NASDAQ:XFOR X4 Pharmaceuticals Q2 2023 Earnings Report $3.22 -0.08 (-2.42%) Closing price 05/6/2025 04:00 PM EasternExtended Trading$3.38 +0.16 (+4.81%) As of 05/6/2025 07:40 PM Eastern Extended trading is trading that happens on electronic markets outside of regular trading hours. This is a fair market value extended hours price provided by Polygon.io. Learn more. Earnings HistoryForecast X4 Pharmaceuticals EPS ResultsActual EPS-$20.40Consensus EPS N/ABeat/MissN/AOne Year Ago EPSN/AX4 Pharmaceuticals Revenue ResultsActual Revenue$1.90 millionExpected RevenueN/ABeat/MissN/AYoY Revenue GrowthN/AX4 Pharmaceuticals Announcement DetailsQuarterQ2 2023Date8/24/2023TimeN/AConference Call DateN/AConference Call TimeN/AConference Call ResourcesConference Call AudioConference Call TranscriptPress Release (8-K)Quarterly Report (10-Q)Earnings HistoryCompany ProfilePowered by X4 Pharmaceuticals Q2 2023 Earnings Call TranscriptProvided by QuartrAugust 10, 2023 ShareLink copied to clipboard.There are 13 speakers on the call. Operator00:00:00Welcome 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. Operator00:00:22Please begin. Speaker 100:00:24Thank you, operator, and good morning, everyone. Presenting on today's call will be Exforge's Chief Executive Officer, Doctor. Paula Ragan the company's Chief Financial Officer, Adam Mostafa and Interim Chief Medical Officer, Doctor. Murray Stewart. Following prepared remarks by each, We will open the call to your questions and we'll be joined by Chief Scientific Officer, Art Tavares Chief Commercial Officer, Mark Baldry and Chief Operating Officer, Mary DiBiase. Speaker 100:00:54As 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 Exforge'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, Doctor. Paula Ragan. Speaker 100:01:26Paula? Speaker 200:01:28Thanks, Dan. Hello, everyone. We'll be covering a lot of exciting updates this morning. So thank you for joining us on this call. Adamai will be providing an update on our Q2 and recent events and will then focus the rest of the on 3 key updates regarding our ongoing chronic neutropenia program. Speaker 200:01:48First, we'll provide some further insights on what we estimate to be the minimum addressable U. S. Market for MAVERICK'S AFFO 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 This was another extremely productive quarter for X4. Speaker 200:02:19Importantly, we presented new data from our Phase 3 for WIM trial in May that followed disclosure in late 2022 that the trial had met its primary endpoint and 1st key secondary endpoint and was well tolerated throughout the trial. In addition to demonstrating that MAVERICK's before treatment statistically significantly And durably raised both absolute neutrophil and lymphocyte counts, both ANC and ALC Versus placebo, these new data revealed that MAVERICK's 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 before oral presentation at 2 notable conferences. First, the Annual Meeting of the Clinical Immunology Society or CIF, where Doctor. Speaker 200:03:20Rafael Badalado presented the data And second, the European Hematology Association or EHA, where Doctor. Jean Donadue presented the data to a standing These data have generated much excitement throughout the immunology and hematology physician communities around MAVERICK for both for its potential to be the 1st disease modifying treatment for WIM syndrome and for supporting its potential to be the 1st new treatment option and potentially the only oral therapy to date for people with chronic neutropenia 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 mavericksof4 for the treatment of people aged 12 years and older with WHIMS syndrome. Speaker 200:04:11There 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 MAVERICK's 4 in June. This granted patent, The 3rd issued patent covering MAVERICK's 4's composition of matter protects compositions of matter comprising MAVERICK's 4 and related drug substances formed during the MAVERICK's for manufacturing process through December of 2,038. And we are thrilled to have recently announced the appointment of Doctor. Christophe Arbet Engels, our new Chief Medical Officer. Speaker 200:04:47Doctor. Arbet Engels is a very seasoned executive with significant experience in drug discovery, 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 science 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 Doctor. Murray Stewart, who's been serving as our Interim Chief Medical Officer And leading the MAVERICK's for WAM NDA submission efforts. Speaker 200:05:33Rest assured Murray will still be staying on as a consultant to the company to finalize the NDA submission and help onboard Christophe 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 Estafa, our CFO, to quickly cover the financial highlights of the quarter and recent updates before we turn our focus to our chronic neutropenia program. Adam? Speaker 300:06:03Thanks, Paula, and thanks to all of you on the call today. Concurrent with the announcement of the positive additional Phase 3 4 WIM results in mid May, we were able to complete a pipe financing priced at the market, raising approximately $65,000,000 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 3,000 Index when the index completed its annual reconstitution in late June. As a reminder, the annual reconstitution captures the 4,000 largest U. Speaker 300:06:40S. Stocks as of April 28, 2023, ranking them by total market capitalization and membership in the index remains in place for 1 year. And just last week, we announced the completion A $115,000,000 debt facility with Hercules Capital. We believe this overall transaction is strategically impactful to Exfor 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 $142,300,000 as of June 30, 2023. Speaker 300:07:24We believe that these funds Plus the $22,500,000 drawn down from the debt facility upon closing extend our cash runway into 2025. And we note that this projection does not include potential additional drawdowns on the debt facility and does not include the I'll now pass it back to Paula to provide the updates across our chronic neutropenia program. Paula? Speaker 200:07:58Thanks, Adam. Before we get into our new data, let's quickly review MAVERICKS-four for those who may not be familiar. MAVERICK support is an orally available CXCR4 antagonist that we're developing for a number of chronic neutropenic disorders and WIM syndrome, a rare If we're successful, MAVERICK CIFOR would be the first therapy for those with WIM syndrome and in chronic neutropenia, MAVERICK In trials to date, MAVERICK 4 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 health We've also successfully completed a Phase 1b clinical trial of MAVERICKISSE-four in certain chronic neutropenic disorders and are currently studying MAVERICK's 4 in a Phase 2CN trial. As a reminder, we previously that our market research using ICD-ten code diagnosis methods suggest that roughly 50,000 people in the U. S. Speaker 200:09:23Have 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's before across the spectrum of these 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 and 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. Speaker 200:10:20This robust methodology has provided some valuable insights into the real world What this research has confirmed is that there remains significant unmet needs across The broader CN patient population despite the availability and use of G CSF therapy. And it has helped us quantify what we believe 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 MAVERICK's 4 can have an impact. This aligns with the population we intend to study in our planned Phase Given this initial segmentation, we then looked at those who experienced severe or We can characterize this initial target group as patients with high unmet need. Our research suggests that the High unmet need population approximates 1 third of the total estimated 50,000 people diagnosed with chronic neutropenia in the U. S. Speaker 200:11:40We would consider this a minimum initial addressable population for MAVERICK score, a number that has the potential to expand significantly if we include younger populations, Those with intolerance to or poor quality of life on G CSF, those ineligible for G CSF and or those with more moderate disease presentation. In all cases, we are excited to potentially deliver the 1st oral treatment option to reduce infection and treatment burden in the patient population. I'll now pass the call over to Doctor. Murray Stewart, our Interim CMO, to share some initial Phase 2 trial data, which are further informing our regulatory discussions and our Phase 3 trial design. Murray? Speaker 400:12:25Thank you, Paula. As a reminder, we completed our Phase 1b study in people's idiopathic, cyclical of Congenital Chronic Neutropenia and reported results in late 2022. This 25 patient study of a single dose of MAVERICKS per demonstrated 100% response rate. All participants with or without concurrent G CSF dosing Achieved an increase in ANC of at least 500 cells per microliter at peak versus baseline. We consider this a profoundly positive result across the spectrum of CNS disorders studied. Speaker 400:13:05Based on these exciting data, We quickly advanced to study chronic dosing of MavriXpert in the same CN population. In the Phase 2 portion of the study, MABRIX004 is being dosed daily on top of each participant's baseline standard of care, either nothing or injectable GCFF. During the Phase 2 trial, mean ANCs are being evaluated monthly, where the mean is the average of neutrophil counts at time 0 and at 4 hours post dosing. Where time 0 represents the nadir and 4 hours approximates the peak ANC post mavericks for dosing. The goal of the ongoing Phase 2 study is to determine if MAVERICK's full results and an increase in ANC response. Speaker 400:13:55If this response is durable and maintained over months of treatment and where appropriate to set that patients can reduce G CSF therapy With A and C 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 3 months of dosing data, all of whom were on stable doses of G CSF at baseline. Given the market research results we've just shown correlating the high unmet need despite GCFF available to induce, We believe it's important to show that MAVERICK SPA safely increases ANC count, that response is durable Notably, the 3 G CSF treated participants dosed with Mavriksberg showed robust increases in ANC counts versus baseline. And all patients achieved normalization of neutrophil counts, including the 2 participants who had significant neutropenia at baseline despite being on GCSF. Speaker 400:15:23Nutrieval evaluations were durable and robust. In fact, the increases in ANC, which reached just over 10,000 cells per microliter enabled physicians to decrease G CSF dosing by at least 50% as early as the 2 month time point. In two cases, GCF dosing has now been withdrawn completely Patients continue on study to set ANC levels while on MAVERICK's for monotherapy. Importantly, MAVERICK's safety profile, whether in combination with G CSF or as a single We thought it might be helpful to visualize these data. So let's walk through an example of durable ANC changes over time And reduction in G CSF dosing in participant 1, who is a profile consistent with the planned inclusion criteria of our Phase 3 trial. Speaker 400:16:27First, let's orientate you to what we're looking at. On the y axis, our mean ANC measured in months on study. Baseline or the time zero value represents A and C levels prior to the addition of maverixibor. The low light red band on the graph generates neutropenia or ANC levels below 1500 cells per microliter. The light green zone represents a normal range of absent neutrophil counts. Speaker 400:17:06Participant 1 who was diagnosed with Chronic idiopathic neutropenia or CIN was neutropenic at baseline despite being on chronic G CSF. Baseline A and C was about 1100 cells per microliter as shown on the graph at time 0. Here we see changes in mean ANC levels after 2 months of dosing of MAVERICK's for and stable GCFF. Mean A and C counts increased to just above the upper limit of normal, an increase of about 9,000 cells per microliter or 9 fold versus baseline. When the NC can't meaningfully increase, physicians are given the option to decrease either MAVERICK SBIRT or G CSF as per protocol. Speaker 400:17:52In this case, the treating physician recommended GCS dosing be decreased, at which time participant 1's G CSF dose was reduced by 50% and the MAVERICK spread dose remained unchanged. At month 3, mean A and C counts were again assessed. Neutropl counts remained solidly within the normal range and still robustly above baseline counts. This therefore supported a further reduction in G CSF to 25% of the regional dose at the 3 month time point. Finally, month 4, after being on MAVERICK's for 400 milligrams daily At 25% of baseline G CSF doses, neutrophil counts continue to stay within the normal range, supporting the decision to withhold G CSF This participant has continued on study to assess A and C levels on MAVERICK's for monotherapy. Speaker 400:18:532 other participants were concurrently treated with MAVERICK's for anti CSF for 3 months or longer In both cases, physician decided to reduce or eliminate G CSF dosing while maintaining Mabryx for a 10 oral once daily dose of 400 milligrams. 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 MAVERICK SBIRT in combination with G CSF. 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. Speaker 400:19:47With chronic dosing of MAVERICK's in combination with G CSF, Large increases in MENA and C were observed durably over months in treatment, which supported physician decisions to reduce or eliminate G CSF dosing. We continue to believe that the neuro well tolerated once daily treatment could be transformative for this patient population, whose only current treatment option is an injectable drug that carries 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 maverixivore, which is consistent with the market research we've just shared, an estimated population of approximately 15,000 people in the U. Speaker 400:20:59S. 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 for the diagnosis of chronic idiopathic congenital or acquired primary neutropenia. We will study adolescents and adult subjects who are neutropenic and to also demonstrate severe or recurrent infections regardless of background therapy. Speaker 400:21:30The trial will be randomized, 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. G CSF 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 program. We're finalizing 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. Speaker 400:22:19We'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 4 WIM trial, 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 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? Speaker 200:22:58Thank you, Murray. As you can hopefully hear in our voices, we 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 WIM Phase 3 results, where MAVERICK's for treatment demonstrated durable ANC increases and reduced Given that, we're planning to provide an update on our launch readiness, physician outreach efforts and updates on the WIM market in our Q3 earnings call, And we hope you'll join us for that. And today, we've shared 3 important new advances. 1st, Data clarifying our initial target population in CN as being the approximately 15,000 diagnosed in the U. Speaker 200:23:50S. With high unmet need. 2nd, our favorable emerging data of long term MAVERICK's for treatment, where the durable large increases in And see over months of dosing led to physicians' election to reduce G CSF dosing. And third, We've completed initial FDA discussions based on our emerging data and gained further clarity around our CN Phase 3 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 and WIM and the launch of our next Phase 3 in CN in the first half of next year. Speaker 200:24:29We 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. Operator? Operator00:24:49Thank Our first question is from Stephen Willey with Stifel. Please proceed. Speaker 500:25:16Yes, 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 to 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 50% reduction, a 25% reduction and then fully off? Speaker 500:25:49Or could Patient 1 just have been taken off GCSF at any time point for the subjective assessment of the investigator. Speaker 200:25:57Thanks, Steve. I'll pass it over to Marie to answer that. Speaker 400:26:00So in this specific protocol, We in Phase 2, 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 the protocol have either stopped the GCSF or stopped Maverick's. And In the cases we've described, we've actually chosen to taper. Now, at the moment regarding your second point is, Do they taper 50%, 25%. Speaker 400:26:40We in Phase 2 are open to the physician deciding on how they want Taper, when we move into Phase 3, I think it's got to be a lot more coordinated in terms of thresholds to taper And maybe a couple of comments regarding tapering. So in most other diseases, if you're tapering, say, off steroids, You've got to do it very carefully because you could have what you call a rebound effect. In the case of tinkering GCSF, you can't actually just You don't have a problem other than obviously the risk of the can't going low. So we don't need to be Structured doesn't take things with steroids. We can actually do it in 1 or 2 steps. Speaker 400:27:23And that's the thing we're considering how to make Clear propositions to follow, a 1 or 2 step process in discontinuation. Speaker 600:27:33Okay. Speaker 500:27:34And 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 A and Cs As the tapering has increased, I guess, what's your level of confidence that, I guess, at the next time point, month 5, month 6, 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 loan? Speaker 400:27:59Yes. So 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 have surprised it's happening so quickly. So as a physician Observing patients in this study seeing the ANC response to robustly in combination, the fact after a couple of months They are able to take on GCSF is really exciting clinically. Speaker 400:28:29So 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. Speaker 500:28:36Okay. And then maybe the last question Speaker 200:28:39I'm sorry. Go ahead. Speaker 700:28:40No, I Speaker 200:28:40was just going to add, The 9,000 cell increase in neutrophil count is attributed to maverickza 4. So that's been a very impressive initial response. And then the question is, obviously, the drugs are acting in concert together. So the question is how low can we go With GCSF ideally 0 or ideally as infrequently as possible and all the evidence today supports that we can get some patients across that paradigm. Speaker 500:29:08Okay. 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 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. Speaker 400:29:28Thanks. Yes. You'd be glad to know there's more than 3. I'm not going to give that specific number. But the reason we spoke about these 3 is They've got more than 3 months. Speaker 400:29:38We've got 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, we're pleased with what we're seeing, which is why we're sharing the data. This might be being a little We'd like over the summer. We hope it will pick up and we'll have more data later in the year. Speaker 500:29:58All right. Thanks for taking the questions. Operator00:30:03Our next question is from Kristin Kluska with Cantor Fitzgerald. Please proceed. Speaker 800:30:10Good 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 And what your expectations at baseline might be for some of these patients and ultimately what would be deemed clinically meaningful here? Speaker 200:30:41Sure. Thanks, Kristen. I'll turn it over to Mark to answer that. Speaker 900:30:45Yes. Hi, good morning. We continue to believe there are about 50,000 people living in the U. S. With chronic neutropenia. Speaker 900:30:52What's new is that we have 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 So this is a significant opportunity for X4 as we're focused on bringing oral maverixa forward to target the underlying disease and address the unmet needs in these patients. And as Marty explained in his presentation, these are important insights that have now informed our preparations for the Phase 3 trial in chronic neutropenia. Speaker 800:31:42Thank 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 that 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? Speaker 400:32:07Yes, it's Murray. So, in Phase 2, we did allow people with different ranges of ANC, but it's important to To show an example of someone who would exactly fit the criteria for the PAC, which is below normal ANC. And we know people Who have an ANC below normal are at risk of infection compared to people who normal ANC. And in the Phase 3 study, we're recruiting people who've got Hello, NC and have had prior history of infection. So we know some people coming into the Phase 2 have had prior history of infection. Speaker 400:32:42It's too early to see any infection data. And as you may remember from our WIM study, we started seeing really after 3 months the reduction in infection The increase in NANDC translate to reduction infection over time. And that's why the Phase 3 study to show effect on infection is a year. Speaker 800:33:04Okay. 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 3 trial? Speaker 800:33:14Like is there a threshold, a number that they have had to Experience in the past or how are you thinking about that definition? Speaker 400:33:25Yes. So, at a high level, they have to at least have 1 or 2 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. Speaker 800:33:44Okay, got it. Thanks for taking my questions and hope to see you in San Diego. Speaker 200:33:50Look forward to it. Operator00:33:53Our next question is from Ted Tenthoff with Piper Sandler. Please proceed. Speaker 1000:33:59Thank 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? Speaker 1000:34:16Are there any inspections that need to occur? And I mean, maybe it's early to tell, but with rapid review cycle, would you anticipate an AdCom? Thanks for reviewing all that. Okay. Speaker 400:34:33So, we're very encouraged where we are at the NDA. So, there's no data. There's no content waiting. Those who have done an NDA will know it's a lot of its QC and Publishing. So it's really just tying up the loose ends in the next Few weeks. Speaker 400:34:50Regarding the inspection, once we submit, it wouldn't be unusual for the FDA to want to inspect Product that is up for approval and the quality team are ready for inspection if they choose to come and visit us. Speaker 1000:35:09Excellent. Thank you. And on an AdCom? Speaker 400:35:14So I'd be Shocked if we get an adcom. Yes. And the reason I say that is because It's if it was borderline or didn't work, then they might want an outcome or there were some safety issues. So we don't have any safety issues that warrants an We've got clear clinical efficacy and that's why I think it's highly unlikely. Speaker 600:35:39Awesome. Great. Well, best of luck. Speaker 200:35:43Thanks, Ted. Operator00:35:44Our next question is from Mark Frahm with Cowen and Company. Please proceed. Mark, your line is live. Please check and see if you're muted. Speaker 1100:35:59Thanks for taking my questions. Congrats on the data. And obviously, a ninefold changes It seems quite significant in A and C, but can you just review the kind of enrollment process and kind of how many measures leading up to That baseline measure of ANC you're able to capture and can you speak to the variability you're seeing in The one patient presenting, but maybe also more broadly in the trial. Speaker 400:36:26Yes. So in the Phase 2 that 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 sense, providing they do that, it can be very variable. But the important thing clinically is the response of 500. Speaker 400:36:50And providing you get that, I'm less concerned about the variability. And obviously, we've got a threshold that Well above normal for titration, but we're seeing different individuals do that, but all the individuals show their response. Speaker 200:37:05So Mark, so far in the Phase 2, every time we're examining a patient durably, we see exactly what we've seen in the Phase 1, Which is every patient is responding with at least a 500 sol per microliter jump. Obviously, with 9,000 being an example, More patients are certainly along those lines, given the concurrence of G CSF and our excitement for the patients and for us is How can we get them to the low or no dose of GCSF? Speaker 1100:37:35Okay. That's great. And then Maybe on to that point of that being an important goal, would you expect an endpoint around that to be maybe not the primary, but in your Phase 3 To be formally assessed, GCSS sparing ability? Yes. Speaker 400:37:53So certainly that's under consideration. I think what you've got to say is How is a clinical endpoint? Is it withdrawal completely? Is that the endpoint? Is it related to the clinical benefit of Drawing should be related to some of the issues like bone pain. Speaker 400:38:09So all that's under consideration. Speaker 1100:38:13Okay. Thank you. Operator00:38:17Our next question is from Mayank Bantami with B. Riley, please proceed. Speaker 700:38:25Hey, guys. It's Madison on for Thanks for taking our call and congrats on the data. If I can ask you a quick Follow-up regarding your imminent NDA. I'm wondering if that package is going to include your recent impressive 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? Speaker 700:38:57And then lastly, if I can get a quick one in, Your market research, did that factor in patient or like clinician perspective or excitement? Thanks. Speaker 200:39:09I'll let Marie take the first part of that and Mark can jump in for the second. Speaker 400:39:13Yes. So from a regulatory point of view, We submit all the data to the NDA based on data cutoffs. So there was a data cut off earlier in the year where we put all And then there's an opportunity for either a 90 or 120 day review where we then put in all the data up to, say, August or August to 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. Speaker 200:39:46So I think just to clarify the question, Murray, because we're very excited about this. The data that we showed in May, which Reductions in frequency, severity and duration of MAVERICK's foreign women 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 So the final label is to be determined, but it's a very key element of the proposed NDA filing. Speaker 400:40:17Yes. No, sorry about 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. Speaker 200:40:30And then Mark, do you want to comment? Speaker 900:40:32Just 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 neutropenia patients. So these are insights directly from those physicians. They're looking at the So it's a real world picture of the CN landscape. Speaker 700:41:00Got it. I see. Thanks guys. Operator00:41:05Our next question is from Trevor Allred with of Oppenheimer and Company. Please proceed. Speaker 600:41:10Hey, good morning. Thanks for taking the question. Could you guys talk a bit The FDA feedback on the Phase 3 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? Speaker 400:41:31Yes. 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 2 major issues we The topics we discussed were related to the primary endpoint. And I think it's Clearly, we 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 us. And the study design is therefore very similar to Wim. Speaker 400:42:08We shared the data we shared with you today with the FDA deliberately to discuss whether tapering would be appropriate. The FDA were aware of that and clearly said consider that and how you want to capture that and that's Operator00:42:33Our next question is from RK with H. C. Wainwright. Please proceed. Speaker 1200:42:40Thank you. Good morning, Paolo and Adam. Most of my questions have been answered, but In general, with the data that you have seen so far with mavrixophore, What additional indications could you highlight as a possible way of label expansion from here beyond the CN? Speaker 200:43:06Yes. So, I'll take that our case. I mean, maybe just a quick review. So, we're thrilled about WAM, right? We see this massive elevation across all white blood Some type including neutrophils and that's led us to chronic neutropenia and kind of that correlation of increased neutrophils, reduced infection rates. Speaker 200:43:25In WIM Phase 3, 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 mind share 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 WIM certainly that nice correlation and reduction in You can appreciate there's a nice landscape for the next round of pipeline expansion, but we'll get to that next year. Operator00:44:09We have reached the end of our question and answer session. I would like to turn the conference back over to Paula for closing comments. Speaker 200:44:17We really appreciate everyone joining us today. You can appreciate how thrilled we are with such productive 12 weeks since we last had our WIM Phase 3 update, Operator00:44:32Thank you. This does conclude today's conference. You may disconnect at this time and thank you again for your participation.Read morePowered by Conference Call Audio Live Call not available Earnings Conference CallX4 Pharmaceuticals Q2 202300:00 / 00:00Speed:1x1.25x1.5x2x Earnings DocumentsPress Release(8-K)Quarterly report(10-Q) X4 Pharmaceuticals Earnings HeadlinesBrookline Capital Management Weighs in on XFOR Q3 EarningsMay 6 at 2:11 AM | americanbankingnews.comHC Wainwright Increases X4 Pharmaceuticals (NASDAQ:XFOR) Price Target to $7.00May 5 at 1:29 AM | americanbankingnews.comHere’s How to Claim Your Stake in Elon’s Private Company, xAII predict this single breakthrough could make Elon the world’s first trillionaire — and mint more new millionaires than any tech advance in history. And for a limited time, you have the chance to claim a stake in this project, even though it’s housed inside Elon’s private company, xAI.May 7, 2025 | Brownstone Research (Ad)X4 Pharmaceuticals Inc (XFOR) Q1 2025 Earnings Call Highlights: Progress in Maverick 4 ...May 2, 2025 | finance.yahoo.comX4 Pharmaceuticals, Inc. (NASDAQ:XFOR) Q1 2025 Earnings Call TranscriptMay 2, 2025 | insidermonkey.comX4 Pharmaceuticals, Inc. (XFOR) Q1 2025 Earnings Call TranscriptMay 1, 2025 | seekingalpha.comSee More X4 Pharmaceuticals Headlines Get Earnings Announcements in your inboxWant to stay updated on the latest earnings announcements and upcoming reports for companies like X4 Pharmaceuticals? Sign up for Earnings360's daily newsletter to receive timely earnings updates on X4 Pharmaceuticals and other key companies, straight to your email. Email Address About X4 PharmaceuticalsX4 Pharmaceuticals (NASDAQ:XFOR), a late-stage clinical biopharmaceutical company, focuses on the research, development, and commercialization of novel therapeutics for the treatment of rare diseases. Its lead product candidate is mavorixafor, a small molecule inhibitor of the chemokine receptor C-X-C chemokine receptor type 4 (CXCR4), which is in Phase III clinical trial for the treatment of patients with warts, hypogammaglobulinemia, infections, and myelokathexis syndrome; and Phase II clinical trial to treat congenital, idiopathic, or cyclic neutropenia. The company is also developing X4P-003, a CXCR4 antagonist for the treatment of CXCR4 dependent disorders and primary immunodeficiencies; and X4P-002, a CXCR4 antagonist for the treatment of blood-brain barrier diseases. It has a license agreement with Abbisko Therapeutics Co Ltd. to develop, manufacture, and commercialize mavorixafor in combination with checkpoint inhibitors or other agents in oncology indications. 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There are 13 speakers on the call. Operator00:00:00Welcome 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. Operator00:00:22Please begin. Speaker 100:00:24Thank you, operator, and good morning, everyone. Presenting on today's call will be Exforge's Chief Executive Officer, Doctor. Paula Ragan the company's Chief Financial Officer, Adam Mostafa and Interim Chief Medical Officer, Doctor. Murray Stewart. Following prepared remarks by each, We will open the call to your questions and we'll be joined by Chief Scientific Officer, Art Tavares Chief Commercial Officer, Mark Baldry and Chief Operating Officer, Mary DiBiase. Speaker 100:00:54As 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 Exforge'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, Doctor. Paula Ragan. Speaker 100:01:26Paula? Speaker 200:01:28Thanks, Dan. Hello, everyone. We'll be covering a lot of exciting updates this morning. So thank you for joining us on this call. Adamai will be providing an update on our Q2 and recent events and will then focus the rest of the on 3 key updates regarding our ongoing chronic neutropenia program. Speaker 200:01:48First, we'll provide some further insights on what we estimate to be the minimum addressable U. S. Market for MAVERICK'S AFFO 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 This was another extremely productive quarter for X4. Speaker 200:02:19Importantly, we presented new data from our Phase 3 for WIM trial in May that followed disclosure in late 2022 that the trial had met its primary endpoint and 1st key secondary endpoint and was well tolerated throughout the trial. In addition to demonstrating that MAVERICK's before treatment statistically significantly And durably raised both absolute neutrophil and lymphocyte counts, both ANC and ALC Versus placebo, these new data revealed that MAVERICK's 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 before oral presentation at 2 notable conferences. First, the Annual Meeting of the Clinical Immunology Society or CIF, where Doctor. Speaker 200:03:20Rafael Badalado presented the data And second, the European Hematology Association or EHA, where Doctor. Jean Donadue presented the data to a standing These data have generated much excitement throughout the immunology and hematology physician communities around MAVERICK for both for its potential to be the 1st disease modifying treatment for WIM syndrome and for supporting its potential to be the 1st new treatment option and potentially the only oral therapy to date for people with chronic neutropenia 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 mavericksof4 for the treatment of people aged 12 years and older with WHIMS syndrome. Speaker 200:04:11There 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 MAVERICK's 4 in June. This granted patent, The 3rd issued patent covering MAVERICK's 4's composition of matter protects compositions of matter comprising MAVERICK's 4 and related drug substances formed during the MAVERICK's for manufacturing process through December of 2,038. And we are thrilled to have recently announced the appointment of Doctor. Christophe Arbet Engels, our new Chief Medical Officer. Speaker 200:04:47Doctor. Arbet Engels is a very seasoned executive with significant experience in drug discovery, 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 science 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 Doctor. Murray Stewart, who's been serving as our Interim Chief Medical Officer And leading the MAVERICK's for WAM NDA submission efforts. Speaker 200:05:33Rest assured Murray will still be staying on as a consultant to the company to finalize the NDA submission and help onboard Christophe 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 Estafa, our CFO, to quickly cover the financial highlights of the quarter and recent updates before we turn our focus to our chronic neutropenia program. Adam? Speaker 300:06:03Thanks, Paula, and thanks to all of you on the call today. Concurrent with the announcement of the positive additional Phase 3 4 WIM results in mid May, we were able to complete a pipe financing priced at the market, raising approximately $65,000,000 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 3,000 Index when the index completed its annual reconstitution in late June. As a reminder, the annual reconstitution captures the 4,000 largest U. Speaker 300:06:40S. Stocks as of April 28, 2023, ranking them by total market capitalization and membership in the index remains in place for 1 year. And just last week, we announced the completion A $115,000,000 debt facility with Hercules Capital. We believe this overall transaction is strategically impactful to Exfor 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 $142,300,000 as of June 30, 2023. Speaker 300:07:24We believe that these funds Plus the $22,500,000 drawn down from the debt facility upon closing extend our cash runway into 2025. And we note that this projection does not include potential additional drawdowns on the debt facility and does not include the I'll now pass it back to Paula to provide the updates across our chronic neutropenia program. Paula? Speaker 200:07:58Thanks, Adam. Before we get into our new data, let's quickly review MAVERICKS-four for those who may not be familiar. MAVERICK support is an orally available CXCR4 antagonist that we're developing for a number of chronic neutropenic disorders and WIM syndrome, a rare If we're successful, MAVERICK CIFOR would be the first therapy for those with WIM syndrome and in chronic neutropenia, MAVERICK In trials to date, MAVERICK 4 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 health We've also successfully completed a Phase 1b clinical trial of MAVERICKISSE-four in certain chronic neutropenic disorders and are currently studying MAVERICK's 4 in a Phase 2CN trial. As a reminder, we previously that our market research using ICD-ten code diagnosis methods suggest that roughly 50,000 people in the U. S. Speaker 200:09:23Have 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's before across the spectrum of these 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 and 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. Speaker 200:10:20This robust methodology has provided some valuable insights into the real world What this research has confirmed is that there remains significant unmet needs across The broader CN patient population despite the availability and use of G CSF therapy. And it has helped us quantify what we believe 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 MAVERICK's 4 can have an impact. This aligns with the population we intend to study in our planned Phase Given this initial segmentation, we then looked at those who experienced severe or We can characterize this initial target group as patients with high unmet need. Our research suggests that the High unmet need population approximates 1 third of the total estimated 50,000 people diagnosed with chronic neutropenia in the U. S. Speaker 200:11:40We would consider this a minimum initial addressable population for MAVERICK score, a number that has the potential to expand significantly if we include younger populations, Those with intolerance to or poor quality of life on G CSF, those ineligible for G CSF and or those with more moderate disease presentation. In all cases, we are excited to potentially deliver the 1st oral treatment option to reduce infection and treatment burden in the patient population. I'll now pass the call over to Doctor. Murray Stewart, our Interim CMO, to share some initial Phase 2 trial data, which are further informing our regulatory discussions and our Phase 3 trial design. Murray? Speaker 400:12:25Thank you, Paula. As a reminder, we completed our Phase 1b study in people's idiopathic, cyclical of Congenital Chronic Neutropenia and reported results in late 2022. This 25 patient study of a single dose of MAVERICKS per demonstrated 100% response rate. All participants with or without concurrent G CSF dosing Achieved an increase in ANC of at least 500 cells per microliter at peak versus baseline. We consider this a profoundly positive result across the spectrum of CNS disorders studied. Speaker 400:13:05Based on these exciting data, We quickly advanced to study chronic dosing of MavriXpert in the same CN population. In the Phase 2 portion of the study, MABRIX004 is being dosed daily on top of each participant's baseline standard of care, either nothing or injectable GCFF. During the Phase 2 trial, mean ANCs are being evaluated monthly, where the mean is the average of neutrophil counts at time 0 and at 4 hours post dosing. Where time 0 represents the nadir and 4 hours approximates the peak ANC post mavericks for dosing. The goal of the ongoing Phase 2 study is to determine if MAVERICK's full results and an increase in ANC response. Speaker 400:13:55If this response is durable and maintained over months of treatment and where appropriate to set that patients can reduce G CSF therapy With A and C 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 3 months of dosing data, all of whom were on stable doses of G CSF at baseline. Given the market research results we've just shown correlating the high unmet need despite GCFF available to induce, We believe it's important to show that MAVERICK SPA safely increases ANC count, that response is durable Notably, the 3 G CSF treated participants dosed with Mavriksberg showed robust increases in ANC counts versus baseline. And all patients achieved normalization of neutrophil counts, including the 2 participants who had significant neutropenia at baseline despite being on GCSF. Speaker 400:15:23Nutrieval evaluations were durable and robust. In fact, the increases in ANC, which reached just over 10,000 cells per microliter enabled physicians to decrease G CSF dosing by at least 50% as early as the 2 month time point. In two cases, GCF dosing has now been withdrawn completely Patients continue on study to set ANC levels while on MAVERICK's for monotherapy. Importantly, MAVERICK's safety profile, whether in combination with G CSF or as a single We thought it might be helpful to visualize these data. So let's walk through an example of durable ANC changes over time And reduction in G CSF dosing in participant 1, who is a profile consistent with the planned inclusion criteria of our Phase 3 trial. Speaker 400:16:27First, let's orientate you to what we're looking at. On the y axis, our mean ANC measured in months on study. Baseline or the time zero value represents A and C levels prior to the addition of maverixibor. The low light red band on the graph generates neutropenia or ANC levels below 1500 cells per microliter. The light green zone represents a normal range of absent neutrophil counts. Speaker 400:17:06Participant 1 who was diagnosed with Chronic idiopathic neutropenia or CIN was neutropenic at baseline despite being on chronic G CSF. Baseline A and C was about 1100 cells per microliter as shown on the graph at time 0. Here we see changes in mean ANC levels after 2 months of dosing of MAVERICK's for and stable GCFF. Mean A and C counts increased to just above the upper limit of normal, an increase of about 9,000 cells per microliter or 9 fold versus baseline. When the NC can't meaningfully increase, physicians are given the option to decrease either MAVERICK SBIRT or G CSF as per protocol. Speaker 400:17:52In this case, the treating physician recommended GCS dosing be decreased, at which time participant 1's G CSF dose was reduced by 50% and the MAVERICK spread dose remained unchanged. At month 3, mean A and C counts were again assessed. Neutropl counts remained solidly within the normal range and still robustly above baseline counts. This therefore supported a further reduction in G CSF to 25% of the regional dose at the 3 month time point. Finally, month 4, after being on MAVERICK's for 400 milligrams daily At 25% of baseline G CSF doses, neutrophil counts continue to stay within the normal range, supporting the decision to withhold G CSF This participant has continued on study to assess A and C levels on MAVERICK's for monotherapy. Speaker 400:18:532 other participants were concurrently treated with MAVERICK's for anti CSF for 3 months or longer In both cases, physician decided to reduce or eliminate G CSF dosing while maintaining Mabryx for a 10 oral once daily dose of 400 milligrams. 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 MAVERICK SBIRT in combination with G CSF. 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. Speaker 400:19:47With chronic dosing of MAVERICK's in combination with G CSF, Large increases in MENA and C were observed durably over months in treatment, which supported physician decisions to reduce or eliminate G CSF dosing. We continue to believe that the neuro well tolerated once daily treatment could be transformative for this patient population, whose only current treatment option is an injectable drug that carries 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 maverixivore, which is consistent with the market research we've just shared, an estimated population of approximately 15,000 people in the U. Speaker 400:20:59S. 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 for the diagnosis of chronic idiopathic congenital or acquired primary neutropenia. We will study adolescents and adult subjects who are neutropenic and to also demonstrate severe or recurrent infections regardless of background therapy. Speaker 400:21:30The trial will be randomized, 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. G CSF 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 program. We're finalizing 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. Speaker 400:22:19We'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 4 WIM trial, 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 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? Speaker 200:22:58Thank you, Murray. As you can hopefully hear in our voices, we 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 WIM Phase 3 results, where MAVERICK's for treatment demonstrated durable ANC increases and reduced Given that, we're planning to provide an update on our launch readiness, physician outreach efforts and updates on the WIM market in our Q3 earnings call, And we hope you'll join us for that. And today, we've shared 3 important new advances. 1st, Data clarifying our initial target population in CN as being the approximately 15,000 diagnosed in the U. Speaker 200:23:50S. With high unmet need. 2nd, our favorable emerging data of long term MAVERICK's for treatment, where the durable large increases in And see over months of dosing led to physicians' election to reduce G CSF dosing. And third, We've completed initial FDA discussions based on our emerging data and gained further clarity around our CN Phase 3 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 and WIM and the launch of our next Phase 3 in CN in the first half of next year. Speaker 200:24:29We 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. Operator? Operator00:24:49Thank Our first question is from Stephen Willey with Stifel. Please proceed. Speaker 500:25:16Yes, 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 to 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 50% reduction, a 25% reduction and then fully off? Speaker 500:25:49Or could Patient 1 just have been taken off GCSF at any time point for the subjective assessment of the investigator. Speaker 200:25:57Thanks, Steve. I'll pass it over to Marie to answer that. Speaker 400:26:00So in this specific protocol, We in Phase 2, 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 the protocol have either stopped the GCSF or stopped Maverick's. And In the cases we've described, we've actually chosen to taper. Now, at the moment regarding your second point is, Do they taper 50%, 25%. Speaker 400:26:40We in Phase 2 are open to the physician deciding on how they want Taper, when we move into Phase 3, I think it's got to be a lot more coordinated in terms of thresholds to taper And maybe a couple of comments regarding tapering. So in most other diseases, if you're tapering, say, off steroids, You've got to do it very carefully because you could have what you call a rebound effect. In the case of tinkering GCSF, you can't actually just You don't have a problem other than obviously the risk of the can't going low. So we don't need to be Structured doesn't take things with steroids. We can actually do it in 1 or 2 steps. Speaker 400:27:23And that's the thing we're considering how to make Clear propositions to follow, a 1 or 2 step process in discontinuation. Speaker 600:27:33Okay. Speaker 500:27:34And 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 A and Cs As the tapering has increased, I guess, what's your level of confidence that, I guess, at the next time point, month 5, month 6, 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 loan? Speaker 400:27:59Yes. So 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 have surprised it's happening so quickly. So as a physician Observing patients in this study seeing the ANC response to robustly in combination, the fact after a couple of months They are able to take on GCSF is really exciting clinically. Speaker 400:28:29So 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. Speaker 500:28:36Okay. And then maybe the last question Speaker 200:28:39I'm sorry. Go ahead. Speaker 700:28:40No, I Speaker 200:28:40was just going to add, The 9,000 cell increase in neutrophil count is attributed to maverickza 4. So that's been a very impressive initial response. And then the question is, obviously, the drugs are acting in concert together. So the question is how low can we go With GCSF ideally 0 or ideally as infrequently as possible and all the evidence today supports that we can get some patients across that paradigm. Speaker 500:29:08Okay. 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 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. Speaker 400:29:28Thanks. Yes. You'd be glad to know there's more than 3. I'm not going to give that specific number. But the reason we spoke about these 3 is They've got more than 3 months. Speaker 400:29:38We've got 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, we're pleased with what we're seeing, which is why we're sharing the data. This might be being a little We'd like over the summer. We hope it will pick up and we'll have more data later in the year. Speaker 500:29:58All right. Thanks for taking the questions. Operator00:30:03Our next question is from Kristin Kluska with Cantor Fitzgerald. Please proceed. Speaker 800:30:10Good 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 And what your expectations at baseline might be for some of these patients and ultimately what would be deemed clinically meaningful here? Speaker 200:30:41Sure. Thanks, Kristen. I'll turn it over to Mark to answer that. Speaker 900:30:45Yes. Hi, good morning. We continue to believe there are about 50,000 people living in the U. S. With chronic neutropenia. Speaker 900:30:52What's new is that we have 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 So this is a significant opportunity for X4 as we're focused on bringing oral maverixa forward to target the underlying disease and address the unmet needs in these patients. And as Marty explained in his presentation, these are important insights that have now informed our preparations for the Phase 3 trial in chronic neutropenia. Speaker 800:31:42Thank 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 that 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? Speaker 400:32:07Yes, it's Murray. So, in Phase 2, we did allow people with different ranges of ANC, but it's important to To show an example of someone who would exactly fit the criteria for the PAC, which is below normal ANC. And we know people Who have an ANC below normal are at risk of infection compared to people who normal ANC. And in the Phase 3 study, we're recruiting people who've got Hello, NC and have had prior history of infection. So we know some people coming into the Phase 2 have had prior history of infection. Speaker 400:32:42It's too early to see any infection data. And as you may remember from our WIM study, we started seeing really after 3 months the reduction in infection The increase in NANDC translate to reduction infection over time. And that's why the Phase 3 study to show effect on infection is a year. Speaker 800:33:04Okay. 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 3 trial? Speaker 800:33:14Like is there a threshold, a number that they have had to Experience in the past or how are you thinking about that definition? Speaker 400:33:25Yes. So, at a high level, they have to at least have 1 or 2 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. Speaker 800:33:44Okay, got it. Thanks for taking my questions and hope to see you in San Diego. Speaker 200:33:50Look forward to it. Operator00:33:53Our next question is from Ted Tenthoff with Piper Sandler. Please proceed. Speaker 1000:33:59Thank 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? Speaker 1000:34:16Are there any inspections that need to occur? And I mean, maybe it's early to tell, but with rapid review cycle, would you anticipate an AdCom? Thanks for reviewing all that. Okay. Speaker 400:34:33So, we're very encouraged where we are at the NDA. So, there's no data. There's no content waiting. Those who have done an NDA will know it's a lot of its QC and Publishing. So it's really just tying up the loose ends in the next Few weeks. Speaker 400:34:50Regarding the inspection, once we submit, it wouldn't be unusual for the FDA to want to inspect Product that is up for approval and the quality team are ready for inspection if they choose to come and visit us. Speaker 1000:35:09Excellent. Thank you. And on an AdCom? Speaker 400:35:14So I'd be Shocked if we get an adcom. Yes. And the reason I say that is because It's if it was borderline or didn't work, then they might want an outcome or there were some safety issues. So we don't have any safety issues that warrants an We've got clear clinical efficacy and that's why I think it's highly unlikely. Speaker 600:35:39Awesome. Great. Well, best of luck. Speaker 200:35:43Thanks, Ted. Operator00:35:44Our next question is from Mark Frahm with Cowen and Company. Please proceed. Mark, your line is live. Please check and see if you're muted. Speaker 1100:35:59Thanks for taking my questions. Congrats on the data. And obviously, a ninefold changes It seems quite significant in A and C, but can you just review the kind of enrollment process and kind of how many measures leading up to That baseline measure of ANC you're able to capture and can you speak to the variability you're seeing in The one patient presenting, but maybe also more broadly in the trial. Speaker 400:36:26Yes. So in the Phase 2 that 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 sense, providing they do that, it can be very variable. But the important thing clinically is the response of 500. Speaker 400:36:50And providing you get that, I'm less concerned about the variability. And obviously, we've got a threshold that Well above normal for titration, but we're seeing different individuals do that, but all the individuals show their response. Speaker 200:37:05So Mark, so far in the Phase 2, every time we're examining a patient durably, we see exactly what we've seen in the Phase 1, Which is every patient is responding with at least a 500 sol per microliter jump. Obviously, with 9,000 being an example, More patients are certainly along those lines, given the concurrence of G CSF and our excitement for the patients and for us is How can we get them to the low or no dose of GCSF? Speaker 1100:37:35Okay. That's great. And then Maybe on to that point of that being an important goal, would you expect an endpoint around that to be maybe not the primary, but in your Phase 3 To be formally assessed, GCSS sparing ability? Yes. Speaker 400:37:53So certainly that's under consideration. I think what you've got to say is How is a clinical endpoint? Is it withdrawal completely? Is that the endpoint? Is it related to the clinical benefit of Drawing should be related to some of the issues like bone pain. Speaker 400:38:09So all that's under consideration. Speaker 1100:38:13Okay. Thank you. Operator00:38:17Our next question is from Mayank Bantami with B. Riley, please proceed. Speaker 700:38:25Hey, guys. It's Madison on for Thanks for taking our call and congrats on the data. If I can ask you a quick Follow-up regarding your imminent NDA. I'm wondering if that package is going to include your recent impressive 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? Speaker 700:38:57And then lastly, if I can get a quick one in, Your market research, did that factor in patient or like clinician perspective or excitement? Thanks. Speaker 200:39:09I'll let Marie take the first part of that and Mark can jump in for the second. Speaker 400:39:13Yes. So from a regulatory point of view, We submit all the data to the NDA based on data cutoffs. So there was a data cut off earlier in the year where we put all And then there's an opportunity for either a 90 or 120 day review where we then put in all the data up to, say, August or August to 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. Speaker 200:39:46So I think just to clarify the question, Murray, because we're very excited about this. The data that we showed in May, which Reductions in frequency, severity and duration of MAVERICK's foreign women 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 So the final label is to be determined, but it's a very key element of the proposed NDA filing. Speaker 400:40:17Yes. No, sorry about 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. Speaker 200:40:30And then Mark, do you want to comment? Speaker 900:40:32Just 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 neutropenia patients. So these are insights directly from those physicians. They're looking at the So it's a real world picture of the CN landscape. Speaker 700:41:00Got it. I see. Thanks guys. Operator00:41:05Our next question is from Trevor Allred with of Oppenheimer and Company. Please proceed. Speaker 600:41:10Hey, good morning. Thanks for taking the question. Could you guys talk a bit The FDA feedback on the Phase 3 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? Speaker 400:41:31Yes. 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 2 major issues we The topics we discussed were related to the primary endpoint. And I think it's Clearly, we 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 us. And the study design is therefore very similar to Wim. Speaker 400:42:08We shared the data we shared with you today with the FDA deliberately to discuss whether tapering would be appropriate. The FDA were aware of that and clearly said consider that and how you want to capture that and that's Operator00:42:33Our next question is from RK with H. C. Wainwright. Please proceed. Speaker 1200:42:40Thank you. Good morning, Paolo and Adam. Most of my questions have been answered, but In general, with the data that you have seen so far with mavrixophore, What additional indications could you highlight as a possible way of label expansion from here beyond the CN? Speaker 200:43:06Yes. So, I'll take that our case. I mean, maybe just a quick review. So, we're thrilled about WAM, right? We see this massive elevation across all white blood Some type including neutrophils and that's led us to chronic neutropenia and kind of that correlation of increased neutrophils, reduced infection rates. Speaker 200:43:25In WIM Phase 3, 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 mind share 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 WIM certainly that nice correlation and reduction in You can appreciate there's a nice landscape for the next round of pipeline expansion, but we'll get to that next year. Operator00:44:09We have reached the end of our question and answer session. I would like to turn the conference back over to Paula for closing comments. Speaker 200:44:17We really appreciate everyone joining us today. You can appreciate how thrilled we are with such productive 12 weeks since we last had our WIM Phase 3 update, Operator00:44:32Thank you. This does conclude today's conference. You may disconnect at this time and thank you again for your participation.Read morePowered by