Intellia Therapeutics, Inc 2026 Q2 Earnings Call

Please proceed. Thank you, operator, hello, everyone.

Earlier this morning, we issued a press release outlining recent business updates in our second quarter financial results. This document can be found on the Investors and Media section of 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, Intellia undertakes no duty to update this information unless required by law. Joining me on the call are John Leonard, our Chief Executive Officer, and Ed Dulac, our Chief Financial Officer. With that, I'll now turn the call over to John to begin our business discussion.

Thank you, Jason, good morning, everyone. We're excited to be speaking with you to recap the tremendous progress we made in our phase III development programs of lonvo-z in hereditary angioedema, or HAE, nex-z in transthyretin amyloidosis, or ATTR. The full results of our phase III HALO trial in HAE position us very well for potential approval and launch of the world's first in vivo gene-editing product in the first half of next year. We also have gained important new genomic insights that further our understanding of nex-z's profile and could help position us even more favorably within a large and dynamic ATTR market. Let's begin with lonvo-z. Simply put, the second quarter was a momentous period for this program. In April, we reported positive top-line results from HALO and got our rolling BLA submission underway with the FDA.

This was followed by our late-breaking oral presentation at EAACI and a concurrent publication in "The New England Journal of Medicine," Intellia's sixth manuscript in this prestigious journal. HALO was an unequivocal success as we achieved statistical significance for the primary and all key secondary endpoints. More specifically, during the six-month primary observation period, we reported an 87% reduction in mean monthly attacks for lonvo-z versus placebo. 62% of patients were entirely attack-free and therapy-free in the lonvo-z arm. A 23-point improvement was observed for the lonvo-z arm in the total angioedema quality of life score from baseline. For context, a change of just six points is considered to be clinically meaningful. The New England Journal manuscript also contained compelling figures and analyses underscoring the unique value proposition that could be afforded by this one-time therapy if it's approved.

For instance, patient-level data demonstrated that all patients in the lonvo-z arm experienced attack rate reductions from baseline for weeks five to 28. In other words, every single patient received a clinical benefit, including those who are not yet fully attack-free during that six-month period. A subgroup analysis demonstrated meaningful attack rate reductions in the lonvo-z arm regardless of age, sex, race, weight, geography, baseline attack rate, or prior therapy. The publication also included a figure depicting the mean number of HAE attacks over time. It traced patients from when they were on prior therapies before screening through the entire efficacy evaluation period and into crossover, and it showed that mean attack rates for the lonvo-z arm dropped well below the pre-screening attack rates by week four. Attacks continued to decline in the months that followed and approached zero in the crossover period after week 28.

In the placebo arm, not surprisingly, mean attack rates didn't drop below pre-screening levels until patients crossed over to lonvo-z. At that point, they dropped steeply and approached zero within a few months. Also, notably, all patients who received lonvo-z at baseline or in crossover remained free from long-term prophylaxis therapy as of the data cutoff. Finally, favorable safety and tolerability data were observed. The most common treatment emergent adverse events were infusion-related reactions, headache, and fatigue. All treatment emergent adverse events were grade 1 or grade 2, and there were no serious adverse events observed in the lonvo-z arm as of the data cutoff. These results are unsurpassed by chronic long-term prophylaxis therapies or LTPs. We believe it is clear, moreover, that they truly stand alone in the HAE space, given that this is a one-time treatment.

Most patients were attack-free and therapy-free for the entire six-month efficacy observation period following a single lonvo-z dose. Based on our preclinical work and observations from our phase I/II trial, our expectation is that this percentage will increase further over time as patients who have lived with HAE their entire lives adjust to their new normal. What's next for us? We expect to be in a position to announce the FDA's acceptance of a BLA filing for lonvo-z by the end of this year. In the meantime, our pre-commercial readiness efforts are advancing well as we prepare for a potential U.S. launch in the first half of next year. Most of these efforts are well underway, including work streams across medical engagement, payer outreach, treatment center readiness, distribution planning, and access strategy.

We've completed hiring for our field medical, reimbursement, and strategic accounts teams, and they're now engaging with treatment centers around the country to ensure they are well-prepared to address patient needs shortly after approval. We're also building awareness of the many burdens associated with HAE. During the second quarter, we launched haereframed.com, a disease awareness initiative designed to elevate understanding of the challenges patients face, including those related to lifelong chronic therapy. Together, these efforts reflect meaningful progress in building the infrastructure, awareness, and access pathways needed to support our planned launch. Let's turn to the progress we've made with nex-z, our potential one-time treatment for patients with ATTR cardiomyopathy and polyneuropathy. We were pleased to resolve the clinical holds on our phase III trials quite rapidly earlier this year.

I'm excited to report today that we were able to resume enrollment and dosing in both trials in Q2. Investigator engagement enthusiasm remain high, and our screening rate is rapidly increasing globally once again. ATTR is a large, growing, and highly underdiagnosed market with significant unmet need. Today, patients are predominantly served by stabilizers, silencers, or a combination of the two. About a month ago, disappointing top-line results were shared from CARDIO-TTRansform, the pivotal trial of eplontersen, a TTR silencer for patients with ATTR-CM. Since then, there's been some debate about whether a silencer can work on top of a stabilizer. We and others believe the negative outcome is specific to eplontersen in this particular trial, and it does not speak to combination outcomes in general. We remain firm believers that combination therapy will work, but only with the right agent.

This belief is based empirically on clinical evidence. First, we would point to the fact that another chronically dose silencer, patisiran, has already shown a directional benefit on top of stabilizers in a well-controlled trial. Even more importantly, we would point to what was observed in the monotherapy data for each of the chronically dosed stabilizers and silencers. If you go back and look at the readouts for approved stabilizers like tafamidis and acoramidis and approved silencers like eplontersen and patisiran, you'll see that patients continue to progress while they're on those therapies. Why is that? Well, we and others are convinced it's because they inadequately reduce or control TTR protein. Focusing in on the approved silencers, you'll see that mean TTR reductions for each of them are about 80%. However, the details behind that number matter.

For instance, it takes many months for those silencers to achieve their 80% data of reduction. There's significant variability in TTR from patient to patient, with some achieving a 90% knockdown and many others receiving reductions of only 50% or 60%. Even within an individual patient, the knockdown fluctuates due to issues with PK and issues with dose interruptions and adherence, whether due to patient behavior or toxicity. Simply put, it appears today's silencers and stabilizers are leaving efficacy on the table. In a progressive disease with high mortality like ATTR-CM, every day and every microgram per milliliter of TTR counts. nex-z has demonstrated its ability to deliver an unsurpassed knockdown of TTR protein for patients in both relative and absolute terms. Our phase I data demonstrated a mean TTR reduction of 90%. While that percentage is impressive, we believe the absolute TTR reduction is even more clinically relevant.

When nex-z is provided as monotherapy, mean serum TTR was less than 20 micrograms per milliliter, about one-third of the absolute level seen with the leading chronic silencer. That knockdown was achieved rapidly within one month of the infusion, and it was extremely consistent across all patients. Best of all, patients began receiving therapeutic doses of nex-z in 2021, and as of our latest data cutoff, intra-patient TTR control was constant and was maintained across all patients following their one-time nex-z treatment. We look forward to presenting updated long-term durability data at future congresses. We believe nex-z's distinct TTR knockdown is why disease stabilization or reversal is observed in most patients in our phase I, while our would-be competitors have observed disease progression.

Additionally, the response has been consistent across patients of all New York Heart Association classes, those with either variant or wild-type disease, and it also includes patients who have progressed on past silencers. We continue to have significant confidence in our ability to show a benefit on top of tafamidis and MAGNITUDE. Additionally, unlike CARDIO-TTRansform, which was a time-bound study, MAGNITUDE's primary endpoint is strictly event-based. We've enrolled well over 650 patients in MAGNITUDE. We've been accruing events for quite some time. And those events continued unabated through the clinical hold. While it's still premature for us to guide as to data timing, what I can say today is that the blinded event rate in the trial remains within the range we'd projected internally. We're looking forward to reviewing the detailed CARDIO-TTRansform data later this month at ESC.