Data support ability of company’s gene editing
platform to precisely and efficiently correct the underlying
disease-causing mutation and restore adult hemoglobin expression
with curative potential
Data show minimal off-target editing using
company’s exclusively licensed high fidelity Cas9 and robust
long-term engraftment
Company on track to enroll first patient in
Phase 1/2 CEDAR trial in 2H 2021
Graphite Bio, Inc. (Nasdaq: GRPH), a clinical-stage,
next-generation gene editing company focused on therapies that
harness targeted gene integration to treat or cure serious
diseases, announced today the presentation of preclinical data for
GPH101, an investigational therapy designed to directly correct the
genetic mutation responsible for sickle cell disease (SCD). Data
were presented at the 49th Annual Sickle Cell Disease Association
of America (SCDAA) National Convention in a poster
presentation.
“These positive preclinical data are foundational to our sickle
cell disease program and support the evaluation of GPH101 in our
Phase 1/2 CEDAR trial, for which we are on track to enroll our
first patient before the end of the year,” said Josh Lehrer,
M.Phil., M.D., chief executive officer at Graphite Bio. “These
encouraging data reinforce our belief that GPH101 has the potential
to directly correct the underlying disease-causing mutation to
decrease production of sickle hemoglobin and restore the expression
of normal adult hemoglobin with minimal off-target editing. Gene
correction has been viewed as the optimal approach to potentially
cure sickle cell disease, and the preclinical data we have
generated indicate we can do this precisely and efficiently and at
rates that are considered potentially curative based on extensive
data from patients who have undergone allogeneic stem cell
transplant.”
Graphite Bio presented data establishing the reproducibility of
the company’s gene editing platform to generate gene-corrected
hematopoietic stem cells (HSCs) for the treatment of SCD. Using
Graphite Bio’s gene correction platform, which uses an engineered
high fidelity Cas9 to reduce off-target cleavage by 30-fold, the
company was able to achieve greater than 60% of gene-corrected
beta-globin alleles in vitro with minimal off-target activity.
After transplant into mice, long-term engraftment (16 weeks) of
gene-corrected cells in vivo was achieved, with gene correction
frequencies much greater than the predicted curative threshold of
15% gene correction, which is equivalent to 20% cell correction.
These correction frequencies support the potential for this
approach to be equivalent or superior to allogeneic hematopoietic
stem cell transplant (allo-HSCT) in restoring the expression of
normal adult hemoglobin and red blood cell biology.
Additionally, the data showed that gene-corrected red blood
cells went from producing 100% sickle hemoglobin to expressing more
than 90% normal adult hemoglobin. Long-term preclinical safety data
revealed no evidence of abnormal hematopoiesis, genotoxicity or
tumorigenicity, including no detectable chromosomal translocations.
These preclinical data support Graphite Bio’s CEDAR clinical trial,
a Phase 1/2 study evaluating the safety, pharmacodynamics,
engraftment success, gene correction rates and total hemoglobin, as
well as other clinical and exploratory endpoints of GPH101 in
patients with severe SCD.
The data presented today were previously published in the June
16 edition of Science Translational Medicine. A copy of the poster
presentation is available under the Publications section of the
Graphite Bio website.
About Sickle Cell Disease (SCD)
SCD is a serious, life-threatening inherited blood disorder that
affects approximately 100,000 people in the United States and
millions of people around the world, making it the most prevalent
monogenic disease worldwide. SCD is caused by a single mutation in
the beta-globin gene that leads to red blood cells that are
responsible for delivering oxygen to tissues and organs throughout
the body to become misshapen, resulting in anemia, blood flow
blockages, intense pain, increased risk of stroke and organ damage,
and reduced life span of approximately 30 years. Despite
advancements in treatment and care, progressive organ damage
continues to cause early mortality and severe morbidity,
highlighting the need for curative therapies.
About GPH101
GPH101 is an investigational next-generation gene-edited
autologous hematopoietic stem cell (HSC) therapy designed to
directly correct the genetic mutation that causes sickle cell
disease (SCD). GPH101 is the first investigational therapy to
utilize a highly differentiated gene correction approach that seeks
to efficiently and precisely correct the mutation in the
beta-globin gene to decrease sickle hemoglobin (HbS) production and
restore normal adult hemoglobin (HbA) expression, thereby
potentially curing SCD.
Graphite Bio is evaluating GPH101 in the CEDAR trial, an
open-label, multi-center Phase 1/2 clinical trial designed to
assess the safety, engraftment success, gene correction rates,
total hemoglobin, as well as other clinical and exploratory
endpoints and pharmacodynamics in patients with severe SCD.
About Graphite Bio
Graphite Bio is a clinical-stage, next-generation gene editing
company harnessing high efficiency targeted gene integration to
develop a new class of therapies to potentially cure a wide range
of serious and life-threatening diseases. Graphite Bio is
pioneering a precision gene editing approach that could enable a
variety of applications to transform human health through its
potential to achieve one of medicine’s most elusive goals: to
precisely “find & replace” any gene in the genome. Graphite
Bio’s platform allows it to precisely correct mutations, replace
entire disease-causing genes with normal genes or insert new genes
into predetermined, safe locations. The company was co-founded by
academic pioneers in the fields of gene editing and gene therapy,
including Maria Grazia Roncarolo, M.D., and Matthew Porteus, M.D.,
Ph.D.
Learn more about Graphite Bio by visiting www.graphitebio.com
and following the company on LinkedIn.
Forward-Looking Statements
Statements we make in this press release may include statements
which are not historical facts and are considered forward-looking
statements within the meaning of Section 27A of the Securities Act
of 1933, as amended (the “Securities Act”), and Section 21E of the
Securities Exchange Act of 1934, as amended (the “Exchange Act”).
These statements may be identified by words such as “aims,”
“anticipates,” “believes,” “could,” “estimates,” “expects,”
“forecasts,” “goal,” “intends,” “may,” “plans,” “possible,”
“potential,” “seeks,” “will,” and variations of these words or
similar expressions that are intended to identify forward-looking
statements. Any such statements in this press release that are not
statements of historical fact, including statements regarding the
clinical and therapeutic potential of our gene editing platform and
our product candidates, and the timing for enrollment of the first
patient in our Phase 1/2 clinical trial of GPH101 and the
availability of initial proof-of-concept data, may be deemed to be
forward-looking statements. We intend these forward-looking
statements to be covered by the safe harbor provisions for
forward-looking statements contained in Section 27A of the
Securities Act and Section 21E of the Exchange Act and are making
this statement for purposes of complying with those safe harbor
provisions.
Any forward-looking statements in this press release are based
on Graphite Bio’s current expectations, estimates and projections
only as of the date of this release and are subject to a number of
risks and uncertainties that could cause actual results to differ
materially and adversely from those set forth in or implied by such
forward-looking statements, including the risk that we may
encounter delays in patient enrollment and in the initiation,
conduct and completion of our planned clinical trials. These risks
concerning Graphite Bio’s programs and operations are described in
additional detail in its periodic filings with the SEC, including
its quarterly report on Form 10-Q filed with the SEC on August 12,
2021. Graphite Bio explicitly disclaims any obligation to update
any forward-looking statements except to the extent required by
law.
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version on businesswire.com: https://www.businesswire.com/news/home/20211012005679/en/
Company Contact: Stephanie Yao VP, Communications and
Investor Relations 443-739-1423 syao@graphitebio.com
Investor Relations: Stephanie Ascher Stern IR, Inc.
212-362-1200 ir@graphitebio.com
Media Contact: Christy Curran Sam Brown, Inc.
615-414-8668 media@graphitebio.com
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