Intellia Therapeutics, Inc. (NTLA) Earnings

Management highlights

### Lombosi (Flamvozi) for Hereditary Angioedema (HAE) – Phase 3 & Pre-Commercial Progress - Positive top-line results from the Phase 3 HALO trial were reported in April 2026, with results published in the *New England Journal of Medicine* (Intelia's sixth publication in the journal) and presented at IACI as a late-breaking oral presentation. The trial met the primary endpoint and all key secondary endpoints with statistical significance. - Key efficacy results: 87% reduction in mean monthly HAE attacks for Lombosi vs placebo; 62% of Lombosi patients were entirely attack-free and therapy-free during the 6-month primary observation period; all Lombosi patients experienced attack rate reductions from baseline by weeks 5-28, with meaningful reductions across all patient subgroups regardless of age, sex, baseline attack rate, or prior therapy; mean attack rates fell below pre-screening levels by week 4 and approached zero in the post-observation crossover period. - Favorable safety profile: All treatment-emergent adverse events were grade 1 or grade 2, with no serious adverse events reported in the Lombosi arm as of the data cutoff. The most common adverse events were infusion-related reactions, headache, and fatigue. - Rolling BLA submission to the FDA is underway, with FDA acceptance of the filing expected by the end of 2026. Pre-commercial preparations for a potential U.S. launch in H1 2027 are well advanced, including completion of hiring for field medical, reimbursement, and strategic account teams, payer outreach, treatment center preparation, and distribution planning. A new disease awareness website, haereframe.com, was launched in Q2 to educate stakeholders on the burden of chronic HAE therapy. ### Nexi for Transthyretin Amyloidosis (ATTR) – Phase 3 & Scientific Progress - Clinical holds on the two Nexi Phase 3 trials (Magnitude for ATTR cardiomyopathy, ENLIGHTEN for ATTR polyneuropathy) were resolved earlier in 2026, and enrollment and dosing resumed in Q2 2026. Global screening rates are rapidly increasing, with high investigator enthusiasm. - Intelia management notes that recent disappointing top-line results from the CardioTransform trial of competitor eplannersin (a TTR silencer) are specific to that agent, not evidence that all combination therapy with stabilizers and silencers is ineffective. Nexi delivers a more consistent, rapid, and deep TTR knockdown than approved chronic therapies: Phase 1 data shows a mean 90% TTR reduction achieved within one month, with mean serum TTR falling below 20 mcg/mL (one-third the absolute level of the leading chronic silencer), and durable, consistent TTR control maintained across all patients since the first doses were given in 2021. This profile positions Nexi to deliver clinical benefit on top of background stabilizer therapy. - The Magnitude trial (for ATTR cardiomyopathy) has enrolled over 650 patients, with event accrual continuing uninterrupted through the earlier clinical hold; the blinded event rate remains within the company's internal projected range. The company will review the full CardioTransform data at the upcoming ESC congress and may consider trial design optimization based on new learnings. - The company identified a genetic risk signal for rare high-grade transaminase elevations: sequencing of over 600 patient samples found that the HLA allele C0501 (carried by ~12% of the study population) is associated with a significantly higher rate of grade 3+ transaminase elevations, though the vast majority of C0501-positive patients do not experience severe elevations. The finding confirms the company's hypothesis that elevations are caused by an adaptive immune response, and allows pre-screening to identify at-risk patients. Updated trial protocols now require pre-treatment HLA typing for all patients, with results shared with investigators and patients to inform treatment decisions.

Guidance

- BLA filing acceptance for Lombosi is expected by the end of 2026, with a potential U.S. launch in the first half of 2027. - The company expects the current cash balance of $628.4 million to provide a runway into at least 2028; this guidance is conservative and excludes any potential future product revenue. - Enrollment in the Nexi Phase 3 Magnitude trial is on track to be completed by the end of 2026. It is still too early to provide guidance on the readout timing for Magnitude, though the blinded event rate remains within internal projections.

Segment performance

Intelia Therapeutics is a clinical-stage biotech company with no commercial product sales as of Q2 2026. All revenue is generated from collaboration agreements. Collaboration revenue for Q2 2026 was $7.7 million, a decrease from $14.2 million in the year-ago quarter, driven by reduced revenue from partner Regeneron. Research and Development (R&D) expenses were $82.6 million in Q2 2026, down from $97 million in Q2 2025; the decrease was primarily driven by lower external costs for the company's two lead programs (Lombosi and Nexi) and reduced stock-based compensation, partially offset by higher employee expenses from increased headcount. Stock-based compensation included in R&D was $9.4 million for the quarter. General and Administrative (G&A) expenses were $37.8 million in Q2 2026, up from $27.2 million in the year-ago quarter; the increase reflects ongoing build-out of commercial infrastructure for upcoming launches, higher legal costs, and increased stock-based compensation. Stock-based compensation included in G&A was $8.6 million for the quarter. Net loss for Q2 2026 was $106.6 million, compared to a net loss of $101.3 million in Q2 2025. As of June 30, 2026, the company held $628.4 million in cash, cash equivalents, and marketable securities, following an equity financing completed in April 2026 that generated $195 million in net proceeds.

Risks & headwinds

- Less than 1% of Nexi trial patients experienced grade 4 transient transaminase elevations, with higher risk among carriers of the HLA C0501 allele. While the vast majority of C0501 carriers do not experience severe elevations and mitigation measures are in place, the risk of liver adverse events could impact the benefit-risk profile of Nexi if approved. - It is still unclear how the FDA will respond to the new HLA typing and risk mitigation protocols for Nexi, and how this will affect trial enrollment or eventual regulatory approval. - The negative outcome of the competitor CardioTransform trial for ATTR cardiomyopathy has created market uncertainty around combination therapy for ATTR, which could impact trial design, investor sentiment, or eventual adoption of Nexi if approved. - Regulatory approval of both Lombosi and Nexi is not guaranteed, even with positive Phase 3 results.

Analyst Q&A

• Q: What are the implications of the HLA C0501 allele finding for at-risk patients, and how will it be managed? /

  A: The finding confirms that the elevated transaminase risk is linked to an adaptive immune response, which validates the existing mitigation measures. Only 12% of patients carry the allele, and most of these carriers do not experience severe elevations. All patients will be genotyped during screening, and carriers will be informed of their elevated risk to make an informed decision about whether to proceed with treatment; many carriers may choose to self-exclude, which is considered appropriate. For the 88% of patients who do not carry the allele, the finding confirms their risk of severe elevation is extremely low, which builds confidence in Nexi's safety profile.

• Q: Is the HLA C0501 risk specific to Nexi, or does it also apply to Lombosi? /

  A: This finding is almost certainly specific to Nexi and has no implications for Lombosi. The HLA allele binds a peptide sequence specific to Nexi's construct, and there is no signal of elevated transaminases in any Lombosi patients, which is confirmed by the published New England Journal of Medicine Phase 3 data. Only a small subset of C0501 carriers experience severe elevations.

• Q: What potential changes to the Magnitude ATTR trial is Intelia considering after the negative CardioTransform trial results? /

  A: The company will not make any changes until it reviews the full CardioTransform data at the upcoming ESC congress. Management believes the negative CardioTransform results are specific to competitor eplannersin, not generalizable to all TTR silencer combination therapy. Key factors to evaluate from the data are the degree and consistency of TTR reduction, speed of effect, and durability, as inconsistent or incomplete TTR reduction is likely what drove eplannersin's poor outcome. All trial modifications (enrollment increases, longer follow-up, etc.) are on the table, but no changes will be made until the full data is understood.

• Q: What is the purpose of the HAE Reframe disease awareness website, and what data will be presented at the upcoming HAE symposium? /

  A: HAE Reframe is designed to educate payers, physicians, and patients on the full burden of chronic lifelong HAE therapy, which goes beyond just attack frequency — including the burden of recurring prior authorizations, daily adherence, and ongoing disease impact even with treatment. This highlights the benefit of Lombosi's one-time curative approach. At the upcoming symposium, the company will present new molecular-level data on Lombosi's mechanism, including a deep dive on a single outlier patient who did not achieve attack-free status, and confirms the patient's ongoing symptoms were due to an unrelated condition, reinforcing Lombosi's efficacy for HAE specifically.

• Q: What explains the rare mild LFT excursions observed in the published Lombosi Phase 3 data supplement? /

  A: There is no safety signal for elevated LFTs with Lombosi; no LFT elevation greater than grade 2 has been observed across the entire Lombosi program. All mild grade 2 elevations had clear unrelated confounding factors, including late elevations caused by unrelated patient health events, one case linked to alcohol use that resolved rapidly, and another linked to a pre-existing viral infection during screening. All observed elevations were benign, and the safety profile of Lombosi remains clean as it moves toward BLA approval.