Greetings, and welcome to the X4 Pharmaceuticals First Quarter 2025 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 Lifesci Advisors. Please begin.

Thank you, operator, and good morning everyone. Presenting on today's call will be X4's Chief Executive Officer, Dr. Paula Ragan; and Chief Financial Officer, Adam Mostafa. Following prepared remarks by each, we will open the call to your questions, and will be joined by Chief Commercial Officer, Mark Baldry; and Chief Medical Officer, Dr. Christophe Arbet-Engels. As a reminder on today's call, the company will be making forward-looking statements regarding regulatory and product development plans. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted. A description of these risks can be found in X4's most recent filings with the SEC, including last year's Form 10-K and this past quarter's Form 10-Q which is expected to be filed after market close today. Please note that the X4 investor deck was updated this morning on the company website to include slides detailing some of the data analyses mentioned in this morning's press release and on this call today. I'd now like to turn the call over to X4's President and CEO, Dr. Paula Ragan. Paula?

Thank you, Dan, and thanks to all of you for joining us this morning. The first quarter of 2025 was an extremely productive and value-building period for X4 with clinical trial advancement in chronic neutropenia, continued progress in the commercialization of XOLREMDI for WHIM syndrome in the US and our achievement of several significant milestones towards expanding the global potential of mavorixafor for patients. Let's begin with mavorixafor for chronic neutropenia or CN. As you know, having successfully developed mavorixafor, branded XOLREMDI for patients with WHIM syndrome in the US, we are now also developing mavorixafor for the larger indication of chronic neutropenia. There are currently about 50,000 people diagnosed with some form of CN in the US based on retrospective ICD-10 code analyses. Of those currently diagnosed with primary CN, we estimate that approximately 15,000 individuals or about 30% to 40% have remaining health challenges and continue to experience low absolute neutrophil counts or ANCs and recurrent infections despite available standard of care. We define this as the high unmet need CN patient population. And it is with this population in mind that we are launching our ongoing 4WARD trial, a global pivotal Phase III clinical trial evaluating the safety and efficacy of once-daily oral mavorixafor in people with certain chronic neutropenic conditions including primary autoimmune, idiopathic and congenital neutropenia and who are experiencing recurrent and/or serious infections. As we reported on our last call, we're now screening and enrolling participants in over 20 countries with more than 90% of our target global trial sites being activated. Additionally, we've now finalized the trial design based on the feedback we also discussed previously from both the FDA and EMA to focus on those with the highest unmet needs, a population that matches up well with mavorixafor's targeted commercial CN patient population. The trial is enrolling with those with moderate to severe CN or ANC below 1000 cells per microliter and experiencing two or more infections over the past 12 months. We also finalized the ANC response endpoint. The definition of ANC response is now uniform across all participants and is defined as an increase in ANC greater than 500 cells per microliter versus baseline ANC and occurring at 50% or more of the time points evaluated in the trial. The trial seeks to demonstrate statistically significant increases in ANC response and corresponding decreases in annualized infection rates between those on mavorixafor versus placebo. To date, the demographics of the enrolled population are balanced and representative of the target commercial CN patient populations and baseline ANCs and historical infection rates are consistent with this high unmet need population. We recently completed some additional data analyses that further increase our confidence in the success of the 4WARD trial. Individual patient data from both the mavorixafor Phase 3, 4WHIM trial and the completed Phase 2 CN trial have now been analyzed applying this just mentioned 4WARD trial ANC response criteria. The full details of these analyses can be found in the updated investor deck that is on the front page of the Investors section of our website. In summary, we created what we're calling heat maps, which detail individual ANC responses across all trial participants at all the assessed time points. Specifically, the 4WHIM Phase 3 heat map provides a benchmark for ANC responses that translated into a 60% reduction in annualized infection rates when comparing mavorixafor treatment to placebo. The CN Phase 2 heat map demonstrates the impact of mavorixafor on durable increases in ANC across those with idiopathic cyclic and congenital chronic neutropenia. ANC outcomes in the CN Phase 2 trial look similar to ANC responses seen in the mavorixafor arm of the 4WHIM trial. When taken together these heat map analyses provide evidence supporting the potential success of the CN Phase 3 trial, where we believe that the expected ANC responses resulting from mavorixafor treatment will correspond to a significant decrease in annualized infection rates. We also continue to believe that the 4WARD trial is rigorously designed and powered to demonstrate the impact of mavorixafor in CN. The trial is powered at greater than 95% to assess the ANC response endpoint and the 150 participant sample size independently supports robust powering at greater than 90% for the infection rate results. As of today, we continue to anticipate full enrollment in the trial in the third or fourth quarter of 2025, which would enable disclosure of top line data in the second half of 2026. Lastly on the CN front, we have good news from the US patent office. We received a notice of allowance on our application which claims include the use of mavorixafor in treating severe chronic idiopathic and autoimmune neutropenia in patients without a CXCR4 genetic variant. The patent is expected to expire in the US in March of 2041. Similar patent applications are pending in Europe, China, Japan and Canada. To conclude, we remain confident that we'll be able to deliver on our upcoming milestones in CN that will have long-term patent protection in the indication and that the value proposition for mavorixafor in CN could represent a $1 billion to $2 billion opportunity in the US alone. With that let's turn now to our progress with mavorixafor in WHIM syndrome. At the end of March of this year cumulative sales of XOLREMDI reached $3.5 million since our mid-May launch last year. This quarter's sales were slightly lower than those reported in the fourth quarter because of the fluctuations in the timing of inventory resupply, which causes some lumpiness to sales. This is typical with markets anchored in small patient populations and early in launch. We do expect this to even out over time with the increasing demand that we're already seeing. We are currently in the thick of conference season and continue to have fruitful engagements with all of our targeted top-tier immunologists and hematologists increasing the visibility of WHIM syndrome. And we're seeing success in our educational efforts that support HCPs and finding WHIM patients with new patients now representing approximately 40% of our current XOLREMDI treated population at the end of the first quarter. In addition, we're just about to kick off our WHIM patient ambassador program and hope these efforts will continue to build demand for XOLREMDI in the US. As we discussed on our last call, we made significant progress in our efforts to expand the potential global reach of mavorixafor in WHIM during the first quarter. In January, we announced that our submitted MAA was accepted by European regulatory authorities for review. With a typical 12- to 15-month review process, we anticipate potential approval from the EMA as early as the first quarter of 2026. We also announced the completion of two international partnerships in the first quarter. The first with Norgine, a leading European specialty pharmaceutical company to commercialize mavorixafor in Europe, Australia and New Zealand. Norgine will be launching mavorixafor for the WHIM indication in the EU should we receive approval there next year and we are working closely with them to ready for that possibility. The second partnership is with Taiba Rare, another specialty pharmaceutical company to commercialize XOLREMDI in the Middle East and North Africa or MENA region following any approvals there. The MENA region does have a compassionate use program that allows physicians to prescribe drugs approved in other countries to local patients with no other treatment options. We'll keep you updated on our progress there. Lastly, we're continuing to advance the understanding of WHIM syndrome as well as the impact of mavorixafor on the disease. We had two abstracts accepted for publication at the Annual Meeting of the Clinical Immunology Society or CIS which starts today. From the 4WHIM Phase III open-label extension or OLE, we'll be presenting two-year data that demonstrate a marked clinical improvement in wart severity as assessed by a standard measurement, the clinical global impression of severity across 70 defined wart areas. We're also presenting results from the first-ever survey looking into infection burden in WHIM patients. 20 WHIM patients provided responses, none were on XOLREMDI at the time. The survey revealed that 60% of those under 18 years and 73% of those 18 or over reported experiencing at least one infection in the previous three months with 25% requiring overnight hospitalizations due to infection. The study concludes that the frequency and severity of infections requiring medical care and hospitalizations underscores the urgency to proactively treat patients with WHIM syndrome. Needless to say, we're very proud to be able to have developed this first approved therapy for WHIM in the US and look forward to commercial updates and continued global advancement milestones in the coming quarters. I'll now turn it over to Adam to run through our financials. Adam?

Thanks, Paula. As we disclosed in the press release this morning, we ended the first quarter of 2025 with just under $90 million in cash and cash equivalents. We continue to believe that we have sufficient funds to support company operations into the first half of 2026. We reported net XOLREMDI revenues of just under $1 million for the first quarter of 2025. As Paula mentioned, this brings our cumulative total sales since our May 2024 launch to about $3.5 million. Our R&D expenditures totaled $18.5 million for the first quarter and our SG&A expenses were $15 million for the first quarter. And finally, we had a small amount of net income in the first quarter due to the recognition of $28 million in license and other revenue from our partnership with Norgine, and a gain of $10.8 million on our outstanding Class C warrants which are measured at fair value each quarter. We also note that our 1-for-30 reverse stock split became effective on Monday following shareholder and Board approval, and we believe this should cure our current deficiency with the NASDAQ listing rules. Lastly, we have now completed the majority of the actions we laid out during our announced strategic restructuring in February. We continue to expect that these efforts will decrease our spending by about $30 million to $35 million annually. We'll now open the call up to your questions.

Thank you. We'll take our first question from Ted Tenthoff with Piper Sandler. Please go ahead.

Great. Thank you. Can you give us a sense if you have any visibility into the types of patients that are being enrolled? Is it largely in line with what you expect is enrolled in the Phase II trial? And then a follow-up on...

Good morning, Ted. We're having trouble hearing you; could you provide some clarity on the enrollment profile of the commercial market? So of course, we mentioned that we're very pleased with the overall profile. And I'll turn it over to Christophe for his remarks.

The study has very specific criteria, and so far, the profile of the patients we're enrolling is quite good, and we are actively monitoring this. From my discussions with some of the principal investigators, it seems that many of them would like to include more patients than we currently have in the study. They often have patients ready to participate, but they cannot alter their treatment just to accommodate the study requirements. However, there is clearly a strong interest and demand to include as many patients as possible in the research.

Sure. Maybe Mark just add one more comment there.

Yeah. Ted, I was just going to say we're continuing to build our insights into the CN market itself and actually just completed a large survey with about 95 US physicians who treat chronic neutropenia. And what we're finding is the case loads of patients that these physicians have are much higher than in WHIM. So in WHIM, it's a very fragmented model. But in chronic neutropenia, it's much more concentrated, much more defined because there are distinct definitive ICD-10 diagnosis codes. So we can clearly see where these patients are and the unmet need in this refractory population.

So I think just to quickly summarize to you Ted, very sick patients being enrolled in the study to enrich for success on the infection endpoint, higher demand both locally in the trial because they'd love to get their patients in the trial, but of course we can't accept everybody. And then Mark is seeing that pull-through in terms of the higher case flows through our market research.

Great. Thanks very much. Thank you.

Thank you, Ted.

Our next question comes from RK with H.C. Wainwright. Please go ahead.

Thank you. Good morning, Paula and Adam. A couple of quick questions. In the patient, the amount of patients that you said who are being diagnosed with CN, which is like 50,000 people and out of that 15,000 are the ones that seem to be having the high unmet need. These numbers are they just US or are they worldwide?

They're just US, RK, yes. We did ICD-10 analysis and the US claims data.

Okay, okay. Perfect. And then from your comments to Ted's question, you were stating that only very sick patients are being enrolled into the study. So I'm thinking about the label when what sort of the target population would you be looking at on the label? Is it the very sick population? Or is that beyond that? And how do we define that population?

So because, RK, this is Christophe here. Because we do have already also from the CN Phase 2 experience with also other populations even if the Phase 3 study includes moderate and severe patients, we are going to build a case for the label for the entire CN population and we do have already data to support this including from the WHIM study etc. So we are anticipating a broad label. But, obviously, this will be a matter of discussions with the FDA at the time when it comes.

RK, to clarify the value proposition, we are concentrating on treating patients who experience severe recurrent infections and have limited treatment options. When engaging with payers globally, our focus will be on this significant unmet need. We aim to illustrate the value of XOLREMDI for mavorixafor, particularly in the context of CN XOLREMDI and WHIM, while maintaining our pricing strategy. There is a strong correlation between the severity of the disease, the design of our trials, and the value we believe we can deliver to patients.

Thank you. I have one last question, and I apologize for that. Regarding the agreement with Norgine for commercialization in Europe and Australia, does that pertain to specific indications or to the overall period of mavorixafor?

Yeah. Thanks RK. It's Adam. So it covers WHIM and CN. So it's a license to across both indications. Obviously, first will be WHIM commercially followed by CN.

Okay. Perfect. Thanks. Thanks for taking my questions.

Thank you, RK.

Thank you. We will move next with Stephen Willey from Stifel. Please go ahead. Your line is open.

Yeah. Good morning. Thanks for taking the question. I guess, with the understanding that the commercial history here in WHIM is a bit abbreviated thus far, is there anything that you can say about just patient persistency and compliance that you're seeing?

Sure. Good morning, Steve. Mark here. We are pleased to see that compliance and adherence rates are higher than expected for a daily oral medication. This indicates a significant need for treatment, and both patients and physicians recognize that this disease requires management, with XOLREMDI being the solution when used correctly. We are investing considerable time in educating patients and the community. In fact, we recently launched a new website dedicated to patient education. I encourage you to visit whimsyndrome.com to see our new site, featuring WHIM patients sharing their experiences and providing various resources to support them in their journey with WHIM and XOLREMDI.

Okay. And are most patients getting a 30-day supply? Or are some patients getting three months' worth of drug via a single script?

The majority of patients are on the higher dose. Of course, it's weight based. So if the patient is of a lighter weight they get a lighter dose.

And I guess, the question was if the prescription unit size that most patients are getting is it a month's supply? Or are some patients getting three months' worth of drug with a single script?

It's a month supply at this stage.

Okay. And then understanding that the 4WARD trial is blinded. But can you just remind us what your assumption was around patient dropout? And if there's any data that you're able to see on a blinded basis that would suggest that that assumption is holding up in the clinical trial.

Yes. So Steve what we're targeting, as we shared, is about 150 patients that are enrolled and all of that has some degree of assumptions of either dropout or screen failures etc. So we're building that funnel. I think more importantly what we can see with the already enrolled subjects is really about their profile like are we in good shape on the 150 because that sort of sets our cost; the answer there is definitely yes. We're seeing the right blend of idiopathic autoimmune and congenital balanced nicely. And then, of course, this is all blinded, but we're seeing the event rates that you would want to see early in the study to confirm our assumptions. So in terms of powering the 150 is belt and suspenders for the co-primary endpoints. So I think that gives you some confidence. In terms of the rate, there's so many ins and outs. What we can say is certainly based on everything we're seeing we're on track for that Q3 Q4 and full enrollment.

Okay. Very helpful. Thanks for taking the questions.

Thank you, Steve.

Thank you. Now we show no further questions at this time. I will turn the call back to Paula Ragan for closing remarks.

Well, thank you very much for joining us today. We're happy to follow-up offline with any other questions, and wish you all an excellent rest of your day. Thank you.

And this does conclude today's program. Thank you for your participation. You may disconnect at any time.