X4 Pharmaceuticals, Inc Q4 FY2021 Earnings Call

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. A question-and-answer session will follow the formal presentation. 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 prepared remarks by each, we will 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 results 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 do 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 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 and their needs. 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, we not only completed enrollment in the pivotal Phase III trial of mavorixafor in WHIM syndrome for the 4WHIM trial but we also enrolled enough patients in our two earlier stage trials to achieve proof of concept for mavorixafor in two additional rare disease indications with many thousands of patients that have a great medical need for additional treatments: Chronic neutropenia and Waldenström macroglobulinemia. 31 adult and pediatric patients have been enrolled in the 4WHIM trial, originally designed to enroll 18 to 28 patients. This clinical trial evaluates 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 in 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 continue to support the 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 continues 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. 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 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 chronic periods of dosing. One of our posters showed, for the first time, that mavorixafor is able to raise the total count 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 Waldenström 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 cell and neutrophil counts anywhere from two to six fold across all indications as well as in healthy subjects. Early data from our Phase Ib clinical trial in chronic neutropenia mirrored these results but showed elevations in white blood cells and absolute neutrophil, lymphocyte, and monocyte counts across the first four patients enrolled in the trial. As a reminder, chronic neutropenia refers to the condition of sustained or recurrent abnormally low neutrophil counts lasting at least three months. It's estimated that 6 in 10,000 people have chronic neutropenia, which can be present in a variety of severities: 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 CXCR4 mutation status. In aggregate, these results have encouraged us to think much more broadly about how mavorixafor could impact larger numbers of patients with primary immunodeficiency, whether caused by CXCR4 mutation as seen in WHIM syndrome or via antagonism of the wild-type CXCR4 signaling pathway in many other cellular immunodeficiencies. We also presented results from our ongoing Phase Ib clinical trial in people with Waldenström 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, dosing, and elucidate proof of concept of mavorixafor in individuals with Waldenström facing significant unmet needs resulting from mutations in both their MYD88 and CXCR4 genes. The data showed a 100% overall response rate in the 10 evaluable double mutation patients, sustained decreases in serum IgM levels, and a trend towards normalization of hemoglobin levels. We also announced this morning that the 600-milligram dose of mavorixafor was cleared in the ongoing study. All eligible patients in Cohorts A and B, 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 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 information on one of these mutations, the D84H mutation, was just presented at the American Academy of Allergy, Asthma and Immunology 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 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 two of 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 present new data demonstrating the additive and synergistic activity of mavorixafor when combined with any BTK inhibitor, including zanubrutinib and ibrutinib. With that update complete, I would like to take some time today to share some insights on 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. This 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 diseases. Due to the heterogeneous symptom presentation and lack of physician awareness, WHIM syndrome is often difficult to diagnose. This leads to long diagnostic journeys and delayed access to symptomatic treatment for the current standard of care. People with WHIM syndrome often visit numerous medical specialties before being diagnosed. As discussed previously, we sponsored a no-charge genetic testing and counseling program, Path Forward, for individuals who might carry indications associated with congenital neutropenia, including WHIM syndrome, to aid in patient identification and 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, which 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 clinical phenotypes resembling WHIM that may have been previously undiagnosed due to inconsistent symptom presentation. As noted last year, the understanding of WHIM is like a puzzle, but with our ongoing research and that of the physician scientists 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 as a critical component towards achieving our goals. 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, as we mentioned, we continue to conduct research on the underlying genetics of this syndrome. We have built strong in-house research programs that leverage world-class collaborations to advance bench-to-bedside research, as we continue to establish correlations between clinical presentations and new genetic variants associated with WHIM. This, in turn, will improve our ability to identify undiagnosed patients, including those who may potentially benefit from mavorixafor treatment in the event of FDA approval. Of course, building a sustainable rare disease business is not solely rooted in supporting patients and physicians. There is much more required beyond that that we need to deliver, and we are well on our way. We have made significant 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 prepare mavorixafor's future commercial trade dress 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 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, 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, 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 non-cash expenses, of which $9.8 million is an impairment of goodwill charge, 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.

We have a question from Stephen Willey with Stifel. Your line is open.

Yes, good morning, guys. Thanks for taking the question. I guess as you think about the WHIM data, I know we get the top-line disclosure in the fourth quarter, subsequently be talking to payers and getting a sense of what reimbursement might look like. Just curious how that information you get from payers and reimbursement will inform, if at all, the target patient population 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 two infection events a year or those on chronic G-CSF? Just wondering how you're thinking about how the WHIM data shapes the patient population for chronic neutropenia?

Steve, thank you for the question. I think we kind of view it almost on two 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. For 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 would have any sort of pricing impact on how we go out with WHIM. We don't think with chronic neutropenia larger numbers will impact our overall pricing strategy. And then I think you're correct; ultimately, what we're trying to do is answer a high unmet need. We've shared already today that there are about 5,000 patients with chronic neutropenia that have very severe, we call them serious infection events, at least two per year or more. 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 present the value proposition that would support a uniform pricing strategy across multiple indications.

And I know you mentioned clearing the 600 mg dose in Waldenström. How many patients were initiated on the 600 mg dose? Is that the six patients in that third cohort?

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

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

Yes, the goal was, yes.

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. Lastly, about 1 million of options and RSUs. So, 40 million or so is a good number, fully diluted.

Great. Thanks for taking the questions.

Thanks, Steve.

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

Thanks for taking my question. Maybe Paula, with the work you've done identifying novel mutations, what are your latest thoughts on how many WHIM patients actually exist in the U.S.? Is this mostly just reinforcing 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. 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 look forward to providing some updates this year about the variants 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 confidence. Again, you can appreciate we want to always go up; that’s the strategy of the company. So confidence in that 1,000 to 3,700 is our position today, but certainly, there are probabilities that could increase that in the future.

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

Yes. As we presented data on the first all patients at ASH, we are actively identifying and enrolling patients, so we are prepared to release data on more than four 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 is also something that is helping us.

And then maybe one for Adam. The cash guidance seems to be tied to the year-end cash balance, but you need to 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 can you remind us what the minimum cash covenants are for some of the debt?

Sure. Yes. Thanks, Marc. 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 six months of cash. We did recently amend it, and if we raised $30 million from any source by June 30th, that minimum cash covenant becomes a fixed $30 million. So more flexibility and less than six months of cash currently, and that test kicks in on September 1st as we also pushed that test date out recently.

Okay, great. Very helpful. Thank you.

We have a question from Mayank Mamtani with B. Riley Securities.

Good morning. Thanks for the detailed updates. A 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?

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

Yes.

Yes. 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. We look for the best venue at that time to disseminate the data. We're really looking forward to it. Top-line data will only be part of that. The study has many other endpoints, and through the following months and other conferences, we plan to disclose all the other valuable data that we are collecting.

And just 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, will there be some more information on those patients? Or should we just wait until the final top-line?

Yes. Soon, at an incoming conference, there will be a poster that will include baseline characteristics, so you will be able to see there the types of patients enrolled in the trial. That's coming very soon.

Awesome. And then on the reported missense mutation, the poster you had at the recent conference, just about the implications of that—does that help expand presence or also identify the pace with that in-type? Could you just clarify that?

Just to clarify, again, I think this is in reference to the D84H disclosure where we identified a series of patients with that. The good news is, as I think was indicated in an earlier question, this does increase our confidence. 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 will be more data to come this year. Art?

Yes. As we've been characterizing a number of mutations that we've identified throughout our own research, through the clinical programs, through literature, and through the Path Forward program, we've transfected cells to try to characterize their pathogenicity. We've done that with many tens, actually well over 50 mutations right now. We will be communicating that data set throughout the year. We have the S341Y which is coming up at CIS, and the D84H we presented last year. In that process, we look at the number of genomic databases and calculate, what I would say is a very conservative number of prevalence. This allows us to understand the pathogenicity, and we work with others to communicate the details of the pathogenic findings we observe; this is all part of educating the community. We anticipate many more patients are out there with these various pathogenic mutations that demonstrate some phenotype of WHIM. So that's really about the future, and we're happy to disclose information as we keep moving forward.

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

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

Thanks. Thank you for taking our questions.

We have a question from Arthur He with H.C. Wainwright. Please go ahead.

Hey, good morning everyone. This is Arthur in for RK. Thanks for taking my question. Just want to follow up on the patient enrollment for the Waldenström study. How many total patients have right now been enrolled in the total study, and how many patients have been dosed for the 600-milligram dose level?

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

And maybe a follow-up on that. Are the newly enrolled patients or folks on both arms including naive and refractory patients, or are they more concentrated in the refractory patients?

So the current protocol allows for enrollment of either frontline or relapsed refractory patients. There is an effect of the label. Ibrutinib is approved in the U.S. for frontline but not in Europe. It really depends on which site is enrolling. 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.

Thanks for taking my questions.

Thank you. 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.