Intellia Therapeutics, Inc.

Good morning and welcome to Intellia Therapeutics' second quarter 2024 financial results conference call. My name is Drew and I will be your conference operator today. Following formal remarks, we will open the call up for a question and answer session. This conference is being recorded at the company's request and will be available on the company's website following the end of the call. As a reminder, all participants are currently in listen-only mode. If anyone requires operator assistance during the conference, please press star zero on your telephone keypad. I will now turn the conference over to Ian Karp, Senior Vice President of Investor Relations and Corporate Communications at Intelia. Please proceed.

Thank you, operator, and good morning, everyone. Welcome to Intelia Therapeutics' second quarter 2024 earnings call. Earlier this morning, Intelia issued a press release outlining the company's progress this quarter, as well as topics for discussion on today's call. This release can be found on the Investor and Media section of Intellia's website at intelliatx.com. This call is being broadcast live, and a replay will be archived on the company's website. At this time, I'd like to take a minute to remind listeners that during the call, Intellia management may make certain forward-looking statements and ask that you refer to our SEC filings available at sec.gov for discussion of potential risks and uncertainties. All information presented on this call is current as of today, and Intellia undertakes no duty to update this information unless required by law. Joining me from Intelia are John Leonard, Chief Executive Officer, Lorisept Lorenzino, Chief Scientific Officer, Ed Dulac, Chief Financial Officer. Also in the room and available for the Q&A is Leron Walsh, Head of Development for Indevo Programs. Our Chief Medical Officer, David Levwall, is unable to join us today, but he will be participating in upcoming investor conferences. John will begin with updates on our clinical pipeline progress and recent business highlights. Laura will then provide R&D updates, and Ed will review our financials before we open the call for questions. And with that, I'll now turn the call over to John, our Chief Executive Officer.

Thank you, Ian. Good morning, everyone, and thank you all for joining us today. At Intelia, we're harnessing the power of CRISPR-based gene editing for developing potentially curative treatments. Now, with over 150 patients dosed with our investigational therapies and multiple programs in clinical development, We are undoubtedly at the forefront of the gene editing revolution. We're proud to report another quarter of substantial progress and continued innovation across our full spectrum pipeline and platform. I'll start with NTLA-2002 for the treatment of hereditary angioedema, also known as HAE. It is a debilitating and potentially fatal condition that manifests as recurrent episodes of unpredictable swelling. Despite existing treatments, we've heard loud and clear from patients and physicians and through our market research that HAE patients are seeking improved efficacy and convenience. Beyond that, patients tell us that what they want most is to live a life free from their disease and the many challenges that come with it, even while on chronic treatments available today. While current and other emerging therapies attempt to differentiate themselves with modest improvements in attack rate reduction or extending dosing intervals for prophylactic therapy, what we are pursuing is a total paradigm shift in the treatment of HAE. Our goal for NTLA-2002 is to provide a complete response that is a treatment outcome in which patients are both free from attacks and untethered from the requirements of chronic treatment. after a single administration. This is the outcome patients and physicians seek, and with revolutionary advancement of our gene editing technology, we believe we are making it a reality. In June, we reported positive long-term data from the Phase 1 study of mTLA-2002. Of the 10 patients treated, eight continued to be completely attack-free for 18 to 26 months following a single administration of the drug. And across all patients, we observed a 98% reduction in attacks with the latest follow-up. Importantly, the data from these 10 patients continue to demonstrate a favorable safety profile. The most frequent adverse events were infusion-related reactions and fatigue, which were mostly grade one. These unprecedented results reinforce the potential of NTLA-2002 to be a one-time functional cure for this life-threatening disease. Today, we're thrilled to announce that NTLA-2002 met its primary efficacy and all secondary endpoints in the 16-week primary observation period of the phase two study. As a reminder, the ongoing phase two was a randomized placebo-controlled study to further evaluate the safety and efficacy of the 25 milligram and 50 milligram doses. The key objective of the phase two was to determine which of the two doses to move forward into the global pivotal phase three trial. The primary efficacy endpoint was the reduction in the number of angioedema attacks per month during the 16-week primary observation period. Key secondary endpoints included safety, the number of angioedema attacks per month during weeks five to 16, the number of angioedema attacks per month requiring acute therapy, and the change from baseline and the total plasma calitrine protein level. We plan to present the detailed results at a medical meeting in the fourth quarter of this year. As such, we will be limiting our discussion of the top line results to what we disclosed in today's press release. A single 25 or 50 milligram dose of NTLA-2002 led to deep reductions in attacks for patients with HAE. No new safety findings were observed. We have now selected the 50 milligram dose to advance into the global phase three trial because we saw a greater calotriene reduction and importantly, a higher number of patients who achieved complete elimination of attacks compared to the 25 milligram dose cohort, which is consistent with the prior phase one results. In addition to the positive results, we recently completed a successful end of phase two meeting with the FDA. We believe we have completed addressing their questions and have a clear understanding of the path forward. We are on track to begin the phase three trial in the second half of this year, and if positive, plan to submit the BLA for NTLA-2002 in 2026. We anticipate that NTLA-2002 will be the first in vivo gene editing therapy to come to market, and most importantly, we strongly believe it will reset the standard of care for HAE. Switching now to NTLA-2001 for the treatment of ATTR amyloidosis, the drug now has a new name, Nexagurin Zyklumarine, or Nex-Z for short. Recent competitor data confirmed our longstanding hypothesis that TTR reduction leads to a clinically meaningful improvement in patients with cardiomyopathy. This is an important advancement in the field's understanding of the disease. And this result further increases our confidence that NexZ could lead to even better clinical outcomes for patients. Our belief is based on the consistently deep and durable PTR reductions observed in the phase one study. Further, the competitor clinical data recently reported reaffirm that the ongoing magnitude trial is well designed. As appropriate, we will incorporate additional learnings into our trial as they become available. The rapid enrollment of the magnitude trial continues to track well ahead of our internal projections. In addition to the significant physician and patient interest in the trial, we're also progressing well with global regulatory approvals for the study. In total, we've now received regulatory clearance in over a dozen countries and are actively enrolling at over 35 sites around the world. Building on our significant progress in cardiomyopathy, we are on track to initiate the pivotal trial for polyneuropathy by year end. As previously announced, the study is expected to be a small placebo-controlled trial of approximately 50 patients conducted in XUS regions with limited or no access to TTR silencers. Finally, we look forward to presenting data from the ongoing phase one study in the second half of 2024. We plan to include safety and TTR reduction data from both the CM and PN arms, as well as other clinical endpoints, such as NT ProBNP, six-minute walk test, and MNIST plus seven. We anticipate these data will build upon insights recently reported in other TTR silencer clinical trials. With three pivotal phase three trials and our first gene insertion study, all expected to be active by year end, and telling us closer than ever to transforming the future of medicine with our one-time in vivo gene editing therapies. In parallel to our clinical execution, we're making strategic investments for our exciting evolution from late-stage clinical development to a commercial organization. This is exemplified by the recent appointment of Brian Goff, who are our Board of Directors, and Ed Dulac, the Chief Financial Officer and Treasurer. Brian's extensive global commercialization experience, coupled with his track record of success leading rare disease product launches, will be invaluable. Similarly, Ed's deep financial and business development experience at clinical and commercial stage biotech companies will be critical as we enter the next chapter in our evolution. I'll now hand the call over to Laura, our Chief Scientific Officer, who will provide updates on the NTLA 31 program and our R&D efforts.