Greetings and welcome to X4 Pharmaceuticals’ Third Quarter Financial and Operating Results Conference Call. At this time all participants are in a listen-only mode. [Operator Instructions] As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Dan Ferry from LifeSci Advisors. Thank you, Mr. Ferry. You may begin.

Thank you, operator, and good morning, everyone. Presenting on today’s call will be X4’s Chief Executive Officer, Dr. Paula Ragan; Chief Commercial Officer, Mark Baldry; and Chief Medical Officer, Dr. Christophe Arbet-Engels. Following the prepared remarks by each, we will open up the call to your questions and will be joined by Chief Financial Officer, Adam Mostafa; Chief Scientific Officer, Art Taveras; and Chief Operating Officer, Mary DiBiase. As a reminder, on today’s call, the company will be making forward-looking statements regarding regulatory and product development plans as well as research activities. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted. Description of these risks can be found in X4’s most recent filings with the SEC, including this quarter’s Form 10-Q, which is expected to be filed after market close today. I’d now like to turn the call over X4’s President and CEO, Dr. Paula Ragan. Paula?

Thanks, Dan. Good morning everyone, and thank you for joining us on the call today. To start, I’ll be reviewing our third quarter events and recent highlights, the first two of which will be the primary focus of our discussion today. As you can see here, it’s again been a very busy and productive period at X4, which culminated in the great news last week that our NDA seeking approval of our lead drug candidate mavorixafor, for the treatment of WHIM syndrome, was accepted by the FDA for Priority Review. The FDA has set a PDUFA, or action date, of April 30, 2024, which sets us up for a potential second quarter 2024 launch in the U.S. if approved. In anticipation of this, we have continued to build out our fit-for-purpose commercial organization. Mark Baldry, our Chief Commercial Officer, will run through some of the details of our launch readiness and pre-launch activities to date, all of which aim to further the understanding of WHIM syndrome and educate both patients and physicians on the importance and benefits of early diagnosis. We do want to remind everyone here that due to mavorixafor’s rare pediatric disease designation for WHIM syndrome in the U.S., X4 is eligible to receive a Priority Review Voucher or PRV if mavorixafor is approved, that we can use to either obtain priority review for a subsequent application or to sell to another drug sponsor. Turning now to our mavorixafor chronic neutropenia program, we have continued to advance our Phase 2 study and have now enrolled more than 15 participants in the trial. Importantly, key learnings from this ongoing study, along with the data from previous trials and input from the FDA have enabled us to finalize the design of what we believe will be the global pivotal Phase…

Thanks, Paula, and thanks to all of you on the call today. We thought it would be helpful to start by highlighting some of the ways that we’ve been engaging with the WHIM community, developing an understanding of the market landscape and establishing a foundation for a successful introduction of mavorixafor to physicians, patients and payers. As Paula mentioned, there are currently no approved therapies for WHIM syndrome. Physicians are limited to managing their patients’ symptoms using repurposed symptomatic treatments. For example, immunoglobulin replacement therapy, which is injected or infused into the body, and or prophylactic antibiotics, all of which carry their own challenges and do not address the underlying cause of the disease. Diagnosing WHIM syndrome is also a challenge given that the clinical presentation of the disease is so variable, and in fact, only about 20% of patients present with all four of the hallmark symptoms and manifestations of WHIM. Some physicians use genetic testing to help identify WHIM or confirm its diagnosis, while other physicians rely more on the clinical presentation of the patient. Due to the rarity of the disease and lack of investment in treatment innovation, there is limited awareness of WHIM syndrome in the general physician community, and the patient journey often includes visits to multiple types of doctors as they try to uncover what might be causing the symptoms. Given this lack of historical attention and investment, we recognize the significant opportunity to not only address the unmet needs of currently diagnosed WHIM patients, but also to use our resources to identify additional patients in what we believe to be a larger population of undiagnosed people living with WHIM syndrome who could potentially benefit from mavorixafor treatment. The next slide provides an overview of our efforts to date, which have focused on partnering…

Thanks so much, Mark. Really great summary of all of our efforts to increase disease awareness, enable earlier diagnosis and support patients in need as we head towards our anticipated launch in WHIM. Let’s now change gears a bit and focus on our chronic neutropenia program. We thought it would be helpful here as well to remind everyone what would make the biggest difference to people living with chronic neutropenia and their physicians. That is, where are the greatest needs in those that we serve. If you recall, a little over a year ago, we held an investor event focused on CN and our initial Phase 1b trial results. At that time, we shared that 100% of the 25 patients enrolled achieved robust ANC responses from a single dose of mavorixafor, regardless of background therapy. Additionally, from our interviews, we gathered valuable insights from patients and physicians where they highlighted their needs as related to the product profile of a potential new treatment for CN. Their preferred attributes included an oral formulation that is safe, well tolerated, and easy to administer or take, and one that durably increases ANCs over time. Mavorixafor has already demonstrated these attributes across a number of populations. Additionally, patients [ph] and clinicians criteria for a new treatment includes a therapy that decreases infection burden and also decreases the toxicities and challenges associated with taking lifelong GCSF. Our successful WHIM Phase 3 trial, where infection rate, severity and duration were meaningfully reduced, provides evidence that this benefit of mavorixafor could also translate into helping the CN community. Most importantly, our CN Phase 2 study is beginning to build direct evidence in chronic neutropenic patients across the key metrics of durable ANC increases safety and reduction of GCSF use. I’ll now pass it over to Christophe Arbet-Engels, our Chief Medical Officer, to share an update on the status of the promising CN program. Christophe?

Thanks so much, Paula. As you know, following the successful completion of our Phase 1b clinical trial, evaluating the ability of a single dose of mavorixafor to raise absolute neutrophil counts, or ANC, in CN patients. We launched a Phase 2 trial to evaluate chronic use of mavorixafor in the same patient population, with or without concurrent GCSF treatment. The study is designed to assess mavorixafor ability to durably raise ANC within the first few months and to see whether patients could possibly reduce or eliminate their GCSF dose longer term. Importantly, we also assess for safety of mavorixafor in combination with GCSF. We have seen a nice acceleration in trial enrollment and now have more than 15 participants receiving treatment in the trial. On our last quarterly conference call, the team presented initial data from the first three participants in the study, all of whom were on GCSF treatment at study initiation, but had identified unmet needs. All achieved large, durable increases in ANC and the two neutropenic patients achieved normal ANC levels despite having low ANC while on GCSF therapy as they entered the study. Notably, the ANC increase scene would meet the responder criteria that we’ve established for the Phase 3 study design, which I will go into in more detail shortly. Importantly, the robust ANC response in the early months of the trial enabled the successful dose decrease or complete withdrawal of the GCSF in some patients. Mavorixafor has also demonstrated an acceptable safety profile in combination with GCSF. The full data set on these three subjects will be presented in a poster at the Annual ASH Meeting in December. In addition, we expect to be able to present a comprehensive update from at least 15 of the participants in the Phase 2 trial during the…

Thanks so much Christophe. We hope it’s clear from our discussions today why we are so excited about the future of our company. We have a robust data set maturing in our CN Phase 2 study. Given all the positive data in hand and clear FDA guidance, we are gearing up for a potential launch of our global CN Phase 3 pivotal trial. And finally, we are headed for a potential first approval of mavorixafor and WHIM syndrome in the U.S. and subsequent launch. We look forward to the potential of delivering mavorixafor, a much needed treatment option to this underserved group of patients. We very much look forward to the continued periods of growth and accomplishment in the coming years. And with that, we’ll now open up the call for your questions. Operator?

Thank you. We will now be conducting a question-and-answer session. [Operator Instructions] The first question comes from the line of Eva Privitera with TD Cowen. Please go ahead.

Hi. Good morning and thanks for taking our questions. I was wondering if you could talk about the CN patients who are on GCSF is still neutropenic, what are the reasons for their inadequate response? Is it mostly due to intolerance or other reasons they’re refractory or have inadequate response? I guess I’m trying to get a sense of how heterogeneous this patient population is.

It’s an excellent question, Christophe. Our CMO will provide some commentary on that.

Yes, thanks. Yes, it is indeed a very heterogeneous population. We do have the plan to have congenital and idiopathic neutropenic patients in our Phase 3 study. There are different reasons, obviously, if there’s the genetic mutations in those congenital patients, and the response with GCSF varies within these patients, so some have a defect in the maturation of the neutrophils and GCSF may not address all the aspects of the different phenotypes you can see in this patient.

Maybe just to add, we had an excellent recent clinical meeting and what we’ve heard even from some of our clinicians is, how happy some of these patients are to be considered for study around an oral therapy. Given the very difficult tolerance levels, even when they can respond to GCSF, it’s a tough treatment to take.

Great. Thanks for that. And the second on WHIM. Just based on all your commercialization and market building efforts in WHIM, how do you expect the launch trajectory to look? Do you expect a bolus of patients at launch?

Yes, we’ve actually been really pleased with the level of engagement we’ve had with physicians and patient groups to date, and it’s actually given us continuing confidence in our prevalence estimates of about 1,000 patients with WHIM in the U.S. So we’re building the foundations for a launch that will get the product to patients as quickly as possible after approval.

Great. Thank you so much for taking my question.

Thank you. Next question comes from the line of Stephen Willey with Stifel. Please go ahead.

Yes, good morning. Thanks for taking the question. Can you say whether or not, I guess you’ve brought any additional sites online in the Phase 2, I think you had previously said you were at around six. And then how many sites are you planning for the Phase 3?

Sure. Thanks, Steve. So we have some good lessons learned on the Phase 2. We did have those six. We maintained it at six, which is why there’s a little bit of a hiccup in enrollment. But we’re very pleased with the 15 plus patients now enrolled. So we’ll have a robust data set. But it’s a great lessons learned to prepare us for the Phase 3 and Christophe will share some more on that.

Yes, so we’ve learned a lot from the Phase 2 study and from the PIs of the Phase 2 study. We’re going to apply those to the Phase 3. We are evaluating exactly the number of sites that we’re going to have ex-U.S. and in the U.S. at this time, we’re confident. We’ve identified a large proportion of the patients that we plan to enroll in the U.S. and ex-U.S. And the feasibility seems to really match with tracking with what our expectations are. So we’re confident we can enroll this Phase 3 study.

Yes, maybe just to give you a little bit of a benchmark, Steve, I think we had around 20 sites just using rough numbers for WHIM. We have about three times as many patients in CN, so you should expect about three times as many sites for the Phase 3 trial. We’re still finalizing those exact numbers, but it’s definitely going to be a robust number to make sure we hit that one year enrollment.

Okay, that’s helpful. And then with respect to the Phase 3 protocol in chronic neutropenia, I guess, how are you standardizing GCSF reduction withdrawal? Is that just investigator subjectivity? And then is there a way that you’re going to try to statistically quantify that at all?

Right, so GCSF, as you know, is prescribed individually to patients and there is a lot of variability. So we’re asking our patients in the Phase 3 to remain stable. We want to establish the effectiveness of mavorixafor versus placebo. And we’re going to maintain this. We’re going to allow only modifications of death under a blinded, adjudicated committee for safety reasons. So, for example, if their ANC goes too high or if there is a safety event. But we’re going to be trying to enforce stable treatment of GCSF for the 52-weeks of the trial.

Okay. Thanks for taking my questions.

Thank you. Next question comes from the line of Edward Tenthoff with Piper Sandler. Please go ahead.

Thank you very much. And good morning, everyone. Two questions, if I may. Firstly, I think I should know this, but is there any open-label extension work being done in WHIMs? In other words, are there currently any patients on mavorixafor? And then the second question, I think you mentioned, if I heard you correctly, that there will be the three patients. More data on those three patients from ASH. Could there be more patients just because of additional time between abstract submission and the actual presentation? Thank you.

Sure. So I’ll just do a quick summary. The WHIM OLE is ongoing. We expect to present data on that on the first half of next year. So we’ll look forward to sharing some updates on the patients who are on placebo moving into mavorixafor and those on long term mav [ph]. So stay tuned for that. And then in terms of the three patients in the ASH poster, our intent is to really make sure we have a robust data set around those 15 patients in the first half of next year. I think that’ll tell the fulsome story around how the drug is acting, but we’re really looking forward to presenting the six month data on those three patients on GCSF. There’s a lot of exciting new information amongst those three patients, so stay tuned for that as well, Ed.

Great. Awesome. I’m looking forward to that. And can you remind me, I know the majority of patients rolled over. How many patients are in the OLE for WHIM? Thanks.

So we haven’t given any cuts updates, but I think 90% plus of them rolled over. And I’m actually not sure where the cut is at this point, but we’ll certainly be disclosing that when we get the data updates. Yes.

Thanks, Paula.

Thanks, Ed.

Thank you. Next question comes from the line of Kalpit Patel with B. Riley Securities. Please go ahead.

Hey, good morning. This is Andy Fleszar on for Kalpit. Thank you for taking the questions. Are you able to give any additional granularity on the timing of the next comprehensive update for the 15 patients? Or if there’s a certain amount of follow up that you’ll be looking for before presenting the results?

Sure. Christophe, go ahead. Yep.

Yes, no, there will be, we will have all of those data in a more comprehensive manner in the first half of next year. The ASH poster will help share some preliminary information and we hope to continue this. I want to remind you that the Phase 2 studies is a six-month study. It’s an open-label, so we could do different analysis. But it is important that we see those six months data and we see this in the largest number of patients to raise the confidence of the preliminary data we are going to be seeing at ASH.

Okay. And then as a follow up to that. Do you anticipate the Phase 2 data to be enriched for cyclic, congenital, or idiopathic CN?

No, I think what we’re doing for the Phase 2, of course, is all comers, because there’s two questions we’re trying to answer, obviously making sure that our Phase 3 study design is robustly incorporating any responses that we’re seeing. And then secondly, there’s the longer term question around GCSF. So both of those questions need to be answered. That’s why we are including a diverse population with no prespecified numbers in any of those categories.

That makes sense. And then one final question from us. From your market research, can you speak about what level of GCF reduction is clinically meaningful to patients and prescribers? Obviously, more reduction is better, but any color that you can provide on what success might look like would be helpful.

That’s an excellent question. And our answer is, come to the ASH poster, because we’ll be actually providing some very meaningful market research around that exact question.

Sounds great. We look forward to seeing you there. Thank you.

Thank you.

Thank you. Next question comes from the line of Kristen Kluska with Cantor Fitzgerald. Please go ahead.

Hi. Good morning, everyone. Thanks for taking the question. When I look at your finalized Phase 3 CN study design, in a lot of ways, as you mentioned, it really does mirror what the trial looked like for WHIM, which, of course, was successful. So can you talk about how you think that gives you the confidence in this particular study and any differences we should really be thinking about related to the mechanism in these subset of patients versus WHIM?

No. So we have worked with one of our consultants, Professor Tom Fleming from the FDA, in designing that study very closely with him. We are confident that we have the power for our primary endpoint to be achieved, and we have the right sample size. We have two populations that we’re going to be included in that study, which is the monotherapy and the patients on GCSF. And because it’s a randomized, double-blind controlled trial versus placebo, we will be able to establish the effectiveness, the efficacy of mavorixafor. We also incorporated in that study the requirements from and the feedback from the FDA that we received. And so we believe we have all the elements to recruit and see positive data in this Phase 3 study.

And maybe just to remind folks, in the WHIM Phase 3, we saw about a 60% reduction across those patient populations. We actually took a fairly conservative approach, even reducing that, to plan for the stats on the Phase 3, which is why we feel very confident.

Okay, thanks for that. And it’s nice to see the uptick in enrollment in this update. Can you maybe talk about what you think? Some of the factors are that it was originally slower than expected. Now that you’ve seen this uptick, so were it things like seasonality? And again, how this also helps for planning for Phase 3. Thanks again.

Yes, sure. I think trial enrollment is a challenge for every biotech out there, especially in a new field such as chronic neutropenia. But I think what we just learned is the summer is tough for some of the younger patients. We actually have fairly sick patients in this trial, but they certainly wanted to have some downtime as is expected. The trial enrollments picked up nicely. I mean, more importantly, Phase 3s are very different from Phase 2s. They’re a very heavy operational lift. You want to create a large pool of patients waiting that are co-localized with your sites. We actually have a very nice start to that with quite a robust patient pool already identified to the sites that are coming on board. So we look forward to certainly hitting that 12 month enrollment with high confidence.

Are you done with the question, Ms. Kluska?

Yes. Thank you.

Thank you. Next question comes from the line of Swayampakula Ramakanth with H.C. Wainwright. Please go ahead.

Thank you. Good morning, Paula and Adam. A lot of my questions have been answered just looking into the Phase 3 study in CN disorders. What’s the label you’re looking for? Or once we get into the application stage? And also, do you foresee either increasing the size of the trial as the trial progresses so that you maintain a certain number of patients in these individual populations so that you can get a broad label?

So regarding the label based on the previous label for GCSF, for example, we should see a label that addresses the reductions of infections in the patient populations that we include in this trial. And so we haven’t finalized the label yet with the FDA, obviously, but this is what we think could be happening, and we’re looking at this reduced infection rate. With regards to in this…

Yes, I think he was just asking about subpopulation, I mean similar to GCSF, subpopulations were kind of catch as you catch can, but it’s based on the inclusion. And then the label covered all the variable patient populations.

Yes. The trial again is powered 90% for our primary endpoint. So we’re planning to have this study executed as with the sample size, and we’re confident that we should be able to hit our primary endpoint with the current sample size.

Okay. Thank you. Thanks for taking my question.

Thank you. Next question comes from the line of David Bautz with Zacks Small Cap Research. Please go ahead.

Hey, good morning, everyone. Thanks for the update this morning. Just one question for me. I’m curious what type of doctor ends up typically making the diagnosis for WHIM? And I guess what I’m trying to get at is how are you sure that you’re reaching the correct physician population with your outreach program?

Yes, it’s a great question. And because of the variable presentation of the disease, These patients have a different journey, diagnostic journey, depending on their symptoms. So some of the patients end up under the care of immunologists, and some of the patients end up under the care of a hematologist or a hemoc. So this is what we’ve been focused on for the past few months, is really looking at the data, engaging with key institutions, and learning about who are the physicians most likely to have these patients, so that once we get approved, we know where to prioritize our efforts. We’ve also been complementing this with our digital marketing, which I talked about earlier in the presentation. And this is an efficient way of extending our reach.

Okay, great. Thanks for that.

Thank you. This concludes today’s question-and-answer session. I would now like to turn the floor over to Paula Ragan for closing comments.

Well, thank you very much again today for joining the call. We look forward to providing continued updates in the future as we make our exciting progress as a company. Have a great day.

Thank you. This concludes today’s teleconference. You may disconnect your lines at this time. Thank you for your participation.