Nexiguran ziclumeran

CAMBRIDGE, MA, USA I November 16, 2024 I Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading clinical-stage gene editing company focused on revolutionizing medicine with CRISPR-based therapies, today announced positive new clinical data from the ongoing Phase 1 trial of nexiguran ziclumeran (nex-z, also known as NTLA-2001) in patients with transthyretin (ATTR) amyloidosis. Nex-z is an investigational in vivo CRISPR-based gene editing therapy in development as a one-time treatment for ATTR amyloidosis. Development and commercialization of nex-z is led by Intellia as part of a multi-target collaboration with Regeneron. The Phase 1 trial is an open-label, two-part study evaluating the safety and activity of nex-z in patients with either ATTR amyloidosis with cardiomyopathy (ATTR-CM) or hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN). New results from the Phase 1 study were as of the data cut-off date of August 21, 2024. The data from the ATTR-CM arm of the Phase 1 study were presented in a late-breaking oral presentation at the 2024 American Heart Association (AHA) Scientific Sessions in Chicago, Illinois, and published online in the New England Journal of Medicine . “The Phase 1 data presented today offer compelling evidence that deep and persistently low levels of TTR reduction achieved with nex-z, an investigational in vivo CRISPR-based gene editing therapy, may favorably impact disease progression for people living with ATTR amyloidosis,” said Intellia President and Chief Executive Officer John Leonard, M.D. “The stability or improvement observed after a single dose of nex-z in multiple markers of cardiac disease progression is remarkable, especially considering the high proportion of patients with cardiomyopathy who had advanced heart failure. We observed similarly positive and consistent trends, indicative of a disease-modifying effect, in patients with hereditary ATTR amyloidosis with polyneuropathy. These results from the ongoing Phase 1 study increase our belief in the likelihood of success of our active Phase 3 studies based on our hypothesis that greater TTR reduction may lead to greater clinical benefit.” ATTR-CM Arm Results Consistent with the cardiac disease marker data, assessment of cardiac structure with either echocardiography or MRI, as well as measurements of cardiopulmonary exercise testing also showed a similar pattern of stability at month 12. The hospitalization rate for cardiovascular events among the 36 patients with ATTR-CM was 0.16/patient/year (95% CI: 0.08 to 0.36). ATTRv-PN Arm Results *n=14, †n=19, ‡n=20, N/A: Data for this time point is not yet available for the full cohort and will be reported in the future. Intellia Therapeutics Investor Webcast Information Intellia will host a live webcast, today, November 16, 2024, at 11:00 a.m. CT / 12:00 p.m. ET to discuss the nex-z Phase 1 data. Joining the Intellia management team will be Marianna Fontana, M.D., Ph.D., Professor of Cardiology and Honorary Consultant Cardiologist, University College London Centre for Amyloidosis, London, UK. 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 the MAGNITUDE Study The pivotal Phase 3 MAGNITUDE clinical trial is a randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of nex-z in approximately 765 patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM). The primary endpoint of the study is a composite endpoint of cardiovascular (CV)-related mortality and CV-related events. Adult patients with hereditary or wild type ATTR-CM will be randomized 2:1 to receive a single 55 mg infusion of nex-z or placebo. For more information on MAGNITUDE (NCT06128629), please visit clinicaltrials.gov . About the MAGNITUDE-2 Study MAGNITUDE-2 is a randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of nex-z in 50 adults with ATTRv-PN. Patients will be randomized 1:1 to receive a single 55 mg infusion of nex-z or placebo. Patients randomized to the placebo arm will be eligible for optional crossover to receive nex-z. The primary endpoints are the change from baseline in modified Neuropathy Impairment Score +7 (mNIS+7) at month 18 and serum TTR at day 29. For more information on MAGNITUDE-2 (NCT06672237), please visit clinicaltrials.gov . About nexiguran ziclumeran (nex-z, also known as NTLA-2001) Based on Nobel Prize-winning CRISPR/Cas9 gene editing technology, nex-z has the potential to become the first one-time treatment for transthyretin (ATTR) amyloidosis. Nex-z is designed to inactivate the TTR gene that encodes for the transthyretin (TTR) protein. Interim Phase 1 clinical data showed the administration of nex-z led to consistent, deep and long-lasting TTR reduction. Intellia leads development and commercialization of nex-z as part of a multi-target discovery, development and commercialization collaboration with Regeneron. 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. There is no known cure for ATTR amyloidosis and currently available medications are limited to slowing accumulation of misfolded TTR protein. About Intellia Therapeutics Intellia Therapeutics, Inc. (NASDAQ:NTLA) is a leading clinical-stage gene editing company focused on revolutionizing medicine with CRISPR-based therapies. The company’s in vivo programs use CRISPR to enable precise editing of disease-causing genes directly inside the human body. Intellia’s ex vivo programs use CRISPR to engineer human cells outside the body for the treatment of cancer and autoimmune diseases. Intellia’s deep scientific, technical and clinical development experience, along with its people, is helping set the standard for a new class of medicine. To harness the full potential of gene editing, Intellia continues to expand the capabilities of its CRISPR-based platform with novel editing and delivery technologies. Learn more at intelliatx.com and follow us @intelliatx . SOURCE: Intellia Therapeutics

Alnylam’s experimental RNAi treatment for a rare form of cardiomyopathy has shown signs of efficacy in an early-stage trial of healthy volunteers, but analysts said development could be challenging as new treatments near the market. The Phase 1 study tested six doses of Alnylam’s nucresiran versus placebo in 48 healthy volunteers. The 300 mg dose achieved an average of 90.3% serum TTR reduction at 15 days, changing to 92.6% at 180 days. The 600 mg dose achieved a 95% serum TTR reduction at 15 days, changing to 96% at 180 days, according to data presented Sunday at the American Heart Association’s (AHA) scientific sessions in Chicago. Nucresiran was well tolerated at all doses, and the majority of side effects were mild to moderate, according to Alnylam. The drugmaker expects to share registrational development plans for the treatment early next year, with the trial’s initiation set to follow in the second half of 2025, the company said in the release. The only FDA-approved treatment for transthyretin amyloid cardiomyopathy (ATTR-CM) is Pfizer’s Vyndaqel/Vyndamax, but competition is looming. Alnylam submitted Amvuttra to the regulator last month, and the FDA is expected to decide whether to approve BridgeBio’s acoramidis within weeks. The Phase 1 data suggest that nucresiran has the potential for “superior durability” to Amvuttra, Leerink analysts said Sunday. Nucresiran could be dosed twice or even once each year compared with once every three months for Amvuttra, TD Cowen analysts wrote Monday. But being able to enroll enough participants in a Phase 3 trial could be a difficult task, according to the Leerink analysts. “We see a cardiovascular outcomes trial as likely necessary, a study that would be quite challenging to enroll in a market with multiple approved agents,” they wrote. Nonetheless, the Leerink analysts noted that the Phase 1 data for nucresiran compare well with Intellia Therapeutics’ CRISPR gene-editing ATTR candidate, nex-z. Intellia’s therapy achieved an average of 90% reduction in serum TTR at 12 months in a Phase 1 trial, according to results presented Saturday at the AHA sessions.