On March 17, 2022 X4 Pharmaceuticals, Inc. (Nasdaq: XFOR), a leader in the discovery and development of novel CXCR4-targeted small molecule therapeutics to benefit people with diseases of the immune system, reported financial results for the fourth quarter and twelve months ended December 31, 2021, and provided a corporate update (Press release, X4 Pharmaceuticals, MAR 17, 2022, View Source [SID1234610310]).

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"We are very pleased with our many accomplishments in 2021, particularly completing enrollment in the pivotal 4WHIM Phase 3 clinical trial in WHIM syndrome, the first indication we are pursuing for our oral, first-in-class CXCR4 inhibitor, mavorixafor," commented Paula Ragan, Ph.D., President and Chief Executive Officer of X4 Pharmaceuticals. "We also continued enrolling and treating patients in both our chronic neutropenia and Waldenström’s macroglobulinemia Phase 1b clinical trials, which are designed to expand the potential market opportunities for mavorixafor, and we look forward to reporting key clinical and regulatory updates for these programs throughout the year."

Dr. Ragan continued, "Our clinical and research efforts into the potential of CXCR4 antagonism have also resulted in the discovery of several novel WHIM-causing CXCR4 mutations associated with expanded disease characteristics, which we believe further underscore WHIM syndrome as an underrecognized condition and strengthen our confidence in prevalence being potentially higher than the current estimates of WHIM patients in the U.S. We look ahead to the remainder of 2022 with great excitement, as we continue to anticipate top-line data from 4WHIM by the end of the year, and additional clinical and research data throughout the year, further supporting the broad clinical and commercial potential of mavorixafor across multiple indications."

Fourth Quarter 2021 Highlights
•Completed enrollment in the ongoing pivotal 4WHIM Phase 3 clinical trial of mavorixafor in patients with WHIM (Warts, Hypogammaglobulinemia, Infections, Myelokathexis) syndrome. Thirty-one adult and pediatric patients have been enrolled in the 4WHIM trial, which was originally designed to enroll 18 – 28 patients. Top-line data from the 4WHIM trial are expected in the fourth quarter of 2022.
•Presented a wide range of clinical and research data at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting supporting the potential use of mavorixafor across a number of immunodeficiencies and certain cancers:

Exhibit 99.1
◦Ongoing studies across a wide variety of diseases, including Waldenström’s macroglobulinemia (WM), clear cell renal cell carcinoma, WHIM syndrome, and chronic idiopathic neutropenia, showed that oral administration of mavorixafor increased blood neutrophils, lymphocytes, and monocytes regardless of the presence or absence of CXCR4 mutations.
◦Mavorixafor efficacy has been clinically observed with short-term and long-term treatment both alone and in combination with other therapies, including axitinib, ibrutinib, and granulocyte-colony stimulating factor (G-CSF).
◦Additional data from the Phase 2 open-label extension study of mavorixafor in WHIM patients continued to show durable increases in neutrophils, lymphocytes, and monocytes; decreased frequency, severity, and duration of infections; fewer hospital/doctor visits; and sustained improvements in warts. Chronic daily administration of mavorixafor continued to be well tolerated (median treatment duration = 148.4 weeks).
◦Clinical and laboratory research resulted in the identification of a novel missense CXCR4 mutation, D84H, that further supports the company’s WHIM prevalence estimate of at least 1,000 to 3,500 patients in the U.S.
◦Initial results from the ongoing mavorixafor Phase 1b clinical trial in people with chronic neutropenia concurrently treated with granulocyte colony stimulating factor (g-CSF) and mavorixafor demonstrated elevations in white blood cells and absolute neutrophil, lymphocyte, and monocyte counts (n=4); enrollment continues, with additional data expected in the second or third quarter of 2022.
◦In December 2021, interim results reported from the ongoing Phase 1b clinical trial in WM from the low- (200 mg) and mid-level (400 mg) dose groups (October 2021 data cut) showed a 100% overall response rate (n=10, median treatment duration of 272.5 days), sustained decreases in serum IgM (n=14), and trends towards normalization of hemoglobin levels (n=14 at baseline, n=3 at 12 months).
▪As of March 2022, cohort B evaluating 600 mg of mavorixafor in combination with ibrutinib met the safety requirements to allow for the dose escalation of patients enrolled in cohort A and previously treated at low- and mid-level doses. All eligible patients are being escalated to receive 600 mg of mavorixafor once daily in combination with ibrutinib. Additional data from this trial are expected in the second half of 2022.

Upcoming Presentations
Clinical Immunology Society (CIS)
X4 will present three posters at the CIS 2022 Annual Meeting: Immune Deficiency and Dysregulation North American Conference, March 31 – April 3, 2022:
•PATH4WARD: A Genetic Testing Program to Aid in Molecular Diagnosis of Congenital Neutropenia and Other Primary Immunodeficiencies Including WHIM Syndrome.
•Characterization of CXCR4(S341Y) Variant of Uncertain Significance in the Setting of Infections, Hypogammaglobulinemia, and Warts.
•4WHIM: Evaluating the Oral CXCR4 Antagonist Mavorixafor in Patients With WHIM Syndrome via a Global Phase 3, Randomized, Placebo-Controlled Trial With Open-label Extension.

American Association for Cancer Research (AACR) (Free AACR Whitepaper)
X4 will present emerging preclinical data on mavorixafor’s ability to significantly enhance the tumor cell killing activity of the leading commercial and clinical Bruton Tyrosine Kinase Inhibitors (BTKi) including

Exhibit 99.1
ibrutinib, zanubrutinib, pirtobrutinib (LOXO-305) and nemtabrutinib (ARQ-531), at the 2022 AACR (Free AACR Whitepaper) Annual Meeting, taking place April 8 – 13, 2022.
•e-Poster #6093: Mavorixafor Enhances Efficacy of Bruton Tyrosine Kinase Inhibitors by Overcoming the Protective Effect of Bone Marrow Stroma on Tumor Cells in Waldenström’s Macroglobulinemia.
Session: OPO.TB06.01 – Tumor Microenvironment
E-posters are expected to be released at 12:00 PM CT on Friday, April 8.

Fourth Quarter and Full Year 2021 Financial Results
•Cash, Cash Equivalents & Restricted Cash: X4 had $83.1 million in cash, cash equivalents, and restricted cash as of December 31, 2021. The company expects that its cash and cash equivalents will fund company operations into the fourth quarter of 2022.
•Research and Development (R&D) Expenses were $12.2 million and $50.6 million for the fourth quarter and full year ended December 31, 2021, as compared to $12.3 million and $41.9 million for the comparable periods in 2020. R&D expenses include $0.7 million and $2.7 million of certain non-cash expenses for the quarter and full year ended December 31, 2021, respectively.
•General and Administrative Expenses (G&A) were $7.1 million and $24.7 million for the fourth quarter and full year ended December 31, 2021, as compared to $5.4 million and $20.9 million for the comparable periods in 2020. G&A expenses include $0.9 million and $3.5 million of certain non-cash expenses for the quarter and full year ended December 31, 2021, respectively.
•Net Loss: X4 reported a net loss of $30.2 million and $88.7 million for the quarter and full year ended December 31, 2021, as compared to a net loss of $18.4 million and $62.1 million for the comparable periods in 2020. Net loss for the current quarter and full year period includes a non-cash goodwill impairment charge of $9.8 million. There was no goodwill impairment charge in the prior year periods. Net losses include $1.6 million and $6.2 million of stock-based compensation expense for the quarter and full year ended December 31, 2021, respectively. Net losses included $1.4 million and $5.4 million of stock-based compensation expense for the quarter and full year ended December 31, 2020, respectively.

Conference Call and Webcast
X4 will host a conference call and webcast today at 8:30 am EDT to discuss financial results and business highlights. The conference call can be accessed by dialing (866) 721-7655 from the United States or (409) 216-0009 internationally, followed by the conference ID: 9772687. The live webcast can be accessed on the investor relations section of X4 Pharmaceuticals’ website at www.x4pharma.com. Following the completion of the call, a webcast replay of the conference call will be available on the website.