X4 Pharmaceuticals, Inc.

Greetings and welcome to X4 Pharmaceuticals Fourth Quarter Financial and Operating Results Conference Call. At this time, all participants are in the 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, Dan Ferry of LifeSci Advisors. Please begin.

Thank you, Operator, and good morning, everyone. Thanks for joining us. Presenting on today's call will be X4's Chief Executive Officer, Dr. Paula Reagan, and the company's Chief Financial Officer, Adam Mustafa. Following prepared remarks by each, we will open up the call to your questions. And we'll be joined by Dr. Diego Cadavid, Chief Medical Officer, Art Tavares, Chief Scientific Officer, and Mary D'Avasi. 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 filing with the SEC. I'd now like to turn the call over to Paula Regan. Paula?

Thanks, Dan, and thank you, everyone, for joining us on the call this morning. We hope that you are all safe and healthy. As with many companies, 2020 threw some unexpected and significant challenges our way. Certainly, the COVID pandemic was chief among them, and working within a community where many patients are immunocompromised, that resulted in challenges for the enrollment of our clinical trials. However, I'm extremely proud of the work done by our team in mitigating these obstacles. We made significant progress in the clinical development of our lead candidate, Mavarixifor, and have an experienced leadership team in place to execute on our 2021 goals and beyond. As a reminder, Mavarixifor is our first-in-class small molecule antagonist of the chemokine receptor CXCR4, being developed as a once-daily oral therapy to treat a number of conditions caused by excessive signaling in the CXCR4 receptor. CXCL12 pathway. Our most advanced Mavericksivor program is in WIM syndrome. As you may recall, WIM is a rare inherited primary immunodeficiency disease caused by gain-of-function CXCR4 mutations that prevents the healthy trafficking of the immune cells and effective immunosurveillance. We believe Mavericksivor has the potential to be the first disease-modifying therapy for the more than 3,500 estimated diagnosed and undiagnosed WIM patients in the U.S. We are currently conducting a global Phase III clinical trial in WIM syndrome. The 4-WIM trial is a randomized, double-blinded, placebo-controlled, multicenter study designed to evaluate the safety and efficacy of maverixifor in genetically confirmed WIM patients. The primary efficacy endpoint for the trial will compare the level of circulating neutrophils relative to a clinically meaningful threshold in response to treatment with maverixifor versus placebo, measured over the course of 52 weeks. Secondary endpoints include infection rates, warp burden, and assessments of immune system function and quality of life. Given the current pace of enrollment and the fact that this is a 52-week study, we continue to anticipate top line data from this phase three trial in 2022. Notably, during the fourth quarter of 2020, we received both fast track and rare pediatric designations from the FDA for maverixifor for the treatment of WHIM syndrome. These FDA designations further recognize WHIM as a serious condition with a clear unmet need in both adult and pediatric populations and underscore the importance of our efforts to advance this program as rapidly as possible. Through the FAST-TRACK program, we will be eligible for more frequent meetings with the FDA to discuss the drug development plan, protocols, and the clinical data that would support maverixifor's potential approval for WHIM. As you may recall, maverixifor was previously granted breakthrough therapy designation by the FDA as well as orphan drug status by the FDA and the European Commission for the treatment of WHIM syndrome. With the rare pediatric designation, we may qualify in the future for a priority review voucher, which, if awarded, could potentially be monetized. In the meantime, we expect additional data this year to further support our confidence in the outcome of the 4-WHIM trial. Notably, the open-label extension of our Phase II clinical trial on WHIM has continued to dose patients. We anticipate presenting detailed updated results from this study within the next year. Since we expect that Mavarixor will be used as a chronic therapy if approved, these long-term data are quite meaningful to the patient and physician communities. We are also continuing our research into WHIM prevalence, characterizations of specific WHIM mutations, and compiling patient case studies, all for the potential presentation at upcoming medical conferences and other venues in 2021 and beyond, again, with a goal of a better understanding of the WIM market for future commercialization and also increasing our visibility in the WIM patient, physician, and KOL communities. Turning now to our other ongoing Maverick Sephora clinical programs, Enrollment is progressing in our Phase 1b trial, investigating the safety and efficacy of maverixifor in combination with ibrutinib for the treatment of a subset of CXCR4 mutant patients with Wallenstrom's macroglobulinemia, a rare form of non-Hodgkin's lymphoma. We look forward to presenting initial data from the study in the first half of 2021 with a more robust data set expected to be presented later this year. As previously discussed, Waldenstrom's results from a somatic mutation in the MYD88 gene that is present in more than 90% of patients. Approximately 30 to 40% of these patients have a second mutation in the CXCR4 gene. These double mutant patients with both the MYD88 and CXCR4 mutations typically present with a more severe disease profile and do not achieve the same depth and robustness in responses as in patients with a single MYD8 mutation treated with the current standard of care. We are targeting this high-need, double-mutant subset of Waldenstrom's patients as we assess the potential of Maverick's force treatment in combination with ibrutinib in our ongoing Phase 1B trial. The Phase 1B multicenter open-label dose escalation clinical trial is expected to enroll approximately 12 to 18 patients, In addition to safety, dose, and pharmacodynamic markers, the study is designed to evaluate changes in serum immunoglobulin M and hemoglobin from baseline, both key biomarkers of clinical response in Waldenstrom's patients. And lastly, regarding our Phase 1b trial in severe congenital neutropenia, we continue to anticipate initial Phase 1b data from the study later in 2021. As you can see, we expect that 2021 will be a year of key value-driving catalysts for X4 across clinical data readouts, enrollment completions, and breadth of opportunity initiatives. On our last call, we briefly introduced you to Dr. Art Tavares, who had just joined as our new Chief Scientific Officer. As we mentioned, he has a wealth of experience in discovering and developing novel next-generation CXCR2 antagonists. Art is an ideal fit to lead our R&D initiatives and has already had significant positive impact on our research activities and on our earlier stage pipeline initiatives. Following Art's joining in November, we also welcomed Dr. Diego Cadavid as our new chief medical officer. Having previously served in key senior medical leadership roles at Fulcrum Therapeutics and Biogen, Diego has brought us broad and deep clinical experience in the rare disease space. He has also proven invaluable to us already as we continue to advance our multiple clinical programs in parallel and further advance our preclinical pipeline towards the clinic. With that summary, I'll now turn the call over to Adam to discuss our financial results for the quarter. Adam?