CAMBRIDGE, Mass. and
TARRYTOWN, N.Y., Feb. 28, 2022 /PRNewswire/ --
Achieved 86% and 93% mean serum TTR reduction by day 28 at
0.7 mg/kg and 1.0 mg/kg doses, respectively, with dose-dependent
reductions observed across all four dose levels
Durable serum TTR reductions observed with patient follow-up
ranging from 2 to 12 months
NTLA-2001 was generally well tolerated at all dose
levels
On track to initiate polyneuropathy dose-expansion cohort
(Part 2) in Q1 2022
Intellia to host investor event today, Monday, February 28, at 4:30 p.m. ET
Intellia Therapeutics, Inc. (NASDAQ: NTLA) and Regeneron
Pharmaceuticals, Inc. (NASDAQ: REGN) today announced positive
interim data from an ongoing Phase 1 clinical study of their lead
in vivo genome editing candidate, NTLA-2001, which is being
developed as a single-dose treatment for transthyretin (ATTR)
amyloidosis. The interim data released today include 15 hereditary
ATTR amyloidosis with polyneuropathy (ATTRv-PN) patients treated
across four single-ascending dose cohorts. Single doses of 0.1
mg/kg, 0.3 mg/kg, 0.7 mg/kg, and 1.0 mg/kg of NTLA-2001 were
administered via intravenous infusion and changes from baseline
values of serum transthyretin (TTR) protein were measured for each
patient. Treatment with NTLA-2001 led to dose-dependent reductions
in serum TTR and achieved maximal reductions by day 28, with mean
reductions of 52%, 87%, and 86% among the three patients each in
the 0.1 mg/kg, 0.3 mg/kg, and 0.7 mg/kg dose groups, respectively,
and 93% among the six patients in the 1.0 mg/kg dose group.
Mean serum TTR reduction remained durable through the
observation period, with patient follow-up ranging from two to 12
months. Additionally, the serum TTR reduction observed was
consistent across all patients receiving doses at or greater than
0.3 mg/kg. At the 1.0 mg/kg dose level, all six patients
achieved greater than 80% reduction and four of six patients
achieved greater than 90% reduction by day 28. Further, the
reduction in serum TTR observed at day 28 was sustained through the
last measured timepoint for each of the six patients, which ranged
from two to six months.
"Today's update reinforces Intellia's progress in opening a new
era of medicine. These data suggest that treatment with a one-time,
systemically delivered CRISPR-based investigational therapy has the
potential to substantially reduce levels of a disease-causing
protein. Data from the ongoing, first-in-human study of NTLA-2001
demonstrated rapid, deep and durable reduction of serum TTR
protein. At 1.0 mg/kg, the highest dose level studied, patients
with polyneuropathy reached a 93% mean serum TTR reduction by day
28. We believe this deep and consistent reduction shows promise for
halting and even reversing disease progression in people with ATTR
amyloidosis," said Intellia President and Chief Executive Officer
John Leonard, M.D. "The NTLA-2001
proof-of-concept further validates our CRISPR technology platform
and also supports the continued development of our genome editing
approaches for a variety of diseases. Based on the safety and
activity data generated to date, we believe we have increased the
probability of success for our broader pipeline. Intellia looks
forward to advancing our second in vivo clinical candidate,
NTLA-2002, for the treatment of hereditary angioedema and
additional in vivo candidates in 2022 in our pursuit of
harnessing the full potential of genomic medicines."
NTLA-2001 is the first CRISPR/Cas9-based therapy candidate to be
administered systemically for precision editing of a gene in
humans. It is designed to inactivate the TTR gene in liver
cells to reduce the production of misfolded TTR protein, which
accumulates in tissues throughout the body and causes the
debilitating and often fatal complications of ATTR amyloidosis.
"Our Intellia collaboration continues to move the tremendous
promise of genetics-based medicines closer to reality. Today's data
provide further insights from the first pioneering clinical trial
in which CRISPR-based technology has been used to precisely edit a
disease-causing gene in humans, and the durability results support
the notion that this approach could one day be deployed for
long-lasting benefit," said George D.
Yancopoulos, M.D., Ph.D., President and Chief Scientific
Officer of Regeneron. "Regeneron has always thrived at the
intersection of biology and technology. We continue to expand both
our research efforts through the Regeneron Genetics Center and our
toolkit of cutting-edge technologies for genetics-based
therapeutics, many of which are being developed in collaboration
with Intellia. Genetics medicine holds enormous potential to treat,
and potentially even cure, many life-threatening diseases, and we
look forward to advancing this next chapter of medicine."
At all four dose levels, NTLA-2001 was generally well
tolerated. The majority of adverse events were mild in
severity with 73% (n = 11) of patients reporting a maximal adverse
event severity of Grade 1. The most frequent adverse events
included headache, infusion-related reactions, back pain, rash, and
nausea. There were no clinically significant liver findings
observed. There was a single related serious adverse event of
vomiting (Grade 3) reported in a patient with concomitant medical
history of gastroparesis in the 1.0 mg/kg dose group. Per the study
protocol, the 1.0 mg/kg dose group was subsequently expanded from
three to six patients to further characterize safety at this dose
level. No additional patients in the 1.0 mg/kg dose group reported
a Grade 2 or higher related adverse event. In addition, there was a
single unrelated serious adverse event of COVID-19 pneumonia
reported in the 0.7 mg/kg dose group.
The Phase 1 study, run by Intellia as the program's development
and commercialization lead, is evaluating NTLA-2001 in patients
with ATTRv-PN and ATTR amyloidosis with cardiomyopathy (ATTR-CM).
Part 2 of the Phase 1 study will be a single-dose ATTRv-PN
expansion cohort expected to begin in the first quarter of 2022. A
fixed dose of 80 mg, which is expected to deliver a similar
exposure to the 1.0 mg/kg dose, was selected for evaluation in Part
2 pending regulatory feedback. The transition from weight-based
dosing to fixed dosing is based on the safety, tolerability,
pharmacokinetic and activity profile of NTLA-2001 observed in Part
1 of the polyneuropathy arm. Patients also continue to be dosed
with NTLA-2001 in Part 1 of the cardiomyopathy arm at the 0.7 mg/kg
dose level, with plans to dose escalate to 1.0 mg/kg.
Intellia expects to complete enrollment of the Phase 1 study for
both ATTRv-PN and ATTR-CM subjects in 2022 and present additional
data at a medical meeting later this year. Intellia and Regeneron
plan to move towards pivotal studies for both forms of ATTR
amyloidosis, with an initial focus on the cardiomyopathy
manifestations of the disease.
"In this Phase 1 study, NTLA-2001 was generally well tolerated
as a single-dose treatment for ATTR amyloidosis patients with
polyneuropathy, resulting in deep and durable reductions of serum
TTR. These observations are consistent with animal data indicating
potential life-long serum TTR suppression," said Ed Gane, M.D., Professor of Medicine at the
University of Auckland, New
Zealand and Chief Hepatologist, Transplant Physician and
Deputy Director of the New Zealand Liver Transplant Unit at
Auckland City Hospital, and study investigator. "Importantly, these
early results suggest NTLA-2001 has the potential to deliver
profound benefits for patients around the world."
Intellia Therapeutics Investor Event and Webcast
Information
Intellia will host a live webcast today, Monday, February 28, 2022, at 4:30 p.m. ET to review today's data. To join the
webcast, please visit this link or the Events and
Presentations page of the Investors & Media section of the
company's website at www.intelliatx.com. A replay of the webcast
will be available on Intellia's website for at least 30 days
following the call.
About Transthyretin (ATTR) Amyloidosis
Transthyretin amyloidosis, or ATTR amyloidosis, is a rare,
progressive and fatal disease. Hereditary ATTR (ATTRv) amyloidosis
occurs when a person is born with mutations in the TTR gene,
which causes the liver to produce structurally abnormal
transthyretin (TTR) protein with a propensity to misfold. These
damaged proteins build up as amyloid in the body, causing serious
complications in multiple tissues, including the heart, nerves and
digestive system. ATTRv amyloidosis predominantly manifests as
polyneuropathy (ATTRv-PN), which can lead to nerve damage, or
cardiomyopathy (ATTRv-CM), which can lead to heart failure. Some
individuals without the genetic mutation produce non-mutated, or
wild-type TTR proteins that become unstable over time, misfolding
and aggregating in disease-causing amyloid deposits. This
condition, called wild-type ATTR (ATTRwt) amyloidosis, primarily
affects the heart. There are an estimated 50,000 people worldwide
living with ATTRv amyloidosis and between 200,000 and 500,000
people with ATTRwt amyloidosis.
About NTLA-2001
Based on Nobel Prize-winning CRISPR/Cas9 technology, NTLA-2001
could potentially be the first single-dose treatment for ATTR
amyloidosis. NTLA-2001 is the first investigational CRISPR therapy
candidate to be administered systemically, or through a vein, to
edit genes inside the human body. Intellia's proprietary non-viral
platform deploys lipid nanoparticles to deliver to the liver a
two-part genome editing system: guide RNA specific to the
disease-causing gene and messenger RNA that encodes the Cas9
enzyme, which carries out the precision editing. Robust preclinical
data, showing deep and long-lasting transthyretin (TTR) reduction
following in vivo inactivation of the target gene, supports
NTLA-2001's potential as a single-administration therapeutic.
Intellia leads development and commercialization of NTLA-2001 as
part of a multi-target discovery, development and commercialization
collaboration with Regeneron. The global Phase 1 trial is an
open-label, multi-center, two-part study of NTLA-2001 in adults
with hereditary transthyretin amyloidosis with polyneuropathy
(ATTRv-PN) or transthyretin amyloidosis with cardiomyopathy
(ATTR-CM). Visit clinicaltrials.gov (NCT04601051) for more
details.
About Regeneron
Regeneron (NASDAQ: REGN) is a leading
biotechnology company that invents life-transforming medicines for
people with serious diseases. Founded and led for over 30 years by
physician-scientists, our unique ability to repeatedly and
consistently translate science into medicine has led to nine
FDA-approved treatments and numerous product candidates in
development, almost all of which were homegrown in our
laboratories. Our medicines and pipeline are designed to help
patients with eye diseases, allergic and inflammatory diseases,
cancer, cardiovascular and metabolic diseases, pain, hematologic
conditions, infectious diseases and rare diseases.
Regeneron is accelerating and improving the traditional drug
development process through our proprietary
VelociSuite® technologies, such as
VelocImmune®, which uses unique genetically
humanized mice to produce optimized fully human antibodies and
bispecific antibodies, and through ambitious research initiatives
such as the Regeneron Genetics Center®, which is
conducting one of the largest genetics sequencing efforts in the
world.
For additional information about the company, please visit
www.regeneron.com or follow @Regeneron on Twitter.
About Intellia Therapeutics
Intellia Therapeutics, a
leading clinical-stage genome editing company, is developing novel,
potentially curative therapeutics leveraging CRISPR-based
technologies. To fully realize the transformative potential of
CRISPR-based technologies, Intellia is pursuing two primary
approaches. The company's in vivo programs use intravenously
administered CRISPR as the therapy, in which proprietary delivery
technology enables highly precise editing of disease-causing genes
directly within specific target tissues. Intellia's ex vivo
programs use CRISPR to create the therapy by using engineered human
cells to treat cancer and autoimmune diseases. Intellia's deep
scientific, technical and clinical development experience, along
with its robust intellectual property portfolio, have enabled the
company to take a leadership role in harnessing the full potential
of genome editing to create new classes of genetic medicine. Learn
more at intelliatx.com. Follow us on
Twitter @intelliatx.
Regeneron Forward-looking Statements and Use of Digital
Media
This press release includes forward-looking statements that
involve risks and uncertainties relating to future events and the
future performance of Regeneron Pharmaceuticals, Inc. ("Regeneron"
or the "Company"), and actual events or results may differ
materially from these forward-looking statements. Words such as
"anticipate," "expect," "intend," "plan," "believe," "seek,"
"estimate," variations of such words, and similar expressions are
intended to identify such forward-looking statements, although not
all forward-looking statements contain these identifying words.
These statements concern, and these risks and uncertainties
include, among others, the impact of SARS-CoV-2 (the virus that has
caused the COVID-19 pandemic) on Regeneron's business and its
employees, collaborators, and suppliers and other third parties on
which Regeneron relies, Regeneron's and its collaborators' ability
to continue to conduct research and clinical programs, Regeneron's
ability to manage its supply chain, net product sales of products
marketed or otherwise commercialized by Regeneron and/or its
collaborators or licensees (collectively, "Regeneron's Products"),
and the global economy; the nature, timing, and possible success
and therapeutic applications of Regeneron's Products and product
candidates being developed by Regeneron and/or its collaborators or
licensees (collectively, "Regeneron's Product Candidates") and
research and clinical programs now underway or planned, such as
NTLA-2001 (a product candidate being developed for transthyretin
(ATTR) amyloidosis under a multi-target discovery, development, and
commercialization collaboration between Regeneron and Intellia
Therapeutics, Inc.); the extent to which the results from the
research and development programs conducted by Regeneron and/or its
collaborators or licensees (including the Phase 1 clinical study
evaluating NTLA-2001 discussed in this press release) may be
replicated in other studies and/or lead to advancement of product
candidates to clinical trials, therapeutic applications, or
regulatory approval; the potential of the CRISPR/Cas9 gene-editing
technology discussed in this press release for in vivo therapeutic
development; uncertainty of the utilization, market acceptance, and
commercial success of Regeneron's Products and Regeneron's Product
Candidates and the impact of studies (whether conducted by
Regeneron or others and whether mandated or voluntary), including
the Phase 1 clinical study evaluating NTLA-2001 discussed in this
press release, on any of the foregoing or any potential regulatory
approval of Regeneron's Products and Regeneron's Product Candidates
(such as NTLA-2001); the likelihood, timing, and scope of possible
regulatory approval and commercial launch of Regeneron's Product
Candidates and new indications for Regeneron's Products; the
ability of Regeneron's collaborators, licensees, suppliers, or
other third parties (as applicable) to perform manufacturing,
filling, finishing, packaging, labeling, distribution, and other
steps related to Regeneron's Products and Regeneron's Product
Candidates; the ability of Regeneron and/or its collaborators to
manufacture and manage supply chains for multiple products and
product candidates; safety issues resulting from the administration
of Regeneron's Products and Regeneron's Product Candidates in
patients, including serious complications or side effects in
connection with the use of Regeneron's Products and Regeneron's
Product Candidates (such as NTLA-2001) in clinical trials;
determinations by regulatory and administrative governmental
authorities which may delay or restrict Regeneron's ability to
continue to develop or commercialize Regeneron's Products and
Regeneron's Product Candidates; ongoing regulatory obligations and
oversight impacting Regeneron's Products, research and clinical
programs, and business, including those relating to patient
privacy; the availability and extent of reimbursement of
Regeneron's Products from third-party payers, including private
payer healthcare and insurance programs, health maintenance
organizations, pharmacy benefit management companies, and
government programs such as Medicare and Medicaid; coverage and
reimbursement determinations by such payers and new policies and
procedures adopted by such payers; competing drugs and product
candidates that may be superior to, or more cost effective than,
Regeneron's Products and Regeneron's Product Candidates;
unanticipated expenses; the costs of developing, producing, and
selling products; the ability of Regeneron to meet any of its
financial projections or guidance and changes to the assumptions
underlying those projections or guidance; the potential for any
license, collaboration, or supply agreement, including Regeneron's
agreements with Sanofi, Bayer, and Teva Pharmaceutical Industries
Ltd. (or their respective affiliated companies, as applicable), as
well as Regeneron's collaboration with Intellia Therapeutics, Inc.
discussed in this press release, to be cancelled or terminated; and
risks associated with intellectual property of other parties and
pending or future litigation relating thereto (including without
limitation the patent litigation and other related proceedings
relating to EYLEA® (aflibercept) Injection,
Dupixent® (dupilumab), Praluent®
(alirocumab), and REGEN-COV® (casirivimab and
imdevimab)), other litigation and other proceedings and government
investigations relating to the Company and/or its operations, the
ultimate outcome of any such proceedings and investigations, and
the impact any of the foregoing may have on Regeneron's business,
prospects, operating results, and financial condition. A more
complete description of these and other material risks can be found
in Regeneron's filings with the U.S. Securities and Exchange
Commission, including its Form 10-K for the year ended December 31, 2021. Any forward-looking statements
are made based on management's current beliefs and judgment, and
the reader is cautioned not to rely on any forward-looking
statements made by Regeneron. Regeneron does not undertake any
obligation to update (publicly or otherwise) any forward-looking
statement, including without limitation any financial projection or
guidance, whether as a result of new information, future events, or
otherwise.
Regeneron uses its media and investor relations website and
social media outlets to publish important information about the
Company, including information that may be deemed material to
investors. Financial and other information about Regeneron is
routinely posted and is accessible on Regeneron's media and
investor relations website (http://newsroom.regeneron.com) and its
Twitter feed (http://twitter.com/regeneron).
Intellia Forward-looking Statements
This press release contains "forward-looking statements" of
Intellia Therapeutics, Inc. ("Intellia", "we" or "our") 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 beliefs and
expectations regarding the safety, efficacy and advancement of our
clinical program for NTLA-2001 for the treatment of ATTR
amyloidosis, including the ability of NTLA-2001 to halt and reverse
disease progression in people with ATTR amyloidosis, the expected
timing of data releases, regulatory filings, and the initiation and
completion of clinical trials; our ability to successfully secure
additional clinical studies authorizations, such as investigational
new drug applications ("IND") and clinical trial applications
("CTA"); our belief that NTLA-2001 can be approved as a single-dose
therapy; our plans to present data at upcoming scientific
conferences; the advancement, expansion, acceleration and success
of our CRISPR/Cas9 technology and in vivo pipeline to develop
breakthrough genome editing treatments for people living with
severe diseases; ability to demonstrate our platform's modularity
and replicate or apply results achieved in preclinical studies,
including those in our ATTR program, in any future studies,
including human clinical trials for NTLA-2002 for the treatment of
hereditary angioedema; our ability to optimize the impact of our
collaborations on our development programs, including but not
limited to our collaboration with Regeneron Pharmaceuticals, Inc.
("Regeneron"); statements regarding the timing of regulatory
filings and clinical trial execution, including dosing of patients,
regarding our development programs; and potential commercial
opportunities, including value and market, for our product
candidates.
Any forward-looking statements in this press release 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 our ability to protect and maintain our
intellectual property position; risks related to our relationship
with third parties, including our licensors and licensees; risks
related to the ability of our licensors to protect and maintain
their intellectual property position; uncertainties related to
regulatory agencies' evaluation of regulatory filings and other
information related to our product candidates; uncertainties
related to the authorization, initiation and conduct of studies and
other development requirements for our product candidates; the risk
that any one or more of our product candidates, including those
that are co-developed, will not be successfully developed and
commercialized; the risk that the results of preclinical studies or
clinical studies will not be predictive of future results in
connection with future studies; and the risk that our
collaborations with Regeneron or our other 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 report on Form 10-Q, as well as discussions
of potential risks, uncertainties, and other important factors in
Intellia's other filings with the Securities and Exchange
Commission ("SEC"). All information in this press release is as of
the date of the release, and Intellia undertakes no duty to update
this information unless required by law.
Regeneron
Contacts:
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|
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Media
Relations
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Investor
Relations
|
Alexandra
Bowie
|
Vesna
Tosic
|
+1-202-213-1643
|
Tel: +1
914-847-5443
|
alexandra.bowie@regeneron.com
|
Vesna.Tosic@regeneron.com
|
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Intellia
Contacts:
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Media
Relations
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Investor
Relations
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Matt
Crenson
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Ian
Karp
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Ten Bridge
Communications
+1-917-640-7930
|
Senior Vice
President, Investor Relations
and Corporate Communications
|
media@intelliatx.com
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+1-857-449-4175
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mcrenson@tenbridgecommunications.com
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ian.karp@intelliatx.com
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Lina
Li
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Director, Investor
Relations
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+1-857-706-1612
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lina.li@intelliatx.com
|
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SOURCE Regeneron Pharmaceuticals, Inc.