X4 Pharmaceuticals Q4 2024 Earnings Call Transcript

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March 25, 2025

There are 11 speakers on the call.

Operator

Greetings and welcome to the X4 Pharmaceuticals Fourth Quarter and Full Year twenty twenty four Financial and Operating Results Conference Call. 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. And it is now my pleasure to turn to your host, Dan Ferry from LifeSight Advisors.

Operator

Please begin.

Speaker 1

Thank you, operator, and good morning, everyone. Presenting on today's call will be X Force's Chief Executive Officer, Doctor. Paul Regan and Chief Financial Officer, Adam Mostafa. Following prepared remarks by each, we will open the call to your questions and we'll be joined by Chief Commercial Officer, Mark Baldry Chief Medical Officer, Doctor. Christophe Arvid Engels and Chief Operating Officer, Mary DiBiase.

Speaker 1

As a reminder, on today's call, the company will be making forward looking statements regarding regulatory and product development plans. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted. A description of these risks can be found in X4's most recent filings with the SEC, including this year's Form 10 K, which is expected to be filed after market close today.

Speaker 2

I'd now like to turn

Speaker 1

the call over to X Force President and CEO, Doctor. Paula Reagan. Paula?

Speaker 3

Thank you, Dan, and thanks to all of you for joining us this morning. As expected, 2024 was a transformative year for the company and for those with WIM syndrome, and we are very pleased to continue to deliver as we progress into 2025. As you know, we became a fully integrated company in 2024 with The U. S. Approval and launch of our first product, Mavrexa four, which we branded as Zolremdi in The U.

Speaker 3

S. For the treatment of WIM syndrome, an ultra rare primary immunodeficiency. Our commercialization strategy remains focused on a multi pronged approach as is typical in the rare disease space. Over the past year, we significantly advanced disease awareness with both treating physicians and WEM patients through a combination of in person and digital education campaigns and through strengthened relationships with our rare disease patient advocacy group partners. A peer to peer speaker program was also launched in the second half, enabling physicians to share their experiences in managing WIM syndrome and treating with Zolremdi.

Speaker 3

In addition, our suite of patient services including our X4 Connect and Nurse Educator programs continue to provide access and support for patients prescribed ZolremD And journal publications and presentations of clinical data at top medical meetings, including those of the American Society of Hematology or ASH, the American Academy of Allergy, Asthma and Immunology or QuadAI and the Clinical Immunology Society have provided further visibility. And we've been very encouraged by some recently received testimonials from our patients on ZulremD. We heard from one patient who described his normally functioning immune system and his significant improvement in skin infections, warts and periodontal issues. He said he now knows what it's like to lead a quote, normal unquote, life with lower anxiety about getting sick, ability to travel, and that he, quote, didn't know how sick he was until he finally felt better, unquote. Another patient has told us about his near normal ANC levels, his increased energy, increased productivity and engagement at work and the importance of him not having to miss any family or social events anymore.

Speaker 3

It's really been quite inspiring. Our 2024 Zolremity sales topped 2,500,000 which covered the seven point five months since our mid May launch last year. Throughout 2024, we successfully engaged with all of our target top tier immunologists and hematologists. We expect that these efforts will continue to deliver through both increased patient finding and shortening the time to pull through to a ZulremD prescription. In addition to our progress across The U.

Speaker 3

S, we've also made significant progress in our efforts to expand the potential global reach of MAVERICKS four and WIM. In January, we announced that our submitted MAA was accepted by the EMA for review. With a typical twelve to fifteen month review process, we would expect potential approval for the EMA as early as the first quarter of twenty twenty six. We've also entered into two international partnerships. The first with Neurogene, a leading European specialty pharmaceutical company.

Speaker 3

Under this license and supply agreement, Neurogene will commercialize Mavericks for for WIM and chronic neutropenia in Europe, Australia and New Zealand following regulatory approvals in those areas. We received EUR 28,500,000.0 upfront and are eligible to receive up to EUR $226,000,000 in potential regulatory and commercial milestone payments. In addition to tier double digit royalties up to the mid 20% range. We continue to believe that the Neurajene deal is a great fit for us given both their focus on rare disease and specialty markets and our shared vision of putting patients first. The second deal we announced was with a company called TABA Rare, another specialty pharmaceutical company.

Speaker 3

The agreement enables TABA to use its expertise towards orphan drug marketing, sales and distribution in The Middle East and North Africa or MENA region. TABA will be marketing Zolremby for WIM syndrome across the region. We expect that the formal approvals will be sought in Saudi Arabia and Kuwait, But in the meantime, pending any regulatory approvals, TABA expects to be able to provide Zolremity to WIM patients through a named patient or compassionate use program that allows physicians to prescribe medicines approved in other countries to local patients with no other treatment options. So a lot to look forward to in WIM, but now let's turn our continued advancement of MAVERICKS-four to treat the larger potential indication of chronic neutropenia. During 2024, we successfully completed a Phase two clinical trial of MAVERICKS-four across several CN disorders with and without concurrent injectable G CSF, which is the current standard of care and the only drug approved for severe chronic neutropenia.

Speaker 3

Throughout the year, we announced both interim and then full data from this trial that we believe significantly derisks our ongoing Phase three CN trial. The six month open label clinical Phase two trial ended up enrolling 23 participants and demonstrated one that once daily oral MABRIX-four was generally well tolerated with and without G CSF with no drug related serious adverse events reported and consistent with our previous clinical studies. Two, that MAVERICKS four treatment durably and meaningfully increased participants mean absolute neutrophil counts or ANC across all study populations and three, that physicians were willing and able to reduce the use of G CSF and participants also treated with MAVERICKS-four and were able to maintain mean ANC levels within the normal range. Given these positive data, we initiated a global pivotal Phase III CN trial called the FORWARD trial last year. The FORWARD trial is a twelve month placebo controlled trial aiming to enroll 150 participants with congenital acquired primary autoimmune or idiopathic CN who are experiencing recurrent and or serious infections.

Speaker 3

More recently, based on FDA and EMA guidance, we have refined and simplified the FORWARD protocol. We are now enrolling only moderate to severe neutropenic participants or those with ANCs below 1,000 cells per microliter. Given the trials and section inclusion criteria, this ANC level was already consistent with our targeted patient population for MAVERICKS-four, if approved, focuses on those with the highest unmet need and consistent with almost all of the subjects already enrolled in the trial. In addition, the ANC component of the co primary endpoint, which comprises both ANC increase and infection benefit will now be uniform across all participants. This primary endpoint seeks to demonstrate that infection benefit for MAVERICKS-four treatment results from a durable increase in ANC of at least 500 cells per microliter over the twelve month duration of the study.

Speaker 3

As you may recall, participants in our Phase three LUM trial were severely neutropenic at baseline with an average ANC well below 500 cells per microliter. Importantly, MAVERICKS-four was able to raise ANC by 600 to 800 cells per microliter on average in the MAVERICKS-four treatment population, which resulted in clinical benefit in the rates, duration and severity of infections in that study. For these reasons, we believe that these trial protocol refinements in CN increase our chances of success in this trial on top of what we believe to be an already highly powered and robustly designed study. We also announced this morning that the FORWARD trial has now been activated at about ninety percent of our targeted sites worldwide. Given this and the average screening success rates currently being observed, we expect that this trial will be fully enrolled in the third or fourth quarter of this year, which should enable us to disclose top line data in the second half of twenty twenty six.

Speaker 3

Before I turn over the call to Adam to discuss our financials, I do want to briefly touch on our recent strategic restructuring where we announced that our revised business scope is expected to decrease our spending by about $30,000,000 to $35,000,000 annually. We implemented these changes in early February to sharpen our focus on maximizing the opportunity for mavericks four in chronic neutropenia. We believe this is a much larger potential market opportunity for us and given the challenging macro environment we all find ourselves in currently, we believe the best path to maximizing shareholder value and to giving us the greatest chance of success. With that, I'll turn it over to Adam.

Speaker 4

Thanks, Paul.

Speaker 5

As we disclosed in the press release this morning, we ended 2024 with just under $103,000,000 in cash and cash equivalents, pro form a for the EUR 28,500,000.0 received from Noregene and the expected financial impact of the strategic restructuring announced in February, we believe we have sufficient funds to support company operations into the first half of twenty twenty six. We reported net ZorMD revenues of $1,400,000 and $2,600,000 for the fourth quarter and full year 2024. Our R and D expenditures totaled $21,700,000 and $81,600,000 for the fourth quarter and full year, which included $1,200,000 and $4,300,000 in non cash expenses respectively. Our SG and A expenses were $15,100,000 and $61,500,000 for the fourth quarter and full year of 2024, which included $1,000,000 and $3,900,000 in non cash expenses respectively. Our net loss was $39,800,000 in the fourth quarter and for the full year was $37,500,000 but keep in mind this annual figure reflects the one time sale of our priority review voucher in May of last year for $105,000,000 We'll now open up the call to your questions.

Speaker 5

Operator?

Speaker 6

Thank you.

Operator

We'll take our first question from Stephen Willey with Stifel. Please go ahead.

Speaker 7

Yes, good morning. Thanks for taking the questions.

Speaker 8

I was just wondering if you

Speaker 7

could maybe just kind of expand a little bit around the regulatory conversation that was had regarding taking the ANC threshold to below 1,500 to below 1,000. Was this a discussion that was had, I guess, prior to the initiation of the trial? Is this something that FDA and I guess EMA came back to you with? And do you think that there's any risk around needing to potentially upsize the trial to get more of the sub 1,000 patients? And then I just have a follow-up.

Speaker 3

Yes. Thanks for the question, Steve. I'll kick it off with some high level commentary and then turn it over to Christophe. So I think the most important thing that we learned from our engagement with the FDA is that they're very interested enabling our success for this trial. They had experiences of a broader range of patients and other non malignant team areas that have failed.

Speaker 3

So they are very interested in ensuring the trial design has maximum opportunity for success, which is why we're in alignment on focusing on the moderate severe patients. We don't think this actually impacts our trial in terms of its case because already the requirement was always at least two infections per year previously. So we've already seen that narrow our funnel certainly more substantially than anything around ANC. But again, I think we're extremely pleased with the engagement. We feel that this alignment is very tightly correlated now.

Speaker 3

And I'll turn it over to Christophe to add some more color.

Speaker 9

Yes. We've had a really positive interactions with the agencies, both DSD and DEMA and both are very supportive of the approach that we're taking. With regard to Vansy in particular, again, it's a non validated biomarker, so there is a number of factors. There is no consensus or recommendation. So we've taken the approach that is the most reasonable, both in our eyes and the agencies.

Speaker 9

Actually, even the EMA is not asking for the ANC and looking more at the clinical outcomes of infection. So again, infections benefits is really what we're trying to demonstrate here because it is the clinical outcome. And to Paula's point, we've got several investigator meetings with a lot of participations. We've had webinars with more than 90 people per webinars attending. So we've been extremely pleased with the engagements and the interests that we've received regarding the study and its conduct.

Speaker 7

Okay. And then, I guess, with the tightening up of the eligibility criteria around baseline A and C, would you expect that to potentially slow down the pace of enrollment a little bit? I know I think it seems like the guidance here is maybe modestly pushed out just a little bit. Does that reflect the tightening of that A and C requirement?

Speaker 9

Yes. No, it is not because we never expected that my patients would represent a substantial amount of patients. And because of the history of infections, these were at lower risk of infections. So and we haven't seen in our screening many of these patients at all. So we're really having no concern with regard to the enrolled in timelines.

Speaker 7

Okay.

Speaker 3

Just to add to that point, Dusty, we are trying to make sure that we hit our timelines and we have not seen a lot of patients enroll with a mild spectrum, but we want to make sure that we cover any uncertainties in the future by to your point moving us out a tiny bit forward in 2025.

Speaker 7

Understood. And then maybe just a quick financial question. Can you just I think there were some comments made earlier in the year regarding having to work through maybe a little bit of additional inventory at the distributor level. Can you just kind of speak to where inventory sits now? And then maybe just anything that you can say on just kind of early discounting trends that you're seeing?

Speaker 7

Thank you.

Speaker 3

Adam, do you want to take that one?

Speaker 5

Sure. Yes. Thanks, Steve. Thanks, Paul. So you'll see on our balance sheet the updated inventory metric, which reflects where we are with respect to a bit of stocking up in the fourth quarter related to what translated into sales from the specialty pharma orders that came in.

Speaker 5

As you know, similar to sales that will likely be lumpy over time. So, I wouldn't expect particular trends that we can point to just yet, but some of that will be based on the progress and pace of demand over the course of the year.

Speaker 7

And then just anything you're seeing on the discounting front? I know it's early, it's only been a few quarters, but on the gross to net side?

Speaker 5

Yes. Go ahead, Mark. Yes. I was going to say,

Speaker 4

this is Mark here. Are you talking about discounting with the payers?

Speaker 7

Yes, correct.

Speaker 4

Yes. No, we're we have a tight distribution channel through our specialty pharmacy and we're not engaging in discounting at this time.

Speaker 7

Okay. Thanks for taking the questions.

Speaker 6

Thank you. And

Operator

we'll take our next question from Ed Tenthoff with Piper Sandler. Please go ahead.

Speaker 8

Great. Thank you. Good morning, everyone. I guess I'll ask you a couple of questions on the launch. Can you tell us give or take how many patients are on drug right now?

Speaker 8

And did you have any price increase to start 2025 for Zolremity?

Speaker 4

Yes. Good morning, Ted. We're not giving out patient numbers at this time because we're still building demand. Demand is still building and we're still engaging with physicians, building awareness. And now we're actually really pivoting our efforts to focus on the patient community and raising awareness there as we roll out some new patient campaigns and patient ambassador programs.

Speaker 4

We did take a slight price increase as is typical coming into the new year.

Speaker 8

And can you share how much that is or?

Speaker 4

It was a 7% price increase.

Speaker 8

7%. Thank you. Looking forward to more progress this year. Thanks so much.

Speaker 9

Thanks, Ed.

Operator

And we'll take our next question from Kristin Klusko with Cantor Fitzgerald. Please go ahead. Kristin, your line is open. Please go ahead.

Speaker 6

Hi. Sorry about that. Good morning. This is Ayan on the line for Kristin. Thank Questin.

Speaker 6

For the Phase three trial, how are you doing with the screening of these patients? What percent of the patients that go through the screening are you getting on the drug versus those who are not?

Speaker 3

I mean, so the site activation is the first wave and as we highlighted, we're at about ninety percent of our target number of sites. Screening, the screening ramp is coming up very nicely and then of course patients on drug are not really breaking down anything further beyond site activations in terms of screening rates or screen failures other than to say what we've already observed for the last several months will put us on trajectory of the Q3, Q4 full enrollment. Christoph, any other color you want to add?

Speaker 9

No. We're pleased with the again, very pleased with the site activations, the engagements at all these sites and the screening is picking up as expected, so from those site activations. So we're in the right right now.

Speaker 3

Thank you for that.

Operator

And we'll next go to Doug Macpherson with H. C. Wainwright. Please go ahead.

Speaker 10

Hi there. Good morning. Curious about any further commentary you might have on commercialization sort of what you've learned and experienced in the first seven or so months since launch specifically. I know you said you're not giving exact patient numbers, but I think last time we checked all the patients in The U. S.

Speaker 10

Had been previously enrolled in the trial that now continue treatment. Have you seen patients in sort of come on treatment beyond those that had previously been in the trial? Have you seen a decrease in diagnosis time and time from sort of initial seeing the doctor into getting on treatment? We'll start there with that multi part question.

Speaker 4

Thanks. Sure. Thanks. Let me try and give you a bit of a flavor for what we've learned and our excitement for 2025. So we came into this market, which was a market where there really were no approved therapies and very low awareness of the disease.

Speaker 4

And so we focused on building that awareness and engaging with our target physicians to really build their knowledge of WIM syndrome and increase screening and diagnosis rates. And we were successful in doing that as we came into the back end of last year. And so we enrolled all of the patients that were in The U. S. Patients that were in the clinical trial have all enrolled onto the product and we've seen continuing building demand for the products over time.

Speaker 4

We're just entering now what we call conference season and we were recently at the Quad AI conference out in San Diego where we engaged with a lot of our customers and we actually found another two or three patients that we weren't aware of. And so as we progress through this conference season with some additional meetings like CIS and ASPO, we're looking forward to continuing to engage with these physicians, helping them identify patients in their practice and see the build in demand for Zolremby over time.

Speaker 10

Great. Thanks for that. And then looking at your commercialization agreements in the ex U. S. Geographies, there's still some regulatory hurdles, but regulatory milestones to hit.

Speaker 10

With your partners in the agreements, are there any sort of like clauses regarding timing or milestones for registration in order to really engage with those commercial partners?

Speaker 3

I'll take that and then Adam if you want to chime in afterwards. But no, our the next key wave of regulatory milestones are certainly around WAM approval, potential approval in Europe, which is really where Nurogen can bring its excellence in launching that product. So we're nicely on track. We've already filed that application with EMA and it's been accepted. So we are continuing to project approval, potential approval on the first half of twenty twenty six on launch.

Speaker 3

And then in terms of CN, I think they recognize the value of the huge market potential that can unlock with a CN approval. So and certainly they've seen the case that we've been making progress there. So there's no real timeline associated with the release of success based milestones and across that both regulatory and sales future sales.

Speaker 7

Great. Thanks for that. And then if

Speaker 10

I can sneak in one last one before we move on. Your current expected patient numbers for both women Centimeters, U. S, ex U. S?

Speaker 3

Yes. So we have not learned anything differently. Just change our guidance around one thousand total diagnosed lung patients in The U. S. The ramp to get there is certainly something we're learning more about and will take some time.

Speaker 3

But chronic neutropenia is certainly much more straightforward. There are ICD-ten codes that are associated with these diseases, so they are much better tracked over time in EMR. So we feel confident with the total population that we have learned through research on ICD-ten. The total bucket is about fifty thousand, five thousand, but we're targeting the refractory severe end of that population with our current study and that's about fifteen thousand in The U. S.

Speaker 3

Alone.

Speaker 10

Okay. Thank you so much for taking my questions. I really appreciate it.

Speaker 5

Thank you.

Speaker 6

Thank you. We'll take

Operator

our next question from David Bautz with Zacks Small Cap Research.

Speaker 2

Hey, good morning, everybody. So with I'm not sure if you're doing formal sales guidance for 2025, maybe you could just talk a little bit about goals sales goals for 2025, what a successful year is going to look like for Zolremity sales?

Speaker 3

Yes. I mean, as you highlighted, we're not giving forecast, but I think what we are striving for is continued to increase demand because that will show the sort of fruits of our labor in terms of increased education and awareness. I know Mark and the team are already seeing that nice steady pace, but if you'd like to provide any color, Mark, that would be great.

Speaker 9

Sure. As we were

Speaker 4

talking earlier, we're really trying to build a new market here. And so it starts with building awareness, building education around the disease, which is where we've really been investing our time, particularly with the physician community. We're pivoting now. We're actually leveraging the physicians that have already got experience with the product and experience treating WIM patients. We've initiated a speaker program, a peer to peer speaker program where those physicians can educate other physicians.

Speaker 4

So we're actually leveraging that experience. And we're pivoting now to focus on the patient community, building a community of interest around WIM, so that these patients who, as you heard earlier in the call, they don't really know what they don't know. They've accepted a new normal, so we are educating the patients now, encouraging them to reengage with their physicians. And when we do that, when we have an activated physician and an activated patient together in the room, we have a drug that works. It's already worked.

Speaker 4

It's demonstrated the efficacy in the Phase three trials. And so we quickly move through to a prescription. And on the other piece of good news there is that the payer the payers are seeing the value in this product and they're reimbursing this product quite quickly. So that's pretty much our mission this year.

Speaker 2

All right. Sounds good. And a quick follow-up. I understand if it's too early for this data, but is there any numbers on what percentage of the patients who have come on drug have refilled their prescription?

Speaker 4

Yes. I mean, without getting into specific numbers, we're pleased with the level of adherence and compliance we're seeing on the product. It's actually higher than you would expect to see with a daily oral medication. We put that down to the success of our patient support services and the strong partnership we have with our specialty pharmacy, Panther.

Speaker 2

Okay, great. And lastly on the FORWARD trial, you talked just a second ago about total patient numbers and that kind of fifty thousand number versus the fifteen thousand that you're kind of targeting with this trial. Do you see the change in your primary outcome for this trial may possibly affecting the label again if you're approved in chronic neutropenia?

Speaker 9

No, we don't believe that there is any impact at this point in time on the label. We also have it's not that this population has not been studied. We have some of them in our CRC and Phase II as well. So the entire package will represent the entire chronic neutropenia population.

Speaker 2

Okay, great. Thanks for taking the questions.

Speaker 6

Thank you. And at this

Operator

time, we have no further questions. I'd like to turn the call back over to management for any final or closing remarks.

Speaker 3

Well, thank you all for joining the call today. If you have any additional questions, feel free to reach out to management. And thanks and enjoy the rest of your day.

Operator

Thank you. Ladies and gentlemen, that does conclude today's conference. We appreciate your participation. Have a wonderful day.

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