X4 Pharmaceuticals, Inc. (XFOR) Earnings Call Transcript & Summary

Greetings, and welcome to X4 Pharmaceuticals Post-EHA Corporate Update Conference Call. [Operator Instructions] As a reminder, this conference call is being recorded. It is now my pleasure to introduce your host, Candice Ellis, Director of Corporate Communications and Investor Relations at X4. You may begin.

Thank you, Andrew, and good morning, everyone. Thanks so much for joining us as we discuss the positive clinical data on our lead candidate, mavorixafor, in patients with WHIM syndrome, which was presented virtually earlier this morning at the 25th European Hematology Association or EHA Annual Conference. As a reminder, we will be making forward-looking statements regarding our regulatory and product development plans as well as our research activities. 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 Form 10-K on file with the SEC. Presenting on today's call will be our Chief Executive Officer, Dr. Paula Ragan; and our Medical Director of Rare Diseases, Dr. Sarah Cohen. In addition, our Chief Scientific Officer, Dr. Renato Skerlj; our Chief Financial Officer, Adam Mostafa; and our Senior Vice President of Technical Operations and Quality, Mary DiBiase, will be available during the Q&A session following our prepared remarks. Please note our EHA poster is available within the Posters tab on our website. I'd now like to turn the call over to our Chief Executive Officer, Paula Ragan.

Thanks, Candice, and thank you, everyone, for joining us on the call this morning. We are highly encouraged by the positive biomarker, efficacy and safety data presented at EHA today from our ongoing Phase II open-label extension trial evaluating mavorixafor in patients with WHIM syndrome. Before we review our exciting EHA results, though, let me begin on Slide 4 by providing some brief background on WHIM syndrome and the unmet need. As you may know, WHIM is a rare genetic primary immunodeficiency that results from a gain-of-function mutation in a single gene that encodes for the CXCR4 receptor, a primary player in the signaling pathway that regulates proper immune cell trafficking and surveillance. The genetic mutation leads to premature truncations in CXCR4, causing the receptor to remain in an on state longer than normal due to the overstimulation by its ligand. The result is immobilization of mature immune cells in the bone marrow, reducing the body's ability to achieve a healthy immune response. The bone marrow of WHIM patients is filled with degenerating white blood cells, including apoptotic neutrophils, rendering them immunocompromised. The W-H-I of WHIM stands for breadth of clinical presentations of the disease which include warts, hypogammaglobulinemia, infections and myelokathexis. And I'll share more about what that all means in the life of a patient shortly. But importantly, for patients in their journey towards healthier lives, genetic testing is available and used to definitively diagnose WHIM syndrome. However, genetic testing of WHIM is available on a limited basis due to reimbursement limitations in the earlier stages of diagnostics. And this has led to challenges in understanding the true prevalence of WHIM syndrome. At X4, we've taken it upon ourselves to better understand this. And based on external market research and studies we've conducted over the past year, we believe there are more than 3,500 diagnosed and undiagnosed WHIM patients in the U.S. today. Unfortunately, for these patients, there are currently no approved therapies to treat WHIM syndrome. Therefore, as Slide 5 indicates, there remains a substantial opportunity to treat the problems of WHIM syndrome, which are defined by 3 core issues, a three-legged stool, if you will. These 3 distinct unmet needs are low white blood cell count, chronic bacterial infections and severe wart burden due to HPV and its associated cancer risks. So a bit more about these problems associated with the 3 legs of the stool. Low white blood cell counts are caused by myelokathexis, which is the M in WHIM syndrome. These dramatically low white blood cell counts lead to neutropenia and lymphopenia and their associated risks. Increased bacterial infections are the second leg of the stool and impact multiple organ systems. Repeated bacterial infections of the lung leads to loss of lung function and bronchiectasis. Chronic bacterial infections of the ear can lead to loss of hearing. Severe skin infections such as cellulitis, meningitis and sepsis have all been reported as a result of bacterial infections in WHIM syndrome. The third problematic leg of the stool is defined by their inability to clear the HPV virus, which can result in disfiguring and massive wart burden and an increased risk of HPV-associated cancers. As mentioned, there are currently no approved therapies specifically for WHIM. Standard of care includes nonspecific treatments, such as antibiotics, G-CSF and immunoglobulins, but none of these approaches address the mechanism of the disease and the totality of the severe symptoms associated with it. Turning to Slide 6. I'll now introduce mavorixafor, a drug which has the potential to be disease-modifying for these patients. Importantly, I will provide the scientifically-founded rationale as to why mavorixafor has the potential to robustly address all components of WHIM's three-legged stool. Mavorixafor was designed to target the problematic gain of function over signaling in the receptor, which is the root cause of WHIM. The drug is a first-in-class oral small molecule antagonist of CXCR4 that has high potency and selectivity. Mavorixafor binds the extracellular transmembrane regions to allosterically inhibit receptor signaling by its ligand, thus targeting the mechanism of the disease directly. As a small molecule with a 22-hour half-life, we are developing mavorixafor as a once-daily oral capsule. We now have significant experience with mavorixafor in nearly 200 patients. We've demonstrated dose-dependent mobilization of neutrophils and lymphocytes, a favorable safety profile in patients on therapy for more than 30 months, and we have developed clinical points of validation through our successful Phase II trial in WHIM and in multiple other Phase I/II trials in other indications. We have strong alignment on our global Phase III design with both U.S. and European regulators, which, if successful, would support full approval of mavorixafor for WHIM syndrome. Additionally, we have received breakthrough therapy designation in the U.S., which we believe recognizes the meaningful data generated in our Phase II trial in support of these patients' high unmet need. And we've also received orphan drug status in the U.S. and Europe, and our critical U.S. composition of matter and U.S. patents are expected to provide patent protection through 2038. Moving to Slide 7. I'd now like to provide a brief introduction to our EHA Abstract #EP852, a summary of our Phase II clinical trial of mavorixafor in WHIM patients. The headline that I hope you walk away with today is that data generated in our Phase II open-label extension study, where we treated WHIM patients chronically with mavorixafor, favorably impacted all 3 problematic legs of the WHIM syndrome stool and robustly support the Phase III trial design. Our Phase II study demonstrated, first, large increases in white blood cell counts in all patients, and that these increases were durably maintained over the 28 months of dosing; second, decreases in bacterial infections that showed deepening responses with time on drug; and third, major reductions in wart burden, and specifically visible and profound reductions in warts for one of our patients most impacted by this aspect of the disease. And with that, I'd like to turn the call over to Sarah for a more detailed discussion of these important data. Sarah?

Thank you, Paula. I'd first like to review the protocol for our Phase II study on Slide 8. As Paula mentioned, WHIM syndrome can be thought of as a three-legged stool, because WHIM manifest as reduced total white blood cells, increased infections and increased human papillomavirus or HPV warts. We conducted an open-label prospective dose escalation Phase II study at 2 clinical trial sites located in Australia and the United States. The objective of the study was to assess the safety and long-term efficacy of mavorixafor in patients with WHIM syndrome. We conducted dose escalation over 25 to 52 weeks with patients dosed with mavorixafor once-daily from 50 milligrams and up to 400 milligrams. We observed the effect of each dose on the total white blood cell count, absolute neutrophil count and absolute lymphocyte count. To do this, blood samples were drawn at 11 time points during 24-hour in-resident periods at weeks 5, 13 and 21 and then during the extension period. The study also focused on the clinical impact of this treatment and, in particular, on changes in infection rates and wart burden. To do this, we compared the annualized infection rates at each dose to the infection rates in the 12 months prior to the study. And we evaluated the dermatological response by counting the number of warts on the hands and feet. With this approach, we consider that the study would enable us to determine the potential for mavorixafor to have a disease-modifying impact across all 3 key elements of WHIM syndrome: white blood cells, bacterial infections and warts. The trial included patients aged 18 years and older with a confirmed pathogenic CXCR4 mutation and with baseline neutrophils below 400 cells per microliter and/or lymphocytes below 650. As you know, WHIM patients have very low neutrophils and lymphocytes, which makes them susceptible to bacterial infections and warts. Exclusion criteria listed here included the use of treatments that could introduce bias in the levels of neutrophil and/or lymphocyte counts or which could cause predictable drug-drug interactions. Moving to Slide 9. We see that mavorixafor positively impacted the white blood cell count, which, you will recall, is the first leg of the stool. As you can see on the figure on the top right, mavorixafor effected a dose-dependent increase in total white blood cells and the 400-milligram dose resulted in the highest change in white blood cells compared to baseline values, supporting this dose as a selected dose for the Phase III study. Additionally, we examine the impact of mavorixafor on neutrophil levels and lymphocytes and set predefined thresholds for success. The threshold for neutrophil count success was 500 cells per microliter, which corresponds to a clinically-accepted low-risk profile for infections. The threshold for lymphocytes was set to 1,000 cells per microliter, which approaches the lower limit of normal. The figures on the bottom show that increase in doses of mavorixafor enabled dose-dependent increases in absolute neutrophil counts and absolute lymphocyte counts. From this trial, we defined a very important parameter, which is called the time above threshold for absolute neutrophil count. This time above threshold for neutrophil is a primary endpoint in the Phase III trial and is defined as the time in hours during which we are able to elevate the neutrophil count above the 500 cells per microliter threshold. As you can see on the figure on the bottom left, it is clear that the 300- and 400-milligram per day doses were required to maintain the neutrophils above the 500-cell threshold. And what's really interesting is that while some patients did respond at 300 milligrams, increasing the dose to 400 milligrams allowed even more patients to elevate their neutrophil above the threshold of 500 cells and meet the criteria for success. Here on Slide 10, as Paula covered earlier, you can see the impact of treatment on infections, which are the second leg of the stool for patients suffering with WHIM syndrome. In this Phase II study, we examined yearly infection rates for patients -- for each patient in the 12 months prior to enrollment and then monitored their infection rates while on treatment. As you can see on the figure on the bottom left, the yearly infection rate in the 12 months prior to the trial was 4.6 events, while in contrast, we observed a decreased yearly infection rate of close to 2 events at the 400-milligram once-daily dose. Perhaps most meaningfully, the Phase II study showed a deepening reduction in infection rates in correlation with the length of time on treatment. As you can see in this graph, on the bottom right, the 7 patients treated with a 300- or 400-milligram doses had a pre-study yearly infection rate of almost 5 infections per year. After 6 months, that rate dropped by 1/3. By 12 months, it dropped to less than 50%. And beyond 12 months, it dropped by almost 80%. While this is a small study of 7 patients, this magnitude of drop in infection rates supports the hypothesis that mavorixafor can deliver a disease-modifying impact for WHIM patients. Finally, as seen on Slide 11, we also examined wart burden, the third and final leg of the stool for WHIM syndrome, caused by human papillomavirus and which are linked to an increased risk of malignancy in WHIM. In patients with warts at baseline and treated with mavorixafor up to 300 and 400 milligrams once daily, we observed a 75% reduction in the numbers of cutaneous warts. We are pleased to have been able to measure this meaningful reduction. As they say, a picture is worth a thousand words. Here are the photographs of the hands of 1 patient on the study who had the most severe wart burden. Over the course of the trial, we observed a gradual but marked disappearance of the warts. After 6 months, a more than 50% decrease in the number of warts was observed. And as you can see on the image on the right, the skin dramatically improved over the 18 months of treatment. So in conclusion, on Slide 12, we have found that mavorixafor was well tolerated in patients with WHIM for prolonged duration. And we have shown that the 400-milligram oral dose increased total white blood cells, neutrophil and lymphocyte counts in WHIM patients. As you will recall, we talked about the time above threshold for absolute neutrophil count. This is the number of hours during which the absolute neutrophil count is raised above the 500 cells per microliter threshold. This time above threshold for neutrophil is an objective and consistent biomarker of the response to CXCR4 antagonist therapy in WHIM patients. And this measurement is the agreed-upon primary endpoint of our Phase III registrational trial with regulatory authorities. We believe these improvements reflect global immunological improvements and white blood cell mobilization that correlate with clinical endpoints of infections and warts to secondary clinical endpoints in the Phase III trial. Based on our results of the Phase II, the Phase III study is well-designed, and if successful, will support the full approval of mavorixafor for the treatment of WHIM syndrome. I'd now like to pass back the call to Paula. Paula?

Thank you, Sarah. Moving on to slide now 13, we are extremely encouraged by the positive therapeutic profile of mavorixafor emerging from the study. These results suggest that mavorixafor is a promising disease-modifying therapy based on the meaningful improvement in all 3 problematic legs of the stool: multiple fold increases in white blood cell counts and more specifically, neutrophils; a meaningful reduction in infection rates that's durable and deepening; and in wart burden reductions as well. Combined, these could lead to improved and durable outcomes for WHIM patients. We view these data as a significant derisking event for our ongoing pivotal Phase III clinical trial from which we expect top line data in 2022. And with that, let's open up the call for questions. Andrew?

[Operator Instructions] And our first question comes from the line of Stephen Willey with Stifel.

Congratulations on the update. Can you -- I just -- I guess, how an infection event was defined in this trial? And then I guess, when you speak to the 75% [Audio Gap] reduction statistic [Audio Gap]

Steve, I think you broke up a little bit on your questions. So it would be helpful if you could repeat it, if you can hear me okay?

I'm sorry. Yes. Can you hear me any better, Paula?

I can. Thank you very much.

Okay. Sorry about that. So can you just remind us how an infection event was defined in the trial? And when you speak to the 75% reduction in cutaneous warts that was observed, how many patients are included within that reduction statistic?

Sure. So the first question, I'll actually defer to Sarah in terms of defining infection rates. The one highlight I would like to comment here on is in the Phase III, we've actually developed a more granular tool to assess infection rates. So what Sarah will just be describing is kind of a blunt instrument, frankly, and we're encouraged by already what we've seen with that type of instrument. But let me shift it over to Sarah so she can give you a little bit more depth on that.

Thanks, Paula. I'm happy to take this question. So during the study, infections were reported by the investigators and scored according to CTCAE clinical scores. Overall, during the 12 months prior to the study, the most common types of infections involved lower respiratory tract and upper respiratory tract and skin infections, and on studies, the most common infections concerned the upper, followed by lower respiratory tract. Regarding the warts, we counted the number of warts that were present at baseline on the hands and feet, and then further evaluated the number of warts at different time points throughout the trial, again, by counting the number of warts that were present on the hands and feet.

I guess, what proportion of patients again?

Yes. Thank you. So on the trial, we had about -- we had 4 patients that had warts present at baseline and that were evaluable for this analysis.

Okay. And just lastly, I think there's going to be a manuscript that was previously mentioned of this Phase II experience. I guess, is that something that we should expect in the near term? And within that manuscript, should we anticipate seeing any additional data points such as supportive care, like G-CSF, that might have been required by patients throughout the open-label extension phase?

Sure, Steve. We are in the process of a manuscript publication, so we expect that second half of this year. The types of detail that you're asking, there will be a lot more data detail. I can't, off the top of my head, recognize if we have G-CSF, my -- but I think we've disclosed great amount of detail in the manuscript. So I think you'll be hopefully satisfied with the type of information you'll receive.

And our next question comes from the line of Joel Beatty with Citi.

Congrats on the data. The first question is on the annualized infection rate, a follow-up question from what you're talking about before. And any thoughts on what could be causing that trend of continuing to decrease over time? And then the second question is, not just on this point, but overall, could you talk a little bit about the consistency of results across patients and what you're seeing there?

Sure. I will start, and then I'll certainly ask Sarah to jump in. The first question was around the rationale behind the deepening of responses and infections. The bone marrow and your immune system is a complicated organ and functioning system that is certainly, better functions with experience. So I think if you think about WHIM syndrome as trapping white blood cells in the bone marrow, they, on average, the -- your immune system is not surveying and identifying pathogens so it gains the right experience to create long-term lasting infection responses. These -- of course, this is all hypothesis. But we believe the longer patients are on drug, the more normalized their immune system becomes so that daily surveillance is actually becoming part of their longer-term memory. We certainly need to address some of this by our measurements in the Phase III, but we do think this is one of the underpinnings and yet-to-be-discovered aspects of WHIM syndrome in terms of the translation of acute to chronic memory of the immune system. But Sarah, please chime in, I'd certainly welcome your additional commentary.

Yes. Thanks, Paula. Thank you for this question. So maybe what I would add is I think that we can really observe a maturation of the immunological system in these patients. So not only are we increasing neutrophils, but we're also increasing lymphocytes and maturing lymphocyte subsets as well as increasing monocytes. And I think that one of the things that happens over time and this is perhaps more of a hypothesis, is that since the most frequent infections that were observed both in the 12 months prior to the study and then on-study concerns along, I think that there is an element of reparation of the epithelial barriers which is allowed to occur. Again, this is not confirmed, but it's a good hypothesis. And concerning how we -- so every patient, I would say, had variability in presentation, but overall, the decrease in infection over time was consistent across all 5 patients who remain on the extension study.

And our next question comes from the line of Leland Gershell with Oppenheimer.

Just a question on the time above threshold, my slides were coming through a little bit choppy. This may have been shown. But just wanted to ask what the range was in terms of what you saw in -- on TAT for the patients in the open label?

Yes. So Leland, the average TAT that was reported in the EHA poster is a reflection of the 300- and 400-milligram dose patients throughout the open-label study, and then we also compared them to some of the lower doses. In the manuscript that we mentioned, there will be additional detail on kind of all the subsets and the data that will more specifically address your question, and that's forthcoming in the second half of this year. But we are certainly pleased with the robust response we're seeing, and I think that's quite reflective of what you'll see in the more granular data.

Okay. And then also just a question with the current program you have with Invitae, I wanted to ask if you're able to share any rates of positive confirmation of WHIM syndrome in those who are getting tested.

Sure. Great question. We will look forward to providing kind of a data update on Invitae in the future. We're not guiding to specifically when that will occur, because we certainly want to make sure we build a robust data set from which can report a nice outcome on. So stay tuned on that one.

And our next question comes from the line of Laura Christianson with Cowen.

I guess this might also be coming with the manuscript, but I am curious how many patients were taking G-CSF in the 1-year prior to enrollment and how that factors into your thoughts about the reductions in infection that you're seeing?

Sarah, I'm not -- why don't you try and take that question.

Yes. So I mean, that's an excellent question, trying to understand how can component in our prior treatments could interfere our lead bias into these results. So sometimes, it's kind of difficult to make a strong comparison given that while all patients had received various regimens of prophylactic G-CSF at some time in their life prior to the trial, they didn't all receive G-CSF in the prior 12 months, which is the period that we're looking at. So I think in detail, there is 1 patient that had some prophylaxis in the 12 months prior; 1 patient that just had in the 12 months prior to G-CSF, one time point with components with some oral surgery; 1 patient which had been enrolled in a crossover investigational study, in which -- it was being compared to G-CSF in the 12 months prior. But apart from those 3 patients, no other patients had received G-CSF in the prior 12 months. I would say really episodic use in the prior 12 months and then no use at all, obviously, while they were on trial.

And our next question comes from the line of Mayank Mamtani with B. Riley.

Congrats on the update. Can you just maybe call out what is the incremental update on -- I know it's a longer follow-up, but relative to the ASH abstract in 2018, could you maybe just talk to the infection rate that was reported at that time, the improvement per patient, per month? Just curious, relative to that incremental, what did we learn today? And how does that inform you as you think about the longer-term impact of mavorixafor in WHIM syndrome patients?

Sure. I'll kick that off and then Sarah can chime in. But I think the most encouraging and new data that we presented today is around those infection rates that are deepening with time. So I think this clearly demonstrates that the drug is chronically impacting the sequelae of a chronic disease. That is very meaningful. These are the same data that the FDA reviewed to grant us Breakthrough Therapy Designation. And so I think the highlight there is really that aspect of deepening and certainly profound reductions in infection rates that we're quite pleased with.

Yes. And I would add that compared to the ASH 2018 abstracts, we have 5 patients who remain on study for more than a year after that data cutoff, which really enabled us to confirm the reduction in infection rates with prolonged use.

Okay. Great. And can you just remind us -- I'm sure this would be in the manuscript. I believe there were 2 patients at the time that had some antibiotic use systemic. At this update, has there been more use of antibiotics on the trial?

Sarah -- I mean my understanding there, during the trial, there's been exceedingly limited use of antibiotics. So I think there's -- certainly not prophylactic. We, of course, can't withhold antibiotics in the case of an acute infection. But there's not been a chronic prophylactic use of antibiotics throughout this treatment period.

That's absolutely correct. There are no prophylactic antibiotic regimens on the trial. Of course, in the case of acute infections, patients received adequate standard of care antibiotic prescriptions.

Okay, great. And just last question, just could you maybe comment on some of the feedback from the -- especially the investigator community folks obviously participating some of -- in the study -- in the Phase III study and how that could influence also enrollment and things like that?

Well, I think our investigators have always been enthusiastic and have been part of this journey with us today. Certainly, as we published EHA and certainly the full manuscript, their ability to share and talk about these data is increased. So I think the groundswell of awareness, excitement and education, they'll be continued spokespersons for the company in the trial. The trial in terms of recruitment, I think, in a good way, we've been very dedicated to enrolling this trial well before these data. So I think it may help the patients certainly feel more enthusiastic about their continued involvement. But I think more importantly, this is a longer-term effort to really build education awareness and long-term commitment to our investigations of this drug.

And our next question comes from the line of RK Ramakanth with H.C. Wainwright.

Congratulations, Paula, on multiple fronts, I guess. A couple of quick questions. Most of my questions have been answered, but I just want to kind of understand a little bit on the wart reduction. So in the presentation, you say 75% reduction in the number of cutaneous warts. So how do you define this in the sense -- the particular patient whose hands we see, is that region defined and you say that within this region, how many warts have gone down from baseline to now or during the treatment period? Is that how it is looked at? And also, is there a thinking about our quantification about the quality of the wart in the sense of the size of the wart? And the third piece within the wart question is, do you also look out for any new warts erupting during the treatment period and the follow-up period, not in the defined area where -- which has started off at the baseline, but outside of that defined period -- defined area?

Sure. So I will turn that over to Sarah. But I think if I can repeat your question, it sounds like, how do you count the warts? And then the third question was what happens if a new wart occurs? I apologize, RK, I couldn't recall the second question.

Yes. The second question is like if the size of the wart could reduce but not...

Oh sure, it's part of the qualitative. Yes, yes, yes. So I'll let Sarah answer that question, and then we can also talk about what we've learned and what will improve upon even in the Phase III, but why don't you address the Phase II, Sarah?

Thank you, Paula, and thank you for this question. It's a really excellent question which we've given a lot of thought to. So I would say that in the Phase II, we did a rather growth evaluation, looking at 8 areas of interest on the hands and the feet, basically the palms and the dorsal sides of the hands and the feet. And then really counting visually any wart regardless of its size. And what we actually discovered in patients that had very large lesions, with that one large lesion in the process of decreasing in size and volume would often actually divide kind of into multiple smaller warts before progressively disappearing entirely. So this -- we realized that this evaluation, if you leave patients on trial for a sufficient amount of time, eventually shows you a decrease. But it's not optimal because as you're pointing out, it doesn't really give you that assessment entirely of what the size of the warts. And so we've designed something. We've learned a lot, and we've designed something very different for our Phase III trial, where, first of all, we're using standardized photography to photograph warts and we monitor for the light, we monitor for the distance, and it's the same across all of the visits for an individual patient and across all of our sites internationally. And we're also using a different score that looks not only at the improvement, but also at the severity of the wart in the Phase III. So I would say that in the Phase II, regarding your question about new warts, new warts that were present in those regions would just be counted as an additional wart, but not captured specifically. Whereas in the Phase III, we are specifically looking at the appearance of new warts as an event. I hope I answered your question.

Yes, excellent.

And our next question comes from the line of Zegbeh Jallah with ROTH Capital Partners.

Congrats on the data, which seems to be maturing very nicely. But based on that time-dependent improvement in infection rates that was mentioned, just curious if that 21-week, for example, patients were responding more robustly in terms of keeping their neutrophil count above the threshold versus that 5 weeks, for example?

Zegbeh, maybe if you're asking if there's sort of a consistent response of neutrophil throughout sort of the same time course that we're seeing the infection rates drop? Is that a correct summary?

Yes. I was just trying to see if there were any changes in terms of time on how robustly patients were responding to the same dose, for example. So perhaps at week 21, if they responded a lot better to the same dose than they did at week 5?

Sure. So I'll ask Sarah to chime in, but my understanding is the durability and consistency of the data, once patients reach steady state at particular dose, is quite consistent. There isn't sort of dramatic highs or lows around the same dosage form as patients are treated for many months, but I'll certainly ask Sarah to chime in on that.

Yes. What I would add maybe for clarity, is that because the initial portion of the trial was a dose escalation study, some patients started, for example, at week 5, they were only at 50 milligrams, and were progressively subsequently increased to up to 300 or 400 milligrams. So it's not always -- so we see the higher the dose, the higher the neutrophil count. But definitely, a general trend is that the more hours above the A&C threshold, the more reduction in infections was observed.

Thank you, and I show no further questions. So with that, I'll turn the call back to Paula Ragan for closing remarks.

Thank you so much, everyone. We greatly appreciate your participation today and look forward to updating you on the further progress of mavorixafor in WHIM syndrome. And certainly, if you have any further questions, please don't hesitate to reach out to Candice. I hope you all have a great day and a great weekend. Thank you. Bye-bye.

Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program, and you may all disconnect.