X4 Pharmaceuticals Q2 2023 Earnings Call Transcript

Quartr
Provided by Quartr
August 10, 2023

There are 13 speakers on the call.

Operator

Welcome to X4 Pharmaceuticals Second Quarter 2023 Financial and Operating Results Conference Call. At this time, all participants are in a listen only mode. A question and answer session will follow the formal presentation. As a reminder, this conference call is being recorded. It is now my pleasure to introduce your host, Dan Ferry from Lakeside Advisors.

Operator

Please begin.

Speaker 1

Thank 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 1

As a reminder, on today's call, the company will be making forward looking statements regarding regulatory and product development plans as well as research activities. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasts. A description of these risks can be found in 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 1

Paula?

Speaker 2

Thanks, 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 2

First, 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 2

Importantly, 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 2

Rafael 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 2

There is a palpable excitement at the company these days as you can well imagine. We're also pleased to receive notice of issuance of an additional patent on 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 2

Doctor. 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 2

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 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 3

Thanks, 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 3

S. 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 3

We 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 2

Thanks, 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 2

Have been diagnosed with chronic neutropenia. Specifically, about 40,000 of these are diagnosed with chronic idiopathic neutropenia and about 8,000 of these are diagnosed with congenital and cyclic neutropenia. A key question that all of us have been aiming to better understand is the size of the expected initial target population for MAVERICK'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 2

This 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 2

We 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 4

Thank 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 4

Based 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 4

If 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 4

Nutrieval 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 4

First, 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 4

Participant 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 4

In 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 4

2 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 4

With 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 4

S. 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 4

The 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 4

We'll provide further updates when we have final clarity on these remaining aspects of the trial. Importantly, the overall objectives, design and duration of the study is similar to that of our 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 2

Thank 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 2

S. 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 2

We are well positioned to potentially deliver a meaningful oral option, First to those with WIM syndrome, next to those with CN, and our hope is to expand beyond these initial indications to bring new options to even more patients throughout the world. And with that, we'll now open up the call for your questions. Operator?

Operator

Thank Our first question is from Stephen Willey with Stifel. Please proceed.

Speaker 5

Yes, 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 5

Or could Patient 1 just have been taken off GCSF at any time point for the subjective assessment of the investigator.

Speaker 2

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

Speaker 4

So 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 4

We 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 4

And that's the thing we're considering how to make Clear propositions to follow, a 1 or 2 step process in discontinuation.

Speaker 6

Okay.

Speaker 5

And 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 4

Yes. 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 4

So I'm optimistic, but I'm also realistic and I think we need to wait for a long term date to See how this plays out.

Speaker 5

Okay. And then maybe the last question

Speaker 2

I'm sorry. Go ahead.

Speaker 7

No, I

Speaker 2

was 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 5

Okay. And then maybe just last quick question. I guess, can you just speak to how many patients you've enrolled to date? And I guess, How many of those patients 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 4

Thanks. 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 4

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, 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 5

All right. Thanks for taking the questions.

Operator

Our next question is from Kristin Kluska with Cantor Fitzgerald. Please proceed.

Speaker 8

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 And what your expectations at baseline might be for some of these patients and ultimately what would be deemed clinically meaningful here?

Speaker 2

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

Speaker 9

Yes. Hi, good morning. We continue to believe there are about 50,000 people living in the U. S. With chronic neutropenia.

Speaker 9

What'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 8

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?

Speaker 4

Yes, 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 4

It'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 8

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?

Speaker 8

Like is there a threshold, a number that they have had to Experience in the past or how are you thinking about that definition?

Speaker 4

Yes. 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 8

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

Speaker 2

Look forward to it.

Operator

Our next question is from Ted Tenthoff with Piper Sandler. Please proceed.

Speaker 10

Thank you. Good morning. And again, really, sense the excitement and understand why so much good progress going on. Just wanted to tighten up a little bit on the NDA. What remains to be done?

Speaker 10

Are 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 4

So, 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 4

Regarding 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 10

Excellent. Thank you. And on an AdCom?

Speaker 4

So 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 6

Awesome. Great. Well, best of luck.

Speaker 2

Thanks, Ted.

Operator

Our 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 11

Thanks 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 4

Yes. 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 4

And 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 2

So 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 11

Okay. 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 4

So 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 4

So all that's under consideration.

Speaker 11

Okay. Thank you.

Operator

Our next question is from Mayank Bantami with B. Riley, please proceed.

Speaker 7

Hey, 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 7

And 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 2

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

Speaker 4

Yes. 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 2

So 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 4

Yes. 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 2

And then Mark, do you want to comment?

Speaker 9

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 So it's a real world picture of the CN landscape.

Speaker 7

Got it. I see. Thanks guys.

Operator

Our next question is from Trevor Allred with of Oppenheimer and Company. Please proceed.

Speaker 6

Hey, 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 4

Yes. 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 4

We 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

Operator

Our next question is from RK with H. C. Wainwright. Please proceed.

Speaker 12

Thank 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 2

Yes. 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 2

In 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.

Operator

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.

Speaker 2

We 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,

Operator

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

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Key Takeaways

  • X4 is preparing to submit its first New Drug Application (NDA) to the FDA for once-daily oral maverixofor in WHIM syndrome after Phase 3 data showed durable and statistically significant increases in ANC and ALC along with reductions in infection rate, severity, and duration.
  • Through a combination of a $65 million PIPE and a $115 million debt facility from Hercules, X4 bolstered its balance sheet to $142.3 million in cash and equivalents as of June 30, 2023, extending its runway into 2025 without accounting for further drawdowns.
  • New market research triangulating physician surveys and claims data indicates a minimum initial U.S. addressable population of approximately 15,000 chronic neutropenia patients (≥ 12 years old) with severe or recurrent infections despite G-CSF therapy.
  • Emerging Phase 2 data from three patients on stable G-CSF plus maverixofor for at least three months demonstrated robust, durable ANC normalization (increases up to ~9,000 cells/µL), enabling physicians to reduce or withdraw G-CSF while maintaining neutrophil counts in the normal range with no new safety signals.
  • X4 has incorporated FDA feedback into a planned 12-month, randomized, placebo-controlled Phase 3 trial in chronic neutropenia in adolescents and adults, featuring co-primary endpoints of ANC increase and clinical benefit (infection burden and quality of life) alongside G-CSF tapering.
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Earnings Conference Call
X4 Pharmaceuticals Q2 2023
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