Intellia Expands Phase III Trial to 1,200 Patients in ATTR Cardiomyopathy Study

Key Highlights from Intellia Therapeutics' Q2 2025 Earnings Call

Intellia Therapeutics, a leader in gene-editing therapies, shared significant updates during its Q2 2025 earnings call, highlighting progress across multiple clinical programs and financial performance. The company's leadership emphasized strong execution, increased enrollment in key trials, and confidence in future milestones.

John M. Leonard, President and CEO, stated that "2025 is proving to be a year of excellent execution and exciting clinical updates." He noted that the company is meeting or exceeding its objectives, which support a clear path through several major milestones, including the anticipated launch of Lonvo-z for hereditary angioedema (HAE) in the first half of 2027.

Leonard also announced that the company now expects to complete enrollment earlier in its HAE and ATTR polyneuropathy programs than previously thought. Additionally, the company plans to enroll more patients this year in its cardiomyopathy program than originally planned. This increase in patient enrollment reflects strong interest from both patients and physicians.

Expansion of Phase III Trials

The company has decided to expand the Phase III study evaluating nex-z in ATTR cardiomyopathy to approximately 1,200 patients, pending health authority review. Leonard attributed this decision to "strong interest from both patients and physicians" and noted that the expanded trial will provide a more robust data set, particularly in the stabilizer stratum.

In addition to trial expansions, the company has made key commercial and medical team hires, including the appointment of Head of U.S. Sales and Head of Commercial Operations. Leonard emphasized that the company is well on its way to becoming a commercially ready organization.

Leonard also announced the planned retirement of Chief Medical Officer David Lebwohl in August 2026, with a search for his successor already underway to ensure continuity.

Financial Performance and Outlook

Edward J. Dulac, Chief Financial Officer, reported that the company’s cash, cash equivalents, and marketable securities totaled approximately $630.5 million as of June 30, 2025. Collaboration revenue reached $14.2 million in Q2 2025, driven primarily by Regeneron Pharmaceuticals.

Dulac added that the company continues to expect a year-over-year decline in GAAP operating expenses, now guiding to an approximately 10% reduction this year. He confirmed that the current cash balance is sufficient to fund operating plans into the first half of 2027.

Management expects to complete enrollment of the Phase III HAELO study of lonvo-z during the third quarter of 2025. The Phase III magnitude study for ATTR cardiomyopathy is expanding to 1,200 patients, with a targeted cumulative enrollment of at least 650 patients by year-end 2025 and full enrollment by early 2027.

Enrollment in magnitude 2 for hereditary ATTR polyneuropathy is now expected to be completed in the first half of 2026. Leonard stated that the company is poised to complete enrollment across all studies by early 2027 and achieve several important clinical and regulatory milestones before the end of 2026.

Q&A Session and Analyst Questions

During the Q&A session, analysts probed various aspects of the company’s operations, including target proportions of stabilizer use in the expanded ATTR-CM trial, the impact of expanded enrollment on the cash runway, and event accrual rates in Phase III studies.

Leonard estimated that around 70% of patients may be on stabilizers in the expanded trial, though this was not a set target. Dulac explained that the recent decision to increase the trial size to 1,200 patients would result in an immaterial uptick in costs, which the company can absorb without affecting its cash runway or net cash burn guidance.

Analysts also asked about enrollment pace compared to competitors, with Lebwohl noting that the company’s plan to reach more than 650 patients by year-end and 1,200 by early 2027 is unprecedented and very exciting.

Sentiment and Market Positioning

Analysts were generally positive but inquisitive, focusing on trial design, patient mix, cost implications, and competitive landscape. Management maintained a confident and upbeat tone, emphasizing "robust demand," "unprecedented enrollment," and "strong execution."

Compared to the previous quarter, management exhibited increased confidence, especially regarding trial expansions and operational execution, while analysts continued to focus on enrollment metrics, trial design, and financial sustainability.

Operational and Strategic Shifts

The current quarter saw an increase in enrollment targets for the Phase III ATTR cardiomyopathy study (1,200 patients vs. previous guidance of 765), reflecting accelerated trial progress and heightened patient/physician demand. Guidance for year-end cumulative enrollment in magnitude was raised from "more than 550" to "at least 650" patients.

Operational focus shifted more toward commercial readiness, with significant leadership hires completed. Management's tone was more assertive on execution and upcoming milestones, while analysts continued to probe on enrollment pace, statistical powering, and commercial readiness.

No major change in expense guidance was reported, but there was a firmer commitment to a 10% year-over-year operating expense decline.

Risks and Concerns

Management acknowledged that the expanded trial size could pose operational challenges but reassured that the improvements gained from a larger study size do not impact previously projected enrollment or the cash runway.

Safety updates noted mild and manageable adverse events, with no new serious safety signals reported in ongoing trials. Analysts highlighted potential risks around enrollment pace, statistical powering, and competitive market entrants, but management consistently emphasized robust preparedness and adaptability.

Final Takeaway

Intellia Therapeutics signaled a pivotal quarter by dramatically expanding its Phase III ATTR cardiomyopathy program to 1,200 patients, citing strong global demand and operational momentum. The company reaffirmed confidence in its cash runway through early 2027, highlighted robust patient and physician interest across pipeline programs, and underscored commercial readiness with key leadership appointments. Management remains focused on achieving accelerated clinical milestones and delivering three prospective launches by 2030, positioning Intellia at the forefront of gene-editing therapeutics.