X4 Pharmaceuticals, Inc (XFOR) September 2026 Conference Transcript

All right, everyone, I think we'll get started here with the next fireside discussion. My name is Derek Archilla. I'm one of the senior biotech analysts here at Wells. Very excited to have X4 Pharmaceuticals from the company. We have Adam Craig, executive chairman. So, Adam, good to see you.

Good to see you, Derek, and thank you for the invite.

Yeah, we were just talking. So, you know, for me, it seems like long ago because it's been a busy two days, but it was really just recently, you know, you put out an update, you know, regarding your lead program. But maybe just to kind of give a high level of the company and what you guys are working on and then we can kind of dig into that update.

Yeah, so we're a Boston-based company that works in the area of rare hematologic disease. We're currently developing for a second indication a drug called Mabarixifor, which is a drug that increases the neutrophil counts in patients where they have, in conditions such as chronic neutropenia, where there are low neutrophil counts. We have a phase three that's nearing the end of enrollment called the Forward Trial. and on Monday we announced sample size readjustment with the FDA and the sample is now going to be 126 patients which we aim to complete that enrollment by the end of the year.

So I guess maybe talk us through the decision to do that in terms of you guys came in, new management team, and operationally what was going on with the company to kind of get to this decision point and provide this update.

Yeah, so we came in as a new management team a year ago So we're still learning, and we learned a lot in the last year. Initially, we did get the impression the trial was overpowered. There were two endpoints. One is a reduction in infection, and the other endpoint is an increase in neutrophil count. And as the year progressed and we learned more about the trial, we decided to take another look at the powering. So we got our statisticians to look at it. and we worked out that we could answer the question about whether the drug works in that setting, but we could answer the question with a smaller number of patients. And the benefits of that, obviously, you don't want to over-enroll a trial with patients and put them on the trial unless they need to, and also there's significant financial savings. So we ended up with a number of 126, and we ran that by the FDA. by the FDA. We requested a type C meeting, and we got written comments back from the FDA. They were happy with that. The study was adequately powered at that number, so we cancelled the meeting, and we announced it to the street on Tuesday morning, and we're moving forward with that number. I'm pleased to say that having recently changed our CRO, who we had some problems with, we've now got Paracel in place. We've got very good enrolment at the moment, a good number of patients in screening. And we are confident that we will complete enrollment by the end of the year.

Excellent. So I guess in terms of like how you got to the number, you know, for 126, I mean, is there a level of conservatism kind of built in that number and the powering assumptions here?

Yeah, all along, even before we joined the company a year ago, there's always been very conservative assumptions based on for the forward trial. We've kept those assumptions. But what we've done is by reducing software, reduce the powering in each of the endpoints. So the infection endpoint has 88% powering and the ANC endpoint has 93%. So that's a little lower. I think it was 96 plus previously. So that's a little lower, but still very well powered for phase three trial. But the actual fundamental example, the fundamental assumptions of the trial have not changed and they have always been conservative.

Excellent.

I guess, you know, the other component is on the flip side on safety you know was there a discussion with the FDA or what do you need to show from a safety database you know to get this approved yeah that was the second question you always whenever you go to the agency should always ask do you have enough patients for safety database we have over 500 patients who have received mavericks before healthy volunteers and patients and the agency didn't indicate that we didn't have enough they said it would be a review issue which in agency speakers it's okay but we need to take a look at it Can you discuss where you are in terms of enrollment, like where you are today?

And I guess now you're kind of anticipating completing that enrollment by the end of the year. So what's the delta and what gets you confident you can meet that time?

Yeah, we're in triple-digit enrollment. I'm not going to give a specific number, but you can see we're in sort of a healthy position. I think the thing that we've noticed most recently with the change of the CRO is an increase in number of patients in screening. And obviously that indicates that patients go through screening before they're enrolled. and it's really healthy, the number of patients in screening at the moment, which is very encouraging. And I'm pleased to say we've enrolled and we've got patients from the U.S. in screening as well. When we joined the company over just a year ago, there were no U.S. patients on the trial, which we were not happy with. We're now getting enrollment in the U.S. and we're getting new patients being screened in the U.S.

How important was it to kind of look at the data on a blinded basis to kind of come to this decision? And also, you guys have shared some baseline characteristics in the past. Has that kind of changed at all?

No, the baseline characteristics are important. The FDA made a comment to the company before we joined a couple of years ago. You've got to enroll patients in whom you can show a difference. So for us, that's patients with low ANCs who have multiple infections. The protocol requires an ANC less than 1,000 and two infections in the prior year to come onto the trial. we're actually seeing a median ANC of just in the low 400s and 75% of our patients have three or more infections in the prior year so we are enrolling a population that is quite sick and that's what the you know that's what the FDA wanted us to do so we can hopefully show a difference and when we've when you've got those baseline characteristics it that gave me confidence that reducing the sample size would be okay because we're enrolling the right kind of patients. So it wasn't the primary driver of the decision, but it was some supportive data to say this is okay to do this.

Gotcha. So, I mean, it sounds like mainly the issues with the CRO is more of a operational, not like whether the data integrity or, you know, actual population that was coming in.

No, I'm not worried that we get asked by investors quite a lot the last few days, you know, does this mean there aren't enough patients out there to enroll? Not at all. This was an operational issue this was a change we needed to make particularly with the CRO and we've already seen with that change and improvement in enrollment and improving patients and screening so yeah very much an operational issue which I believe we're now seeing you know on the other side of gotcha so maybe to move on just in terms of the trial itself so you know what what are you looking for in terms of like you know effect size on these two endpoints, and I guess, you know, from your standpoint, the KOLs that you've talked to, what do you think is clinically meaningful in this population? Yeah, so the, well, we're, in this population, it's an interesting, because there hasn't been an agent like Maverixifor before. The main agent patients have is GCSF, and when they receive GCSF, the patients that come in our trial almost refractory to it, they've been on such a long time. We've modeled about a one-third improvement in infection rate. That's generally how the trial is designed. I think if we demonstrated that improvement in infection rate of one-third, I think that would be fantastic commercially. I know there's some feel it should be higher or lower, but I think data from a placebo-controlled randomized trial with a one-third reduction would be very, very well received.

Gotcha. What do you think the control arm should do in this trial? What's the expectation?

I haven't said publicly what it would do, but in any trial, you always assume there'll be something in the control arm. But we've not stated publicly what that number is.

And I guess one of the components here is that you're kind of enrolling a pretty broad kind of population, congenital, acquired autoimmune, idiopathic. So how should we think about varying response rates based on kind of the population that's being enrolled?

Yes. Yes, I'm, you know, the congenital patients can be a little trickier to enroll, sorry, to not enroll, to treat. The majority of our patients, about 50%, is idiopathic anyway. We've not powered the trial to look at individual response rates in all the disease types. The FDA is looking at this as a whole, as a disease, chronic neutropenia. But I would say probably the congenital, some of the congenital patients can be quite hard to treat. I think idiopathic is a population where it would be easier for us to show a benefit, and I'm pleased that's the largest group that we're enrolling.

Have you broken down what the stratification is there?

We don't stratify like that. There's no stratification on this study. We do randomize between whether the patients have GCSF or not, but there is no stratification. So there are no statistics looking at the individual disease types.

And, yeah, you bring up a good point. So, like, how are you looking at, you know, GCSF, you know, use that baseline and ultimately controlling for that?

Yeah, GCSF, we're assuming these patients are almost refractory. So within the statistical, and I've said this publicly, we're assuming a greater treatment effect in patients who are not on GCSF and a slightly smaller treatment effect on GCSF. And the one-third, I quote you, is the combination of the two. Some of these GCSF patients have been on it a long time and just aren't responding to it. So it makes sense that we would expect a smaller treatment effect in that population. Gotcha.

And is there a cap on either of those?

No, and it hasn't really changed. The split is about 60-40, and that number has not changed since we started a year ago.

And maybe can you tell us about a little history on, like, you know, the dose chosen to bring into this trial? Like, what gets you confident in terms of, you know, the exposure needs and coverage for the patients?

Yeah, so I knew you were going to ask me that, so I went back and had a look. The decision to pick the dose, 400 milligrams once a day, is based on a lot of data that goes back, a lot of pharmacokinetic data that goes back to healthy volunteers' trials. So we're very, very confident it's the right dose, it's the right schedule for the patients. There's a lot of data and a lot of modelling that supports that. And clinically, we know from the Phase 2 chronic neutropenia study where we saw increases in ANC, the drug is working. There's a pharmacodynamic effect with that dosing. So I have no concerns about the dosing at all.

I mean, you know, WIM is a different indication, and you guys have been proven effective there. But is there any read-through, at least even just from the pharmacodynamics, or anything kind of key learnings that we should take from that experience to chronic neutropenia?

You know, one of the reasons why I personally joined the company is I knew the drug worked in WIM. You could see it had a pharmacodynamic effect. So there's no reason to think it wouldn't be in the broader chronic neutropenia population. But what interests me most about WIM, WIM patients are pretty sick. Not only do they have low ANC, they have low gamma globulins as well. And we still showed a treatment effect in that setting. So I'm very encouraged in a population that's a little bit broader with chronic eutropenia, we can show a benefit as well.

And so one of the things that we've heard from docs that we've spoken with is that this is great. We'll see this data. It'll be effective. but it's more about, you know, can we reduce these patients' GCSF use, maybe get them completely off it. So, you know, what will we learn from the phase three? And I know that you guys will be starting another trial specifically to look at this question, but, you know, are there any things that we can glean from the phase three trial?

Yeah, the phase three trial, I think, is brilliant. I think that the team before us wrote a really good protocol. It's really well-conceived. It's well-powered. I'm very pleased with it. The one limitation of it is that at the request of the FDA, the GCSF dose is flat. And I think the reason behind that would be to remove too many variables in the analysis. So we still need to have data out there with which we can guide physicians on how to manage Mavericks for and GCSF together. So we're in the process of putting together what we call GCSF titration study, where patients will start with who on GCSF will then have Mavericks for for a period of time, and then they'll enter a period where we will try and deescalate the dose of GCSF. The idea is to complete that study and have it in manuscript form before we go into the field so that the MSLs and the reps can have a data source guiding physicians on how actually to use GCSF with Mavrovix before because you don't get all that from the forward trial because the GCSF dose is fixed.

So for the patients that you'd roll into that trial, what would be, you know, I guess the patient best suited to win and show that effect? Like what level of GCSF?

We were talking about that this morning. There will be a patient who, the patient will enroll, someone who's doing very well from an infection point of view, but is on GCSF and find that's a burden. They're getting bone pain. They don't feel well. They've got concern about risk of long-term malignancy. And the proposition for the patient is to move away from this injectable to an oral compound with as far as we can tell with very tolerable toxicity. So that's the proposition. So we're enrolling patients. Well, I suspect that trial will enroll quite well because there are a lot of patients who don't want to be on GCSF.

In terms of how you would think about a protocol, is it a fixed titration or is it more at physician discretion and removing the GCSF?

Within the protocol. Yeah, we haven't announced fully, but at the moment, the concept we're still discussing with the team would be there would be every four weeks an option to reduce the dose by a certain amount, and then over about a 20-week period, you can potentially go to zero.

And so how will you disclose kind of the updates? This is, I think, an open-label trial, potentially.

This will be an open-label trial. I think we will, towards the end, depending on where we are as a team, we're a small team, But towards the end of the year, we'll hopefully be able to announce that we've started the trial. And then we'll include it on our corporate deck and we'll talk about it. But we've been sort of telling investors about it early because, as you alluded to, the forward trial has this one sort of gap. And that's it won't generate data on how to use GCSF with Mavericks before. And that's the gap we're trying to fill.

So is there, like, a de-escalation rate that you can show before we even get to, like, the final primary endpoint of that trial?

So we'll report, we plan to report currently the de-escalation phase, and then we will report the long-term follow-up phase as well. But myself and John Valpone, our chief operating officer, we're talking about we need to report the de-escalation because that's the first thing, but we also need to report long-term safety as well. So I imagine we will have a primary endpoint and then there'll be a long-term follow-up.

And I'm sure there's a spectrum, but it's like zero reduction to no GCSF at all. What would be the ideal reduction?

Well, we saw, as you know, Derek, we had a very small phase two data set inherited, but there were patients who came off completely. Overall, I think it was about a 70% reduction in GCSF. I think there were three patients who came off completely. I don't think that's an unrealistic expectation. If Mavericks of four can maintain the ANC at a decent rate, then we could get patients off completely. So I think that should be our objective, but we'll report the data when we've got it.

Excellent. I mean, anything else on the trial that we should be focused on? I mean, now it's more execution mode, finish the enrollment, and then kind of get to the end of the trial. But any other kind of things that we should be looking at based on the update and what's going on?

No, I think the question we've got is when will data come out? And I think, you know, if we finish enrollment by the end of the year, that patient will get to, the last patient will get to 52 weeks at the end of next year. And then we're looking at getting the data out, you know, realistic time is between sort of eight to 12 weeks to get top line data. So we're gonna work hard towards that.

Gotcha. So maybe just shifting gears to the market opportunity, you know, within CN and, you know, how you guys view this, you know, we were just talking about some of the benchmarks and the metrics that maybe that docs want to see. But, you know, where do you kind of see the low hang fruit, you know, in the market and then ultimately the overall pie here?

Yeah, I think we've quoted 15,000 patients, and we're pretty confident in that number. But the more we learn about the market, the more we see where the drug can be used. It's obvious that there are patients who are getting recurrent and serious infections. That's the obvious area. But that's not just restricted to patients with ANCs less than 1,000. Mild patients can get recurrent infections as well. There are patients who take long-term antibiotics. They're not on GCSF. They take long-term antibiotics. There's patients on GCSF. Some who take it regularly. Some who take it intermittently. And then there's patients who don't want to be on anything. So we've got this broad range. And if we can develop the drug in that area, I think we can go beyond just the forward trial. But obviously, we would only promote on label. And if we get a label in serious and recurrent infections, then that's where we'll focus on. But I think there is an opportunity for us to expand beyond that with a development program.

I guess, what do you say to, like, docs who are like, GCSF is fine. Like, there's really no need for something, you know, like, never except for. I guess, you know, is that true or is that true for some patients?

Well, GCSF has been around a long time. There are always going to be docs who are very happy with it. But what we're learning from patients is very different. The patients do not want to, you know, if you're a patient in your 30s, you know, the median age on one of our trials is 30 years old. Do you really want to be on GCSF for 40 years with the risk of long-term malignancy? And the answer is normally no. Do you want, you know, I was a practicing oncologist. I used to give GCSF injections to my patients, and it's not nice for children, even young adults, to get injections. It causes bone pain. They don't feel well. So I think the patient perspective will be very important here. But the physicians we've spoken to, the markets research we have conducted, shows there is a market for an oral agent that can maintain ANCs. The injectable component of GCSF is really quite problematic. And the market will change when there's a new opportunity.

And it seems, given that a lot of these patients are on GCSF or getting a test to see if you have low neutrophils is pretty easy, but I guess, so would you say that these patients are fairly accessible and known to the healthcare system?

Yeah, they are. Our market research shows that the patients can get infections, they could go to the dermatologist, the emergency room, but they all come through the hematologist because eventually they'll need a bone marrow. If you've got low ANC, you're going to need a bone marrow examination. So, yes, we do think they're accessible. Most of the market will be the benign hematology market. Some of those patients will have gone back to primary care, but will know where they are. So, yeah, I think they are going to be very accessible. We know from our experience at CTI with Von Joe where these prescribers are, and we know that the majority of them will actually be in the community practices, not in academia, but we'll obviously work in both areas. And I think we will find them accessible, yes.

Yeah, I know we hit on this theme a little earlier, but the big question is just given some of the challenges with enrollment over the years and ultimately predating you, people are just like, is there a real market here? So maybe give us a little bit more confidence to where these patients are.

I'm more than confident there is a real market here. I wouldn't have taken this opportunity. unless I thought otherwise. We actually, years ago when we were at CTI, looked at this opportunity as a management team, and we always thought there was a market there. The problem with enrolment was operational. It's nothing to do with it. We think there are about 15,000 patients who have ANCs less than 1,000 and who have recurrent infections, who have a history of infections. The split or the typical split in the marketplace for 80% of those will be in the community and about 20% of those will be in the academia. We will focus primarily on the hematologists because that's how the patients are identified and diagnosed. And I think it's very similar to what we did at CTI. I think we can be quite successful here.

And then maybe just in terms of the burden to the healthcare system for these patients with these recurrent infections and how you start to think about pricing and the overall value here.

I think there's two components to it. So we need to do some work on the cost of the health care system. Hospitalization, surgical drainage of abscesses and stuff, that's a substantial health care cost. And that's the kind of infections we're talking about, skin infections. So that's early days for us. With respect to pricing, I think there is an opportunity here to have premium pricing against GCSF if we improve against infections. um we haven't uh the current pricing of for the whim indication is in the five hundred thousand dollars a year it's not going to be high that i suspect we're going to be in around two to three hundred thousand um but we we need to do more research as a company but based on prior experience i suspect that's where we're going to end up gotcha and then just competitive landscape here i mean is there really anything other than you know obviously gcsf is kind of the incumbent here but uh you anything else that's kind of on your radar that you're looking at or um not at this stage no there isn't um um but we have to be vigilant and make sure no one else you know if there is someone behind us but there's no one at this advanced stage that we're aware of gotcha so i guess when you think about the company you know you came here you've kind of right to the ship we're in execution mode um you know what's what's kind of beyond maver and what what do you kind of think about in terms of building this company into you know a heme you know specialized specialized focused company yeah I'd very much like to do that we've got some really good people who've got a lot of experience in the heme space both benign and malignant and I really would like to see the company develop with new assets coming developing more as a broader hematology company so we can really make use of who we have and the people we have that obviously has not been our priority today. Our main priority has been the completion of the enrollment of Ford, but in the future, if there was a good opportunity to expand the portfolio in our area of expertise, we would certainly look at it.

I guess what do you take from your prior experience at CTI and working with the Heme division and all that?

I mean, how helpful is that for this whole process and the upcoming potential regulatory interactions I'm a big fan of the benign hematology division because I think they're really patient focused and they tell you what they're thinking it I really am a big fan of the division the communication we just had with them is very straightforward and we fortunately we know a lot of the people in the division still we've worked with them before and I hope to continue a good relationship a relationship where it's trustworthy on both sides, but this is benign, non-malignant hematology, I think is a really good area to develop a drug in because the FDA is very, very patient-focused, as we are. So, so far, it's been very good.

And is the idea to commercialize this yourself in the U.S. or partner ex-U.S., what's kind of a future launch?

Certainly commercialized in U.S. Norjean, who is our partner in Europe for WIM, will have the option of whether they want to opt-in once the data is out for chronic neutropenia in Europe but yes we're we are we've already hired a former colleague as a head of marketing and we're very we're working hard on the marketing plan and we plan to launch in the US.

What does the footprint look like and I guess is this a concentrated population?

I think it's gonna be very similar to what we did with CTI I think the split, as I said previously, is between 80 and 20 between community and academia. We're talking probably around 50, 60 reps, five or six regional business managers, a very, very similar profile to before. A lot of these large community practices where we sell Von Joe will also look after chronic neutropenia patients. So I think it will be the same number of about 2,000, 2,500 thousand physicians very very achievable for a smaller company and then maybe just last set of questions so in terms of the funding here so you can you push out the timelines a little bit so just talk to us about your runway and what's funded you know what you're funded through yeah so we're funded into 29 very comfortable thanks to the work of David Kursky my CFO David has been very good at reducing the spend to the company and we are some of the cost savings from the forward trial will go into the gcsf titration style so we have enough money to to launch and you know we're putting the launch activities

planning them for 2028 and so we're in a good position so the next update we should get is just enrollment completion is that something that you know is that a press release or how you disclose?

Yeah, we'll announce it. I think the street needs an announcement on that. That would be the appropriate thing to do. And hopefully at some point we'll be able to announce the start of the GCSF titration study as well. That would be good.

Would you anticipate like kind of completing a little bit over the target number 126 or?

My experience is you always go over a little bit because at the end of a trial, I was in Europe last week talking to some physicians and they've got patients they're going to consider to put on the trial at the end. You always get a little bit of an uptick at the end. I'm very comfortable with that. The agency will not criticize us if we're 5-10% over. That will be absolutely fine.

Maybe just last question. Next 12-18 months seems pretty consequential. You'll be reading out that trial. Maybe just make sure we know all the key updates here and anything else that we should know in that Yes, so the main thing, as you say, is the completion of enrolment.

I think the street needs to hear that. Hopefully that will be before the end of the year. Then the data itself will be in early 28, hopefully around 8 to 12 weeks after we enrol the last patient. And then based on whether FDA grants us priority review, You're talking about a launch maybe end of 28, early 29. It really depends on how long the agency takes, whether we get priority review. But certainly, the first quarter of 29 is probably about as late as it will be. So that's where we're heading for the next 18 months to two years.

Well, Adam, I think we'll leave it there. Thank you so much. Thank you for your time. Good to see you.