A second positive Phase III data readout in two months is a major reason why Intellia Therapeutics (Nasdaq: NTLA) shares have soared more than 76% over the past six months—including a 29% surge this past week that followed the CRISPR gene editing therapy developer’s lead pipeline candidate lonvoguran ziclumeran (lonvo-z) meeting three key secondary endpoints in a pivotal study in patients with hereditary angioedema (HAE).
Lonvo-z met the Phase III HAELO trial’s (NCT06634420) primary endpoint, Intellia announced back in April, by showing an 87% reduction (p<0.0001) in mean monthly attacks in the lonvo-z arm vs. the placebo arm during the efficacy evaluation period (weeks 5-28). Lonvo-z also aced the trial’s key secondary endpoint by showing that 62% of the 52 patients in the lonvo-z arm were entirely attack-free and therapy-free for the six-month efficacy evaluation period, vs. just 11% of the 28 patients in the placebo arm (p<0.0001).
On June 13, Intellia presented and published additional data showing lonvo-z to have achieved positive results on three other key secondary endpoints:
- Monthly rate of attacks requiring on-demand treatment, Weeks 5–28, mean (0.19 vs. 1.79, 95% CI).
- Monthly rate of moderate/severe attacks, Weeks 5–28, mean (0.11 vs. 1.23, 95% CI).
- Change from baseline to Week 28 in AE-QoL total score, mean ( — 23.51 vs. — 6.47, 95% CI).
Intellia presented the data at the European Academy of Allergy & Clinical Immunology (EAACI) Annual Congress 2026 in Istanbul, Türkiye, and published the results in The New England Journal of Medicine.
The data was strong enough for Intellia to continue the rolling Biologics License Application (BLA) submission that it began in April. The company expects to complete the BLA filing by year’s end and hopes to gain FDA approval and launch lonvo-z in the first half of 2027.
“Super pleased”
“We were super pleased with the results that we saw,” John Leonard, MD, Intellia’s president and CEO, told GEN. “We’re essentially replicating what we’ve seen throughout the program, where most of the patients reached a status of no attacks, no therapies over the course of this extended observation period. For those patients who didn’t, they appeared to be on their way to reaching that kind of a state. And critically important was that every single patient who got the drug was off long-term prophylaxis.”
“Across the board, and across all subgroups, the drug performed extremely well. So, we think it speaks to physicians, it’s going to speak to payers in terms of how they think about the drug and its ultimate, excellent utility,” Leonard said.
Investors and analysts appeared to share that enthusiasm this past week, as Intellia’s stock price rose over three of the four trading sessions following the release of data on the secondary endpoints. Intellia shares jumped 23% on June 15, the first trading day since the news, rising from $12.11 to $14.92. After a day of profit-taking that saw shares dip 2.5%, to $14.55, Intellia’s stock resumed its upward trajectory, rising nearly 4.5% to $15.20 on Wednesday, then another 3% Thursday, closing the week at $15.67. Markets were closed on Friday for the Juneteenth holiday.
Since December 18, 2025, when Intellia shares closed at $8.88, the stock has soared nearly 76.5%, accounting for most of its one-year gain of 62%. Lonvo-z accounted for three of Intellia’s four stock price peaks in 2026: The dosing of the first patient in HAELO, announced January 22, led the stock to climb 13%, from $14.03 to $15.90.
Shares surged 12% March 2, from $13.78 to $15.44, when the FDA lifted a clinical hold on the company’s Phase III MAGNITUDE trial (NCT06128629) assessing nexiguran ziclumeran (nex-z) in transthyretin amyloidosis with cardiomyopathy (ATTR-CM). The FDA imposed the hold after an elderly patient died during a study of Nex-z, an in vivo CRISPR-based therapy developed in partnership with Regeneron Pharmaceuticals (Nasdaq: REGN) to treat ATTR-CM by inactivating the TTR gene.
The third peak, an 8% gain from $15.31 to $16.57 on April 22, followed Intellia reporting positive data for lonvo-z, showing that it met HAELO’s primary endpoint, while the fourth peak followed the secondary endpoint announcement.
Misperceived market
“Hereditary angioedema has, in the last 10 to 15 years, had a variety of therapies arrive that are better than the ones that were there 20 years ago. Twenty years ago, circumstances were pretty grim for patients with HAE,” Leonard recalled. “I think some investors have looked at this incorrectly as a satisfied market, only because there are other therapies available.”
Among those therapies are three that won FDA approval last year. Last August, the agency approved Dawnzera® (donidalorsen), a prekallikrein-directed antisense oligonucleotide designed to prevent HAE attacks in patients ages 12+, marketed by Ionis Pharmaceuticals (Nasdaq: IONS). A month earlier, the FDA authorized Ekterly® (sebetralstat), a plasma kallikrein inhibitor indicated for the treatment of acute attacks of HAE in patients ages 12+, marketed in the United States by KalVista Pharmaceuticals (Nasdaq: KALV).
And in June 2025, the FDA approved Andembry® (garadacimab-gxii), an activated Factor XII (FXIIa) inhibitor (monoclonal antibody) and the first long-term prophylactic HAE treatment designed to target Factor XIIa, administered as a once-monthly subcutaneous injection for patients ages 12+, marketed by CSL Behring, the largest business unit of Australian-owned CSL (ASX: CSL).
“What we’re showing is that a lot of efficacy and a lot of utility has been left on the table, and that it’s possible for patients to get pretty close to something resembling a normal person who does not have HAE and all of the things, benefits that come with that,” Leonard said. “As people have looked at the data more completely, I think they’re seeing more and more that that’s the case, and maybe some of those original premises that they had are not quite correct.”
In research notes, three analysts said Intellia’s latest data strengthened the company’s future case to regulators for pursuing approval of lonvo-z as a one-time HAE treatment.
“We view these data as furthering Intellia’s case for regulatory approval following its expected completion of a rolling BLA,” Myles R. Minter, PhD, a partner and biotechnology analyst with William Blair, wrote June 15.
A day earlier, Jefferies equity analyst Maury Raycroft, PhD, commented that Intellia’s latest data will help lonvo-z gain more than a foothold in the HAE market.
“Positive implications”
“Big picture, we believe total HAE data have positive implications for commercial positioning” of lonvo-z, Raycroft wrote. “Editing is expected to be durable (we have seen longer term ph.I/II data out to 3-yrs); therefore, NTLA’s approach could eliminate need for lifelong chronic tx [therapy], justifying the value proposition of a 1X tx, despite competition in a crowded HAE space.”
Raycroft cited market research from Intellia showing that 64% of surveyed patients on LTPs [long-term prophylaxis drugs] are extremely likely to transition to a one-time therapy, while 54% surveyed docs expressed intent to prescribe such a treatment.
Mani Foroohar, MD, senior managing director, genetic medicines, and a senior research analyst with Leerink Partners, said Intellia’s latest results “again demonstrate lonvo-z’s clean safety and best-in-class efficacy and convenience.”
Writing in NEJM, the team of HAELO investigators reported no serious adverse events in patients treated with lonvo-z: “The most common adverse reactions were infusion-related reactions, which were generally transient and resolved without intervention. Elevated levels of serum aspartate aminotransferase and alanine aminotransferase, which occurred in approximately 10 to 15% of patients treated with lonvo-z, were transient, asymptomatic, and resolved without intervention.”
Foroohar sided with optimistic investors over their pessimistic counterparts in arguing that patients will warm up to a one-time treatment, though it will likely be costlier than current therapies.
Bears and bulls
“Bears argue limited patient demand to move up the innovation curve in a market with several approved treatments. We take the other side of this and see onetime therapy (vs lifetime chronic dosing) and patient desire to be attack-free as potent tailwinds to adoption,” Foroohar wrote. “Longer follow-up and crossover data (caveat – small n [number of patients studied]) provide an early glimpse at the improving profile of lonvo-z over time. We look to more data ahead of 1H27 launch to further educate physicians/patients.
“Subgroup analyses demonstrate clear benefit across all patient populations (prior LTP use, historical attack severity/frequency, etc.), supporting broad uptake as SoC [standard of care] across HAE—recognizing this will take time to play out as physicians gain comfort with this (likely) first approved in vivo gene editing therapy,” Foroohar added.
Intellia has not set a price for lonvo-z.
“We have said publicly we’re not going to set any new records beyond prices that have been precedented,” Leonard said.
HAE patients, he continued, “are some of the most costly patients that payers have. They’re small in number, but high in cost, with the therapies they take and their healthcare resource utilization exceeding $1 million a year.
“When you consider that these are patients that are oftentimes treated, or first diagnosed in adolescence or young adulthood, the lifetime costs are frighteningly high,” Leonard explained. “We are confident that, and we have this as an intended outcome, that we will save lifetime health, resources in very, very substantial terms, in a way that payers see and can recognize. We want to make it easy for patients to get onto the therapy, and we want to make it very competitive, cost-competitive for physicians taking care of them.”
Leaders and laggards
- Elicio Therapeutics (Nasdaq: ELTX) shares plunged 72.5% from $14.85 to $4.08 on June 15 after the developer of immunotherapies to treat high-prevalence cancers said it was evaluating multiple strategic financing and partnership opportunities to advance its planned Phase III adjuvant pancreatic cancer immunotherapies program and broader AMP platform. The action came after ELI-002 7P, a 7-peptide formulation of its lead candidate ELI-002, failed the Phase II AMPLIFY-7P trial (NCT05726864) in patients with mKRAS-driven pancreatic ductal adenocarcinoma (PDAC). ELI-002 7P missed the pre-specified primary endpoint of disease-free survival (DFS) in the intent-to-treat population. Elicio said the ELI-002 7P arm had a higher proportion of R1 resected (higher residual disease) patients vs. the observation arm (19% vs. 10%), and that post-hoc analyses showed significant DFS improvement (R0: HR 0.65, p=0.048) in the 121 lower residual disease (R0 completely resected) patients, a subgroup representing approximately 84% of enrolled patients. Elicio said the trial results will shape a Phase III strategy focused on a defined R0 resected population and additional ELI-002 7P dosing.
- Neumora Therapeutics (Nasdaq: NMRA) shares plummeted 49% from $1.78 to 91 cents on June 15 after the brain disease drug developer said it was chopping its workforce by approximately 35% or about 34 jobs, ending development of its major depressive disorder (MDD) candidate navacaprant, and refocusing on advancing the rest of its pipeline. The actions came after navacaprant missed statistical significance on the primary and key secondary endpoints of the Phase III KOASTAL-2 trial (NCT06058013) and KOASTAL-3 trial (NCT06058039) in MDD. The primary endpoint was the change from baseline to week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS). Neumora projected the job cuts would save it approximately $10 million annually, to be partially offset this year by approximately $2 million in one-time restructuring costs. Neumora said current cash and cash equivalents are expected to provide runway into Q3 2027, including multiple expected key clinical milestones. Neumora’s pipeline includes NMRA-511 in Alzheimer’s disease agitation, NMRA-898 in schizophrenia, and NMRA-215 in cardiometabolic disease.
- uniQure (Nasdaq: QURE) shares zoomed 78% from $26.99 to $48.16 Wednesday after the gene therapy developer announced the FDA’s revised position that a three-year analysis from its two-trial, Phase I/II study (United States, NCT04120493, and Europe (NCT05243017) of AMT-130 in Huntington’s disease was now acceptable as the primary basis of a Biologics License Application (BLA) for accelerated approval of the gene therapy. Researchers hailed “game-changing” data last year showing significant slowing of Huntington’s disease (HD) progression, but the FDA disagreed while its Center for Biologics Evaluation and Research (CBER) was headed by Vinayak (Vinay) Prasad, MD, who resigned in April. uniQure said the FDA seeks to align on the confirmatory study design prior to the BLA submission, including considering allowing concurrent control on standard-of-care therapy instead of a sham procedure. “FDA communicated that they would work as expeditiously as possible with uniQure on this effort. The company is committed to conducting the confirmatory study without delay and expects to further align with the FDA on the details of such a study prior to BLA submission,” uniQure stated.
The post StockWatch: Positive Phase III Data Sells Investors on Intellia appeared first on GEN – Genetic Engineering and Biotechnology News.
