Greetings, and welcome to the X4 Pharmaceuticals Call and Webcast. 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. Thank you for joining us today for the special earnings call during which X4 will focus on providing a business update and, importantly, data and results from its now completed Phase II study of mavorixafor in chronic neutropenia. As a reminder, on today's call, the company will be making forward-looking statements regarding regulatory and product development and commercialization plans, as well as research activities and financial projections. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted. Description of these risks can be found in X4's most recent filings with the SEC, including this year's Form 10-K, which was filed on March 21, 2024, and in the company's Form 10-Q for the third quarter, which is expected to be filed shortly. Presenting on today's call will be Dr. Paula Ragan, X4's President and CEO; and the company's Chief Medical Officer, Dr. Christophe Arbet-Engels. I'll now turn it over to Paula Ragan to run through today's agenda. Paula?

Thank you, Dan, and thank you all for joining us. Today, we will provide an update on our operational achievements, including activities supporting the launch of XOLREMDI in the U.S. and the substantial progress to date with our ongoing Phase III clinical trial of mavorixafor in people with chronic neutropenia or CN. In addition, we're excited to present the positive data from our recently completed Phase II study of mavorixafor in CN. These results include the final mavorixafor monotherapy data, which remains very encouraging and consistent with the data we presented in June from the interim Phase II analysis. We will also be presenting new data from the study. Results showing that most of the participants who were treated with mavorixafor and G-CSF ended up having their G-CSF dose adjusted downward during the study, while the mean neutrophil count for this group remained in the normal range. These data provide a first glimpse into how mavorixafor could be used in the real world if ultimately approved in CN. Equally exciting are the new insights we've gained from assessing the functionality of circulating neutrophils in a subset of the Phase II study participants as well as healthy donors for a comparison. And we'll briefly review this updated safety data from the study as well. We'll then conclude and open it up for your questions when we will be joined by our Chief Commercial Officer, Mark Baldry; our Chief Financial Officer, Adam Mostafa, our Chief Operating Officer, Dr. Mary DiBiase; our Chief Scientific Officer, Dr. Art Taveras; and our Head of Corporate and Patient Affairs, Jose Juves. So let's quickly run through the operational update as we know you're all eager to hear about the CN Phase II study results and analysis. As you know, we received U.S. FDA approval in late…

Thanks so much, Paula, and hello to everyone on the call. Let me begin with a quick refresher on chronic neutropenia. The hallmark of chronic neutropenia is abnormally low levels of circulating neutrophils that are the defense mechanism our body uses to fight pathogens. As we've presented previously, there is a well-established correlation between circulating levels of neutrophils or absolute neutrophil count, ANC, and the risk of frequent and/or serious infection. Note that the lower limit of normal for neutropenia diagnosis is 1,500 cells per microliter. Below that, grades are divided based on the infection risk in increments of 500 cells per microliter from mild to moderate to severe. As you can see, severely neutropenic patients have ANC of less than 500, and this corresponds to the highest risk of infection. To reduce the risk of infection in these patients, it is critical to move them from the most severe grade towards less severe grade to achieve as normal a level of neutrophil as possible. Therefore, an increase of 500 cells per microliter is an important clinical practice objective. Through its mechanism of action, mavorixafor has been shown to do precisely that, increase the number of circulating neutrophils. This ability is clearly stated in the mavorixafor label from the FDA approval in WHIM syndrome based on results from a pivotal Phase III trial. These results demonstrated that mavorixafor sustainably raised ANC over the 52 weeks of the trial and consequently reduced the annualized rate of infection along with the duration and severity of infections in trial participants. This infection benefit was achieved through an increase in mean ANC of more than 500 cells per microliter. These results and the WHIM approval in the U.S. provide confidence in our plan to potentially bring mavorixafor to those with other chronic neutropenic conditions…

Thanks so much, Christophe. Great job sharing our exciting update on mavorixafor's potential in CN. To conclude, over the last six months, we have made significant progress as a company in bringing innovation to the immunodeficiency community. By gaining approval for and launching XOLREMDI in the U.S. for WHIM syndrome and by exploring additional geographies for mavorixafor's approval and distribution in WHIM, we are seeking to maximize the global opportunity to help those with WHIM. And by completing and reporting out these positive Phase II results and initiating our pivotal Phase III trial of mavorixafor in those with chronic neutropenia, we are seeking to further expand the market opportunity for mavorixafor and have a positive impact on a much larger potential patient population. In terms of our financial results, I direct you to our press release from this morning and our 10-Q to be issued shortly. We ended the third quarter of 2024 with cash and equivalents of almost $136 million. We continue to believe this gives us the runway into late 2025, and note that this does not include the expected ramp-up of sales of XOLREMDI throughout next year. As always, we thank you for your continued support and would now be happy to take your questions. Operator?

Thank you. [Operator Instructions] And we'll take our first question from Kristen Kluska with Cantor. Please go ahead. Your line is open.

Hi. Good morning, everybody. Congrats on these new great data you shared with us. Really appreciate it. So questions that I have are related to the new data today. So I wanted to ask what the biggest criteria were in the trial that made the physicians comfortable to reduce and lower the G-CSF usage? And while I recognize it wasn't a formal endpoint measured, I'm curious if the doctors had any anecdotes to share about any early signals of reduced pain or better convenience benefits for patients.

Yeah, Kristen. Thank you for the question. I'll start and then Christophe will add some color. So I mean the important thing about the Phase II study is we really put the choice in the physicians' and patients' hands. So there's a wide variety of patients. They have real-world experience with them. So really, what gave them comfort to adjust G-CSF dosing was the high and robust ANC responses due to the addition of mavorixafor. That is confidence in data, and of course, they acted on that. But Christophe, why don't you give some more color on that?

Sure. Yes, no, we are really happy with the results and the choice that 75% of those physicians with their patients have decided to decrease G-CSF. This is a really high percentage of those decisions without any mandates from the protocol or any prescriptions that we ask them to do this. With regard to the choice to do it is, as mentioned, a choice between patients and the physician. And it's a balance between the level of ANC, as Paula just mentioned. And so they were very comfortable with the level of ANC and the clinical manifestations that these patients were having. So we could not identify a specific pattern, but this is really what drives most of those decisions.

Okay. Thanks. And then any early anecdotes or it's a little too early to make that assessment?

I think it's early to make that assessment. And of course, what we're most pleased with is the broad applicability, the broad reduction in G-CSF across the 75% of patients and even some of them completely coming off. So certainly, a lot more study to be done, Kristen, but thanks for the highlights.

Yeah. And if I may ask one more question then. Can you talk a little bit more in terms of what lower G-CSF usage actually means? Is it that physicians are assessing it every other day for usage? Is it the amount of G-CSF that's administered is lowered? And then do we have a general sense to give us whether -- what correlation of G-CSF of reducage could ultimately like truly lead to alleviating some of the dangerous side effects and the inconvenient ones?

Yeah. So we'll take the second part first. So what we've been reporting on from patients and physicians in some of our early research is that about 25% reduction either in dose and/or frequency seems to be the threshold for something that's clinically meaningful for them. And obviously, the lower, the better in terms of the short- and long-term toxicities experienced by dosing. And then just in terms of percent reductions, that's always based off of the patient's entry criteria. The challenge with G-CSF is the heterogeneity of each patient is different. So we treated them as such as clinicians do. So that reduction reflects their entry -- changes in their entry baseline levels.

Thanks, again and congratulations.

Thank you.

Thank you. Our next question comes from Ted Tenthoff with Piper Sandler. Please go ahead. Your line is open.

Great. Thank you very much. Good morning, everyone and congrats on the Phase II data. I had a one quick follow-up question. When it comes to the Phase III trial, and I'm wondering how -- is there a way or are you looking at benefits, kind of following up on the last question, from G-CSF reduction? Is there any way to capture those in terms of improved tolerability, improved safety? And then I have a quick one on XOLREMDI. Thanks.

Sure. I'll turn that over to Christophe.

Yes. No, so the Phase III trial is designed for as a registration approval trial as per the FDA requirements. So we will be looking at those aspects as a follow-on study to that Phase III trial.

Great. Okay. Yes, that makes a lot of sense. And also, I have to imagine it might take some time for some of those to emerge, but yes, that's great. And then when it comes to XOLREMDI, you guys announced a new initiative. Can you just provide a little bit more detail around that in terms of reaching out to the patients?

Sure. Ted, just to clarify, a little bit more color on our sort of patient ambassador efforts?

Yes. Thank you.

Sure. Mark?

Yeah. Thanks, Ted. And you’re right, we’re laser-focused right now on raising disease awareness and driving screening for WHIM and presenting XOLREMDI as a treatment that has proven to work in WHIM. So we’ve just launched a new patient-directed campaign. This is a combination of digital campaigns with websites as well as hard copy material that we can provide to patients. And we think this will help to educate patients and encourage them to go and have a discussion with their physician about WHIM syndrome.

Great. Excellent. Well, thank you very much. Appreciate the time.

Thanks so much, Ted.

Thank you. Our next question comes from RK with HCW. Please go ahead. Your line is open.

Thank you, and good morning, Paula and team. I just want to focus a little bit on XOLREMDI and the uptake in the market. Can you educate us on how many patients are on the drug? And how -- what is the commercialization setup right now? And I'm just trying to understand how long do you think it would take for the drug to be adopted in a decent fashion.

Thanks, RK. I'll turn it over to Mark.

Yeah. Thanks, RK. As I mentioned, we are right now laser-focused on raising disease awareness and driving that screening for WHIM, encouraging physicians to look for WHIM patients in their practice, helping them recognize these patients in their practice. Up to now, there’s been no approved treatment for this disease. So everything starts with raising disease awareness and encouraging physicians to identify the patients in their practice. And then we have a discussion with them about XOLREMDI, and we share the data that shows XOLREMDI works. So that’s really where we are now. And it’s building the foundation for our ramping up into 2025, and we’ll be able to share more details with you then.

Thank you. Thanks for taking my question.

Thank you. Our next question comes from Stephen Willey with Stifel. Please go ahead. Your line is open.

Yeah. Good morning. Thanks for taking the questions. Maybe one on the data, one on XOLREMDI. So I guess on the data side, was there any correlation between CN subtype and the rapidity and magnitude of G-CSF dose reduction? And then I guess, was there also any correlation between the G-CSF dose these patients were receiving at baseline and then the magnitude of the dose reduction they were able to achieve?

Sure. I'll start and then Christophe will provide more color. But in terms of the CN subtype, the good news is the drug seems to be robustly and consistently working. We did break out the severity of those patients because those are the toughest to treat, and we saw a robust response there. But in terms of CIN or congenital, we're seeing a very consistent effect. In terms of G-CSF percent reduction from their baseline, again, we're not really seeing any variability in response based on their G-CSF profiles. But I know Christophe has had a lot of data analysis, and Christophe can provide some more color there.

Yeah. No, thank you. So the CN Phase II, the sample size and the number of patients in that study is too small to start drawing directions where we're going with the different type of patients. So we know that in all of the type of patients that were included in the Phase II study decrease -- any type of those patients decreased G-CSF and chose to decrease G-CSF voluntarily. That, we know for sure. The Phase III trial will help us in having that bigger picture of how those different subtypes, the congenital, the different mutations in the congenital, etc., all this will be analyzed in the Phase III study with much more detail.

Okay. And then on XOLREMDI, I know you've hit 100% of your target accounts. I think you also mentioned 60% of HCPs have increased their screening. But I guess, do you have a sense of how many of these HCPs that you're targeting are indeed actively screening? Just wondering, I guess, how low of a base you're starting at here and what kind of runway you might have? Thanks.

Yeah. So again, the way we identify physicians that we think have a WHIM patient in their practice is really using claims analysis and our market research. And these are the physicians that we’re going out to really make them aware of WHIM syndrome and encourage them to start screening for the patients in their practice. And this is really where we’re getting the most engagement at this point. And the other thing that we’re really trying to do is reach the physicians where they are. And so we’ve really doubled down on our conference presence this year. As you know, these physicians come from different specialties. So we mainly focus on hematology and immunology and try to really meet those physicians where they are.

All right. Thanks for taking the questions.

Thank you. Our next question comes from David Bautz with Zacks. Please go ahead. Your line is open.

Hey. Good morning, everyone. For XOLREMDI, I'm curious if you will be able to provide any type of sales guidance numbers moving into 2025. And then for the new Phase II data this morning, I mean I realize the numbers are small, but was there any data collected on infections, number of infections or types and then particularly for those patients where G-CSF was reduced?

Sure. So sales guidance for 2025, we're not yet providing that. We certainly -- as Mark mentioned, we'll provide some more robust insights into our commercial launch as we head into the year. In terms of infection data, I mean, as you can appreciate, this is a Phase II study. It was not designed to assess infection rates, no randomized comparator or comparator arm, no history collected. Importantly, though, we'd really like to remind everybody, in this population, ANC is proven to correlate with infection risk that is based on the G-CSF clinical trials and everyday use. So we're extremely pleased that with the fact that our ANCs are robustly increasing and the neutrophils are functional, we've actually gone one step further beyond the data with G-CSF in our own study. So we really hope we can remind everybody as it relates to infections, of course, that was part of our safety database, which will be published at a future point. But really, we’re incredibly excited about the totality of evidence and are locked and loaded for the Phase III.

Okay. Great. Thanks for taking the questions.

Thank you. And this concludes our Q&A session. I will now turn the call over to Paula Ragan for closing comments.

Well, thank you so much for joining us on the call today. As you can appreciate, we are very excited about these data, and we are on track to deliver value. So from all of us at X4, stay classy, and have a great day.

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