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

Greetings, and welcome to X4 Pharmaceuticals Third Quarter Financial and Operating Results Conference Call. [Operator Instructions] As a reminder, this conference call is being recorded. It is now my pleasure to introduce your host Dr. Glenn Schulman, Head of Investor Relations. Please begin.

Thank you, operator, and good morning, everyone. Presenting on today's call will be X4's Chief Executive Officer, Dr. Paula Ragan; and the company's Chief Financial Officer, Adam Mostafa. Following some prepared remarks by each, we will then open the call to your questions where we'll also be joined by our Chief Scientific Officer, Art Taveras; Chief Medical Officer, Diego Cadavid; and Chief Operating Officer, Mary DiBiase. As a reminder, on today's call X4 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 risks to differ from those forecasted. A description of these risks can be found in X4's most recent filings with the SEC, including our Form 10-K being filed today. I'd now like to turn the call over to Paula Ragan, President and CEO. Paula?

Thanks, Glenn, and thank you, everyone, for joining us on the call this morning. Before we get started, I did want to officially introduce our new Vice President of Investor Relations and Corporate Communications, Glenn Schulman, who you just heard from. He has a Master’s in Public Health and a PharmD and an extensive public life sciences company experience, leading successful Investor Relations and Corporate Communications teams and programs. Glenn joined us in mid-November and has been a great addition to the team. Welcome, Glenn. 2021 was an important year for X4, a year of execution across our multiple ongoing clinical trials and significant progress advancing our lead candidate, mavorixafor, closer to patients in need. And importantly, we expect 2022 to be a pivotal year for the company, a year of clinical results that will shape the future of X4 for years to come. During 2021, not only do we complete enrollment in the pivotal Phase III trial of mavorixafor in WHIM syndrome for the 4WHIM trial, but we also enrolled enough patients in our 2 earlier stage trials to achieve proof of concept for mavorixafor in 2 additional rare disease indications with many thousands of patients that have great medical need for additional treatments: chronic neutropenia and Waldenstrom macroglobulinemia. 31 adult and pediatric patients have been enrolled in the 4WHIM trial, which was originally designed to enroll 18 to 28 patients. As you know, this clinical trial is evaluating the safety and efficacy of a single daily oral dose of mavorixafor in patients with WHIM syndrome, a rare genetic immunodeficiency disorder caused by gain-of-function mutations to the CXCR4 receptor. The disease is characterized by HPV-associated warts, hypogammaglobulinemia, multiple types of infections and myelokathexis, which causes leukopenia and neutropenia in most patients, reducing the body's ability to mount a healthy immune response. Results from the ongoing open-label extension of our Phase II clinical trial of mavorixafor in WHIM patients continues to support this indication, with data showing durable increases in neutrophils, lymphocytes and monocytes, decreased frequency, severity and duration of infections, fewer hospital doctor visits and sustained improvement in warts. Mavorixafor continued to be well tolerated over a median treatment duration of almost 150 weeks. We continue to anticipate top line data from the 4WHIM trial in the fourth quarter of 2022. We ended last year with our largest ever presence at a scientific meeting, the Annual Meeting of the American Society of Hematology, or ASH, and we held a company virtual seminar immediately following with several key thought leaders in the industry. Our posters and abstracts at the ASH meeting contained a broad array of both clinical and scientific data. Data that we believe not only further establishes X4 as a leader in the CXCR4 related research space, but also supports the broadening scope of the clinical potential of mavorixafor due to its ability to selectively inhibit CXCR4. At the meeting, we shared data demonstrating the effect of mavorixafor across multiple disease states, multiple cell types and over chronic periods of dosing. One of our posters showed for the first time that mavorixafor is able to raise total counts of all the acute white blood cells necessary to mount an appropriate immune response across a wide spectrum of diseases over both short- and long-term treatment periods. Data were presented from ongoing clinical trials in Waldenstrom macroglobulinemia, clear cell renal cell carcinoma, WHIM syndrome and for the first time, early data from our ongoing Phase Ib trial in patients with chronic neutropenia. These data demonstrated that mavorixafor broadly increased white blood cells and neutrophil counts anywhere from two to sixfold across all indications as well as in healthy subjects. Early data from our Phase Ib clinical trial in chronic neutropenia mirrored these results, but demonstrated elevations in white blood cells and absolute neutrophil, lymphocyte and monocyte counts across the first 4 patients enrolled in the trial. As a reminder, chronic neutropenia refers to a condition of sustained or recurrent abnormally low neutrophil counts lasting at least 3 months. It's estimated that 6 in 10,000 people have chronic neutropenia, which can be present in a variety of severity, mild, moderate or severe, and can increase the risk of serious and recurrent infections in patients. Enrollment in our Phase Ib trial continues with additional data expected in the second or third quarter of 2022. It was a compelling set of consistent responses irrespective of disease state and irrespective of CXCR4 mutation status. And in aggregate, have encouraged us to think much more broadly about how mavorixafor could impact larger numbers of patients with primary immunodeficiencies, whether caused by CXCR4 mutation as in the case of WHIM syndrome, or via antagonism of the wild-type CXCR4 signaling pathway and many other cellular immunodeficiencies. We also presented results from our ongoing Phase Ib clinical trial in people with Waldenstrom macroglobulinemia, a rare B-cell lymphoma at low 200 milligram and mid-level 400 milligram dosing of mavorixafor combined with the BTK inhibitor, ibrutinib, with a median treatment duration of 272 days. As a reminder, the Phase Ib trial is designed to demonstrate safety, dose and elucidate proof of concept of mavorixafor in people with Waldenstrom with significant unmet needs resulting from mutations to both their MYD88 and CXCR4 gene. The data showed a 100% overall response rate in the 10 evaluable double mutation patients, sustained decrease in serum IgM levels and a trend towards normalization of hemoglobin levels. We also announced this morning that 600 milligram dose of mavorixafor was clear of the ongoing study. All eligible patients in cohorts A and B or the low and mid-level cohorts are now being dose escalated to receive 600 milligrams of mavorixafor once daily in combination with ibrutinib. We expect to report updated data from this trial during the second half of the year. At ASH last December, we also announced that our research efforts have led to the discovery of several novel WHIM causing CXCR4 mutations, the incidence of which further strengthens our confidence that there are more than 3,500 WHIM patients in the U.S. alone. More detailed data on one of these mutations, the D84H mutation was just presented at the American Academy of Allergy, Asthma and Immunology, or AAAAI meeting in late February. The poster for this is available on our website. Looking forward, our participation at major medical conferences continues in 2022, where we are working hard to educate the medical community and raise awareness of WHIM. At the upcoming 2022 Clinical Immunology Society, or CIS conference, we will present for the first time another recently identified novel WHIM variant, the S341 WHIM variation. This combined with the D84H mutation are just 2 of the many novel WHIM variants that have been sequenced, characterized and published into literature, stemming from our world-class research center in Vienna. Next month at the AACR conference, our preclinical team will be presenting new data demonstrating the additive to synergistic activity of mavorixafor when combined with any BTK inhibitor, including zanubrutinib and ibrutinib. With that update complete, I would like to take a little time today to share some insights in our commercial approach as we near our first Phase III clinical data of mavorixafor for the treatment of WHIM syndrome. The first is our early engagement with patient communities through patient advocacy. Patient voices are at the center of all decisions we make at X4. Early in the mavorixafor clinical development process, we appointed a Vice President of Patient Advocacy who engaged with patient advocacy groups long before entering the Phase III trial, which enabled us to understand the diverse disease journeys and unmet needs of our patients. We worked closely with patient advocacy groups, all along to develop disease awareness materials and other resources to help educate on testing resources, disease presentation, access to medical experts and treatment options available or in clinical development. The second is our educational support and access to genetic testing to improve diagnosis. As you likely know, diagnosis and patient identification are the main challenges for rare disease. Due to the heterogeneous symptom presentation and lack of physician awareness, WHIM syndrome is often difficult to diagnose. This leads to long diagnosis journeys and delayed access to the symptomatic treatment that are the current standard of care. People with WHIM syndrome often visit numerous medical specialties before being diagnosed. As we have discussed previously, we sponsor a no-charge genetic testing and counseling program, PATH4WARD, for individuals who might carry mutations associated with congenital neutropenia, including WHIM syndrome to aid in patient identification and to help bring patients one step closer to an accurate diagnosis. We also employ the use of artificial intelligence and machine learning tools to enhance our understanding of the prevalence and burden of disease. WHIM is thought to be underdiagnosed due to the absence of an International Classification of Disease, or ICD-10 code as well as inconsistent coding for key symptoms. We have utilized artificial intelligence and machine learning platforms to identify patients with WHIM look-alike clinical phenotypes that might have been previously undiagnosed due to inconsistent symptom presentations. As we talked about last year, this space of WHIM is like a puzzle, but with our ongoing research and that of the physician, scientist and patient communities, there is increasing clarity as the understanding of the disease continues to evolve as is often the case with many rare diseases. We have also assembled a strong medical affairs team. Building a specialized team geared towards physician education and creating partnerships to increase awareness of WHIM syndrome is a critical [ bridge ] to achieving our goal. Collectively, we feel passionately about empowering medical professionals and their patients to understand their unique journeys so that they can get answers and find available treatments. Lastly, and as we just mentioned, we continue to conduct research on the underlying genetics of WHIM. We have built strong in-house research programs that leverage world-class collaborations to advance bench-to-bedside research. By continuing to establish correlations between clinical presentation and new genetic variants associated to WHIM, we can improve our ability to identify undiagnosed patients, including those who may potentially benefit from mavorixafor treatment in the event it gains approval. Of course, building a sustainable rare disease business is not fully rooted in supporting patients and physicians. There’s much more needed beyond that, that we need to deliver on, and we are well on our way. We have made great progress in adding leadership to the company with our VP of U.S. Commercial and our new Board Director, both with significant life science commercialization experience. More key hires, including a Chief Commercial Officer are slated for 2022. In terms of our ultimate commercial product, we have taken the appropriate steps in terms of registration and validation batches to support our NDA filing and are advancing our work to support mavorixafor's future commercial trade reps and third-party logistics providers to enable a successful U.S. launch. Finally and importantly, given the disease modifying impact that mavorixafor may have on this rare WHIM syndrome population, we are engaging with payers with research and education in the U.S. and key European territories. All of these platforms and initiatives are working in concert to enable us to be ready to deliver for our patients in the event of our first approval. With that update, I now turn it over to Adam to discuss results for the quarter before we open up the call for questions. Adam?

Thanks, Paula, and thanks to all of you on the call today. As presented in our press release this morning, I will summarize our financial activities and results for the fourth quarter ended December 31, 2021. At the end of 2021, X4 had $83.1 million in cash, cash equivalents and restricted cash. We continue to expect that our cash and cash equivalents will fund our operations into the fourth quarter of 2022. Research and development expenses were $12.2 million for the fourth quarter ended December 31, 2021, as compared to $12.3 million for the comparable period in 2020. General and administrative expenses were $7.1 million for the fourth quarter ended December 31, 2021, as compared to $5.4 million for the comparable period in 2020. Finally, X4 reported a net loss of $30.2 million for the fourth quarter of 2021, which includes approximately $11.4 million in noncash expenses, of which $9.8 million is an impairment of goodwill charge, as compared to a net loss of $18.4 million for the comparable period in 2020. We'll now open up the call for your questions. Operator?

[Operator Instructions] We have a question from Stephen Willey with Stifel.

I guess as you think about the WHIM data, I know we get the top line disclosure in the fourth quarter, you'll subsequently be talking to payers and getting a sense of what reimbursement might look like. Just curious as how that information that you get from payers and reimbursement will inform, if at all, the target patient population that you choose to pursue in chronic neutropenia? I guess is there a chance here that you just select the more severe patients, i.e., those that have more than 2 infection events a year or those on chronic G-CSF? Just wondering how you're thinking about how the WHIM data shapes the [ TPP ] for chronic neutropenia?

Steve, thank you for the question. So I think we kind of think about it almost on 2 different axes. There's sort of a patient number question which I think the rare disease community is familiar with in terms of the ability to gain appropriate value propositions for these ultra-orphan diseases and then it kind of sometimes correlates with patient numbers. So with WHIM, we've tested that, and we actually think we have a fairly broad width of patient numbers that certainly supports the current WHIM numbers that we have and actually well beyond that. So as additional patients and additional indications come on, we don't think that, that would have any sort of pricing impact on how we go out with WHIM. So we don't think with chronic neutropenia’s larger numbers, it would impact our overall pricing strategy. And then I think you're correct. I mean ultimately, what we're trying to do is answer a high unmet need. We've shared already today that there's about 5,000 patients with chronic neutropenia that have these very severe -- we call them serious infection events, at least 2 per year or more. And certainly, in some ways, those patients are as severe, if not more severe than those that we've seen with WHIM syndrome. So I think we're continuing to focus on the high unmet need and to present the value proposition that would support sort of a uniform pricing strategy across multiple indications.

Okay. That’s helpful. And I know you'’ve mentioned clearing the 600 mg dose in Waldenstroms. How many patients were initiated on the 600 mg dose? Is that the 6 patients in that third cohort?

Yes. Steve, this is Diego. Yes, the cohort B, the goal was to enroll 6 patients and 5 out of 6 minimum with no major safety events and that was accomplished. That's why this morning, we announced that the 600 milligram, the top dose, has now been cleared and all remaining patients in the trial who were at the lower doses are being dose escalated. So we expect at the end of -- when we report updated results in the second half, everyone who is eligible will be at 600 milligrams for a number of months.

Okay. And you'll have 5 patients then who were initiated at the 600 mg dose?

Yes. The goal was 6. Yes.

Okay. And then just lastly for Adam, do you have a share count as of year-end?

Yes. So it's about 30 million basic shares outstanding. And then we have another 9 million if you include the Class A and Class B warrants. And then lastly, about 1 million of options RSUs. So 40 million or so is a good number, fully diluted.

Our next question comes from Marc Frahm with Cowen and Company.

Maybe, Paula, with the work you've done on identifying novel mutations, I guess, what are your latest thoughts on how many WHIM patients actually exist in the U.S.? Has this mostly just reinforced your confidence in the numbers you put out? Or are you thinking maybe those numbers need to be increased?

I think so. For us, it's always about confidence first. And so of course, these additional variants are increasing our very deep confidence in the 1,000 to 3,700 range that we have presented. Certainly, as we learn more, and we'll look forward to providing some updates even this year about the variance that we're identifying through multiple avenues, we will think about revising as we think that's appropriate. But for now, it's really about the confidence. And again, you can appreciate we want to always go up is the strategy of the company. So confidence in that 1,000 to 3,700 is our position today, but certainly, there's probabilities that could increase that in the future.

Okay. That's helpful. And then on the SCN update that we're expecting, can you just give a little more clarity on kind of the number of patients we should expect, the amount of follow-up that they'll likely have had versus what we saw back in December?

Yes, we -- as you know, we presented data on the first 4 patients at ASH. We are actively identifying and enrolling patients. So we are prepared to release data on more than 4 patients. Certainly, the study is up to 25, and we are working with all the sites. There's interest in the study and the conditions of the pandemic have improved and that's also something that is helping us.

Okay. That's helpful. And then maybe one for Adam. The cash guidance it seems to be kind of tied to the year-end cash balance, but you did do a private placement the other day. Is that actually included in the cash guidance? And if not, how does that impact your guidance around there? And then related to that is, can you remind us what the minimum cash covenants are for some of the debt?

Sure. Yes. Thanks, Marc. So our guidance remains into the fourth quarter. That includes the $6 million or so you referenced that we raised since the beginning of the year. It just puts us further into the fourth quarter. On the Hercules side, we have a minimum cash covenant of 6 months of cash. We did recently amend it. And if we raise $30 million from any source by June 30, that minimum cash covenant becomes a fixed $30 million. So more flexibility, less than 6 months of cash currently. And that test kicks in on September 1 as we also pushed that test date out recently.

Our next question comes from Mayank Mamtani with B. Riley Securities.

So couple of questions from us. Just on the 4WHIM study, in terms of how you're thinking about presenting the data top line and also the full data set? Would you have information on the patient level analysis? And if at all, you're targeting any medical conferences towards the end of the year?

Mayank, just -- I think we heard your question was around how are we -- how and kind of what are we going to present around the top line data, both in terms of initial top line and then possibly at a medical conference, just to reiterate, is that correct?

Yes.

Okay. Diego?

Yes. So we always aim to present top line data at medical conferences. So right now, we have not specifically pointed to what conference, but Q4 is when we are tracking. And so obviously, we'll look for the best venue at that time to disseminate the data. We're really looking forward to it. Top line data is -- will be only part of that. The study has many other end points. So through the following months and other conferences, we plan to disclose all the other valuable data that we are collecting.

Okay. And just maybe on that, do you plan to disclose additional baseline characteristics kind of information? Now that you have a lot of information on these 31 patients that are enrolled, would there be some more information on those patients? Or should we just wait until the final top line?

Yes. So soon, at an incoming conference, there will be a poster that will include baseline characteristics. So you will be able to see there the type of patients that were enrolled into the trial. So that's coming very soon.

Awesome. And then on the D84H missense mutation, the poster you had at the [ Cord ] conference, just about the implications of that, is that help expand prevalence or also identify maybe more severe patients with that WHIM phenotype. Could you just clarify that?

D84H -- sorry, Mayank, just to clarify, again, I think this is in reference to the D84H disclosure that we had where we identified a series of patients with that. So the good news is, I think, that, as I think earlier question, does that increase our confidence and then does it change our numbers. So right now, I think we're very squarely in the camp of increasing our confidence in the 1,000 to 3,700, even just based on that one mutation alone. However, maybe I'll invite Art to just comment broadly on some of the additional work that we're doing on additional variants and there'll be more data to come this year. Art?

Yes. So as you know we've been characterizing a number of mutations that we've identified throughout our own research through the clinical programs, through the literature, through Invitae in the PATH4WARD program, and then we transfect cells and try to characterize their pathogenicity. So we've done that with many 10s -- or actually well over 50, I'll just say right now, and then we're going to be communicating that data set throughout the year. We have the S341Y, which is coming up at CIS. D84H, we presented, as you know, last year. And then as part of that, we look at the number of genomic databases and calculate what I would say is a very conservative number of prevalence. And so for that, it actually allows us to understand the pathogenicity. We work with other people to try to communicate the details of the pathogenetic findings that we're seeing, and that's all part of educating the community, and we anticipate that there are many more patients out there with these various mutations that actually are pathogenic and demonstrates some phenotype of WHIM. So that's really about the future, and we're happy to disclose a lot of that information as we keep moving forward.

And then my final question on volumes front, great to see the 600 mg dose clearing. Can you just clarify what your target for deepening of responses look like now that you're at higher dose and exposure is going beyond 12 months for these patients. So just -- could you just clarify what sort of MR, VGPR numbers you might be targeting?

Yes. Thank you for the question. So the study was designed as intra-patient dose escalation. Everybody started at 200 milligrams in combination with ibrutinib. Once 200 milligram was deemed safe, everybody eligible was dose escalated to 400, and then they stay at 400 until the 600 milligram dose was deemed safe which just happened. And now we have a good number of patients already at 600 and another good number that are being escalated to 600. So this will result on a variability of exposure at 600 over time. Some patients will be on it for much longer, others for shorter time. And overall, we believe this is a really good news, combination of ibrutinib with these highest tested dose we believe over time gives this a possibility of having deeper, more durable, more pronounced clinical responses. Over the next few months, we will be looking at all this data and we will communicate it in the second half as this data becomes available.

[Operator Instructions] We have a question from the line of Arthur He with H.C. Wainwright.

This is Arthur in for RK. So I guess I just want to follow-up on the patient enrollment for the Waldenstrom study. So how many patients -- total patients you have right now being enrolled in the total study? And how many patients has been dosed for 600-milligram dose level?

Yes. The study calls for the enrollment of 12 to 18 patients. We have not communicated the exact number, but we are in a good position to meet that enrollment goal. And as I said recently, everyone eligible will be at the 600 milligram dose. And we believe that, that sample size at that dose will give us the information we need to plan for the next step.

Okay. And maybe a little bit follow-up on that. Is the newly enrolled patients or folks on both are including naive and refractory patient? Or it -- has it more concentrated in the refractory patients?

So the current protocol allows for enrollment of either frontlines or relapsed refractories. There’s an effect of the label. Ibrutinib is approved in the U.S. for frontline, but not in Europe. So it really depends on which site is enrolling. But we -- as we communicated at ASH, we have been enrolling both types, and we believe the combination treatment has the potential to help both types of patients.

And I'm not showing any further questions in the queue. I will turn the call back to Paula Ragan for her final remarks.

Well, thank you again for joining us today. We look forward to seeing many of you at the various upcoming investor conferences and at medical meetings throughout the year. Please, if you have any further questions, don't hesitate to reach out to Glenn, and we hope you enjoy the rest of your day. Thanks so much.

And with that, ladies and gentlemen, we conclude our program for today. Thank you for participating. You may now disconnect.