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spk08: Greetings. Welcome to X4 Pharmaceuticals Second Quarter 2023 Financial and Operating Results Conference Call. At this time, all participants are in a listen-only mode. A question and answer session will follow the formal presentation. As a reminder, this conference call is being recorded. It is now my pleasure to introduce your host, Dan Ferry from Lakeside Advisors. Please begin.
spk10: Thank you, Operator, and good morning, everyone. Presenting on today's call will be X4's Chief Executive Officer, Dr. Paula Regan, the company's Chief Financial Officer, Adam Mostafa, and Interim Chief Medical Officer, Dr. Murray Stewart. Following prepared remarks by each, we will open the call to your questions and will be joined by Chief Scientific Officer, Art Tavares, Chief Commercial Officer, Mark Baldry, and Chief Operating Officer, Mary DiBiase. As a reminder, on today's call, The company will be making forward-looking statements regarding regulatory and product development plans, as well as research activities. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasts. A description of these risks can be found in X4's most recent filings with the SEC, including this quarter's Form 10-Q, which is expected to be filed after market close today. I'd now like to turn the call over to X4's President and CEO, Dr. Paula Reagan. Paula?
spk07: Thanks, Dan. Hello, everyone. We'll be covering a lot of exciting updates this morning, so thank you for joining us on this call. Adami will be providing an update on our second quarter and recent events, and we'll then focus the rest of the call on three key updates regarding our ongoing chronic neutropenia program. First, we'll provide some further insights on what we estimate to be the minimum addressable U.S. market for Mavericks of 4 in the CN populations we're pursuing. Next, we'll report on some exciting emerging data from our ongoing Phase 2 trial. And finally, we'll also provide a regulatory update as we prepare for a Phase 3 clinical trial in 2024. We'll then conclude and open it up to your questions. This was another extremely productive quarter for X4. Importantly, we presented new data from our Phase III 4WIM trial in May that followed disclosure in late 2022 that the trial had met its primary endpoint and first key secondary endpoint and was well tolerated throughout the trial. In addition to demonstrating that Maverick support treatment statistically significantly and durably raised both absolute neutrophil and lymphocyte counts, both ANC and ALC versus placebo, these new data revealed that Mavericks for treatment also resulted in a statistically significant reduction in annualized infection rate and affected clinically meaningful reductions in both the severity and duration of infections versus placebo. We presented these data initially at our company webinar in mid-May. Additionally, the data were also accepted for oral presentation at two notable conferences. First, the annual meeting of the Clinical Immunology Society, or CIS, where Dr. Rafael Batalado presented the data. And second, the European Hematology Association, or EHA, where Dr. Jean Donadieu presented the data to a standing-only crowd in Frankfurt, Germany. These data have generated much excitement throughout the immunology and hematology physician communities around Mavericks for both for its potential to be the first disease-modifying treatment for WHIM syndrome and for supporting its potential to be the first new treatment option and potentially the only oral therapy to date for people with chronic utropenia in more than 30 years. And we are now poised to submit our first new drug application with the FDA seeking U.S. approval of oral, once daily Mavericks IV for the treatment of people aged 12 years and older with WHIM syndrome. There is a palpable excitement at the company these days, as you can well imagine. We're also pleased to receive notice of issuance of an additional patent on Mavericks IV in June. This granted patent, the third issued patent covering Mavericks 4's composition of matter, protects compositions of matter comprising Mavericks 4 and related drug substances formed during the Mavericks 4 manufacturing process through December of 2038. And we are thrilled to have recently announced the appointment of Dr. Christoph Arbett-Engels, our new Chief Medical Officer. Dr. Arbett Engels is a very seasoned executive with significant experience in drug discovery, translational research, clinical development, regulatory and medical affairs, and product launch and lifecycle management. Experience that spans a broad range of therapeutic areas, including rare and orphan diseases. He's held leadership roles at both large and small life sciences and pharmaceutical companies and is expected to bring great strategic global perspective to our team here at X4 when he starts next week. While we have a minute, I'd like to express our sincere gratitude to Dr. Murray Stewart, who's been serving as our interim chief medical officer and leading the Mavericks for WIM NDA submission efforts. Rest assured, Murray will still be staying on as a consultant to the company to finalize the NDA submission and help onboard Christoph, and will continue on as a continuing member of our board of directors. Thank you so much to Murray for all you've done for X4. I'll now pass the call over to Adam Mustafa, our CFO, to quickly cover the financial highlights of the quarter and recent updates before we turn our focus to our Chronic Atropinia program. Adam?
spk11: Thanks, Paula, and thanks to all of you on the call today. Concurrent with the announcement of the positive additional Phase III 4WIM results in mid-May, we were able to complete a pipe financing priced at the market, raising approximately $65 million in gross proceeds. Participants in the financing comprised both new and existing life science investors. During the quarter, we also announced that X4 was added to the Russell 3000 index when the index completed its annual reconstitution in late June. As a reminder, the annual reconstitution captures the 4,000 largest U.S. stocks as of April 28, 2023, ranking them by total market capitalization and membership in the index remains in place for one year. And just last week, we announced the completion of a $115 million debt facility with Hercules Capital. We believe this overall transaction is strategically impactful to X4 as it creates expanded future optionality beyond the equity capital markets as we head into an important growth trajectory for the company. In our release earlier this morning, we disclosed that we had cash, cash equivalents, restricted cash, and marketable securities totaling $142.3 million as of June 30, 2023. We believe that these funds, plus the $22.5 million drawn down from the debt facility upon closing, extend our cash runway into 2025. And we'd note that this projection does not include potential additional drawdowns on the debt facility and does not include the potential monetization of the priority review voucher we would expect to receive should Mavericks IV be approved for women's syndrome in the U.S. in 2024. I'll now pass it back to Paula to provide the updates across our chronic neutropenia program. Paula?
spk07: Thanks, Adam. Before we get into our new data, let's quickly review Mavericks 4 for those who may not be familiar. Mavericks 4 is an orally available CXCR4 antagonist that we're developing for a number of chronic neutropenic disorders and WHIM syndrome, a rare primary immunodeficiency. If we're successful, Maverick Sephora would be the first therapy for those with WHIM syndrome, and in chronic neutropenia, Maverick Sephora would be the first oral treatment option in a market currently only served by injectable therapies associated with treatment-limiting adverse events. In trials to date, Maverick Sephora has proven its ability to increase the mobilization of white blood cells, including neutrophils and lymphocytes, into the bloodstream where they can perform immunosurveillance and help fight infections. As I just mentioned, we successfully completed a Phase III clinical program in WHIM syndrome and are poised to submit the U.S. NDA for Maverick support in that indication. We've also successfully completed a Phase IB clinical trial of Maverick support in certain chronic uterpenic disorders and are currently studying Maverick support in a Phase II CN trial. As a reminder, we previously reported that our market research using ICD-10 code diagnosis methods suggests that roughly 50,000 people in the U.S. have been diagnosed with chronic neutropenia. Specifically, about 40,000 of these are diagnosed with chronic idiopathic neutropenia, and about 8,000 of these are diagnosed with congenital and cyclic neutropenia. A key question that all of us have been aiming to better understand is the size of the expected initial target population for Maverick Sephora across the spectrum of these estimated 50,000 individuals diagnosed with chronic neutropenia. We've now completed this additional market research, and we'll share our approach and results next. Our recent work has focused on advancing the understanding of the unmet needs in patient segmentation across CN through additional market research that included physician interviews and surveys alongside longitudinal patient chart reviews, both of which were further triangulated by separate claims data analyses. This robust methodology has provided some valuable insights into the real-world CN landscape in the U.S., What this research has confirmed is that there remains significant unmet needs across the broader CN patient population despite the availability and use of GCSF therapy. And it has helped us quantify what we believe could be the minimum addressable market for Maverick Sephora in chronic neutropenic indications and its potential for further market expansion. Firstly, please note that we purposely considered those patients who are 12 years of age and older for now and only counted those CN disorders where we believe Mavericks 4 can have an impact. This aligns with the population we intend to study in our planned Phase 3 CN trial. Given this initial segmentation, we then looked at those who experienced severe or recurrent symptoms, as well as those whose symptoms are deemed severe enough by physicians to warrant treatment with injectable GCSF. We can characterize this initial target group as patients with high unmet need. Our research suggests that this high unmet need population approximates one-third of the total estimated 50,000 people diagnosed with chronic neutropenia in the U.S. We would consider this a minimum initial addressable population for Mavericks for a number that has the potential to expand significantly if we include younger populations, those with intolerance to or poor quality of life on GCSF, those ineligible for GCSF, and or those with more moderate disease presentation. In all cases, we are excited to potentially deliver the first oral treatment option to reduce infection and treatment burden in this patient population. I'll now pass the call over to Dr. Murray Stewart, our interim CMO, to share some initial Phase II trial data, which are further informing our regulatory discussions and our Phase II trial design. Murray?
spk13: Thank you, Paula. As a reminder, we completed a Phase Ib study in people with idiopathic, cyclical, or congenital chronic neutropenia and reported results in late 2022. This 25-patient study of a single dose of Mavericksbur demonstrated a 100% response rate. All participants, with or without concurrent GCSF dosing, achieved an increase in ANC of at least 500 cells per microlitre at peak versus baseline. We consider this a profoundly positive result across the spectrum of CN disorders studied. Based on these exciting data, we quickly advanced to study chronic dosing of mavericks fur in the same CN population. In the Phase 2 portion of the study, mavericks fur is being dosed daily on top of each participant's baseline standard of care, either nothing or injectable GCFS. During the Phase 2 trial, mean ANCs are being evaluated monthly, where the mean is the average of neutrical counts at time zero and at four hours post-dosing. where time zero represents the nadir and four hours approximates the peak ANC post-mavericks for dosing. The goal of the ongoing Phase 2 study is to determine if mavericks for results in an increase in ANC response. If this response is durable and maintained over months of treatment, and where appropriate to assess if patients can reduce GCSF therapy with ANC values being maintained in the normal range when recommended by treating physicians. Safety and tolerability are also being assessed during the study period. We are pleased to share emerging data from the first three participants in the study with at least three months of dosing data, all of whom were on stable doses of GCSF at baseline. Given the market research results we've just shown correlating the high unmet need despite GCSF availability and use, We believe it's important to show that Mavericks VR safely increases ANC counts, that the response is durable, and that Mavericks VR can enable the reduction in GCSF use. Reduced GCSF may benefit patients by also reducing the known adverse events and risks associated with this therapy, consequently improving quality of life. Notably, The three GCSF-treated participants dosed with Mavrixpir showed robust increases in ANC counts versus baseline, and all patients achieved normalization of neutrophil counts, including the two participants who had significant neutropenia baseline despite being on GCSF. Neutrophil evaluations were durable and robust. In fact, the increases in ANC, which reached just over 10,000 cells per microliter, enabled physicians to decrease GCSF dosing by at least 50% as early as the two-month time point. In two cases, GCSF dosing has now been withdrawn completely while patients continue on study to assess ANC levels while on Mavericks for monotherapy. Importantly, Mavericks for safety profile, whether in combination with GCSF or as a single agent, continues to demonstrate good tolerability supporting chronic use. We thought it might be helpful to visualize these data. So let's walk through the example of durable ANC changes over time and reduction in GCSF dosing in participant one, who is a profile consistent with the planned inclusion criteria of our phase three trial. First, let's orientate you to what we're looking at. On the y-axis are mean ANC, or absolute neutrophil counts, assessed over four hours, as previously described. On the x-axis is time, measured in months on study. Baseline, or the time zero value, represents ANC levels prior to the addition of Mavarixivir. The low light red band on the graph delineates neutropenia, or ANC levels, below 1500 cells per microlitre. The light green zone represents the normal range of absolute neutropil counts. Participant 1, who was diagnosed with chronic idiopathic neutropenia, or CIN, was neutropenic at baseline, despite being on chronic GCSF. Baseline ANC was about 1,100 cells per microlitre, as shown on the graph at time 0. Here we see changes in mean ANC levels after two months of dosing of Maverick Spur and stable GCSF. Mean ANC counts increase to just above the upper limit of normal, an increase of about 9,000 cells per microlitre, or ninefold versus baseline. When ANC counts meaningfully increase, physicians are given the option to decrease either Maverick Spur or GCSF as per protocol. In this case, the treating physician recommended GCSF dosing be decreased, at which time participant 1's GCSF dose was reduced by 50% and the Mavericksford dose remained unchanged. At month 3, mean A and C counts were again assessed. Neutral counts remained solidly within the normal range and still robustly above baseline counts. This therefore supported a further reduction in GCSF to 25% of the regional dose at the three-month time point. Finally, at month four, after being on Mavericks for 400 mg daily and 25% of baseline GCSF doses, neutrophil counts continued to stay within the normal range, supporting the decision to withhold GCSF dosing altogether. This participant was continued on study to assess ANC levels on Mavericksburg monotherapy. Two other participants were concurrently treated with Mavericksburg and GCSF for three months or longer and achieved large increases in mean ANC versus baseline finds. In both cases, the physician decided to reduce or eliminate GCSF dosing while maintaining Mavericksburg at a normal once-daily dose of 400 mg. These participants also remain on study. So overall, we could not be more pleased with these emerging data. Importantly, we believe that the data demonstrate an acceptable safety profile of MavriXpert in combination with GCSF. Additionally, the initial results of the Phase 2 study, where long-term dosing is being assessed, are consistent with what was demonstrated in the 1B portion, assessing a single dose response. With chronic dosing of Mavericks in combination with GCSF, larger increases in mean ANC were observed durably over months in treatment, which supported physician decisions to reduce or eliminate GCSF dosing. We continue to believe that a neural, well-tolerated, once-daily treatment could be transformative for this patient population, whose only current treatment option is an injectable drug that carries associated adverse events and long-term risks. These data are included in an abstract just submitted to this year's ASH meeting. We expect to share these and additional data from the ongoing trial at that time. Additionally, these data were also included as part of our recent discussions with the FDA in support of our proposal for the Phase 3 trial design, which we'll now cover in more detail. Here we share the current outline of the Phase 3 trial design to support a potential label expansion for Mavarixivor, which is consistent with the market research we've just shared, an estimated population of approximately 15,000 people in the US with significant unmet needs. We've incorporated feedback from our meeting with the FDA into this proposed study design. We expect the population will include participants with a diagnosis of chronic idiopathic congenital or acquired primary neutropenia. We will study adolescents and adult subjects who are neutropenic and who also demonstrate severe or recurrent infections regardless of background therapy. The trial will be randomised, placebo-controlled and blinded over a 12-month treatment period, examining changes in A and C levels over time, as well as the clinical impact on infection burden and quality of life. GCSF tapering is also under consideration as part of the study, given the strong interest from physicians and given the potential clinical benefits for patients. The same once-daily dosing used in the WIM Phase 3 trial is supported for the CN Phase 3 programme. We are finalising our primary and secondary endpoints. and Statistical Analysis Plan, or SAP. The primary endpoint will likely be a co-primary endpoint involving increases in ANC and clinical benefit. We'll provide further updates when we have final clarity on these remaining aspects of the trial. Importantly, the overall objectives, design, and duration of the study is similar to that of our four WIM trials. which assessed and demonstrated increases in ANC levels and meaningful reductions in the frequency, severity, and duration of infections, and for which we are poised to submit our first NDA. We are very excited about the path forward to help those in need with a range of chronic neutropenic disorders. I'll now turn the call back over to Paula. Paula?
spk07: Thank you, Murray. As you can hopefully hear in our voices, we are thrilled at the tremendous progress that we've made in just a few short months for a range of immunocompromised patients with high unmet needs. Last quarter, we shared our positive WHIM Phase III results, where Mavericks IV treatment demonstrated durable ANC increases and reduced frequency, severity, and duration of infections, and we're now poised to submit our first NDA for Mavericks IV. Given that, we're planning to provide an update on our launch readiness, physician outreach efforts, and updates on the WIM market in our third quarter earnings call, and we hope you'll join us for that. And today, we've shared three important new advances. First, data clarifying our initial target population in CN as being the approximately 15,000 diagnosed in the U.S. with high unmet need. Second, our favorable emerging data of long-term Mavericks IV treatment, where the durable, large increases in ANC over months of dosing led to physicians' election to reduce GCSF dosing. And third, we've completed initial FDA discussions based on our emerging data and gained further clarity around our CN Phase III trial, keeping us on track to initiate the study in the first half of next year. We're now forging ahead with both the commercial launch in WIM and the launch of our next phase three in CN in the first half of next year. We are well positioned to potentially deliver a meaningful oral option, first to those with WIM syndrome, next to those with CN, and our hope is to expand beyond these initial indications to bring new options to even more patients throughout the world. And with that, we'll now open up the call for your questions.
spk08: Operator, Thank you. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star 2 if you would like to remove your question from the queue. And for participants using speaker equipment, it may be necessary to pick up the handset before pressing the star keys. Our first question is from Steven Willie with Stifel. Please proceed.
spk00: Yeah, good morning, guys. Thanks for taking the questions, and congrats on the quarter and the updated data. I guess, can you remind us within the Phase 2 CN protocol if there's a threshold ANC at which the investigator makes the GCSF tapering decision? And I guess, does that have to be a structured taper in terms of a 50% reduction, a 25% reduction, and then fully off? Or could patient one just have been taken off GCSF at any time point per the subjective assessment of the investigator?
spk07: Thanks, Steve. I'll pass it over to Marie to answer that.
spk13: So, in this specific protocol, we, in phase two, we want patients to taper for safety reasons as they get above 10,000. But we're also open to discussions with the PIs if they feel they want to taper at another level. So, and you could obviously in the protocol have either stopped the GCSF or stopped Mavericksburg. And in the cases we've described, we've actually chosen to taper. Now, at the moment, your second point is, do they taper? We, in phase two, are open to the position deciding on how they want to taper. But when we move into phase three, I think it's got to be a lot more coordinated in terms of thresholds to taper and volume tapering. And maybe a couple of comments regarding tapering. So in most other diseases, if you're tapering, say, osteoids, you've got to do it very carefully because you can have what you call a rebound effect. In the case of tapering GCSF, you can actually just stop GCSF. You don't have a problem other than, obviously, the risk of the count going low. So we don't need to be structured as in tapering with steroids. We can actually do it in one or two steps. And that's the thing we're considering, how to make it clear for physicians to follow a one- or two-step process in discontinuation.
spk00: Okay. I guess I'll follow up with the obvious question. I mean, you've seen kind of a little bit of a stepwise reduction in ANCs as the as the tapering has increased, I guess, what's your level of confidence that, I guess, at the next time point, month five, month six, that you're still going to be kind of comfortably above the normal range in terms of ANC with this patient who's on Mevrix for a long time?
spk13: Yes, obviously, I'd like data before I comment fully on that, and that's partly why we want to continue following the patients out. But I think the reason we're excited to share this data is actually clinically, I was surprised it was happening so quickly. So as a physician, observing patients in this study, seeing the ANC response robustly in combination, the fact after a couple of months, they are able to get GCSF is really exciting clinically. So I'm optimistic, but I'm also realistic. And I think we need to wait for a long-term date to see how this plays out.
spk07: I was just going to add, you know, the 9,000 cell increase in neutrophil count is attributed to Maverick's A4. So that's been a very impressive initial response. And then the question is, you know, obviously the drugs are acting in concert together. So the question is, how low can we go with GCSF? Ideally zero or ideally as infrequently as possible. And all the evidence today supports that we can get some patients across that paradigm.
spk00: Okay. And then maybe just last quick question. I guess, can you just speak to how many patients you've enrolled to date? And I guess how many of those patients are, will be included in this next disclosure. Just trying to get a sense as to how many patients, how long of a follow-up we'll see. Thanks.
spk13: Yeah, you'd be glad to know there's more than three. I'm not going to give a specific number. But the reason we spoke about these three is they're the furthest along. They've got more than three months. We've got a few patients a lot earlier on, and obviously later in the year we'll have more long-term data to give a more comprehensive picture. But we're pleased with what we're seeing, which is why we're sharing the data. Recruitment's maybe been a little bit slower than we'd like over the summer. We hope it'll pick up, and we'll have more data later in the year.
spk04: All right, thanks for taking the questions.
spk08: Our next question is from Kristen Kluska with Cantor Fitzgerald. Please proceed.
spk01: Good morning, everybody, and congrats on all these updates today. First, I wanted to ask at CIS this year, you had a pretty detailed poster on understanding the real world analysis of these patients. So first, can you help contextualize how these findings also helped you in terms of your phase three protocol design and what your expectations at baseline might be for some of these patients and ultimately what would be deemed clinically meaningful here?
spk07: Sure. Thanks, Kristen. I'll turn it over to Mark to answer that.
spk14: Yeah, hi. Good morning. We continue to believe there are about 50,000 people living in the U.S. with chronic neutropenia. What's new is that we have a better understanding now of the unmet need in this market. So, as you know, it's standard practice and marketing strategy to segment a market based on groups of customers with similar needs. And here we've identified that about a third of the people diagnosed with chronic neutropenia are suffering from severe disease symptoms and infections or have been deemed severe enough that their physicians have decided to prescribe some dose of GCSF. So, this is a significant opportunity for X4 as we're focused on bringing oral maverick support to target the underlying disease and address the unmet needs in these patients. And as Mari explained in his presentation, these are important insights that have now informed our preparations for the phase three trial in chronic neutropenia.
spk01: Thank you for that. And I recognize that the data update today is only a few months of follow-up, but can you give us some sense of, at baseline, were these patients experiencing infections? And then also, ultimately, how long in follow-up do you think that you'll be able to see some general early trends to be able to determine if the drug does have an impact on infections?
spk13: Yes, it's Murray. So, in Phase 2, we did allow people with different ranges of ANC, but it was important to show an example of someone who would exactly fit the criterion for the phase C, which is below normal ANC. And we know people who have an ANC below normal are at risk of infection compared to people with normal ANC. And in the Phase 3 study, we're recruiting people who've got a low ANC and have had prior history of infection. So we know some people coming into the Phase 2 have had a prior history of infection. It's too early to see any infection data. And as you may remember from our WIM study, we started seeing really after three months the reduction in infection or the increase in ANC translate to reduction in infection over time. And that's why the Phase 3 study to show effect on infection is a year.
spk01: Okay, thanks. And then last question for me, I'm going a little bit into the weeds here, but how are you specifically going to define recurrent and severe infections for the phase three trial? Like, is there a threshold, a number that they have had to experience in the past, or how are you thinking about that definition? Okay.
spk13: Yeah, so, you know, at a higher level, you know, they have to at least have one or two serious infections. And by that, I mean that it's not just colds or sniffles. They will have needed to be prescribed antibiotics or hospitalized. In other words, a serious infection that needed medical attention.
spk01: Okay, got it. Thanks for taking my questions and hope to see you in San Diego.
spk04: Looking forward to it.
spk08: Our next question is from Ted Penhoff with Piper Sandler. Please proceed.
spk02: Thank you. Good morning. And again, really sense the excitement and understand why so much good progress going on. Just wanted to tighten up a little bit on the NDA. What remains to be done? You know, are there any inspections that need to occur? you know, I mean, maybe it's early to tell, but with a rapid review cycle, would you anticipate an ad come? Thanks for reviewing all that.
spk13: Okay, so we're very encouraged where we are at the NDA. So there's no data, there's no content waiting. Those who've done an NDA will know it's a lot of it's QC and publishing. So it's really just tying up the loose ends in the next few weeks. Regarding the inspection, once we submit, it wouldn't be unusual for the FDA to want to inspect a product that is up for approval and the quality team are ready for inspection if the FDA choose to come and visit us.
spk02: Excellent. Thank you. And on an adcom?
spk13: So, I'd be shocked if we get an adcom. Yeah, and the reason I think the reason I say that is because it's if it was borderline or didn't work, then they might want an outcome or that there were some safety issues. So we don't have any CDC issues that wants an outcome. We've got clear clinical efficacy and that's why I think it's highly unlikely.
spk14: Awesome. Great. Well, best of luck. Thanks, dad.
spk08: Our next question is from Mark Fromm with Cowan and Company. Please proceed. Mark, your line is live. Please check and see if you're muted.
spk09: Thanks for taking my questions. Congrats on the data. Obviously, a nine-fold change seems quite significant in ANC, but can you just review the enrollment process and how many measures leading up to that baseline measure of ANC you're able to capture and can maybe speak to the variability you're seeing in the one patient presenting, but maybe also more broadly in the trial.
spk13: Yeah, so in the phase two, they came in with different levels of ANC. And I think what we're really seeing is all a robust response. So what's clinically relevant is greater than 500 cells. So in some senses, providing they do that, it can be very variable. But the important thing clinically is the robust response of 500 cells. And provided you get that, I'm less concerned about the variability. And obviously, we've got a threshold if it's well above normal for titration. But we're seeing different individuals do that, but all the individuals show the response.
spk07: So Mark, so far in the phase two, every time we're examining a patient, durably, we see exactly what we've seen in the phase one, which is every patient is responding with at least a 500 cell per microliter jump. Obviously with 9,000 being an example, more patients are certainly along those lines, given the concurrence of GCSF and our excitement for the patients and for us is, how can we get them to the low or no dose of GCSF?
spk09: Okay, that's great. And then maybe on to that point of, you know, that being an important goal, would you expect an endpoint around that to be maybe not the primary, but, you know, in your phase three to be formally assessed, you know, kind of GCSF sparing ability?
spk13: Yeah, so certainly that's under consideration. I think what you've got to say is how is it a clinical endpoint? Is it withdrawal completely? Is that the endpoint? Is it related to the clinical benefit of withdrawing, which would be related to some of the issues like bone pain? So all that's under consideration.
spk04: Okay, thank you.
spk08: Our next question is from with B. Riley. Please proceed.
spk05: Hey, guys. It's Madison Ofer, MAIC. Thanks for taking our call. Congrats on the data. If I can ask a quick follow-up regarding your imminent NDA, I'm wondering if that package is going to include your recent press of infectious data, and if that could really improve the strength of your label. And are you maybe thinking expecting a different label for different patient populations? either by age or severity. And then lastly, if I can get a quick one in, your market research, did that factor in patient or clinician perspective or excitement? Thanks.
spk07: So I'll let Marie take the first part of that, and Mark can jump in for the second.
spk13: Yeah, so from a regulatory point of view, we submit all the data to the ND based on data cutoffs. So there was a data cutoff earlier in the year where we put all the data into this file. And then there's an opportunity for either a 90 or 120-day review where we then put in all the data up to, you know, say August or September. So we will be including all the past data, and then the recent data will be in the natural follow-up request by the FDA for 120-day follow-up.
spk07: I think just to clarify the question, Murray, because we're very excited about this, The data that we showed in May, which reflected reductions in frequency, severity, and duration of Maverick's for and when patients, versus placebo is absolutely submitted, and we are absolutely positioning that in the label. Of course, we need to see how the FDA responds, but it's a huge clinical benefit demonstration of the drug, which is what the FDA asked for us. So the final label is to be determined, but it's a very key element of the proposed NDA filing.
spk13: Yeah, no, sorry about that. I thought you were talking about the recent, any recent data now. But yes, part of the NDA submission includes all the data that we previously presented.
spk07: And then, Mark, would you want to come in?
spk14: Just to clarify, indeed, the market research that we just conducted did gather insights directly from both community-based as well as academic physicians who treat large numbers of chronic atropinia patients. So these are insights directly from those physicians. They're looking at the charts of their own patients. So it's a real-world picture of the CN landscape.
spk04: Got it. I see. Thanks, guys.
spk08: Our next question is from Trevor Allred with Oppenheimer and Company. Please proceed.
spk06: Hey, good morning. Thanks for taking the question. Could you guys talk a bit about the FDA feedback on the phase three trial design? For example, I mean, given the magnitude of benefit that we've seen, do you guys think that you need a 12-month trial? Is that something from the FDA? And then can you also talk about the FDA's thoughts on the tapering inclusion?
spk13: Yeah, so first of all, we had a very good meeting with the FDA, and we do have a path forward with the Phase 3. The two major issues we discussed with them, or not issues, the topics we discussed were related to the primary endpoint, and I think it's clear they want some clinical aspect into that, which is why I mentioned in my presentation looking at ANC, which we are very confident we will hit, and also clinical benefits, and we've gotten up patients that were powered for this. And the study design is therefore very similar to WHIM. We shared the data we've shared with you today with the FDA deliberately to discuss whether tapering would be appropriate. And the FDA were aware of that and clearly said, you know, consider that and how you want to capture that. And that's what we're doing at the moment.
spk04: Okay, thanks.
spk08: Our next question is from RK with HC Wainwright. Please proceed.
spk12: Thank you. Good morning, Paula and Adam. Most of my questions have been answered, but in general, you know, with the data that you've seen so far with Maverick so far, what additional indications, you know, could you highlight as a possible way of, you know, label expansion from here beyond the CN?
spk07: Yeah, so I'll take that our case. I mean, maybe just a quick review. So we're thrilled about WHIM, right? We see this massive elevation across all white blood cell subtypes, including neutrophils, and that led us to chronic neutropenia and kind of that correlation of increased neutrophils, reduced infection rates. In WHIM phase three, there's additional data that does suggest sort of a breadth of impact across the immune system. We previously kind of directed kind of a mindshare to around the adaptive immunity. So there's certainly a number of immunodeficiencies that have deficiencies in the adaptive component of their immune system. So I think more of it's just stay tuned given the breadth of mechanism of action impacting the immune system. And right now with WHIM, certainly that nice correlation and reduction in frequency severity of infections. You can appreciate there's a nice landscape for the next round of pipeline expansion, but we'll get to that next year.
spk12: Thank you. Thank you for taking my question.
spk08: We have reached the end of our question and answer session. I would like to turn the conference back over to Paula for closing comments.
spk07: We really appreciate everyone joining us today. You can appreciate how thrilled we are with such a productive 12 weeks since we last had our WIM Phase 3 update, and we look forward to continuing to update everyone throughout the rest of the year. Enjoy the rest of your day.
spk08: Thank you. This does conclude today's conference. You may disconnect at this time, and thank you again for your participation.
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