Good morning, everyone, and welcome to the Intellia Therapeutics HAE investor event. At this time, all attendees are in a listen-only mode, and a question-and-answer session will follow the formal presentation. To our analysts joining us live, please use the raise hand feature under the reactions button at the bottom of your screen to indicate that you have a question, and we kindly ask that you limit yourself to one question and one follow-up. As a reminder, this call is being recorded, and a replay will be made available on the Intellia website following the conclusion of the event. With that, I will now hand the call over to Jason Fredette, Vice President of Investor Relations and Corporate Communications at Intellia Therapeutics. Please go ahead, Jason.
Thank you, operator, and hello, everyone. Welcome to our investor event focusing on lonvo-z, Intellia's one-time gene editing candidate for people living with hereditary angioedema. This webcast is taking place in Phoenix, Arizona, at the 2026 American College of Allergy, Asthma & Immunology Scientific Meeting. Just a few moments ago, we issued a press release highlighting our seven presentations at this congress. You can access the press release on the investors and media section of Intellia's website at intelliatx.com. The presentations themselves will be available in the scientific publications and presentation section of our website at the start of their respective sessions. At this time, I would like to take a minute to remind listeners that we will make certain forward-looking statements during this event. 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. The agenda for today is shown here. Our CEO, Dr. John Leonard, will begin by providing an overview. He'll be followed by Dr. Marc Riedl, Professor of Medicine at UC San Diego and Clinical Director of the HAEA Angioedema Center. He'll share his perspective about HAE, today's standards of care, and the unmet needs that continue to be experienced by many patients. Our Chief Medical Officer, Dr. Jing Marantz, who joined Intellia last month, will then provide insights about the new clinical data we're presenting at this week's congress. Dr. Danny Cohn of the Amsterdam University Medical Center will share perspective from patients who received lonvo-z and his own personal experience as an investigator in our clinical trials.
Our Senior Vice President of Commercial, Maria Natale, will then share additional color about our market opportunity, the interest we're seeing in lonvo-z among patients, physicians, and payers, and our commercial readiness efforts. Following this, we'll take questions from the audience. With that, let me turn things over to our President and Chief Executive Officer, John Leonard.
Thank you, Jason, and good morning, everyone. We are really excited to share additional clinical data, hear insights from two of the world's leading key opinion leaders in HAE, and for the first time, allow you to get some perspective from patients who have received lonvo-z. We will also highlight some of our new market research, share our view of the market opportunity, and discuss our preparations to launch the world's first in vivo CRISPR-based medicine. Let's start with some broader context about our ongoing work at Intellia Therapeutics. Our goal has been to translate the promise of in vivo gene editing into transformative treatments for people living with severe diseases. Intellia's leadership by the numbers is encapsulated here. As of today, we have dosed more than 600 patients with our investigational in vivo gene editing therapies. We believe this is more than all other companies in the world combined.
We have up to six years of follow-up on some of these patients, and very importantly, we have yet to see any waning of pharmacodynamic or clinical effect. Earlier this year, we reported positive data for lonvo-z from HAELO, and we have two additional phase III trials ongoing for nex-z and transthyretin amyloidosis. On the right, you can see that Intellia's clinical and scientific leadership has been recognized repeatedly in the New England Journal of Medicine. Our pioneering work began more than a decade ago, and we have accomplished a series of world-first milestones in rapid succession since that time. From our first patient dosed in 2020 to the initiation of phase III development in 2024 to our positive readout in HAELO. Our excitement continues to grow as we approach what would be our most important world-first milestone, lonvo-z's expected approval.
As we announced in September, the FDA accepted our biologics license application, or BLA, for lonvo-z and granted it Priority Review. The agency set a PDUFA action date of March 10th, 2027, and it also stated that it did not currently plan to hold an advisory committee meeting to discuss the application. We believe lonvo-z is not only well-positioned to receive FDA approval, we also expect it to be a commercial success. This would set it apart from most one-time treatments that have been approved for other indications in the past. While AAV and ex vivo gene editing therapies have represented significant scientific advances, they brought with them a range of inherent limitations and challenges in the real world, some of which are listed here. These realities meaningfully reduce the eligible patient pool, their perceived clinical benefit, and the willingness to prescribe by doctors or receive the therapy by patients.
All one-time therapies are not created equally, and lonvo-z is a one-time treatment unlike any other. We simply don't face these same limitations. Leveraging a combination of CRISPR gene editing, lipid nanoparticles, and an in vivo delivery approach, lonvo-z was intentionally designed to avoid each of the challenges listed here. As a result, we think it will be among the first one-time treatments to actually deliver on the promise of one-time treatments. With that as a backdrop, let's outline four themes for our event today. First and foremost, if approved, lonvo-z will stand alone in the HAE space. Today, patients are served by chronically dosed long-term prophylactic medications, or LTPs, and by on-demand medications that are taken as needed. Lonvo-z is being developed as a one-time therapy that's intended to eliminate both attacks and the need for lifelong treatment. This is our definition of a disruptive therapy.
Second, you will hear loud and clear today that the HAE community is highly informed, engaged, and empowered. Patients play a large and important role in making treatment decisions, and our HAELO enrollment and market research clearly show that patients want lonvo-z. Third, preparations are well underway for potential approval and our planned launch. We have a strong commercialization strategy in place. We already have hired and onboarded our full field team, and wheels are in motion to educate HCPs, build our treatment network, and ensure broad patient access. Finally, we believe lonvo-z is well-positioned to deliver value to all stakeholders, patients, doctors, payers, and investors, once it is approved. Of course, it all begins with the patient. Before we turn to the clinical discussion, let's pause and hear about one person's journey with lonvo-z.
Matt is a patient living in the U.K. who received a one-time treatment in our phase I/II trial back in July of 2023.
I had HAE all of my life, although I didn't know that until I was diagnosed till I was 24. I am 53 now. Pre-diagnosis, I spent a lot of time in and out of hospital when I was young because they just didn't know what it was. It was such a rare disorder. That obviously impacted home life, going out with my friends, and the impact on my parents, missing school days, which again impacted my parents. I was given medication, and the attacks did become less frequent, but they didn't cease. It was much of the same, but just less frequent. It still impacted everybody. It still impacted my wife and where we could go, and whether I'd have to take medication with me or icatibant injections, et cetera. So, no way of predicting when the attacks were going to happen.
It sort of has a mental impact on you because you do become a little bit fearful of being abroad, for example. At the time, obviously, I didn't know anything particularly about it. It was a very new thing to me. It wasn't a case of a new medication taken over, which was then I'd be on for the rest of my life. There was lots of information to read through in terms of before making a decision. They obviously said that it was new, so there was no long-term data with regards to the infusion, and they were very thorough in terms of explaining how the infusion took place through speaking to my family. So, I went into it with my eyes open. Since I've had the infusion of medication that I received, my attacks stopped.
I have not had one attack, not even a mild attack, and I had the infusion two and a half years ago now. I am not on any medication. I think after the infusion, you are still fearful that you are going to have an attack because you do not know whether it has worked or not.
But as the weeks go by and the months go by, you have had a whole year without an attack and not on any medication, then you start to believe that you are never going to have an attack again. I am very thankful that I decided to have the infusion. Physically, there is not really much to talk about physically after the infusion because I have not had any attacks. I would like to say a massive thank you to all of the scientists and all the people who work in the laboratories at Intellia.
It is stories like these that motivate all of us at Intellia each and every day. Now let us hear more from Dr. Riedl. He will share some perspective about how treatment decisions are made and some of the unmet needs and burdens that many patients are still facing.
Thank you, Dr. Leonard. It is a pleasure to be here. HAE is a rare genetic condition that causes unpredictable, recurrent, painful, and potentially life-threatening swelling attacks. You can see some images on the right of people living with the condition before and during HAE attacks. But it is important to note that dangerous airway and debilitating gastrointestinal attacks are not always visible to the naked eye. HAE is caused by a deficiency or dysfunction of C1 inhibitor, which disrupts the kallikrein-kinin system and leads to excess bradykinin production. Symptoms often emerge in childhood, and while patients in the U.S. are diagnosed at about age 20 on average, the time of diagnosis can vary significantly from patient to patient. As a genetic condition, HAE requires lifelong management.
As Dr. Leonard mentioned, the condition is currently managed with two therapeutic strategies that are used chronically over a patient's lifetime, namely long-term prophylaxis therapies, or LTPs, and on-demand therapies, or ODTs. About 2/3 of people living with type 1 and type 2 HAE in the U.S. are taking both types of medications. The remaining 1/3 take only on-demand medication as needed. There are several oral and injectable LTPs and ODTs available today, and they leverage a few different mechanisms of action shown here at the bottom. How does someone decide which medication or medications to take? Well, per HAEA Medical Advisory Board guidelines, this is a shared decision that is made by both the physician and the patient. The HAE specialist physician's first job is to learn about the patient's experience with the condition.
Experiences can vary greatly from person to person, and an individual patient's experience can vary greatly over time. Of course, this is a rare condition that many physicians are unfamiliar with, so they may refer patients to HAE specialists or centers to have deeper discussions about their condition and treatment options. Step two in the process is to discuss treatment options together. Like many other physicians, I routinely present all available options to my patients and determine which might be the best match for their medical need, life circumstances, and personal preference. If the patient already is on therapy, we discuss their current treatment experience and whether a change in the management plan might be beneficial. Step three is to make the treatment decision together with the patient. An important part of the process is to ensure that they feel empowered to advocate for themselves.
In HAE, this often isn't an issue, as many people living with HAE are highly informed and educated about their condition and its available treatment options, which can make decision-making easier. One of the primary reasons this community is so well-informed is because of the work of the US Hereditary Angioedema Association, known as HAEA. This organization includes nearly 12,000 patients and caregivers. HAEA has for many years provided comprehensive educational resources and programs, offered strong patient support services, and directed research and advocacy efforts for HAE patients and families. Their work has led to an extremely collaborative and well-informed community, which has driven progress in clinical care and promoted shared decision-making in the management of HAE. Their work has yielded a highly interconnected network, facilitating insights, guidance, and discussions about the condition and its treatment.
There are people living with HAE today who are doing very well with current medications. Others continue to be burdened by the disease, and the burdens tend to come in two forms. First, there are disease burdens, namely continued HAE attacks with the associated pain, disruption, and disability, the fears and anxiety related to their next unpredictable attack, and the lengths that they go to in an effort to avoid an attack. Then there are burdens related to their ongoing treatment. These include the need to adhere to chronic medications, the ongoing financial toll these medications can have on families, and all the red tape that's associated with continued treatment. Here you see data that was compiled in 2025 based on interviews with 100 individuals with HAE.
The fraction of them who reported having attacks on a monthly basis was 34%, and 80% of patients experienced at least one HAE attack during the past year. Most also ranked mental health as one of their most impactful disease burdens, and nearly three-quarters said they were actively avoiding activities that could trigger an HAE attack. As mentioned earlier, disease control is a primary objective, but there are additional factors to consider, including the burdens associated with the need to take medications on an ongoing basis, whether it be oral or injectable treatments. Apart from this genetic condition, many patients are otherwise very healthy, so chronic use of therapies to manage HAE can be a constant reminder of their condition and a significant barrier to living an otherwise normal life.
In that same 2025 study we just spoke about, nearly 70% of patients reported the need for lifetime medication was a top concern. Their concern is often closely related to medication access and insurance issues. On the left, you can see one final panel from that same 2025 study. Medication costs and access were a concern for most of the 100 patients who were surveyed. When speaking with the subset of 89 patients who were on LTP therapies, 80% reported they were concerned their health insurance would change and impact access to their medication. On the right, you can see a smaller study conducted by HAEA. This focused specifically on patients who reported delays or denials in HAE treatment from insurance carriers. 20% of patients reported being unable to regain access to their medication, 70% reported more frequent attacks without medication, and nearly all reported increased anxiety without their medication.
This is a vicious cycle that plays out all too often in HAE. Patients experience attacks, they take treatment for their attacks, they get stressed about losing access to medication, and this triggers even more HAE attacks. Before we move on from this topic, it's important to point out that HAE medication access is also an issue for physicians and healthcare providers. Since the cost of most HAE therapies is high, the authorization and reauthorization process requires a lot of time and energy for both patients and for medical office staff. At my center, I'm fortunate to have a team that focuses entirely on the insurance authorization process, but we're likely an outlier, as medical practices often struggle with the administrative burdens associated with prescribing and maintaining access to HAE medications for their patients.
Before handing the call over to Dr. Marantz, let me also personalize things a bit by discussing my own center's experience in the HAELO phase III clinical trial. We saw considerable patient interest in this trial. However, as we were among the last centers to come online, we were only able to screen and enroll one of our patients. This participant had type 1 HAE with frequent and severe angioedema attacks. She had cycled through a number of LTP therapies since her diagnosis and was continuing to experience breakthrough attacks. We discussed her treatment options, which included other approved LTPs in clinical development, and lonvo-z. Ultimately, she decided to enter HAELO for a couple of reasons. First, based on the clinical data that had been reported at that time, she saw the potential for this therapy to reduce her HAE attacks and the burdens associated with taking chronic medicine.
Just as importantly, she also wanted to do this for her young son, who also has HAE. She saw the trial as a way to pay it forward and contribute to a potential path for him and others to have a better life than she experienced with HAE up until that point. This participant was dosed in the summer of 2025, and she says that she's benefited tremendously from lonvo-z. She actually has described her participation in HAELO, and these are her own words, as a, quote, "life-changing event." Now, I'll turn the meeting over to Dr. Marantz for the clinical data review.
Thank you, Dr. Riedl, and good morning, everyone. I am thrilled to join Intellia at such a pivotal and exciting time. First, a brief background on the lonvo-z mechanism of action. As Dr. Riedl mentioned earlier, HAE is driven by the dysregulation of the kallikrein-kinin system illustrated here. In healthy individuals, the C1 inhibitor acts as a brake, regulating the kallikrein-kinin system and preventing the overproduction of bradykinin. In people with HAE, a deficiency or dysfunction of the C1 inhibitor removes this regulatory brake, leading to the overproduction of bradykinin and causing debilitating swelling. To target this underlying pathway that drives HAE attacks, lonvo-z is designed to permanently inactivate the KLKB1 gene via just a single dose. This then reduces the production of kallikrein and bradykinin, leading to the rebalancing of the system. One thing that sets lonvo-z apart from the other one-time therapies is its relatively simple administration.
The diagram here illustrates how lonvo-z was administered in our phase III HAELO trial. The process closely approximates how we envision it to be used in the real world. Starting from the left, participants were given oral dexamethasone, which was taken at home the day before the administration. On the day of the infusion, as lonvo-z was being prepared, participants first received another dose of dexamethasone along with histamine blockers to minimize potential infusion-related reactions. They also received a C1 inhibitor as short-term prophylaxis to avoid HAE attacks on the infusion day. After that, lonvo-z was administered over the course of about four hours. Following the infusion, they were monitored for a period of time before returning home on the same day.
Before I walk you through some exciting new data, a quick reminder that lonvo-z' placebo-controlled phase III HAELO trial achieved its primary endpoint and all key secondary endpoints with high statistical significance, including on the quality of life endpoint. On the left-hand side, you can see that treatment with lonvo-z resulted in an 87% mean reduction in attacks compared with placebo. Importantly, 100% of participants in the lonvo-z arm experienced a decrease in the number of attacks compared to baseline. In addition, as shown on the right, 62% of participants in the lonvo-z arm were completely free from attacks. Moving to the next slide, we are very pleased to be sharing seven presentations at the college meeting this week. I will highlight just a few in the next few slides. We will start with some additional data from the HAELO trial.
As you saw from Dr. Riedl's presentation, about 2/3 of participants with type 1 and type 2 HAE are taking LTP medications today. So we wanted to take a closer look at these specific participants. Represented on the left are the 35 participants who were on LTP just prior to the screening and were randomized to the lonvo-z arm. These participants reported a mean of about 1.2 attacks per month while receiving these LTPs before the washout period. During the efficacy observation period from weeks five to 28 post-dosing, the attack rate decreased by 81%. The panel on the right looks at the attack-free rate for those same participants. The bar on the left shows that 20% of participants reported attack-free being their best response to LTP at study entry.
Following lonvo-z treatment, 63% of these participants achieved complete control during the efficacy observation period, more than tripling the attack-free rate. This is a forest plot looking at the attack ratio across different subgroups of participants enrolled in the HAELO trial. As you can see, all the results favored lonvo-z regardless of which subgroup the participants were in. What is also striking is that all the confidence intervals are far to the left of the midline, illustrating substantial benefit for all the subgroups evaluated. This included, starting from the top, whether participants were on LTP or not. Right below that, whether participants were on the leading LTP and then on lanadelumab, followed by historical attack frequency, severity, or baseline attack rate. Regardless of which subgroup participants were in, the benefit ratios were remarkably consistent, all favoring lonvo-z.
The next presentation I wanted to highlight is an integrated analysis of lonvo-z data from our phase I, II, and III clinical trials. In total, 117 participants have received lonvo-z in our clinical trials, with up to four years of follow-up in some participants. As of the data cutoff, 93 of those participants received a single lonvo-z treatment of 50 milligrams, our proposed commercial dose, and that is the population we will focus on next. As I mentioned earlier, lonvo-z is designed to permanently reduce the production of plasma prekallikrein, and consequently lowers the production of kallikrein and bradykinin to prevent HAE attacks. As such, plasma concentration of kallikrein serves as a reliable pharmacodynamic marker for its biological effect. Looking at the line graph from left to right, you can see that kallikrein levels dropped steeply immediately after dosing and consistently across the 93 participants.
The mean reduction is over 80% by month two, and it remained deep, consistent, and durable through four years. It is important to note that lonvo-z is a liver-directed therapy. Virtually 100% of liver cells turn over within just three years. So we believe that these four-year data confirm that lonvo-z is doing exactly what it is designed to do. Now, how does the pharmacological effect translate to disease control of participants clinically? This line graph illustrates this point beautifully. The y-axis on the left measures monthly attack rate. On average, participants were experiencing more than three attacks per month at baseline. Following lonvo-z treatment, that level decreased to below 0.5 by month two and remained consistently below that level through year four. Now, we overlay the dark blue line, which is the percentage of participants achieving attack-free status, shown by the y-axis to the right.
The percentage exceeded 80% by month four and remained consistently above that level out through four years. And finally, and importantly, all 93 participants were free from LTP therapy as of our latest data cutoff. From a safety and tolerability standpoint, lonvo-z's profile remains favorable. Shown here are all treatment-emergent adverse events that have been reported through data cutoff. I want to point out that the majority of AEs you see at the top of the table, including infusion-related reactions, headache, and fatigue, occurred within the first month following lonvo-z administration. Consistent with our previous presentations, no long-term risks have been observed for lonvo-z. To summarize, our phase III HAELO data showed that HAE participants who were on LTP prior to study entry experienced substantial reductions in their attack rates, with a 3x increase in the proportion achieving attack-free status following lonvo-z dosing.
Importantly, the benefits were consistent across all the subgroups analyzed, regardless of their disease severity or previous LTP treatment. The integrated analysis showed deep and durable reduction in plasma kallikrein through four years, confirming that lonvo-z's gene edit is doing exactly what our scientists designed it to do. The pharmacodynamic effect translated into clinical benefit, with substantial reduction in attack rates and 100% of participants free from the LTP therapy at their last follow-up. With that, I'd like to turn the call over to Dr. Danny Cohn of the Amsterdam University Medical Center to highlight one other presentation that's taken place here in Phoenix.
Thank you for the introduction and for having me here, Dr. Jing Marantz. My section will include some highlights from a poster presentation taking place tomorrow. It focuses on actual reports from clinical trial participants about their lived experiences with hereditary angioedema, both before and after receiving a one-time lonvo-z treatment. First, some background. In order to take part in this study, the participants must have completed lonvo-z's phase I or II clinical trial, they must have received a dose of at least 50 milligrams of lonvo-z, and they must also have enrolled in the long-term follow-up study. In total, 31 trial participants were contacted for the study, and 23 consented and were interviewed by telephone or video. On average, the interviewed participants had about 2.5 mean angioedema attacks per month prior to dosing and 0.1 angioedema attacks per month since dosing.
It is also important to note that the median follow-up on participants at the time of their interviews was nearly 2.5 years. Here's a summary of findings from the interviews. Starting at the top left, when reflecting on life before lonvo-z, just 48% of participants considered that their HAE was well-controlled. After lonvo-z, all 23 considered their HAE to be well-controlled. While that is impressive, it also should be noted that their own definitions of control changed meaningfully. In total, 86% of participants redefined what well-controlled meant to them. Before lonvo-z, well-controlled meant fewer and less severe attacks, more manageable symptoms, and daily life continuing despite the disease. The bar was raised significantly after lonvo-z because now, well-controlled means no symptoms or attacks, a significantly reduced treatment burden, and HAE being less or not at all prominent in their lives.
At the bottom, you can see that about three-quarters of survey participants thought about their HAE all of the time before lonvo-z, and after lonvo-z, 87% never thought about HAE or only thought about the disease when others reminded them about it. Now on to some of the actual interview excerpts. As you see on the left, when discussing life before treatment, many talked about the anxiety and frustration they felt. For some, this related largely to their impending angioedema attacks, and for others, it related to medication access. Sadness was also an emotion mentioned by multiple participants. They recalled the shame and embarrassment they felt about this disfiguring disease and about having to cope with HAE through changes in their lifestyle.
On the right, you see a few related quotes, some speaking about having an inferiority complex, about missing opportunities and being frustrated, and being really frightened that they would lose access to therapy. That was before. This is after receiving lonvo-z. The figure on the left shows the new themes that emerged in the interviews. They reported being freed from stress and anxiety, and they reported feelings of calmness, happiness, and relief. On the right, you see some of their quotes, words like, "I feel like I've never been ill. It's like I haven't got HAE anymore. It's completely controlled, and I no longer need to make life choices based on my HAE." Finally, virtually all participants, 22 out of the 23, described lonvo-z as an optimal treatment. When asked to explain what this meant to them, three themes emerged.
They noted the one-time nature of administration is highly appealing, and they liked the fact that it was giving them freedom from attacks. Most importantly, they came back to the repeated theme that the treatment allowed them to live more normal lives. I would also note that the one participant who did not describe lonvo-z as optimal said this was because they occasionally experienced some subtle symptoms that they associated with hereditary angioedema. On the bottom are a couple of final quotes, with one participant calling lonvo-z the new gold standard, and the other saying there is no comparison with other therapies. In closing, I would like to share my own personal experience with lonvo-z. The Amsterdam University Medical Center was a treatment site in the phase I, II, and III trials.
In total, we administered lonvo-z to 17 trial participants, a majority of whom had previously been on long-term prophylactic medications. What I found early on was that many of them already knew about lonvo-z during our initial discussions about the clinical trial, and they were quite motivated to enroll. Generally speaking, their motivations were similar to those you heard from Dr. Riedl. They were seeking freedom from the burdens of their disease and its ongoing treatment. Also, given their experience with the disease, they viewed enrollment as a way they could potentially give back and provide future generations with improved treatment options. In terms of the infusions themselves, they were quite straightforward. Since their infusions, the participants' experiences have closely mirrored what you already heard from the ACAAI presentation.
All of our participants have reported a benefit, and we were one of the initial treatment centers to administer lonvo-z back in 2022, and none of our trial participants have reported a waning of effect. In my discussions with them, many have described the treatment as a real turning point in their lives. Thank you for the opportunity to share this perspective. I'll now turn the meeting over to Maria.
Thank you, Dr. Cohn, and good morning, everyone. I have had the privilege of launching several medicines in my career, but I have never heard feedback like this. It is why our team is so focused on being ready. If approved, we want lonvo-z in the hands of physicians as quickly as possible. Today, HAE care is chronic, lifelong dosing, refills, and insurance reauthorizations. Each step adds burden for the patients, families, physicians, and payers. Lonvo-z has the potential to completely transform the treatment paradigm. Designed as a one-time infusion, it has the potential to turn decades of chronic care into a one-day event. We believe lonvo-z's value proposition should resonate with every stakeholder. For patients, there is the potential for attack and treatment freedom with a one-time infusion. For physicians, there is the potential to reduce administrative burdens and provide more time for actual patient care.
For payers, there is the potential for significant reductions in the long-term financial burden of HAE. But potential is only the beginning. The real question is, once approved, how we will turn lonvo-z into the preferred treatment option for patients and physicians? I will answer that question in four parts. First, the market. What are we hearing from physicians and patients? Finally, how are we readying for approval and launch, including our work with payers on access? Let's begin with the market. Today, about 7,500 patients are treated in the U.S. for type 1 or type 2 HAE. As Dr. Riedl mentioned, most are on LTPs with or without on-demand treatment. This is a well-defined market. Patients are already diagnosed, already treated, and already seen by specialists, and that makes a focused launch possible. On the right is the cost of treating just one of these patients.
HAE is rare, but it puts an outsized burden on the healthcare system. Most LTPs are priced well in excess of $500,000 per year, and on-demand therapies also tend to cost hundreds of thousands of dollars per year. HAE is lifelong, so most patients are on therapy for decades. Even assuming no price increases, the cumulative cost of a single decade of therapy is typically in the multi-millions and more than $6 million for a patient on LTP and nearly $5 million for a patient on on-demand therapy only. We have a well-defined market, but will physicians want to prescribe lonvo-z? To determine that, we recently surveyed over 150 healthcare professionals who together care for about 20% of all U.S. HAE patients. First, let us hear what they said about the burden of HAE.
When asked about the burdens of HAE on patients, nearly 100% said they recognize the disease significantly impacts patients' lives and that the goal for treatment should be to allow their patients to lead as normal a life as possible. The strong majority worry that their patients will need to take therapies for the rest of their lives, and over 80% agree that getting insurance to approve HAE therapies is a big burden for patients and for their own practices. We looked at the healthcare practice issue more closely and found that HAE patients represented only about 3% of the total patients cared for by these HCPs. However, these HCPs reported that on average, about 17% of their staff's time is spent on HAE. Roughly a 6x disproportion.
It is important to keep in mind that nearly all of this time is spent on administrative work that is not reimbursed by payers, activities like submitting prior authorizations and reauthorizations, and managing denials and appeals. The pressure is real for patients and for practices. This raises an important question. If a one-time therapy existed, would HCPs prescribe it? lonvo-z's profile and clinical data from HAELO were shared with over 150 HCPs on a blinded basis. 88% said they would prescribe this one-time therapy to at least one patient. In fact, 54% said they would prescribe it to at least half of their patients if approved. When asked how quickly they would prescribe lonvo-z, most said they would do so within 12 months of approval. Most HCPs intend to prescribe and will do so quickly. Next, we will look at which patients they would treat first.
Physicians naturally prioritize patients who are not doing well. In our research, 77% said they were likely to extremely likely to prescribe it to patients who are not well controlled on their LTP. Interest also extends beyond that group. Over 40% said they would prescribe to patients who were well controlled on their LTP, and about half of them also said they would prescribe to patients who were only taking on-demand medication. When asked which patients they would prioritize for a one-time treatment, they pointed to those with multiple treatment switches, those who continued having breakthrough attacks, and importantly, those proactively seeking a treatment like lonvo-z. As Dr. Riedl highlighted earlier, 80% of surveyed patients reported at least one attack in the past year, underscoring the ongoing burden and opportunity to redefine what control means in HAE. Now, let's turn to the most important stakeholder, patients.
We recently surveyed over 150 patients and asked what they thought about chronic therapy and how they view a one-time treatment like lonvo-z. 79% reported they are very worried about their need for lifelong therapy, and 78% of patients reported that they wanted to avoid LTP therapy. Many patients want to avoid lifelong treatment. The next question is, would they ask about lonvo-z? We shared lonvo-z's profile and data with patients in a blinded fashion. Overall, 83% said they were likely to extremely likely to ask their physician about it. As you can see here, the intent to ask is high, regardless of their current treatment type or disease control. Even for those who are well controlled on their LTP, the appeal of no longer having to take a chronic medication is very high. Now, let's compare that with the HCP responses we saw earlier.
Patient interest and HCP prescribing intent are similar for patients who are not well controlled on LTP. For well-controlled LTP patients and those using on-demand treatment, patient interest is high. Of course, these measures answer different questions. Patients are considering a conversation with their physician, while HCPs are deciding whom they believe is appropriate to treat. The gap highlights an opportunity for us to continue educating HCPs about our clinical data. In HAELO, patients benefited similarly regardless of disease control. It also is important to echo something that Dr. Riedl said. Patients with HAE generally are highly educated, they are empowered, and they have a shared role in decision-making. Also, as a reminder, the HCPs reported in their survey they will prioritize patients who proactively seek a treatment like lonvo-z. Finally, patients were asked what they would do if their healthcare provider was unable to prescribe lonvo-z to them.
Over 70% reported they are likely to seek a new HCP if that were to be the case. We also explored whether interest in lonvo-z differs based on the patient's current LTP product. The data on the left here focuses specifically on patients who were on an LTP at the time of the survey. As you can see, regardless of which LTP they were taking, a strong majority intended to ask about lonvo-z. While the treatments are different, they all require chronic dosing. That may help explain the broad interest in lonvo-z. That interest also could lead to early conversations. Across all survey patients, 68% indicated they are highly likely to discuss lonvo-z with their HCP within six months of product approval. We also wanted to see how lonvo-z stacks up against other treatments still in development.
We asked patients to rank it alongside approved LTPs and other pipeline options, including some that could extend dose intervals to as long as six months. As the data shows, lonvo-z was the clear favorite, with nearly 3x as many patients ranking it first compared with the next clinical stage candidate. One patient's comment helps bring that preference to life. What stood most to them was the efficacy, followed by the one-time dose. Even with future options in the mix, lonvo-z was clear top choice. Finally, on the patient front, we believe the baseline characteristics and enrollment dynamics from our HAELO study provided very clear real-world evidence of the interest in lonvo-z. All types of patients participated in this trial.
About 70% were on LTPs when they entered the study, and as you heard earlier, about 20% of the enrolled population reported complete attack control as their best response to prior LTP. Enrollment was rapid, 80 patients within nine months, well above our target of 60, and we had to turn patients away at multiple centers. About half of the patients were enrolled in the U.S. Participation also required real trade-offs, exposure to a new in vivo CRISPR modality with limited data, LTP washout with a risk of more attacks for an extended period of time, and a 33% chance of placebo. Patients accepted these trade-offs despite having six approved LTPs options in the U.S. Lonvo-z could ease burdens for patients, physicians, and payers. In HAELO, lonvo-z's attack reduction was in line with the best chronic LTP. Its differentiation lies in all the other areas you see here.
If approved, it will be the only option for patients seeking freedom from attacks and chronic treatment with a single infusion while easing ongoing access and administrative burdens. Finally, while it's premature to discuss pricing, we have a plan that we believe will ensure broad payer coverage and patient access while also reducing long-term financial burden to the overall healthcare system. The market is well-defined, and the patient and physician interest is clear. Now, let's turn to our final topic, launch execution. Upon approval, we will seek to convert interest into treatment as efficiently as possible. Every stakeholder who plays a role in the journey must be ready to support patients who are seeking lonvo-z. A one-time treatment is a new paradigm in HAE, so we must forge a new path. Fortunately, we're not starting from zero.
Some of the other commercialization lessons from other one-time treatment launches are transferable, which we will cover next. As John mentioned, success stories for one-time treatments have been limited today, but those early launches have taught us a lot of good lessons. Teams were sometimes hired too late or lacked the right experiences. Education was lacking for some key audiences. Access and reimbursement was difficult for some, and it took time to get patients to treatment centers. We are using those lessons to take a different approach with lonvo-z. Our first response to the lessons is the team. A strategy is only as good as the team that executes it. We have hired very seasoned team members. Most have HAE or cell and gene therapy experience, and their combined experience spans all approved HAE products. It is a lean but highly specialized organization.
Every step of the patient journey is supported by team members with expertise in that area. We have established what we believe is the right approach for a one-time therapy. Let me highlight a few things we did differently. We built the payer account team earlier than would be the case for a chronic therapy because we needed to engage payers early. We formed an experienced strategic accounts team dedicated to building and managing our infusion network. Reimbursement and access are top priorities. That is why we have dedicated reimbursement specialists supporting provider reimbursement and dedicated nurse case managers to keep patients well-informed about the status of their case. And because HAE is a competitive space, a dedicated sales organization is essential to building demand.
This team is already engaging HCPs today on the burden of HAE, and after approval, they will shift their focus to educating HCPs on lonvo-z so they can make informed treatment decisions. The team is in place. Next, I will show you the work that they have been doing ahead of launch. Over the past couple of years, our medical teams have been educating physicians and patients about CRISPR. They have successfully executed a significant number of educational initiatives, including gene editing seminars at multiple medical congresses, lab tours at our facilities, and patient-centric webinars. The community has responded with strong enthusiasm, and the appreciation for our technology and approach has grown. Earlier this year, we launched HAE Reframe. This educational campaign plays a key role in raising awareness of the hidden burden of HAE in a way that has never been discussed before.
Since May, our digital campaign has reached nearly all HAE prescribers, and more recently, our field team began its disease education outreach to about 1,300 healthcare providers. Upon approval, we will be initiating product promotion efforts through digital and field engagement. Now, let us take a few minutes to discuss the HAE access landscape, starting with who pays. About 68% of HAE lives are covered by commercial insurance plans. This is a much heavier commercial mix compared with past one-time therapies, which we believe is an advantage for a few reasons. First, commercial payers have experience developing policies and reimbursing one-time therapies. Second, policies for new therapies are typically issued within three months-12 months of approval. And based on access ramp for other one-time treatments, a large proportion of lives are expected to be covered between seven and nine months.
For a one-time therapy, getting policies in place quickly is especially important because it builds provider confidence to prescribe and helps accelerate time to treatment. Fourth, meaningful patient volume is concentrated among national payers, so a focused set of conversations can reach a large portion of the population. Lastly, since most patients have commercial insurance, Intellia can offer copay support that could enable eligible patients to have zero copay, which gives us an important tool to address affordability for a large proportion of patients. We began our payer outreach nearly two years ago and have had multiple rounds of discussions with payers covering more than 280 million lives. We have shared lonvo-z's profile and clinical data with them and asked for their reactions. What we have generally heard is that they recognize the potential value of a therapy like lonvo-z.
They see the benefit of one-time dosing, which could eliminate adherence issues with chronic therapy. They also recognize that the cost of our in vivo administration will be a small fraction of what they are paying for all ex vivo therapies. Lastly, they cite our four-year durability as a primary value driver versus LTPs. Because we have educated them on the mechanism of action, which is intended to provide a permanent edit, they are increasingly confident in its potential for economic benefit. We also have been laying the foundation for our nationwide network of authorized treatment centers, or ATCs. We have a firm handle on where HAE patients live, and we plan to make lonvo-z convenient for them to access. Our goal is for most patients to have an ATC located within a 100-mile drive.
We expect to have dozens of ATCs across the country, including academic centers and certain community practices that treat many HAE patients. Earlier this year, we began our ATC engagement, and since then, our team has identified key decision-makers, assessed capabilities, confirmed interest, and began training ATCs' teams on access, billing and coding, and product handling. Importantly, we intentionally built a flexible distribution network. ATCs will be able to choose to either buy and bill directly or use a specialty pharmacy, which can eliminate upfront funding and reimbursement exposure. Delays in treatment center readiness slow prior other one-time therapy launches, so we are preparing sites now ahead of a potential approval. Let us spend a minute setting expectations in terms of how we expect demand, access, and our ATC network to evolve over the first year, assuming approval.
In the first three months, initial patient prescriptions will move through medical exception processes while ATCs begin their committee reviews. From months three- six, we expect early referrals to convert, many commercial policies to be put in place, and we will treat our first wave of patients. This is when we expect revenue recognition to begin. By month nine, most commercial lives should be covered and most ATCs will be up and running. By month 12, we expect to be in our full commercial ramp with the network fully activated. We believe a therapy with the potential to benefit all stakeholders is one that is destined to succeed. As you have heard, for people living with HAE, the burden does not end with the attacks. It continues with lifelong treatment. 79% of patients worry about it. Physicians feel the burden too.
HAE is consuming an outsized proportion of their time, and about 90% of that time, it is not reimbursed. Payers are also feeling it, with chronic LTPs costing often exceeding $6 million per patient per decade. lonvo-z has the potential to change all of that, a single treatment that could provide durable control without the chronic treatment burden, so patients can focus on living, not managing disease. For physicians, that means less administrative work and more time for patient care, and for payers, it means lower long-term cost. The early signals are encouraging. In our research, patients express strong preference for lonvo-z, and 88% of surveyed physicians will prescribe it to at least one patient. We believe a commercial-heavy payer mix will translate into faster, more predictable access, and most patients are expected to incur zero copay. Assuming FDA approval, we believe Intellia is well-prepared to achieve commercial success.
We have established what we believe is the right commercial model for a one-time therapy. Our patient and HCP education efforts are ongoing, payer outreach has been underway since early 2025, and we are readying our treatment network. This is a once-in-a-lifetime opportunity for all of us here at Intellia, and we are excited to make a reality starting early next year. Now, let me turn the meeting back over to John to close things out.
Thank you, Maria. In closing, let me just reemphasize a few points that we made at the outset. First, we believe lonvo-z will be among the first one-time therapies to actually deliver on the promise of one-time treatment by disrupting and completely redefining the HAE treatment paradigm. Second, people living with HAE are highly educated, motivated, and empowered, and many want a treatment like lonvo-z. Third, as you just heard, we are well-prepared for our planned launch. Finally, we believe lonvo-z has the potential to deliver value to all stakeholders, including our shareholders. We appreciate you all tuning in, and we are now happy to take your questions.
Great. Thank you, John. At this time, we will be conducting a question-and-answer session with our speakers. As a reminder to our analysts joining us live, please use the raise hand feature under the reactions button at the bottom of your screen to indicate you have a question, and we kindly ask that you limit yourself to one question and one follow-up. Please hold for a brief moment while we pull for questions. Our first question comes from Maury Raycroft at Jefferies. Please go ahead, Maury. Maury, you might be on mute. We will go to the next analyst while we wait for Maury to unmute himself. Our next question is from Joe Thome at TD Cowen. Please go ahead.
Hi there. Thank you for the presentation. It was excellent. Maybe one for the physicians on the line if they are still here. We saw some great metrics about adoption overall in the poll surveys. Maybe if the physicians could talk a little bit about how they are going to incorporate this in their practice if approved, given that it sounds like there is some pretty strong inbound interest. Second, for the company, it was nice to see that there is going to be interest in both the long-term prophylactic and on-demand segments. Do you anticipate reimbursement or any sort of step edits to be different for those two populations? Thank you.
Maybe we could take the second question first, and Maria, if you just want to say a word about any differences you could see in terms of how patients get to lonvo-z starting from LTP or on-demand therapy.
Yeah, sure. Thank you for the question. We do expect, as for all new therapies, step edits to be present for assessing lonvo-z. We expect, though, that most of the patients that are on LTP would qualify for lonvo-z. That is number one for LTP patients. For on-demand patients, we know from our research as well that about half of that population has been on an LTP previously. These are patients that decided to discontinue LTP either because of lack of efficacy or because of the burden of the condition. We expect some of those patients to qualify as well. If the patient is really motivated about getting into lonvo-z and a step edit is required, they would have to take their time and to go on an LTP first in order to access lonvo-z.
The drug will be available to both patient populations, we would expect.
Exactly.
Maybe we could turn to Dr. Riedl and tell us how you think about the drug in your practice.
Sure, thanks. I mean, my general practice, and I think most of my colleagues that treat HAE, we discuss really all of the treatment options as we see patients. I think lonvo-z would be right there on the list if approved by the FDA. It was in the presentation, but I think shared decision-making is a really important issue in HAE, just because there is so much variability from patient to patient, not only in terms of how their symptoms manifest, but how the condition actually affects their lives. That's why there's very little us telling patients what to do, so to speak. It's a lot about what's important to them, what are they comfortable with. I think, as you've heard and seen, lonvo-z is very unique as a one-time treatment with very high efficacy.
I think we will be having those discussions with many patients. I sort of expect we're going to see a lot of patients coming in and actually asking to discuss this based on the profile that we're seeing from the clinical studies. The last thing I'll say is, I will admit it's very difficult for me to predict what treatment an individual patient will elect to proceed with, but I think that's part of why we have these detailed discussions, so that both the patient and we can feel comfortable with whatever decision is made. I think this will be a very important addition to our options.
Dr. Cohn, you treated a lot of patients, and I know you're based in the Netherlands, so there may be a timing difference here, but maybe you could just say-
Yeah, I can echo Marc's comments, especially that many patients are so much interested in this treatment that they bring it up themselves during the consultations, even though it's not yet approved. They are asking me, "When can I get this treatment?" I think this comes up in almost all conversations at the clinic nowadays.
Thanks.
Perfect. Thank you.
Thanks for the question, Joe. It looks like Maury was able to unmute, so Maury, please go ahead. We'll just go to John Miller at Evercore next. John, please go ahead.
Sorry for taking your place, Maury. Thanks so much for all the new detail, guys, and thanks so much for taking my question. Maybe just generally for the team, I'd like to start with, it's great to see so much general interest in lonvo-z, but I'd like to ask about urgency to treat. Even among patients who are, generally speaking, interested and interested in having these discussions, what is your expectation for the rate of conversion from general interest to folks actually getting into the treatment funnel and making the choice to treat? Maybe dovetailing that to our prescribers on the line, among patients who you speak to who are not enthusiastic or maybe cautious about a one-time therapy or have reservations, what's holding them back from feeling enthusiastic? What's holding them back from wanting to do a one-time therapy immediately?
Maria, why don't we start with you? Why don't you tell us a little bit about how you expect the market to evolve over the first 12 months or so?
Yeah, absolutely. We know, and from my prior experience as well launching drugs in this community before, that this is a community that is highly empowered and they move very, very quickly. You can see that in the adoption of the most recently launched products as well. But as we know, lonvo-z is one of its kind, right? It is a different therapy. It is not chronically administered. It is not dispensed by the specialty pharmacies. We expect time to treatment to be longer than for a chronic therapy. There are a number of steps that are unique to a one-time therapy.
For example, securing financial coverage between the payers and the ATCs that do not exist today for chronic therapies, all the logistics around managing the infusion and scheduling that infusion and making sure that the schedule works for the ATC as well as for the patient. We expect the first three months for most of the patients to go through medical exception processes, as we talked about in the call. We expect to see our first wave of patients getting treatment in the second quarter after launch, and we expect to be in our full commercial ramp by month 12 after approval as well. The first six months will be primarily dedicated to making sure that we have policies in place to secure coverage for patients, as well as that we have activated our ATC network.
Thanks, Maria. Maybe Dr. Riedl, if you could share a little bit about how patients are thinking about this. What do they need to learn? How can we help them, if at all?
Yeah, we've had a lot of conversations about lonvo-z and gene therapy in general, as there were other programs that are no longer running. But for the study and now with the study results, lots of patients asking. We've sort of picked their brains a little bit, and you heard some of the survey data, but my own experience is there's clearly a group of what I would call early adopters. They're ready to go, they're convinced, and they will be the first to go to get the treatment. To your question, there is also a group of people who are a little more wait and see, and this is not unusual, right?
With every new treatment that's come to HAE, we have the early adopters and we have the people that sit back and say, "That sounds really great, but I'd like to wait and see how it goes in the real world for a little while." So I think mostly those patients are waiting to see more information or data on both safety and durability. I don't know what the magic number is. Of course, we have data out to four years now, as you heard. But I think there is a group of patients that are very interested and anticipate at some point will get the treatment, but sort of want to see how it goes in the real world first. That's totally normal. We see that all the time. So that's kind of been my experience, that more data, more experience is important for some patients.
Dr. Cohn, you've participated in phase I, phase II, and phase III. You've treated many patients. How has the word spread, and have attitudes changed at all in your patients over time?
Some patients indeed, when they were invited to participate in phase I, wanted to see some more evidence before considering their participation. But in the end, they decided to participate in phase II or phase III portion. I think what stands out to me mostly is that we did an analysis amongst patients about their having children, and up to 40% of patients in the past decided to refrain from having children because of the severity of their condition. But now with these kinds of treatments on the horizon, this has shifted tremendously, and now patients are having children even though they have a 50% chance of passing on the condition. But they think that with these perspectives, they feel pretty confident now that their children won't have to face the same issues that they had.
And this, especially, they bring up a one-time treatment as one of those major breakthroughs for their offspring.
Thank you for that.
Thanks for the questions, John. Our next question comes from Silvan Türkcan at Citizens. Please go ahead.
Yeah, good morning, and thanks for this very informative webinar. You've shown cumulative costs of on-demand or long-term prophylaxis therapy per year and per decade here. Does it include the price of attacks and hospitalization, and would that be an additional saving, given that 60% of your patients are attack-free and long-term prophylaxis-free? Then maybe just around the hospitals, what are the resources and processes required for the hospital for this therapy? What do they need to get in order before they can dose patients, maybe in terms of ordering systems or handling or infrastructure, if there is any? Thank you.
Maria, you can tell us where the numbers come from and what is included in them, and then we will come back to the second question.
Yes. This was an analysis that was done and published and based on claims data, and includes total healthcare costs. It included the cost for the medications as well as hospitalization, ER visits, outpatient visits. It is total inclusive of everything that is related to HAE. It is hard for us to right now tell you what is going to be the cost savings in the long term. We are in the process of putting together the budget impact model, and we will be able to publish that in the future as well. That is for your first question. For the second question, related.
Yes. We will have authorized treatments.
Yeah.
Maybe you could talk about the steps involved in bringing them online.
Yeah. The steps are, it depends. As we mentioned, we would have a flexible ATC network. That will be composed of community sites that are treating a large number of HAE patients. These are primarily private practices, as well as health systems and academic centers as well. The steps are different depending on the type of site. For the community sites, it is a more straightforward process. For health systems and academic centers, they have to go through their own P&T committees, they have to go through high-cost committees in order to get the drug in their formulary. Our teams have been working with them ahead of schedule to map all that out. In terms of infrastructure that they have to have in place in order to administer a product, they have to have an infusion facility, obviously, because this is an outpatient infusion.
They have to have freezers. We have been able to map out and identify all the organizations that have all the technical capabilities to infuse our product, as well as the access capabilities to be able to financially procure the product as well. All those activities are undergoing right now ahead of the launch. By the time that we get approval, hopefully we will have an ATC network that is ready to go.
Thanks, Maria.
Thank you.
Thanks for the question, Silvan. Our next question comes from Alec Stranahan at Bank of America. Please go ahead, Alec.
Hey, guys. Thanks for hosting this. It's been really informative. I guess maybe two questions just around LTP, like prior LTP use. I noticed in the 35 patients in HAELO that were on LTP before treatment, obviously the attack rate fell 81%, and I think 63% reached complete control. I guess which LTPs were they on, if they have that information? I guess did the results differ by drug? I am curious if you are seeing anything from the claims data, patients that maybe were not taking their LTP therapy consistently. Do you think that this is maybe an apt subgroup of patients to target for the launch? I guess how will you go about identifying them? Thanks.
Maybe I can just say a word about baseline LTP. It broadly reflected the market that is out there. Lanadelumab is about 40% or so of patients, and that is about what was there coming into the study. The efficacy of the drug did not vary across the LTP that a patient may have been starting with. I do not know if we are in a position to comment from our own data in terms of claims data, in terms of how patients have access to drug and when they miss prescriptions. I do not know, Dr. Riedl, or if you have some experience in terms of what you have observed with your own practice.
Yeah, as people know, we do have effective LTPs, and as you have seen, and is true for my practice too, the majority of patients are on long-term prophylaxis currently. But the challenges there are a few. I am not sure if this directly addresses your question, but treatment burden is a real thing.
We hear about this quite often. People are thankful for the medicines that they have, but taking either a daily oral medicine or periodic subcutaneous treatments, that does wear on people over months and years because of the lifelong therapy. So, adherence can be an issue. I will be honest, my experience is that most HAE patients are pretty adherent to their medicine because if they do not take it, they get sick. So, there is sort of a negative feedback loop there if you are non-adherent. I think that is not a huge issue in my experience.
Where we do run into significant problems is with payer authorization, and it is actually quite frequent that people's treatment is interrupted because of insurance problems, denials, and the authorization process. That is actually a very real issue that happens to, I think, most patients. As was alluded to in the presentation, it caused a lot of stress, which unfortunately then exacerbates their condition. The disruption or interruption of their LTP is also a very common issue, mostly related to insurance coverage. Thank you.
Thank you.
Thank you for the questions, Alec. All right, I think Maury was able to unmute. Maury, please go ahead.
Yeah. Thanks for taking the question. Sorry for the technical difficulties earlier. I wanted to just ask a question about what the efficacy that you are seeing and with the longer follow-up, and with the attacks basically going to zero, it is a key point of differentiation. How are you thinking about what FDA could ultimately allow in the label to capture both the attack-free efficacy and the ability to remain prophylaxis-free versus competing prophy therapies?
Maury, it's good to hear your voice finally. Good morning, and thanks for the question. I think it's a little early to speculate on exactly what the label's going to be, but I would say this. The way we designed the program and the way we ran the phase III program was to broadly address the patient population. You saw some of the data that was presented today in terms of the performance of the drug, when you look across a variety of different preexisting conditions, different drugs, different ages, different severity of disease, et cetera, et cetera. So, our hope is that the label will reach a very, very broad set of patients. Of course, this will be limited to patients with type 1 or type 2 disease.
Understood. Okay, thanks for taking my question.
Thanks, Maury. Our next question comes from Brian Cheng at J.P. Morgan. Please go ahead.
Hey, guys. Thanks for taking our questions today. Maybe just one on payer feedback. I'm curious if your team has initially started any conversation with payers, just based on the profile of lonvo-z today. Curious if you have any early feedback on how they think about the profile, and also any early discussion in terms of access as well. Thank you.
Maria, I know your team's been very actively working with payers, and maybe you can tell us, reiterate some of the learnings that you have and how that appears to be shaping up.
Yes. Our team has been in the field engaging with payers since early 2025. For us, it was really important to start payer engagement early because it's an opportunity to share even our early phase I and phase II data. From a payer perspective, as we mentioned in the presentation, durability is the core piece of the value proposition of this drug, and our phase I and phase II is what allows us to show the durability of the product. We started very, very early on, and we brought them along with the phase III, and now most recently also with up to four years of long-term follow-up for our phase I and phase II data. They are encouraged to see the durability. They see that as a core differentiation versus LTPs.
They also see the differentiation related to how this product is administered in the outpatient setting. This is significantly less costly than ex vivo therapies that they are very used to, bearing the cost for the drug as well as the cost for the administration. It's very encouraging to see all the feedback. Obviously, now as we approach approval and having pricing in hand, that's when the real conversations will start as it relates to the payer policies. But so far, very, very promising from our perspective. We see this as a really important piece of the treatment journey, making sure that patients have access. And we have hired very experienced people to be able to engage with those payers and people that have previous experience in cell and gene therapy. We're well underway.
Right. And you made reference in your presentation that this is largely a commercial market.
Yep.
Can you just remind us how many patient lives you think that we are already addressing with the payers that we are speaking with?
Yes. So, we are engaging with payers that are covering up to 280 million lives in the U.S., and 70% of the payer mix is commercial insurance. So, we see the benefits of that in the payer mix because commercial payers know one-time therapies. They have done this before. They also are faster in terms of setting policies. We are expecting to have most lives covered by month nine. It is a great advantage of the HAE space for a one-time therapy.
Thank you, Maria.
Thanks for doing this call. Thank you.
Thanks, Brian. Our next question comes from Jeff Stith at Wells Fargo. Please go ahead, Jeff.
Hey, this is Jeff on for Yan, and thanks for hosting this event and for taking our questions. First, for the physicians, just digging a little deeper into the demand for lonvo-z. At the time of approval, what proportion of your patients currently on long-term prophylaxis versus on-demand do you think would be willing to pursue treatment initially, like ready and willing to go? Then for the company, in the phase III HAELO study, there were four patients who received lonvo-z, including crossover patients, or about 6%, that received less than the intended dose for various reasons, like infusion-related reactions. If this were to occur commercially, how do you envision managing those patients, including potential redosing and any reimbursement implications? Thanks.
Maybe we could start with Dr. Riedl. I mean, there is the market out there. There is your practice. It is hard to speak for everybody else up there, but maybe you can just say a word about how you are thinking about it.
Yeah. I will be honest, I do not like to answer this question because I do not know. That is the honest answer. I do not know what percentage of patients will be ready to do this out of the gate. They are out there. We have had these conversations, and I do have patients who say, "Let me know when this is available because I want to pursue it." I think, as I mentioned before, many of our patients are interested in this and are asking about it. My honest opinion is I think it will take a little bit of time for uptake.
I think people need to learn about this. I think the educational component that was mentioned earlier is going to be really important because I think while patients sort of hear on the news this or that about gene editing, I am not sure they fully understand that. I think that, in my opinion, it's really important that patients understand what we know and what we don't know about this right now. We're going to have those conversations. I think that'll be very exciting. But in terms of giving you a number of who's going to get this in the next year after approval, if it's approved, I just don't have a good handle on that, so I won't guess.
Yeah, and with respect to the second question, the vast majority of patients got the full infusion within the allotted time. We'll have procedures in place for that small set of patients who may have an interruption or whatever. We will make sure that patients get the full dose that will give them the benefit that they're looking for.
Okay. Thanks. Appreciate it.
Thanks, Jeff. Our next question comes from John Boyle at William Blair. Please go ahead, John.
Hi, team. This is John Boyle on for Myles Minter. Thanks so much for taking our question. Maybe one for both the physicians and for the broader team. Wondering if you envision that you or other physicians may recommend patients try Dawnzera before switching to lonvo-z to test out a silencing mechanism before a permanent edit. Then as a follow-up from the payer perspective, do you see any potential for a step edit specific to a silencer therapy, or do you anticipate that step edits will just be for any LTP therapy more generally?
Maybe, Maria, we can start with you. We talked a little about step edits and the role that they will play for many patients who have already met that, but maybe you could just
Yeah
focus in on that a little bit.
Step edits are a very common payer management tool that we have seen being used across all approved therapies. In the HAE space, as we talked about, HAE patients and physicians are very used to navigating all of those access requirements. So, we do not expect this to be specific for our therapy. In fact, there are many payer policies that require step edits for new products that were recently approved as well.
Maybe Dr. Cohn.
Yeah.
Do you have a treatment strategy in mind to get to the drug?
Well, in general, I don't think that it will be necessary to dose someone with any other drug before considering this drug. However, I would like to mention one thing in particular, that some patients report symptoms of whom we do not necessarily know that they are all really hereditary angioedema attacks. It might be helpful to have patients on another LTP to assess whether or not they respond and not use this treatment as a trial to see if their symptoms will improve or not. But in general, I would consider this as just one of the other options of long-term prophylactic treatment in HAE patients.
Do you have any other thoughts to add to that, Marc?
No, I agree with that. I think that we generally have not had sort of staged treatment, so to speak. I think the efficacy data from the clinical trials for lonvo-z sort of speaks for itself. It seems to work across all of the patients, or at least the vast majority of patients, regardless of prior treatment. I wouldn't envision prescribing drug X before we move to this.
Thank you.
Thanks, John. Our next question comes from Binita Shah at RBC. Please go ahead.
Oh, hi. This is Binita on for Luca. Thanks for taking my question, and thank you for putting this webinar together. Just one from me, following up with Dawnzera. Recent HAE launches show patients will switch for differentiated options, but conversion takes time. What's your read-through for lonvo-z? Does a one-time therapy accelerate that switching dynamic, or should we expect a similar multi-quarter ramp once approved? Thank you.
Maria, do you want to say a word of what's relevant out there to what we're doing, if anything?
This is a very unique therapy, right? Lonvo-z will be the very first one-time therapy approved in HAE and the very first one-time therapy that is an in vivo CRISPR therapy. We are very careful about taking another product's uptake and applying to our own, and we believe that the better approach is really looking into the patient's and the physician's willingness to use the product, as well as how access is evolving over time as a way to see the leading indicators on how the product is going to evolve. But as we said, we expect the first six months to be focused on getting access, putting policies in place, and getting ATCs ready to administer the product. We expect the volume to grow over time, and especially starting after six months of launch.
Right. And we will not be in a position where we can take preexisting patients from clinical trials on an open-label extension and move them over.
Yeah.
We will be starting from.
Zero
basically.
Exactly.
Right. Thank you.
Thank you.
Thanks for the questions, Binita. Our next question comes from Andy Chen at Wolfe. Please go ahead, Andy.
Hey, thank you for taking the question, and thank you for the informative presentation. One question for the physicians. Among patients already on therapy, do you only discuss new options and offer new options to patients who are dissatisfied, or would lonvo-z be visible and offered to new patients, or to all patients? Perhaps as a comparator, if you can discuss how garadacimab and donidalorsen have been offered since approval. Were they offered to all new patients or just dissatisfied patients?
Dr. Riedl, how do you talk about new therapies as they become available, if at all, I guess was the question.
Yeah, when new therapies come online, I discuss them with everybody. At a follow-up visit, of course, we go over how patients are doing, what's their current treatment, symptoms, tolerability, overall quality of life. Then we move to, okay, what's new? Even, to be honest, what other options have been around, right? If there is any indication that they're interested in switching, we would kind of revisit all of the options. The short answer to your question, we discuss all treatment options with each and every patient. Of course, if they're very satisfied with what they're doing, that conversation can be pretty short, but it can end up being pretty lengthy if they have an interest in doing something differently. Yeah, apply that conversation to any and all patients that we see for follow-up. Dr. Cohn, anything to add?
Yeah, I agree. This is part of the shared decision-making, and of course, it depends. Some patients have consultations every three months, and other patients we see just annually. But we will definitely discuss all the various options at every visit when we also evaluate disease control and quality of life.
Thank you.
Thanks, Andy. Our next question comes from Jasmine Fels at Barclays. Please go ahead, Jasmine.
Hi, this is Jasmine on for Ellie Merle from Barclays. Thank you so much for hosting this event. I just wanted to ask some follow-ups about the commercial dynamics. You presented a little bit of data on the interest from the patient survey, but practically, do you see a greater proportion of switches to lonvo-z coming from any specific therapies more so than others? Essentially, I'm asking, are there pools of patients based on the demographics of who's on each available therapy that are more likely to switch to lonvo-z? Then a more general one, we know that some HAE patients can feel pretty loyal to treatments that they've been on and have been working adequately from them, even if they're not ideal.
What are your strategies to unlock this more inert patient population and convince patients who have been on their therapy for a long time to consider lonvo-z?
Maria, do we have insight from our market research in terms of how patients may react to any one drug that they're currently taking?
No. We have seen interest across the board, as we showed during the presentation. It was a pretty vast majority of the patients regardless of the LTP product that they are currently in. That was pretty uniform.
Yeah. I think the second question spoke to what was called loyalty to a drug.
Yep.
Meaning, how do you see things evolving from our side? Then maybe we can ask the physicians again in terms of what they see with their practices.
Yeah. One thing that was very interesting from our patient survey, we were expecting that the patients who were not well-controlled will be the first ones to say yes to this therapy. We actually saw a significant proportion was actually the highest group that is considered well-controlled being interested in lonvo-z. This is a very interesting fact. Our hypothesis behind that is because the product is very unique and these patients are probably the ones that are on top of their disease the most, and that is the reason probably they are well-controlled. They are always in pursuit of the best therapy and the next therapy that is available. Lonvo-z really appeals to them because of the high efficacy, obviously, comes first, and then also the one-time nature and the opportunity to get rid of the chronic burden of the disease.
I think that's one of the most important features. In terms of how do we unlock some of those patients that might be standing in the sidelines in the wait and see, as Dr. Riedl said before, some of these patients will require to hear from other patients on how they are doing. We know this is really important in the HAE community. It's a pretty tight community. Patients talk to one another, and they wanted to see sometimes others to go first and have a positive experience. This is also most of the patients have family history of HAE, so having some of the other family members going first and having a positive experience can also unlock other members of the family over time as well. We think adoption of lonvo-z is a matter of time. It's not a matter of if the patients will adopt.
As you can see from our survey, the interest was very, very broad.
Maybe Dr. Cohn, since you've been involved with the program for several years now, you've seen an evolution in terms of how patients think about it, and does that relate to the therapy that they're on in any way?
Yeah, absolutely. I think there was a lot of interest also in the media, on the national news even, after the phase I trial results that they released. This interest was also taken up by the patients' organization. Indeed, patients are all in touch with each other, also on social media, and discussing, and well, that's part of their enthusiasm. I agree that it might take time for some loyal patients to roll over to other treatments, not necessarily only patients who are well-controlled, but also the not-so-well-controlled patients. In the most extreme form, even patients who are still using androgens, despite the healthcare risks associated with this treatment. But then we have learned that you need to re-counsel those patients during follow-up visits, and then ultimately, they will definitely consider maybe more suitable treatments for them.
Dr. Riedl, we talked earlier about how things may evolve and that there are different patients who have different needs, et cetera. Anything to add to what we heard here?
Yeah, two quick points, because I think it is a really interesting question. One is, I just want to be clear that there are patients that are doing very well on their current HAE treatment. I just want to be clear about that. We have come a long way in the past 10 or 15 years, and so some of that loyalty is because patients are doing well. They are very happy with their current therapy. That being said, my second point is that it has been very interesting in the last year or two, as we have had a couple of new LTPs come to market, that patients who previously told me they were doing, quote, "fine," would come in and say, "You know what? I have had this issue.
We never really talked about it because I did not think there was a better option out there." It has been a little eye-opening for me to see that people are certainly willing to change their treatment approach if there is a better option that is significantly different from, has some differentiating factors. I think because lonvo-z is so unique, for all the reasons we have talked about, it will be very interesting to see how that goes, because it has been my experience that even patients who tell me they are doing fine, that either the burden of treatment or tolerability or efficacy, there is something that they view could be improved on if there is a differentiating therapy out there. We will see.
Again, I do not like to try to predict the future, but I think this is such a unique therapeutic approach that we may be having many more of those conversations in the coming year, if approved.
Maybe Dr. Cohn, you could build on that, because it is an interesting point, and it is something you commented on in the presentation here, how in the information that is going to be presented, patients evolved in terms of how they thought they were doing, pre and post. Maybe you could just remind us a little bit about that.
Yeah, that is absolutely right. Where first patients just mentioned to have the least number of angioedema attacks per month was the only goal or perspective. They now really think that they have achieved the normal life without thinking of their HAE whatsoever. So, even no longer treatment reminders, because it is a one-time treatment. They really stopped forgetting that they have hereditary angioedema, which is completely distinct from the previous observation.
Wow. Yeah, that is incredibly helpful. Thank you so much.
Thanks, Jasmine. Our next question comes from Lydia Erdman at Goldman Sachs. Please go ahead, Lydia.
Hi, this is Lydia on for Salveen Richter. Thanks so much for the presentation and for taking our questions. Could you maybe just speak to the anticipated shape of the launch curve post that 12-month inflection that you outlined in the presentation, and the key hurdles to reaching that inflection? Thanks so much.
Yeah. We're not going to be in a position to give you a shape of the curve. What Maria walked through, and I would encourage you to look at the slides again, is we expect a series of phases as the drug gets approved, authorized treatment centers get online, payment policies are put in place, and then patients begin to be treated. We tried to describe that in terms of numbers and rate and all that. We'll see as that plays out. We fully expect by 12 months, we'll be exactly in the place that we hope to be, and as the launch unfolds, we'll be updating.
Great. Thanks for the questions, Lydia. Our next question comes from Debanjana Chatterjee at Jones Trading. Please go ahead, Debanjana.
Hi. Thanks for taking my question. In the presentation, you shared that the vast majority of HCPs would like to prescribe lanadelumab to at least one patient, with a majority of prescribers prescribing it to more than 50% of patients. Just looking at the other half, for the somewhat late adopters, what do you think is holding them back? Are they just waiting to see real-world safety data or longer durability of efficacy? Basically, what would bring them into the fold as well?
Maybe we will just turn to the doctors again. We talked a little bit about this, but there is a gradient. Maybe you can tell us how you see that unfolding over time.
Yeah. The question was about the physicians, right? The prescribers, yeah. It is not dissimilar from what we discussed about the patients. I think there is an educational process. I think part of this is our colleagues becoming comfortable with the data, and that is why it is so important you saw the number of presentations that are going to be presented here at the college meeting in the next couple of days. I think more data will make our colleagues more comfortable with this approach. I think the other piece is just the logistical piece that you have heard a lot about, and I am not the expert at that, but how is this done? How is the infusion given? What are any risks involved with that?
This is such a sort of innovative therapy, certainly in our field, but in all of medicine, that I think there will be education and data that needs to continue to be put in front of our colleagues who see HAE patients. Certainly, I think all of that is doable. Anything new, most physicians are going to embrace that to stay on top of the latest technology. But it will take a little bit of time, and I think I am sitting across from Danny here, who has some of the most experience in the world with this treatment, and interested in his thoughts. But I think amongst my colleagues, it is just a matter of seeing the data, digesting it, and then being able to discuss that with their patients.
Thank you.
I think
Sorry.
I think Dr. Danny Cohn has some thoughts to add. Go for it.
Yeah, I agree. From this logistical part, I think the actual treatment is really straightforward. It is just a two-four-hour, one-time infusion. If there are physicians that might be reluctant about all the logistics, then it is very easy to refer a patient to one of those centers that has more experience with the treatments, with the IV treatments. Yeah.
It's an important point, and Maria's team is building that network so that some sites have many, many patients, and some physicians have many fewer. We're trying to give them access to whatever they need to feel comfortable with the drug.
Yeah.
We can go to the next question.
Great. Thanks for the question, Debanjana. Our final question comes from Jade Montgomery at H.C. Wainwright. Please go ahead.
Hi. Thanks. This is Jade on for Mitchell Kapoor. Obviously, you've already put a lot of work into this launch. Just kind of following on from a lot of what people have been asking. At this point, though, what's really the major hurdle that you feel will be faced in getting lanadelumab into patients? Is it the payer, physician, or patient, and where exactly would that be? Then, just for the physicians, what would your long-term management plan for a patient after treatment with lanadelumab be? Could you walk us through that?
Maybe let's start with that. After a patient's been treated, Dr. Danny Cohn, you've had the most experience, so what do you do?
The patients that have been treated all entered the long-term follow-up study, which will last for 15 years. So these patients will be followed up for 15 years. But in general, if patients are very well controlled, then we have an annual checkup where we discuss quality of life, disease control, et cetera. I imagine that also patients that have been treated might just have a single telephone conversation once a year to check in.
Dr. Riedl, my guess is the guidelines at some point will be very important for this kind of work. How do you see that evolving?
Yeah, I think the main thing that I think is still important, and I will discuss with our patients, we discuss with every patient, is I will still want to ensure they have rescue treatments available. While we have seen, you saw the data, we have seen the attacks going to zero for a lot of the patients, I think we still have to be safe here. If there are breakthrough attacks, we want patients to be able to manage that. One would anticipate that the need for rescue medicine goes towards zero, but I think that's where the longer-term data is needed. How many of these patients absolutely become attack-free, and if so, for how long? I think that's the main thing, that it appears that the study patients have not needed any additional long-term prophylactic therapy.
It is the follow-up, as Danny mentioned, and then just making sure they still have a rescue treatment plan, the very tiny chance that they have symptoms.
Finally, Maria, I mean, I am glad the work and the effort that you and your team have been putting into this for the last two years is apparent. But as we draw close to the launch, any one thing that you think that deserves special attention or that is the most difficult thing to achieve?
Yeah. As you said, our team has been working on this for a long time, and we have learned a ton from the prior one-time therapy launches. It is really about making sure that we have access, making sure that we have reimbursement, making sure that the sites are ready. I think we are well underway across the board in all of our efforts to make sure that we have a launch that is as seamless as possible for the physicians and the patients. The patient experience is so critical. It is a one-time experience, and we wanted it to make sure that it is the best experience of their life, because this community is so tight and talk to one another very often. So that is our commitment, and we know that it is not going to be all perfect, right?
This is the first time we are launching a product as an organization, and we are taking that very, very seriously. But we will be adjusting as we go to best serve patients as best as possible.
Thank you.
Thank you so much.
Thanks for the questions, Jade. This concludes our Q&A session for today. I will now turn the call back over to Jason for closing remarks.
Thanks, operator, and thanks, everyone, for joining us. We are going to look forward to seeing many of you in London next week at the Jefferies Conference. That concludes today's meeting.