Prime Medicine, Inc. (Nasdaq: PRME), a biotechnology Company
committed to delivering a new class of differentiated, one-time
curative genetic therapies, today reported new preclinical data
demonstrating the ability of liver-targeted Prime Editors to
efficiently and precisely correct one of the most prevalent
disease-causing mutations of glycogen storage disease 1b (GSD1b) in
non-human primates (NHP) and mouse models. The data were presented
today at the European Society of Gene and Cell Therapy (ESGCT) 2023
Congress in Brussels, Belgium.
“The data presented today are highly
encouraging, both for patients and caregivers impacted by GSD1b, as
well as for Prime Medicine and the field of gene editing,” said
Jeremy Duffield, M.D., Ph.D., Chief Scientific Officer of Prime
Medicine. “These data are the first Prime Editing data in NHPs and
provide further proof-of-concept for our Prime Editing approach to
potentially address a wide range of diseases, in this case, by
targeting a specific gene with a liver-directed LNP. We have
designed our Prime Editors for GSD1b to correct the two most
prevalent disease-causing mutations of the disease – p.L348fs and
p.G339C – and are highly encouraged by the efficient and precise
corrections we have observed across in vitro evaluations, in vivo
rodent studies and now, NHP studies. Importantly, we continue to
observe minimal to no detectable off-target edits with our Prime
Editors, providing further confidence in the precision of this
technology.”
GSD1b is a rare, serious progressive disease
that causes impaired glycogen metabolism and affects approximately
1,500 patients. It results from mutations in the
glucose-6-phosphate transporter (G6PT), which is encoded by the
gene SLC37A4. Deficiencies in this transporter result in
hypoglycemia, or low blood glucose levels, which can be fatal if
patients do not adhere to a strict dietary regimen, including
consuming slow-release glucose and overnight feeding. P.L348fs and
p.G339C mutations are known to be the most prevalent
disease-causing mutations and are found in approximately 46-52% of
the GSD1b patient population. According to scientific literature
and Prime Medicine research, correcting SLC37A4 gene mutations in
fewer than 10% of liver cells may be sufficient to reverse many
manifestations of this disease.
To address the underlying genetic cause of
GSD1b, Prime Medicine is advancing Prime Editors that are delivered
to the liver by single intravenous infusion and designed to enable
a precise correction of the disease-causing mutations, restoring
G6PT protein expression and glucose homeostasis. The Prime Editors
are composed of a Prime Editor guide RNA (pegRNA) targeting the
respective mutations, a nick-guide RNA (ngRNA) and a messenger RNA
(mRNA) packaged in Prime’s universal lipid nanoparticle (LNP)
formulation that includes a ligand targeting the LNP to
hepatocytes. Through high-throughput screening and subsequent
optimization, Prime researchers identified pegRNAs that precisely
corrected the p.L348fs and p.G339C mutations in liver cells, which
were then evaluated in vitro, demonstrating average editing of 77%
and 37%, respectively.
In today’s presentation at ESGCT, Prime Medicine
highlighted data from in vivo rodent and NHP studies with its Prime
Editor targeting the p.L348fs mutation. Key findings from the
studies showed:
- Up to 50% whole liver precise
editing of p.L348 in NHPs at day 14 without significant on-target
unintended edits. Up to 83% of the key target cells, liver
hepatocytes, were estimated to have both alleles precisely edited
by this single LNP administration.
- Up to 56% whole liver precise
correction of the p.L348fs mutation in a GSD1b humanized mouse
model with on-target unintended editing of less than 0.2% across
dose levels evaluated.
- Prime Editing of up to 44% led to
restored levels of G6PT protein expression of up to 46%, with the
extent of correction directly correlating with the extent of G6PT
protein restoration in the humanized mouse model.
- Redosing of the universal LNP in
non-naïve animals was tolerated similarly to naïve animals with no
infusion reactions, no body weight changes, and transient, modest
liver function changes that resolved by day 7; minimal transient
cytokine abnormalities were observed.
- No detectable off-target edits were
observed in patient-derived induced pluripotent stem cells (iPSCs)
following a comprehensive off-target screening analysis, consistent
with what has been observed to date across Prime Medicine’s
extensive off-target analyses for each of its programs.
These findings provide important
proof-of-concept for Prime Medicine’s LNP liver-targeted delivery
approach, and support the further advancement of the Company’s
Prime Editors targeting the p.L348fs and p.G339C mutations in
GSD1b, as well as its additional liver-targeted programs.
Presentation Details
- Title: OR79. Prime
Editing Precisely Corrects Prevalent Pathogenic Mutations Observed
in Glycogen Storage Disease Type 1b (GSD1b) Patients
- Date & Time:
October 27, 2023
- Session: Gene
Editing: Towards Clinical Trials
- Location:
Brussels, Belgium
About Prime MedicinePrime
Medicine is a leading biotechnology Company dedicated to creating
and delivering the next generation of gene editing therapies to
patients. The Company is leveraging its proprietary Prime Editing
platform, a versatile, precise and efficient gene editing
technology, to develop a new class of differentiated, one-time,
potentially curative genetic therapies. Designed to make only the
right edit at the right position within a gene while minimizing
unwanted DNA modifications, Prime Editors have the potential to
repair almost all types of genetic mutations and work in many
different tissues, organs and cell types.
Prime Medicine is currently progressing a
diversified portfolio of eighteen programs initially focused on
genetic diseases with a fast, direct path to treating patients or
with a high unmet need because they cannot be treated using other
gene-editing approaches. Over time, the Company intends to maximize
Prime Editing’s therapeutic potential and advance potentially
curative therapeutic options to patients for a broad spectrum of
diseases. For more information, please visit
www.primemedicine.com.
Forward Looking StatementsThis
press release contains forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995, as
amended, including, without limitation, implied and express
statements about Prime Medicine’s beliefs and expectations
regarding: the initiation, timing, progress, and results of its
research and development programs, preclinical studies and future
clinical trials, and the release of data related thereto, our
ability to demonstrate additional preclinical data in NHPs that
provide further proof-of-concept for our Prime Editing approach to
address a range of diseases, the potential of Prime Editors to
reproducibly correct disease-causing genetic mutations across
different tissues, organs and cell types, the continued development
and optimization of our universal liver-targeted LNP delivery
approach, the further advancement of Prime Editors to maximize
their versatility, precision and efficiency, and the potential of
Prime Editing to offer curative genetic therapies for a wide
spectrum of diseases. The words “may,” “might,” “will,” “could,”
“would,” “should,” “expect,” “plan,” “anticipate,” “intend,”
“believe,” “expect,” “estimate,” “seek,” “predict,” “future,”
“project,” “potential,” “continue,” “target” and similar words or
expressions are intended to identify forward-looking statements,
although not all forward-looking statements contain these
identifying words.
Any forward-looking statements in this press
release are based on management’s current expectations and beliefs
and are subject to a number of risks, uncertainties and important
factors that may cause actual events or results to differ
materially from those expressed or implied by any forward-looking
statements contained in this press release, including, without
limitation, risks associated with: uncertainties related to the
authorization, initiation, and conduct of preclinical and
IND-enabling studies and other development requirements for
potential product candidates, including uncertainties related to
opening INDs and obtaining regulatory approvals; risks related to
the development and optimization of new technologies, the results
of preclinical studies, or clinical studies not being predictive of
future results in connection with future studies; the scope of
protection Prime Medicine is able to establish and maintain for
intellectual property rights covering its Prime Editing technology;
Prime Medicine’s ability to identify and enter into future license
agreements and collaborations; and general economic, industry and
market conditions, including rising interest rates, inflation, and
adverse developments affecting the financial services industry.
These and other risks and uncertainties are described in greater
detail in the section entitled “Risk Factors” in Prime Medicine’s
most recent Annual Report on Form 10-K, as well as any subsequent
filings with the Securities and Exchange Commission. In addition,
any forward-looking statements represent Prime Medicine’s views
only as of today and should not be relied upon as representing its
views as of any subsequent date. Prime Medicine explicitly
disclaims any obligation to update any forward-looking statements
subject to any obligations under applicable law. No representations
or warranties (expressed or implied) are made about the accuracy of
any such forward-looking statements.
© 2023 Prime Medicine, Inc. All rights reserved.
PRIME MEDICINE, the Prime Medicine logos, and PASSIGE are
trademarks of Prime Medicine, Inc. All other trademarks referred to
herein are the property of their respective owners.
Investor ContactHannah
DeresiewiczStern Investor Relations,
Inc.212-362-1200hannah.deresiewicz@sternir.com
Media ContactDan Budwick,
1ABdan@1ABmedia.com
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