Intellia Therapeutics, Inc. Q2 FY2025 earnings call

• John Leonard highlighted 2025 as a year of excellent execution with clinical updates, restructuring delivering benefits, and strong enrollment in Phase III studies. Clinically, long-term follow-up data from trials show potential for new standards in HAE and ATTR amyloidosis. Operational excellence leads to accelerating guidance, including expanding the ATTR cardiomyopathy study to 1,200 patients and targeting 650 patients by year-end for the HAELO study.
• David Lebwohl provided updates on lonvo-z for HAE, noting strong enrollment in the Phase III study and positive long-term follow-up data. For nex-z in ATTR amyloidosis, he discussed expansion of the ATTR cardiomyopathy study, positive Phase I data, and progress in ATTR polyneuropathy trials.
• Ed Dulac reviewed financials, noting cash balance, collaboration revenue, R&D and G&A expenses, and guidance on GAAP operating expenses decline and cash runway.

No detailed product segment financial performance with absolute terms and revenue contribution % provided in the transcript.

• Anticipate completing enrollment earlier in HAE and ATTR polyneuropathy programs than previously thought.
• Expect to enroll more patients in the ATTR cardiomyopathy program than originally planned, with the study expanded to 1,200 patients.
• Target at least 650 patients cumulatively by year-end in the ATTR cardiomyopathy program.
• Guidance on GAAP operating expenses decline and cash runway remains unchanged despite study expansion.

No specific risks detailed in the transcript beyond general forward-looking statement disclaimers from SEC filings.

Q: Now that you've increased the target number for the ATTR-CM study, do you have a target proportion of patients you would like to be on stabilizers to be able to see -- or to be powered to see the benefit in combination?

A: As we started the study, we estimated that we would have 50% to 60% of the patients on stabilizers. It's become apparent over the course of the study that these stabilizers has become more and more the standard of care. We estimate that we may have 70-ish percent of patients who are on stabilizers. This is a study that looks at the addition of nex-z on top of standard of care.

Q: Could you walk us through how cash runway won't have a major change after this trial expansion?

A: Generally, we do take a conservative approach to our long-range planning and for significant investments like clinical studies so that we can run the business with confidence. For our late-stage clinical programs, which may last years from planning to execution and completion. We always assess different scenarios, different potential time lines, different potential investment needs at a pretty standard practice for us here at Intellia. For magnitude specifically, we consider the possibility of increasing enrollment within our scenario planning. Based on the emerging data from our peers in the TTR space, our own maturing Phase I data from our TTR program. And then we have increasingly more market research that we are getting from physicians and payers to inform our thinking here. And so we've only recently made the decision to increase the 1,200 patients, which relative to our 3-year plan represented a modest uptick, immaterial uptick in costs that we can absorb without impacting our cash runway or our net cash burn guidance that we provided through 2025 and 2026.

Q: For nex-z, while you're accruing longer-term Phase I/II data, what is the latest regarding your assumptions on Phase III events accrual rate? And if that also prompted you to expand the study to 1,200 patients.

A: We're not talking about specific event rates. But obviously, we look at information that's become available from a variety of sources -- as we said in our comments to open the call, we've seen information has come from competitors in the space, which we think provides useful information in terms of the current standard of care and how patients are treated and the weight of their disease progression. We supplement that with databases that comes from other sources that, again, we think, gives us contemporaneous information in terms of how patients with the disease progress. But also of significant importance is the information we're collecting from our own Phase I patients, which we've reported on previously, and we will extend the reports later this year. And what we've seen in work that was published in New England Journal and presented elsewhere that the very deep, rapid and sustained levels of TTR reduction translate into what we've long expected to be a lower event rate. And so as we continue to monitor those patients, that also figures into our calculation. So when you step back and look at the changes in total, we expect that we will have an even more robust outcome than we expected before, not only for the overall, but for patients on stabilizer. We'll be able to have enrollment fall within the original guidance, which we're very excited about and be in a position to march towards what we think will be 3 prospective launches by 2030.

Q: With respect to the Phase 1 ATTR-CM update later this year, can you just give us a little bit more color around what level of progression you all would normally expect to see on the various functional measures in patients just given the patient population enrolled in that study and the amount of follow-up.

A: As mentioned, the first thing is to look at the effect on TTR. So the levels come down within a month, and they come down to levels of about 90% reduction in all patients, very consistently. No patient is left behind with that. With that, what we showed at AHA last year was that there is -- when you have the measures of progression such as proBNP, such as 6-minute walk, unlike placebo patients and unlike patients from other agents, they do not show the worsening that those -- in those trends that we've seen historically. And there's now a lot of data available for multiple Phase III trials. What we do see is stabilization and in some cases, improvement in the patients in those measures. So this is unprecedented really with any drug. Based on that, we've also looked, as John mentioned, at event rates and the event rates in this group of patients who are actually at high risk of worsening because they're 50% Class III patients, a high percentage of variant patients. Despite all that, the event rate is very low relative to what we see historically in other settings. So all that comes together to say that in this data update, we look forward to seeing it. We have more extended data in this group of patients. And as we said, we're excited about what we're seeing in those Phase I patients.