Q2 2026 Intellia Therapeutics Inc Earnings Call

August 6, 2026

Operator: Hello, and welcome to Intellia Therapeutics' Q2 conference call. My name is Chloe, and I will be your conference operator today. Please be advised that today's call is being recorded. I would now like to turn the call over to Jason Fredette, Vice President of Investor Relations and Corporate Communications at Intellia. Please proceed.

Operator: Hello, and welcome to Intellia Therapeutics' Q2 Conference Call. My name is Chloe, and I will be your conference operator today. Please be advised that today's call is being recorded. I would now like to turn the call over to Jason Fredette, Vice President of Investor Relations and Corporate Communications at Intellia. Please proceed.

Speaker #1: Hello, and welcome to Intellia Therapeutics Q2 conference call. My name is Chloe, and I will be your conference operator today. Please be advised that today's call is being recorded.

Speaker #1: I would now like to turn the call over to Jason Fredette, Vice President of Investor Relations and Corporate Communications at Intellia. Please proceed.

Speaker #2: Thank you, operator, and hello, everyone. outlining recent business updates in our Q2 financial results. This document can be found on the Investors and Media section of Intellia's website at intellia-tx.com.

Jason Fredette: Thank you, operator, and hello, everyone. Earlier this morning, we issued a press release outlining recent business updates in our Q2 financial results. This document can be found on the Investors and Media section of Intellia's website at intelliatx.com. At this time, I would like to take a minute to remind listeners that during this call, Intellia management may make certain forward-looking statements. We ask that you refer to our SEC filings available at sec.gov for a discussion of potential risks and uncertainties. All information presented on this call is current as of today, and Intellia undertakes no duty to update this information unless required by law. Joining me on the call are John Leonard, our Chief Executive Officer, and Edward Dulac, our Chief Financial Officer. With that, I'll now turn the call over to John to begin our business discussion.

Speaker #2: At this time, I would like to take a minute to remind listeners that during this call, Intellia management may—earlier this morning, we issued a press release—make forward-looking statements.

Speaker #2: We ask that you refer to our SEC filings available at sec.gov for a discussion of potential risks and uncertainties. All information presented on this call is current as of today, and Intellia undertakes no duty to update this information unless required by law. Leonard, our Chief Executive Officer, and Ed Dulac, our Chief Financial Officer.

Speaker #2: We ask that you refer to our SEC filings available at make certain forward-looking sec.gov for a discussion of potential risks and uncertainties. All information presented on this call is current as of today, and Intellia undertakes no duty to update this information unless required by law.

Jason Fredette: We ask that you refer to our SEC filings available at sec.gov for a discussion of potential risks and uncertainties. All information presented on this call is current as of today, and Intellia undertakes no duty to update this information unless required by law. Joining me on the call are John Leonard, our Chief Executive Officer, and Ed Dulac, our Chief Financial Officer. With that, I'll now turn the call over to John to begin our business discussion.

Speaker #2: Joining me on the call are John business discussion.

Speaker #3: Thank you, Jason, and good morning, everyone. We're excited to be speaking with you to recap the tremendous progress we made in our Phase III development programs of LANVOSI, Inherentary Angioedema, or HAE, and NEXI in transthyretin amyloidosis, or ATTR.

John Leonard: Thank you, Jason, and good morning, everyone. We're excited to be speaking with you to recap the tremendous progress we made in our phase III development programs of lonvo-z in hereditary angioedema, or HAE, and nex-z in transthyretin amyloidosis, or ATTR. The full results of our phase III HAELO trial in HAE position us very well for potential approval and launch of the world's first in vivo gene-editing product in the H1 of next year. We also have gained important new genomic insights that further our understanding of nex-z's profile and could help position us even more favorably within a large and dynamic ATTR market. Let's begin with lonvo-z. Simply put, the Q2 was a momentous period for this program. In April, we reported positive top-line results from HAELO and got our rolling BLA submission underway with the FDA.

Speaker #3: The full results of our Phase III HALO trial in HAE position us very well for a potential approval and launch of the world's first in vivo gene editing product in the first half of next year.

Speaker #3: We have also gained important new genomic insights that further our understanding of NEXI's profile and could help position us even more favorably within a large and dynamic ATTR market.

John Leonard: We also have gained important new genomic insights that further our understanding of nex-z's profile and could help position us even more favorably within a large and dynamic ATTR market. Let's begin with lonvo-z. Simply put, Q2 was a momentous period for this program. In April, we reported positive top-line results from HAELO and got our rolling BLA submission underway with the FDA.

Speaker #3: Let's begin with LANVOSI. Simply put, the Q2 was a momentous period for this program. In April, we reported positive top-line results from HALO and got our rolling BLA submission underway with the FDA.

Speaker #3: This was followed by our late-breaking oral presentation at IACI and a concurrent publication in the New England Journal of Medicine, Intellia's sixth manuscript, in this prestigious journal.

John Leonard: This was followed by our late-breaking oral presentation at EAACI and a concurrent publication in "The New England Journal of Medicine," Intellia's sixth manuscript in this prestigious journal. HAELO was an unequivocal success as we achieved statistical significance for the primary and all key secondary endpoints. More specifically, during the 6-month primary observation period, we reported an 87% reduction in mean monthly attacks for lonvo-z versus placebo. 62% of patients were entirely attack-free and therapy-free in the lonvo-z arm. A 23-point improvement was observed for the lonvo-z arm in the total angioedema quality of life score from baseline. For context, a change of just 6 points is considered to be clinically meaningful. The "New England Journal" manuscript also contained compelling figures and analyses underscoring the unique value proposition that could be afforded by this one-time therapy if it's approved.

Speaker #3: HALO was an unequivocal success as we achieved statistical significance for the primary and all key secondary endpoints. More specifically, during the six-month primary observation period, we reported an 87% reduction in mean monthly attacks for LANVOSI versus placebo.

Speaker #3: 62% of patients were entirely attack-free and therapy-free in the LANVOSI arm, a 23-point improvement was observed for the LANVOSI arm in the total angioedema quality-of-life score from baseline.

John Leonard: 62% of patients were entirely attack-free and therapy-free in the lonvo-z arm. A 23-point improvement was observed for the lonvo-z arm in the total angioedema quality of life score from baseline. For context, a change of just 6 points is considered to be clinically meaningful. The "New England Journal" manuscript also contained compelling figures and analyses underscoring the unique value proposition that could be afforded by this one-time therapy if it's approved.

Speaker #3: For context, a change of just six points is considered to be clinically meaningful. The New England Journal manuscript also contained compelling figures and analyses underscoring the unique value proposition that could be afforded by this one-time therapy if it's approved.

Speaker #3: For instance, patient-level data demonstrated that all patients in the LANVOSI arm experienced attack rate reductions from baseline for weeks 5 to 28. In other words, every single patient received a clinical benefit including those who are not yet fully attack-free during that six-month period.

John Leonard: For instance, patient-level data demonstrated that all patients in the lonvo-z arm experienced attack rate reductions from baseline for weeks 5 to 28. In other words, every single patient received a clinical benefit, including those who are not yet fully attack-free during that 6-month period. A subgroup analysis demonstrated meaningful attack rate reductions in the lonvo-z arm regardless of age, sex, race, weight, geography, baseline attack rate, or prior therapy. The publication also included a figure depicting the mean number of HAE attacks over time. It traced patients from when they were on prior therapies before screening through the entire efficacy evaluation period and into crossover, it showed that mean attack rates for the lonvo-z arm dropped well below the pre-screening attack rates by week 4. Attacks continued to decline in the months that followed and approached zero in the crossover period after week 28.

John Leonard: For instance, patient-level data demonstrated that all patients in the lonvo-z arm experienced attack rate reductions from baseline for weeks five to 28. In other words, every single patient received a clinical benefit, including those who are not yet fully attack-free during that six-month period. A subgroup analysis demonstrated meaningful attack rate reductions in the lonvo-z arm regardless of age, sex, race, weight, geography, baseline attack rate, or prior therapy.

Speaker #3: A subgroup analysis demonstrated meaningful attack rate reductions in the LANVOSI arm regardless of age, sex, race, weight, geography, baseline attack rate, or prior therapy.

Speaker #3: The publication also included a figure depicting the mean number of HAE attacks over time. It traced patients from when they were on prior therapies before screening, through the entire efficacy evaluation period, and into crossover.

John Leonard: The publication also included a figure depicting the mean number of HAE attacks over time. It traced patients from when they were on prior therapies before screening through the entire efficacy evaluation period and into crossover, it showed that mean attack rates for the lonvo-z arm dropped well below the pre-screening attack rates by week four. Attacks continued to decline in the months that followed and approached zero in the crossover period after week 28.

Speaker #3: And it showed that mean attack rates for the LANVOSI arm dropped well below the pre-screening attack rates by week four. Attacks continued to decline in the months that followed, and approach zero in the crossover period after week 28.

Speaker #3: In the placebo arm, not surprisingly, mean attack rates didn't drop below pre-screening levels until patients crossed over to LANVOSI. At that point, they dropped steeply and approached zero within a few months.

John Leonard: In the placebo arm, not surprisingly, mean attack rates didn't drop below pre-screening levels until patients crossed over to lonvo-z. At that point, they dropped steeply and approached zero within a few months. Also, notably, all patients who received lonvo-z at baseline or in crossover remained free from long-term prophylaxis therapy as of the data cutoff. Finally, favorable safety and tolerability data were observed. The most common treatment-emergent adverse events were infusion-related reactions, headache, and fatigue. All treatment-emergent adverse events were grade 1 or grade 2. There were no serious adverse events observed in the lonvo-z arm as of the data cutoff. These results are unsurpassed by chronic long-term prophylaxis therapies or LTPs. We believe it is clear, moreover, that they truly stand alone in the HAE space, given that this is a one-time treatment.

Speaker #3: Also, notably, all patients who received LANVOSI at baseline or in crossover remained free from long-term prophylaxis therapy as of the data cutoff. And finally, favorable safety and tolerability data were observed.

Speaker #3: The most common treatment emergent adverse events were infusion-related reactions, headache, and fatigue. All treatment emergent adverse events were grade 1 or grade 2, and there were no serious adverse events observed in the LANVOSI arm as of the data cutoff.

John Leonard: The most common treatment-emergent adverse events were infusion-related reactions, headache, and fatigue. All treatment-emergent adverse events were Grade 1 or Grade 2. There were no serious adverse events observed in the lonvo-z arm as of the data cutoff. These results are unsurpassed by chronic long-term prophylaxis therapies or LTPs. We believe it is clear, moreover, that they truly stand alone in the HAE space, given that this is a one-time treatment.

Speaker #3: LTPs. We believe it is clear moreover that they truly stand alone in the HAE space given that this is a one-time treatment. Most patients were attack-free, and therapy-free, for the entire six-month efficacy observation period following a single LANVOSI dose.

John Leonard: Most patients were attack-free and therapy-free for the entire six-month efficacy observation period following a single lonvo-z dose. Based on our preclinical work and observations from our phase I/II trial, our expectation is that this percentage will increase further over time as patients who have lived with HAE their entire lives adjust to their new normal. What's next for us? Well, we expect to be in a position to announce the FDA's acceptance of a BLA filing for lonvo-z by the end of this year. In the meantime, our pre-commercial readiness efforts are advancing well as we prepare for a potential US launch in H1 of next year. Most of these efforts are well underway, including work streams across medical engagement, payer outreach, treatment center readiness, distribution planning, and access strategy.

Speaker #3: Based on our preclinical work and observations from our Phase I, II trial, our expectation is that this percentage will increase further over time as patients who have lived with HAE their entire lives adjust to their new normal.

Speaker #3: So what's next These results are a position to announce the FDA's acceptance of a BLA filing for LANVOSI by the end of this year.

John Leonard: What's next for us? Well, we expect to be in a position to announce the FDA's acceptance of a BLA filing for lonvo-z by the end of this year. In the meantime, our pre-commercial readiness efforts are advancing well as we prepare for a potential US launch in H1 of next year. Most of these efforts are well underway, including work streams across medical engagement, payer outreach, treatment center readiness, distribution planning, and access strategy.

Speaker #3: In the meantime, our pre-commercial readiness efforts are advancing well as we prepare for a potential U.S. launch in the first half of next year.

Speaker #3: Most of these efforts are well underway, including work streams across medical engagement, payer outreach, treatment center readiness, distribution planning, and access strategy. We've completed hiring for our field medical, reimbursement, and strategic accounts teams.

John Leonard: We've completed hiring for our field medical, reimbursement, and strategic accounts teams, and they're now engaging with treatment centers around the country to ensure they are well-prepared to address patient needs shortly after approval. We're also building awareness of the many burdens associated with HAE. During Q2, we launched HAEreframed.com, a disease awareness initiative designed to elevate understanding of the challenges patients face, including those related to lifelong chronic therapy. Together, these efforts reflect meaningful progress in building the infrastructure, awareness, and access pathways needed to support our planned launch. Let's turn to the progress we made with nex-z, our potential one-time treatment for patients with ATTR cardiomyopathy and polyneuropathy.

Speaker #3: And they're now engaging with treatment centers around the country to ensure they are well prepared to address patient needs shortly after approval. We're also building awareness of the many burdens associated with HAE during the Q2 we launched HAE Reframe.com, a disease awareness initiative designed to elevate understanding of the challenges patients face, including those related to lifelong chronic therapy.

John Leonard: During Q2, we launched HAEreframed.com, a disease awareness initiative designed to elevate understanding of the challenges patients face, including those related to lifelong chronic therapy. Together, these efforts reflect meaningful progress in building the infrastructure, awareness, and access pathways needed to support our planned launch. Let's turn to the progress we made with nex-z, our potential one-time treatment for patients with ATTR cardiomyopathy and polyneuropathy.

Speaker #3: Together, these efforts reflect meaningful progress in building the infrastructure, awareness, and access pathways needed to support our planned launch. So let's turn to the progress we've made with NEXI, our potential one-time treatment for patients with ATTR cardiomyopathy and polyneuropathy.

Speaker #3: We were pleased to have resolved the clinical holds on our Phase III trials quite rapidly earlier this year, and I'm excited to report today that we were able to resume enrollment and dosing in both trials in Q2.

John Leonard: We were pleased to have resolved the clinical holds on our phase III trials quite rapidly earlier this year, and I'm excited to report today that we were able to resume enrollment and dosing in both trials in Q2. Investigator engagement enthusiasm remain high, and our screening rate is rapidly increasing globally once again. ATTR is a large, growing, and highly underdiagnosed market with significant unmet need. Today, patients are predominantly served by stabilizers, silencers, or a combination of the two. About a month ago, disappointing top-line results were shared from CARDIO-TTRansform, the pivotal trial of eplontersen, a TTR silencer for patients with ATTR cardiomyopathy. Since then, there's been some debate about whether a silencer can work on top of a stabilizer. We and others believe the negative outcome is specific to eplontersen and this particular trial, and it does not speak to combination outcomes in general.

Speaker #3: Investigators' engagement, enthusiasm remain high, and our screening rate is rapidly increasing globally once again. ATTR is a large, growing, and highly underdiagnosed market with significant unmet need.

Speaker #3: Today, patients are predominantly served by stabilizers, silencers, or a combination of the two. About a month ago, disappointing top-line results were shared from cardiotransform, the pivotal trial of Eplantarsan, a TTR silencer, for patients with ATTR cardiomyopathy.

John Leonard: Today, patients are predominantly served by stabilizers, silencers, or a combination of the two. About a month ago, disappointing top-line results were shared from CARDIO-TTRansform, the pivotal trial of eplontersen, a TTR silencer for patients with ATTR cardiomyopathy. Since then, there's been some debate about whether a silencer can work on top of a stabilizer. We and others believe the negative outcome is specific to eplontersen and this particular trial, and it does not speak to combination outcomes in general.

Speaker #3: Since then, there's been some debate about whether a silencer can work on top of a stabilizer. We and others believe the negative outcome is specific to Eplontersen and this particular trial, and it does not speak to combination outcomes in general.

Speaker #3: We remain firm believers that combination therapy will agent. This belief is based empirically on clinical evidence. First, we would point to the fact that another chronically dosed silencer, Fritrizarid, has already shown a directional benefit on top of stabilizers in a well-controlled trial.

John Leonard: We remain firm believers that combination therapy will work, but only with the right agent. This belief is based empirically on clinical evidence. First, we would point to the fact that another chronically dosed silencer, patisiran, has already shown a directional benefit on top of stabilizers in a well-controlled trial. Even more importantly, we would point to what was observed in the monotherapy data for each of the chronically dosed stabilizers and silencers. If you go back and look at the readouts for approved stabilizers like tafamidis and acoramidis, and approved silencers like eplontersen and patisiran, you'll see that patients continue to progress while they're on those therapies. Why is that? Well, we and others are convinced it's because they inadequately reduce or control TTR protein. Focusing in on the approved silencers, you'll see that mean TTR reductions for each of them are about 80%.

Speaker #3: But even more importantly, we would point to what was observed in the monotherapy data for each of the chronically dosed stabilizers and silencers, if you go back and look at the readouts for approved stabilizers like tafamidus and acaramidus, and approved silencers like Eplantarsan and Fritrizarid, you'll see that patients continue to progress while they're on those therapies.

John Leonard: If you go back and look at the readouts for approved stabilizers like tafamidis and acoramidis, and approved silencers like eplontersen and patisiran, you'll see that patients continue to progress while they're on those therapies. Why is that? Well, we and others are convinced it's because they inadequately reduce or control TTR protein. Focusing in on the approved silencers, you'll see that mean TTR reductions for each of them are about 80%.

Speaker #3: Why is that? Well, we and others are convinced it's because they inadequately reduce or control TTR protein. Focusing in on the approved silencers, you'll see that mean TTR reductions for each of them are about 80%.

Speaker #3: However, the details behind that number matter. For instance, it takes many months for those silencers to achieve their 80% nadir of reduction. There's significant variability in TTR from patient to patient.

John Leonard: However, the details behind that number matter. For instance, it takes many months for those silencers to achieve their 80% data of reduction. There's significant variability in TTR from patient to patient, with some achieving a 90% knockdown and many others receiving reductions of only 50% or 60%. Even within an individual patient, the knockdown fluctuates due to issues with PK and issues with dose interruptions and adherence, whether due to patient behavior or toxicity. Simply put, it appears today's silencers and stabilizers are leaving efficacy on the table. In a progressive disease with high mortality like ATTR-CM, every day and every microgram per milliliter of TTR counts. nex-z has demonstrated its ability to deliver an unsurpassed knockdown of TTR protein for patients in both relative and absolute terms. Our phase I data demonstrated a mean TTR reduction of 90%.

Speaker #3: With some achieving a 90% knockdown and many others receiving a reductions of only 50 or 60 percent. And even within an individual patient, the knockdown fluctuates due to issues with PK and issues with dose interruptions and adherence, whether due to patient behavior, or toxicity.

John Leonard: Even within an individual patient, the knockdown fluctuates due to issues with PK and issues with dose interruptions and adherence, whether due to patient behavior or toxicity. Simply put, it appears today's silencers and stabilizers are leaving efficacy on the table. In a progressive disease with high mortality like ATTR-CM, every day and every microgram per milliliter of TTR counts.

Speaker #3: Simply put, it appears today's silencers and stabilizers are leaving efficacy on the table. In a progressive disease with high mortality like ATTRCM, every day and every microgram per milliliter of TTR counts.

Speaker #3: NEXI has demonstrated its ability to deliver an unsurpassed knockdown of TTR protein for patients, in both relative and absolute terms. Our Phase I data demonstrated a mean TTR reduction of 90%.

John Leonard: Nex-z has demonstrated its ability to deliver an unsurpassed knockdown of TTR protein for patients in both relative and absolute terms. Our phase I data demonstrated a mean TTR reduction of 90%.

Speaker #3: While that percentage is impressive, we believe the absolute TTR reduction is even more clinically relevant. When NEXI is provided as monotherapy, mean serum TTR was less than 20 micrograms per milliliter, about one-third of the absolute level seen with the leading chronic silencer.

John Leonard: While that percentage is impressive, we believe the absolute TTR reduction is even more clinically relevant. When nex-z is provided as monotherapy, mean serum TTR was less than 20 micrograms per milliliter, about one-third of the absolute level seen with the leading chronic silencer. That knockdown was achieved rapidly within one month of the infusion, and was extremely consistent across all patients. Best of all, patients began receiving therapeutic doses of nex-z in 2021, and as of our latest data cutoff, intra-patient TTR control was constant and was maintained across all patients following their one-time nex-z treatment. We look forward to presenting updated long-term durability data at future congresses. We believe nex-z's distinct TTR knockdown is why disease stabilization or reversal is observed in most patients in our phase I, while our would-be competitors have observed disease progression.

Speaker #3: That knockdown was achieved rapidly, within one month of the infusion, and it was extremely consistent across all patients. Best of all, patients began receiving therapeutic doses of NEXI in 2021, and as of our latest data cutoff, intrapatient TTR control was constant and was maintained across all patients following the one-time NEXI treatment.

John Leonard: Best of all, patients began receiving therapeutic doses of nex-z in 2021, and as of our latest data cutoff, intra-patient TTR control was constant and was maintained across all patients following their one-time nex-z treatment. We look forward to presenting updated long-term durability data at future congresses. We believe nex-z's distinct TTR knockdown is why disease stabilization or reversal is observed in most patients in our phase I, while our would-be competitors have observed disease progression.

Speaker #3: We look forward to presenting updated long-term durability data at future congressors. We believe NEXI's distinct TTR knockdown is why disease stabilization or reversal is observed in most patients in our Phase I, while there would be competitors who have observed disease progression.

Speaker #3: Additionally, the response has been consistent across patients of all New York Heart Association classes, those with either variant or wild type disease, and it also includes patients who have progressed on past silencers.

John Leonard: Additionally, the response has been consistent across patients of all New York Heart Association classes, those with either variant or wild-type disease, and it also includes patients who have progressed on past silencers. We continue to have significant confidence in our ability to show a benefit on top of tafamidis and MAGNITUDE. Additionally, unlike CARDIO-TTRansform, which was a time-bound study, MAGNITUDE's primary endpoint is strictly event-based. We've enrolled well over 650 patients in MAGNITUDE. We've been accruing events for quite some time, and those events continued unabated through the clinical hold. While still premature for us to guide as to data timing, what I can say today is that the blinded event rate in the trial remains within the range we'd projected internally. We're looking forward to reviewing the detailed CARDIO-TTRansform data later this month at ESC.

Speaker #3: And so we continue to have significant confidence in our ability to show a benefit on top of tafamidus and magnitude. Additionally, unlike cardiotransform, which was a time-bound study, magnitude's primary endpoint is strictly event-based.

Speaker #3: We've enrolled well over 650 patients in MAGNITUDE, we've been accruing events for quite some time, and those events continued unabated through the clinical hold.

John Leonard: We've enrolled well over 650 patients in MAGNITUDE. We've been accruing events for quite some time, and those events continued unabated through the clinical hold. While still premature for us to guide as to data timing, what I can say today is that the blinded event rate in the trial remains within the range we'd projected internally. We're looking forward to reviewing the detailed CARDIO-TTRansform data later this month at ESC.

Speaker #3: While still premature for us to guide as to data timing, but it can say today is that the blinded event rate in the trial remains within the range we had projected internally.

Speaker #3: We're looking forward to reviewing the detailed cardiotransform data later this month at ESC, and of course, we have the opportunity to consider changes that further optimize magnitude's design based on what we learn.

John Leonard: Of course, we have the opportunity to consider changes that further optimize MAGNITUDE's design based on what we learn. Now let's move on to one other encouraging update we're able to share today related to nex-z. As we reported late last year, grade 4 liver transaminase elevations had been observed in less than 1% of patients enrolled in MAGNITUDE. These were transient, and in most cases, they resolved without any intervention. Based in part on the fact that the observations consistently occurred 2 to 5 weeks after dosing, we hypothesized they were caused by an adaptive immune response. As a result, we implemented mitigation measures to enhance monitoring for transaminase elevations and intervene if they are observed. These measures are very straightforward and could easily be implemented in a real-world commercial setting if required. We also went further.

Speaker #3: Now let's move on to one other encouraging update, we're able to share today related to NEXI. As we reported late last year, grade 4 liver transaminase elevations had been observed in less than 1% of patients enrolled in magnitude.

Speaker #3: These were transient and in most cases, they resolved without any intervention. Based in part on the fact that the observations consistently occurred two to five weeks after dosing, we hypothesized they were caused by an adaptive immune response.

John Leonard: Based in part on the fact that the observations consistently occurred 2 to 5 weeks after dosing, we hypothesized they were caused by an adaptive immune response. As a result, we implemented mitigation measures to enhance monitoring for transaminase elevations and intervene if they are observed. These measures are very straightforward and could easily be implemented in a real-world commercial setting if required. We also went further.

Speaker #3: As a result, we implemented mitigation measures to enhance monitoring for transaminase elevations, and intervene if they are observed. These measures are very straightforward and could easily be implemented in a real-world commercial setting if required.

Speaker #3: We also went further. Working with Regeneron and other external experts, we sequenced and analyzed data from over 600 patient samples across all NEXI clinical trials today.

John Leonard: Working with Regeneron and other external experts, we sequenced and analyzed data from over 600 patient samples across all nex-z clinical trials to date. Our goal was to understand if there were subpopulations that might be most susceptible to higher grade transaminase elevations. This work focused on HLAs, which are proteins on the surface of cells that play a key role in regulating the immune system and helping to distinguish native and foreign peptides. This blinded analysis revealed one statistically significant finding. Patients carrying one specific HLA allele that is known as C*05:01 had a significantly higher rate of grade 3 or greater transaminase elevations than the broader population. In fact, each of the five highest elevations observed following dosing occurred in patients carrying this allele. Some important context on what this does and doesn't mean.

Speaker #3: Our goal was to understand if there were subpopulations that might be most susceptible to higher-grade transaminase elevations. This work focused on HLAs, which are proteins on the surface of cells that play a key role in regulating the immune system and helping to distinguish native and foreign peptides.

Speaker #3: This blinded analysis revealed one statistically significant finding. Patients carrying one specific HLA allele that's known as C0501 had a significantly higher rate of grade 3 or greater transaminase elevations than the broader population.

John Leonard: This blinded analysis revealed one statistically significant finding. Patients carrying one specific HLA allele that is known as C*05:01 had a significantly higher rate of grade 3 or greater transaminase elevations than the broader population. In fact, each of the five highest elevations observed following dosing occurred in patients carrying this allele. Some important context on what this does and doesn't mean.

Speaker #3: In fact, each of the five highest elevations observed following dosing occurred in patients carrying this allele. Now, some important context on what this does and doesn't mean.

Speaker #3: Only 12% of the 600-plus samples we analyzed carry this allele. And the strong majority of C0501-positive patients did not experience severe transaminase elevations. So we continue to see the potential for a favorable benefit-risk profile even in this subgroup, particularly with the mitigation strategy that is now in place.

John Leonard: Only 12% of the 600-plus samples we analyzed carry this allele, and the strong majority of C*05:01-positive patients did not experience severe transaminase elevations. We continue to see the potential for a favorable benefit/risk profile even in this subgroup, particularly with the mitigation strategy that is now in place. 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. In doing so, it further increases our confidence in nex-z's ability to deliver on its long-recognized potential. Here are our next steps. We are engaging with FDA to review the findings. In the meantime, we already have updated our protocols, investigators brochures, and informed consents to incorporate HLA typing for all patients in the phase III trials.

Speaker #3: What the finding gives us is valuable. A mechanistic explanation for a general signal we'd already flagged and a way to identify patients who are more likely to be affected before it happens.

Speaker #3: In doing so, it further increases our confidence in NEXI's ability to deliver on its long-recognized potential. So here are our next steps: we're engaging with the FDA to review the findings.

John Leonard: In doing so, it further increases our confidence in nex-z's ability to deliver on its long-recognized potential. Here are our next steps. We are engaging with FDA to review the findings. In the meantime, we already have updated our protocols, investigators brochures, and informed consents to incorporate HLA typing for all patients in the phase III trials.

Speaker #3: In the meantime, we already have updated our protocols, investigators' brochures, and informed consents to incorporate HLA typing for all patients in the Phase III trials.

Speaker #3: These documents are in the process of being rolled out to regulatory authorities, IRBs, and sites globally. Following the reviews, investigators and patients will be informed about the HLA results string screening or prior to crossover so they can make more informed treatment decisions.

John Leonard: These documents are in the process of being rolled out to regulatory authorities, IRBs, and sites globally. Following the reviews, investigators and patients will be informed about the HLA results during screening or prior to crossover so they can make more informed treatment decisions. To close, I am exceedingly proud of all the team continues to accomplish here at Intellia. We are marching towards the world's first potential launch of an in vivo gene editing therapy with lonvo-z. We are on track to complete enrollment in Magnitude 2 later this year, and we are demonstrating precision medicine at its finest with our HLA work on nex-z. These achievements layer on top of all the other pioneering work we have undertaken as we seek to harness the power of gene editing to deliver optimal treatment outcomes for patients with just one dose.

Speaker #3: And so to close, I'm exceedingly proud of all the team continues to accomplish here at Intellia. We're marching towards the world's first potential launch of an in vivo gene editing therapy with Lanvozi.

Speaker #3: We're on track to complete enrollment in magnitude two later this year, and we're demonstrating precision medicine at its finest with our HLA work on NEXI.

John Leonard: We are on track to complete enrollment in Magnitude 2 later this year, and we are demonstrating precision medicine at its finest with our HLA work on nex-z. These achievements layer on top of all the other pioneering work we have undertaken as we seek to harness the power of gene editing to deliver optimal treatment outcomes for patients with just one dose. With that, let's now turn the call over to Ed to share some financial color.

Speaker #3: These achievements layer on top of all the other pioneering work we've undertaken as we seek to harness the power of gene editing to deliver optimal treatment outcomes for patients with just one dose.

Speaker #3: So with that, let's now turn the call over to Ed to share some financial color.

John Leonard: With that, let's now turn the call over to Ed to share some financial color.

Speaker #1: Thank you, John. And hello, everyone. In addition to the tremendous clinical pre-commercial and scientific progress we made in the second quarter, we also kept the company on sound financial footing.

Edward Dulac: Thank you, John, and hello, everyone. In addition to the tremendous clinical, pre-commercial, and scientific progress we made in Q2, we also kept the company on sound financial footing. In April, we completed an equity financing that yielded approximately $195 million in net proceeds for the company. Cash, cash equivalents, and marketable securities were $628.4 million as of 30 June 2026, compared to $605.1 million on 31 December 2025. We believe this cash balance will be sufficient to get us at least into 2028. Importantly, while we expect to obtain approval and launch lonvo-z in the US in H1 2027, our cash runway guidance is conservative in that it excludes all product revenues. Collaboration revenue was $7.7 million for Q2 2026, compared to $14.2 million for the prior year quarter. This change is primarily due to a reduction in revenue from Regeneron.

Ed Dulac: Thank you, John, and hello, everyone. In addition to the tremendous clinical, pre-commercial, and scientific progress we made in Q2, we also kept the company on sound financial footing. In April, we completed an equity financing that yielded approximately $195 million in net proceeds for the company. Cash, cash equivalents, and marketable securities were $628.4 million as of 30 June 2026, compared to $605.1 million on 31 December 2025.

Speaker #1: In April, we completed an equity financing that yielded approximately $195 million in net proceeds for the company. Cash, cash equivalents, and marketable securities were $628.4 million, as of June 30th, 2026, compared to $605.1 million on December 31st, 2025.

Speaker #1: We believe this cash balance will be sufficient to get us at least into 2028. Importantly, while we expect to obtain approval and launch Lanvozi in the US in the first half of 2027, our cash runway guidance is conservative in that it excludes all product revenues.

Ed Dulac: We believe this cash balance will be sufficient to get us at least into 2028. Importantly, while we expect to obtain approval and launch lonvo-z in the US in H1 2027, our cash runway guidance is conservative in that it excludes all product revenues. Collaboration revenue was $7.7 million for Q2 2026, compared to $14.2 million for the prior year quarter. This change is primarily due to a reduction in revenue from Regeneron.

Speaker #1: Collaboration revenue was $7.7 million for the second quarter of 2026, compared to $14.2 million for the prior year quarter. This change is primarily due to a reduction in revenue from Regeneron.

Speaker #1: R&D expenses were $82.6 million for the second quarter of 2026, compared to $97 million during the prior year quarter. The decrease was primarily driven by lower external costs related to Lanvozi and NEXI and reduced stock-based compensation, partially offset by higher employee-related expenses due to increased headcount.

Edward Dulac: R&D expenses were $82.6 million for Q2 2026, compared to $97 million during the prior year quarter. The decrease was primarily driven by lower external costs related to lonvo-z and nex-z, and reduced stock-based compensation, partially offset by higher employee-related expenses due to increased headcount. Stock-based compensation expense included in R&D was $9.4 million for Q2 2026. G&A expenses were $37.8 million during Q2 2026, compared to $27.2 million for the prior year quarter. This increase was primarily driven by costs associated with the ongoing build-out of our commercial infrastructure, higher legal expenses, and stock-based compensation. Stock-based compensation expense included in G&A was $8.6 million for Q2 2026. Net loss for Q2 of this year was $106.6 million, which compared with the $101.3 million for the prior year quarter.

Ed Dulac: R&D expenses were $82.6 million for Q2 2026, compared to $97 million during the prior year quarter. The decrease was primarily driven by lower external costs related to lonvo-z and nex-z, and reduced stock-based compensation, partially offset by higher employee-related expenses due to increased headcount. Stock-based compensation expense included in R&D was $9.4 million for Q2 2026. G&A expenses were $37.8 million during Q2 2026, compared to $27.2 million for the prior year quarter.

Speaker #1: Stock-based compensation expense included in R&D was $9.4 million for the second quarter of 2026. G&A expenses were $37.8 million during the second quarter of 2026, compared to $27.2 million for the prior year quarter.

Speaker #1: This increase was primarily driven by costs associated with the ongoing build-out of our commercial infrastructure, higher legal expenses, and stock-based compensation. Stock-based compensation expense included in GNA was $8.6 million for the second quarter of 2026.

Ed Dulac: This increase was primarily driven by costs associated with the ongoing build-out of our commercial infrastructure, higher legal expenses, and stock-based compensation. Stock-based compensation expense included in G&A was $8.6 million for Q2 2026. Net loss for Q2 of this year was $106.6 million, which compared with the $101.3 million for the prior year quarter. With that, we are ready to begin our question and answer session. Operator, would you please open the line for questions?

Speaker #1: And finally, net loss for the second quarter of this year was $106.6 million. Which compared with the $101.3 million for the prior year quarter.

Speaker #1: With that, we are ready to begin our question-and-answer session. Operator, would you please open the line for questions?

Edward Dulac: With that, we are ready to begin our question and answer session. Operator, would you please open the line for questions?

Speaker #2: We will now begin the question-and-answer session. To ask a question, you may press star then one on your touch-tone phone. If you're using a speakerphone, please pick up your handset before pressing the keys.

Operator: We will now begin the question and answer session. To ask a question, you may press star then one on your touchtone phone. If you're using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star then two. Please limit yourself to one question, and if you have additional questions, you may rejoin the queue. At this time, we will pause momentarily to assemble our roster. The first question today comes from Maury Raycroft with Jefferies. Please go ahead.

Speaker #2: To withdraw your question, please press star then two. Please limit yourself to one question. And if you have additional questions, you may rejoin the queue.

Speaker #2: At this time, we will pause momentarily to assemble our comes from Mari Raycroft with Jefferies. Please go ahead.

Speaker #3: Hi, good morning. Congrats on the progress, and thanks for taking my question. I'll ask one on the allele finding. Which is interesting. For that C0501 allele, can you talk about the implications for the 12% of patients where there could be some added risk?

Maury Raycroft: Hi, good morning. Congrats on the progress and thanks for taking my question. I'll ask one on the allele finding, which is interesting for that C*05:01 allele. Can you talk about the implications for the 12% of patients where there could be some added risk? Is there another parameter that you could use to help fine-tune patient selection? Lastly, is there more you can share on the biologic relationship or what exactly is triggering the immune response?

Maury Raycroft [Equity Research Analyst: Hi, good morning. Congrats on the progress and thanks for taking my question. I'll ask one on the allele finding, which is interesting for that C*05:01 allele. Can you talk about the implications for the 12% of patients where there could be some added risk? Is there another parameter that you could use to help fine-tune patient selection? Lastly, is there more you can share on the biologic relationship or what exactly is triggering the immune response?

Speaker #3: And is there another parameter that you could use to help fine-tune patient selection? And lastly, is there more we can share on the biologic relationship for what exactly is triggering the immune response?

Speaker #1: Thanks, Mari. For your question, so we think that the finding confirms our initial thinking about an adaptive immune response, as many will know. HLAs are deeply implicated in cell-mediated immunity.

John Leonard: Thanks, Maury, for your question. We think that the finding confirms our initial thinking about an adaptive immune response. As many will know, HLAs are deeply implicated in cell-mediated immunity. This would be an important part of understanding what we saw with our early observations with timing of the immune response. It gives us significant confidence that the mitigation measures that we've put in place are appropriate and are on target for what seems to be going on. With respect to the patients that carry 05:01, as I said in my comments during the earlier portion of the call here, we're making that information available to all investigators and patients. There's a relationship that's significant, but many of the patients that carry 05:01 do not have ALT elevations.

Speaker #1: And this would be an important part of understanding what we saw with our early observations with timing of the immune response. So it gives us significant confidence that the mitigation measures that we put in place are appropriate in our target for what seems to be going on.

Speaker #1: With respect to the patients that carry 0501, as I said in my comments during the earlier portion of the call here, we're making that information available to all investigators and patients.

John Leonard: With respect to the patients that carry 05:01, as I said in my comments during the earlier portion of the call here, we're making that information available to all investigators and patients. There's a relationship that's significant, but many of the patients that carry 05:01 do not have ALT elevations.

Speaker #1: There's a relationship that's significant, but many of the patients that carry 0501 do not have LFT elevation. So the first order of business is to make sure that, if patients have that, they're aware of it, and they can discuss the elevated risk with their physicians and make a determination of what's appropriate for them.

John Leonard: The first order of business is to make sure that if patients have that, they're aware of it, and they can discuss the elevated risk with their physicians and make a determination of what's appropriate for them. Our expectation, just based on conferring with our steering committee members and the experts that we've been working on this during the course of our findings, is that many of the patients may choose to self-exclude, and that's appropriate for them. For those who believe that the state of their disease and the other opportunities available to them warrant continuing to receive the therapy and advancing the trial, we're making the drug available for them. As we continue to learn during the course of our trial, we discuss with the FDA these findings and any further implications.

Speaker #1: Our expectation, just based on conferring with our steering committee members and people, the experts that we've been working on this during the course of our findings, is that many of the patients may choose to self-exclude and that's appropriate for them.

Speaker #1: But for those who believe that the state of their disease and the other opportunities available to them warrant continuing and to receive the therapy and advancing the trial, we're making the drug available for them.

John Leonard: For those who believe that the state of their disease and the other opportunities available to them warrant continuing to receive the therapy and advancing the trial, we're making the drug available for them. As we continue to learn during the course of our trial, we discuss with the FDA these findings and any further implications.

Speaker #1: As we continue to learn, during the course of our trial, we discussed with the FDA these findings and any further implications, but in the meanwhile, we think that this will give enhanced confidence to the physicians and patients who are entering that they can derive the best possible outcome all things considered.

John Leonard: In the meanwhile, we think that this will give enhanced confidence to the physicians and patients who are entering that they can derive the best possible outcome, all things considered.

Speaker #2: The next question comes from Joseph Foam with TD Cowen. Please go ahead.

Operator: The next question comes from Joseph Thome with TD Cowen. Please go ahead.

Speaker #4: Hey, this is Jacob on for Joe. Thanks for taking our question. Just sticking with the HLA allele, I wanted to confirm that this was something specific to NEXI and not Lanvozi.

[Analyst] (TD Cowen): Hey, this is Jacob on for Joe. Thanks for taking our question. Just sticking with the HLA allele, wanted to confirm that this was something specific to nex-z and not Lonbosi. Then also you said, I believe that it was 12% of the 600 samples that carried the allele, but only a fraction of that 12% actually had elevations. Is that correct?

Jacob Ormes [Equity Research Associate: Hey, this is Jacob on for Joe. Thanks for taking our question. Just sticking with the HLA allele, wanted to confirm that this was something specific to nex-z and not Lonbosi. Then also you said, I believe that it was 12% of the 600 samples that carried the allele, but only a fraction of that 12% actually had elevations. Is that correct?

Speaker #4: And then also you said I believe that it was 12% of the 600 samples that carried the allele, but only a fraction of that 12% actually had elevations.

Speaker #4: Is that correct?

Speaker #1: Yes, in my comments, I said that across the study, there's about 12% of patients who carry the C0501. And that broadly reflects what's seen in a North American Western European population.

John Leonard: Yes. In my comments, I said that across the study, there's about 12% of patients who carry the C*05:01, and that broadly reflects what's seen in a North American, Western European population. There will be some variance across different ethnic groups with numbers sometimes lower than that, but that's what we've observed in the study. With respect to specificity, almost certainly this would be specific to nex-z and not have any implications for Lonbosi. There's a couple reasons for that. When you think about what an HLA molecule is, it binds to a very specific short peptide, and we wouldn't expect those peptides to be implicated in any way with the Lonbosi treatment effect. That's further supported by the fact that, as shown in The New England Journal of Medicine publication that was recently released, there's no signal in patients with Lonbosi.

Speaker #1: There will be some variance across different ethnic groups with numbers sometimes lower than that, but that's what we've observed in the study. With respect to specificity, almost certainly this would be specific to NEXI and not have any implications for Lanvozi.

Speaker #1: And there's a couple of reasons for that. When you think about what an HLA molecule is, it binds to a very, very specific short peptide.

John Leonard: There's a couple reasons for that. When you think about what an HLA molecule is, it binds to a very specific short peptide, and we wouldn't expect those peptides to be implicated in any way with the Lonbosi treatment effect. That's further supported by the fact that, as shown in The New England Journal of Medicine publication that was recently released, there's no signal in patients with Lonbosi. At this point, we think that this is just a finding that's going to be limited to nex-z.

Speaker #1: And we wouldn't expect those peptides to be implicated in any way with the Lanvozi treatment effect. So that's further supported by the fact that, as shown in the New England Journal publication, it was recently released, there's no signal in patients with Lanvozi.

Speaker #1: And at this point, we think that this is just a finding that's going to be limited to NEXI.

John Leonard: At this point, we think that this is just a finding that's going to be limited to nex-z.

Speaker #3: And I'll just add one thing, John. I think there's a comment about just the vast majority of those patients that had 0501 did not experience severe transaminase elevations.

Edward Dulac: I'll just add one thing, John. I think there's a comment about just the vast majority of those patients that had C*05:01 did not experience severe transaminase elevations. 12% of the samples do represent those that are carrying the allele, but only a small subset have had these higher grade elevations.

Ed Dulac: I'll just add one thing, John. I think there's a comment about just the vast majority of those patients that had C*05:01 did not experience severe transaminase elevations. 12% of the samples do represent those that are carrying the allele, but only a small subset have had these higher grade elevations.

Speaker #3: So 12% of the samples do represent those that are carrying the allele, but only a small subset have had these higher-grade elevations.

Speaker #2: The next question comes from Luca Isey with RBC Capital Markets. Please go ahead.

Operator: The next question comes from Luca Issi with RBC Capital Markets. Please go ahead.

Speaker #5: Oh, great. Yeah, thanks so much for taking my question and congrats. Obviously, all the progress. Obviously, we have yet to see the full cardiotransform trial.

Luca Issi: Well, great. Thanks so much for taking my question, and congrats, obviously, on all the progress. Obviously, we have yet to see the full CARDIO-TTRansform trial. I was looking forward to that data at European Society of Cardiology. I think, John, you already mentioned potential to maybe optimizing your trial to maximize the probability of success. Can you just talk about what are the options that you're contemplating at this point? Can you enroll more patients? Can you extend the minimum follow-up longer than 18 months? I don't know. Can you limit the use of SGLT2? Just walk us through a big picture of how you're thinking about potentially tweaking your trial. Thanks so much.

Speaker #5: Obviously, looking forward to that data. European Society of Cardiology. But I think, John, you already mentioned potential to maybe optimizing your trial to maximize the probability of success.

Speaker #5: Can you just talk about what are the options that you're contemplating at this point? Can you enroll more patients? Can you extend the minimum follow-up longer than 18 months?

Luca Issi: Can you just talk about what are the options that you're contemplating at this point? Can you enroll more patients? Can you extend the minimum follow-up longer than 18 months? I don't know. Can you limit the use of SGLT2? Just walk us through a big picture of how you're thinking about potentially tweaking your trial. Thanks so much.

Speaker #5: I don't know. Can you limit the use of SGLT2? Just walk us through a big picture of how you're thinking about potentially tweaking your trial.

Speaker #5: Thanks so much.

Speaker #1: Thanks for the question, Luca. I mean, the first order of business is really understanding the data. That comes from the cardiotransform study. As I said in the prepared comments, we believe based on everything we know thus far, that the findings are likely specific to a plantarson and not generally applicable to how we think about treatment of patients with TTR disease or patients with receiving combination therapy.

John Leonard: Thanks for the question, Luca. The first order of business is really understanding the data that comes from the CARDIO-TTRansform study. As I said in the prepared comments, we believe based on everything we know thus far, that the findings are likely specific to eplontersen and not generally applicable to how we think about treatment of patients with TTR disease or patients receiving combination therapy. What we think is going to be the most important information is the degree to which TTR is reduced. The variability or lack thereof, as we see in our own patients. The speed with which treatment effect is achieved, and obviously the durability as patients go through the many months of observation where variability may be attributable to pharmacokinetics or interruptions for toxicity, for example.

Speaker #1: What we think is going to be the most important information is the degree to which TTR is reduced. The variability or lack thereof, as we see in our own patients, the speed with which treatment effect is achieved, and then obviously the durability as patients go through the many, many months of observation.

John Leonard: What we think is going to be the most important information is the degree to which TTR is reduced. The variability or lack thereof, as we see in our own patients. The speed with which treatment effect is achieved, and obviously the durability as patients go through the many months of observation where variability may be attributable to pharmacokinetics or interruptions for toxicity, for example.

Speaker #1: That we're variability may be attributable to pharmacokinetics or interruptions for toxicity, for example. All of those elements will erode the overall treatment effect. And it's important, I think, to really understand that before we jump to conclusions about combination therapy and how best to use it.

John Leonard: All of those elements will erode the overall treatment effect. It's important, I think, to really understand that before we jump to conclusions about combination therapy and how best to use it. With an understanding in hand, we will of course work with experts who are deep in the data. We'll consider if there's anything that we need to change. We remain open-minded. We adapt as necessary, and we certainly try to learn at a prodigious rate as information becomes available. The factors that you mentioned are possible to change. We don't start with a thesis in mind until we have a really good understanding of the data. Like you all on this call, and many others, we're very anxious to see what that information is before we make any changes.

Speaker #1: But with an understanding in hand, and we will, of course, work with experts who are deep in the data, we'll consider if there's anything that we need to change, we remain open-minded.

John Leonard: We'll consider if there's anything that we need to change. We remain open-minded. We adapt as necessary, and we certainly try to learn at a prodigious rate as information becomes available. The factors that you mentioned are possible to change. We don't start with a thesis in mind until we have a really good understanding of the data. Like you all on this call, and many others, we're very anxious to see what that information is before we make any changes.

Speaker #1: We adapt as necessary, and we certainly try to learn at a prodigious rate as information becomes available. The factors that you mentioned are possible to change.

Speaker #1: But we don't start with a thesis in mind until we have a really good understanding of the data. And like you all on this call and many others, we're very, very anxious to see what that information is before we make any changes.

Speaker #2: The next question comes from Salveen Richter with Goldman Sachs. Please go ahead.

Operator: The next question comes from Salveen Richter with Goldman Sachs. Please go ahead.

Speaker #6: Good morning. Thanks for taking my question. Can you remind us of the background stabilizer used in the study? And if you expect that to change given recent cardiotransform results, also on the HLA filing finding, do you see enrollment changes just given screening for HLA?

Salveen Richter: Good morning. Thanks for taking my question. Can you remind us of the background stabilizer used in the study, and if you expect that to change given recent CARDIO-TTRansform results? Also, on the HLA finding, do you see enrollment changes just given screening for HLA? Thank you.

Speaker #6: Thank you.

Speaker #1: Thanks for the question, Salveen. 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.

John Leonard: Thanks for the question, Salveen. 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. That does not appear to be changing one way or the other. I think it reflects how stabilizers are broadly used around the world and obviously in sites where we're doing the investigation. With respect to HLA, as we talk to investigators and people who we're working with in this trial, most of them view this as confidence building in terms of how to think about patients and who to enter and potentially who to exclude should the patient or the doctor think that that's the most appropriate course of action for any particular patient.

Speaker #1: And so, that does not appear to be changing one way or the other. I think it reflects how stabilizers are broadly used around the world, and obviously in the sites where we're doing the investigation.

Speaker #1: With respect to HLA, as we talked to investigators and people who are working within this trial, most of them view this as confidence-building in terms of how to think about patients and who to enter and potentially who to exclude should the patient or the doctor think that that's the most appropriate course of action for any particular patient.

John Leonard: With respect to HLA, as we talk to investigators and people who we're working with in this trial, most of them view this as confidence building in terms of how to think about patients and who to enter and potentially who to exclude should the patient or the doctor think that that's the most appropriate course of action for any particular patient.

Speaker #1: But across the board, as we've gone through the data with people who are practicing cardiologists and experts in the field, to a person, all of them have viewed this as a very, very favorable finding that enhances overall confidence.

John Leonard: Across the board, as we've gone through the data with people who are practicing cardiologists and experts in the field to a person, all of them have viewed this as a very favorable finding that enhances overall confidence. Our job now is to make that information available to those doctors and physicians in the trial and patients in the trial as quickly as possible, and that's well underway.

Speaker #1: And our job now is to make that information available to those doctors and physicians in the trial and patients in the trial as quickly as possible.

Speaker #1: And that's well underway.

Speaker #2: The next question comes from Sylvan Turkin with Citizens. Please go ahead.

Operator: The next question comes from Silvan Tuerkcan with Citizens. Please go ahead.

Silvan Tuerkcan: Hey, good morning. Maybe can you talk a little bit about the patient gateway that you're building with HAE Reframed and is that more to get data points to you for potentially their marketing, or is that to push a message out around some of these endpoints where one-time treatment could be helpful? If so, what are those? Maybe related to that, what can we see at the Bradykinin Symposium data that's coming up here? Thank you so much.

Silvan Türkcan: Hey, good morning. Maybe can you talk a little bit about the patient gateway that you're building with HAE Reframed and is that more to get data points to you for potentially their marketing, or is that to push a message out around some of these endpoints where one-time treatment could be helpful? If so, what are those? Maybe related to that, what can we see at the Bradykinin Symposium data that's coming up here? Thank you so much.

John Leonard: Let me speak first to the symposium that you referenced. You'll remember that across the entire HAE program, virtually every single patient at some point gets to something that resembles no attacks and no therapy. It takes some patients longer to get there than others, but virtually everybody ceases to use long-term prophylaxis and almost all the patients no longer require on-demand therapy. They may carry it with them, but the overall utilization for these patients really plummets, which we think is exciting for the patients, for the doctors, and certainly for the payers who are supporting these patients. At the symposium, we'll go through what we think is very important information for how the drug behaves from a molecular level and how you can trace that with respect to the high molecular weight kininogen.

John Leonard: They may carry it with them, but the overall utilization for these patients really plummets, which we think is exciting for the patients, for the doctors, and certainly for the payers who are supporting these patients. At the symposium, we'll go through what we think is very important information for how the drug behaves from a molecular level and how you can trace that with respect to the high molecular weight kininogen.

John Leonard: That has specific reference to one particular patient who had a significant benefit from the drug but did not reach an attack-free status. The long and short of it is, the patient probably has a second process, unrelated HAE, and we will speak to that. I think that is really exciting information that speaks to one particular patient who stood out from the vast majority of patients who have all done very, very well. With respect to the website, we are trying to make sure that people have a good understanding of what the burden of HAE really is. We typically talk about disease attacks and the efficacy and safety of drugs that they receive.

John Leonard: With respect to the website, we are trying to make sure that people have a good understanding of what the burden of HAE really is. We typically talk about disease attacks and the efficacy and safety of drugs that they receive.

John Leonard: What is left out of the discussion many times is what patients have to go through just to get that and stay on their therapy, and still how HAE continues to affect their lives, because for all practical purposes, they continue to suffer from the disease. By having a better understanding of what patients need to do to get the drug on a recurring basis, sometimes requiring prior authorizations even twice in a year, we want to make sure that payers, patients, and doctors have a really good understanding of what that burden is. When they see the profile of lonvo-z, the contrast will be very, very apparent.

John Leonard: By having a better understanding of what patients need to do to get the drug on a recurring basis, sometimes requiring prior authorizations even twice in a year, we want to make sure that payers, patients, and doctors have a really good understanding of what that burden is. When they see the profile of lonvo-z, the contrast will be very, very apparent.

Operator: The next question comes from Leah Cann with Brookline Capital Markets. Please go ahead.

Leah Cann: My question has been answered.

Operator: The next question comes from Jonathan Miller with Evercore ISI. Please go ahead.

Yuanyuan Ang: Hello, this is Yuanyuan Ang for John. Thanks for taking my question. I would like to double-click on the allele analysis. Two questions. First, how many patients with grade 3 liver signals do not carry the allele? Are there any patients with lower grade signals that actually carry the allele? The second question is, are you considering additional prophy for patients carrying the HLA-C*05:01 allele? What are the additional risks to consider for those carriers? Any particular bad antigens on the cell surface that has caught your attention that may be relevant for the liver injuries? Thanks.

Yuanyuan He [Equity Research Analyst: Hello, this is Yuanyuan Ang for John. Thanks for taking my question. I would like to double-click on the allele analysis. Two questions. First, how many patients with grade 3 liver signals do not carry the allele? Are there any patients with lower grade signals that actually carry the allele?

Yuanyuan He [Equity Research Analyst: The second question is, are you considering additional prophy for patients carrying the HLA-C*05:01 allele? What are the additional risks to consider for those carriers? Any particular bad antigens on the cell surface that has caught your attention that may be relevant for the liver injuries? Thanks.

John Leonard: Yes. Thank you for the question. With respect to the full data set and the analysis, we'll release that information at the appropriate time, go through the molecular findings, the statistics that support that, et cetera, that's not something that we're in a position to do today. You asked, are we doing something different for patients who choose to participate in a study if they're 0501 positive? At this point, the answer to that is no. We believe the mitigation measures that are put in place are entirely appropriate for a cell-mediated immune adaptive response, which now we have some increased confidence that that's exactly what's occurring in these patients with these high LFT elevations.

John Leonard: At this point, the answer to that is no. We believe the mitigation measures that are put in place are entirely appropriate for a cell-mediated immune adaptive response, which now we have some increased confidence that that's exactly what's occurring in these patients with these high LFT elevations.

John Leonard: What we have found is that we can identify patients before the event occurs and give them the opportunity not to participate, recognizing that the likelihood of their having one of these increases is higher, substantially higher than the broader patient population. To flip it around, I think a helpful way to think about this is for the approximately 90% of people who don't carry 0501, the likelihood of a high LFT elevation is extremely low, and that is confidence-building for anyone who may wonder about what the likelihood might be for them, given the general data that's been released previously. As was stated earlier, even for the 0501s, most patients will not have the elevations, but we do know that when they do occur, these tend to be the ones that are most severe.

John Leonard: To flip it around, I think a helpful way to think about this is for the approximately 90% of people who don't carry 0501, the likelihood of a high LFT elevation is extremely low, and that is confidence-building for anyone who may wonder about what the likelihood might be for them, given the general data that's been released previously. As was stated earlier, even for the 0501s, most patients will not have the elevations, but we do know that when they do occur, these tend to be the ones that are most severe.

Operator: The next question comes from Terence Flynn with Morgan Stanley. Please go ahead.

Operator: Great. This is Chris Ang for Terence, thank you for taking our question. Maybe just double-click on the HLA genotyping finding. Just kind of looking ahead, do you expect that to be potentially on the label if approved?

Chris Yu: Great. This is Chris Ang for Terence, thank you for taking our question. Maybe just double-click on the HLA genotyping finding. Just kind of looking ahead, do you expect that to be potentially on the label if approved? In the commercial setting, do you expect every patient to get genotyped? Thank you.

Operator: In the commercial setting, do you expect every patient to get genotyped? Thank you.

John Leonard: 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. That's a bridge that we'll pass when we get to that point. I think in the meanwhile, what we're excited about and what our investigators are excited about is that this will give really good information with respect to how to focus in the best possible way, the benefit-risk on those patients who can most benefit from it. We will collect information during the screening process in the study. We don't think that it will slow down screening at all. This is a relatively straightforward process, and many of our investigators believe that this will actually pick up the pace of screening, which is already rapidly accelerating.

John Leonard: We will collect information during the screening process in the study. We don't think that it will slow down screening at all. This is a relatively straightforward process, and many of our investigators believe that this will actually pick up the pace of screening, which is already rapidly accelerating. We are very, very excited about this finding and the very, very positive things it can do for us.

John Leonard: We are very, very excited about this finding and the very, very positive things it can do for us.

Operator: The next question comes from Myles Minter with William Blair. Please go ahead.

Myles Minter: Hey. Thanks for the question. I've been getting a few inbounds since you published in the New England Journal on lonvo-z in HAE in the supplement. You show the ALT ASTs over time. I think in the ASTs at week 30 to 32 in patients that got lonvo-z first up at randomization, it looks pretty benign to me, but there are three patients that have kind of got an excursion outside of the reference range. Is that just variability or is there something else going on there at the later stages? Thanks very much.

Myles Minter [Equity Research Analyst: Hey. Thanks for the question. I've been getting a few inbounds since you published in the New England Journal on lonvo-z in HAE in the supplement. You show the ALT ASTs over time. I think in the ASTs at week 30 to 32 in patients that got lonvo-z first up at randomization, it looks pretty benign to me, but there are three patients that have kind of got an excursion outside of the reference range. Is that just variability or is there something else going on there at the later stages? Thanks very much.

John Leonard: Yes. Thanks for the question, Myles. The data's laid out in the New England Journal for anybody who wants to see it. Across the entire program, there's never been an LFT elevation greater than grade 2. Of those, there are other confounding reasons to consider them. In one case that, as you're referring to, this is somebody late, many, many months after receiving the drug, and this is almost certainly related to another thing that was occurring for the patient, and that's what his investigator thought. The elevation was benign. Nothing was done with respect to it, and it was low grade. For other patients that we've reported in the various stages of active clinical observation, patients either were confounded by the ongoing use of alcohol with one patient with a grade 2 that resolved rapidly.

John Leonard: The elevation was benign. Nothing was done with respect to it, and it was low grade. For other patients that we've reported in the various stages of active clinical observation, patients either were confounded by the ongoing use of alcohol with one patient with a grade 2 that resolved rapidly.

John Leonard: In a second case, again, reported in the phase III study here, a patient had LFT elevations during the screening phase and had a grade 2 elevation with a concomitant viral infection. Across the board, we see no signal. There's variability, as we all know about patients, how they live their lives. We're very excited about the efficacy and the safety profile of the drug as we move towards what we hope will be BLA approval.

Operator: The next question comes from Yanan Zhu with Wells Fargo. Please go ahead.

[Analyst] (Wells Fargo): Hi, this is Jeff on for Yanan. Thanks for taking our questions. For the lonvo-z BLA, can you mention if the final BLA has been submitted to the FDA, and if not, which remaining modules need to be completed? Based on your conversations with clinical sites for lonvo-z, are you expecting a bolus of patients at launch if approved? Thanks.

Jeff Stith [Equity Research Associate: Hi, this is Jeff on for Yanan. Thanks for taking our questions. For the lonvo-z BLA, can you mention if the final BLA has been submitted to the FDA, and if not, which remaining modules need to be completed? Based on your conversations with clinical sites for lonvo-z, are you expecting a bolus of patients at launch if approved? Thanks.

John Leonard: We are far into the BLA filing, and I would anticipate that the next time you'll hear from us, we'll be announcing what we hope will be the acceptance of the BLA. With that, we'll all gain a lot more information with respect to PDUFA dates, priority review, and things like that. We've been excited with the team's preparation, the very rapid and efficient way that they've been able to work with the FDA, and we're very excited about the progress that we've made.

Operator: Again, if you have a question, please press star then one. The next question comes from Andy Chen with Wolfe Research. Please go ahead.

[Analyst] (Wolfe Research): Thank you so much for taking my question. This is Jason taking it for Andy. Just wanted to ask really quickly about the HLA genotyping, if this is specific for ATTR-CM, or do we see this in other indications, like maybe PN, maybe? Do we see any sort of genotyping for maybe some of your other trials coming up? Thank you.

Jason Zhang: Thank you so much for taking my question. This is Jason taking it for Andy. Just wanted to ask really quickly about the HLA genotyping, if this is specific for ATTR-CM, or do we see this in other indications, like maybe PN, maybe? Do we see any sort of genotyping for maybe some of your other trials coming up? Thank you.

John Leonard: Thank you. We're not currently doing genotyping on a standard basis for any program that we begin. We don't think that that would be necessary. It would be hard to know what to look for, as we believe that what we're finding here is a very specific finding. Could you repeat your first question? Maybe Ed, if you heard it, I didn't hear one.

Operator: Your line is open now, Andy.

[Analyst] (Wolfe Research): Thank you. Just wanted to ask if this genotyping was unique for ATTR-CM, and maybe if it's usable in polyneuropathy. Yeah. Thank you.

Jason Zhang: Thank you. Just wanted to ask if this genotyping was unique for ATTR-CM, and maybe if it's usable in polyneuropathy. Yeah. Thank you.

John Leonard: Yeah. No, the genotyping is done across the entire program, irrespective of the indication. We're treating it as a relevant finding for both polyneuropathy and for cardiomyopathy and are applying the same rules and providing the same information for both studies.

Operator: This concludes our question and answer session. I would like to turn the conference back over to Jason Fredette for any closing remarks.

Operator: This concludes our question-and-answer session. I would like to turn the conference back over to Jason Fredette for any closing remarks.

Includes our question and answer session. I would like to turn the conference back over to Jason for that for any closing remarks.

Jason Fredette: Thanks, operator, thanks everyone for joining us. We hope you have a great end to the summer, we'll look forward to seeing many of you at the upcoming conferences in September. That concludes the call.

Uh, thanks operator. And thanks everyone for joining us. Uh, we hope you have a great end to the summer and we'll look forward to seeing many of you at the upcoming conferences in September, uh, that concludes the call.

Operator: The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.

The conference has now concluded, thank you for attending today's presentation. You may now disconnect

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