Intellia Therapeutics, Inc.

Hello and welcome to Intellia Therapeutics' fourth quarter and full year 2025 conference call. My name is Drew and I will be your conference operator today. Please be advised that today's call is being recorded. I will now turn the call over to Jason Fredette, Vice President of Investor Relations and Corporate Communications at Intellia. Please proceed.

Thank you, operator, and hello, everyone. Earlier this morning, we issued a press release outlining recent business updates and our fourth quarter and full year financial results. This document can be found on the investors and media section of Intellia's website at intelliatx.com. At this time, I would like to take a minute to remind listeners that during this call, Intellia management may make certain forward-looking statements. We ask that you refer to our SEC filings available at sec.gov for a discussion of potential risks and uncertainties. All information presented on this call is current as of today, and Intelia undertakes no duty to update this information unless required by law. Joining me on this call are John Leonard, our Chief Executive Officer, and Ed Dulac, our Chief Financial Officer. With that, I'll turn the call now over to John to begin our business discussion.

Thank you, Jason, and thanks to all of you who have tuned in for today's call. We'll begin with a brief recap of our 2025 accomplishments, and we'll then review the status of our NEXE program in ATTR amyloidosis. After that, we'll provide updates on the significant progress we've made with LOMVOSI, which is being developed as a potential one-time treatment for patients with hereditary angioedema, or HAE. And we will close with Ed's financial review. First, let's take a step back to the origins of Intellia Therapeutics. This company was formed over a decade ago based on the belief that we could help revolutionize medicine utilizing CRISPR gene editing. From the outset, we designed our gene editing product candidates to reset the treatment standard in our disease areas of interest. This new standard would raise the bar by conferring highly competitive and durable efficacy for patients via one-time treatment that is administered in an outpatient setting. We believe our two lead candidates, Lombosi and Nexi, fit this profile. Now, with up to three years of patient follow-up, we have yet to see any waning of effect in serum calocrine or TTR levels in the extended follow-up of our Phase I and II trials. Even more encouraging, the observations of improvement in clinical and disease measures that we track in the Phase I and II trials also have not waned. Given these clinical data and our preclinical work showing the edits we make are permanent and edited cells, and in all subsequent generations of those cells, we expect patients to benefit for many, many years, if not their entire lives. And both LOMVOSI and NEXI are administered in an outpatient setting. After a simple prophylaxis regimen to reduce the risk of infusion-related reactions, Patients visit a clinic where they receive an IV infusion over the course of two to four hours, and then they go home. And so a decade plus after our founding, it's for good reason that our excitement is building as we approach the world's first phase three data readout for an in vivo gene editing candidate by mid this year. Now for some reflections on 2025. Simply put, it was a time of both accomplishment and resiliency for Intelia. With Lombosi, we rapidly enrolled Halo, our phase three clinical trial in HAE, and we did this well ahead of schedule. Until the clinical hold in October, we achieved similar enrollment success with Nexi. At the start of the year, we were expecting to have enrolled about 550 patients with ATTR amyloidosis with cardiomyopathy in our magnitude phase three clinical trial by year end. and we had not yet begun enrollment in magnitude two, our phase three trial for patients with polyneuropathy. By October, just 10 months later, we'd enrolled more than 650 patients in magnitude, and we're already approaching full enrollment in magnitude two. We and many others believe this type of enrollment enthusiasm is a good indicator of a product candidate's commercial potential. In late October, after elevated liver transaminases and total bilirubin were observed in a magnitude patient that met the trial's protocol-defined pausing criteria, we suspended enrollment in magnitude and magnitude two. Shortly thereafter, the trials were placed on clinical hold by the FDA. Our team immediately took action to address the hold, working in concert with external experts, our clinical sites, investigators, and regulatory authorities. In late January, we were pleased to announce that the FDA lifted the clinical hold on magnitude 2. We aligned with the agency on certain study modifications. These include addition of supplementary liver laboratory tests in the weeks following patient's enrollment and dosing, and guidance that patients receive a short-term steroid regimen if elevated liver transaminases are detected in the weeks immediately following dosing. The rationale for this is that the LFT elevations appear to be consistent with an immune-mediated reaction. We also have modified our screening criteria to exclude the enrollment of patients who may be the most susceptible to a potential liver injury. These include patients with significantly elevated liver enzymes at screening and those with a history of MASH or autoimmune hepatitis. We expect these new criteria will help to safeguard patients while also having a minimal impact on our screen failure rate. As a reminder, we've already enrolled 47 patients in Magnitude 2. As part of the protocol amendment, we also proposed, and the agency accepted, that we increase the trial's target enrollment from 50 patients to approximately 60 patients. This allows us to accommodate patients who had already been identified for screening prior to the hold. Since Magnitude 2 is being enrolled outside the United States, we are now working through the relevant local regulatory processes to resume patient screening, and we're confident we can complete enrollment in the second half of this year. At the same time, our FDA engagement is ongoing as it relates to Magnitude. As we've mentioned in the past, Magnitude and Magnitude 2 are very different trials enrolling very different patient populations, and we were considering these factors in our ongoing work. While nothing is done until it's done, we've made a lot of progress in our effort on this front. And given the positive phase one data that's been presented for Nexi, including the encouraging post hoc mortality data derived from a contemporaneous and well-matched cohort of nearly 1800 patients that we shared at AHA this past November, we continue to believe strongly in this candidate's potential to benefit patients with ATTR amyloidosis. Now let's move on to LOMVOSI and HAE. We completed enrollment in the HALO Phase III clinical trial with 80 patients in September, just nine months after we dosed our first patient in the trial. This is due in large part to the tremendous amount of interest we have seen in LOMVOSI among those with HAE and the treating physicians. This interest is also reflected in market research we recently conducted and shared at J.P. Morgan in January. In late 2025, 104 U.S. patients and caregivers were surveyed by a third party. They were shown a target product profile based on data from our phase one and two trials on a blinded basis and were told the data was from a gene editing candidate. They were then asked if they would be likely to take the treatment if it were to be approved. 99% of the patients responded they would at least be somewhat likely, and nearly two-thirds said that they would be extremely or very likely to take it. The interest also carried over to prescribing physicians. 151 U.S. healthcare providers were presented the same target product profile and then asked if they could identify a patient in their practice to whom they would prescribe the drug. 92% of them said yes. These HCPs reported they were managing the care of more than 4,000 patients collectively, which would represent about 60% of the entire treated patient population in the United States. When asked how many of these patients would they prescribe Lombosi to, that number came out to about 2,200 patients, or 54% of the patients under their care. So what's driving this interest? Well, it's because a substantial unmet need still exist despite today's available HEE therapies. At ACAAI in November, we presented data from another 100 patients who were surveyed, about 90% of whom were on long-term prophylaxis therapies, otherwise known as LTPs. The results shed further light on the burdens that many patients continue to face, the burden of their disease and the burden of their chronic treatment. The results show that nearly 70% of patients were concerned about having to take LTP and or on-demand medications for the rest of their lives. Nearly 60% were concerned about the unpredictable nature of their HAE, and most patients also concerned about the logistical and financial burdens of the disease. Also striking was the fact that only 20% of surveyed patients reported they were attack-free for the past 12 months. This 20% figure contrasts with the clinical data we presented in November from our phase one to pooled analysis, showing that 76% of patients who were at least a year beyond the 50 milligram dose of Lombosi were free from both attacks and ongoing therapy for at least 12 months. We're looking forward to presenting more insights from this patient burden study at the Quad AI meeting that is taking place this weekend in Philadelphia. And so, Our march continues toward top-line data by the middle of this year and a planned BLA submission in the second half of this year. We've been asked from time to time what our expectations are for this readout. When looking at the Phase III data for approved LTPs, the best attack reduction rates have been in the 80s, and the very best attack-free rate we have seen from an LTP is approximately 60% of patients. And of course, these results were achieved only with chronic therapy. In our placebo-controlled HALO trial, we believe the LOMVOSI arm will be highly competitive with those numbers, with the added and unique benefit that it is a one-time therapy. And as was shown in the pooled analysis that was presented to ACAAI, LOMVOSI could perform even better outside of a placebo-controlled trial and in the real-world setting where patients know they are on active treatment. As I've laid out, it's going to be a big year for Intellia with many meaningful milestones. We look forward to updating you on our progress along the way. I'll now hand the call over to Ed, our Chief Financial Officer, who will provide an update on our financial results for the fourth quarter of 2025.