Trial-in-progress poster of Phase 1/2 CEDAR
trial evaluating GPH101 for sickle cell disease to be presented as
an encore
Graphite Bio, Inc. (Nasdaq: GRPH), a clinical-stage,
next-generation gene editing company harnessing the power of
high-efficiency precision gene repair to develop therapies with the
potential to treat or cure serious diseases, today presented
preclinical data for GPH102, the company’s differentiated gene
replacement program for beta-thalassemia, in an oral presentation
at the American Society of Gene and Cell Therapy (ASGCT) 25th
Annual Meeting. The hybrid meeting is taking place virtually and at
the Walter E. Washington Convention Center in Washington, D.C.,
from May 16-19.
“Our gene replacement program for beta-thalassemia is a natural
application of our powerful gene editing platform and the result of
our own internal discovery efforts. With GPH102, we aim to replace
the mutated beta-globin gene with a functional gene. This is the
first approach that has the potential to normalize the hundreds of
mutations in the beta-globin gene that cause beta-thalassemia and
restore adult hemoglobin expression to healthy levels, thereby
directly addressing the underlying cause of the disease,” said Josh
Lehrer, M.D., M.Phil., chief executive officer of Graphite Bio. “We
believe our gene replacement approach could be the optimal way to
treat beta-thalassemia and potentially provide a definitive cure to
patients. We look forward to continuing to build the body of
preclinical evidence supporting this program and plan to submit an
Investigational New Drug Application by mid-2024, pending feedback
from regulatory authorities.”
GPH102: An optimal approach to treat
beta-thalassemia by replacing the mutated beta-globin gene with a
functional gene The oral presentation (Abstract #66)
provides an overview of the development of a precise beta-globin
gene replacement strategy that could be the optimal approach to
treat beta-thalassemia, a genetic disorder caused by more than 300
mutations in the beta-globin gene. By replacing the mutated
beta-globin gene with a functional gene, GPH102 aims to restore
expression of adult hemoglobin to levels similar to those who do
not have the disease.
Graphite Bio researchers sought to develop a gene replacement
approach using the company's UltraHDR™ gene editing platform to
overcome the challenge of achieving high levels of gene replacement
that result in high adult hemoglobin (HbA) expression. In
particular, where the donor gene shares high nucleotide sequence
identity with the targeted mutant allele, undesired partial
recombination events can lead to incomplete or unsuccessful
integration of the entirety of the intended donor sequence.
To address this challenge, researchers devised a novel knock-in
strategy that uses heterologous introns and diverged coding
sequences. These were screened using a T2A-EGFP reporter system,
which served as a predictive screening tool for protein expression.
After screening 39 versions of T2A-EGFP-tagged beta-globin coding
sequences containing various heterologous introns and
polyadenylation signals, two top DNA donor candidates for
beta-globin gene replacement were identified. The selected DNA
donors were then further optimized by truncating the introns to
create a smaller donor cassette.
The optimized DNA donors were tested in hematopoietic stem and
progenitor cells (HSPCs) from sickle cell disease (SCD) patients,
which served as a therapeutically relevant model to determine if
the DNA donors can effectively replace a dysfunctional beta-globin
gene. Use of the optimized DNA donors resulted in homology directed
repair (HDR) rates of up to 40% in the sickle cell HSPCs and
restoration of HbA expression. These results support further
advancement of GPH102 for beta-thalassemia.
An encore of this abstract detailing the preclinical gene
replacement data for GPH102 was accepted as a poster presentation
at the European Hematology Association (EHA) 2022 Hybrid Congress,
which will take place virtually and at the Messe Wien Exhibition
& Congress Center in Vienna from June 9-12. The encore abstract
is now available online at https://ehaweb.org with additional
details following:
Abstract P1436: Development of a Beta-Globin Gene
Replacement Strategy as a Therapeutic Approach for Beta-Thalassemia
Presenting Author: Beeke Wienert, Ph.D., associate director,
gene engineering, Graphite Bio Date and Time: Friday, June
10, 16:30-17:45 CEST
GPH101: Gene correction for sickle cell
disease Phase 1/2 CEDAR trial encore poster presentation
At the ASGCT Annual Meeting, Graphite Bio will present an encore of
the trial-in-progress poster (Abstract #806) for the company’s
Phase 1/2 CEDAR trial for GPH101, an investigational therapy
designed to directly correct the genetic mutation responsible for
SCD. The CEDAR trial is an open-label, single-dose, multi-site
clinical trial evaluating GPH101 in approximately 15 participants
with severe SCD. The trial-in-progress poster is being presented by
John DiPersio, M.D., Ph.D., professor of medicine at Washington
University School of Medicine and an investigator in the CEDAR
trial. Information about this trial was previously presented at the
63rd American Society of Hematology (ASH) Annual Meeting &
Exposition in December 2021.
About GPH102 for Beta-Thalassemia GPH102 is Graphite
Bio’s research program for the treatment of beta-thalassemia, one
of the most common autosomal recessive disorders with approximately
68,000 people worldwide born with the disease each year.
Beta-thalassemia is a genetic blood disorder characterized by
reduced production of beta-globin, a protein that forms
oxygen-carrying hemoglobin with alpha-globin. Individuals with the
most severe form of beta-thalassemia fail to produce functional
beta-globin, which results in severe anemia and transfusion
dependency. Using Graphite Bio’s gene replacement approach, GPH102
is designed to replace the mutated beta-globin gene with a
functional gene and restore adult hemoglobin (HbA) expression to
levels similar to individuals who do not have the disease.
About GPH101 for Sickle Cell Disease 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). 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. GPH101 is the first investigational therapy to
use 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
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 the power of
high-efficiency precision gene repair 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 UltraHDR™ gene editing
platform is designed to precisely correct genetic mutations,
replace entire disease-causing genes with functional 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
UltraHDR™ gene editing platform and our GPH101 and GPH102 product
candidates, including our plans to submit an Investigational New
Drug Application for GPH102, and the timing thereof, 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 views about our plans, intentions,
expectations, strategies and prospects 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 regulatory hurdles or
delays, for example, in patient enrollment and dosing, and in the
progress, conduct and completion of our Phase 1/2 CEDAR trial and
our other 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 most recently
filed periodic report, and subsequent filings thereafter. 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/20220516005196/en/
Company Contact: Stephanie Yao VP, Communications and
Investor Relations 443-739-1423 syao@graphitebio.com
Investors: Stephanie Ascher Stern IR, Inc. 212-362-1200
ir@graphitebio.com
Media: Julia Stern Real Chemistry 763-350-5223
media@graphitebio.com
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