X4 Pharmaceuticals Inc (XFOR) 2023 Q2 法說會逐字稿

Greetings. Welcome to X4 Pharmaceuticals second-quarter 2023 financial and operating results conference call. (Operator Instructions) As a reminder, this conference call is being recorded.

It is now my pleasure to introduce your host, Dan Ferry, from LifeSci Advisors. Please begin.

Thank you, operator, and good morning, everyone. Presenting on today's call are the X4's Chief Executive Officer, Dr. Paula Ragan; 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 we'll be joined by Chief Scientific Officer, Art Taveras; 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 forecasted. A discussion 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 Ragan. Paula?

Thanks, Dan. Hello, everyone. We'll be covering a lot of exciting updates this morning, so thank you for joining us on this call. Adam and I 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 insight on what we estimate to be the minimum addressable US market for mavorixafor 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 3 4WHIM trial in May that followed its closure 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 mavorixafor treatments statistically significantly and durably raised both absolute neutrophil and lymphocyte counts, both ANC and ALC, versus placebo, these new data revealed that mavorixafor treatment also resulted in a statistically significant reduction in annualized infection rate and effective 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. Raffaele Badolato 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 mavorixafor, 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 neutropenia in more than 30 years. And we are now poised to submit our first new drug application with the FDA, seeking US approval of oral, once-daily mavorixafor for the treatment of people aged 12 years and older with WHIM syndrome. There's 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 mavorixafor in June. This granted patent, the third issued patent covering mavorixafor's composition of matter, protects compositions of matter, comprising mavorixafor and related drug substances formed during the mavorixafor manufacturing process through December of 2038.

And we are thrilled to have recently announced the appointment of Dr. Christophe Arbet-Engels, our new Chief Medical Officer. Dr. Arbet-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 mavorixafor WHIM 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 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 Mostafa, 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?

Thanks, Paula, and thanks to all of you on the call today. Concurrent with the announcement of the positive additional Phase 3 4WHIM 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 US 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 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 mavorixafor be approved for WHIM syndrome in the US in 2024.

I'll now pass it back to Paula to provide the updates across our chronic neutropenia program. Paula?

Thanks, Adam. Before we get into our new data, let's quickly review mavorixafor for those who may not be familiar. Mavorixafor 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, mavorixafor would be the first therapy for those with WHIM syndrome. And in chronic neutropenia, mavorixafor would be the first oral treatment option in the market, currently only served by injectable therapies associated with treatment-limiting adverse events.

In trials to date, mavorixafor 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 3 clinical program in WHIM syndrome and are poised to submit the US NDA for mavorixafor in that indication. We've also successfully completed a Phase 1b clinical trial of mavorixafor in certain chronic neutropenic disorders and are currently setting mavorixafor in a Phase 2 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 US 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 mavorixafor 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 and patient segmentation across the end 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 US.

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 could be the minimum addressable market for mavorixafor 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 mavorixafor 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 experience severe or recurrent symptoms as well as the symptoms are deemed severe enough by physicians to warrant treatment with injectable G-CSF. 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 US. We would consider this the minimum initial addressable population for mavorixafor, a number that has the potential to expand significantly if we include the 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 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 2 trial data, which are further informing our regulatory discussions and our Phase 3 trial design. Murray?

Thank you, Paula. As a reminder, we completed a Phase 1b study in people's idiopathic, cyclical, or congenital chronic neutropenia and reported results in late 2022. This 25-patient study of a single dose of mavorixafor demonstrated a 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 CN disorders studied.

Based on these exciting data, we quickly advanced to study chronic dosing of mavorixafor in the same CN population. In the Phase 2 portion of the study, mavorixafor was being dosed daily on top of each participant's baseline standard of care, either nothing or injectable G-CSF.

During the Phase 2 trial, mean ANCs are being evaluated monthly, where the mean is the average of neutrophil counts at time zero and at four hours post-dosing. Time zero represents the [nay] here, and four hours approximates the peak ANC post-mavorixafor dosing.

The goal of the ongoing Phase 2 study is to determine if mavorixafor results in an increase in ANC response. If this response is durable and maintained over months of treatment -- and where appropriate, [decisive] patients can reduce G-CSF therapy with ANC volumes 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 G-CSF at baseline. Given the market research results we've just shown correlating the high unmet need despite G-CSF available and use, we believe this [important] showed mavorixafor safely increases ANC count, that response is durable, and that mavorixafor can enable the reduction in G-CSF use.

Reduced G-CSF may benefit patients by also reducing the known adverse events and risks associated with the therapy, consequentially improving quality of life. Notably, the three G-CSF-treated participants dosed with mavorixafor showed robust increases in ANC count versus baseline; and all patients achieved normalization of neutrophil count, including the two participants who had significant neutropenia at baseline despite being on G-CSF.

Neutrophil evaluations were durable and robust. In fact, the increases in ANC, which reads just over 10,000 cells per microliter, enabled physicians to decrease G-CSF dosing by at least 50% as early as that two-month time point. In two cases, G-CSF dosing has now been withdrawn completely, but patients continue on study to assess ANC levels while on mavorixafor monotherapy.

Importantly, mavorixafor safety profile, whether in combination with G-CSF 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 examples of durable ANC changes over time and reduction in G-CSF dosing in participant one with a profile consistent with the planned inclusion criteria of our Phase 3 trial.

First, let's (inaudible) take you to what we're looking at. On the y-axis our main ANC, or absolute neutrophil count, are set over to four hours as previously described. On the x-axis is time measured in months on study. Baseline of the time zero value represents ANC levels prior to the addition of mavorixafor. The low light red band on the graph denotes neutropenia or ANC levels below 1,500 cells per microliter. The light green zone represents a normal range of absolute neutrophil counts.

Participant one who is diagnosed with chronic idiopathic neutropenia, or CIN, was neutropenic at baseline despite being on chronic G-CSF. Baseline ANC was about 1,100 cells per microliter, as shown on the graph at time zero. Here, we see changes in mean ANC levels after two months of dosing of mavorixafor and stable G-CSF. Mean ANC count increased to just above the upper limit of normal, an increase of about 9,000 cells per microliter or nine-fold versus baseline.

For the ANC count to meaningfully increase, physicians are given the option to decrease either mavorixafor or G-CSF as per protocol. In this case, the treating physician recommended the G-CSF dosing be decreased, at which time participant one's G-CSF dose was reduced by 50% and the mavorixafor dose remained unchanged.

At month three, mean ANC counts were again assessed. Neutrophil counts remained solidly within the normal range and still robustly above baseline count. This therefore supported a further reduction in G-CSF to 25% of traditional dose at the three-month time point.

Finally, at month four, after being on mavorixafor for 400 milligrams daily and 25% of baseline G-CSF doses, neutrophil counts continued to stay within the normal range, supporting the decision to withhold G-CSF dosing altogether. This participant has continued on study to assess ANC levels on mavorixafor monotherapy.

Two other participants were concurrently treated with mavorixafor and G-CSF for three months or longer and achieved large increases in mean ANC versus baseline volumes. In both cases, the physician decided to reduce or eliminate G-CSF dosing while maintaining mavorixafor at an 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 mavorixafor 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.

With chronic dosing of mavorixafor in combination with G-CSF, large increases in mean ANC would observe durably over months in treatment, which supported physician decisions to reduce or eliminate G-CSF dosing. We continue to believe that an oral, 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 pipeline of the Phase 3 trial designed to support a potential label expansion from mavorixafor, which is consistent with the market research we just shared, an estimated population of approximately 15,000 people in the US with significant unmet need. We've incorporated feedback from our meeting with the FDA into this proposed study design.

We expect the population to include participants with the 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 randomized, placebo-controlled, and blinded over a 12-month treatment period to examine changes in ANC 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 WHIM Phase 3 trial is supported by 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. We'll provide further updates when we have final clarity on these remaining aspects of the trial.

Importantly, the overall objective, design, and duration of the study is similar to that of our 4WHIM 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 to submit our first NDA. We are very excited about the path forward to help those in need with a range of chronic neutropenia disorders.

I'll now turn the call back over to Paula. Paula?

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 3 results, where mavorixafor treatment demonstrated durable ANC increases and reduced frequency, severity, and duration of infections. And we're now poised to submit our first NDA for mavorixafor. Given that, we're planning to provide an update on our launch readiness, physician outreach efforts, and updates on the WHIM 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 US with high unmet need; second, our favorable emerging data of long-term mavorixafor treatment, where the durable, large increases in ANC 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 in WHIM and the launch of our next Phase 3 in CN in the first half of next year. We are well positioned to potentially deliver a meaningful oral option, first to those with WHIM 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?

Thank you. (Operator Instructions) Stephen Willey, Stifel.

Yeah. Good morning, guys. Thanks for taking my 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 G-CSF 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 had been taken off G-CSF at any time point for the subjective assessment of the investigator?

Thanks, Steve. I'll pass over to Murray to answer that.

So in this specific protocol, we -- in Phase 2, we want patients to taper, for safety reasons, at about 10,000. But we're also open to discussions with the PIs if they feel they want to take part at another level. And they can obviously, in the protocol, either stop the G-CSF or stop mavorixafor. And in the cases we've described, they've actually chosen to taper.

Now at the moment, regarding your second point is, do they taper, 50%, 25%? We, in Phase 2, are open to the physician deciding on how they want to taper. But when we move into Phase 3, I think that'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, steroids, you've got to do it very carefully because you can have what you call a rebound effect. In the case of tapering G-CSF, you can actually just stop G-CSF. You don't have a problem other than obviously the risk of the count going below.

So we don't need to be structured in tapering the steroids. We can actually do it in one or two steps. And that's the thing we're considering, how to make it clear propositions to follow a one- or two-step process in discontinuation.

Okay. Then I guess I'll follow up with the obvious question. I mean, you've seen a little bit of a stepwise reduction in ANCs 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 comfortably above the normal range in terms of ANC with this patient who is on mavorixafor?

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 am surprised it is happening so quickly.

So as a physician observing patients in this study, seeing the ANC response robustly in combination; the fact that after a couple of months, we are able to taper G-CSF is really exciting clinically. So I'm optimistic, but I'm also realistic. And I think we need to wait for long-term data to see how this plays out.

Okay. And then maybe the last question -- yeah. Go ahead.

I'm sorry. Go ahead. No, I was just going to add. The 9,000-cell increase in neutrophil count is attributed to mavorixafor. 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 G-CSF, ideally zero or ideally as infrequently as possible? And all the evidence today supports that we can get some patients across that paradigm.

Okay. And then maybe just last quick question. I guess, can you just speak to how many patients you've enrolled to date? 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 and how long of a follow-up we'll see. Thanks.

Yeah. If you've got 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 furthest along. They've got more than three months. We'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. But we're pleased with what we're seeing, which is why we're sharing the data.

Look -- and this might have been a little bit slower than we'd like over the summer. We hope it'll pick up and we'll have more detail later in the year.

All right. Thanks for taking my questions.

Kristen Kluska, Cantor Fitzgerald.

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 help you in terms of your Phase 3 protocol design and what your expectations at baseline might be for some of these patients? And ultimately, what would be deemed clinically meaningful here?

Sure. Thanks, Kristen. I'll turn it over to Mark to answer that.

Yeah, hi. Good morning. Yeah, we continue to believe there are about 50,000 people living in the US 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 in 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 G-CSF.

So this is a significant opportunity for X4, as we're focused on bringing oral mavorixafor to target the underlying disease and address the unmet needs in these patients. And as Murray explained in his presentation, these are important insights that have now informed our preparations for the Phase 3 trial in chronic neutropenia.

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 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?

Yes, it's Murray. So in Phase 2, we did allow people with different ranges of ANC. But it's important to show an example of someone who would exactly fit the criteria [DAC], 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 have got a low ANC and have had a 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 WHIM study, we started seeing really after three months a 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 an effect on infection is a year.

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 3 trial? Is there a threshold, a number, that they have had to experience in the past? Or how are you thinking about that definition?

Yeah. So at a high level, they have to at least have one or two serious infections. And by that, I mean, that is not just cold or sniffles. They will have needed to be prescribed antibiotics or hospitalized. In other words, a serious infection that needed medical attention.

Okay, got it. Thanks for taking my questions and hope to see you in San Diego.

Looking forward to it.

Ted Tenthoff, Piper Sandler.

Thank you. Good morning. And I can really sense the excitement and understand why with some of the progress going on. Just wanted to tighten up a little bit on the NDA. What remains to be done? Are there any inspections that need to occur? And I mean, maybe it's early to tell. But with a rapid review cycle, would you anticipate an AdCom? Thanks for reviewing all that.

Okay. We're putting cards away. We are at the NDA, so there's no data. There's no content waiting. Those who had 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 chooses to come and visit us.

Excellent. Thank you. And on the AdCom?

So I'd be shocked if we get an AdCom. And the reason I say that is because -- if it was borderline or didn't work, then they might want an AdCom or there are some safety issues. So we don't really see the safety issues that warrants an AdCom. We've got clear clinical efficacy, and that's why I think it's highly unlikely.

Awesome. Great. Well, best of luck.

Thanks, Ted.

Thank you.

Marc Frahm, Cowen and Company.

Thanks for taking my question. Congrats on the data. And obviously, a nine-fold change seems quite significant in ANC. But can you just review the kind of enrollment process and how many measures leading up to that baseline measure of ANC you were 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?

Yeah. 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 senses, providing they do that, they can be very variable. But the important thing clinically is the robust response of 500. And provided you get that, I'm less concerned about availability.

And obviously, we've got a threshold if it's well above normal for titration. But we're seeing different individuals do that. All the individuals show the response.

But Marc, 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-cell-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 G-CSF?

Okay, that's great. And then maybe on that point of that being an important goal, do you expect an end point around that to be -- maybe not the primary, but in your Phase 3 to be formally assessed -- G-CSF sparing ability?

Yeah. So certainly, that's under consideration. I think what you're going to see is how is it a clinical endpoint. Is it withdrawn completely? Is that the endpoint? Is it related to the clinical benefit of withdrawing for it to be related to some of the issues like bone pain? So all that under consideration.

Okay. Thank you.

Mayank Mamtani, B. Riley.

Hey, guys. It's [Madison] on for Mayank. 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, on your market research, did that factor in patient or clinician perspective or excitement? Thanks.

So I'll let Murray take the first part of that, and Mark can jump in for the second.

Yeah. So from a regulatory point of view, we submit all the data to the NDA based on data cutoffs. So there was a data cutoff earlier in the year, where we put all the data into this bar. 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 September. So we will be including all the past data, and any recent data will be in the natural follow on request by the FDA for a 120-day follow-up.

I think just to clarify the question, Murray, because we're very excited about that. The data that we showed in May, which reflected reductions in frequency, severity, and duration of mavorixafor in WHIM patients versus placebo, they're 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 to be determined, but it's a very key element of the proposed NDA filing.

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've previously presented.

And then Mark, if you want to comment --

And 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 neutropenia 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.

Got it. I see. Thanks, guys.

Trevor Allred, Oppenheimer & Co.

Hey, good morning. Thanks for taking the question. Could you just talk a bit about 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?

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 discuss with them -- 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 got enough patients that were powered for that. 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. The FDA were aware of that and clearly said, consider that and how you want to capture that. And that's what we're doing at the moment.

Okay. Thanks.

RK, H.C. Wainwright.

Thank you and good morning, Paula and Adam. Most of my questions have been answered. But in general, with the data that we've seen so far with mavorixafor, what additional indications could you highlight as a possible way of label expansion from here, beyond the CN?

Yes. So I'll take that, RK. I mean, maybe just a quick review. So we're thrilled about WHIM. We see this massive elevation across all white blood cell subtypes, including neutrophils. And that's led us to chronic neutropenia and that correlation of increased neutrophils, reduced infection rates.

In WHIM Phase 3, there's additional data that does suggest a breadth of impact across the immune system. We previously directed 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 WHIM, certainly that nice correlation and reduction of 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.

Thank you. Thank you for taking my questions.

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.

We really appreciate everyone joining us today. You can appreciate how thrilled we are with the productive 12 weeks since we last had our WHIM Phase 3 update. And we look forward to continuing to update everyone throughout the rest of the year. Enjoy the rest of your day.

Thank you. This does conclude today's conference. You may disconnect at this time. And thank you again for your participation.