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
Interim data from the cardiomyopathy arm of the Phase 1 study of NTLA-2001 showed deep and sustained mean serum transthyretin (TTR) reductions of 93% and 92% at 0.7 mg/kg and 1.0 mg/kg doses, respectively, at day 28
NTLA-2001 was generally well-tolerated at both dose levels
Intellia to discuss data at investor event today,
Mean (min, max) % serum TTR reduction 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
"ATTR amyloidosis is a multifaceted disease in need of additional treatment options. These new interim results demonstrate that NTLA-2001 can profoundly reduce serum TTR levels in patients whose condition results in cardiomyopathy," said Intellia President and Chief Executive Officer
"We're encouraged to see profound and sustained serum TTR reductions in people with cardiomyopathy manifestations of this rare and fatal disease, further bolstering the prospects for a one-time, in vivo treatment for multiple ATTR patient groups," said
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 Intellia 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.
In a separate press release issued earlier today, Intellia announced positive interim clinical data from an ongoing Phase 1/2 clinical study of NTLA-2002, its second in vivo genome editing candidate, for the treatment of hereditary angioedema (HAE). Please visit this link, or the Press Releases section of the company's website at www.intelliatx.com.
Intellia will host a live webcast today,
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.
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.
Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents life-transforming medicines for people with serious diseases. Founded and led for nearly 35 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.
This press release contains "forward-looking statements" of
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 the successful enrollment of patients in the Phase 1 study for NTLA-2001 for the treatment of ATTRv-PN or ATTR-CM; risks related to Intellia's ability to protect and maintain its intellectual property position; risks related to the authorization, initiation and conduct of studies and other development requirements, including manufacturing, for its in vivo and ex vivo product candidates, including NTLA-2001; the risk that any one or more of Intellia's product candidates, including NTLA-2001, will not be successfully developed and commercialized; the risk that the results of preclinical studies or clinical studies, including for NTLA-2001, will not be predictive of future results in connection with future studies; and the risk that Intellia's will not be able to demonstrate its platform's modularity and replicate or apply results achieved in preclinical studies to develop additional product candidates, including to apply its proprietary CRISPR/Cas9 technology platform successfully to additional product candidates. 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 of Form 10-Q, as well as discussions of potential risks, uncertainties and other important factors in Intellia's other filings with the
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