex Herrera. M.D., Chief, Division of Lymphoma, Department of
Hematology & Hematopoietic Cell Transplantation at The City of
Hope
Dr. Chang will also present the 2024 Platform Vision at the 42nd
Annual J.P. Morgan Healthcare Conference on Wednesday, January 10,
2024, at 8:15 a.m. Pacific Time. This event will be held in San
Francisco at the Westin St. Francis.
Conference Call DetailsAllogene will host a
live conference call today at 2:00 p.m. Pacific Time / 5:00 p.m.
Eastern Time to discuss the 2024 Vision for Allogene. If you would
like the option to ask a question on the conference call, please
use this link to register. Upon registering for the conference
call, you will receive a personal PIN to access the call, which
will identify you as the participant and allow you the option to
ask a question.
JP Morgan ConferenceA live audio webcast of the
presentation will be made available on the Company's website
at www.allogene.com under the Investors tab in the News and
Events section.
Following these live audio webcasts, replays will be available
on the Company's website for approximately 30 days. The materials
presented will be available on the Allogene website.
About Cemacabtagene Ansegedleucel (Previously Known as
ALLO-501A)Cemacabtagene ansegedleucel, or cema-cel is a
next generation anti-CD19 AlloCAR T™ investigational product for
the treatment of large B cell lymphoma (LBCL). This product
candidate is currently being studied in an ongoing potentially
pivotal Phase 2 trial in relapsed/refractory (r/r) LBCL. The ALPHA3
pivotal Phase 2 trial in first line (1L) consolidation for the
treatment of LBCL is expected to begin mid-2024. In June 2022,
the U.S. Food and Drug Administration granted
Regenerative Medicine Advanced Therapy (RMAT) designation to
cema-cel in third line (3L) r/r LBCL.
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
(formerly Twitter) and LinkedIn.
Cautionary Note on Forward-Looking Statements for
AllogeneThis 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 “predicts,” “projects,”
“believes,” “potential,” “proposed," “continue,” “estimates,”
“anticipates,” “expects,” “plans,” “intends,” “may,” “could,”
“might,” “will,” “should” 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: ALPHA3 being a pivotal
trial; the pace, timing and extent to which we may enroll patients
in our clinical trials or release data from such trials; the timing
and ability to progress the ALPHA2, EXPAND, ALPHA3 and TRAVERSE
trials; 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
our Dagger™ technology including the ability 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 reduce
or eliminate the need for standard chemotherapy while targeting
CD19+ B-cells and CD70+ activated T-cells in autoimmune disease,
and our plans to deploy the Dagger™ technology; the potential for
our product candidates to be approved; the potential benefits of
AlloCAR T products; the ability of our product candidates to treat
various stages and types of cancers including hematological and
solid tumors or to treat autoimmune disease; our level of operating
expenses and the extent of our cash runway; our ability to expand
indications or therapeutic fields for our allogeneic CAR T product
candidates; our ability to broaden patient access to CAR T therapy;
the modes of action or the biologic impacts of our product
candidates including the engraftment, expansion, persistence and
efficacy of allogeneic CAR T cells, the ability of AlloCAR T cells
from being recognized by host T cells without triggering an immune
response, and the ability to selectively eliminate CD70 positive
alloreactive host immune cells; the incidence, severity and
manageability of side effects of allogeneic CAR T therapies; the
extent to which our clinical trials will support regulatory
approval of our product candidates; the extent to which and type of
lymphodepletion strategies that may be required in conjunction with
our product candidates; 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 Phase 1 data from our clinical trials 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; challenges with manufacturing or
optimizing manufacturing of our product candidates; and our ability
to obtain additional financing to develop our products and
implement our operating plans. 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 Annual
Report on Form 10-K for the year ended December 31, 2022, and in
its Quarterly Report on Form 10-Q for the quarter ended September
30, 2023. 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’s investigational oncology products utilize
TALEN® gene-editing technology pioneered and owned by
Cellectis. ALLO-501 and cemacabtagene ansegedleucel (previously
known as ALLO-501A) are anti-CD19 AlloCAR T™ investigational
products being developed under a collaboration agreement
between Servier and Allogene based on an exclusive
license granted by Cellectis to Servier. Servier grants
to Allogene exclusive rights to ALLO-501 and cemacabtagene
ansegedleucel in the U.S.
Allogene Media/Investor Contact:Christine
CassianoEVP, Chief Corporate Affairs & Brand Strategy
OfficerChristine.Cassiano@allogene.com
i Tilly H, Morschhauser F, Sehn LH, Friedberg JW, et al.
Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell
Lymphoma. N Engl J Med. 2022;386(4):351-363
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