Item 7.01 Regulation FD Disclosure.
On September 16, 2022, Intellia Therapeutics, Inc. (the “Company” or “Intellia”)
issued a press release titled “Intellia and Regeneron Announce Initial Data from
the Cardiomyopathy Arm of Ongoing Phase 1 Study of NTLA-2001, an Investigational
CRISPR Therapy for the Treatment of Transthyretin (ATTR) Amyloidosis”. A copy of
the press release is furnished as Exhibit 99.1 to this Current Report on Form
8-K and is incorporated herein by reference.
On September 16, 2022, Intellia issued a press release titled “Intellia
Therapeutics Announces Positive Interim Clinical Data for its Second
Systemically Delivered Investigational CRISPR Candidate, NTLA-2002 for the
Treatment of Hereditary Angioedema (HAE).” A copy of the press release is
furnished as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated
herein by reference.
The information under this Item 7.01, including Exhibit 99.1 and Exhibit 99.2
hereto, are being furnished herewith and shall not be deemed “filed” for the
purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the
“Exchange Act”), or otherwise subject to the liabilities of that section, nor
shall such information be deemed incorporated by reference into any filing under
the Securities Act of 1933, as amended, or the Exchange Act, except as expressly
set forth by specific reference in such filing.
Item 8.01 Other Events.
Interim Clinical Data of NTLA-2001
On September 16, 2022, the Company announced, together with Regeneron
Pharmaceuticals, Inc. (“Regeneron”), additional positive interim results from an
ongoing Phase 1 clinical trial of NTLA-2001. The interim data include 12 adult
patients with ATTR amyloidosis with cardiomyopathy (“ATTR-CM”) with New York
Heart Association (NYHA) Class I – III heart failure. Single doses of 0.7 mg/kg
and 1.0 mg/kg of NTLA-2001 were administered via intravenous infusion, and the
change from baseline in serum transthyretin (“TTR”) protein concentration was
measured for each patient.
Administration of NTLA-2001 led to rapid and deep reductions in serum TTR by day
28 as follows:
Mean (min, max) % serum TTR reduction Cohort by day 28
0.7 mg/kg, NYHA Class I/II (n=3)* 92% (91%, 95%)
0.7 mg/kg, NYHA Class III (n=6)*
94% (91%, 97%) 1.0 mg/kg, NYHA Class I/II (n=3) 92% (90%, 95%)
* Mean (min, max) % serum TTR reduction by day 28 for 0.7 mg/kg cohort (n=9) was
93% (91%, 97%).
These profound reductions in serum TTR were sustained throughout the observation
period, with patient follow-up ranging from two to six months as of the data
cut-off date of July 1, 2022. The Company believes these data support
NTLA-2001’s potential as a one-time treatment to permanently inactivate the TTR
gene and reduce the disease-causing protein in people with ATTR-CM.
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.
At both dose levels, NTLA-2001 was generally well tolerated. Two of 12 patients
reported transient infusion reactions, which was the only observed
treatment-related adverse event. One patient in the 0.7 mg/kg dose NYHA
Class III cohort experienced a Grade 3 infusion-related reaction, which resolved
without clinical consequence. Per the study protocol, this group was
subsequently expanded from three to six patients to further characterize safety
at this dose level. No additional patients in the 0.7 mg/kg dose NYHA Class III
cohort reported a treatment-related adverse event. No clinically significant
liver findings were observed at either dose level.
The Phase 1 study, run by the Company as the program’s development and
commercialization lead as part of a multi-target collaboration with Regeneron,
is evaluating NTLA-2001 in patients with either ATTR-CM or hereditary ATTR
amyloidosis with polyneuropathy (“ATTRv-PN”). A protocol amendment has been
submitted to evaluate a fixed dose corresponding to 0.7 mg/kg in the
dose-expansion portion, with enrollment across both arms expected to be
completed by the end of 2022, subject to regulatory feedback.
Interim Clinical Data of NTLA-2002
On September 16, 2022, at the 2022 Bradykinin Symposium, the Company presented
positive interim results from an ongoing Phase 1/2 clinical study of our second
in vivo genome editing candidate, NTLA-2002, which is being developed as a
single-dose treatment for hereditary angioedema (“HAE”). The interim data
presented are from the initial six adult patients with HAE treated in the
ongoing dose-escalation study with a data cut-off date of July 27, 2022. Single
doses of 25 mg (n=3) and 75 mg (n=3) of NTLA-2002 were administered via
intravenous infusion, and changes from baseline values of plasma kallikrein
protein were measured for each patient. Administration of NTLA-2002 led to
dose-dependent reductions in plasma kallikrein and achieved maximal reductions
by week eight, with mean reductions of 65% and 92% in the 25 mg and 75 mg dose
cohorts, respectively. Furthermore, these reductions have been sustained through
at least 16 weeks in the 25 mg cohort and 8 weeks in the 75 mg cohort for which
complete cohort biomarker data were available.
In addition to plasma kallikrein levels, HAE attack rates are also being
measured in the study, with the first analysis occurring at the end of the
pre-specified 16-week primary observation period. To date, all three patients in
the 25 mg dose cohort have reached the end of this initial observation period.
Patients in this group had a baseline HAE attack rate ranging from 1.1 to 7.2
attacks per month, as confirmed by the investigator. Treatment with a single
dose of 25 mg of NTLA-2002 resulted in a mean reduction in HAE attacks of 91%
throughout the 16-week observation period. Additionally, two of the three
patients have not had a single HAE attack since treatment, and all three
patients have been attack free since week 10 (follow-up through weeks 24 – 32).
Patients in the 75 mg cohort have not completed the primary 16-week observation
period, and attack rate data for this cohort will be presented at the American
College of Allergy, Asthma & Immunology Annual Scientific Meeting, November 10
-14 in Louisville, Kentucky.
Prophylaxis medications are permitted in the Phase 1 part of the study. Two of
the three patients in the 25 mg cohort were actively receiving prophylaxis
therapy prior to administration of NTLA-2002. For these two patients, the study
protocol permitted investigators to withdraw the patient’s prophylaxis therapy
after completion of the 16-week primary observation period. This treatment
approach was implemented for the two applicable patients in this cohort, and
neither patient has had an HAE attack since discontinuing their prophylaxis
therapy through the latest follow-up.
At both dose levels, NTLA-2002 was generally well tolerated, and the majority of
adverse events were mild in severity. The most frequent adverse events were
infusion-related reactions, which were mostly Grade 1 and resolved within one
day. There have been no dose-limiting toxicities, no serious adverse events and
no adverse events of Grade 3 or higher observed to date. No clinically
significant laboratory abnormalities were observed, including any significant
elevation in liver enzymes.
Based on the interim data presented in September 2022, the Company selected a
third dose of 50 mg to be evaluated in the ongoing dose-escalation portion of
the Phase 1/2 study. Dosing at this level has recently been completed and the
Company expects to select up to two doses to further evaluate in the Phase 2,
placebo-controlled dose expansion portion of the study, which is expected to
begin in the first half of 2023. The Company anticipates expanding country and
site participation, including U.S. clinical sites, as part of the Phase 2 study.
NTLA-2002 is designed to inactivate the KLKB1 gene in liver cells. By targeting
the KLKB1 gene, NTLA-2002 reduces the production of kallikrein protein, whose
uncontrolled activity is responsible for the overproduction of bradykinin, which
leads to the recurring, debilitating and potentially fatal swelling attacks that
occur in people living with HAE.
Forward Looking Statements
This Current Report on Form 8-K and certain of the materials furnished or filed
herewith contain forward-looking statements within the meaning of the Private
Securities Litigation Reform Act of 1995, as amended. The words “may,” “will,”
“could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,”
“estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar
expressions are intended to identify forward-looking statements, although not
all forward-looking statements contain these identifying words. These
forward-looking statements include, but are not limited to, express or implied
statements regarding Intellia’s beliefs and expectations regarding its: ability
to enroll and dose the necessary subjects in the clinical studies for NTLA-2001
for the treatment of ATTR amyloidosis and NTLA-2002 for the treatment of HAE;
provide timing on data readouts from the clinical studies, and successfully
secure additional clinical studies authorizations, such as investigational new
drug applications (“IND”) and CTA, in other countries; ability to evaluate
NTLA-2001 in a broader ATTR amyloidosis population; expectation that clinical
results will support NTLA-2001’s safety and activity profile; belief that
NTLA-2001 can be approved as a single-dose therapy or that it can halt and
potentially reverse ATTR amyloidosis progression; ability to evaluate NTLA-2002
in a broader HAE population advancement, expansion and acceleration of our
CRISPR/Cas9 technology and in vivo pipeline to develop breakthrough genome
editing treatments for people living with severe diseases; ability to optimize
the impact of our collaborations on our development programs, including but not
limited to our collaboration with Regeneron; and statements regarding the timing
of regulatory filings and clinical trial execution, including enrollment and
dosing of patients, and regarding our development programs.
Any forward-looking statements 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, including, without
limitation, uncertainties related to market conditions as well as on the timing
and anticipated results of its clinical trials, strategy and future operations;
the delay of any current or planned clinical trials or the development of the
Company’s drug candidates; the risk that the results of its clinical trials may
not be predictive of future results in connection with future clinical trials;
the Company’s ability to successfully demonstrate the safety and efficacy of its
drug candidates; the timing and outcome of its planned interactions with
regulatory authorities; and obtaining, maintaining and protecting its
intellectual property. These and other risks and uncertainties are described in
greater detail in the section entitled “Risk Factors” in Intellia’s most recent
annual report on Form 10-K and quarterly report on Form 10-Q filed with the U.S
Securities and Exchange Commission (“SEC”), as well as discussions of potential
risks, uncertainties, and other important factors in Intellia’s other filings
with the SEC, including those contained or incorporated by reference. Any
forward-looking statements represent Intellia’s views only as of the date hereof
and should not be relied upon as representing its views as of any subsequent
date. Intellia explicitly disclaims any obligation to update any forward-looking
statements, except as required by law.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits. Exhibit No. Description 99.1 Press release, dated September 16, 2022 99.2 Press release, dated September 16, 2022 104 104 Cover Page Interactive Data File (embedded within the Inline XBRL document).
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