Intellia Therapeutics (NASDAQ:NTLA) management used its fourth-quarter and full-year 2025 earnings call to highlight progress across its two lead in vivo CRISPR gene-editing programs—lonvo-z in hereditary angioedema (HAE) and Nex-z in transthyretin (TTR) amyloidosis—while providing updates on the regulatory status of its ATTR clinical trials and outlining commercial preparation for a potential HAE launch.
Company sets up for phase 3 readouts in 2026
Chief Executive Officer John Leonard framed 2025 as a year of “accomplishment and resiliency,” emphasizing the company’s focus on one-time outpatient IV infusions intended to deliver durable clinical benefit. He said Intellia has up to three years of follow-up from phase 1 and 2 studies without “any waning of effect” in serum kallikrein (for HAE) or TTR levels (for ATTR), and he said clinical and disease measures tracked in those early-stage trials also have not waned.
lonvo-z: Phase 3 enrollment complete; BLA planned for second half
Leonard said Intellia completed enrollment in HAELO, its phase 3 HAE trial, with 80 patients in September 2025—nine months after dosing the first patient. He attributed the pace to strong interest from patients and treating physicians and pointed to third-party market research Intellia shared at the J.P. Morgan meeting in January.
In that survey, Leonard said 104 U.S. patients and caregivers were shown a blinded target product profile based on phase 1/2 data and told it was from a gene-editing candidate. According to management, 99% said they would be at least somewhat likely to take the treatment if approved, and nearly two-thirds said they would be extremely or very likely. In a separate survey of 151 U.S. healthcare providers presented the same profile, Leonard said 92% reported they could identify a patient for whom they would prescribe the therapy; those providers collectively managed care for more than 4,000 patients, and they estimated prescribing to about 2,200 patients (54% of patients under their care).
Leonard also cited a separate 100-patient survey presented at ACAAI in November, where about 90% of respondents were on long-term prophylaxis therapies. He said nearly 70% were concerned about taking long-term prophylaxis and/or on-demand medications for life, nearly 60% were concerned about HAE’s unpredictable nature, and most cited logistical and financial burdens. He noted that only 20% of surveyed patients reported being attack-free over the past 12 months, contrasting with Intellia’s pooled phase 1 analysis presented in November showing that 76% of patients at least a year beyond a 50-mg lonvo-z dose were free from both attacks and ongoing therapy for at least 12 months.
Looking ahead, Leonard reiterated Intellia’s expectation for top-line HAELO data by mid-2026 and a planned BLA submission in the second half of 2026. He said that in phase 3 trials for approved long-term prophylaxis therapies, the best attack-reduction rates have been in the 80% range, and the best attack-free rate he has seen is approximately 60% with chronic therapy. In HAELO’s placebo-controlled setting, Leonard said Intellia believes the lonvo-z arm will be “highly competitive” with those benchmarks while offering a one-time treatment approach.
During Q&A, management said the phase 3 population was designed to be representative of typical HAE patients with a range of severities and background therapies, including market-leading drugs. Leonard also noted that U.S. trial participation required patients to stop existing drugs, wash out, establish a baseline attack rate, and then enter a placebo-controlled double-blind phase—something he suggested reflects patient interest.
Commercial and manufacturing readiness for HAE
Chief Financial Officer Ed Dulac said Intellia has been preparing for a potential lonvo-z launch by scaling its field medical team, increasing engagement with physicians and patient advocacy groups, engaging with payers, and developing a launch strategy. For 2026, he said the company plans to continue building sales and reimbursement field teams, finalize distribution models, identify U.S. treatment centers, and finalize pricing and contracting strategy, while noting it is premature to share specifics on pricing.
Dulac discussed the economics of HAE chronic therapies, saying long-term prophylaxis treatments carry “ultra-orphan price tags” and that lifetime treatment costs can be measured in the “$multi-millions,” given diagnosis often occurs around age 20 and on-demand medications are also needed. He said Intellia believes a one-time therapy could offer savings to patients and payers and reduce administrative burdens such as repeated prior authorizations.
On market sizing, Dulac said about 7,000 patients receive treatment for HAE in the U.S. He added that if lonvo-z achieved a mid-single-digit market share in a given year, resulting cash flows could potentially enable Intellia to fully fund operations, given anticipated margins and expected cost structure.
On payer mix, Dulac said roughly 70% of the opportunity is commercial payers for lonvo-z. He also said payer discussions to date have been “very encouraging,” with payers recognizing unmet need and the potential value of a one-time therapy, though the company has not discussed price specifically.
On manufacturing, Leonard said Intellia believes it is in “complete preparation” from a CMC standpoint and noted that HAELO is using material that would be the same as commercial material, with no need for end-of-study comparability work due to manufacturing-site changes. Dulac added that lonvo-z CDMO providers are long established, primarily in Europe, and that commercial-scale processes have been validated.
Nex-z (ATTR): clinical hold dynamics and protocol changes
Leonard recapped rapid enrollment in Intellia’s ATTR programs prior to a clinical hold. In 2025, management originally expected about 550 patients enrolled in MAGNITUDE (ATTR with cardiomyopathy) by year-end, and MAGNITUDE-2 (ATTR with polyneuropathy) had not yet begun enrollment at the start of the year. By October, Intellia had enrolled more than 650 patients in MAGNITUDE and was approaching full enrollment in MAGNITUDE-2.
Intellia suspended enrollment in MAGNITUDE and MAGNITUDE-2 in late October after elevated liver transaminases and total bilirubin in a MAGNITUDE patient met protocol-defined pausing criteria, and the FDA subsequently placed the trials on clinical hold. Leonard said that in late January the FDA lifted the clinical hold on MAGNITUDE-2 (polyneuropathy), and the company aligned with the agency on modifications:
- Supplementary liver lab tests in the weeks following enrollment and dosing
- Guidance for a short-term steroid regimen if elevated liver transaminases are detected in the weeks immediately following dosing
- Modified screening criteria excluding patients with significantly elevated liver enzymes at screening and those with a history of MASH or autoimmune hepatitis
Leonard said Intellia expects the new criteria to safeguard patients with minimal impact on screen-failure rates. He also said 47 patients had already been enrolled in MAGNITUDE-2 and that the protocol amendment increased target enrollment from 50 to approximately 60 to accommodate patients identified for screening before the hold. Because MAGNITUDE-2 is enrolled outside the U.S., Leonard said the company is working through local regulatory processes to resume screening and believes it can complete enrollment in the second half of 2026.
For MAGNITUDE (cardiomyopathy), Leonard said FDA engagement is ongoing and that the trials enroll “very different patient populations.” He repeatedly cautioned that the hold is not lifted until it is lifted but said the company has made substantial progress.
During Q&A, Leonard described the patient death referenced in connection with MAGNITUDE as a complicated case. He said the patient experienced Grade 4 transaminase elevations and a bilirubin increase but ultimately died from a ruptured duodenal ulcer, which “may or may not have been related” to treatment. Leonard said the company may never know exactly what happened, calling the patient an outlier. He also stated that Grade 4 elevations occurred in less than 1% of the MAGNITUDE patient population.
Leonard said the liver-lab pattern appears most consistent with an immune-mediated reaction and noted that observed LFT rises occurred typically within a three-to-five-week window and have not appeared later in follow-up. He said most patients experiencing rises recovered rapidly, generally without therapy, and that steroid use—triggered by protocol-defined LFT thresholds—would likely apply to a low single-digit percentage of patients.
Management also addressed why the FDA lifted the hold in polyneuropathy but not cardiomyopathy, citing differences in patient populations: polyneuropathy patients tend to be younger, while cardiomyopathy patients are often in their 70s or older, with more comorbidities and polypharmacy. Leonard added that Intellia has seen a “very good safety profile” in the polyneuropathy study to date.
Financial results and cash runway
Dulac reported cash, cash equivalents, and marketable securities of $605.1 million as of Dec. 31, 2025, down from $861.7 million a year earlier. He said the company believes its cash is sufficient into the second half of 2027 and beyond several milestones, including restarting enrollment in MAGNITUDE, completing enrollment in MAGNITUDE-2 in 2026, and launching lonvo-z next year.
Fourth-quarter collaboration revenue was $23.0 million, up from $12.9 million in the prior-year quarter, driven mainly by revenue recognized from termination of a license and collaboration agreement with SparingVision and increased cost reimbursement from the Regeneron collaboration.
Fourth-quarter R&D expense was $88.7 million, down from $116.9 million, reflecting reduced employee-related costs, stock-based compensation, research materials, and contracted services, partially offset by higher lonvo-z clinical trial expenses. Stock-based compensation in R&D was $10.5 million. G&A expense was $33.1 million, roughly flat year over year, including $6.2 million in stock-based compensation. Net loss for the quarter was $95.8 million, compared with $128.9 million a year earlier.
About Intellia Therapeutics (NASDAQ:NTLA)
Intellia Therapeutics, Inc (NASDAQ: NTLA) is a clinical‐stage biotechnology company focused on developing potentially curative genome editing therapies using the CRISPR/Cas9 platform. The company’s research spans both in vivo and ex vivo applications of CRISPR/Cas9, aiming to correct or disable disease‐causing genes with a single administration. Intellia’s lead in vivo program targets transthyretin amyloidosis (ATTR) by delivering CRISPR/Cas9 machinery directly to the liver, while additional preclinical efforts pursue treatments for hemophilia A, hereditary angioedema and other genetic disorders.
Beyond its in vivo pipeline, Intellia collaborates with strategic partners to extend the impact of its genome editing approach.
