Beam Therapeutics Presents First In Vivo Proof of Concept Preclinical Data on Multiplex Base Edited ESCAPE Platform for Non-Genotoxic Conditioning Regimen for Patients with Sickle Cell Disease Ahead of Autologous Transplant
December 10 2022 - 10:00AM
Beam Therapeutics Inc. (Nasdaq: BEAM), a biotechnology company
developing precision genetic medicines through base editing, today
announced new preclinical data from its Engineered Stem Cell
Antibody Paired Evasion (ESCAPE) conditioning approach aimed at
overcoming toxicity challenges associated with currently available
conditioning regimens. Beam is advancing ESCAPE as part of its
long-term strategy to support broad accessibility of base editing
treatments for patients with sickle cell disease (SCD) and other
hematologic diseases. “Wave 2” of this strategy is focused on
improving the safety and tolerability of conditioning regimens, a
required pretreatment for patients receiving ex vivo gene editing
treatment via autologous transplant that can be coupled with a
treatment for SCD through multiplex base editing.
Beam is currently advancing two ESCAPE programs: “ESCAPE-1” and
“ESCAPE-2.” In both strategies, hematopoietic stem cells (HSCs) are
multiplex edited to generate point mutations in the CD117 gene and
a therapeutic edit for the treatment of SCD. The base edit to
CD117, a well-categorized conditioning target, results in amino
acid substitutions and is intended to allow these HSCs to evade
elimination by the conditioning antibody. ESCAPE-1 has been
designed to induce a therapeutic edit for SCD at the HGB1/2 gene to
enable upregulation of fetal hemoglobin, while ESCAPE-2 is designed
to install the therapeutic HbG-Makassar edit. Beam’s ESCAPE
strategy is intended to allow the conditioning antibody to
selectively clear unedited host cells while allowing cells
containing the CD117 edit to engraft and proliferate in the
presence of the antibody.
“We continue to make important progress with our ESCAPE strategy
to improve conditioning regimens for patients ahead of autologous
transplant, with a goal of expanding the number of patients who may
be able to benefit from our novel therapeutic candidates,” said
Giuseppe Ciaramella, Ph.D., president and chief scientific officer
of Beam. “We’re excited to share the first in vivo data from
ESCAPE, which provide further evidence of our approach’s potential
to enable less toxic pre-transplant conditioning, while minimizing
treatment-related toxicities that arise from current busulfan-based
conditioning. The latest findings for both ESCAPE-1 and ESCAPE-2
support their continued advancement as treatment approaches for SCD
and other hematologic conditions in the future.”
ESCAPE-1 Data Summary ESCAPE-1 consists of
multiplex base edited HSCs that include a therapeutic edit for SCD
at the HGB1/2 gene and an additional edit at CD117. Findings to be
presented today include the first in vivo data for the program
which build upon data shared earlier this year demonstrating that
ESCAPE antibodies bound to wild-type CD117 and blocked binding of
its ligand. In addition, the ESCAPE antibodies led to the depletion
of unedited cells, while enriching for edited cells. Further,
today’s data show:
- Beam’s CD117 variants functioned comparably to its wild-type
form in proliferation, differentiation, viability, and
phosphorylation assays in vitro, supporting the notion that the
edit does not alter the biological function of CD117
- CD117 base-edited human CD34+ HSCs led to multilineage
reconstitution in a mouse model comparable with unedited HSCs,
consistent with the cells having retained their stem-like
engraftment potential
- Fc-engineered mAb-7 (anti-CD117 monoclonal antibody) did not
induce mast-cell degranulation in vitro
- Multiplexing CD117 sgRNA with therapeutic sgRNAs (e.g. HBG1/2)
with a single adenine base editor achieved greater than 85% A
to G editing at CD117 in HSCs, which also contain the therapeutic
edit
- Multiplex base edited HSCs evaded mAb-mediated effects and
CD117-ligand blocking, allowing for escape from
depletion in vitro and in vivo
- mAb-7 selectively depleted unedited cells from the bone marrow
of mice transplanted with a 1:1 mixture of unedited and edited
HSCs
Title: Engineered Stem Cell Antibody Paired
Evasion 1 (ESCAPE-1): Paired HSC Epitope Engineering and
Upregulation of Fetal Hemoglobin for Antibody-Mediated Autologous
Hematopoietic Stem Cell Therapy Conditioning for the Treatment of
Hemoglobinopathies (1955)Session Name: 701.
Experimental Transplantation: Basic and Translational: Poster I
Date & Time: Saturday, December 10, 2022,
5:30-7:30 p.m. Location: Ernest N. Morial
Convention Center, Hall D
ESCAPE-2 Data SummaryIn ESCAPE-2, Beam
scientists screened two adenine base editor sgRNAs that could
install the therapeutic HbG-Makassar edit and an edit in CD117
which was compatible with the conditioning mAb (“mAb-7”) previously
developed for ESCAPE-1. In preclinical studies, Beam’s ESCAPE-2
strategy demonstrated highly efficient base editing of CD117 of
HSCs and favorable mAb properties in vitro. Further, findings
showed that primary human HSCs harboring the engineered epitope
could effectively evade depletion by blocking of the CD117 ligand
binding by a highly specific and potent mAb in vitro. Early in
vitro biological assessment of receptor function suggested that the
engineered CD117 epitope is compatible with normal function. During
the poster session, Beam will also present additional in vivo data
on ESCAPE-2, supporting its continued advancement and
evaluation.
Title: Engineered Stem Cell Antibody Paired
Evasion-2 (ESCAPE-2): Paired HSC Epitope Engineering and Direct
Editing of Sickle Allele for Antibody-Mediated Autologous
Hematopoietic Stem Cell Therapy Conditioning for the Treatment of
Sickle Cell Disease (4585)Session Name: 701.
Experimental Transplantation: Basic and Translational: Poster III
Date & Time: Monday, December 12, 2022,
6:00-8:00 p.m. Location: Ernest N. Morial
Convention Center, Hall D
About Beam TherapeuticsBeam Therapeutics
(Nasdaq: BEAM) is a biotechnology company committed to establishing
the leading, fully integrated platform for precision genetic
medicines. To achieve this vision, Beam has assembled a platform
that includes a suite of gene editing and delivery technologies and
is in the process of building internal manufacturing capabilities.
Beam’s suite of gene editing technologies is anchored by base
editing, a proprietary technology that is designed to enable
precise, predictable and efficient single base changes, at targeted
genomic sequences, without making double-stranded breaks in the
DNA. This has the potential to enable a wide range of potential
therapeutic editing strategies that Beam is using to advance a
diversified portfolio of base editing programs. Beam is a
values-driven organization committed to its people, cutting-edge
science, and a vision of providing life-long cures to patients
suffering from serious diseases.
Cautionary Note Regarding Forward-Looking
StatementsThis press release contains forward-looking
statements within the meaning of the Private Securities Litigation
Reform Act of 1995. Investors are cautioned not to place undue
reliance on these forward-looking statements, including, but not
limited to, statements related to: our upcoming presentations at
the ASH Annual Meeting and Exposition; the therapeutic applications
and potential of our technology, including with respect to SCD and
our conditioning regimens; and our ability to develop life-long,
curative, precision genetic medicines for patients through base
editing. Each forward-looking statement is subject to important
risks and uncertainties that could cause actual results to differ
materially from those expressed or implied in such statement,
including, without limitation, risks and uncertainties related to:
our ability to develop, obtain regulatory approval for, and
commercialize our product candidates, which may take longer or cost
more than planned; our ability to raise additional funding, which
may not be available; our ability to obtain, maintain and enforce
patent and other intellectual property protection for our product
candidates; the potential impact of the COVID-19 pandemic,
including its impact on the global supply chain; the uncertainty
that our product candidates will receive regulatory approval
necessary to initiate human clinical studies; that preclinical
testing of our product candidates and preliminary or interim data
from preclinical studies and clinical trials may not be predictive
of the results or success of ongoing or later clinical trials; that
enrollment and initiation of our clinical trials may take longer
than expected; that our product candidates may experience
manufacturing or supply interruptions or failures; risks related to
competitive products; and the other risks and uncertainties
identified under the headings “Risk Factors Summary” and “Risk
Factors” in our Annual Report on Form 10-K for the year ended
December 31, 2021, our Quarterly Report on Form 10-Q for the
quarter ended September 30, 2022, and in any subsequent filings
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Contacts:
Investors:Chelcie ListerTHRUST Strategic
Communicationschelcie@thrustsc.com
Media:Dan Budwick1ABdan@1abmedia.com
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