Hereditary Complement Deficiency Diseases

Deep attack rate reductions achieved in both dose levels tested; a single 50 mg dose resulted in a mean monthly attack rate reduction of 77% and 81% compared to placebo during weeks 1-16 and 5-16, respectively Eight of 11 patients in the 50 mg arm were completely attack free following a one-time infusion through the latest follow-up; data support NTLA-2002’s potential to be a functional cure for hereditary angioedema (HAE) NTLA-2002 demonstrated an encouraging safety and tolerability profile Data published in The New England Journal of Medicine and will be presented at the 2024 ACAAI Scientific Meeting Actively screening patients in the global pivotal Phase 3 HAELO study evaluating the 50 mg dose of NTLA-2002 Intellia to host investor webcast on Thursday, October 24 at 8:30 a.m. ET Oct. 24, 2024 -- Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading clinical-stage gene editing company focused on revolutionizing medicine with CRISPR-based therapies, today announced positive Phase 2 data from the ongoing Phase 1/2 study of NTLA-2002 in patients with hereditary angioedema (HAE), with results continuing to indicate that NTLA-2002 has the potential to eliminate HAE attacks following a one-time infusion. NTLA-2002 is an investigational in vivo CRISPR-based gene editing therapy in development as a one-time treatment for HAE, a rare genetic condition that leads to potentially life-threatening swelling attacks. Results were published online today in The New England Journal of Medicine and will be presented on Saturday, October 26 at the 2024 American College of Allergy, Asthma & Immunology (ACAAI) Scientific Meeting in Boston, Massachusetts. “These positive NTLA-2002 Phase 2 results underscore the tremendous potential of our in vivo CRISPR gene editing therapy to be a functional cure and redefine the treatment paradigm for HAE,” said Intellia President and Chief Executive Officer John Leonard, M.D. “The Phase 2 data demonstrated that a majority of patients in the 50 mg arm experienced a complete response — no attacks at all and no further treatment needed — after a one-time infusion of NTLA-2002 through the latest follow-up, consistent with the long-term Phase 1 data. We are highly encouraged by these results, which we believe sets NTLA-2002 apart from other prophylaxis treatments. What was previously an unimaginable potential to be free of chronic therapy is one step closer to becoming a reality for the HAE community.” “Approved HAE therapies can reduce but frequently do not eliminate all angioedema attacks and require chronic administration, resulting in a significant treatment burden and a major impact on the quality of life for people living with HAE,” said Danny Cohn, M.D., Ph.D., Internist, Department of Vascular Medicine, Amsterdam University Medical Center and the Phase 2 study’s lead principal investigator. “These NTLA-2002 Phase 2 data are remarkable, showing this investigational therapy could permanently stop swelling attacks with a single infusion. I am optimistic that NTLA-2002 will change the way we treat HAE and put an end to the need for a lifetime of chronic treatment.” The Phase 2 study is a randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety, pharmacodynamics and pharmacokinetics of NTLA‑2002. A total of 27 participants were enrolled and randomized to receive one of two single doses of NTLA-2002 (25 mg or 50 mg) or placebo via intravenous infusion. The data cut-off date for the analysis was April 4, 2024, when the 25th patient completed the 16-week primary observation period. Single dose of NTLA-2002 led to deep attack rate reductions during the primary observation period. The mean monthly attack rates relative to placebo were reduced by 75% and 77% for the 25 mg and 50 mg arms during weeks 1 – 16, and by 80% and 81% during weeks 5 – 16, respectively. In the 50 mg arm, eight of 11 patients experienced a complete response after a single dose of NTLA-2002, with no attacks at all during the 16-week primary observation period; these eight patients continued to be attack-free through the latest follow-up (median of eight months) and no subsequent treatment has been required. In contrast, four of the 10 patients in the 25 mg arm experienced a complete response and zero patients in the placebo arm. Similarly, patients who received the 50 mg dose achieved a greater kallikrein protein reduction, with an 86% mean reduction from baseline compared to 55% in the 25 mg arm at week 16. At both dose levels, NTLA-2002 was well tolerated. The most frequent adverse events (AEs) were headache, fatigue and nasopharyngitis. There have been no serious AEs and all AEs were either Grade 1 or 2, except for one patient in the placebo arm who experienced a serious AE of Grade 4 edema of the tongue with breathing impairment that was attributed to their underlying HAE. No clinically significant laboratory abnormalities were observed. The safety, tolerability and efficacy data from the Phase 2 study are consistent with the long-term Phase 1 data presented at the European Academy of Allergy and Clinical Immunology (EAACI) Congress in Valencia, Spain on June 2, 2024. Based on these results, Intellia selected 50 mg for evaluation in the global, pivotal Phase 3 HAELO study, which is actively screening patients. For more information on HAELO (NCT06634420), please visit clinicaltrials.gov. Intellia Therapeutics Investor Webcast Information Intellia will host a live webcast, today, October 24, 2024, at 8:30 a.m. ET to discuss the NTLA-2002 Phase 2 data. Joining the Intellia management team will be Dr. Danny Cohn, Internist, Department of Vascular Medicine, Amsterdam University Medical Center, and the Phase 2 study’s lead principal investigator as well as Dr. Paula Busse, Professor of Medicine, Division of Clinical Immunology, Icahn School of Medicine at Mount Sinai. 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. Based on Nobel-prize winning CRISPR/Cas9 technology, NTLA-2002 has the potential to become the first one-time treatment for hereditary angioedema (HAE). NTLA-2002 is designed to prevent HAE attacks by inactivating the kallikrein B1 (KLKB1) gene, which encodes for prekallikrein, the kallikrein precursor protein. NTLA-2002 has received five notable regulatory designations, including Orphan Drug and RMAT Designation by the U.S. Food and Drug Administration, the Innovation Passport by the U.K. Medicines and Healthcare products Regulatory Agency (MHRA), Priority Medicines (PRIME) Designation by the European Medicines Agency, as well as Orphan Drug Designation by the European Commission. Hereditary angioedema (HAE) is a rare, genetic disease characterized by severe, recurring and unpredictable inflammatory attacks in various organs and tissues of the body, which can be painful, debilitating and life-threatening. It is estimated that one in 50,000 people are affected by HAE. Although there is no known cure for HAE, there are preventative and on-demand treatment options to help manage the condition, including long- and short-term prophylaxis used to prevent swelling attacks. Current treatment options often include life-long therapies, which may require chronic intravenous (IV) or subcutaneous (SC) administration as often as twice per week or daily oral administration to ensure constant pathway suppression for disease control. Despite chronic administration, breakthrough attacks still occur. Kallikrein inhibition is a clinically validated strategy for the preventive treatment of HAE attacks. Intellia Therapeutics, 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. The content above comes from the network. if any infringement, please contact us to modify.

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here . It’s earnings season! Our reporters will be closely following announcements next week from Pfizer, Novartis, Eli Lilly, GSK, AbbVie, Merck and more. Stay tuned for the latest. — Nicole DeFeudis In a 74-page presentation, activist investor Starboard Value said this week the company’s board needs to “ hold management accountable ” after not being able to capitalize on what it described as one of the best pipelines in biopharma. Though Starboard did not call for changes to the board or Pfizer’s management team, it’s not unusual for activists to make such declarations to test the waters for a company’s response. Endpoints’ founding editor takes a look at some of 2024’s biggest industry trends as they stand at the end of the third quarter. Among the highlights: AI appears to be driving higher M&A figures, licensing deals are down, venture totals are up and IPOs have been a mixed bag. Check out John’s full analysis here . Intellia Therapeutics said this week that its experimental gene editing therapy reduced patients’ mean rate of monthly swelling attacks caused by hereditary angioedema by about 80%. Danny Cohn , a doctor who led the Phase 2 study, said he was “overwhelmed by the clinical response.” Ryan Cross has the details here . Just six months after launching with $100 million, Boston’s latest neuropsychiatry startup Seaport Therapeutics closed a $225 million Series C this week. The company spun out of publicly traded PureTech and is developing prodrugs of molecules that have already been tested or approved. Seaport is starting in depression, with a Phase 2b study expected for a prodrug version of allopregnanolone. Roche is taking a stance on Novo Holdings’ planned acquisition of Catalent . CEO Thomas Schinecker said on Wednesday that antitrust regulators shouldn’t clear the deal, citing concerns that it could limit competition from a broader industry perspective. Why would the company try to block the deal? Drew Armstrong unpacks the news here. The companies will no longer partner on a program called bepranemab . Roche and Genentech had ponied up $120 million upfront and promised up to $2 billion in milestones to team up back in 2020. It’s not the first Alzheimer’s deal Roche and Genentech have broken off this year: In January, the two ended a partnership with AC Immune after lackluster readouts. UCB regained global rights to the program. SPOTLIGHT Editas pivots away from ex vivo sickle cell therapy in favor of in vivo approach ‘It’s not right.’ Califf slams pharma over weight loss drug prices R&D FDA+ PHARMA FINANCING DEALS MANUFACTURING HEALTH TECH

iStock, Panuwach Jefferies analyst Maury Raycroft said in a note to investors that Thursday’s mid-stage readout pointed to the “unprecedented” complete response rate of Intellia’s investigational in vivo CRISPR-based gene editing therapy in the disorder. Intellia Therapeutics on Thursday unveiled Phase II data for its investigational CRISPR treatment NTLA-2002, touting a steep reduction in monthly attack rates in patients with hereditary angioedema, a disorder characterized by recurrent episodes of severe swelling. The results, to be presented this weekend at the 2024 Scientific of the American College of Allergy, Asthma & Immunology in Boston, showed that a one-time, 25-mg dose of NTLA-2002 reduced monthly attacks by 80% from weeks five through 16 of follow-up. The higher 50-mg dose lowered attacks by 81% during this time period. Expanding the observation period from weeks one through 16, the 25-mg and 50-mg doses of NTLA-2002 resulted in a 75% and 77% decrease in attack rate, respectively. According to Intellia, eight of the 11 patients given a single 50-mg infusion reached complete response, experiencing “no attacks at all” during the 16-week observation period. Complete treatment response was durable in the eight patients through the latest follow-up at a median of eight months. Four of the 10 patients in the 25-mg group achieved this outcome, while none of the placebo comparators did so. In terms of safety, both doses of NTLA-2002 were well-tolerated with the most common side effects being headaches, fatigue and nasopharyngitis. There were no serious toxicities, except for one patient in the placebo arm who developed grade 4 tongue edema that compromised breathing. There were also no clinically significant laboratory abnormalities. Intellia CEO John Leonard in a statement said that the biotech is “highly encouraged” by these mid-stage findings, which “underscore the tremendous potential of our in vivo CRISPR gene editing therapy to be a functional cure” for hereditary angioedema (HAE) and “redefine the treatment paradigm” for this condition. “What was previously an unimaginable potential to be free of chronic therapy is one step closer to becoming a reality for the HAE community,” Leonard said. Intellia will take NTLA-2002’s 50-mg dose into late-stage development. The Phase III HEALO study is currently actively screening patients, according to the company. Analysts appear to be optimistic about NTLA-2002’s prospects—though cautiously so. Jefferies analyst Maury Raycroft in a note to investors said that Intellia’s readout on Thursday pointed to the “unprecedented complete response rate” of NTLA-2002 in HAE. The strong efficacy showing is further bolstered by NTLA-2002’s one-time dosing profile, which “is the key differentiator vs other … programs and points to potential for a functional cure for HAE,” Raycroft wrote. Shareholders, however, seem to be underwhelmed. Intellia’s shares were down 9% in premarket trading on Thursday, following the Phase II data, according to Seeking Alpha . Maury chalked the negative stock reaction up to an “overreaction” from investors, who had expected better monthly attack rate reductions based on promising Phase I data . Meanwhile, Truist Securities analyst Joon Lee pointed to competitive—and potentially better—HAE data from Pharvaris, which touted a 93% reduction in monthly attack rate for its oral daily pill. William Blair analyst Myles Minter said that despite these pressures, “we still see potential for NTLA-2002 in HAE given the impressive magnitude of response when achieved.” Nevertheless, HAE is a “competitive space,” not only with several currently available treatment options, but also with upcoming therapies with strong potential, according to Minter.