X4 Pharmaceuticals, Inc.

Greetings and welcome to X4 Pharmaceuticals' third quarter 2022 conference call. At this time, all participants are in a listen-only mode. A question-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 Perry from Lifesize Advisors. Please begin.

Thank you, Operator, and good morning, everyone. Presenting on today's call will be X-Force Chief Executive Officer, Dr. Paula Reagan, and Chief Medical Officer, Diego Cadavid. We'll also hear briefly from the company's new Chief Commercial Officer, Mark Baldry, and company board member and incoming Interim Chief Medical Officer, Dr. Murray Stewart. Following prepared remarks, we'll open the call to your questions. We'll be joined by Chief Financial Officer, Adam Mustafa, Chief Scientific Officer, Art Tavares, 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. A description of these risks can be found in X4's most recent filings with the SEC, including this quarter's 10-Q, which is expected to be filed after market close today. I'd now like to turn the call over to X4's president and CEO, Dr. Paula Reagan. Paula?

Thanks, Dan, and thank you, everyone, for joining us on the call this morning. As we shared in the press release this morning, and as Dan just mentioned, Diego will be transitioning out of his role as chief medical officer and becoming a senior medical consultant to X4, and our board member, Dr. Murray Stewart, former chief medical officer of GSK and Rhythm Pharmaceuticals, will be joining X4 as interim CMO. At the end of today's call, Murray will say a few words of introduction. As we welcome new team members, we are extremely excited to share the progress that we've been making as we sharpen our focus as a company with a mission to develop therapeutics to treat the broad patient population with chronic neutropenic disorders, including our first potential indication of WHIM syndrome. and where we believe there's a significant need for an oral efficacious therapy with low treatment burden and good tolerability. With no oral therapeutic approved for approximately 50,000 chronic neutropenia patients in the U.S., we believe that Maverick Sephora, if approved, could represent a new opportunity to transform the treatment landscape and create a new standard of care. Today, the focus of the call will be to provide updates on Mavericks IV's progress in our Global Pivotal Phase III Trial in WHIM Syndrome, and to highlight how we are getting appropriately prepared to ramp into commercial launch. Mavericks IV is being studied in an ongoing Phase III for the treatment of WHIM Syndrome, which is a population of people with severe neutropenia, as well as other immune system deficiencies. WHIM syndrome is considered a combined immunodeficiency because patients with WHIM not only have profoundly low neutrophil counts, but also low lymphocyte and monocyte counts, and sometimes low antibody production, which is referred to as hypogamuloglobulinemia. We believe that Mavericks 4 has the potential to favorably impact the combined immunodeficiencies of those with WHIM syndrome and also has the potential to favorably impact a potentially broader population diagnosed with chronic neutropenic disorders. I'd like to take a minute now to review WHIM syndrome and how patients are diagnosed. Next slide, please. As I mentioned, WHIM syndrome is a combined immunodeficiency impacting people from birth. Patients have profoundly low neutrophil counts, as well as abnormally low lymphocyte and monocyte counts. and in many cases, low immunoglobulin levels. The W, H, I, and M of WHIM represent the variable presentation of the disease, which can range from severe wart presentations, the W, and HPV-associated disease to low immunoglobulin levels, the H for hypogamyloglobulinemia, increased susceptibility to frequent infections, the eye, and retention of neutrophils in the bone marrow called myelocathexis, the M, which explains the severe chronic neutropenia. Patients can present with one or more of these disease manifestations in addition to low neutrophils, lymphocytes, and monocytes. In view of this variable and complex clinical phenotype, a range of inputs is utilized by clinicians to diagnose WHIM syndrome. According to leading experts in this field, one of the most reliable ways to begin the journey of diagnosing WHIM is to examine total white blood cell counts, which includes neutrophils, lymphocytes, and monocytes, and look for multiple decreased white blood cell types, referred to as panleukopenia. As a consequence of this panleukopenia, People with WHIM syndrome experience lifelong risk of bacterial, fungal, and viral infections, with particular susceptibility to refractory warts due to infection by human papillomavirus, which can evolve into HPV-related cancers. Infections can be severe, including sepsis. Bone marrow biopsies can be utilized in the diagnostic journey. although it may not always be done due to the pain and potential morbidity associated with this needle-based invasive procedure. Upon microscopic evaluation, the hypermature or hypersegmented neutrophils in the bone marrow are important findings to corroborate the diagnosis of limb syndrome. In fact, the disease was initially called myelocaphexis before there was knowledge about genetic mutations. Genetic testing to look for gain-of-function mutations in the CXCR4 receptor is the conformational assessment most often used. Interestingly, genetic analysis in patients with a clinical diagnosis of WIMP syndrome but without CXCR4 mutations have identified new genetic mutations, including mutations in genes associated with the signaling cascade, such as CXCR2. In fact, in these individuals, Neutrophils share functional alterations of CXCR4-mediated responses despite the lack of CXCR4 mutations. Finally, a family history of WIMP syndrome also supports the ultimate diagnosis in any individual patient due to the autosomal dominant nature of the disease for those with CXCR4 mutations. We continue to support the needs of the medical community to facilitate awareness and earlier and accurate diagnosis of WHIM syndrome via multiple approaches, including knowledge of the variable clinical manifestations, pathologic abnormalities in the bone marrow, genetic mutations, and family history assessments. Importantly, there are no approved treatments specifically for WHIM syndrome. Existing treatments only address individual components of the disease, such as giving high-dose immunoglobulin to treat the low antibody levels or GCSF injections to treat the neutropenia, which is often poorly tolerated for chronic use. We recently completed the randomized placebo-controlled portion of the Phase III study of Mavericks 4 in WIM which is testing for the first time in a registrational study a targeted treatment that specifically addresses the root cause with the potential to improve the full spectrum of problems associated with the disease. I'll now turn it over to Diego to review our Phase III study design and our historical data that supports why we are so excited about our pending pivotal trial results. Diego?