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 April for our first product, mavorixafor, branded XOLREMDI, for the treatment of WHIM syndrome, a rare primary immunodeficiency disease. As with ultra-rare disease launches, our initial commercial strategy has been focused on disease awareness to support patient identification and diagnosis.

While we do recognize that sales appear to be flat quarter-over-quarter, we want to remind everyone that some of the sales in the second quarter were products stocking with our specialty pharma as is typical during initial launch.

I'm pleased to report this past quarter, we hit our most important launch goal, having engaged with all 3,400 of the initial immunologists and hematologists targeted for the first phase of our launch. And these visits and digital engagements are bearing fruit, as you can see here.

Recently completed market research comparing pre- and post-launch metrics indicate that knowledge of WHIM syndrome and these likely XOLREMDI prescribers has increased and is now at more than 75%.

In addition, an increasing number of physicians are screening their patients for WHIM, and 80% of HCP surveyed report that they would consider prescribing XOLREMDI for their WHIM patients.

Over the past six months, we've also stepped up our conference attendance, launched a peer-to-peer speaker program and initiated a patient-focused campaign, which includes a website, new materials and an HCP discussion guide.

Reimbursement and access continue to go well with favorable policy decisions resulting in more than 150 million lives now covered. So very good progress there. Importantly, the activities we are conducting in WHIM are yielding insights that may support our efforts to advance mavorixafor into the much broader indication of chronic neutropenia.

And while our commercial efforts are exclusively focused on WHIM today, we do see a significant overlap between the WHIM and CN communities. Based on our claims analysis and experience in the field, we observed that a majority of hematologists that we're calling on for WHIM also see chronic neutropenia patients.

And of course, there's overlap within the patient advocacy communities we engage with as well. If mavorixafor is approved for use in CN, we certainly expect to be able to leverage our commercial infrastructure and relationships within the WHIM community to support a potential launch into chronic neutropenia.

As you all know, success in CN will be dependent on the results of our global pivotal Phase III trial, which is progressing well, and currently participants are being screened and dosed across multiple countries. Our 4WARD, as we've named it, is a global trial that will engage patients and physicians across 20 to 25 countries.

We can report today that we have already received health authority authorizations to initiate the trial in approximately 85% of these countries. We can also now report that approximately 40% of our planned sites worldwide are initiated, and we expect to have the majority of sites initiated in early '25.

This trial is expected to enroll 150 participants at 90 to 110 sites with a planned enrollment of one to two participants per site, which is typical in a rare disease clinical trial. Most importantly, we are on track and continue to expect full trial enrollment in mid-2025.

With that, I'll now turn it over to Christophe to get to the heart of our call today, data results from the completed Phase II study in chronic neutropenia.

Christophe?.

the phagocytosis assay, which assesses the neutrophil's ability to engulf pathogens; and an assay for ROS production, ROS is reactive oxygen species, or the ability to damage or kill pathogens that have been engulfed.

These neutrophil function studies were conducted on the sample from nine eligible participants with a mix of CN types and monotherapy and combination use. We also recruited five healthy individuals to provide a benchmark for comparison.

For simplicity today, we are only showing the phagocytosis data, but we note that the ROS assay results closely mirrored the phagocytosis results.

While participants with chronic neutropenia have fewer neutrophils than healthy donors, you can see here that those neutrophils that do make it into the circulation are, in fact, functional with a similar percent of functionality between the neutropenic and healthy donor population.

Note that the bars here represent the percentage of neutrophils that demonstrated phagocytosis after challenge with opsonized bacteria. We've also broken out the congenital CN subset to see if genetic variant affects functionality differently than in the other groups.

Looking now at the full results, we see that the percentage of functional neutrophil in the healthy donors, the full group of participants and the congenital CN subset are essentially the same following six months of mavorixafor therapy.

And note, while we are showing you here the data for fibrocystic function, we generated very similar data on the percentage of neutrophils generating ROS after bacterial challenge.

Recall in our 52-week WHIM Phase III clinical trial, we saw that an increase in circulating mature neutrophils corresponded with a 60% reduction in the annualized infection rate as well as reduction in the severity and duration of infection.

By increasing the number of functional circulating neutrophils, we believe that mavorixafor treatment could correspondingly reduce the infection rate in the larger chronic neutropenia population. And we are hopeful to see similar results in our ongoing registrational Phase III chronic neutropenia trial.

Mavorixafor with or without concurrent G-CSF therapy was generally well tolerated throughout the study. The overall safety profile was consistent with previous studies. And the most frequent treatment-related, treatment-emergent AEs were GI-related, nausea and diarrhea, which were mild to moderate and typically resolved over time.

As we noted in our June presentation, we did see three discontinuations in the study. These occurred early in the execution of the study. And after implementing an education program on possible GI side effects, there were no further discontinuation. Rest assured, we have incorporated this education into the Phase III CN trial.

In summary, we could not be more pleased with the results of this Phase II study having met all of the goals we set forth. We have shown that mavorixafor can durably and meaningfully increase mean ANC as a monotherapy even in the most severe CN population and can do likewise when dosed in combination with G-CSF.

We show that mavorixafor enabled clinicians and their patients to meaningfully lower the use of G-CSF while maintaining mean ANC at normal levels. Critically, we showed that mavorixafor increased total count of functional circulating neutrophils even in the most difficult-to-treat individuals with CN.

And importantly, we demonstrated that mavorixafor was generally well tolerated on its own and in combination with G-CSF. These results give us great confidence in the chance of success of our ongoing Phase III trial and mavorixafor's potential to reduce infection rate.

They also provide hope that mavorixafor could be the innovation that the CN community is looking for. As you've heard previously, through our interviews with physicians and CN patients, what they need and want is a well-tolerated oral option, one that can enable them to safely reduce the use of injectable G-CSF.

And so far, our results have shown that mavorixafor fits that profile well as either a monotherapy or in combination use. I'll now turn it back to Paula to conclude.

Paula?.

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..