Intellia Therapeutics (NTLA) Q2 FY26 earnings call: guidance and Q&A

What are the implications of the C*05:01 allele finding for the 12% of patients at added risk? Are there other parameters for patient selection, and what is the biologic relationship triggering the immune response?

The finding confirms an adaptive immune response, supporting current mitigation measures. Information on the allele will be provided to investigators and patients, allowing them to make informed decisions. Many C*05:01 carriers do not experience elevations, but the allele increases the likelihood of severe events. The company will discuss further implications with the FDA.

“What the finding gives us is valuable, a mechanistic explanation for a general signal we had already flagged and a way to identify patients who are more likely to be affected before it happens.”

asked by Maurice Raycroft · answered by John Leonard

Is the HLA allele finding specific to nex-z and not lonvo-z? Also, is it correct that only a fraction of the 12% of C*05:01 carriers actually had elevations?

The finding is almost certainly specific to nex-z due to the nature of HLA molecules and the absence of a signal in lonvo-z patients. Yes, while 12% of samples carry the allele, only a small subset experienced higher-grade transaminase elevations.

“almost certainly, this would be specific to nex-z and not have any implications for lonvo-z.”

asked by Unknown Analyst · answered by John Leonard

What options are being contemplated to optimize the MAGNITUDE trial design after reviewing CARDIO-TTRansform data, such as enrolling more patients, extending follow-up, or limiting SGLT2 use?

The primary focus is to fully understand the CARDIO-TTRansform data, which is believed to be specific to eplontersen. The company will consider if any changes are needed, remaining open-minded and adaptive, but will not pre-emptively decide on specific tweaks until the data is thoroughly analyzed.

“The first order of business is really understanding the data that comes from the CARDIO-TTRansform study.”

asked by Luca Issi · answered by John Leonard

Can you remind us of the background stabilizer use in the MAGNITUDE study and if it's expected to change? Also, will the HLA finding impact enrollment?

Background stabilizer use is around 80% and is not expected to change. Most investigators view the HLA finding as confidence-building, as it helps identify patients and manage risk. While some patients may self-exclude, the overall impact is expected to enhance confidence and potentially accelerate screening.

“Background stabilizer use is running around 80%, which is what we projected when we set out and what we've been confirming on various data releases along the way.”

asked by Salveen Richter · answered by John Leonard

How many patients with Grade 3 liver signals did not carry the C*05:01 allele, and were there lower-grade signals in carriers? Are additional prophylactic measures considered for C*05:01 carriers, and what are the additional risks?

Full data will be released at an appropriate time. No additional prophylaxis is planned for C*05:01 carriers beyond existing mitigation measures, which are deemed appropriate for an adaptive immune response. The finding allows identification of patients with a substantially higher likelihood of elevation, but most carriers will not experience them. For non-carriers, the likelihood of high LFT elevation is extremely low.

“For the approximately 90% of people who don't carry C*05:01, the likelihood of a high LFT elevation is extremely low.”

asked by Unknown Analyst · answered by John Leonard

Do you expect HLA genotyping to be on the label if nex-z is approved, and will every patient be genotyped in a commercial setting?

It's too early to say if HLA genotyping will be on the label. The current focus is on providing good information to physicians and patients to optimize benefit-risk. Genotyping will be collected during screening in the study and is not expected to slow down screening; rather, it may pick up the pace.

“I think it's too early to say. Oftentimes, as you well know, labels reflect many of the aspects of how clinical trials are done and the data that they accumulate.”

asked by Unknown Analyst · answered by John Leonard

The NEJM supplement for lonvo-z showed 3 patients with AST excursions outside the reference range around week 30-32. Is this variability or something else?

Across the lonvo-z program, no LFT elevation greater than Grade 2 has been observed. The specific cases mentioned were benign, low-grade, and likely related to other confounding factors or viral infections, not the drug itself. The overall efficacy and safety profile remains strong.

“Across the entire program, there's never been an LFT elevation greater than Grade 2.”

asked by Myles Minter · answered by John Leonard

Is HLA genotyping specific for ATTR-CM, or is it also relevant for polyneuropathy? Is genotyping being done for other upcoming trials?

The genotyping is done across the entire nex-z program, irrespective of the ATTR indication (cardiomyopathy or polyneuropathy), and is considered a relevant finding for both. The company is not currently doing genotyping on a standard basis for any other new programs, as the nex-z finding is considered very specific.

“No, the genotyping is done across the entire program irrespective of the indication. And we're treating it as a relevant finding for both polyneuropathy and for cardiomyopathy and are applying the same rules and the same -- providing the same information for both studies.”

asked by Unknown Analyst · answered by John Leonard