Good afternoon. Welcome to the X4 Pharmaceuticals webinar. At this time, all participants are in a listen-only mode. A question and answer session will follow the formal presentations. If you would like to submit a question, you may do so at any time throughout the webinar by using the Q&A function at the bottom of the webcast player. A reminder to our analysts to please raise your hand to indicate you would like to join the queue. It is now my pleasure to introduce our host for the event, Dr. Paula Ragan, Founder, President, and Chief Executive Officer of X4 Pharmaceuticals.
Thank you. Thanks to all of you for joining us today to review and discuss the exciting data from our phase III trial of Mavorixafor in WHIM syndrome. Before we begin, I'd like to remind everyone that on today's call we will be making forward-looking statements regarding our regulatory and product development plans. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted. A description of these risks can be found in our most recent Forms 10-K and 10-Q, both on file with the SEC. We will begin today's program with a brief overview of our lead investigational candidate, Mavorixafor, and its potential to address the many unmet needs of individuals with WHIM syndrome and our exploration of its potential in additional chronic neutropenic disorders.
We will discuss the key challenges that people with WHIM face, followed by a presentation of our new data from our phase III clinical trial, which focused mostly on the beneficial effects that Mavorixafor had on the rate, severity, and duration of infections. We will provide an update on our regulatory path forward on Mavorixafor and WHIM, and on other possible indications, including CN disorders, before concluding and taking your questions. Throughout our event today, we will be hearing from both WHIM patients and from leading physicians who treat people with WHIM and/or a range of chronic neutropenic disorders and who study the underlying biology of these immunodeficiencies.
Joining us today to comment on the phase III results and the unmet medical needs of WHIM and CN patients are a mix of immunologists, hematologists, and rheumatologists, all of whom have expertise in treating immunodeficiencies and several of whom are investigators in the 4WHIM phase III trial. You'll be hearing commentary today from Dr. Charlotte Cunningham-Rundles, a Professor and immunologist at the Icahn School of Medicine at Mount Sinai. Dr. Jean Donadieu, a pediatrician in the Hemato-Oncology Department of Trousseau Hospital in Paris, and importantly, coordinator of the French Registry for Chronic Neutropenia. Dr. Peter Newburger, Professor of Pediatrics and Molecular Cell and Cancer Biology at UMass Chan Medical School. Dr. Akiko Shimamura, Director of the Bone Marrow Failure and Myelodysplastic Syndrome Program at Boston Children's Hospital and Professor of Pediatrics at Harvard Medical School. And Dr.
Teresa Tarrant, Associate Professor and Director of the Clinical Immunology Laboratory at Duke University School of Medicine, and Vice Chief of Translational Research for Rheumatology and Immunology. We will also hear the unique perspectives from three individuals Gabrielle, Willow, and Courtney, all of whom have been diagnosed with WHIM and who have been experiencing WHIM symptoms since birth. We are honored that they all agreed to speak with us and share their insights with our investor audience. Joining me during the main program will be our interim Chief Medical Officer and current X4 board member, Dr. Murray Stewart. During the Q&A session, we will be joined by Doctors Shimamura and Tarrant, along with the rest of our leadership team Chief Scientific Officer, Dr. Art Taveras, Chief Commercial Officer Mark Baldry, Chief Financial Officer Adam Mostafa, and Chief Operating Officer Dr. Mary DiBiase.
We believe Mavorixafor has the potential to play a historic role in transforming the current treatment landscape for those affected by a range of chronic neutropenic disorders, first, beginning with WHIM syndrome. Since the mid-1950s, when the first congenital neutropenia disorder was described, just a single treatment, one only available by injection, has been approved for certain forms of chronic neutropenia. Amazingly, there has been no innovation in this field in almost 30 years. Our belief in Mavorixafor is based on demonstrated improvements seen in clinical trials to date across a wide range of immunodeficiency measures in WHIM and in certain chronic neutropenic disorders.
Mavorixafor has demonstrated the ability to increase white blood cell counts, including improvements in neutrophils, lymphocytes, and monocytes, and has been well tolerated in long-term studies to date, with more than 200 individuals now dosed with Mavorixafor, some for as long as four years now. Mavorixafor earned breakthrough therapy designation with the FDA based on clinical impact seen in our phase II trial and has received other favorable designations as well, including orphan drug designation in both the U.S. and in Europe. At the end of 2022, we presented the first data from our global pivotal phase III trial of Mavorixafor in WHIM syndrome, the 4WHIM trial, showing that the trial met its primary and a key secondary endpoint.
The field is ready for a breakthrough, and we believe that as an oral, once daily, well-tolerated treatment, Mavorixafor could significantly improve the lives of WHIM patients if ultimately approved. At X4, we serve as an advocate to improve treatment options for the close to 50,000 patients across certain chronic neutropenic disorders, including idiopathic, cyclic, and congenital neutropenias and WHIM syndrome. One of the main shared clinical experiences of these patients is the increased risk of frequent, severe, and long-lasting infections due to a dysfunctional immune system. Today, we're announcing that Mavorixafor treatment demonstrated statistically significant and clinically meaningful improvements across a number of infection measurements in those diagnosed with WHIM syndrome in our pivotal phase III trial.
This benefit, which will be readily apparent in the coming presentation, is yet another step in delivering that breakthrough that is deeply needed and deserved for those diagnosed with WHIM and provides further inspiration to us to advance Mavorixafor as quickly as possible for those with broader CN disorders. What exactly is WHIM syndrome? Here's a quick overview. WHIM is most often an inherited combined immune deficiency that creates significant hardship for people from birth. Their weakened immune system results from bone marrow overcrowded with all types of white blood cells, including neutrophils, that remain stuck there and unable to perform immune surveillance, a necessary role in identifying and fighting infections. This weakened function often leaves the people less able to successfully resolve infections. As a result, those with WHIM syndrome experience much more frequent, more severe, and longer-lasting infections than unaffected individuals.
These increased infections typically impact the lungs and ears, the heart and skin, among other body parts. Repeated infections in these areas can lead to permanent organ damage and can increase morbidity and mortality and lead to a higher risk of developing certain types of cancers. In addition to infections, the I in WHIM, people with WHIM can experience warts resulting from the infection with HPV, hypogammaglobulinemia, or low levels of circulating immunoglobulin or antibodies, and/or myelokathexis, the condition that describes the failure of neutrophils to leave the bone marrow and move into the bloodstream. As mentioned, WHIM syndrome creates hardship from birth. Symptoms start within the first year of life and increase as years go by, as shown in this graph, which captures the natural history of symptoms. By the time people are entering their twenties, nearly 90% are experiencing chronic neutropenia and infections.
Here you can see the dark red line representing infections tracks with other symptoms of WHIM syndrome, neutropenia, hypogammaglobulinemia, and lymphopenia. While graphs and data help our understanding of the progression of disease, we can never truly appreciate the disease burden until we hear it firsthand from patients and their physicians. Let's take a few minutes to learn directly from these experts.
My name is Gabrielle. I am 27 years old. I work as an associate scientist. I was diagnosed with WHIM in 2019. Growing up, I had always been sick a lot as a child with lots of infections, strep throat, the flu, colds. It was almost constant. My doctors would brush it off a lot as I was in school with a bunch of kids that spread germs around. It was nothing to be concerned about. However, when my mother was diagnosed with an immune deficiency in 2016, the immunologist decided that my sister and I needed to be tested. It turned out we both had hypogam. The most burdensome symptom would have to be the infections.
Even now, with my diagnosis and being on IVIG treatment, I still get infections quite a bit, and I have to miss work. I had to miss school growing up, or when I was in college, I would get infections and miss class. It impacted my grades, now it impacts my income.
I'm Willow Finley. I was diagnosed with Common Variable Immune Deficiency in 2017 when I was 17. Through genetic testing in 2019, that was updated to WHIM syndrome. I would describe WHIM syndrome to those unfamiliar with it by saying that my immune system does not produce enough of what it needs to fight off infections, as well as producing things like warts and other problems. My initial symptoms were recurring infections, things like ear infections when I was a kid, strep throat, mono, other infections like that as I got older. The impact on my daily life from recurring infections has been generally missing school, getting behind on schoolwork like that, and then just general fatigue.
My name is Courtney Anthem. I was diagnosed with WHIM in 2019. Growing up, I'd always had symptoms of Colds and pneumonias, and every time I would get sick, I would get very sick. My sister would get a cold, and she would be better in a couple of days. I would get her cold, and I would end up on high-dose antibiotics or in the hospital, and it would take weeks for me to recover. Frequent respiratory sinus infections, and there was always, you know, just something wrong with me, continuously. I would probably say I'm in and out of the hospital probably four or five times a year, and sometimes it's for a couple of days, and sometimes it can be for a couple of weeks.
Due to the WHIM syndrome, I'm frequently experiencing infections and due to that, I'm on antibiotics quite frequently, which is very challenging and devastating on my body in that I have a very difficult time tolerating most of the antibiotics. If I'm placed on antibiotics, I usually have to have an additional two or three medications to, you know, support the side effects that I have from the antibiotic. With the WHIM syndrome, it kind of ebbs and flows with infection and severity, which is difficult because there's so much uncertainty in this illness. There's not a linear path in that you get sick, you get the medicine, and you get better. That's not the journey for a patient with WHIM. You are constantly sick, and it's just a matter of how sick for how long.
The biggest problem in WHIM syndrome, of course, is recurring infections, that's going to be bronchitis, sinusitis. Over time, what that does is it actually hurts the lung, and then you get this inflammation picture in the lung called bronchiectasis. That's, I would think, one of the things that physicians worry about quite a bit.
Infections are the sine qua non of immune deficiencies. In patients with inborn errors of immunity involving neutrophils, such as WHIM syndrome, bacterial infections are the most important cause of morbidity and mortality.
First challenge is infection, which are not that short-term because we have some way to manage the short-term infection, but the recurrence of infection and the consequence of recurrent infection on several organs like the lungs, like the CNS and like the HPV infection, and warts. That's the first challenge. The second challenge is the challenge of the secondary malignancy in such group of patients, which is later in life, after the age of 30, which are also related to several kind of viral infection like Epstein-Barr virus infection or HPV infection. That's the two main challenge, I think, for the patients with this disease.
We are coming to appreciate that WHIM means different things in different individuals. Infections probably is the number one burden of disease for most patients. I think that. Infections can mean many things. It can be skin infections, it can be warts that are difficult to treat, it can be pneumonias, it can be very difficult to treat sinusitises. It's not just that each infection may be more severe. So there's this piece of the infections are more severe than the average person, but they also happen more often. I think that's something we do not always appreciate as people who have normal immune systems.
I hope that you can appreciate from these insights why X4 was so motivated to study Mavorixafor in WHIM syndrome and aim to reduce the heavy burden of infections, which was a key focus of the 4WHIM phase III trial. I'll now turn it over to Dr. Murray Stewart to review the trial design and present our very promising results.
Thank you, Paula. We designed our 4WHIM global registrational trial to set the potential of Mavorixafor to impact neutropenia and lymphopenia, two of the hallmarks of WHIM, as well as other clinical metrics of this chronic syndrome. The 4WHIM trial was a randomized, placebo-controlled, double-blinded study. The study's inclusion criteria screening required that all patients enrolled had a diagnosis of WHIM and a confirmed absolute neutrophil count or ANC less than or equal to 400 cells per microliter. Remember that less than 500 cells per microliter is the definition of severe neutropenia. Participants aged 12 and above were eligible to enroll. As you can see here, the median ANC at baseline was about 200 cells per microliter. This population was severely neutropenic.
As we described last November, the two arms of the trial, treatment and placebo, were very well-balanced by gender, age, degree of neutropenia and lymphopenia, and by previous or ongoing immunoglobulin use. Participants were assessed for the primary endpoint of TAT-ANC or the time above threshold for the absolute neutrophil count at weeks 13, 26, 39, and 52. Similar assessments at the same time intervals were completed for the calculation of the key secondary endpoints of mean TAT-ALC or absolute lymphocyte count to assess Mavorixafor's effectiveness against lymphopenia, which is defined as less than 1,000 cells per microliter. At the end of the placebo-controlled portion of the trial, all participants were eligible to roll over into an open-label extension or OLE. Notably, more than 90% of eligible participants elected to continue on and receive Mavorixafor treatment in the OLE.
Today, we'll be focusing on the robust datasets measuring differences in various clinical outcome metrics related to the rate, severity, and duration of infections, among others. Importantly, all metrics related to infection were determined by central blinded adjudication committee. This rigorous approach, which minimizes bias, utilized an independent group of physicians who reviewed blinded participant data generated under the trial. All safety data were also assessed by an independent board. Previously, we shared that the trial met its primary endpoint of TAT-ANC, with those in Mavorixafor achieving 15 hours versus 2.8 hours on placebo and a p-value of less than 0.0001. Similar benefit was achieved in the first key secondary endpoint, TAT-ALC. We shared that Mavorixafor was well-tolerated with no treatment-related serious adverse events, no treatment-limiting toxicities, and no treatment discontinuations due to lack of efficacy or safety.
Today, we're announcing that Mavorixafor treatment demonstrated significant and clinically meaningful improvement in infections in those diagnosed with WHIM syndrome in the 4WHIM trial, including the rate, severity, and duration. Today's event follows this morning's publication of our late-breaking abstract that was submitted to the Clinical Immunology Society. As we've announced previously, the abstract was accepted as an oral presentation at the CIS annual meeting, which is taking place May 18th through the 21st in St. Louis. Dr. Raffaele Badolato, Professor of Pediatrics at the University of Brescia in Italy and an investigator in the 4WHIM clinical trial, will present these and some additional data at 11:30 A.M. Central Time on Sunday, May 21st. Although the session is only accessible live to conference attendees, we'll be posting the presentation slides onto our website concurrent with the presentation.
We'd also like to note here that an abstract we submitted to the European Hematology Association was also accepted for presentation at EHA's upcoming annual meeting. Dr. Donadieu, who you've been hearing from today, will be presenting the data for our 4WHIM trial in an encore oral presentation of the results being presented at CIS. With that, let's move on to today's data presentation. This first new dataset that we're presenting today demonstrates mavorixafor's ability to improve white blood cell counts in the trial, as demonstrated by the top graph. The total white blood cell counts are represented here as the mean plus the standard deviation over the 24-hour assessment measured at weeks 13, 26, 39, and 52. Across all time points, mavorixafor treatment significantly elevated mean total white blood cells versus placebo.
In fact, white blood cell counts reached almost near normal levels with Mavorixafor treatment, demonstrating its ability in the phase III trial to improve panleukopenia that is one of the hallmarks of WHIM syndrome. A similar graph specifically quantifying absolute neutrophil counts over time is shown in the bottom half of the slide. Similar to the impact on total white blood cell counts, Mavorixafor significantly improved mean ANC counts over most of the 52 weeks of the trial, improving the severe neutropenia presented by these patients at the start of the trial. White blood cell neutrophil counts are quite meaningful assessments for this patient population, and it's key that Mavorixafor significantly elevated these counts. Importantly, benefit in clinical outcomes was also observed. As we've just heard, infections are the most important sequelae of the impaired immune system in WHIM patients.
Let's now move on to our first dataset demonstrating the impact of Mavorixafor on the rate of infection in the 4WHIM trial. We're very pleased to share that Mavorixafor treatment resulted in a 58% reduction in annualized infection rates when compared to placebo, which was statistically significant with a p-value of less than 0.01. As a reminder, the trial was conducted during a global pandemic, during which most of trial participants were social distancing or isolating. We believe this underscores the strength of the drug effect we are seeing. In fact, if we move on to the next slide, here we show that reductions in annualized infection rates were greater over time on treatment with Mavorixafor.
In this graph, the first set of blue and red bars on the left shows that Mavorixafor reduced the infection rate over the first six months of the study to three infections per year versus four point five for those on placebo. During the following six months of the trial, as depicted in the second set of blue and red bars, an even greater reduction of infection was achieved. Participants treated with Mavorixafor had an infection rate of less than one per year, while the infection rate of four point five was unchanged for those in placebo. The difference in the second six months was statistically significant, with a P-value of < 0.005. We next examined the various subgroups within the study to better understand what might be driving the observed changes.
The subgroup analysis shows that the reduced infection rate observed across the full study was also observed across all key subgroups, including age, gender, and for those on or off immunoglobulin treatment. In all cases, infection rate reduction was consistently observed in those treated with Mavorixafor as compared to placebo. We'd also like to share that trial participants in Mavorixafor also had fewer recurrent infections versus placebo, although we don't have time to review those data today. We also examined infections in various organ systems consistent with the clinical symptoms of WHIM. This benefit seen with Mavorixafor in the 4WHIM trial is consistent with the overall reduction in infection rates.
More specifically, as shown in the graph, the number of infections in patients treated with mavorixafor in the trial, shown by the blue bars, were reduced across almost all infection types as compared to placebo, and improvements were reported across bacterial, viral, and fungal infections. Notably, large reductions occurred in upper and lower respiratory tract infections, with reductions of 60% and 100% respectively. Skin infections were also dramatically reduced in the trial by more than 90%. We also examined pre-existing wart lesions, three lesions per patient, on the arms, legs, and/or trunk regions of the body by taking photographs of the selected lesions at baseline and at weeks 26 and 52. A blinded central adjudication committee reviewed the photographs and scored visual changes in existing lesions for worsening, no change, or improvement.
Although there were no differences measured between the two arms, both arms did show minor improvements across the 52-week trial. Observations of new warts were also assessed. Patients in mavorixafor had either no or fewer new warts compared to patients treated with placebo, which was encouraging. Overall, mavorixafor showed improvement across most metrics related to location and type of infection. We'll now hear from our physician experts to provide their perspectives on these data.
One of the most compelling features of the WHIM trial was the reduction in infections that was noted, that was associated with the improvement in the white blood cell counts, the lymphocyte counts, the neutrophil counts.
The data showed a very significant decrease in the rate of infections in WHIM patients taking Mavorixafor. I think that has major implications both for health and for quality of life.
Well, I think that the reduction of infection globally will offer to the patient a more normal life. Also normal meaning that they will not be hampered by this infection. So they will recover social capacity in on many aspect of what is social life. That's probably the best results we may expect for the patient.
To speak to a WHIM patient about the impact of the trial and how Mavorixafor reduced infection rates, you know, three-fold or more, to explain that to a WHIM patient would be to kinda talk about how we hope to bring your immune system back to within normal range for what normal people experience, people without CXCR4 defects or WHIM. We're optimistic that this medication can have you be more like the normal human experience with respect to infections.
In addition to frequency of infection, the assessment of severity of infection is also an important metric. As we've just heard, these infections often need antibiotic treatment or even hospitalization and can lead to permanent tissue damage and long-lasting effects. Let's now go through the data examining Mavorixafor's impact on the severity of infections in the phase III trial. First, we'd like to orient you to the definition of severity applied here. The blinded central adjudication committee utilized the standard definitions for grade 1 through grade 5 infection severity as set by the U.S. Department of Health and Human Services. These are standard definitions utilized across all clinical trials. X4 defined severe infection as those grade 3 or higher. According to Dr.
Newburger, I quote, "Grade 3 and above represents infections that have very significant morbidity, frankly, make people feel very sick, and have an increased risk of permanent tissue damage and long-lasting effects." In that context, it's particularly important to reduce the numbers of these more severe infections because they have the most immediate and long-term morbidity and potential for mortality. This is the rationale behind our focus on infections grade 3 or higher in this study. As seen in this bar chart, 29% or 5 of the 17 of those on placebo experienced grade 3 or higher infections, with only 7%, only one out of 14 patients of those in mavorixafor experienced a grade 3 or higher infection during the trial. Importantly, the single grade 3 infection in the mavorixafor treatment arm occurred during the first three months of the trial.
After that first three months, there were zero serious infections for the remainder of the study in all participants treated with Mavorixafor, whereas the frequency of severe infections on placebo remained unchanged. Additionally, we looked at antibiotic usage in the two arms. These data demonstrated that participants on placebo needed more medical intervention, which makes sense given the higher rate and greater severity of infections in the placebo group. Here we see that 10 of the 17 participants on placebo were treated with antibiotics over the course of the study, whereas only three of the 14 receiving Mavorixafor were given antibiotics. Again, let's hear reactions to these data from our physicians.
On the Mavorixafor trial, there was a reduction in both the frequency and severity of infections. This has significant clinical impact. Frequency of infection, of course, impacts quality of life in that patients require treatments or even hospitalizations more frequently, which translates in children to time lost from school or in adults, time lost from work.
The long-term consequence of severe infection is destruction of some function of the body, like lung function, respiratory, like also, maybe CNS functioning and so as or maybe joint infection. We, we will change major, the future of the patient in term of quality of life because we preserve the entire body. This is a good perspective for the patient, not at short-term, but also for the rest of his life.
The data showing reduced use of antibiotics in patients receiving Mavorixafor compared to those on placebo are actually quite important because the prolonged and frequent use of antibiotics leads to antibiotic resistance and the use of more broad-spectrum or more, and more expensive antibiotics. From the patient point of view, almost all patients prefer to have less antibiotic use. Most antibiotics have some side effects, particularly GI, and they also are aware of the risks of development of resistance.
Naturally, we're also pleased that the data revealed that Mavorixafor reduced infection rate and severity in the trial. Now we're at the final data set, which reveals results on the duration of these infections. We've heard that infections can prevent people with WHIM from participating in important life activities. As you'll see in the next slide, the results quite clearly favor the Mavorixafor-treated participants in the trial. Here you can see the Mavorixafor treatment reduced the total duration in days of infections by more than 70% as compared to placebo. In fact, those on placebo were sick for a mean duration of seven weeks throughout the year of the trial versus a mean of only two weeks for those treated with Mavorixafor.
Not only did Mavorixafor treatment participants get fewer infections that were less severe, but the total number of days they lived with an infection during the trial was dramatically reduced. This impact on duration of infections was evident in the patient exit interviews we conducted. We'll not be presenting the details of these data today. We can summarize that those on Mavorixafor reported better quality of life outcomes versus those on placebo. Let's again hear the reaction of our physician panel to these data.
The difference between seven weeks and two weeks is really rather striking if you think about it, because seven weeks is the best part of two months. If you're missing, for example, you're in school and you're missing, you know, a number of lectures, you're missing classes for close to two months in the middle of the calendar year, that could be a big problem. From the standpoint of an employee working in a job circumstance, missing close to two months of work, again, is even if it's scattered out throughout the year, that's really quite a bit of time. two weeks is something which is really much more of a handleable period of time to not lose, not only school, but work issues, I would say.
The duration of infection is a very important measure. The decrease in duration associated with Mavorixafor as opposed to placebo is very impressive. The longer an infection lasts, the more tissue damage and long-term sequelae are likely to occur, as well as the duration of antibiotic use and risk of development of resistance.
The implications of that data are several. First, the patient's quality of life and what they are experiencing in those extra five weeks is not to be trivialized. Being sick for seven weeks or effectively two months is extremely impactful, not only in how you're feeling physically but in your mental health. I think the other piece that is important to remember is that the longer you are sick, the more likely there is for the opportunity to develop chronic permanent damage. Clearing an infection more quickly, there is less likely to be perhaps permanent lung damage or scar than there would be in someone who is recurrently sick with a disease burden of two months.
I think that result is very meaningful for WHIM patients in terms of not only just what they experienced in one year and in the individual days of being ill, but also in the repercussions that could lead to down the road many years from now.
Let's now turn briefly to review the safety data from the trial. As a reminder, when we disclosed the top-line data last November, we also shared that Mavorixafor was well-tolerated in the trial, with no drug-related serious adverse events, no treatment-limiting toxicities, and no discontinuation due to safety. About 90% of patients continued on into an open-label extension study, which is ongoing. Most adverse events related to the background disease. The next slide will provide some further details. In this table, it's apparent that the placebo arm had dramatically more infections and infestations, as well as respiratory tract disorders. In fact, about four times as many when compared to those treated with Mavorixafor. As you can see, this is consistent with infection benefit with Mavorixafor treatment in the trial that we just outlined in the prior slides.
The Mavorixafor treatment arm showed an increase in skin disorders, which was mostly characterized as mild rash, eczema, and acne. GI disturbances were higher in the Mavorixafor arm versus those in placebo. The nature of these issues were infrequent nausea and vomiting. With both skin and GI disorders, all events were mild in nature, all resolved, and all patients continued on Mavorixafor treatment. All other safety assessments showed either a balance between Mavorixafor and placebo arms or were considered not drug-related. We believe these data continue to support the potential use of Mavorixafor as a chronic treatment for WHIM syndrome. We're pleased to report that we recently completed our pre-NDA meeting with the FDA. X4 provided the clinical data reviewed here today, along with other relevant data supporting a potential U.S. new drug application submission. The meeting was positive and productive.
Given this positive interaction, we are advancing our NDA preparation and are on track to submit early in the second half of 2023. As a reminder, should Mavorixafor be approved for WHIM syndrome, X4 Pharmaceuticals is eligible for a priority review voucher, which we'd expect to monetize to provide funding to support our commercial launch and continued growth of the company. I'll now turn it back to Paula to share a bit about our preparation for US launch. Paula.
Thank you so much, Murray. As you just heard, we're nicely on track for the U.S. NDA submission in the early part of the second half of 2023. In parallel, X4 is executing on the next steps to bring our innovative science to the market, now backed by this meaningful clinical data in WHIM syndrome. As we prepare for a potential launch in WHIM syndrome, possible in the first half of 2024 if all continues to go well, we are focused in the following areas. Building WHIM syndrome community, establishing X4 as a trusted partner with both the physician and the patient advocacy communities. As we actively engage with those physicians who are likely to see WHIM patients in their practice, we are helping to drive earlier patient diagnosis through disease awareness and genetic testing.
Based on our previously presented market research, we remain confident that there are many more WHIM patients than is currently estimated in the literature. It is our hope that our early outreach to the WHIM community will help us rapidly identify patients, which could lead to better outcomes for these patients. We are also working to enable broad patient access, clearly articulating the Mavorixafor value proposition and setting out to ensure that every patient who wants treatment has access to it, not only through our manufacturing and supply chain preparations, but also through a rapid and smooth reimbursement process. It is important to us that the patient feels supported on their entire journey. Lastly, as we as a company continue to evolve, we are taking a thoughtful approach to the implementation of systems and processes that are fit for purpose to support a launch in WHIM syndrome.
With the ultimate goal of leveraging all of our investments, not only to prepare us for a successful launch in WHIM, but also to lay the foundation for our potential future indications, such as chronic neutropenic disorders and possibly other primary immunodeficiencies. Across different geographies. Let's hear from our experts their final thoughts on the potential future for Mavorixafor.
Targeting the CXCR4 pathway has the potential to improve neutrophil counts, even in patients who lack a mutation in CXCR4. We see improvements in neutrophil counts in patients treated with plerixafor, for example. The pilot data with chronic neutropenia of a variety of causes also gave an encouraging signal that this may be efficacious in treating neutropenia more globally.
The most compelling information is that, of course, a single pill may reverse neutropenia in this group of patients. Of course, not completely. We should have more data, more situation, more genetic background for this demonstration. It's a very promising approach for many chronic neutropenia. A single dose of mavorixafor may improve the neutrophil count. We should demonstrate all the consequence of this in term of infection. It's the first step is to show that it acts on the neutrophils. We are full of expectation. I also will present this in term of action for probably all kind of human beings, because this pathway is something universal.
We know that we can reverse immune deficiency. Probably it open the gate to have a treatment able to improve the situation in various situation like other kind of neutropenia.
As you can appreciate, we and the WHIM-related communities are very pleased to see the significant impact that mavorixafor had on correcting neutropenia and reducing infection rate, severity, and duration in our WHIM phase III trial. We believe these data further support are moving forward as rapidly as possible to advance our trials in CN disorders. While those with chronic neutropenia by definition have low ANC, our research indicates that many of them also experience higher rates of infections than the general population. In fact, this morning's CIS abstracts include our research on this very topic. What we believe is the first study performed confirming the correlation between the annual incidence of serious infectious events, or SIEs, and the severity of chronic neutropenia.
A poster presentation of this robust research will be included at the CIS meeting on Saturday and will be also added to the publications page on our website. As we previously discussed, we currently have an ongoing phase II study assessing for durable increases in absolute neutrophil counts in those with various CN disorders, including idiopathic, cyclic, and congenital, with chronic treatment of once-daily oral mavorixafor. We expect to provide data from this ongoing study in the second or third quarter of this year. Additionally, we plan to engage the FDA to gain their input on a phase III trial design and registration path for mavorixafor in CN disorders in the same second quarter, third quarter timeframe.
As we continue to generate what we believe could be robust data in CN, we remain committed to seeing just how many patients this mechanism could impact, hopefully leading to a long-awaited and well-deserved innovation for the broader CN disorder communities. To conclude, we continue to believe that Mavorixafor has all the components to potentially deliver a transformative new option to people with CN disorders, first starting with WHIM syndrome. We've just successfully completed our first registration trial demonstrating clinically relevant increases in white blood cell counts and clinically significant impact on infections. We have a path forward to an NDA submission to support the potential U.S. launch in WHIM syndrome, and we are pulling out all the stops to advance the study of Mavorixafor in the broader CN disorders. However, we suspect that there are even more patients we could support.
As we continue to evaluate the data from the WHIM phase III trial, we are learning more about mavorixafor's impact on additional components of the immune system, the innate and adaptive components. We believe mavorixafor has the potential to treat additional subsets of patients with primary immunodeficiencies. This entire group of patients is in need of innovative new treatments, and we're committed to being there for as many patients as possible. As we conclude the prepared portion of our presentation today, we'd like to thank you all for joining us and to leave you with some final last words before we take your questions.
The mavorixafor phase III trial is an exciting one because I think the molecular target of CXCR4 has the potential to serve not only the WHIM immunodeficiency community but really does have the potential to expand into as an immunomodulatory agent in other diseases affected by the immune system. I was very excited that, The safety profile was so good, that the efficacy, in reduced infections and the primary endpoint of ANC were met because I think that this oral CXCR4 antagonist has the ability to be impactful beyond WHIM.
I want to express my gratitude for recognizing that we're people and that we are just as important and even with an ultra-rare disease, it's so wonderful to know that people are actually looking at ways to help us.
Thanks to Dr. Tarrant and to Courtney for those meaningful remarks highlighting the importance of our work on behalf of those with rare diseases and communicating the excitement for the potential of Mavorixafor to treat patient populations even beyond those with WHIM. Before we head into Q&A, we'd like to mention a couple of things. One quick correction to our program, which we clearly pre-recorded. We just learned this morning that CIS has pushed out its abstract publication date until this Thursday, May 18th. The abstract is not currently on their website. Given the last minute change, they've granted us an embargo waiver for this event. The oral presentation is still being given by Dr. Badolato this Sunday at 11:30 A.M. Central Time, and we will be uploading those slides to the Posters and Presentations page on our website.
One other update, as we announced earlier today, we are very pleased to have completed a significant financing, raising $65 million in gross proceeds from an at-the-market private placement to further advance our development of mavorixafor. This was done with the support of some new top-tier investors, including Adage, Stonepine Capital, and Kingdom Capital, along with the strong support of our existing investors, including NEA, Bain, Acorn BioVentures, OrbiMed, and others. With these impressive data demonstrating the efficacy of mavorixafor in the 4WHIM trial, a strong balance sheet to support our business into the fourth quarter of 2024, along with the potential to monetize a priority review voucher in 2024, we believe we are well-positioned to continue to grow our business, advance our clinical and commercial efforts around mavorixafor, and deliver this potentially groundbreaking treatment to as many patients as possible. We'll now open the event to questions.
Thank you, Paula. At this time, I'd like to remind the audience on how to submit questions. For our analysts, please raise your hand to indicate you would like to join a queue and ask the questions. To the audience on the webcast, you may submit your questions through the written Q&A function at the bottom of the player. You may have to exit full-screen mode to see that feature. With that, we'll go ahead and take a question from our first analyst here, Edward Tenthoff at Piper Sandler.
Great. Thank you very much. Can you hear me okay?
We can. Thanks, Ed.
Great. Well, thank you for just a fantastic presentation today. I really appreciated all the detail, both from the clinicians as well as the patients on what it's really like to experience WHIM. I had two questions I wanna make that are a little bit different. Firstly, how much does it cost to care for a WHIM patient? Do we have that kind of data? How relevant are those cost savings going to be for potential payers who will ultimately reimburse us? I was intrigued to see sort of the flip side of the mechanism of actually having some skin issues. I don't think they were too severe.
I just wanted to ask the physicians who are logged in if that raises any questions or if that might require any monitoring on their part, just to keep an eye on any kind of autoimmune-like syndrome. Thank you so much.
Sure, Ed. Thanks. I think what I heard was a little bit of how do we think about the value proposition of WHIM in the context of the background disease and our treatment, and secondly, was around the skin-related findings, and we'll ask perhaps Dr. Tarrant that question. I'll take the first one and ask Mark Baldry to join. Really the exciting thing that we're at right now is we've just completed a placebo-controlled trial. What we're really excited about is to determine the true clinical impact of the drug. No one has studied WHIM long term to understand the burden of care, both in terms of costs and patient impact. You heard a lot of the commentary about the long-term sick quality of having repeated infections.
I think we need to just take this data and really do our health economic outcomes research to bring the true value proposition to the payer systems and really capture that as best possible. Of course, these data are a great step forward. I'll now actually ask Dr. Tarrant to please comment if she could, since she was involved in the trial on any perspectives on safety.
In terms of, I guess also to speak to the value of having a medication to prevent long-term complications. To contextualize, I am an internist, so I actually take care of the adult side of immunodeficiency, which is unusual because a lot of folks are in the pediatric space. I end up seeing these patients with some of the long-term health chronic, outcomes in primary immune deficiency. I agree with Paula, this is really hard to put a dollar statement onto that because as you've learned about WHIM, it's so incredibly variable in terms of people's experiences. I don't know if there's just an average patient that you can really speak to do economics on. As you can imagine, multiple hospital admissions for IV antibiotics.
In the case of my patient, one of the patients I care for, she has had maybe 10 or 15 surgeries for HPV, which is the virus associated with the warts. She has had multiple surgeries and cancer treatments for the cancer, cervical cancer and vulvar cancer, that have become extensive since she's now in her 40s. We'd love to think that, you know, when you're addressing a root cause, which the CXCR4 Mavorixafor antagonist is, if you're addressing the root cause of a disease that you could potentially prevent many of the complications that these patients do suffer from long-term, to get at that. Was there something more you wanted me to speak to with the skin?
With respect to the, I guess, is there any way that we could actually promote almost autoimmune-like syndrome if we turn on the immune system too much?
Okay. I think if I'm understanding correctly, it's can one develop autoimmune sequelae from being on chronic administration of Mavorixafor? Is that Am I paraphrasing correctly?
Well, part, yeah, kind of from the mechanism.
Okay.
Again, I don't think there's any signals of that from the clinical data yet.
No.
Is it something in your head is that you might be worried about? Thank you.
It is not. I am a rheumatologist, in addition to allergy immunology, I'm also boarded as a rheumatologist, and I take care of autoimmunity, as kind of the main purview under rheumatology. We don't really think of this target as necessarily being involved in the autoimmune axis of many of our autoimmune diseases, and I would speak to psoriatic arthritis, rheumatoid, multiple sclerosis, inflammatory bowel disease. I have no concerns there as a clinician and someone who's an expert in autoimmunity. You'll never know. Obviously in, you know, a year-long trial, you have only a certain amount of clinical data that you can see in the trial, but both WHIM itself and the target itself do not concern me for enhancing autoimmunity.
That is incredibly helpful. I appreciate your time and perspective.
Thank you for the questions. The next question comes from William Wood at B. Riley.
Hi. Thanks for taking our questions today and many congratulations on the impressive infection data disclosure today. On your FDA interactions, glad to hear you've had a pre-NDA meeting already and wondering if you were able to get any insights on how they may think similarly or differently about severe chronic neutropenia relative to WHIM in terms of choice of ANC endpoint, but also the relevant clinical outcomes. I know there have been some G-CSF studies done in CN, whereas obviously you didn't have insight in WHIM, although they are quite old. Maybe if you just give us any extra color there, that'd be helpful. One follow-up.
Sure. Murray, would you like to, kind of paraphrase where we're at with our regulatory strategy in CN?
Yeah. In CN, we've obviously got the phase I data showing an increase in ANC. We're doing phase two to show whether that's durable. The plan would be to go and discuss with the agency our phase three plans. We've already had some preliminary discussion with them regarding what the study would look like. They agreed that it should be on top of standard of care rather than versus GCSF, given the challenges with the variable doses people are on. We're mapping out a plan of Mavorixafor versus placebo on top of standard of care, which may or may not include GCSF. We are submitting questions to the FDA. The plan will be to discuss that in the next few months.
Excellent. I greatly appreciate that. For the second question for the experts, the infection data looks quite impressive in different ways, you look at it. Are you able to provide similar color on how the wart disease burden is being thought of? Maybe if we could also characterize the skin adverse events that were noted here.
Sure. Teresa Tarrant , would you like to take that?
Yeah. With respect to the warts, one of the things that I think was really outstanding about the way the trial was designed for WHIM is that it was one of the first times that we had a placebo arm. Really, I think we didn't understand the nature of CXCR4 antagonism and warts in general in terms of how to study them, how to measure them, how to follow them over time. We actually learned that warts in and of themselves go up and down regardless of treatment. I think previously we've made some assumptions as clinicians that may not have been correct, that medicines that we were using made the warts go away when actually the natural history is such that they recede, and they come back, and they recede, and they come back.
As you saw from the data, in the group that was on mavorixafor, there were not any evolution really of new or worsening warts. It didn't necessarily make the warts that they had recede in a kinetic that maybe looked different for the brief time shot that we looked at. Remember, this isn't the lifetime of a patient. It's a 52-week trial. For that snapshot in time, we saw no new recurrence of warts. There's many ways you can look at that data. You could say, number one, the natural history of warts, which is very poorly understood, we might need longer time spans to understand the true impact of the drug. That's one thing.
The other thing you could look at is perhaps CXCR4 antagonism works better as a preventative than as a treatment strategy. That makes a lot of sense. That may be. What we might find in these patients that are in the extension, you know, when we're following them much longer, that those patients may have their warts go away, and they may not develop any new ones. I think there's still a lot of questions. You know, CXCR4 is something that in terms of skin and cutaneous manifestations, we are still learning a lot more about. I think that that's just an area still of scientific investigation. Certainly, the data only looked promising. It did not look in any way discouraging.
Got it. Appreciate that extra color. Congratulations again on the great information we saw today. Thanks for taking our questions.
Thank you for the questions. The next question comes from Kristen Kluska at Cantor Fitzgerald.
Hi, everyone. Let me also add my congratulations, and it's really great to see in perspective what it does for the patients, hearing from them directly, so appreciate those comments. The first question I had for you is hearing some of these patients' stories, it seemed the theme was clear that over time they were experiencing a number of infections, and they got diagnosed around their teenage years, early twenties. I wanted to ask, and I know the X4 team's doing a lot of work on patient awareness, but how do you think that adding a potential therapy to the market, driving awareness, is going to potentially lead to some of these patients perhaps getting diagnosed earlier?
Thank you, Kristen. Mark, would you like to address that?
Sure. Thanks, Kristen. Yes, you know, we currently estimate there are 1,000, at least 1,000 patients, living with WHIM in the U.S. But as you say, that's all in the context of poor disease awareness and really no treatment for this disease. There are likely to be, you know, many more undiagnosed patients out there or misdiagnosed patients. With that said, you know, we've got a team out and have been actively engaging with the community to educate and raise disease awareness and help drive earlier diagnosis of these patients because, you know, that leads to better patient outcomes. And we've been really pleased with how we've been received out by the community and their level of engagement.
Looking forward to providing more details regarding our launch readiness later this year.
Thank you for that. Looking at the specifics across the board, there was quite a number of different infections, and some of your thought leaders highlighted that the lungs and bacterial in particular are some of the more problematic. Wanted to ask if the patient population in this is what you would expect in real life, meaning the types of infections that you saw the most. You also highlighted that this was during the COVID-19 pandemic, some of the enrollment. Wondering if that played into a role at all as well. Thank you again.
Murray, would you like to take that and then maybe invite the clinicians as well?
Yeah. I think the population did represent the true WHIM population, so we didn't have any unusual inclusion or exclusion criteria that would have meant we were looking at subpopulation. In fact, we did a screening and I think there were hardly any dropouts in the screening. I think the population does represent the true WHIM population. I was a bit worried with COVID that we wouldn't see that many infections given the isolation. I think obviously it's a speculation, but if they were. The placebo group may have had more infections, and you might have seen an even bigger delta if people weren't isolating. That's speculation. I mean, we've got the data we've got. I think it's a true reflection of WHIM.
The patients were isolating, so, despite that, there were still infections showing how sick the WHIM patients are. They were all severely neutropenic.
Thank you.
Thank you for the questions, Kristen. The next question comes from Stephen Willey at Stifel. Stephen, can you hear us?
Hi. Can you guys hear me okay?
Yes. We can.
Sorry about that. This was great. Thanks for thanks for the presentation. Maybe just for the attending physicians, just curious how you would juxtapose the difficulty of improving infections in a WHIM patient versus, I guess, a more typical CN patient with a non-congenital subtype. I know WHIM's obviously a more complex form of CN, but just trying to think about the read-through of this data into a broader CN population. Maybe just as a follow-up, would you expect the kinetics of infection rate improvement to be similar in CN as well, whereby you're seeing most of the benefit occurring after three to six months of treatment?
Well, thanks, Stephen. Actually, we'll invite Dr. Shimamura to provide her kind of experience with the chronic neutropenia patient population.
Share her perspective on how she thinks about the potential of what we've seen in WHIM with potential of what could be for her patients with CN. Dr. Shimamura, would you like to comment?
Thanks so much for that question. I think the pathophysiology of the congenital neutropenias is somewhat distinct from that of WHIM. In WHIM syndrome patients, they are able to produce neutrophils, but the neutrophils are stuck in the bone marrow, and Mavorixafor helps them mobilize that and get the neutrophils to where they need to go. With congenital neutropenia, the issue is their marrow is having trouble making sufficient neutrophils, and with production can be at different rates. In the pre-G-CSF era, many of these congenital neutropenia syndromes were uniformly fatal early in childhood due to infection. G-CSF was a game changer with congenital neutropenia. You might say, "Well, what is the benefit then of Mavorixafor?" The benefit is huge because there are issues with G-CSF. I can just rattle off a few.
One, it's an injection, often a daily injection. People have tried the long-acting G-CSFs, those are difficult to manage in these patients. We've had much better luck with the daily or, you know, regular injections. As you can imagine, little children hate it, the adolescents hate it, the young adults hate it, and everybody hates it because it's stressful. It's hard to have to travel around with your syringes if you're traveling. Compliance is a big issue, actually. Two, there are side effects to G-CSF, which we're not seeing with the Mavorixafor. They can get severe bone pain that can be debilitating. They can get skin sores from the injection sites.
Lastly, G-CSF, because it works by trying to push production of neutrophils, carries a potential risk of stimulating a sort of pre-leukemic or malignant cells, which you avoid with something like Mavorixafor, where it's not really pushing production, it's just allowing those naturally produced cells to get out of the marrow. I think that there are some important distinctions that, although G-CSF is quite effective, it has those limitations that Mavorixafor nicely addresses.
Okay. That's helpful. I know the company talked about kind of what they're doing on the disease awareness and genetic testing efforts, but I guess just given the underlying variability of the morbidity associated with this disease, can you also speak to approximately what proportion of patients identified would you expect to be candidates for therapy? Is this something that you're giving to all confirmed WHIM diagnoses?
Maybe I can invite Dr. Tarrant or, and also Dr. Shimamura, either one, but I think Dr. Tarrant had a few WHIM patients in her practice currently.
Yeah. You know, kind of again, I've commented on this before, but the idea is that, you know, this medication treats the root cause of the disease. If someone has a molecular defect in CXCR4 and they are clinically presenting with some of the features of WHIM to where you felt confident that they had this immunodeficiency, then I would offer it to the patient. I think that's different. And maybe to kind of get at your question a little bit in a more nuanced way, you know, IVIG, you know, this is a therapy we offer to WHIM patients, but only patients who have very low immunoglobulins that are not working correctly. That is an intervention or a medication that I selectively would offer to patients.
I guess I would speak to the fact that if I had a medication that addressed the root cause of the illness, I would probably offer it, you know, without exception to every patient and counsel them in the, in the benefits as well as side effects and risks, and allow them with shared decision-making to make that choice. It certainly would be offered, and I don't see any reason not to from the patients I care for.
Can I squeeze in one quick more question? I know there wasn't a reduction in, I guess, pre-existing morbid burden per se, but I know that we've heard from a couple of the physicians just about the impact of secondary malignancies that are caused by HPV infection. Just curious if there would be any attempt to serotype HPV in these patients and whether or not you would expect to see a reduction in the oncogenic HPV strains 16 and 18. I guess how important would that be to the overall value proposition? Thank you.
Sure, Steve. I'll kick it off and certainly invite others to comment. We are actually trying to study that. There has been a phase II or phase I/II study reported by the NIH, where they looked at changes in serotype with a different CXCR4 antagonist called plerixafor, and there was actually quite a dramatic and favorable impact in that particular metric. We are repeating some of those same metrics. They're not easy technically to do, but stay tuned. We hopefully will have an additional breadth of data that can help us all appreciate, either through the HPV vaccine or looking at serotypes, what Mavorixafor might be doing to hopefully reduce the risk of HPV associated in this patient population as well.
All right. Thank you very much.
Thank you for the question. The next question comes from Marc Frahm at Cowen.
Thank you. Congrats on the data and the, you know, really strong infection reduction. Maybe during the presentation you discussed reductions in antibiotic use. Were any changes seen in IVIG use also?
I usually see that.
Yeah. We kept IVIG use the same. A few patients came on on IVIG. We deliberately didn't change that. We didn't want any confounding factor. We would do another study about whether people need it. During the phase III, it was appropriate not to change their background therapy.
Okay, thanks. Maybe just if there's any more details you can provide on the severe infections that were seen, maybe if they happen to be Dr. Tarrant, any of your patients, just any color you can give on kind of the difficulty of managing some of these infections that are seen.
Murray, I'm sorry.
Yeah. I was gonna say, with respect to the trial, we're blinded. You know, I can't speak to an individual patient's experience both for HIPAA reasons and for being blinded. Murray can follow up.
Yeah. we saw a spectrum of infections. someone had food poisoning, because they had Fallot's tetralogy, they actually ended up with bacterial endocarditis. We had other individuals with pneumonitis, an individual with really bad cellulitis and abscess formation that continued. what you may have, if you're eagle-eyed, you would have spotted that not only the longest someone was ill was for over 150 days, so they meant they were ill for 6 months. the person with cellulitis and abscess was unwell for months. that's a flavor. I think the type of infections, respiratory, cellulitis, abscesses, pneumonitis, pneumonia, bacterial endocarditis, a range of infections that you do get if you're immunocompromised.
Okay. Then maybe, Dr. Tarrant, you touched on this a little bit, just, you know, maybe some hypotheses as to why the wart burden didn't change. Can you speak more to the difference between kind of the infections that were being seen, the respiratory infections and things like that were certainly going down versus warts and maybe Dr. Shimamura, how you think about that for when we look at the CN indication for the types of infections you have to worry about and what that means for those types of patients?
I'll go first and then I'll let Dr. Shimamura. With respect to warts, and that's kind of what I'll speak to as opposed to chronic neutropenia, which is Dr. Shimamura's area. With respect to warts, if you break down what type of immune cells fight against HPV versus what types of immune responses fight against bacterial infections, they are very different arms of the immune system. In terms of what fights infections quickly, it's antibodies and it's neutrophils. Those are your kind of first in line host defense to respond quickly to infections. You're looking at responses then of your drug on aspects of the immune system that work quickly versus aspects of the immune system like T cells, which are more involved in the antiviral response.
There may be different kinetics of the drug and its effects on different subpopulations of the immune response. When you get a bone marrow transplant, and Dr. Shimamura is gonna tell more about that probably, but when you get a bone marrow transplant, immune cells come back at different rates. T cells are some of the last to come back and behave normally. Here we've got a drug that's working on all immune cells because all immune cells have CXCR4 on its surface, and all immune cells are responding to CXCR4 in the way that they migrate and the way that they proliferate and the way that they leave the bone marrow. It's just a natural part of how immune cells get around the body and move between spleen and bone marrow and where they need to go.
Those responses are probably subtly different in different immune cell subsets. My hypothesis would be that it's having a differential response on T cells, which is more important in HPV host defense. That may be something that takes longer for that to happen than where you'd see a neutrophil response or an antibody response. I'd be delighted to hear more from Dr. Shimamura about her perspective.
I completely agree with all of that. I would say in the neutropenias of... it's really a wide heterogeneous set of disorders, some of which are characterized by solely neutropenia and the immune system that Dr. Tarrant elegantly described. The immune system, the lymphocytes, are intact. In those patients, we don't see the warts, we don't see the increased risk of HPV or viral infections. We basically see problems with bacterial infections and fungal infections. There are also congenital neutropenia disorders other than WHIM that have a combined neutropenia plus immunologic abnormalities. Those patients are more at risk for the viral complications as well.
I was following the data in the WHIM patients with a lot of interest because it's really quite relevant clinically, potentially, if it works, for both the pure neutropenia patients as well as those with these mixed, sort of neutrophil and immune system lymphocyte conditions.
Thanks. Very helpful, and congrats again on the data to the team.
Thanks, Mark. The next question comes from RK at H.C. Wainwright.
Hi, Paula. Can you guys hear me? Thank you for doing this. Congratulations on the data. Certainly a great discussion so far. Obviously, a lot of aspects of the drug and the benefits have been discussed. As physicians on the panel, you know, if you're thinking about the overall clinical benefit because that's what is basically going to be looked at by the regulators. What is clinically meaningful, and for these patients, because talked a lot about infections, a little bit about the secondary issues or concerns that, you know, this drug really helps out with.
Overall, what are the aspects that, you know, as a regulator and as the clinicians who help the regulators you folks are, want to see? You know, if you can discuss through the clinical meaningfulness, that would be helpful just to see an overall aspect of it.
Thanks, Mike. I think just to summarize, there's sort of two layers to this. One layer is how clinically meaningful do you see this data set to the clinicians? I'll probably invite Mary in to comment about kind of how that translates to the FDA's perspectives, given our clinicians have yet to interact with us on the FDA discussions. Dr. Tarrant, would you like to share a little bit more?
I mean, I think, any time you have the opportunity. You guys met virtually, some of our patients and understand, I hope, a little better what it's like to live as a person with an immunodeficiency. We all thankfully on this panel, don't have to do that.
If you have the opportunity to fill a gap, meaning that there's nothing in this space to give these people, you can only imagine if, you know, you're the parent of a small baby who's been sick and you're coming to the doctor, and they're like, "Great news, I know the diagnosis of your baby, and I can tell you what's gonna happen to them, but we don't have anything for you." You know, imagine what that must feel like, you know, as a parent, and then as you're growing up as a kid, you know.
You shouldn't do this 'cause you might get sick." "You know, this might put you in the hospital." If you have a medicine that can address the root cause of a disease that you're born with that cannot otherwise be changed or impacted substantially, you know, this is an incredibly important innovation in medicine. I think the FDA does take that into consideration, which is why we have special types of approvals for orphan diseases, which WHIM is. So like that one patient said to us, you know, "I feel like I'm being seen now. I feel like people actually care about what I'm going through." So this is something that isn't, you know, necessarily a population drug. It's personalized medicine at its best, going from bench to bedside.
I think that that is incredibly meaningful for me now as a doctor to be like, "Great news, I have something that can help you." I'm no just giving you a diagnosis and telling you, "Here's the label, and let's just cross our fingers." I actually have something that can maybe really help you.
I completely agree with everything that was just said, so beautifully. I would say that in addition to all of the points that were made very nicely by all of the physicians, about the risk of severe infections, life-threatening infections or irreparable organ damage, irreversible organ damage. The points that were just made about life, the quality of life is really important. I just saw a patient yesterday, a little baby, who does not have WHIM, but has a neutropenia condition that we're still working out. We're still not sure how to treat them 'cause we're still figuring out the diagnosis. That means that every fever, that family has to go to the emergency room. Fevers always occur in the middle of the night. They never occur when the clinic is open.
They're in that emergency room sometimes every week or every other week, because if it's an infection, a bacterial infection, it's life-threatening. If we wait till they look sick, it's too late. We may not be able to get it under control with antibiotics. We can't wait till they look sick. It's hugely stressful for the parents. It's terrible for the children. That's what it's like for some of these patients to live with these severe immunodeficiencies. A drug that can give you, that can improve your immune system can be life-changing in addition to reducing the infections, but also just reducing this kind of life of living under this shadow of never knowing when the sword's gonna drop.
Thank you both. I think that concludes the verbal portion of the analyst Q&A session. I'll now turn it over to Dan Ferry at LifeSci Advisors for any questions that may have come in over the webcast.
Yes, thank you. Paula, we have a few written questions from the audience. The first is: Would you see this providing support for chemotherapy-induced neutropenia for cancer patients?
Thanks for the question. Of course, we always try to think about where is the unmet need to help as many patients as possible. Certainly there are existing treatments today to support patients with chemotherapy-induced neutropenia. There's always the potential for those that can't be treated or are less tolerant to some of the challenges with the long-term treatments for Neupogen and Neulasta or the other generic versions. We're open, but we really do wanna go where there's the highest unmet need. Hearing today from our clinicians about how they're trying to manage these patients with lifelong neutropenia is really where our heart and our intent is right now. Of course, we always wanna see where the drug might go to help as many as a broader patient as possible.
Okay, thank you. Our next question is: Is management actively pursuing partnerships or deals for WHIM and or the CN indication?
Yeah. I think we even mentioned at the start of the year, of course, with our positive phase III data that we announced in November, as well as now this amazing data showing clinical benefit. There are certainly interest in the, in the global field around immunodeficiencies. There's some very committed companies aiming to improve the lives of patients with immunodeficiencies. We are exploring some ex-U.S. opportunities, but there's nothing to report just yet. Of course, we always wanna do what's best for our company, our patients, and all of the stakeholders, including our clinicians. Early days, but of course, getting this drug to as many patients as is appropriate will certainly be part of our mission.
Okay, excellent. The next question is on pricing. Have you discussed a pricing range with payers?
Yeah. We've done some early work. I'll ask Mark Baldry to just comment a little bit on some of that preliminary work and also help us think through longer term. Mark?
Yeah, thanks. While we're not discussing specific pricing details, we do believe that WHIM syndrome supports orphan drug pricing. I think importantly, what today's data really underscores, showing the benefit of Mavorixafor on infections, our market research indicates that's really where the value lies in the eyes of payers. We're excited by what this data means and when we look to take this data out to payers and engage with them now, as this is what they told us is important to them.
Okay, great. Paula, where do you see this company in the next two years?
Well, we're excited to certainly hopefully gain approval in WHIM in the U.S., continue to advance our ex-U.S. strategy as well. We hope to bring the drug to as many patients in countries across the world. We're really excited about CN. I mean, CN is certainly the next largest patient population that we could hopefully impact. I mean, you heard from Dr. Shimamura these heartbreaking stories about families. It wasn't even something I was fully appreciating until she shared these stories of, you know, the ER is only the place that, you know, seems to call you in the middle of the night.
We're hopeful that in two- years, we'll be well on our way with our CN data, our phase III trial in CN, have this drug launched in U.S. and many other countries, and then continue to explore the potential Mavorixafor. We gave little hints that there's a broader set of data here that may support additional indications beyond WHIM and CN, and we look forward to sharing some further details in the next six to 12 months. We won't stop till we really scientifically understand what this drug can do and then how many patients it can help.
Okay, great. One final question that just kind of came in here. We have time for one more. Why should a drug with this mechanism of action work with CN patients that do not have CXCR4 mutations?
That's a great question for Dr. Shimamura, 'cause I think, she's an expert in thinking about this. I'll pass that over to you for the final comments.
It's a great question. I was actually surprised. I was skeptical that the initial pilot study would show any signal, and it did. Even in congenital neutropenia patients, a lot of the neutrophils that are there, we're not seeing because they're not mobilized. And even in healthy people, if you give them plerixafor, they'll mobilize, right? I think even in healthy people without this mutation, it can cause mobilization of stores. The idea in the CN patients is to do that. Whether the response will be sustained remains to be seen. I think that it's important to test because I would not have predicted that the pilot study would have shown a signal, and that was really very encouraging.
I have to tell you, I direct with Peter Neuberger, the Neutropenia Registry in the U.S., and these patients are ecstatic at the prospect of a potential oral drug, as opposed to these injections. They're very motivated to participate in trials, and I think there's a lot of excitement in the field. You're right, it remains to be seen in trials.
That nicely lines us up for our next corporate milestone, which we will deliver in Q2 and Q3, which is more data on durability in CN patients in our registration trial. Stay tuned, people. Come on back.
Thank you very much, Dr. Paula Ragan and everyone for participating today. This concludes the event. Thanks everyone for participating, you may disconnect your line.