X4 Pharmaceuticals, Inc. Aktie

Good morning, and thank you for joining X4 Pharmaceuticals Investor Day. As a reminder, this event is being recorded.

Before we begin, I would like to remind you that during today's call, we will be making certain forward-looking statements. Various remarks that we make during this call about the company's future expectations, plans and prospects constitute forward-looking statements. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors. Please refer to the risk factors described in our most recent annual report on Form 10-K, quarterly report on Form 10-Q and other SEC filings, which are available on our website as well as the cautionary statements on Slide 2 of today's presentation. In addition, any forward-looking statements represent our views as of today, and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements in the future, we specifically disclaim any obligation to do so even if our views change.

Today's event is accompanied by a slide presentation, which is available in the Events section of X4 Pharmaceuticals' Investor Relations website at x4pharma.com. A replay will be available on the website later today. [Operator Instructions]

Leading our discussion today is Dr. Adam Craig, Executive Chair of X4. Previously, he was CEO of CTI BioPharma, where he oversaw the approval and launch of the company's first product and guided its $1.7 billion acquisition by Sobi. Dr. Craig is a physician specializing in pediatrics and pediatric oncology, and holds a PhD in molecular oncology.

I would now like to turn the call over to Dr. Craig.

Thank you, Remy, and thank you all for joining us this morning. We have a great lineup of speakers today and appreciate the key opinion leaders joining us to share the expertise on the treatment of chronic -- primary chronic neutropenia.

With me today is John Volpone, our President and Chief Operating Officer. John brings more than 2 decades of drug development leadership across oncology and rare disease. Most recently, he was the Executive Vice President and Chief of Staff at CTI BioPharma. And before that, he held business development roles at Bristol Myers Squibb and ZymoGenetics. We also have David Kirske, our Chief Financial Officer, with us today. David has 20 years of strategic financial and operational experience, most recently as CFO of Stratus Therapeutics. Prior to that, David was Executive Vice President and CFO of CTI BioPharma, where he played a central role in the Sobi acquisition.

I'm pleased to introduce Michael Massello, our Senior Vice President of Market Strategy and Development. Michael has nearly 30 years of commercial medical experience in biopharma and has led more than 12 commercial launches in hematology, oncology and rare disease companies, including CTI BioPharma, Amgen, Onyx, Lilly and Seattle Genetics. Most recently, Michael was Global Head of Commercial Strategy and Vice President Markets at Autolus where he helped lead the launch of the company's first cell therapy.

Also honored today to have Dr. Julia Warren, a pediatric hematologist and physician-scientist at CHOP Hospital of Philadelphia with us, and she is an Assistant Professor of Pediatrics at the Perelman School of Medicine. Dr. Warren sees patients in CHOP's Comprehensive Bone Marrow Failure Center and Cancer Predisposition Clinic programs, with a specialized interest in patients with chronic neutropenia. Finally, we welcome Dr. Shreyans Gandhi, a Consultant Hematologist at King's College London. Dr. Gandhi is focused in the field of myeloid disorders -- his practice is focused in the field of myeloid disorders with a primary interest in bone marrow failure, cytopenic disorders and PNH, including cellular therapies and stem cell transplantation.

Please note, Dr. Warren and Dr. Gandhi are Consultants to X4 and the views they express today are their own. For reference, you can access speaker biographies on the right side of the screen or via the button in the top right corner.

So first of all, I'll go through the agenda today. Once I finish with the opening remarks, John Volpone will present the mavorixafor clinical program to update you on the 4WARD trial and introduce to you for the first time the 4STEPS trial of dose adjustments to G-CSF in the presence of mavorixafor. We will then move on to the market opportunity in primary chronic neutropenia, presented by Michael Massello, who will present to you today our market research that has established the market opportunity for mavorixafor in chronic neutropenia. Following Michael's presentation, we'll move on to a fireside chat, which I'll host with Dr. Gandhi and Dr. Warren. And then we will move on to a Q&A session where you can ask questions.

The aim of the company is to deliver on the promise of CXCR4 antagonism through mavorixafor. To do that, the company has had to go through quite substantial corporate transformation, as many of you know, in '25 and '26, 2025 and 2026, but we're now focused on -- able to focus on the completion of the pivotal Phase III 4WARD trial in primary chronic neutropenia. We aim to complete full enrollment by the end of Q4 2026 and expect top line on the primary data in Q1 2028.

If successful, that could lead to a U.S. FDA approval in late '28 and '29. This year, we've also been working on the Phase II trial, the 4STEPS program that I mentioned earlier. And that's a trial to demonstrate if we can safely reduce G-CSF dose in patients with chronic neutropenia following the initiation of mavorixafor. Next slide, please.

So mavorixafor is an oral agent designed to alleviate neutropenia. Its target is CXCR4, which is a -- which regulates the movement of white blood cells throughout the body. If CXCR4 is antagonized with an agent such as mavorixafor, it results in white blood cell migration from the bone marrow into the circulation. And as a result of that, the mavorixafor increases the levels of neutrophils and lymphocytes in the bloodstream. It's this effect that we believe will have an impact on infections in patients with chronic neutropenia. And it's that -- this is what we are testing in the Phase III 4WARD trial. Next slide.

I'd like to introduce John Volpone, who is going to present the clinical program.

Thank you, Adam. I'll begin with an overview of our pivotal Phase III 4WARD trial in primary chronic neutropenia or PCN, and then introduce 4STEPS, our Phase II study designed to evaluate whether G-CSF dosage could be safely reduced in patients who have started treatment with mavorixafor. 4WARD is a global double-blind, placebo-controlled trial with a target enrollment of 126 patients. We designed the inclusion criteria to enroll patients in whom a potential treatment benefit can be clearly measured. Participants must have a diagnosis of congenital, autoimmune or idiopathic chronic neutropenia and an absolute neutrophil count, or ANC, below 1,000 cells per microliter. This is defined as moderate or severe disease.

Participants must also have at least 2 infections requiring intervention in the previous 12 months. These are patients with serious recurrent infections who need better therapies to manage their disease. Patients are randomized 1:1 to receive mavorixafor or placebo in each case with or without G-CSF. ANC is assessed at baseline and at months 1, 2, 3, 6, 9 and 12. The trial has 2 primary endpoints: ANC response defined as an ANC above 500 cells per microliter and annualized infection rate.

With 126 patients, the study is powered at 93% and 89%, respectively, for these endpoints in the intent-to-treat population. Secondary endpoints include severity of disease of infections, antibiotic use, fatigue, quality of life and safety. We expect to complete enrollment in the fourth quarter of this year with top line data expected by the end of the first quarter of 2028.

Now I'd like to share the baseline patient characteristics for 4WARD based on blinded pooled data as of September 2026. Enrollment is evenly divided between moderate and severe disease with median age of participants in the trial of 36 years old and 70% of participants are female. Median baseline ANC is 483 cells per microliter, well below the trial's entry criteria of 1,000. 68% of participants have 3 or more infections at baseline. 4WARD requires at least 2 infections in the prior 12 months for entry, so this is a population with a meaningful burden of infection. 37% of participants are on concurrent G-CSF. As a reminder, we are evaluating mavorixafor as both a monotherapy and in combination with G-CSF. Importantly, we have not seen any new safety signals to date. Taken together, these baseline characteristics give us confidence that we are enrolling the right patients in 4WARD and the patients we believe scan to benefit the most from an oral treatment option.

Today, I would like to introduce our planned 4STEPS clinical trial that is designed to complement 4WARD. In 4WARD patients who entered the study on G-CSF keep the same G-CSF dose for the entire study. So any clinical benefit of mavorixafor can be clearly measured. However, with real-world usage, we expect that patients and physicians will want to reduce the use of G-CSF once mavorixafor started, citing the burden of frequent injections and side effects such as bone pain and fatigue. 4STEPS is designed to evaluate whether G-CSF dosage can be safely reduced while maintaining stable neutrophil counts after mavorixafor has been started. 4STEPS is a single-arm, open-label multicenter Phase II study. We plan to enroll approximately 25 patients with acquired primary autoimmune or idiopathic chronic neutropenia.

Patients must be on stable G-CSF therapy at study entry and have a baseline ANC of at least 1,000 cells per microliter, which makes this a different population from 4WARD. The study will be conducted at approximately 25 sites in the U.S. and the U.K. The primary safety endpoint is the safety and tolerability of mavorixafor. There are 3 primary efficacy endpoints, each measured at 6 months, the percentage of patients who stopped G-CSF entirely, the percent reduction in average daily G-CSF dosage and the percentage who reduced their G-CSF dosage by 75% or more.

Here's how the study is designed. Patients start with a 4-week observation period on G-CSF alone. Mavorixafor is then added for an 8-week run-in, which gives it time to reach the full effect. Next comes a stepwise G-CSF reduction period of 16 to 20 weeks. Patients can step down to reductions of 25%, 50% and 75% and finally stop G-CSF altogether. At each reduction visit, the physician follows the simple ANC-based rules shown on the table at the bottom of the slide. If a participant's ANC is at least 1,000 cells per microliter, the G-CSF dose is reduced. Between 750 and 1,000, it stays the same, between 500 and 750, the physician considers an increase and below 500, the dose is increased.

The primary analyses, including the percentage of patients who have stopped G-CSF takes place at approximately 6 months. A 24-week maintenance period then follows to determine the durability of response. The next 18 months are full of important milestones for X4. We expect to complete enrollment of 126 patients in 4WARD in the fourth quarter of this year. We then expect to enroll the first patients in 4STEPS in the first quarter of 2027. Top line data from both 4WARD and 4STEPS are expected in the first quarter of 2028. If positive, the 4WARD results could support a potential FDA approval of mavorixafor in primary chronic neutropenia in late 2028 or early 2029.

With that, I'll turn it over to Michael Massello, our Senior Vice President of Market Strategy and Development, to discuss our work on establishing the commercial opportunity of mavorixafor. Michael?

Thank you, John, and good morning, everyone. I'm excited to talk to you today about what is happening at X4 with regards to the commercial opportunity with mavorixafor in primary chronic neutropenia. To begin, I want to address the impact of this disease on patients and physicians and the limited treatment options available in PCN. PCN is a rare chronic blood disorder defined by neutrophil counts below 1,500 cells per microliter for more than 3 months. PCN varies from patient to patient and is a heterogeneous disease that occurs in 4 forms: idiopathic, congenital, cyclic and autoimmune. PCN is a large underserved market, and this disease is often underdiagnosed and misdiagnosed. This disease affects every aspect of a patient's life. This is a deeply personal and deeply psychological disease, where patients are immunocompromised and are constantly worried about getting severe infections.

Current treatment options for PCN are extremely limited with patients basically left with a mix of options that are often off-label, unproven or difficult to use. Therefore, PCN remains a very high unmet medical need. Our goal is to reshape and rethink the way PCN is treated today as it has been 30 years since a new treatment has been approved. Importantly, there is no current FDA-approved oral agent for PCN, and we're looking to change this with mavorixafor here at X4.

We have conducted extensive amounts of market research for the past few months covering both the current market dynamics that exist today as well as physician and patient reaction to the clinical research on mavorixafor. I have to tell you, the more research we do, the more excited we become. To allow us to size the PCN market opportunity, we have established rigorous market research. To this end, we have undertaken a two-pronged approach, deep claims analysis and direct physician and patient research. On the claims side, we started with a Veeva claims analysis covering 2023 to 2025 to identify the symptomatic PCN population. We then confirmed that figure with a second independent source, the Komodo claims analysis over the same period.

We then went a step further looking at these claims longitudinally to map the patient journey. That includes how patients are newly diagnosed and what drives diagnosis, the referral dynamics to specialists, what triggers treatment and who makes those decisions. And lastly, how G-CSF and antibiotics are used.

In parallel, we went directly to our potential customers, including hosting advisory boards with both physicians and patient groups. In addition, we conducted a qualitative demand study of 100 physicians looking at unmet medical needs and sources of business. We complemented that with qualitative disease state messaging with 50 physicians and qualitative patient journey research with 30 physicians. We also heard directly from patients through the CONNECT PCN burden of illness and burden of treatment survey with 110 patients who are all treated with PCN and about 90% of whom were on G-CSF. This provided us with their perspective on how PCN affects quality of life and where their social and medical needs remain unmet.

Taken together, these insights have clearly established our view of the U.S. PCN market opportunity for mavorixafor. Just as importantly, they have confirmed our belief that mavorixafor is well aligned to address the unmet medical needs for PCN patients. PCN drives substantial health care utilization and cost. Recurrent and serious infections can lead to complications such as pneumonia, bronchiectasis and sepsis. These often result in emergency room visits and hospitalizations. As you can see on the right, infections can affect nearly every part of the body from the mouth, throat, ears and sinuses to the lungs, skin, gut and bloodstream.

Our recent Komodo claims analysis found that approximately 1 in 4 or 6,300 U.S. patients with PCN were hospitalized due to infections in 2025 with a mean stay of 4 days per infection. These hospitalization stays are not only expensive, they stress the health care system. This truly exemplifies the importance of treating this disease effectively and in a timely manner. The overall burden of this disease is immense. Existing therapies have real limitations, which leaves a high degree of unmet medical need and a great deal of dissatisfaction amongst both patients and physicians.

In 2026, we conducted a burden of illness survey with 110 patients with PCN exploring the impact of this disease, the challenges with treating it and what they look for in a new therapy. From this, 4 themes emerged. First, PCN has a profound emotional impact. Fear of the next infection drives social withdrawal and feelings of isolation. Second, patients have a high motivation to manage their disease despite the heavy burden. Patients are determined to control their disease even with the frequent challenges of injections and antibiotics. Third, the unmet medical need. Serious infections and hospitalizations remain common despite available therapies. And fourth, a strong desire for an oral option to fit their lifestyle that is simple, safe and effective and offers sustained disease control.

As I mentioned earlier, PCN affects every aspect of a patient's life. Patients living with this disease restrict everyday life just in order to cope. In our research, we found that 9 out of 10, or 88%, avoided crowded places such as restaurants and large events at least some of the time. 81% felt especially alert or on guard around others. 78% avoided public transportation, 74% avoided social gatherings and 69% avoided traveling or taking vacations. Many of these patients suffer in silence. They feel isolated and they want to give up the very activities that make up normal life that many of us probably take for granted.

Adults with PCN report a significant impact on work. Among surveyed adults, 64% missed work with a mean of 9.6 days missed over the past year. 54% reduced their work hours and 20% missed a promotion or chose not to pursue a new role. This matters.

Caregivers report a profound emotional toll on adolescents and children. Parents describe the tremendous burden of managing this disease in their children. The physicians who treat the young patients also tell us the psychological impact is often underappreciated. According to caregivers, 60% of adolescents missed school days, 53% reduced their participation in after-school activities and 60% avoided interacting with others. Just stop for a moment and think about the impact on children with this disease and how these numbers translate into real life for parents and their kids. And you'll hear more later from our key opinion leaders, Dr. Warren and Dr. Gandhi about the impact of this disease on adults and adolescents.

Despite this burden, there has been little or no innovation in this space and no new class of therapy being approved in more than 30 years. Two main treatment options exist today. G-CSF injections, first approved in 1994, remain the only treatment that raises neutrophil counts and antibiotics are often used to treat or prevent bacterial infections, but do not address the underlying neutropenia and they're not specifically indicated for PCN. And our claims analysis shows that roughly 1/3 of symptomatic patients are treated with G-CSF and roughly 1/2 are treated with antibiotics and some patients receive both.

Many other patients are managed with a watch-and-wait approach often because they are reluctant to take the burden of daily injections. Patients are actively looking for a new treatment option because of the limitations of what is available today. G-CSF comes with inherent limitations and the injections carry a significant burden. These injections are frequent, recurrent and painful and 63% of G-CSF patients in our survey told us that they have injection fatigue and adolescents are just needle phobic. There are often gaps in protection because neutrophil counts rise and fall between doses and are very inconsistent.

Importantly, there are also long-term safety consequences. In congenital neutropenia, the Severe Chronic Neutropenia International Registry data, or SCNIR, shows that for patients on the long term, high-dose G-CSF have a cumulative risk of acquiring myelodysplastic syndromes or acute myeloid leukemia of approximately 21% at 10 years.

And finally, there's a huge negative quality of life impact. 57% on G-CSF report bone pain and 61% report fatigue. Bone pain can manifest in as little as 1 week. Together, these side effects and long-term safety concerns may be why only 1/3 of patients are on G-CSF because it's so challenging for patients to take injections literally every day for the rest of their life.

Antibiotics can treat infections, but they do not address the underlying neutropenia. They are usually prescribed based on a suspected pathogen and often rotated through to help prevent resistance, but they do nothing to raise neutrophil counts. In our research, about half of the PCN patients are prescribed antibiotics either prophylactically or chronically. Cumulative exposure brings its own side effects and drug interactions. Most importantly, long-term use can drive antibiotic resistance and gut microbiome disruption. Physicians tell us this is a key reason they are reluctant to rely on repeated or chronic antibiotic use. As you can see, there is a well-defined market today that is riddled with 2 main therapeutic options that don't offer the true protection patients need and want.

In our market research, we've also mapped the patient journey, which has 3 main steps depicted on the left side of the slide. First, patients usually see a primary care physician, then the diagnosis is confirmed by a hematologist/oncologist, or hem/onc for short. Treatments are then administered with G-CSF predominantly prescribed by hem/oncs, while antibiotics are managed by both primary care physicians and hem/oncs.

Here's an example. A primary care physician sees a patient and they find that they have an ANC below 1,000. The physician may monitor the patient for a month or 2 and then retest. If the counts remain low, the physician may prescribe antibiotics and refer the patient to a community or academic hematologist. The specialist then rules out other causes with bone marrow aspirate and confirms the PCN diagnosis.

As the middle chart shows, about 87% of patients on G-CSF received their prescriptions from hematologists. About 80% of G-CSF is given in prefilled syringes and 20% by vial, both require injections. On the top right side of the slide, it shows only 27% of antibiotics are prescribed by hem/oncs. Strikingly 100% of patients requiring hospitalization or ER visits received antibiotics. And among these patients, about 72% required IV or injectable administration.

Hematologists and patients agree on what they want from a new treatment. Hematologists told us they want fewer and less severe infections and hospitalizations, the ability to raise and stabilize neutrophil counts and a therapy that is safe and well tolerated. Patients want the same things. They want to stay injection-free and out of the hospital. They want relief from fatigue, pain and the constant vigilance, and they want a treatment that fits into their daily life over the long term.

I'd like to share a few quotes with you from recent market research we conducted that paints a picture of how individuals feel about treating or living with this disease. One hematologist told us, "We are so frustrated for patients who have no other treatments than just a few modalities. We're ready to embrace anything new to treat this disease." Another simply put it, "An oral would be a game changer in PCN." We also heard this profound quote from a patient, "I'm scared to go out of my house, I'm scared to go on vacations. I won't leave the house without 3 antibiotics. I want control of my life back, and I want to focus on the moments that matter." So these quotes really speak to the frustration on the physician side and how desperate and scared patients feel when living with PCN.

I've been in this industry a long time, and I can tell you this disease is ready to be disrupted. We believe mavorixafor is a highly differentiated investigational therapy and to our knowledge, is the first and only therapy in development for PCN that can potentially treat the underlying biology of the disease. It is a once-daily oral therapy. It has a novel mechanism of action as a CXCR4 antagonist that mobilizes neutrophils into the circulation. This is vastly different from how G-CSFs work.

Mavorixafor is being evaluated both as monotherapy and in combination with G-CSF in our Phase III 4WARD trial and will be evaluated as a G-CSF sparing agent in our planned Phase II 4STEPS trial that you just heard from John, giving physicians the potential flexibility to use it alone or alongside existing therapy with the potential of coming off G-CSF.

In our research, physicians and patients describe mavorixafor as being a highly differentiated product with quantifiable and tangible differences over what's readily available today. For hematologists, the #1 differentiator was an oral route of administration. As we heard earlier, an oral therapy would be a game changer. The #2 differentiator was the potential for greater infection control as physicians believe mavorixafor may be able to reduce both the number and severity of infections. In our quantitative survey of 100 hematologists after reviewing a target product profile that assumed FDA approval, approximately 90% said they intend to prescribe mavorixafor and 87% rated it favorably, scoring it above 5 on a 7-point scale.

Now let me go deeper on prevalence. We recently confirmed our estimates with longitudinal analysis of Komodo claims data, which is widely regarded as one of the most complete sources of U.S. claims data. Komodo sources data directly from more than 500 payer organizations and covers pharmacy and medical claims, including Medicaid and Medicare. At the base of the pyramid, we identified approximately 95,000 patients aged 12 and older with confirmed primary chronic neutropenia diagnosis code who were active in 2025. This group includes both symptomatic and asymptomatic patients with ANC less than 1,500.

Moving up one step, approximately 30,000 of these patients had one or more infections in 2025 that were symptomatic with ANC less than 1,000. At the top of the pyramid, approximately 15,000 patients who had 2 or more infections, including ER visits and hospitalizations. These patients were also symptomatic with ANC less than 1,000.

Taking a closer look at our base case, we have high conviction in this core segment of approximately 15,000 patients who closely mirror those we are enrolling on the 4WARD trial. Specifically, we are enrolling participants 12 years and older with recurrent or serious infections. This segment has been validated by the claims data. And if mavorixafor is approved, we believe physicians will be rapid adopters of mavorixafor in this population.

PCN has a significant initial market opportunity with potential for upside. If approved, our initial commercial focus for mavorixafor will be on the approximate 15,000 symptomatic patients with ANC below 1,000 and 2 or more infections in a year. We don't need to convince these patients that they have this disease. They know it and they know how it makes them feel. Beyond this initial group, our latest market research suggests the opportunity for mavorixafor is larger than previous estimates, potentially up to 30,000 patients with an ANC below 1,000 and one or more infections subject to FDA labeling.

We look to potentially maximize this segment. Physicians tell us that for a PCN patient, even one infection, the next one could be life-threatening. Physicians who have lost patients to sepsis or pneumonia feel strongly about intervening earlier, and we've heard in our recent market research, and it's very saddening to hear the true consequences of what PCN can do when someone loses a loved one.

In closing, our goal at X4 is to reshape and rethink how PCN is treated. We believe, if approved, mavorixafor is uniquely positioned to transform the treatment landscape for patients with PCN, those on G-CSF and those on antibiotics. We continue to learn more about this market with research to date strongly supporting the opportunity to use mavorixafor in this 15,000 to 30,000 symptomatic patient population with PCN.

Thank you for your attention. And with that, I'll turn it over to Adam.

So thank you, Michael. Thank you for a great presentation. There clearly is a great opportunity for mavorixafor. So now to provide the clinicians viewpoint, we're honored to have with us today 2 leading hematologists in the area of PCN.

Dr. Warren and Dr. Gandhi, if you would -- you've joined us now to make sure your audio is on.

What I'd like to do is start with maybe Dr. Warren, you could describe your practice, what patients you see, how your patients are referred. And then obviously, the same question to Dr. Gandhi. Dr. Warren?

Yes, of course. Thank you for having me today. My practice here at the Children's Hospital of Philadelphia is my outpatient practice is primarily children, which we would consider anyone under the age of 21 with chronic neutropenia and other bone marrow failure disorders. And we do see a pretty good mix of germline genetic causes, meaning congenital neutropenia or cyclic neutropenia or patients with chronic idiopathic neutropenia. Patients are -- come to see me either through their entry through our hospital system as primary referrals to myself from community, pediatricians.

And I will say that because I have specialized expertise in neutropenia, I do often perform second or third consultation opinions for patients with neutropenia from both the Philadelphia area, and I will say from around the country as well. And I do also see adults with chronic neutropenia as onetime consultation visits to provide additional expertise for their care and partner with their local adult hematologists.

All right. Thank you. Dr. Gandhi, same question.

Thank you, Adam, and the X4 team. Shreyans Gandhi, I'm an adult hematologist based at King's College Hospital in London. And we are a large tertiary teaching university hospital. We receive referrals. U.K. being a smaller country and this being a rare disease, we receive referrals from around the country. I see these patients also from the primary community, referred by GP, referred by primary physicians. Again, it's a mixed bag of patients with inherited bone marrow failure syndromes, congenital neutropenias, but also we have a substantial practice for patients with common variable immunodeficiency syndromes. And last but not the least, an important sector is the rheumatological causes associated with autoimmune neutropenias.

So if I could ask you, Michael was talking about the impact of the disease from our market research. What's your -- Dr. Gandhi, what's your perspective on the impact of the disease, primary chronic neutropenia in patients? What do they tell you?

Thank you, Adam. I think it strikes a chord with me because I mean all of the things that he talked about, particularly the emotional burden, the aspect about people missing out on job opportunities, people waiting, waiting, waiting, women having particular anxieties with regards to getting on with their lives. This is something that sadly we have seen for so long, and we've really never had any kind of research opportunities to kind of investigate and look beyond G-CSF, which in itself has got its own issues and problems, but it's the best we could do and it's the best we've been able to offer up until so far. So -- and sadly enough, I think one of the things John mentioned was also about the loss of patients, which is -- does not just strike -- I'm sure it strikes in a very profound way to patients, families, but it does strike us as well to lose one patient is lose too many, and it stays with you.

Yes. I looked after chronic neutropenia when I was a pediatrician, so I have some experience of that. Julia, the pediatric experience from your perspective, what are the parents and the adolescents and the children telling you?

Yes. I mean this is a very difficult disease for the entire family unit. Of course, the children are suffering. And I do really want to use that word. Our patients are truly suffering from their symptoms, and that includes painful oral ulcers, mucositis. Those ulcers can appear along the entire intestinal tract. Fear of infection is very real and actual infection can carry significant morbidity, mentioning even things like skin infections can leave long-lasting scars because our patients also have difficulty with wound healing. And so really, the symptom burden is very high.

And then the emotional burden on the patients experiencing the disease themselves, knowing what it feels like when they feel at their worst or knowing what it feels like to go to the hospital can then actually propagate quite a lot of anxiety for the patient. But then as a parent, if you can even just imagine being in that position of being told every time your child has a temperature over 101, that could represent a life-threatening infection. You have to drop what you're doing and you need to be in the emergency room within 30 to 60 minutes or your child could die.

And so I think for any parent to try to put yourselves into those shoes, you can then understand and we saw that in some data forms that I can say really reflects in my practice, too, that parents really diminish their social circle and the social interactions for both themselves and their children. And they miss out on birthday parties, family events, social gatherings, really a lot of fear of being out in public, a lot of fear of being around anybody who might be sick. And I do want to also just call out that I see a significant impact on educational opportunities for both young adults and also work opportunities from a pediatric perspective that impact the parents. And I do see really disproportionately impact the mothers in the family unit who may elect to leave a work setting so their child can stay home from daycare or even sometimes be home schooled or are forced to leave the work setting because they had to miss so much work to bring their children for urgent visits. So it's very impactful.

Yes, this is all we've heard. I've heard this from conversations with you and others. There is -- it's time to have something different. We'll get on to that in a second. Can I ask you generally, what's your view? Michael mentioned some patients are watch and wait, some patients have antibiotics, some patients have G-CSF. Generally, how do you treat these patients? And how do you make the decision? And obviously, Dr. Gandhi, it will be the same question for you.

Yes, I could start. So the only approved therapy right now is G-CSF. And in my own practice, that's really the only prophylactic approach that I take. I do recognize and sometimes see patients for second or third opinions who may have received other therapies, including prophylactic antibiotics, which our opinion is that any potential benefit of that has actually not been borne out in retrospective analyses of available data and additionally, as was mentioned, carries the significant side effects of long-term antibiotic use, including the potential to develop antibiotic resistance. So that is not a part of my current practice.

And then I also do see some patients come to me in less -- with less typical approaches such as intravenous or subcutaneous immunoglobulin replacement therapy, even if their immunoglobulins are normal sometimes in an effort to somehow modulate the immune system or -- and I'm very displeased when I see this chronic steroid use, which has, of course, a very, very high long-term symptom burden. So really, when I see a patient who requires treatment, my practice is to reach for really the only approved medication, which is G-CSF.

And I'll ask you, how easy do you find it to administer it? Obviously, you have a large age group range from small children all the way to adolescents. Do the parents administer it? Do the adolescents self-administer? Do you have young people who go on it and then go off because they don't like the injections? What's your experience here?

The experience is wide. I could say, of course, for the little children, the parents have to administer it. For some parents, that's fine. For some parents, that actually causes significant distress. I could say, again, when we talk about family units, I have many families where one parent sort of becomes the injector and that creates a lot of tension between the parents, between one parent child, it really affects the family unit.

Older -- young teens, tweens and teenagers may start self-administering. Some of them find that to be helpful to be in control of the situation. Some of them really never do kind of cross that threshold to be able to do it. And I will say I don't have lots of data on this, but in my experience, I do see a lot of young adults with chronic neutropenia in almost sort of a failure to launch state, right, where they -- maybe they go to school, but they stay nearby and they live at home and their parents are still helping with their injections well into their 20s. And so a needle phobia is definitely a very significant thing that can occur as well. And I will just say that we do struggle sometimes, too, with insurance understanding that it's not a prefilled syringe for a child. Having to sort of dispense a vial that's a single-use vial when you use maybe 1/10 of that volume can actually increase the sort of cost burden of treatment for the families.

Yes. Thank you. Thank you for that. Dr. Gandhi, your experience with the adults, do G-CSF antibiotics, watch and wait? What's your -- how do you treat these patients?

I would completely concur with what Julia has already mentioned. We do not advocate regular usage of prophylactic antibiotics. There's too much of issues with side effects, resistance, so on and so forth. We do advise some of our patients to keep a stash of rescue antibiotics as somebody has already pointed out, the door-to-needle time has to be 60 minutes, less than 60 minutes preferably. And sometimes patients struggle because you go up to ER and you could struggle convincing the ER registrar, "This is a neutropenic state. I need to have my antibiotics. You can do the triaging later on." And so many -- we have audits done that show that so many patients consistently miss that target, the 1 hour target to receive antibiotics.

But the second aspect is that although these are now adults, fully speaking, adults, but there are so many behavioral issues and anxiety-related issues. We had the COVID pandemic, which did not help, but particularly patients who were neutropenic through that phase have spent 1 year, 1.5 years, 2 years in complete total and absolute isolation. And it's been very hard, as you can imagine, and people needing to go for counseling and therapies thereafter, that's a significant burden.

And also having to write to employers, people missing out on opportunities or sometimes almost nearly losing a job is a big ask because you're always writing to their employers. "She was over here in ER. We had to admit her. This was the admission date. She got discharged on this day." And it's not often mentioned because there are strong employment laws these days.

But in spite of all the occupational health assessment and others, I get a feeling that there's some kind of unfavorable outlook towards people who have these kind of conditions to take on as an employee. So the psychiatric element of it, the anxiety element of it, the self-rationalization, you would have patients who will have the self-rationalization because they try to balance out the 2 risks. I want the increment in my neutrophil count, but I'm feeling particularly okay, there are too many side effects that I'm getting with G-CSF. Perhaps I could go with a few more days without a G-CSF injection or a week without G-CSF injection and how far they push themselves is a risk in itself actually. So they do live with a lot of uncertainties, anxieties alongside all of the social and emotional aspects that John has already talked about.

Yes. I greatly appreciate these comments from both of you because we -- one of the things we wanted to get across today is this is a hard disease to have, both for patients, families, caregivers, everyone. And thank you for putting that very clearly. So the obvious question then, Dr. Gandhi, first is that how would an oral agent like mavorixafor fit into the treatment landscape if the 4WARD trial was positive and if the drug was approved in the U.S. and obviously for you in the U.K. How would it fit in? How would it change things?

Well, I particularly am quite hopeful that we see good responses because there is an -- I mean, I couldn't shout louder from the rooftop actually. There is an absolute desperate need to have therapies in this arena, really, really, really needed. I'm sure everybody is going to be in agreement on that one. I hope the results are positive such that we have something that develops that can be offered to our patients. I mean the fact that we can achieve neutrophil counts and our patients know that because some -- a lot of our patients are almost as well educated as we are about neutrophils, whether we need to have neutrophil counts above 500, greater than 1,000, they understand those risks and they titrate those G-CSF doses accordingly.

Having an oral agent definitely helps. And the long-term anxiety that they have with regards to evolution to MDS, as you rightly pointed out, the median age in our cohort has always been about 33, 34 years with all sorts of things. So they practically have their whole social professional academic lives in front of them. So to the point where some -- up until so far before we've had these kind of studies, some patients have contemplated considering a stem cell transplantation for people who've had such profound infections and cytopenia. So I'm particularly very, very keen to see evolution of newer therapies in this area.

Yes. I think in our Phase II, the median age was about 30 as well, just illustrates how long these patients potentially have treatment. Dr. Warren, same question to you. How do you think an agent, an oral agent like mavorixafor would fit into the landscape in your pediatric and young adult practice?

Yes. If I can answer this kind of with respect to 2 buckets of populations of patients. First would be the patients who currently are not on treatment. And I would put a prophylactic antibiotic receiving patients in that category as well. So really patients who are not on a therapy aimed at raising the neutrophil count. So for those patients, I would absolutely offer them mavorixafor as the starting intervention for them because I think that they would benefit from having the opportunity to use an oral agent and benefit from the mechanism of action of having something that helps to release the neutrophils that are present in the marrow, potentially could support the formation of neutrophils. I think we need to learn more about that. And then something that they could take by mouth would be easier for them to fit into their daily life, et cetera. So I think for patients who have never been treated or who are no longer treated with G-CSF due to kind of intolerability. So those are the patients I would absolutely offer mavorixafor to as monotherapy and see how they do.

And then for patients who are currently on G-CSF, I do -- I can say I would have a conversation with every single one of them about what are their goals related to their therapy and how could mavorixafor sort of fit into those goals. And so if they would have a goal to say, I'd like to try to be off of G-CSF, then we can trial sort of addition of mavorixafor and titration down of G-CSF. If I have somebody who has a goal to say, maybe they have an inherited form of neutropenia where there's a long-term increased lifetime risk for the development of malignancy, and we know there's an association between longer-term use of G-CSF or dosage of G-CSF, they may have as a goal to be on a lower dose of G-CSF or space out the frequency of G-CSF dosing. And we would discuss can we add mavorixafor on and see what we can achieve as far as being able to lower the G-CSF dose.

I'm really excited to see the results of both the 4WARD study and then 4STEPS to help us as prescribers better understand what that journey could look like when somebody is already on G-CSF. But I really cannot think of a single situation even for somebody who is already on G-CSF therapy where I wouldn't offer them mavorixafor addition. And then we would work together with goals of is your goal to try to come off or is your goal to try to dose reduce and we can kind of have a partnership in achieving those goals.

That's great. I'm glad you see -- you acknowledge the importance of the 4STEPS trial. We really do need to generate data to guide physicians on how to reduce the G-CSF dose whilst maintaining mavorixafor that as its primary aim. One of the -- Dr. Warren, one of the questions we get asked quite often is about the toxicity of the drug in the product label. There is some GI toxicity mentioned. What's your experience of toxicity? And how do you handle it when you've given patients the drug on clinical trials?

Yes. We did observe that in some of the patients that we treated on the Phase II, and what I could say is that the #1 thing that helped with that was informing patients that, that was a possibility ahead of time. That was sort of the experience that we gained and that patients who did experience that side -- so the majority of patients did not experience GI toxicity. The patients who did, as long as we have provided that education upfront to say, hey, this is a possibility, this is the pattern of the GI side effects we've seen and these are the interventions that we know can help with those side effects, those side effects were very manageable.

I could say as well that our experience was that after somewhere between 1 to 2 months of mavorixafor therapy, those side effects actually waned. And for the very small number of participants who did require something like an over-the-counter medication to help with the GI side effect. And I do just want to add, I never -- I don't believe I did personally ever have to prescribe any medications to help with GI side effects. It was all sort of treatable with anything over-the-counter or required no intervention. Eventually, those participants were able to stop whatever over-the-counter medication they had because those symptoms had improved.

So overall, I do believe that was a very tolerable side effect for subjects who did not know about that, and we had sort of one experience with that, that we then educated ourselves about just that very brief, hey, you might experience this, here's how we'll deal with it, led to a sort of much better experience with the medication. And again, those side effects resolved.

Yes. Thank you. I've experienced this with drug development of other drugs, some early GI toxicity that resolved. And I completely agree with you, informing the patient, informing the families is really important, so it's expected. Dr. Gandhi, your view, your experience of the drug from a toxicity point of view, from a safety point of view?

No, I think it's much the same actually. So I wouldn't know the randomization per se, but speaking to patients, some patients in the first month would come and ask us, "I feel a little bit of nausea," and they're actually happy about it because they see this perhaps as a sign that they are on the active compound. And there's no way of telling that actually. But we've not had -- we've recruited, I think, a good number of patients actually, amongst the largest, I would think. And we've not had any patients who discontinued. We've not had any patients who've complained beyond the first month. But having said that, I wouldn't know whether they are on a placebo or a compound, but some symptom treatments initially in the first few days, first few weeks with some anti-sickness. And since then, I think we've not had any issues.

Yes. Thank you. And I think we should say that Dr. Warren has treated patients on the Phase II and the Phase III, so you have some unblinded open-label experience. And so a common question I've discussed with you both before is what is a meaningful benefit with respect to a reduction in infection rate. The study is powered, the 4WARD, for about a 1/3 reduction in the annual infection rate. What do you think is meaningful? Dr. Gandhi, what do you think is a meaningful outcome for the trial?

Number of infections, important, but reduction in the severity of infections equally important. So I would think that patients generally, when they cross the threshold of 500, you're getting into the somewhat -- not somewhat actually, quite a safe territory. You're less likely -- you may still get infections, but you're less likely to get really serious infections that would warrant hospitalization or ITU admissions. So the severity of infections perhaps would be as important as the reduction in the number of infections.

Just speaking to the cohort of patients that we have seen, we don't know. Again, this is blinded to us. But when people come and tell us that, "My median of infection was needing 10 courses of antibiotics a year has come down to 2 a year. Does that mean I've been on the compound?" And I say, look, I don't know. I'm glad that you've had just the 2 infections this year compared to the 10 infections that you had last year, but I really don't know. We'll have to wait for the trial data to come through. So 1/3 would be very good, but I would perhaps be more optimistic, and I hope to see results that are better than that, and we probably will, and also the severity of infections.

Yes, of course. Dr. Warren, the same question.

Yes. I want to answer in 2 ways, if I could. Dr. Gandhi, you really said something that really resonated with me earlier, which was that, that next one infection can be the infection that kills your patient. So -- I'm paraphrasing, but to me, one fewer infection is meaningful. In all honesty, I'm speaking as myself and not as, of course, the Food and Drug Administration or whoever else might not be treating these patients personally because that one next infection could be the infection that really either has significant morbidity, or unfortunately, mortality for our patients.

I think as far as what would be meaningful to our patients would also include something that I wouldn't necessarily categorize as an infection, but the ability to go home from the emergency room because a lot of our patients are admitted for febrile neutropenia. And although we may not consider that to be a documented, confirmed infection, a patient might have fever that could be even just related to the neutropenia itself, they get all these evaluations to search for any potential causes of infection when their ANC or neutrophil count is under 500, then they get -- very often get admitted to the hospital, get placed on very strong antibiotics, which themselves have side effects in an effort to make sure that the patient is safe.

And so even if we raise the ANC to above 500 and for presentation of fever, that means a patient could avoid hospitalization and avoid long durations of antibiotics. Even in the absence of what might not have been a documented infection, I think that will be highly meaningful. I suspect that beyond even being able to see a reduction in admissions for febrile neutropenia, I just suspect that fewer patients will even be presenting to the emergency room with fever because we do think that fever -- we don't understand this well, but that fever by itself without a concurrent infection can occur when the ANC is under 500, especially when it's under 200. And so I think though that might not technically or officially be one fewer infection, I think it -- we would be very meaningful to also see if patients either go to the hospital, but don't have to be admitted or may even have fewer hospital presentations.

Yes. No, thank you. I appreciate that. We are, of course, collecting a lot of data, not just annualized infection rate, we'll collect other data on severity and other things. And for the people who've joined us today, the infection rate on the trial is adjudicated by a blinded committee. It's not adjudicated by the company. So I'm hoping for a very robust data set.

Julia, there is one question I've discussed with you before, which was following our change to the sample size and the 1-quarter delay in completing enrollment, some of our investors felt that this was a reflection of the pole market opportunity. It was because there weren't enough patients around. I wondered what your thoughts on that are.

Yes. So our experience is that patients were sort of clamoring to participate in this trial, really excited when we opened the study. Some participants who, for whatever reason, were unable to participate in the Phase II, we had a lot of referrals. And I think our experience was not a lack of patients to treat or patient willingness or availability, it was really more that at least here in the United States, our prescribing patterns are -- and I could say maybe at least especially in our region, our prescribing patterns are really to favor use and early use of G-CSF. And so it's really a very rigorous requirement to have ANCs under 1,000 and to have at least 2 significant infections every year when the prescribing patterns, especially in our region are to reach for G-CSF early and to try to target higher ANCs.

And so in the Phase II, of course, participants could -- really did not have that infection requirement for entry on to study. And so I think -- I would disagree with that sentiment that was about either patient -- I understand it, but I can see where it could come from, but I would not say that would reflect our experience. Patients were very -- they're around, and they were very interested in participating. And I think really, it's kind of the stringency of eligibility to me that for us -- well, go ahead.

Yes. The protocol -- I think so people who have joined us today, the -- we should say the protocol is designed for an FDA approval, and it's designed as a confirmatory study for the WHIM approval, has some complexities in it that make it harder. And I personally, and I think you've said this saying, it doesn't quite represent the real world, but it's a regulatory requirement.

Dr. Gandhi, have you found slightly different health care system, obviously, but have you found enrolling patients in the 4WARD trial?

Extremely, extremely easy. I think it's been a privilege actually to speak to people directly, sometimes the medical monitors and other people to kind of look at certain aspects of eligibility and all. It's just a phone call away. You speak to them. And it's been very, very, very busy. We've screened so many patients. Some did not meet the screening criteria, but they -- it's just a testament to how many people want to come forward once they've heard about the trial, once they know that there's something else that's happening in this field.

Some have had self-referrals, some have come through their hematologists from different parts of the country. U.K. being a smaller country, but even so people traveling 300, 400 kilometers to come to your place. We've had a massive amount of interest. Adam, we've shared thoughts on this on many occasions.

And just to kind of carry on with what Julia has just mentioned, in terms of the reduction in numbers, the way I look at it is that I cannot wait for the results to come out. It's not substantially changed the goalpost. But if it makes that slight difference where we get the results out earlier, we have the data out earlier, completing the trial earlier. And once it's out, we have -- we could have a compound that's available for us for our patients, not just patients who met the trial eligibility criteria. So to me, I think I couldn't wait for the results to come out earlier, and that just suits me actually.

Thank you. Well, you've both been great. And always end sessions like this to see if you've got any closing remarks, anything else I haven't asked you, you want to say before we move to Q&A. Julia?

Yes. I just do want to say that the patients have not had access to trials, access to opportunities for new medications in this space for over 30 years. And the enthusiasm from the community has been very high. People in my practice who heard about this through various -- either marketing opportunities, Facebook groups, word of mouth, were really very disappointed if they did not meet the criteria to be able to participate and are continuing to ask me about this medication when we have routine clinical follow-up.

So I do think the community, which is very connected online, especially here in the United States, the community is very, very interested. And so I do think were the results to be positive and were there to be FDA approval that the neutropenia -- chronic neutropenia community, at least here in the United States, has an awareness of this medication, certainly, and there would be sort of high enthusiasm to at least discuss it with their provider.

Great. Thank you for that. Dr. Gandhi, closing remarks from you.

I put the same things what Julia has said. I think the enthusiasm is really high. We are very keen ourselves. We couldn't wait for the results to come out. And we see a huge, huge potential, a huge market, but also lots and lots of patients who could benefit from this therapy if it shows the benefit that we hope it shows.

Excellent. Well, thank you, both. It's been an absolute pleasure interacting with you over the last year and meeting you in your -- in various parts of the world. I also thank you for everything you've said today. I think we've had some very unique insights for our investors and analysts to hear. I really appreciate it.

So now Remy, I'd like to go to Q&A, and I'll turn it back to you.

Yes. So that would be great, Adam. Thank you. We're going to transition to Q&A. Dr. Warren and Dr. Gandhi are going to stay with us. David, John and Michael are also going to join us for the Q&A portion, and I see their cameras are all on.

So Adam, I'll turn it back to you to moderate the discussion.

Yes. So we've had a number of questions. I'll try and sort of group them into the right categories. The first question is going to go to you, Michael. It's from Derek Archila of Wells Fargo. And Derek has asked, how has the new market research informed your view of the estimated 15,000-patient U.S. target market?

Well, thanks so much, Adam, and thanks, Derek, for the question. So initially, we worked with the Veeva claims in 2023 to '25 to validate the work that was done. And we validated this again with Komodo claims in 2023 to '25. And they have more precise algorithms that really allow us to accurately capture the PCN patients. So we're confident with the data regarding the patient numbers for PCN. We're going to use those for commercial purposes.

And I can tell you that having led blockbuster hematology brands, we view this as an underserved market. You think of PNH, you think of some of these other areas. So we know that physicians once they get experience will use mavorixafor more frequently and in additional areas. So we're confident with that base case based on what we're seeing in our market research.

So the second question -- thank you, Michael. The second question again is from Derek, and it says, could you share more color on the mavorixafor product profile used in the survey that showed 90% of physicians' intent to prescribe?

Yes. So we basically used a target product profile that was very reminiscent of what we saw in the Phase II and what we're looking to do in the 4WARD trial. And when we tested it, we saw that mavorixafor has -- they were showing 90-plus percent of the time within the first 3 months they intended to prescribe. They felt it could corner the market basically because it is the first and only oral drug in development to our knowledge. So we feel confident that mavorixafor is going to be adopted readily and quickly.

Excellent. Thank you for that. So the next question, a couple of questions from Michael Schmidt at Guggenheim. John, this one is for you. Any color on the enrollment rates with the old versus new CRO? And any light on -- that you can shed on how the old CRO had impacted enrollment?

So yes, we won't be giving specific numbers out, but I can tell you that with the transition to the new CRO, we've seen the highest number of patients in screening since the inception of the study. So things have definitely improved with the new CRO.

With the previous CRO, there were several operational issues related to site engagement, site payment, vendor payment, things along those lines that just kept the study from really picking up speed because there was constant issues with making sure sites were being compensated for the work that they were doing.

Yes. Thank you, John. Certainly, it's been night and day with Parexel as the CRO, and it's something we've enjoyed working with them.

The next question I'm going to take is about pricing, a very common question we get, again, from Michael Schmidt. What price is assumed for 15,000-patient indication versus the ultra-rare WHIM price?

As many of you know, the WHIM pricing, I think, is about $575,000 -- $580,000 a year. And we've said publicly that this is not sustainable as a price. We do see the price lower for a bigger indication. And based on just prior experience and without formal pricing research, we think a pricing around $250,000 to $350,000 is going to be acceptable. However, we do need to do some formal research.

Michael, the next question from you is, again from Michael Schmidt. Last one from Michael. How does the 15,000 breakdown by subtype, congenital, autoimmune, idiopathic and by current treatment use G-CSF versus none?

Well, thanks again, Adam, and thanks, Michael. So 5,000 -- roughly 5,000 patients out of that 15,000 base case are on G-CSF in that particular segment, roughly 7,500 on some form of antibiotics. And there's probably, let's say, 10% that -- 10% to 15% that are on both. So as we think about these patients, they're desperate. As we've heard from both Dr. Gandhi and Dr. Warren here that they are desperate, right? They're really left with really no viable treatment options that can be endured for the long term. So this is something, again, we just feel confident with the product profile and the differentiation that mavorixafor offers, and we're confident in capturing this segment.

So the follow-on question from Michael, just 2 small ones, one of which I will answer. Can I have the questions back, please, from Michael. They disappeared. The last question was how often do the patients see a hematologist?

Yes. So that's a great question, Adam, and thanks so much. What we're seeing right now is that patients will see hematologists quarterly once they have confirmed the definitive diagnosis for PCN.

Yes. And what we've been discussing internally is what kind of sales force. And my understanding, Michael, from our -- it's very similar to our experience at CTI, about 70% of these patients will be treated in the community and about 30% in academia. So we see this market opportunity as a very similar commercial opportunity as we have at CTI. Is that correct?

Yes, absolutely. I mean, we're thinking about that the exact same way.

Good. Okay.

And the majority, 70 -- yes.

Sorry, please go ahead.

No, no. The majority of these patients will be treated by hematologists, roughly 70% community and 30% academia from what we're seeing.

Excellent. Okay. The next question is from Thomas Smith at Leerink. John, this one is for you. With claims data suggesting that 6,000 CN patients were hospitalized with mean stays of 4 days per infection, how does that durability and infection severity compare to the patients enrolled in 4WARD?

So that is similar to what we've seen with 4WARD. So it's the same patient profile that is being enrolled on the study.

We should say we only look at blinded data, don't we? We are not...

That's baseline enrollment on the study, not experience on the study. Correct.

Yes. And if I could add to that for the people who have joined us today, we haven't seen anything in the blinded data unexpected. In fact, it's very much tracking to what we expected.

So John, another question for you from James at Stifel. Can you remind everyone about your powering assumptions in 4WARD and specifically how it relates to infections?

So the infection endpoint is powered to show a 30% improvement on the mavorixafor arm in the intent-to-treat population versus the placebo. And that's for all patients enrolled on study, both the monotherapy and the combination of G-CSF patients. It's powered based on the WHIM, what the experience was in the WHIM Phase III study.

Yes. Thank you, John. And the next -- the follow-up question from James was how do the baseline characteristics inform your confidence in the trials powering?

As I've said, we are tracking exactly -- almost exactly as predicted. We're very, very comfortable, and we're very comfortable that we have what the FDA asked us, which was to enroll patients in whom we can make a difference. And that was the patients with multiple infections who had moderate or severe neutropenia, and John has already described that.

Okay. I'm going to move on to -- let me just read the questions. Another question from -- it's very long. Let me see if I can summarize it. This is from James Condulis at Stifel. Your market research clearly supports a large rare disease population with considerable unmet need. You've, of course, gone through a significant transformation as a company. What's your response to a skeptical investor who points to the enrollment kinetics here as it implies to the commercial opportunity?

Well, I think we've already answered that question, and Julia and Shreyans kindly answered as well. And I've said this multiple times, the issues with enrollment were operational. It took us a little longer than we expected to identify the issue, and the main was the performance of the CRO. That's now corrected. And as John said, we now have the largest number of patients in screening that we've had, and we're working very well with our new CRO.

Julia, still a comment for you.

Yes. And if I could add, Adam, you said that FDA asked you to enroll patients for whom this drug could make a difference. And I absolutely understand that as far as infection and infection attributable to neutrophils and having a low ANC. I really just want to share from my clinical experience that, that is not -- that is a small slice of the patients for whom, in my opinion, this medication has a very strong potential to make a very significant difference. And so that relationship between kind of the ability to hunt down and enroll patients in that small slice and what our reality is as practicing hematologists and who we see walk in the door and who is having so many neutropenia-related symptoms that are not captured by infection. We really absolutely understand why a study has to be set up in this way to answer these questions very rigorously. But I just really want to emphasize like that's this many patients, and we have so many more who will, I think, have this strong potential to be helped by this medication and aren't necessarily captured in that.

Yes. Julia, I completely and the company, we agree with you, but we have to pick a population to study, and we have to do that in partnership with the FDA, which we did. However, I think the description of Michael, the potential opportunity of 30,000 patients if you take just one infection a year illustrates what you're saying. There's a lot more opportunity there. And obviously, how we use the drug will be dependent on the product label.

There is a question -- of course, please.

I'm sorry, if I could just add one other thing, which is that we don't only make treatment decisions based on infection. I just want to put that out there, too, that when we see somebody coming to us who might have very significant oral ulcers, mucositis with or without very significant fatigue, intermittent fevers that may not actually wind up being classified as and -- or documented as an identifiable infection, those are actually all indications to treat as well that, again, I absolutely understand those not being able to be sort of eligibility or inclusion criteria for a trial, but we do not only use infection as determining who meets the threshold to require treatment.

Yes. And you've also spoken to me about other observations on the trial. Obviously, it would need to be confirmed in a randomized setting. But you've spoken to me previously about fatigue as a potentially -- it may be potentially improved in this setting -- obviously, I should say, it will be tested in the trial. It's one of the endpoints we're looking at. But you've noted fatigue improving in these patients -- in some of your patients, have you not?

Yes. And really like strikingly on the Phase II, the number of patients who reported very significant improvement in their fatigue. And it's not in our textbooks necessarily, but many patients with neutropenia, especially if their neutrophil count might wax and wane a little bit, will tell us things like, I don't know, Dr. Gandhi, if this is your experience, too, I know when my counts are going lower, when they're dipping down under 200 or I know when they're below 300 because I -- first, I get extraordinarily tired. I can't even get out of bed. I can't go to work. I can't do my activities. And so for patients on the unblinded study on the Phase II, where everybody was receiving treatment, that was really very striking to me how many of those participants reported improvement in fatigue.

Dr. Gandhi -- you're in a blinded setting -- yes, please.

No, no. First of all, I would agree because the fatigue element of it, outside of the clinical trial, it's just like immune thrombocytopenia. And immune thrombocytopenia, the most significant symptom, more than 90% of the patients report is actually fatigue. It's not bruising or bleeding. And we've seen similar kind of a picture for patients who have autoimmune neutropenias. Fatigue is by far the most debilitating. Some people attribute it to G-CSF injections and other things, but element of the disease per se brings about a lot of fatigue.

And just along the side of -- and they obviously screen failed because they didn't meet the criteria, but we've been referred patients with low-risk MDS and other forms of aplastic anemia and bone marrow failure patients, just in the belief that their neutropenia, if that would be corrected. There's G-CSF and other therapies that is trialed in MDS and other risk patients. So I think this could be a stepping stone, which is what I'm really hoping for because that, of course, is a much larger cohort of patients that you're talking of.

Yes. Thank you. Thank you. Thank you for that.

Next question, John, this one is for you, can you talk about your confidence in achieving the annualized infection rate endpoint in 4WARD?

And the second part is how should we think about the reduction in annualized infection rate we've seen in the WHIM clinical trial experience it? And how does it translate to 4WARD?

Yes. So in WHIM, a rather significant reduction in infection was observed close to 60% on the mavorixafor arm versus placebo. And what we can say is that we are enrolling, as we discussed, a symptomatic population. So a population of patients, I think, best described as desperate for an option because their disease is largely uncontrolled. And we -- looking at blinded data, I believe we're tracking towards a 30% reduction or better in the mavorixafor arm as planned with the study design.

Okay. Thank you, John. And the next question also for you, another one from Thomas at Leerink. With 37% of the patients enrolled in 4WARD on concurrent G-CSF, can you comment at a high level of G-CSF dosing that -- I think it's the G-CSF dosing patients are receiving high and moderate to severe. Are you able to comment on G-CSF usage?

We're seeing fairly standard G-CSF dosage on study. This isn't anything that is -- it's not they're not receiving very small doses. It's pretty standard for what these patients are prescribed. So they're largely refractory patients to G-CSF.

Okay. And just to keep you earning your money today, John, one more question. Can you comment on the screen failure rate? Can you give any -- has it evolved over time? How do you think about this relative to the potential commercial opportunity for mavorixafor?

So again, the screen failure rate, as alluded to earlier by Julia, there's difference in the U.S. versus ex-U.S. We're seeing the screen failure rate that has evolved over time as with any clinical study. As you gain more experience and physicians gain more experience, the screen failure rate typically goes down. So early on, there was a high screen failure rate, and we've seen it reduced as we've gained experience and physicians have gained experience for what patients are eligible for the study.

Excellent -- yes, please, go on, John.

No, I was just going to say, as it relates to the commercial opportunity, I think those things are decoupled. This is a difficult study to enroll. FDA was very specific for the type of patient population, which I do agree with because it's a very homogeneous patient population with a high disease burden. And so if you're going to see a clinical benefit of mavorixafor, these are the patients you're going to observe it -- being able to observe it in the most.

So that said, as Dr. Warren alluded to, the opportunity here is all these patients that are managing their disease without G-CSF, managing their disease with isolation or with other things to prevent the infections that would have otherwise made them eligible for the study.

If I could perhaps just add a little comment...

Yes, please.

Yes, yes. Adam, it was just about the screen failure, and it almost seems intuitive. But I think when you're screening patients, if at all, it's possible your patients if they could have a short G-CSF holiday. And certainly, you don't want to be screening them the day after they've had their G-CSF injections. As we've learned, actually, some patients have refused to come off the G-CSF and have been screened. And on those occasions, the neutrophil counts happen to be above [ 1 ]. So that was one of the reasons why some of -- we've had some of those failures.

Yes. No, I understand. Okay. I'm going to move to the last question, and it's from an investor about the 4STEPS trial. And it's John. As I understand the question, how do we -- how will we treat a percent reduction in G-CSF dosage over time as opposed a percentage versus an absolute decrease? I think the question is how are we measuring it on the trial?

So it's an absolute decrease. So 25% of the dose over a given period, over a weekly period. So whether that's a reduction in the number of injections or reduction in the absolute dose of G-CSF, both are considered options as the 25% or 50% reduction in G-CSF.

Excellent. All right. Well, thank you, everyone, for -- everyone online for your questions, much appreciated.

Remy, that's it for the Q&A now.

So Adam, I'm just going to bring up the final slide to share to sum up the presentation today.

Yes. So thank you. So what we wanted to get across to you today is obviously, we're on track on delivering the pivotal Phase III data in 2028. But the -- if data, if we're successful in the trial, is positive, there's a significant market opportunity, a baseline case of 15,000 patients and potentially more depending on product label.

We do have -- at the company, we've got a good blue-chip investor base, and we do have an experienced C-suite that has done this before. And it was great to welcome Michael Massello to the team recently, and he's providing a huge amount of input into the commercial experience.

With David on the call, it's important to say we do have a cash runway into 2029, and we're very careful with cash. We don't overspend and we really do focus on the clinical trials. So the proof of concept for mavorixafor in CN has already been demonstrated in the Phase II. Top line data for the 4WARD trial will be in Q1 '28 with approval anticipated late '28, early '29. And as John has said, the 4STEPS trial, we expect to enroll first patient in Q1 '27 and data in '28.

So just to finish off, this is a large market opportunity. It is a rare disease, but the market is quite substantial. And I think one of -- probably for me, the most important thing I've heard today from our guests is that there is a clear unmet medical need for a well-tolerated oral agent that could be used either monotherapy, in combination with G-CSF.

So with that, I'd like to thank everyone for participating. I'd like to thank the speakers. I'd like to thank the X4 team for working very hard on this for a number of years. X4, we're focused on the patients, and we really do want to provide them with the best opportunity to live a meaningful and productive life.

So with that, I wish you all a good day, and you may disconnect.

All right. So welcome to this fireside chat with X4 Pharmaceuticals. I'm Michael Schmidt, Senior Biotech Analyst with Guggenheim. And it's my great pleasure to welcome Adam Craig, Executive Chair of X4 Pharmaceuticals. Adam, thanks for joining us today.

Thank you, Michael. Thanks for having us.

So maybe just starting off with a high-level question. So you and the management team have been in place now for about 6 months or so at X4 Therapeutics. Maybe just remind us of your broader vision for the company and what you're trying to accomplish.

What we're trying to accomplish is being a leading company in the development of new therapies for patients with rare blood disorders. What we're focused on at the moment is the development of our compound mavorixafor for chronic neutropenia for patients who have low white counts and are very exposed to infections.

Over the last 6 months, we spent a lot of time focusing the team on that goal. We've reduced costs. We've reduced headcount, and we've really become a company that's focused on completing our Phase III trial successfully so that we can bring that new indication to patients.

Okay. Yes. Maybe then a few questions about mavorixafor. So this therapy targets CXCR4, which has been shown to have bone marrow mobilizing effects. And so yes, maybe remind us what is the value proposition of mavorixafor relative to other CXCR4 inhibitors or antagonists that -- and also G-CSF, which is used in this category.

Yes. With regard to other CXCR4 compounds, Plerixafor is an IV compound that has demonstrated limited benefit in WHIM, which has our first indication. We don't really have a main competitor in the CXCR4 space in the commercial environment and on our clinical trial, obviously, G-CSF is used extensively in these patients. About 40% of all patients with chronic neutropenia have G-CSF therapy. But it's a therapy that has limitations. It's subcutaneous, whereas mavorixafor is an oral therapy. It causes bone pain.

There's a risk of long-term transformation to leukemia with long-term use. And I know from my personal experience as a pediatric oncologist, a lot of patients do not like having G-CSF. And that's why our market research shows only about 40% of overall of all patients take G-CSF and it's not constant.

Many patients will take it intermittently, particularly if they need to go out into socialize or they're going to a restaurant, they'll take it to give themselves some protection against infections when they're outside their homes.

Okay. And so mavorixafor is already FDA approved actually for a very rare condition called WHIM syndrome. You've discussed in the past that the company is sort of not actively promoting the therapy there. But yes, maybe talk a bit about the data. And to what degree does it validate the therapy? And to what degree does it read through perhaps to the chronic neutropenia opportunity?

Yes. So just to sort of finish that off, WHIM is an ultra-rare indication. And when we took over the company in August of last year, we were -- the company was spending more than it was bringing in revenue. So we've deprioritized the commercialization of WHIM.

We will always provide the drug to patients and it is available to patients that require it, but we're not actively commercializing it. But as you say, the WHIM data is very helpful with regards to understanding chronic neutropenia.

WHIM is a form of severe neutropenia that is patients with ANCs less than 500. They also have hypogammaglobulinemia, and they're very prone to infections. So the WHIM data shows that the -- with treatment of mavorixafor, the ANC can improve and infections can improve in a small sample size, as you'd expect for an ultra-rare indication.

So it's very validating for me for the main hypothesis in the broader chronic neutropenia population that mavorixafor will have a benefit.

Yes. And I know you've -- again, it's not promoted, but there are some sales in WHIM in the U.S. and there are European, I think, approval decisions coming up at some point, too. Do you see upside to the near-term commercial opportunity in WHIM for mavorixafor?

I think the more physicians know about mavorixafor, the more they understand the clinical trial and potential commercialization in a broader indication, yes, there will be benefit from WHIM. At this point, for the WHIM indication, at this point, though, it's just not feasible for us to spend more money on commercialing something than we are getting for revenue coming in. It's just not good business sense.

But as I say, we have picked up a number of patients since we stopped commercializing. So we're still in new patients, but the numbers are very, very small.

Makes sense. Okay. And so you're obviously evaluating the therapy in chronic neutropenia, as you mentioned, in a Phase III study, the 4WARD study. Just maybe remind us of the size of the opportunity in this indication?

We estimate -- we've done some -- we've done a number of market research studies. The most recent was from ClearView Partners in Boston, and we worked with them. And they identified that there are about 15,000 patients with symptomatic severe or moderate chronic neutropenia. And that is patients with ANCs less than 1,000 or less than 500.

The estimate is to start with some of those are on G-CSF and some of them are not. The estimate from ClearView Partners is our base case is about -- we will treat about 1/3 of those patients, about 5,000 patients. Initially, we will penetrate the market, they think more successfully as a monotherapy. And over time, as we develop relationships and share data, we'll have more and more patients who have mavorixafor with G-CSF.

So we're working on a base case of 5,000 out of 15,000 patients. And of course, there are opportunities beyond that if we generate more data.

And maybe talk a bit more about the sort of the major or the main unmet medical need in this patient population. Is it patients that don't respond well to G-CSF? Is it patients that are on it but not happy with tolerability? Or is it other subset of patients?

There are certainly patients who have been on G-CSF for a long time. If you look at their history, they're on higher and higher doses. I was in London last week at Great Ormond Street Hospital, where the -- one of the physicians was describing patients having super doses of G-CSF because over time, they're just not responding. That's true. There are patients who just don't want to be on G-CSF because it causes bone pain because it's uncomfortable because there's a risk of long-term malignancy.

And the life of these patients, the patients we're treating are patients who have infections. On our clinical trial, 70% of patients entering the clinical trial have 3 or more infections a year. And we're not talking about infections like mouth ulcerations. We're talking about infections that require attendance at the emergency room, may require hospital admission, may require antibiotics.

So it's -- the unmet medical need is really quite significant. If we can improve on the infection rate by increasing the ANC of these patients, we will change their quality of life.

Yes. And then yes, perhaps talk about the Phase I and Phase II data that you have already generated with mavorixafor in chronic neutropenia. And to what degree does that -- did that inform the design of the Phase III study?

It was very informative. It's a small data set. I think it's important to make that clear. But the Phase II -- Phase I, Phase II data in chronic neutropenia for me shows two things. The first thing it shows is that mavorixafor can be given to patients with low ANCs and the ANC count can increase above 1,000, above 1,500, where there will be some protection from infection.

The other part of the data set was using the drug in combination with G-CSF and in that population, we showed that the drug can be used safely in combination with G-CSF. Obviously, that will be confirmed by the Phase III. And we also demonstrated that you can lower the dose of G-CSF, but still maintain a decent ANC.

So a small data set. If I had run the trial, probably have done a bigger trial, but it really does prove to me that the principle of using mavorixafor alone and using it in G-CSF is -- the data is good, and it supports the conduct of the 4WARD trial.

Okay. And I mean, Plerixafor, which is a simple mechanism drug is used to mobilize stem cells as well. And so I guess my question is how selective is mavorixafor towards increasing neutrophil counts specifically? And is it -- is there a risk of other cells are being more out of the bone marrow?

Not that I'm aware of. We continue to monitor -- I look at the safety data once a month, both from the market and on the clinical trial blinded data. I've not seen any new signals. I haven't seen any long-term signals, but it's always possible. Plerixafor is IV and our market research shows it's used in about 2% to 3% of the chronic neutropenia market. It's not really a main competitor, first of all, because there's not substantial data in the area. And the other thing is given IV as opposed to G-CSF, which is subcu or our drug, which is oral.

Yes. Makes sense. And then yes, maybe just walk us through the design of the 4WARD Phase III study. So remind us again of the eligibility criteria and what the powering assumptions are.

So it's a trial that includes all groups of chronic neutropenia. It's 176 patients randomized 1:1 between two treatment arms. So it's mavorixafor versus placebo. And on each arm, patients can receive G-CSF. So it's mavorixafor placebo plus or minus G-CSF on each arm.

And we're -- to be eligible for that trial, you need 2 infections a year in the past year. And what we're measuring is a change in the -- an increase in the ANC as one primary endpoint and the co-primary is a reduction in infection. And we do think they will go together. If you increase the ANC, you should reduce infection rate.

So 176 patients split between the 2 arms, and our aim is to complete enrollment by the end of the third quarter of this year. We did inherit when we came in August, a trial that wasn't functioning properly. We've worked very hard to increase the enrollment weight, which we're doing and very hard to find patients and identify them and get them on trial. Operationally, that has been -- the operational conduct of the trial has been our focus.

How are those patients managed today? What types of decisions? Are they hematologists? Or is it more in primary care?

No, they may be identified. This is the difference between WHIM. If you look at where WHIM patients are, they're all over the place, dermatologists, hematologists, immunologists. Chronic neutropenia patients tend to be -- eventually end up with hematologists, very similar prescriber base to what we had when we were running CTI with VONJO in MF.

About 80% of the patients will be within community practice, and they tend to be hematologists. When a patient has a low count identified, they're typically referred to a hematologist for a bone marrow examination, and they'll be managed in that setting. Most of the patients are managed in that setting.

And on the -- in the FORWARD study, you said roughly 40% to 50% of patients will be presumably on G-CSF.

About 40% we're seeing.

Do you allow for down titration of G-CSF?

No, we don't. And that's when we joined, that was the one limitation of the trial that we studied. I'm glad you brought it up. So in consultation with the FDA, it was decided that the G-CSF dose will be fixed. The problem with that is it means we wouldn't have data in the marketplace to say how G-CSF could be used with mavorixafor. So what we're in the process of discussing and working with the clinical development team is looking at a -- doing a small Phase II study where we can titrate the dose of G-CSF against mavorixafor whilst maintaining ANC.

And my objective is by the time we get the approval of -- for mavorixafor in chronic neutropenia, which should be in 2028, we will have a publication in place that will provide some treatment guidelines on how to use G-CSF with mavorixafor. The full trial is well designed, but that's the one bit of data we will not get from the trial. So we need to run a smaller study.

But in forward, so the patients that are on stable G-CSF, they still have to have low ANC count?

Yes. We have patients from all different doses of G-CSF from high to mega doses, super, super doses as some people call them. There are patients who've been in G-CSF for a short period of time, and there's patients who've been on it for a year, particularly the congenital neutropenia patients, some of them have been on it since childhood, and they have very, very high doses of G-CSF, but they're still they still have severe and moderate neutropenia.

Do you expect differences in patients' ability to increase ANC dependent on whether they're on G-CSF, obviously not responding or naive?

Yes. I've spoken to the team about that at the time. The answer is no. We're really dealing with a refractory population for the G-CSF. If you are on G-CSF and you're still getting 2 infections a year, you're not -- it's not being controlled. It's not working.

In fact, I think I've already said 70% of patients coming on trial have 3 or more infections. So we are examining -- we are exploring here a population that is symptomatic and is quite sick despite the use of G-CSF.

Okay. And then the other thing my understanding is Plerixafor or CXCR4 antagonist, they were really fast, right? I mean I think you can mobilize these cells within days or a day. And so how much is known about the long-term effect of that ANC increase? How stable are these increase over time?

We have data. It is maturing. Obviously, the initial data set here is generating the ultra-rare indication of WHIM. But we have patients 3, 4 years out now who are doing very well on mavorixafor, but it's important for us to continue being following up patients. And the 4WARD trial does have a long-term follow-up component to it. So if we get approval for many years, we need to continue.

The answer to your question is I haven't seen anything yet, but it's important that we conduct ourselves properly and have pharmacovigilance looking for any long-term effect nothing at the moment, but we continue to look.

Yes. From a -- and then this is a 1-year study, right, 52 weeks. From a safety tolerability angle, anything you're watching specifically? I think the drug has been very well tolerated, but any concern.

Well, first of all, the independent data monitoring committee met last quarter and didn't make any changes to the study. So that's gone well. I review the blinded data with the clinical team. I did it last week, every quarter -- sorry, every month.

I've not seen any changes in the safety signal. It is blinded, so I'm seeing both treatment arms. But no, nothing new. We know there is some GI toxicity that needs to be treated symptomatically. But to date, there's nothing new to report.

Okay. And then I know you alluded to some changes that you're implementing to the study conduct. Just maybe elaborate a little bit more on what are some of the things that you've done to really ensure the study has the highest possible chance of success.

Yes. The main thing is this is rare disease. So you have to find the patients. So we have -- we moved the MSLs away from commercializing the drug to patient recruitment. And together with the Clin Ops team, our CRO, our job is to identify patients and get them referred to the treatment center.

So if there's a site in L.A., there will be one hospital in L.A. that's conducting the trial, but there are other hospitals that have these patients. So we're using AI to look at databases. We're spending a lot of time in the field. I'm in Europe again next week, Mainland Europe, working with some PIs, developing relationships.

It's really about identifying patients, getting them into screening and then seeing if they can go on the clinical trial but it requires a lot of groundwork, a lot of field work, and that's the change that we've tried to bring to the company. We've made it about relationships, and we've made it about getting into the field and talking to physicians and identifying patients. That's the focus, and it's working.

It sounds like you're tracking towards 3Q enrollment complete.

Yes, we are. I'm not going to give an update today because we're still seeing the benefit of our changes. But towards the end of the year, I'll provide an update to the Street.

Okay. And then -- so presumably, then data would be available one year later, right?

Yes.

And I know it's a little bit early still, but how do you think about pricing and access in the market, especially relative to biosimilar G-CSF, which played really well.

Yes. Well, I think the benefit here is reduced infection, which, as you know, within the American health care system, admission to hospital for infection is very expensive. I think there is an opportunity for premium pricing here. We've not done formal pricing research, but based on my experience, I think there is an opportunity to have premium pricing in a rare disease. I don't think the pricing of the drug will be sustained where it is, which is in the $500,000 range. I think it will be lower than that. But I do think given the benefits and given how rare the disease is, we could have very healthy pricing here.

Okay. Are there any other potential competitive programs in the industry that are in development for this?

Not that we're aware of, if there are, I'd love to know from anyone in the audience, but we're not aware of any competitors at the moment.

Okay. And do you see any other potential label or opportunities beyond chronic neutropenia that could be interesting for...

Yes. Yes. We've had a lot of interest. There are other forms of secondary neutropenias. There are other indications where we could potentially expand the use of the drug. Most patients with chronic neutropenia actually have mild neutropenia counts of 1,000 and above. So I think there's opportunity to do that. At the moment, though, we're focused on getting the beachhead with the chronic neutropenia, severe and moderate indication and then we can expand.

And the team have many ideas as to many of my Board and how we should do that, but it's not the focus at the moment.

Got you. And I mean, when I think about GCS, it's obviously approved in a range of indications. Are there any other things that are obvious opportunities for mavorixafor that are related to G-CSF?

Yes, there are. But that will come out in time. We'll talk about them. Yes, there are -- it's funny when you join a new company, people bombard you with new ideas. And what we've got to do is keep the team focused on achieving the primary goal and then we can work on the other ideas.

And then any -- as we look ahead, so ahead of the 4WARD Phase III data, presumably towards the end of 2027, any other milestones or events investors should be watching out for?

Well, we do later this year, I think we need to present to the Street what we think the market opportunity is. A lot of investors have been asking for that. So we are looking at having some presentation where we can present our work.

I've already mentioned that we think there's room for G-CSF titration study. So these -- and then obviously an enrollment update. So I think this is the news flow for this year. I'm still working on the first one, making sure we've got a very clear and accurate presentation of the market opportunity.

We've had investor meetings, thanks to you this morning. And it's a common question. Can you present the market opportunity and can we see some of your data, and we'll do that.

Are there any analog markets or some precedent that come to mind comparing this to...

Not off the top of my head. Did you have anything in mind?

I didn't. I'm thinking just from a patient number perspective, obviously.

No, I think there's -- because there's not a lot of work going on with other companies on this. And I think it's up to X4 to present to the Street what we've done. And so people can understand and make their own assessment. And that's something we need to do this year.

Great. Well, thank you, Craig. That's all ahead. So thank you for the Q&A session and really appreciate you being here today.

It's always a pleasure. Thank you, Michael. Thanks.