Intellia and Regeneron Present Updated Interim Data from Phase 1 Study of CRISPR-based NTLA-2001 for the Treatment of Transthyretin (ATTR) Amyloidosis Demonstrating that Deep Serum TTR Reductions Remained Durable After a Single DoseIntellia and Regeneron

  • Serum TTR reductions were sustained at all doses tested with follow-up now reaching 12 months in the 0.1 and 0.3 mg/kg and six months in the 0.7 and 1.0 mg/kg cohorts
  • Pharmacokinetic modeling and simulation indicated that an 80 mg fixed dose provides similar exposure to the 1.0 mg/kg dose, where treatment with NTLA-2001 resulted in 93% mean and 98% maximum serum TTR reduction by day 28
  • Intellia to host investor event to discuss updated data from Phase 1 study of NTLA-2001, the first-ever systemically administered in vivo CRISPR investigational therapy today, Friday, June 24, at 8:00 a.m. ET

CAMBRIDGE, MA and TARRYTOWN, NY, USA I June 24, 2022 I Intellia Therapeutics, Inc. (NASDAQ:NTLA) and Regeneron Pharmaceuticals, Inc. (NASDAQ:REGN) today announced additional positive interim data from an ongoing Phase 1 study of their lead investigational in vivo genome editing candidate, NTLA-2001, which is being developed as a single-dose treatment for transthyretin (ATTR) amyloidosis. The data were presented in an oral presentation at the European Association for the Study of the Liver (EASL) International Liver Congress™ 2022, taking place June 22 – 26 in London.

The presentation today included extended follow-up data from 15 patients with hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN) treated across four single-ascending dose cohorts in Part 1 of the study. Results demonstrated sustained durability of serum transthyretin (TTR) reduction through the last measured timepoint in the ongoing observation. These data support NTLA-2001’s continued development as a potential one-time treatment to permanently inactivate the TTR gene and reduce the disease-causing protein. At the highest dose evaluated, treatment with NTLA-2001 at 1.0 mg/kg resulted in a 93% mean and 98% maximum serum TTR reduction by day 28 across the six patients treated. With longer-term follow-up data now available, these deep reductions continue to be sustained through six months, with an observed mean reduction of 93%. Additionally, three patients in the 1.0 mg/kg cohort have reached nine months in the follow-up period with no evidence of a loss in TTR reduction after a single dose. In the 0.7 mg/kg dose cohort, the 86% mean serum TTR reduction observed at day 28 also remained durable through six months. Further, in the 0.1 and 0.3 mg/kg cohorts, patients have now reached 12 months of follow-up, and a durable response to treatment continues to be observed. Notably, patients in the 0.3 mg/kg cohort sustained an 89% mean serum TTR reduction at 12 months.

At all four dose levels, NTLA-2001 was generally well tolerated through the follow-up period (median follow-up of 10 months). The majority of adverse events were mild in severity with 73% (n = 11) of patients reporting a maximal adverse event severity of Grade 1. There was a single possibly 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. The most frequent adverse events included headache, infusion-related reactions, back pain, rash and nausea. All infusion-related reactions were considered mild, resolving without clinical sequelae.

The safety and activity profile of NTLA-2001 observed in Part 1 indicates that NTLA-2001 has a favorable therapeutic window. These data combined with pharmacokinetic modeling and simulation data support the utilization of a fixed dose of 80 mg in Part 2, which is anticipated to yield similar exposures to the 1.0 mg/kg dose. Dosing is ongoing in Part 2, the single-dose expansion cohort of the polyneuropathy arm.

“Based on the interim data shared today, we believe NTLA-2001’s potential to be a transformational treatment for patients with ATTR amyloidosis is becoming clearer. The safety, depth of serum TTR reduction and durability profile demonstrated thus far highlights its potential for halting and reversing the disease after a single dose,” said Intellia President and Chief Executive Officer John Leonard, M.D. “These data further underscore the power of genomic medicines and bolster the probability of success across our broader in vivo genome editing platform. We look forward to progressing the clinical development of the first-ever systemically administered in vivo CRISPR investigational therapy.”

“We’re pleased to share updated data that enhance the safety and durability profile of NTLA-2001, increasing our confidence in its potential as a one-time, systemically delivered and long-lasting CRISPR-based therapy,” said George D. Yancopoulos, Ph.D., M.D., President and Chief Scientific Officer of Regeneron. “Single-dose in vivo gene editing could one day help patients with a variety of hard-to-treat genetic diseases, making it one of the most exciting medical breakthroughs on the horizon today.”

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 ATTRv-PN or ATTR amyloidosis with cardiomyopathy (ATTR-CM). The cardiomyopathy arm, evaluating NTLA-2001 across patients classified with New York Heart Association (NYHA) Class I - III heart failure, is ongoing. The companies plan to present the first interim data from the cardiomyopathy arm in the second half of 2022. Enrollment across both ATTRv-PN and ATTR-CM patient populations is expected to complete in 2022.

Intellia Therapeutics Investor Event and Webcast Information
Intellia will host a live webcast today, Friday, June 24, 2022, at 8:00 a.m. ET, to review the presented 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 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 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 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.

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.

SOURCE: Intellia Therapeutics

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