X4 Pharmaceuticals at Guggenheim Conference: Strategic Focus on Neutropenia

On Monday, 10 November 2025, X4 Pharmaceuticals (NASDAQ:XFOR) presented at the Guggenheim Securities 2nd Annual Healthcare Innovation Conference. The company outlined its strategic focus on advancing its lead program, mavorixafor, for chronic neutropenia. While the restructuring and new financing of nearly $240 million were highlighted as positive steps, the decision to deprioritize WHIM syndrome commercialization was noted as a necessary shift to concentrate resources on a larger market opportunity.

Key Takeaways

• X4 Pharmaceuticals is focusing on mavorixafor for chronic neutropenia, aiming for a 2028 launch.
• The Phase 3 FORWARD study is underway, with over one-third of patient enrollment completed.
• The company has raised nearly $240 million, sufficient to complete the trial and launch.
• X4 is targeting a premium pricing environment and plans US commercialization, collaborating with Norjin for Europe.
• The company aims for a one-third reduction in infection rates in the trial.

Financial Results

• Raised nearly $240 million in cash, ensuring sufficient funds to complete the Phase 3 trial and launch mavorixafor.
• The strategic focus on chronic neutropenia is expected to open up a broader market with approximately 15,000 patients.

Operational Updates

• The company has restructured its management, removing the C-suite and appointing a new team to accelerate the Phase 3 trial.
• Enrollment for the FORWARD study is over one-third complete, with efforts to increase recruitment through US sites and patient advocacy groups.
• The company anticipates finishing enrollment by the end of Q3 2026 and expects top-line data in the second half of 2027.

Future Outlook

• X4 Pharmaceuticals plans to focus on US commercialization while collaborating with Norjin for European rights.
• The chronic neutropenia market is expected to be a premium pricing environment, typical for rare hematology diseases.
• The company aims to generate G-CSF combination data to strengthen its market position.

Q&A Highlights

• Mavorixafor targets CXCR4, releasing neutrophils from the bone marrow into the bloodstream.
• The study is designed with over 96% power for two primary endpoints, focusing on reducing infection rates.
• Approximately 40% of patients currently use G-CSF, and the study aims to provide combination data.

For a more detailed understanding, readers are encouraged to refer to the full transcript.

Full transcript - Guggenheim Securities 2nd Annual Healthcare Innovation Conference:

Michael, Interviewer: It's my great pleasure to welcome Adam Craig, CEO of X4 Pharmaceuticals. Adam, welcome. Thanks for joining us.

Adam Craig, Executive Chair, X4 Pharmaceuticals: Good morning, Michael. It's nice to see you again. I'm Executive Chair. I'm not CEO.

Yeah, I'm very—thanks. Oh, gotcha. All right. Again, you know, Adam, you and the rest of the team just very recently joined X4 Pharmaceuticals about three months ago. Yeah, talk about your decision to join X4 and what opportunity to create value do you see in the company?

We were actually interested in the lead compound mavorixafor three years ago when we were at CTI BioPharma. David, myself, and the management team did look at it and thought the drug had great potential in chronic neutropenia. When the opportunity came this summer to be part of a new management team with restructuring and new financing for the company, it was an easy decision to make. Over the last three months, we've moved the company along. We've raised just under $240 million in cash, and we now have enough to complete the phase 3 trial in chronic neutropenia. We have enough cash to take us all the way to launch.

Yeah, just maybe let's step back a little bit and talk a little bit about the lead program. Just to set the stage, I know it's been approved in a rare indication, and you're working on chronic neutropenia. Maybe just if you step back and just talk a little bit about the company and the story.

The company specializes in rare hematology diseases. There are many diseases out there where patients have very low neutrophil counts. With that, they have increased risk of infection, sometimes life-threatening, often very serious infections. It is a very debilitating condition to have because patients cannot go out into public, cannot without the risk and the concern of getting infections. As you said, the company a couple of years ago got an indication for WHIM, which is a very rare, very ultra-rare indication. The commercial opportunity for the drug is in a much broader indication, which is chronic neutropenia. These patients have low neutrophils. The population we are studying is patients who have moderate or severe chronic neutropenia. That is with neutrophil counts of 1,000 or less.

Most of the people in this room hopefully will have a neutrophil count over 1,500, which is normal, and can fight infection normally. If you're under 1,000, you're at risk. That's where we're focusing on because it's a much bigger market opportunity. We estimate there's approximately 15,000 patients. We're still continuing to refine that number. If that's the case and we get the drug approved in 2028, you can see there's a much bigger market opportunity for us than in the tiny WHIM indication, which is really in numbers, you know, less than 50 patients a year. That was part of the attraction at CTI. David and I were CFO, David Kursky, at the front there. We were able to launch and commercialize a drug in a hematology condition. This is an opportunity to do it again with a very, very similar prescriber base.

Right. So maybe stepping just back for one second. Mavorixafor targets CXCR4, the name of the company, which is very similar to plerixafor, commonly known as Mozobil. Maybe just talk about the mechanism of action and how well established is that.

It's an antagonist of CXCR4. That antagonism leads to the release of neutrophils from the bone marrow. If you look at the bone marrow of many patients with chronic neutropenia, they have neutrophils in their bone marrow. For some reason, they're not being released into the bloodstream. As a result of that, they have low counts. Mavorixafor is very clever in that it allows for the release of these neutrophils from the bone marrow into the bloodstream. It's very different to the other compound you refer to. That was an IV compound. The beauty of Mavorixafor is it's an oral agent. This is a population of patients who currently, not all of them, but about 40% of them have G-CSF. I remember from my time in pediatric oncology, hematology, giving G-CSF to patients is not ideal. It involves injections.

It can cause a lot of bone pain and discomfort. It's not ideal. If we can introduce an oral agent into this setting, I think we can have quite a significant competitive advantage.

Great. Mavorixafor, as you mentioned, is already FDA approved in a rare indication called WHIM syndrome. Maybe just very briefly touch on this opportunity. How do you think about the broader relevance of this as a model for other diseases that could be treated with the molecule?

It's a tiny indication. We've actually deprioritized the commercialization of the WHIM indication. It's for a very simple reason. The company needs to focus its resources on getting the broader indication if it is to be, if we're to be, a commercially successful company. That's really, really important. However, the WHIM data, and it was collected in a randomized trial, not a large one because it's a rare, ultra-rare indication. The WHIM data is very important because patients with WHIM syndrome have severe neutropenia. They have neutrophil counts less than 500. We have been able to glean a lot of information around infections, changes in ANC rates, ANC levels from the WHIM data. It's very important. It's a good model for us to base some of our powering assumptions for the larger trial.

Right. Obviously, as you mentioned, the real value proposition for the story is the chronic neutropenia indication. You mentioned patient numbers a second ago. Maybe just again, stepping back to set the stage, how is chronic neutropenia managed today? Walk us through that process. How do you think about the opportunity for mavorixafor?

It's currently managed in two ways. There's about 40-45% of patients, according to our market research, as I say, we are refining the research, receive G-CSF. G-CSF, because of the bone pain, because of the concerns about infection, there's risk, potential risk of long-term malignancy. It's not a lot of patients, it's not given regularly. Some patients will have it regularly and will have it without issue. Other patients will take it when they're at risk of an acute infection. Some patients are just on and off it. They just don't take it. About 60% of patients are managed with their infections are managed. Some patients are given steroids. It's not a great market. There isn't, from a medical perspective, there isn't a uniform way of treating these patients.

The feedback we've got from our physicians that we speak to, both in market research and on our trials, is the ability to have an oral agent in that setting will be a competitive advantage. The way I see it is the drug will be used as monotherapy in some settings, and it may be used with G-CSF in other settings. We have some phase 2 data that shows that the G-CSF dose can be altered while patients are on mavorixafor without the ANC dropping below normal levels. I think that's how it could be used with G-CSF, with dose adjustments to make it more convenient, less uncomfortable for the patient with the G-CSF. The agent on the other side will be used on its own.

Right. In terms of market size, sort of are drugs like Neupogen, like other good proxies for how we should think about the commercial opportunity? Or is there a different way of thinking about it?

Those agents are used in a large setting, including sort of post-chemo and other settings. It is a much larger population. What we're focusing on at the moment is just those patients with chronic neutropenia. That could be autoimmune, idiopathic, and in some cases, congenital. That is a specific group. We estimate that to be 15,000. You can see for a small company like our own, to commercialize an opportunity of 15,000 means we could really add some value for patients and for investors as well.

Great. Yeah, you did mention the phase two study. I think most recently there were some data presented at EHA, I believe. Can you just remind us of what the key learnings were from the phase two study in chronic neutropenia in terms of efficacy and tolerability?

Yeah, I'll give you my perspective as in sort of with my physician hat on as a new part of the management team. The study, in my view, showed two things. First of all, it showed that mavorixafor could be given alone in congenital neutropenia, and the ANC levels could increase and go above normal, which is really good. There is sort of a pharmacodynamic proof of concept of the drug, which was great. The other side of it were patients who came on G-CSF, some of them with normal ANC levels, but they came in wanting to see if the G-CSF level could be altered. In those patients, when the G-CSF dose went down with mavorixafor, we were still able to maintain normal ANC levels.

I think the phase two data is really, it's not a massive data set, but it's really quite informative. It proves that the drug can be given as a single agent and achieve its pharmacodynamic endpoint, which is ANC increase. It proves that, subject obviously to a randomized trial, it can be given in combination with G-CSF, and the dose can be changed. From a safety perspective, the safety of this drug is really quite consistent. It's been reported before by the previous management team. Patients often get GI symptoms. This can be managed symptomatically with antidiarrheals and antiemetics. It's normally mild or moderate. I think as time's gone on, the company has learned more and more about how to manage that. That's the main toxicity. It occurs within the first five or six days of therapy. Typically, it goes away after a couple of weeks.

Some patients have it for a little bit longer. What we have, as I say, what we're learning is you've got to advise physicians to treat it symptomatically as early as possible.

Okay, great. Yeah, you did mention this is in phase three now. Just remind us of the design of this study and sort of the primary outcomes that are being assessed.

Yeah, so it's the, we call it the forward study. It's 176 patients, and it's double-blinded, placebo-controlled, randomized trial. What it's looking at is mavorixafor plus placebo in a one-to-one distribution. On either arm, you can have G-CSF. So it's mavorixafor plus or minus G-CSF, placebo plus or minus G-CSF. The study is powered for over 96% power for two primary endpoints. One is an increase in the ANC, and another one is a reduction in the analyzed infection rate. The FDA asked us to look not only at ANC increases, but to look to see if it actually works and reduces infection rate, which we expect it to do because the data that we have shows that the neutrophils work when they're released. Quite rightly, the FDA wanted more than just a sort of pharmacodynamic endpoint. They wanted a clinical endpoint.

The study is well designed. David and I took a look at it when we started. We have not made—I'm a physician. I like changing protocols, but I could not really on this one. I thought it was extremely well designed by a very talented team. We have not made any significant changes to endpoints because I thought it was just well powered and well designed.

Okay. How confident are you that the phase two data will translate into phase three? Are there any differences in patient eligibility characteristics or other things?

Yeah, there's a little bit, there's some similarities, but it's a little bit apples to pears, is the honest answer. It's a small data set. Had I run that trial myself, I probably would have done a bigger trial and answered a few more questions. But the basic premise is there. You can give, we know we can give the drug in combination with G-CSF safely. And we know that the ANC levels can increase. That's important because everyone knows in clinical practice, even when I was in practice a long time ago, unless the patient's ANC increases to a certain number, you couldn't send them home from the oncology ward because they'd be at risk of infection. It's been well described that the higher the ANC, the lower the risk of infection. I've got every reason to think that will carry through to the phase 3.

Yeah, how are the infection outcomes measured? Can you talk a bit about the sort of expectations for outcomes in either arm and what your assumptions were when designing a study?

Yeah, first of all, I should have said when you asked earlier, Michael, is patients can to go on study, they have to have an ANC less than 1,000, but they also have had to have at least two infections in the prior 12 months. We're not talking about mouth ulcerations or reactivation of herpes simplex. They've got to be proper infections that required antibiotics or the patient went to the emergency room or the doctor's office. On study, we monitor the infection rate. It's a one-year study. We monitor the infections over the year. One of the things I really, really like about this study, and I think it will go down very well with the FDA, we have an independent monitoring committee for infections.

Any event that appears to be an infection is adjudicated independently by three physicians who are sort of infectious disease, primary care, pediatricians, that kind of cohort of people. They will make an assessment independently of us. We will not be going to the agency with an NDA application where the agency says, well, the company thinks this is an infection. We do not because it is independently assessed. It puts us in a much stronger position. Infections like mouth ulcerations, gingivitis, they are excluded. It has got to be proper infections.

The time frame, you said, is one year?

It's one year. What we will do is we're looking at the analyzed infection rate between the mavorixafor arm versus the placebo arm. We're looking for approximately a one-third reduction in the analyzed infection rate.

All right, super helpful. How has the study been enrolling? How has that been tracking relative to expectations?

We're just over one-third enrolled. Under the prior management, it was not strong. The study was behind. That's why a new management team has been brought in. Part of the problem, obviously, is resourcing. We've restructured the company. We have removed the C-suite. David and myself, my colleague John Valpone, who's President and CEO, we are the management team at X4 Pharmaceuticals. We've come in. John's an operations expert and is leading restructuring of the trial. We're putting more money into it. We're focusing on the US. There haven't been many patients enrolled in the US. We're opening more US sites. We're putting our MSLs back into the field for recruitment, not commercial activities. We're spending time finding the patients. This is a rare disease trial. We know from past experience that you have to work very hard to get the patients.

You can't just rely on them to come to the institution where you're doing this trial. You've got to find them through patient advocacy groups, through databases, through other hospitals. You've got to do the work. We've changed the emphasis. From the company, previously, the focus was on commercialization of WHIM. Now, we'll have a company meeting later this week, and we'll reiterate to the team, the sole focus is the execution of the forward trial.

Okay. What percentage of patients in the study do you expect to be on concomitant G-CSF versus not?

We're tracking it on a blended data set. It's about 40%, which is in keeping, actually, with what market research says. I think we're recruiting, it looks like we're recruiting a population that's pretty representative of what's out there.

Okay. I think you spoke publicly about data could be available in 2027. Is that correct? How should we think about timing?

Yes, we expect recruitment under a new timeline. It is different to what's been said previously. Under a new timeline, the enrollment to finish by the end of Q3 2026 takes a year for the data to come through. The second half of 2027, we should have top-line data. If that's the case, we'll file an SNDA as quickly as possible. That is why we think we can launch this new indication in 2028. We're pleased to say, thanks to the help of Guggenheim and others, we have enough money to do that.

Okay, great. Yeah, I mean, longer term, how do you think about commercializing this and maybe talk about pricing? It's already approved in a rare disease. Also, market access.

I'd love to commercialize this one. It's a very similar prescriber base to the one we had with CTI and with Bendeka. A lot of community practitioners, large community practices who see these patients, academics who see these patients. I think it would be tremendous fun to do it. I think we can get return for shareholders along the way. Pricing, certainly, this is a rare disease. Hematology, it is a premium pricing environment. The actual price, I think we need to do some pricing work on that. We haven't done that yet. Once we have it, I would not be surprised if we're talking about a premium pricing environment. I think that's fairly typical in this situation. It could be very good for the company.

Great. Are there any competitors that we should be paying attention to in this space?

Not oral agents like this, no, not really. Our main competitor, I suppose, is G-CSF at the moment. We have got to generate some G-CSF combination data in the forward study, which we will have. That will put us in a much stronger position. Apart from that, I think that's where the company's focus needs to be as we move to commercialization is how do we tell the story around G-CSF.

Okay. Between now and the phase 3 data in 2027, are there any other events or milestones investors should be paying attention to?

It is the completion of the enrollment. That is something we need to deliver on, and we are very determined to deliver on that. Over time, we do need to tell the market opportunity story more completely. We have not done all the work we want to do on that. As time goes on, we are hoping we will be able to talk to the street in more detail about what we think is the market opportunity so investors can understand where we will be going. I think that is something we do not have at the moment to a level I am happy with. Over the coming months, we will work on that.

Okay. How do you think about commercializing this in the future globally as opposed to?

We have a very good relationship with Norjin in Europe who have European rights. We will be focusing on the US.

Okay, helpful. With that, I think it's time to wrap up. Adam, thank you for the time and very interesting story. Really appreciate it.

Thank you, Michael.

Thanks.

This article was generated with the support of AI and reviewed by an editor. For more information see our T&C.