X4 Pharmaceuticals, Inc. (XFOR) Earnings Call Transcript & Summary

Greetings, and welcome to the X4 Pharmaceuticals XOLREMDI FDA Approval Conference Call and Webcast. [Operator Instructions] As a reminder, this conference call is being recorded. It is now my pleasure to introduce your host, Dan Ferry from LifeSci Advisors.

Thank you, operator, and good morning, everyone. Thank you for joining today on this very exciting day for X4 as they discuss U.S. FDA approval of mavorixafor, being marketed in the U.S. as XOLREMDI, the first therapy approved in patients with WHIM syndrome. 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 year's Form 10-K, which was filed on March 21, 2024. Turning to today's agenda. Dr. Paula Ragan, X4's President and CEO, will begin with an introduction and overview of WHIM syndrome. Dr. Christophe Arbet-Engels, company's CMO, will then provide highlights of the label and a summary of the clinical data supporting the XOLREMDI approval. Chief Commercial Officer, Mark Baldry, will then detail for us the company's commercial launch strategy and execution plans. And then we'll conclude and open up the call to questions, where we'll be joined by Chief Financial Officer, Adam Mostafa; Chief Operating Officer, Mary DiBiase; Chief Scientific Officer, Art Taveras; as well as the company's new VP of Corporate and Patient Affairs, Jose Juves. Before I turn it over to Paula, I would like to take a moment to congratulate the company on this achievement and advancement for the WHIM community. Paula?

Thanks so much, Dan, and welcome, everyone. We are so very pleased to be here today sharing our great news. When we founded X4 in 2014, we had a vision to create a company focused on rare diseases with few to no treatment options, harnessing our expertise in immune system biology and specifically the CXCR4 receptor. We have licensed mavorixafor from Genzyme Sanofi. It was the first oral CXCR4 antagonist in development and we quickly set up about studying the drug across several indications where we thought mavorixafor could make the greatest impact. One of these indications was WHIM syndrome, a rare immunodeficiency. Mavorixafor was granted breakthrough therapy designation and rare pediatric disease designation in the U.S. for WHIM underscoring not only severity of the disease, but also the need for innovation in its treatment. We did hit some challenges along the way, particularly completing a global pivotal Phase III trial in immunocompromised patients during the COVID-19 global pandemic, but we met those challenges head on and succeeded through focus, grit and incredible support from the WHIM community, and we were thrilled when our U.S. new drug application was accepted for priority review last fall. Now nearly 10 years later, our initial vision has become a reality, and we are incredibly pleased that the FDA has granted approval to mavorixafor, branded XOLREMDI, a true innovation for those with WHIM syndrome. As we mentioned in the press release earlier this morning, this approval is a transformational milestone both for X4, now a fully integrated biotech company and more importantly, for the WHIM patient community for whom no targeted treatment options have existed until now. Before I provide a little more color on WHIM syndrome and the unmet needs of this community, I'd like to take a moment to thank everyone who has played a part in helping us realize this breakthrough for those living with this condition. Beginning with the patients, their families and the physicians and health care providers who trusted us and contributed to our trial, to the FDA that has been steadfast in their commitment to advance breakthrough medicines and rare disease treatments and who collaboratively work with us to deliver high-quality research and development, and of course, the entire X4 team, whose hard work and dedication has made today possible, and we are just getting started. So what is WHIM syndrome? For those of you who are new to the story, WHIM syndrome is a combined primary immunodeficiency caused by genetic variations to the CXCR4 receptor, a key regulator of the mobilization of white blood cells, which include neutrophils and lymphocytes from the bone marrow into the peripheral blood and surrounding organs to perform surveillance for infectious pathogens. Patients with WHIM syndrome present with heterogeneous symptoms. Almost all have neutropenia or low blood levels of neutrophils, almost all have recurrent infections, many have lymphopenia or low blood levels of lymphocytes, which include B and T cells and a majority have hypogammaglobulinemia or lower levels of antibodies. Interestingly, fewer than 1 in 4 patients with WHIM present all the manifestations in the WHIM acronym, creating challenges for diagnosis. WHIM is a serious congenital disease, people are born with the intrinsic defect in CXCR4 and therefore this root cause has a lifelong impact on their health and infection risk. It typically presents in childhood, but due to the variety of symptoms and lack of awareness of the disease, it often goes underdiagnosed for years. And over time, patients experiencing repeated infections can have significant morbidities such as impaired hearing and loss of lung function and some experience a higher risk of HPV-associated cancer. WHIM syndrome is an ultra-rare disease. Our market research and early experience in the field indicate there to be at least 1,000 WHIM patients in the U.S. But now with a targeted therapy available, we expect that increasing physician awareness will bring more focus to the WHIM community, enabling earlier recognition and diagnosis, potentially expanding the numbers of those diagnosed with WHIM over time. As I mentioned, WHIM syndrome is caused by dysfunction of the CXCR4 pathway. This is due to genetic variations in the CXCR4 gene. Normally, the CXCR4 pathway regulates the migration of white blood cells from the bone marrow to the peripheral blood. In WHIM syndrome, however, dysfunction of the CXCR4 receptor can result in impaired mobilization of white blood cells and increasing patient susceptibility to severe, prolonged and recurrent bacterial and viral infections. XOLREMDI or mavorixafor is an orally active, selective CXCR4 antagonist and works by inhibiting the binding of the CXCL12 ligand to the receptor. As a result, more white blood cells are mobilized from the bone marrow into the peripheral circulation. If you think about it, during the COVID-19 pandemic, we all gained insight into what it's like to live with a dysregulated immune system. WHIM patients wake up every day knowing they're at risk of experiencing a life-threatening infection. So a big part of what's most exciting about this approval is that for the first time, WHIM patients and their physicians have a treatment that targets the underlying cause of the disease. I'll now turn it over to Christophe to review the XOLREMDI label and the clinical data that supported the efficacy and safety of our now approved drug. Christophe?

Thank you, Paula. As Paula mentioned, the approval of XOLREMDI is a significant breakthrough for people living with WHIM syndrome and their families for whom there has been little innovation. Until now, this patient population has only been treated for their symptoms with nothing to treat the underlying cause of disease. The treatments most commonly used include G-CSF, which is a growth factor that helps the bone marrow produce more neutrophil, one specific type of white blood cell. It's an injectable therapy that has been associated with clinically significant side effects. G-CSF is approved in the U.S. for severe chronic neutropenia. IVIG is intravenous immunoglobulin, a product made up of donated human antibody and is used to treat immune disorder infections and certain immune diseases. WHIM patients can receive IVIG to address the risk of severe infection and their complication. And it's typically administered by a health care provider over a period of up to 4 hours. Antibiotics and antivirals are used to treat infection, and we've heard from patients that they are frequently and consistently on prophylactic antibiotics. However, long-term use of antibiotics can have associated risks, including the development of antimicrobial resistance or GI tolerability issue. XOLREMDI is now the first therapy specifically approved in patients with WHIM syndrome. Here, we provide highlights of the XOLREMDI label. As you can see, it is now approved for use in patients 12 years and older with WHIM syndrome to increase the number of circulating mature neutrophils and lymphocytes. As noted here, the final dosing recommended by the FDA was 400-milligram for those weighing more than 50-kilogram and 300-milligram for those weighing less than or equal to 50 kilograms. You may recall that the Phase III trial included the 200-milligram dose for those weighing 50 kilograms or less. After productive discussions with the FDA, the agency and company aligned on the 300-milligram dose to optimize the benefit for this patient. This approval is supported by the data from our successful pivotal Phase III trial, the largest clinical trial to date in WHIM syndrome. As you know, this was a global randomized double-blind, placebo-controlled Phase III trial conducted in 31 patients with WHIM syndrome. To be eligible, participants had to be 12 years and older, diagnosed with WHIM and their ANC or absolute neutrophil count had to be lower than or equal to 400 cells per microliter, which is severely neutropenic. Participants were treated with oral, once-daily XOLREMDI or with placebo for 52 weeks. Assessment measurements were taken at baseline and then at 13 26, 39 and 52 weeks. The primary endpoint was improvement in ANC as measured by a mean time above threshold of 500 cells per microliter, the measure of severe neutropenia. Secondary endpoints included both improvements in ALC or absolute lymphocyte count as measured by the mean time above threshold of 1,000 cells per microliter, the definition of severe neutropenia, as well as the composite endpoint of total infection score, the calculation of which includes the rate and severity of infection throughout the trial and total wart change score. As you can see here, the trial met its primary ANC endpoint here on the left, with a p-value of 0.0001 versus placebo as well as the ANC secondary endpoint with the same p-value versus placebo demonstrating that XOLREMDI increases both neutrophil and lymphocyte in patients with WHIM syndrome. The increase observed in immunologic parameter is extremely important for immunodeficient patient with the elevation of this count above the level that defines severe disease known to help reduce the risk of infection. On this next slide, we detailed the improvement in infection assessment in those treated with XOLREMDI versus placebo as published in previous scientific posters and presentations. On the left, we show data that demonstrate that patients treated with XOLREMDI in the Phase III trial experienced a 60% drop in the annualized infection rate versus placebo. The published clinical data also show that the duration of this infection ended up being about 5 weeks shorter in the XOLREMDI-treated patient than the infection experience in placebo-treated patients. In addition, the results show that fewer patients treated with XOLREMDI experienced severe infection with just 1 of the 14 patients on XOLREMDI experienced a Grade 3 or higher infection versus 5 of the 17 patients on placebo. Note that the data on the number and severity of these infections supported the calculation of the 40% lower total infection score, for XOLREMDI versus placebo and are reflected in the final product label. There was no difference in wart change score between XOLREMDI and placebo arm during the 52-week trial. Together, these data on the last 2 slides suggest that a significant increase in ANC/ALC can result in a meaningful reduction in infection rate and severity. Throughout the Phase III clinical trial, XOLREMDI was generally well tolerated. As seen in the label, the adverse reaction in greater than or equal to 10% of patients with WHIM syndrome receiving XOLREMDI and more frequently reported than those on placebo are listed in this table. As recently published in Blood, the Journal of the American Society of Hematology, there were no discontinuations during the trial due to treatment-emergent adverse events and none were deemed to be treatment-related. Throughout the trial, no serial treatment-emergent events were observed. And as published at the recent ASCO meeting, our Phase III clinical trial showed that safety and efficacy results were similar in the predefined analysis of the adolescent subgroup versus the full study population. Before I pass it over to Mark, I would like to take a moment and emphasize how much the XOLREMDI approval means to WHIM patients and their caregivers. As one of our academic experts expressed during a recent Scientific and Clinical Advisory Board, it is very exciting to witness this breakthrough therapy being approved after such a long time. We are, therefore, very proud to launch XOLREMDI and provide a safe and efficacious therapy that target the underlying mechanism of WHIM syndrome to help appropriate patients in this very underserved community. I'll now turn it over to Mark Baldry to discuss our commercialization plans for XOLREMDI, Mark?

Thanks so much, Christophe, and thank you all for joining us today. As you've been hearing on this call, there is tremendous excitement across X4 and the WHIM community because our XOLREMDI launch execution begins today. Our go-to-market strategy is built on 3 imperatives: first, educating the market on WHIM syndrome. Through our already successful What If It's WHIM? campaign, we are continuing to educate on the heterogeneity of WHIM and to drive the urgency to diagnose using a variety of patient and physician-targeted resources including our ongoing sponsored genetic testing program path forward. Having already hired and trained our field team, we have been engaging with key physicians over the past months, meeting them in their offices and at key medical conferences, sharing our unbranded disease awareness campaign. It is well established that earlier and definitive diagnosis leads to better patient outcome, and that is ultimately our goal. Second, establishing XOLREMDI as the standard of care for WHIM syndrome with key hematologists and immunologists. Based on our interactions to date with the prescribing community, we know that the mechanism of action of XOLREMDI resonates because it targets the underlying cause of the disease and helps increase circulating levels of neutrophils and lymphocytes. Our team is trained and prepared to engage with physicians, payers and patients and to extend the voice of X4 across the country. And in fact, the team will be on the ground at the upcoming Annual Meeting of the Clinical Immunology Society, or CIS, staffing both our launch and medical affairs booth. Many of our key target immunologists attend this meeting, and we are eager and ready to introduce them to XOLREMDI. In addition, the xolremdi.com website is now live, and we are finalizing our branded promotional materials to be rolled out at our upcoming launch meeting. Our third goal is to enable broad access to drug through our X4Connect program, which aims to address access barriers and provide a full suite of patient support services. We have activated our patient services hub with phone line that are open, and we are ready to assist eligible WHIM patients. I'll be providing more details on the X4Connect program in just a few minutes. As I mentioned, our field team has already been onboarded, is fully trained and has been deployed across the country. The team of about 2 dozen people consists of rare disease specialists who are our sales reps, MSLs, clinical nurse educators and field reimbursement managers, recruited from well-known rare and ultra-rare disease organization, they have between them more than 250 years of experience and demonstrated success in commercial launches. They have significant expertise in the rare disease space, targeting immunologists and hematologists, supporting diagnosis and understanding the patient journey. Throughout their careers, they have fostered excellent relationships with physicians, key thought leaders and with patient advocacy organizations. But most importantly, they share in our patient-centric mission to successfully bring innovation to those most in need and to listen to and meet the customers where they are to maximize engagement. In preparing our go-to-market model for WHIM syndrome, we have been thoughtful and focused in our strategy design. Guided by our market research, we have mapped out and prioritized our initial top immunologist and hematologist targets, and our team is already executing their planned outreach to these key customers. We have also been and will continue to interact with top KOLs in the field to gain a better understanding their needs and to support their educational efforts. And we will continue to leverage our collaborations with key patient advocacy groups including the Jeffrey Modell Foundation and the Immune Deficiency Foundation to further identify target physicians with experience and interest in WHIM syndrome. We know from speaking with people living with WHIM, that there is a significant unmet need in this market and that patients face a high burden of disease. Our market research with physicians confirms this. and they have clearly communicated to us their need for targeted therapy specifically indicated for their WHIM syndrome patients. Our research has shown that 92% of physicians we spoke with believe that WHIM patients are vulnerable, and at risk of serious complications. And that 89% believe there is a high unmet need for a targeted and effective therapy for WHIM syndrome. Our research also showed that 76% of physicians are dissatisfied with the current options for treating the symptoms of WHIM. And when presented with an unbranded product profile, physicians expressed high interest in prescribing a product like XOLREMDI for the treatment of their WHIM syndrome patients. Interest was high across all specialties we interviewed with an average 9 out of 10 rating. Physicians found that the data on infection reduction, the targeted mechanism of action and the oral formulation were the most compelling reasons to prescribe. Just as important as driving prescriptions for WHIM syndrome is helping those prescriptions get filled in a timely manner at lowering barriers to access. We want all XOLREMDI patients to be able to start on therapy quickly and stay on therapy for as long as the medication is proving safe and effective in treating their disease. In order to facilitate this, we have created X4Connect, a personalized patient program with a suite of services designed to provide solutions for eligible patients throughout their treatment journey. X4Connect has been specifically designed to meet the needs of WHIM syndrome patients from prescription to fulfillment, to adherence. We have a single phone number and an easy-to-use enrollment form, and we have dedicated care coordinators, nurse educators and specialty pharmacists who will work one-on-one with patients and their families help address barriers to access and to engage with both providers and payers in support of fulfilling prescriptions. We are also implementing a number of financial assistance programs for eligible patients. These include our Quick Start program to provide a temporary supply of XOLREMDI, should there be a delay in insurance coverage, our Copay Assistance program, which assists qualified patients with out-of-pocket costs up to an annual limit, our Bridge Program, which can also provide a temporary supply of XOLREMDI should a patient's insurance coverage change, and our Patient-Assistance program that helps under and uninsured patients gain access to XOLREMDI while we continue to work with them to obtain insurance coverage. In addition, we have partnered with PANTHERx Rare to support and provide many of these services. PANTHERx is well known as a top-rated specialty pharmacy in the U.S. focused on distributing treatment and supporting patients with rare and ultra-rare condition. We believe that by streamlining all prescriptions to PANTHERx, we can provide a high-touch patient experience that will minimize payer delays, allowing patients to focus on their health and well-being. Prior to launch, we have focused heavily on understanding the value that XOLREMDI would bring to the patient and health care communities. The key drivers of value supporting the use and pricing of XOLREMDI include the fact that it is a targeted breakthrough treatment for an ultra-rare population, and it is now the first FDA-approved therapy indicated in patients with WHIM syndrome. Another key value driver is that XOLREMDI has demonstrated efficacy and safety in the largest ever Phase III clinical trial in this patient population and has the potential to address a high burden of disease by improving relevant aspects of patients' immune response. For all these reasons, we believe that this therapy has the potential to provide significant value to both patients and payers, and we have priced it accordingly. As you can see here, the price per patient on an annual basis will be about $496,000 for patients greater than 50 kilograms and about $372,000 for patients less than or equal to 50 kilograms. Based on our clinical trial experience, we expect the initial population split among these weight groups to be approximately 90% at the 400-milligram dose and 10% at the 300-milligram dose. Note that these numbers are wholesale acquisition costs and do assume full patient compliance. We have already been engaging with payers to educate them on the burden of WHIM syndrome and the need to treat the underlying cause of the disease. And now that we have the first FDA-approved treatment for WHIM, we will be sharing the value proposition of XOLREMDI to drive coverage and inclusion on formularies and plans. And so through our efforts to date, we have learned a lot, interacting with physicians, KOLs, patient advocacy groups, and of course with patients. We have built an organization and a commercial launch strategy that we believe aligns to support the specific needs of the WHIM community. As we've discussed, we've been working hard to support disease awareness and better patient diagnosis. We've launched our field team and targeted programs to establish XOLREMDI as the standard of care and to drive adoption and uptake. And we have activated the X4Connect patient support program and we'll work closely with payers to provide access for patients and ultimately deliver on the promise of XOLREMDI. With that, I'll now pass it back to Paula to conclude.

With the immediate launch of XOLREMDI, we will now be laying a strong foundation throughout 2024 deploying our experienced rare disease field force, engaging with payers to communicate the XOLREMDI value proposition and most importantly, enabling patient access to treatment as quickly as possible. Importantly, concurrent with this approval, we've received a priority review voucher, which we intend to monetize. With these nondilutive proceeds plus our existing funds, we believe we are well positioned to not only deliver on the commercial opportunity in WHIM syndrome in the U.S., but also to advance our global regulatory and commercial plans in WHIM and further our study of mavorixafor in the treatment of chronic neutropenia. To conclude, as we've heard from patients like Courtney shown here and many others, living with chronic neutropenia, lymphopenia and frequent infections is challenging and the road to a WHIM diagnosis is a long one. It's our hope that having a drug finally approved specifically for WHIM will not only raise the visibility of the disease, but will enable earlier diagnosis, potentially reducing the long-term burdens faced by these patients and their families and giving them hope for a brighter future. Thank you again to all the patients and their caregivers, the investigators and medical providers and to our extraordinary employees who have helped make this breakthrough therapy a reality. It is truly a historic and transformative moment for us all. With that, why don't we open it up to questions. Operator?

At this time, we'll be conducting a question-and-answer session. [Operator Instructions] Our first question comes from the line of Kristen Kluska with Cantor Fitzgerald.

Congrats on this very remarkable day in company's history, and we should be very proud of all the work that it took the company to get these patients a therapy, so well done. So I wanted to ask who you think are going to be the early adopters of this therapy, both from a prescriber and patient perspective. And then we constantly hear there being a shortage of things like IVIG. So what are you seeing broadly in the space that some of these patients are willing to do more genetic testing to find out what specific PI they have in light of now your drug approval and then other approvals for other types of PI?

And maybe I'll start by just describing a little bit more about the physicians that we're focused on as we go out into the market and begin engaging with them. We've done some analysis of the claims data and identified the 3,500 physicians or prescribers that we see in the data as having WHIM patients in their practice. And so with that, we're able to kind of score them with a priority score and have a top tier of those around 600 physicians that we'll be prioritizing, and these are physicians that, again, we can see in the data are likely to have a WHIM patient. These are physicians that we've been engaging with and have had discussions with. And these are the ones that we're going to be going to on Day 1. The second question, it was about IVIG.

And increasing possible genetic testing.

Well, the good news is if you look at our label, we've been actually indicated -- the product is now indicated in patients with WHIM syndrome without the need for a genetic test. This is a clinical diagnosis of WHIM syndrome, and that's important. And so we'll be using our -- offering our Path Forward program as an option for physicians to do genetic testing to confirm the diagnosis. And based on our discussion so far with physicians, the majority of patients that have been diagnosed with WHIM syndrome already have a genetic confirmation of that.

Yes, I meant it more in the sense of I think for a long time, a lot of these patients were just being all identified as having a PI. But as a result, we're seeing there's not enough IVIG for everybody. So now that some of these specific forms of PIs now have approvals for that specific indication, whether we're seeing a more willingness to get that specific diagnosis to make sure that everybody has a treatment option.

Yes. I mean, I think in a space like this where you had no treatment for the underlying disease, physicians have really just been treating the symptoms that they can see, for example, using IVIG to try and treat infections. But now we actually have a treatment that's going to target the underlying cause of WHIM, and we believe this will lead to more accurate diagnosis and better patient outcomes.

Our next question comes from the line of Stephen Willey with Stifel.

Congratulations here as well. I know it's been a long time in the making. Just a quick question, I guess, on reimbursement and patient onboarding. I guess I'm just kind of curious as to kind of what your current thoughts or estimates are with respect to the duration of this process in terms of once patient identification has been has been made what the time line would be for then subsequently getting that patient onto drug with full reimbursement and access.

Yes, as I mentioned, the website is up and running, and our enrollment form is ready for physicians to complete and for patients to consent to our services. And our partner, PANTHER is ready to receive these enrollment forms. So the process can begin today. But to your point, we know that having observed some of the more recent rare disease launches, that payers have their standard playbook, and we don't expect to be treated any differently as a new drug to market. So the good news is we have a suite of patient services that we'll be offering to support patients while we navigate the reimbursement landscape. It will probably take payers up to 6 months to a year before they'll be covering XOLREMDI as part of formularies and plans, but in that time, we'll be working with them to go through prior authorization and the exceptions process, and that usually takes anywhere from 1 to 2 months. So that's our current expectation. And again, this is why 2024 for us is really a year of laying that foundation, engaging with payers and really educating them on the burden of WHIM syndrome and how vulnerable these patients are and sharing with them the value that XOLREMDI brings, being the first FDA-approved treatment for the actual disease as well as with the clinical and safety profile that comes with the drug. So we'll be supporting patients while we engage with payers and secure reimbursement.

Okay. That's helpful. And then maybe just a quick financial question as well. Can you just remind us if there's any milestones that are owed to Genzyme as a result of the approval? And then is there a proportion of a potential PRB transaction, which would also be owed to Genzyme?

So we did recently disclose our full schedule of milestone payments and royalties in the 10-K. So that does include a $7 million milestone payment that we will now make linked to receiving FDA approval, and as well, there's a 6% royalty on sales up to $150 million to Sanofi Genzyme as well. We do intend to sell the PRV shortly. We'll provide an update there as soon as we can. There's nothing owed to Sanofi Genzyme related to those potential proceeds.

Our next question comes from the line of RK with H.C. Wainwright.

Congratulations, Paula and Adam. It's great news for the patients and certainly a lot of work went in, and it's a great feeling, I'm sure. Regarding the launch itself, a couple of quick questions. I know in the presentation, you're stating that you're going to target initially, the 3,500 immunologists and hematologists and 20 KOLs. How soon would -- I'm just trying to see, is there a bolus of patients at any one of these KOL centers where you can get started right away? That's question number one. And question number 2 is since some of these patients have been on other therapies, is there any weaning period that they need to undergo before they get off other things, other drugs, whatever they may be for them to get on to XOLREMDI? And how -- I mean, how easy or difficult is that switch?

RK, this is Mark. With regard to your first question, I'll just reiterate, there is no bolus of patients. This is an ultrarare population that has had no treatment to date. And so we're excited to be able to bring XOLREMDI out to the market and begin engaging with physicians to help them recognize patients in their practice and to drive earlier diagnosis. And then we'll be also doing that same thing with payers in terms of educating them on the burden of the disease and sharing with them the value of XOLREMDI and we'll be reaching out to the patient community as well to encourage them to go back and reengage with their physicians. They have a new treatment option to discuss with their physicians. So that really is our work in 2024, and this we believe lay the foundation for a successful 2025 and beyond. Maybe I'll hand over to Christophe just to talk a little bit about transitioning patients from...

Yes. So to transfer patients, it's clearly between the physician and the patients to decide how to best transition the patients on a case-by-case basis, given each patient's profile. There is nothing in our safety database that suggests that there is a specific time frame or a weaning aspect that should be considered. So we'll leave it up to the physicians to decide how to best do that.

[Operator Instructions] Our next question comes from the line of Kalpit Patel with B.Riley Securities.

Congrats on the approval today. Maybe one on the commercial opportunity here. I think in the past, you mentioned there was a global patient registry that was in the works. How many patients have been identified in the U.S. so far through that registry? And then as a follow-up, how are you viewing the consensus estimates of roughly $30 million for 2024 and $16 million for 2025?

Sure. Maybe I'll start just by speaking to the WHIM population here in the U.S. So we've used a variety of different methodologies and analysis to really triage around an estimate of about 1,000 patients here in the U.S. with WHIM syndrome. So that's our estimate using those databases. And maybe I'll turn it over to Adam to talk about...

At this time, we're not providing sales guidance. But as Mark mentioned, we do expect this to be a foundational year for us to set the stage for sales down the road. And as we go, we'll find the right time in place to provide more clarity and thoughts on what sales levels might be in the future.

Okay. And any additional, I guess, color on the label, specifically the warnings and precaution section? It looks like there's embryo-fetal toxicity and QTc prolongation listed there. Were those expected based on clinical trial data? Or was that primarily related to the preclinical data?

So this is Christophe. I'm going to answer this question. The safety profile, the benefit-risk is clearly positive to support the indication in all WHIM patients, 12-year and older. Our safety is showing that the drug is well tolerated. We also have observed no severe adverse events associated with XOLREMDI, no discontinuation due to adverse events. And the QTc aspect is for consideration when drugs that have a risk of QTc prolongation are given concomitantly. So we are happy with the label and really excited to be able to deliver XOLREMDI to the WHIM patients.

And one last question. You have a nice survey data in there. Was that based on primarily U.S.-based prescribers, that survey information you have? Or did that include ex U.S. doctors as well?

No, that was just U.S. physicians. Today, we're focused on the FDA launch, and that research aligns with our focus today.

Our next question comes from the line of David Bautz with Zacks Small-Cap Research.

I will also offer my congrats on the approval this morning. Just one quick one about insurance coverage. Also, is there any sense -- I know this is an orphan indication, but is there any sense about what percentage of patients are covered through insurance? And then also, if you could talk about getting coverage through Medicaid and if that's going to be something that's going to be on your priority list also.

Yes, sure. So I could start by sharing with you just some of the results of our early engagement with payers and sharing with them the value proposition of XOLREMDI and WHIM, we expect most insurers will cover XOLREMDI given the unmet need and the breakthrough innovation that XOLREMDI delivers and the ultra-rare nature of the WHIM syndrome population. So this is really, as I said, the work that lies ahead for us. We will be engaging with payers now with our field team and educating them on the disease and on product. As each patient's insurance situation is unique. We know that not all patients will have full insurance coverage. And so payers typically take some time to review these new therapies and XOLREMDI will face those standard coverage determinations just like any other newly approved drug. But we anticipate that most payers will cover XOLREMDI through a standard prior auth or exceptions process. And in the meantime, we'll be offering X4Connect, a comprehensive set of support services to assist patients who may face any delays in coverage determination.

Ladies and gentlemen, that concludes our question-and-answer session. I'll turn the floor back to Ms. Ragan for any final comments.

Thank you again, operator, and thanks to all of you for joining us today. Note, we will be hosting our First Quarter 2024 Earnings Call on Tuesday, May 7. If you have any further questions, we'd be happy to take them at this time. And thank you, and have a great day.

Thank you. This concludes today's conference call. You may disconnect your lines at this time. Thank you for your participation.