Intellia scientists present first robust
demonstration of CRISPR-mediated insertion of transgenes in
the liver
Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading genome editing
company focused on developing curative therapeutics using
CRISPR/Cas9 technology both in vivo and ex vivo, presented new data
from three of its programs, including the company’s first data on
complex edits, at the 26th Annual Congress of the European Society
of Gene and Cell Therapy (ESGCT), in Lausanne, Switzerland.
“We are extremely pleased to present an outstanding compilation
of data today reflecting progress in our preclinical genome editing
programs,” said Intellia President and Chief Executive Officer John
Leonard, M.D. “We showed that we can efficiently introduce complex
edits in mice by inserting genes to express proteins that are
deficient in some genetic diseases. By using our LNP delivery
system in combination with AAV to deliver template DNA, we are
opening the door for the development of therapies for a wide range
of genetic diseases that require stable gene insertion and
expression. In parallel, we are driving forward our ex vivo
programs and other in vivo programs. Our researchers are gaining
further insights into our ATTR program through our ongoing NHP
studies, as well as working with our collaborators at Ospedale San
Raffaele (OSR) to make excellent progress in our quest to advance
the next generation of engineered cell therapy.”
CRISPR-mediated, Targeted Gene Insertion
Data
In a collaboration between Intellia and Regeneron
Pharmaceuticals, Inc., researchers combined Intellia’s modular
lipid nanoparticle (LNP) delivery system of CRISPR/Cas9 with a
modular adeno-associated viral (AAV) insertion template to achieve
supratherapeutic levels (levels higher than those required in a
clinical setting) of gene expression in mice. Using Factor 9 (F9)
as a model gene, the team demonstrated the first robust, efficient
CRISPR-mediated targeted insertion into the liver. F9 is a gene
that encodes Factor IX (FIX), a blood-clotting protein that is
often missing or defective in hemophilia B patients.
Using Intellia’s proprietary bi-directional template,
researchers detected hybrid mAlb-hF9 transcripts in >50 percent
of hepatocytes following a single dose. Circulating human FIX
protein levels of >30,000 ng/mL were achieved, which are
predicted to correspond to levels 40-300 times higher than those
capable of preventing bleeding episodes in hemophilia B patients,
when using a wildtype or hyperfunctional version of F9 (sources:
George, et al, NEJM, 2017; Simioni et al, NEJM, 2009). Researchers
were able to vary FIX levels by modulating either the LNP or the
AAV dose, and expression levels remained stable and ongoing in all
cases throughout 12 weeks of observation.
This approach was repeated with Intellia’s wholly owned
preclinical in vivo program in alpha-1 antitrypsin deficiency
(AATD), another genetic disease of the liver associated with a
mutation in the SERPINA1 gene that causes liver and lung
dysfunction. Researchers used the LNP-AAV delivery combination of
CRISPR/Cas9 components to insert donor template DNA encoding the
SERPINA1 gene for AATD. The insertion resulted in blood protein
levels in mice that corresponded to a range of SERPINA1 systemic
levels required for normal lung function in humans.
Today’s presentation, titled “Supra-therapeutic levels of
transgene expression achieved in vivo by CRISPR/Cas9 mediated
targeted gene insertion,” was made by Jonathan Finn, Ph.D.,
executive director, platform biology, Intellia. This presentation
will be accessible through the Events and Presentations page of the
Investor Relations section of Intellia’s website at
www.intelliatx.com.
New Non-Human Primate Data from Intellia’s ATTR
Program
Intellia also presented new data from non-human primate (NHP)
studies in its transthyretin amyloidosis (ATTR) program further
demonstrating a high correlation between liver editing and
reduction of the transthyretin (TTR) protein. ATTR is a systemic,
debilitating and fatal disease caused by one of approximately 136
different inherited mutations in the TTR gene. The
company found that a liver editing rate of only ~35-40 percent in
NHPs is needed to achieve a therapeutically meaningful reduction of
TTR, specifically a TTR protein reduction of >60 percent. The
data also demonstrated the transient nature of Intellia’s
proprietary modular LNP delivery system, which was rapidly cleared
from circulation, with all CRISPR/Cas9 components undetectable
within five days of administration. Furthermore, rates of editing
were durable over a six-month period without re-dosing the
animals.
These data included results from ongoing collaborations with
researchers at Regeneron and the University of Porto in Portugal,
where ATTR is endemic in certain populations. Today’s presentation,
titled “Delivering on the therapeutic potential of CRISPR/Cas9:
Development of an LNP-mediated genome editing therapeutic for the
treatment of ATTR,” was made by Yong Chang, Ph.D., vice president,
safety pharmacology, Intellia. This presentation will be accessible
through the Events and Presentations page of the Investor Relations
section of Intellia’s website at www.intelliatx.com.
Data Update from Intellia’s Acute Myeloid Leukemia
Program
In a presentation titled “Hunting novel WT1-specific T cell
receptors for immune gene therapy of acute myeloid leukemia,”
Intellia and its research collaborator, OSR, led by Chiara Bonini,
M.D., Ph.D., deputy director of the Division of Immunology,
Transplantation and Infectious Diseases at San Raffaele Hospital
and University, shared an update on the company’s lead ex vivo
program in acute myeloid leukemia (AML). Researchers presented in
vitro data showing that CRISPR/Cas9 editing resulted in over 90
percent knockout of endogenous T cell receptors (TCRs). Subsequent
transduction of Wilms’ Tumor 1 (WT1)-specific transgenic TCRs led
to high expression of the inserted TCR with over 95 percent purity
in isolated cytotoxic T cells (CD8+ T cells). T cells were fully
functional and specifically killed leukemic blast cells that
expressed the WT1 antigen and HLA-A*02:01 allele. Several
additional TCRs directed to multiple WT1 epitopes and human
leukocyte antigen (HLA) alleles are under investigation, including
undergoing in vitro and in vivo functional testing.
Intellia and OSR are collaborating to develop best-in-class
CRISPR-edited T cells directed to a specific epitope of WT1, a
tumor-associated antigen overexpressed across a wide range of
different tumor types and a known driver of leukocyte blasts in
hematological cancers. Intellia’s first cell therapy tumor target
is WT1 for the treatment of AML and other potential hematological
malignancies, as well as for solid tumors.
About Intellia Therapeutics
Intellia Therapeutics is a leading genome editing company
focused on developing proprietary, curative therapeutics using the
CRISPR/Cas9 system. Intellia believes the CRISPR/Cas9 technology
has the potential to transform medicine by permanently editing
disease-associated genes in the human body with a single treatment
course, and through improved cell therapies that can treat cancer
and immunological diseases by replacing patients’ diseased cells.
The combination of deep scientific, technical and clinical
development experience, along with its leading intellectual
property portfolio, puts Intellia in a unique position to unlock
broad therapeutic applications of the CRISPR/Cas9 technology and
create a new class of therapeutic products. Learn more about
Intellia Therapeutics and CRISPR/Cas9 at intelliatx.com and follow
us on Twitter @intelliatweets.
Forward-Looking Statements
This press release contains “forward-looking statements” of
Intellia Therapeutics, Inc. (“Intellia”) within the meaning of the
Private Securities Litigation Reform Act of 1995. These
forward-looking statements include, but are not limited to, express
or implied statements regarding Intellia’s ability to advance and
expand the CRISPR/Cas9 technology to develop into human therapeutic
products, as well as our CRISPR/Cas9 intellectual property
portfolio; our ability to achieve stable or effective genome
editing; our ability to administer multiple doses of our
CRISPR/Cas9 product candidates; the potential timing and
advancement of our preclinical studies, including continuing
non-human primate studies for our Transthyretin Amyloidosis
(“ATTR”) program and other programs (such as alpha-1 antitrypsin
deficiency (AATD)), and clinical trials; the timing and potential
achievement of milestones to advance our pipeline; our ability to
replicate results achieved in our preclinical studies, including
those in our ATTR, AATD and Wilms’ Tumor 1 (WT1) programs, in any
future studies, including human clinical trials; the potential
development of other in vivo or ex vivo cell therapeutics
of all types, and those targeting WT1 in particular, using
CRISPR/Cas9 technology; our ability to continue to conduct
successful Investigational New Drug (“IND”) enabling studies of a
lead ATTR development candidate and subsequently submitting an IND
application by the end of 2019 that will be accepted by the
regulatory agencies; our intent to present additional data for
organs beyond the liver, additional insertion/repair data, and
preclinical data in support of our first ex vivo programs
on immuno-oncology and autoimmune/inflammation indications during
2018; the expansion of our fully automated bioinformatics platform;
our ability to advance a development candidate for a second
indication by late 2018; our potential ability to conduct a pre-IND
meeting with the U.S. Food and Drug Administration
(“FDA”) for ATTR; the intellectual property position and
strategy of Intellia’s licensors or other parties from which it
derives rights; actions by government agencies; the impact of our
collaborations on our development programs; the potential timing of
regulatory filings regarding our development programs; the
potential commercialization opportunities, including value and
market, for product candidates; our expectations regarding our uses
of capital, expenses, future accumulated deficit and other 2018
financial results; and our ability to fund operations through
mid-2020.
Any forward-looking statements in this presentation are based on
management’s current expectations and beliefs of future events, 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. These risks
and uncertainties include, but are not limited to: risks related to
Intellia’s ability to protect and maintain our intellectual
property position; risks related to the ability of our licensors to
protect and maintain their intellectual property position;
uncertainties related to the initiation and conduct of studies and
other development requirements for our product candidates; the risk
that any one or more of Intellia’s product candidates will not be
successfully developed and commercialized; the risk that the
results of preclinical studies will not be predictive of future
results in connection with future studies; and the risk that
Intellia’s collaborations with Novartis or Regeneron or
its other ex vivo collaborations will not continue or will not
be successful. For a discussion of these and other risks and
uncertainties, and other important factors, any of which could
cause Intellia’s actual results to differ from those contained in
the forward-looking statements, see the section entitled “Risk
Factors” in Intellia’s most recent annual report on Form 10-K and
quarterly reports on Form 10-Q filed with the Securities and
Exchange Commission, as well as discussions of potential risks,
uncertainties, and other important factors in Intellia’s other
filings with the Securities and Exchange Commission. All
information in this presentation is as of the date of the release,
and Intellia Therapeutics undertakes no duty to update
this information unless required by law.
Intellia Contacts:
Media:Jennifer Mound SmoterSenior Vice
PresidentExternal Affairs & Communications+1
857-706-1071jenn.smoter@intelliatx.com
Lynnea OlivarezAssociate DirectorExternal Affairs &
Communications+1 956-330-1917lynnea.olivarez@intelliatx.com
Investors:Lindsey TrickettVice
PresidentInvestor Relations+1
857-285-6211lindsey.trickett@intelliatx.com
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