X4 Pharmaceuticals, Inc. (NASDAQ:XFOR) Q3 2023 Earnings Call Transcript

X4 Pharmaceuticals, Inc. (NASDAQ:XFOR) Q3 2023 Earnings Call Transcript November 9, 2023

X4 Pharmaceuticals, Inc. beats earnings expectations. Reported EPS is $-0.01, expectations were $-0.15.

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

Dan Ferry: Thank you, operator, and good morning, everyone. Presenting on today’s call will be X4’s Chief Executive Officer, Dr. Paula Ragan; Chief Commercial Officer, Mark Baldry; and Chief Medical Officer, Dr. Christophe Arbet-Engels. Following the prepared remarks by each, we will open up the call to your questions and will be joined by Chief Financial Officer, Adam Mostafa; Chief Scientific Officer, Art Taveras; and Chief Operating Officer, Mary DiBiase. As a reminder, on today’s call, the company will be making forward-looking statements regarding regulatory and product development plans as well as research activities. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted.

Description of these risks can be found in X4’s most recent filings with the SEC, including this quarter’s Form 10-Q, which is expected to be filed after market close today. I’d now like to turn the call over X4’s President and CEO, Dr. Paula Ragan. Paula?

Paula Ragan: Thanks, Dan. Good morning everyone, and thank you for joining us on the call today. To start, I’ll be reviewing our third quarter events and recent highlights, the first two of which will be the primary focus of our discussion today. As you can see here, it’s again been a very busy and productive period at X4, which culminated in the great news last week that our NDA seeking approval of our lead drug candidate mavorixafor, for the treatment of WHIM syndrome, was accepted by the FDA for Priority Review. The FDA has set a PDUFA, or action date, of April 30, 2024, which sets us up for a potential second quarter 2024 launch in the U.S. if approved. In anticipation of this, we have continued to build out our fit-for-purpose commercial organization.

Mark Baldry, our Chief Commercial Officer, will run through some of the details of our launch readiness and pre-launch activities to date, all of which aim to further the understanding of WHIM syndrome and educate both patients and physicians on the importance and benefits of early diagnosis. We do want to remind everyone here that due to mavorixafor’s rare pediatric disease designation for WHIM syndrome in the U.S., X4 is eligible to receive a Priority Review Voucher or PRV if mavorixafor is approved, that we can use to either obtain priority review for a subsequent application or to sell to another drug sponsor. Turning now to our mavorixafor chronic neutropenia program, we have continued to advance our Phase 2 study and have now enrolled more than 15 participants in the trial.

Importantly, key learnings from this ongoing study, along with the data from previous trials and input from the FDA have enabled us to finalize the design of what we believe will be the global pivotal Phase 3 clinical trial that will be used as the basis for seeking approval of mavorixafor in certain chronic neutropenic disorders. As discussed on our last quarterly call, Dr. Christophe Arbet-Engels has joined X4 as our new Chief Medical Officer. We thought it would be a good opportunity to hear from him today as we approach some key milestones in our development of mavorixafor in chronic neutropenia, he will be providing an update on this program later in the call. During the quarter, we also strengthened our Board of Directors with the addition of Mr. Keith Woods.

Keith brings significant global commercial strategy and operations experience, most recently at argenx where as Chief Operating Officer he helped build a sustainable enterprise and successfully launch a rare disease product globally. His meaningful experience adds to our board as X4 aims to transition to a global R&D and commercial enterprise as well. As also discussed on our last quarterly call, we completed an expanded loan facility with Hercules Capital, in addition to the possible PRV next year. This facility provides us with financial flexibility and importantly, non-dilutive financing options. Lastly, we believe our current cash and equivalents balance of just over $140 million at the end of the third quarter is sufficient to fund our operations into 2025.

And note that this does not include the debt options or the potential proceeds of the sale of the PRV if NDA approval is obtained. Before I turn it over to Mark, I’d like to present a quick review of WHIM syndrome as a reminder to those not familiar with our lead indication. WHIM syndrome is a rare primary immunodeficiency caused by the over signaling of the CXCL12, CXCR4 pathway, which in many cases results from genetic variance in the CXCR4 receptor gene. This pathway is a key regulator of normal trafficking of white blood cells, which include neutrophils, lymphocytes, and monocytes. In a WHIM syndrome, white blood cells become trapped in the bone marrow, which leads to chronic neutropenia and lymphopenia. These immunodeficiencies lead to a number of clinical manifestations, most notably an increased risk of infection in the lungs, skin and other key organs, and an increase in the incidence of HPV related cancers.

Greatly affecting the quality and length of life of the estimated 1,000 people diagnosed with WHIM in the U.S. With earlier diagnosis, we believe the damage from these infections could be mitigated. As you recall, we were able to show in our successful Phase 3 trial in WHIM syndrome statistically significant increases in both neutrophil and lymphocyte counts, as well as clinically significant reductions in the rate, frequency and severity of infections versus placebo. If approved next spring mavorixafor would be the first therapy available for those individuals diagnosed with WHIM syndrome and the only disease modifying treatment. I’m now going to turn it over to Mark to give you some of our insights and details on our progress and plans for commercializing mavorixafor for WHIM syndrome.

Mark?

Mark Baldry: Thanks, Paula, and thanks to all of you on the call today. We thought it would be helpful to start by highlighting some of the ways that we’ve been engaging with the WHIM community, developing an understanding of the market landscape and establishing a foundation for a successful introduction of mavorixafor to physicians, patients and payers. As Paula mentioned, there are currently no approved therapies for WHIM syndrome. Physicians are limited to managing their patients’ symptoms using repurposed symptomatic treatments. For example, immunoglobulin replacement therapy, which is injected or infused into the body, and or prophylactic antibiotics, all of which carry their own challenges and do not address the underlying cause of the disease.

Diagnosing WHIM syndrome is also a challenge given that the clinical presentation of the disease is so variable, and in fact, only about 20% of patients present with all four of the hallmark symptoms and manifestations of WHIM. Some physicians use genetic testing to help identify WHIM or confirm its diagnosis, while other physicians rely more on the clinical presentation of the patient. Due to the rarity of the disease and lack of investment in treatment innovation, there is limited awareness of WHIM syndrome in the general physician community, and the patient journey often includes visits to multiple types of doctors as they try to uncover what might be causing the symptoms. Given this lack of historical attention and investment, we recognize the significant opportunity to not only address the unmet needs of currently diagnosed WHIM patients, but also to use our resources to identify additional patients in what we believe to be a larger population of undiagnosed people living with WHIM syndrome who could potentially benefit from mavorixafor treatment.

The next slide provides an overview of our efforts to date, which have focused on partnering with the WHIM community, driving earlier diagnosis of WHIM, ensuring broad access for eligible patients and delivering on the promise of mavorixafor. I’ll highlight a few of our key successes here. First, with regard to partnering with the WHIM community, we’ve successfully identified KOLs with expertise and treatment experience in WHIM. We’ve assembled an advisory panel, several of whom you’ve met during our previous data presentation events, and we’ve worked with numerous experts to author many of our publications. We’ve also developed and continue to faster collaborations with immunodeficiency patient advocacy groups and disease focused professional societies in the U.S. and abroad.

Through all of these partnerships and collaborations, we believe X4 is playing a significant role in uniting the WHIM community around a common mission to advance the understanding and management of this rare disease. Next to drive earlier diagnosis of WHIM, we’ve initiated a number of programs and websites to increase disease awareness, including our most recently launched what if its WHIM campaign. As you can see here, through the campaign we’re aiming to educate on the variable clinical presentation of WHIM syndrome, driving home the importance and urgency of early diagnosis, which can lead to better patient outcomes, and providing easy access to additional resources, including direct contact with our field diagnostic team, as well as to free genetic testing.

We’ve also been analyzing medical databases and have completed a significant physician mapping exercise to build our prioritized list of target immunologists and hematologists. We’ve strengthened our presence at key medical conferences, hosting peer-to-peer disease education symposia, and launching our new Congress exhibition booth, which pulls through our what if it’s WHIM campaign. All of which has significantly increased the visibility of X4 and WHIM syndrome, and has connected us directly with a broader group of physicians and patients. In fact, our patient finding efforts have been accelerating nicely and continue to give us confidence in our prevalence estimate of at least 1,000 patients living with WHIM syndrome in the U.S. To ensure that eligible patients have access to therapy after approval, we’ve engaged with payers and are developing materials to communicate the compelling value proposition of mavorixafor.

Our published clinical data from the Phase 3/4 WHIM trial supports our value messaging by providing evidence of improved neutrophil and lymphocyte counts and, importantly, reductions in the rate, severity and duration of infections in trial participants treated with mavorixafor. We will be leveraging these points as we begin to discuss pricing and reimbursement going forward. And finally, we’ve been building an organization that’s truly fit-for-purpose. We’ve made key leadership hires across medical and commercial functions, all of whom have significant rare disease and launch experience, and supports the ramp up of our go-to-market efforts as we head towards an anticipated second quarter 2024 launch in the U.S. I would like to conclude by highlighting the investment synergies here between the WHIM syndrome and chronic neutropenia commercial opportunities.

We believe that if we’re successful in developing mavorixafor for the treatment of chronic neutropenia, we expect to leverage much of the work and many of the relationships developed through commercializing in WHIM with a future potential commercial launch in CN. And now I’ll hand it back to Paula to discuss more about our ongoing development program in CN. Paula?

Paula Ragan: Thanks so much, Mark. Really great summary of all of our efforts to increase disease awareness, enable earlier diagnosis and support patients in need as we head towards our anticipated launch in WHIM. Let’s now change gears a bit and focus on our chronic neutropenia program. We thought it would be helpful here as well to remind everyone what would make the biggest difference to people living with chronic neutropenia and their physicians. That is, where are the greatest needs in those that we serve. If you recall, a little over a year ago, we held an investor event focused on CN and our initial Phase 1b trial results. At that time, we shared that 100% of the 25 patients enrolled achieved robust ANC responses from a single dose of mavorixafor, regardless of background therapy.

Additionally, from our interviews, we gathered valuable insights from patients and physicians where they highlighted their needs as related to the product profile of a potential new treatment for CN. Their preferred attributes included an oral formulation that is safe, well tolerated, and easy to administer or take, and one that durably increases ANCs over time. Mavorixafor has already demonstrated these attributes across a number of populations. Additionally, patients [ph] and clinicians criteria for a new treatment includes a therapy that decreases infection burden and also decreases the toxicities and challenges associated with taking lifelong GCSF. Our successful WHIM Phase 3 trial, where infection rate, severity and duration were meaningfully reduced, provides evidence that this benefit of mavorixafor could also translate into helping the CN community.

Most importantly, our CN Phase 2 study is beginning to build direct evidence in chronic neutropenic patients across the key metrics of durable ANC increases safety and reduction of GCSF use. I’ll now pass it over to Christophe Arbet-Engels, our Chief Medical Officer, to share an update on the status of the promising CN program. Christophe?

Christophe Arbet-Engels: Thanks so much, Paula. As you know, following the successful completion of our Phase 1b clinical trial, evaluating the ability of a single dose of mavorixafor to raise absolute neutrophil counts, or ANC, in CN patients. We launched a Phase 2 trial to evaluate chronic use of mavorixafor in the same patient population, with or without concurrent GCSF treatment. The study is designed to assess mavorixafor ability to durably raise ANC within the first few months and to see whether patients could possibly reduce or eliminate their GCSF dose longer term. Importantly, we also assess for safety of mavorixafor in combination with GCSF. We have seen a nice acceleration in trial enrollment and now have more than 15 participants receiving treatment in the trial.

On our last quarterly conference call, the team presented initial data from the first three participants in the study, all of whom were on GCSF treatment at study initiation, but had identified unmet needs. All achieved large, durable increases in ANC and the two neutropenic patients achieved normal ANC levels despite having low ANC while on GCSF therapy as they entered the study. Notably, the ANC increase scene would meet the responder criteria that we’ve established for the Phase 3 study design, which I will go into in more detail shortly. Importantly, the robust ANC response in the early months of the trial enabled the successful dose decrease or complete withdrawal of the GCSF in some patients. Mavorixafor has also demonstrated an acceptable safety profile in combination with GCSF.

The full data set on these three subjects will be presented in a poster at the Annual ASH Meeting in December. In addition, we expect to be able to present a comprehensive update from at least 15 of the participants in the Phase 2 trial during the first half of 2024. Most importantly, we are pleased to rapidly move forward towards our pivotal Phase 3 trial in CN given all the positive data to date supporting this population. The success we’ve seen thus far across the CN study, as well as the positive impact that mavorixafor has demonstrated in WHIM patients, has inspired us to advance as quickly as we can by delivering an innovative oral therapy. With our current insight and input from the FDA, I’ll now provide a little more detail on our global pivotal Phase 3 clinical trial, which we remain on track to initiate in the first half of 2024.

We’ve now completed multiple interactions with the FDA and have a line on the current study design. The trial will be a global, double-blind, randomized and placebo control trial in participants with or without concurrent GCSF treatment. The dosing of mavorixafor will be the same as our Phase 3 for WHIM clinical trial. Participants on GCSF at baseline will remain on a stable dosing regimen during the 52-week study duration and adjustments in GCSF dosing will be allowed only for safety reasons. Patients included in the study are required to have confirmed idiopathic autoimmune or congenital chronic neutropenia with an ANC less than 1,500 cells per microliter and to have demonstrated a history of infection requiring medical intervention in the last 12 months prior to trial entry.

The trial is currently designed with a two component primary endpoint assessing annualized infection rate and ANC response. Secondary endpoints will include severity and duration of infection, antibiotic use, fatigue, quality of life assessment and safety. Infections will be assessed by a centralized blinded adjudication committee, the same approach used for infectious assessment in the successful WHIM Phase 3 pivotal study. Working with Professor Tom Fleming, an FDA Biostatistics Advisor, is determined the trial size to be 150 participants globally to achieve a power of greater than or equal to 90% for each of the annualized infection rate and ANC response endpoints. With this protocol finalized, we are confident that we will be able to initiate the trial in the first half of 2024.

And further adding to our confidence, we have selected our global CROs who have already begun advancing towards site activation and identifying potential participants for the trial. By leveraging the existing CN patient advocacy groups and global patient’s registries, and through our own efforts to align a large pool of existing patients with the identified site, we believe we are now well positioned to achieve full enrollment in the Phase 3 pivotal trial in approximately 12 months. I’ll now pass it back to Paula.

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

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Q&A Session

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

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

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

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

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

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

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

Eva Privitera: Great. Thank you so much for taking my question.

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

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

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

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

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