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Operator
Greetings, and welcome to X4 Pharmaceuticals' first 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. To ask a question during the session, you'll need to press star 1 on your telephone. As a reminder, this conference call is being recorded. If you require any further assistance, please press star 0. It is now my pleasure to introduce your host, Dan Ferry of LifeSci Advisors. Please begin.
Dan Ferry
Thank you, operator, and good morning, everyone. Thanks for joining us. Presenting on today's call will be XFOR's Chief Executive Officer, Dr. Paula Regan, and the company's Chief Financial Officer, Adam Mostafa. Following prepared remarks by each, we will open the call to your questions. And we'll be joined by Dr. Diego Cadavid, Chief Medical Officer, Art Tavares, Chief Scientific Officer, and Mary DiBiase, Senior Vice President, technical operations, and quality. 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. A description of these risks can be found in X4's most recent filings with the SEC. I would now like to turn the call over to Paul Regan.
Paula Regan
Thanks, Dan, and thank you, everyone, for joining us on the call this morning. Let me start by saying that we could not be more pleased with our accomplishments so far this year. We have achieved significant progress in our Maverick X4 clinical programs and successfully completed a $55 million at-the-market pipe financing that included participation from leading biotech investors, both new to X4, as well as from existing investors. We believe this demonstrates a strong level of investor conviction in the clinical and commercial potential of Maverick Zephyr while also extending our expected cash runway into late 2022 and supporting our additional pipeline programs. As mentioned on our last call, the pace of enrollment in our key clinical programs has ramped up significantly since last year. Specifically, we now expect to be able to announce an important enrollment update in our Phase III trial in WIM syndrome in mid-2021. As a reminder, WIM is a rare inherited primary immunodeficiency disease caused by gain-of-function CXCR4 mutations that prevent healthy immune cell trafficking and effective immunosurveillance. Most patients with WIM disease have lifelong neutropenia and lymphopenia, that can result in a variety of serious chronic infections across multiple organ systems, HPV-associated lesions and increased cancer risk, and other serious life-impacting morbidities. Mavericks 4 is our first-in-class small molecule antagonist of the CXTR4 receptor that we believe has the potential to be the first disease-modifying therapy for the more than 3,500 potential diagnosed and undiagnosed WIM patients in the U.S. The 4WIM Phase III trial is a global, randomized, placebo-controlled, double-blinded, multi-center study designed to evaluate the safety and efficacy of Mavericks A4 over a course of 52 weeks in approximately 18 to 28 genetically confirmed WIM patients. The Phase III primary efficacy endpoint, called time above threshold for absolute neutrophil count, or TAT-ANC, compares the level of circulating neutrophils relative to a clinically meaningful threshold in response to Mavericks 4 treatment versus placebo. As you may recall from our Phase 2 study and published in the journal Blood in 2020, Mavericks 4 demonstrated greater than a 600% increase in time above threshold for neutrophil counts at our selected Phase 3 dose as compared to the lower doses treated for WIM patients. which gives us deep confidence in the potential success of our phase three study. Secondary endpoints include infection rates, warp burden, and assessment of immune system function and quality of life among others. At our current rate of enrollment, we continue to expect top line data from this phase three trial in 2022. We also continue to expect to report new data from the open label extension of our phase two clinical trial and WHIM later this year. We expect these data will continue to provide us insights regarding the long-term safety and durability of chronic Mavericks 4 treatments. Additionally, we anticipate several scientific publications that further support Mavericks 4's mechanism of action and potential for disease modification, as well as demonstrate its breadth of activity across the spectrum of WIM genotypes. Finally, we look forward to sharing new information regarding our additional WIM prevalence research later this year. In addition to our WHIM program, we continue to make good progress in our Phase 1b trial for the treatment of Waldenstrom's macroglobulinemia, a rare form of non-Hodgkin's lymphoma. As a reminder, this Phase 1b study is a multicenter, open-label, dose escalation clinical trial that is expected to enroll approximately 12 to 18 patients. We are very excited to have recently received notice of acceptance of our Phase 1B trial abstracts for a poster presentation at this year's Annual Congress of the European Hematology Association, or EHA, that will be taking place virtually from June 9th to June 17th. The abstract and poster will focus on initial clinical data from the ongoing Phase 1B trial of Maverick Sephora at the study's low and mid doses in combination with ibrutinib and the subset of Waldenstrom's macroglobulinemia patients harboring both the MYD88 and CXCR4 mutations. In addition to safety, pharmacokinetics, and pharmacodynamic markers, the initial data set will evaluate changes in serum immunoglobulin M, or IgM, and blood hemoglobin levels. It is well established that reductions in IgM levels and increases in hemoglobin levels correlate favorably with clinical responses for the treatment in Waldenstrom's patients. Later this year, we expect that the study will mature further such that we should be able to present data sets regarding the determination of the final dose selection for further study and assessment of major response rates, as well as ongoing safety across a range of doses. So as you can see, 2021 has been quite productive for us to date, and we're looking forward to a steady flow of value-adding data presentations and business milestones throughout the rest of the year. With that update, I will now turn the call over to Adam to discuss our results for the quarter and our recent financing announcements. Adam?
Dan
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 results for the first quarter ended March 31st, 2021. As of March 31st, 2021, X4 had $116.7 million in cash, cash equivalents, and restricted cash. This figure includes proceeds from the pipe financing that we completed in mid-March. Through this at-the-market deal, we raised a gross amount of $55 million with the financing including participation from a number of new and existing leading healthcare investors. After the close of this transaction, we now expect our cash and cash equivalents will fund company operations into the fourth quarter of 2022. Our research and development expenses were $12.1 million for the first quarter of 2021 as compared to $8.9 million for the comparable period in 2020. General and administrative expenses were $5.8 million for the first quarter of 2021 as compared to $4.7 million for the comparable period in 2020. And we reported a net loss of $18.7 million for the first quarter of 2021 as compared to a net loss of $11.1 million for the first quarter of 2020. Note that net loss included $1.3 million of certain non-cash expenses for the first quarter of 2021. Why don't we now open up the call to your questions? Operator?
Operator
Thank you. As a reminder, to ask a question, you'll need to press star one on your telephone. To withdraw your question, press the pound key. Please stand by, we'll compile the Q&A roster. Our first question comes from Steven Willie with, Steve, you may proceed with your question.
Steven Willie
Yeah, good morning. Thanks for taking the questions. Paula was maybe wondering if you can just kind of frame up expectations a little bit with respect to, I guess, what kind of data we might see in the abstract when that gets released. I think it's next week. And I guess how that may differ from what we could see at EHA. And it sounds like you said specifically that we'll be seeing data from the low and mid doses. Have you dose escalated patients up to that 600-meg dose yet per the escalation protocol?
Paula Regan
Yeah, so I'll try to break that all down for you, Steve, and thank you so much for the question. So the way to think about Waldenstrom's just as a disease is obviously the heavy burden of IgM levels being excessively high. causing a lot of risk for some serious sequelae like hyperviscosis syndrome. And then that massive bone disease burden from the cancer itself causing hemoglobin impact. So for a patient, you want to see IgM dropping and hemoglobin rising as a function of being treated. So that's really the focus of our EHA data in terms of demonstrating changes in IgM levels and hemoglobin levels that could be indicative of the combination doing better than ibrutinib alone. So we'll really be focusing on that. There's other phase one B studies that, you know, sort of use this, this paradigm as well. So I think we're consistent with giving people the, the, you know, the, the data set that can be indicated indicate our dual combination activity. Um, when we think about, uh, at the end of the year with ash, it's really about response rates and those take time to mature. Actually, typically it takes about six months on treatment before our patients are going for CT scans and bone marrow assessments to really complete the definition of response rate that's required in these patient populations. So that's why we just need longer time on study to be able to support a robust number of assessments across all our patients. And then finally, you did mention the 600. I mean, the study is continuing to dose escalate. You know, as you know, it's an open-label study, and We haven't completed all the cohorts yet, so that's why we'll be focusing on the low to mid doses, but we'll certainly share as much data as we're able to.
Steven Willie
Okay. And I guess, have you internally made the decision as to whether or not you're going to increase the enrollment up to 18? Or I guess, do you think that you're going to get a sufficient amount of data in these first 12 to kind of understand what your recommended phase two dose needs to be?
Paula Regan
Well, the trial itself incorporates a maximum tolerated dose requirement. So the 12 to 18 builds in flexibility in the event that we have those limiting toxicities. So that's where the flexibility comes in. Steve, it's not like we'll continue to try to escalate so long as the safety profile enables us to do so. The first two cohorts will reach through 600, so the last cohort B is a bit rounding out the total number of patients. So just stay tuned on that.
Steven Willie
Understood. And then just lastly, just curious as to where things stand on severe congenital neutropenia, which I don't think was part of your prepared commentary, or if it was, I may have missed it.
Paula Regan
Yeah, no, thank you. So the FDN trial is open and enrolling. In the context of COVID, especially last year and early this year, it was the most challenging study to enroll given the short dosing timeframe. These patients are immunocompromised. The study is two weeks, so we have always tried to prioritize patient safety and their need to come into, you know, hospitals for assessments. We do expect to have some initial data by the end of this year, but just in terms of patient numbers, what we've guided to is a, you know, smaller number of patients than obviously the total trial design. So we'll look forward to sharing what we're able to towards the end of the year.
Steven Willie
Understood. Thanks for taking the questions, and congrats on the progress.
Paula Regan
Thank you so much.
Operator
Thank you. Our next question comes from Mark Fromm with Cowan. You may proceed with your question.
Mark Fromm
Hi. Thanks for taking my questions, and congrats on all the progress across the multiple programs. Paul, can you just remind us the different doses in the Waldenstrom trial, just the kind of relative levels of – CXCR4 inhibition that you're expecting based on kind of all the prior work you've done with the molecule?
Paula Regan
Sure. Actually, I would invite Art Tavares to share with that. He's certainly one of our resident experts in exposure and inhibition. So, Art?
Art Tavares
Yes, hi. And thank you for the question. So the exposures that we're going after are very consistent with what we've seen from our WHIM Phase II trial. So the doses there, of course, are the 200, 400, and then ultimately the 600. And the exposures seem to be adequate to cause leukocyte mobilization, which is one of the key components for us to be able to have efficacy. And so we understand the potency of our molecule. We've measured that in many settings. And we also know that we're able to achieve those exposures to inhibit CXAO4 to give us the efficacy that we're hoping to see.
Mark Fromm
I guess, you know, kind of on traditional metrics of, like, you know, IC50, IC90, like, what type of levels are we at?
Art Tavares
Yes. So the IC50 from Averixa 4 is 4 nanomolar, and the IC90 is about 12 nanomolar.
Paula Regan
And so, Art, just to cross-check, certainly the 400 milligrams per day gets us to the IC50 and then the IC90. We're close to that with the 600, but, of course, it's about maximum tolerated dose. So that's where the window is. The drug is nonlinear in terms of its exposure mark.
Mark Fromm
Okay. That's helpful. Thanks. And then maybe on WIM, can you probably give an update on, to where you are more generally on patient identification efforts, kind of where registries are at these days?
Paula Regan
Yeah, so excellent question. So on patient identification, this is where we continue to partner with existing foundations that have their own registries as well as we have our own internal patient advocacy group that's been connecting with various sort of subgroups that have formed within the WIM community. So we continue to work with them, partner with them, work with existing registries, and we certainly have been formulating our own registry to support the long-term growth of Maverick so far to support these patients. So there's a bit of a stay tuned on sort of X4's specific registry plans, but know that they're in the works, and we're obviously wanting to appropriately dovetail into the communities that exist today and support them via our own efforts. And then in terms of just one patient identification, I think Later this year, we will be focusing on some WIM prevalence work, which will crosswalk into some of the broader patient identification initiatives that we have ongoing. And I think there'll be sort of a good, robust overview of some of those approaches towards the second half of this year.
Mark Fromm
Okay, great. That's very helpful. Thanks.
Paula Regan
Thank you, Mark.
Operator
Thank you. Our next question comes from R.K. Ramakhan with H.E. Wainwright. You may proceed with your question.
R.K. Ramakhan
Thank you. Good morning, Paula. A quick question on Mavericks for most of my questions on the current expectations on the IHA. I got them, but beyond what's going on right now in the Phase 1B study, do you Do you have a general outline as to how you would be going forward with this into the Phase II study? And also, could you kind of give us a rough timeline as to when that could happen?
Paula Regan
Yeah, so thanks, RK. I think I'll start and then I'll invite you to add anything. But I think really for clinical drug development, what we want to determine is the activity and potential benefit of the drug in the phase 1B as well as dose. Once we have a robust data set in hand, it's always best to partner with the FDA and other agencies early in the process. So that would be our intent. And then I think once we both have the FDA input and our data set, we'll then be able to project off of where the study will launch to, in our view, it would be straight into a study that would hopefully support registration. But we really need to generate the data set, of course, to have a mutually agreeable path forward, both for the company and for regulators. Diego, would you like to add anything?
spk00
Yeah, thank you, Paula. Also, yeah, we're actively working with leading investigators who who are really interested in this population of double mutant Waldenstrom to look at the data as it emerges and put together the best study design to present to regulators. Obviously, we have benchmarks of how ibrutinib itself was approved, and that is certainly one area we're carefully addressing and looking at it, but also other potential scenarios. So we will be sharing more with you and others as the work continues. Thank you for the question.
R.K. Ramakhan
Thank you. The second question is on the poor VIM trial. We understand, you know, you're going to give us a little bit of an update regarding enrollment in the midyear. However, you know, considering this population, and your experience so far with the trial. Again, similar question as to when we could see the completion of this study or would we get that update also during the mid-year enrollment update as to how we should think about not only your completing the study but your conversations with the regulators.
Paula Regan
Yeah, so maybe just as a reminder, we have shared that the existing study design, which is randomized, placebo-controlled, and double-blinded, and it's a 12-month dosing period, has been heavily vetted by the FDA and EMA in terms of support for the design and statistical power. So we feel extremely confident with the current study design and that that would be certainly enable an NDA and EMA filing from this one data set, and that continues to hold. So I think the excitement for us is that when we provide guidance on enrollment, that can readily sort of trigger people to do the math and project off of when we'll have top-line data. So that certainly continues to be consistent with our 2022 top-line data guidance, and we'll certainly look forward to being more specific in mid-2021.
R.K. Ramakhan
Thank you. Thank you, Paula.
Paula Regan
Thank you.
Operator
Thank you. Our next question comes from Mayank Bantani with B. Riley. He may proceed with your question.
Mayank Bantani
Hi. Good morning, team. This is Sahil Kazmian from Mayank. Thanks for taking our questions, and congratulations on all the progress. Maybe a brief one on the WIM patient enrollment and how that sort of tracking has been influencing by your efforts in patient identification. And then also on that same train of thought, how the patient identification efforts have had synergies on the SDM side and, you know, how you might think that influencing later stage trials as well.
Paula Regan
Yeah, thank you very much for that great question. So, I'd almost like to have you consider sort of three parallel sort of streams of work that do have leverage with each other. But certainly when we started the 4WIM trial, which from design and planning was certainly set at a timeframe at least, you know, two years ago at this point, really in rare disease you're working with centers of excellence, KOLs with known patients, patients that have had that long chronic unmet need and are sort of pent up demand for innovative study. So that's really been the history around us and how we have enrolled, opened up sites, worked with investigators, and enrolled the trial. Of course, in parallel, we're playing the long game. WHIM is a rare genetic disease, undereducated and underdiagnosed in the broad clinical communities as well as patient communities. So along our journey, as we built our own education and awareness efforts through a great MSL team and great patient advocacy team, We've actually naturally along the way come unearthed new or newly found or newly identified WIM patients that have been appropriately directed to clinicians to learn about our trial and also continue to kind of broaden out the overall connectivity between patients across the community. So I think it's a very natural synergy, but the patient identification efforts are really the long game of to build the potential addressable patient populations if and when Maverick score is approved. And then the third question is the SBN sort of dovetail, and actually that's been a great opportunity for us. One of the positive outputs of the NVTA efforts has been the panel that we're using for free genetic testing for clinicians with patients with immunodeficiencies spans all A large number of congenital neutropenias, of which SBN are some, so some of that has been nicely leveraged with our ongoing studies. And we've also, through our patient advocacy efforts, there's a lot of overlap with some of the patient foundation communities, and we've had a nice synergy in terms of education and awareness to our SBN trial as well. So I hope that addressed your question.
Mayank Bantani
Yeah, absolutely. That's really helpful. And then just maybe one more quick one on WHIM is, Could you provide kind of to the extent you're able to disclose a bit more color on what we might learn from incremental sort of data from this phase two open label extension that you plan to share at the end of the year, whether it be from a safety or sort of durability of response angle?
Paula Regan
Yeah, I mean, you know, I think you summarized it with safety and durability, but obviously the intent with supporting WIM patients is lifelong treatment with Maverick before. That's our expectation based on the data we know today. So any data that we generate under close watch around safety and durability continues to support the totality of data that would enable physicians and patients to be more comfortable with the data. Of course, obviously, the regulators as well. So I think it's just a bit of stay tuned, and we look forward to sharing that as it emerges.
Mayank Bantani
Great. Really appreciate the time. Thanks for taking our questions. Thank you.
Operator
Thank you. Our next question comes from Marlinda Lee with Canaccord. You may proceed with your question.
Marlinda Lee
Hi, guys. Thanks for taking my question. You guys alluded to nearing dose-dominated toxicities. Could you talk a little bit about what you would expect these might be? And then can you comment on whether you expect dosing to be the same across the various disease indications? Thank you.
Paula Regan
Sure. Thanks. Diego, would you like to take that?
spk00
Yes, sure. Yeah, so in terms of Maborixafor, the data we have when it is used as monotherapy, it really has been very well tolerated. So we don't really have any expected dose-limiting toxicities directly from Maborixafor alone. However, when you use it in combination with ibrutinib, I'm sure you know there is... several safety issues with chronic treatment with ibrutinib. They're all very clearly listed in the label, and when you use those in combination, we have to monitor those very carefully and see if adding Maborixafor is having any effects. So that's mostly what we are tracking. Regarding whether we expect the same or different dose, that will depend on the data. We're confident for WIMP syndrome. We have the right dose. That's the 400 milligrams per day. Waldenstrom, we are dose escalating up to 600. And based on the tolerability as well as the efficacy signal, we will choose the dose that gives the best benefit risk profile. I hope that answers your question.
Marlinda Lee
Thank you.
Operator
Thank you. Our next question comes from with Roth Capital Partners. You may proceed with your question. if your line is on mute, please unmute. And I'm not throwing any further questions at this time. I would now like to turn the call back over to Paula Reagan for any further remarks.
Paula Regan
Well, we'd like to say thank you very much for joining the call today. And if you have any further questions, please don't hesitate to reach out, and we hope you enjoy the rest of your day. Thank you so much again.
Operator
Thank you, ladies and gentlemen. This concludes today's conference call. Thank you for participating. You may now disconnect.
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