Neutropenia, Severe Congenital, Autosomal Recessive 3

Treatment with a molecule known as A485 can quickly and temporarily increase levels of white blood cells, a critical part of the body's immune system, an effect that is difficult to deliver with currently available pharmaceuticals, a new Yale study finds. In an experiment, the researchers found that exposure to the molecule in mice caused white blood cells to mobilize from the bone marrow, a response that could inform future treatment for patients who need a boost in immune activity, the researchers say. The findings were reported Jan. 31 in the journal Immunity. Treatment with a molecule known as A485 can quickly and temporarily increase levels of white blood cells, a critical part of the body's immune system, an effect that is difficult to deliver with currently available pharmaceuticals, a new Yale study finds. In an experiment, the researchers found that exposure to the molecule in mice caused white blood cells to mobilize from the bone marrow, a response that could inform future treatment for patients who need a boost in immune activity, the researchers say. The findings were reported Jan. 31 in the journal Immunity. There are certain conditions in which individuals may be affected by low white blood cell counts. These include genetic conditions -- such as severe congenital neutropenia, a rare disease in children who are prone to repeated infections due to low levels of white blood cells called neutrophils -- and acquired conditions, such as reduced white blood cell counts following chemotherapy treatment. Then there are diseases like leukemia where white blood cell levels are too high. However, there are few pharmacological options for adjusting white blood cells counts in patients with abnormal levels. For the new study, researchers observed the effect A485 had on blood cells in mice. The molecule, which the researchers have proposed calling "prohiberin," inhibits proteins that modulate gene expression, essentially turning genes on or off. "We found that this molecule, A485, provoked a strong increase in white blood cells, including those involved in both the adaptive and innate immune systems," said Nikolai Jaschke, lead author of the study and a postdoctoral fellow in the lab of Andrew Wang, associate professor of internal medicine (rheumatology) and of immunobiology at Yale School of Medicine. This increase in white blood cells, deployed from the animals' bone marrow, occurred shortly after exposure to A485. About 12 hours later, the researchers said, cell counts dropped back to previous levels. This short-term effect is key, said Jaschke. "Currently, the main treatment for low white blood cell counts is G-CSF, or granulocyte colony-stimulating factor, which is produced by the body and can be administered as a drug," said Jaschke. "But it has a long-lasting effect, which can be harmful in some circumstances, limiting its wider clinical use. A485 is just as potent as G-CSF but less enduring." To see if this brief increase in white blood cells might be effective in treating infection, the researchers gave A485 to mice that had received chemotherapy -- and, therefore, had damaged bone marrow -- and had also been infected by the bacteria listeria. Even with damaged bone marrow, mice that received A485 survived at higher rates than those that did not, as they were able to clear the bacteria more effectively. This finding is especially important in the context of cancer treatment, said the researchers. "When patients develop low white blood cell counts after chemotherapy, a condition called neutropenic fever, antibiotics are the only approved therapy," said Jaschke. "A485 could be another option." Going forward, Jaschke noted, studies should test A485 against other infections, as listeria is not the most common pathogen patients tend to encounter when immunocompromised. Additionally, more research needs to be done to better understand how A485 has the effect that it does. But the current study offers some clues. Jaschke and his colleagues found that A485 works, in part, through endogenous G-CSF, which is a protein that stimulates the bone marrow to make more blood cells. They also found that combining G-CSF and A485 produced an additive effect on white blood cell mobilization that could be beneficial as a treatment. Further, the study revealed that A485 activates what's known as the body's "stress axis," engaging a hormone that, until now, was believed to only regulate levels of another hormone, cortisol. "But we found that this hormone can regulate neutrophils, which opens up a whole new field of questions," said Jaschke. "Along with A485 working through G-CSF, these findings mean there are pathways that mediate bone marrow mobilization that we don't even know about yet."

U.S. New Drug Application for mavorixafor in WHIM syndrome accepted for Priority Review, establishing a PDUFA target action date of April 30, 2024; X4 eligible to receive Priority Review Voucher if approved Presentations of additional data from ongoing Phase 2 clinical trial of mavorixafor in chronic neutropenia expected in 4Q 2023 and 1H 2024 Pivotal, global Phase 3 trial of mavorixafor in chronic neutropenia expected to initiate in 1H 2024 Conference call to be hosted today at 8:30 a.m. ET BOSTON, Nov. 09, 2023 (GLOBE NEWSWIRE) -- X4 Pharmaceuticals (Nasdaq: XFOR), a company driven to improve the lives of people with rare diseases of the immune system, today reported financial results for the third quarter ended September 30, 2023 and highlighted key recent and upcoming expected milestones. “We could not be more pleased with the significant milestones we’ve achieved in the clinical development of mavorixafor this year,” said Paula Ragan, Ph.D., President and Chief Executive Officer of X4 Pharmaceuticals. “Following the recent FDA acceptance of our New Drug Application seeking approval of mavorixafor for the treatment of WHIM syndrome, we are now preparing for a possible U.S. launch in the second quarter of 2024. With key learnings gleaned from our ongoing Phase 2 trial in chronic neutropenia and input from the FDA, we have now finalized the design of our planned pivotal, global Phase 3 trial evaluating mavorixafor in certain chronic neutropenic disorders and expect to initiate in the first half of 2024.” Recent and Key Anticipated Milestones Advancing Mavorixafor in WHIM Syndrome: In late October 2023, the United States Food and Drug Administration (FDA) accepted for filing X4’s New Drug Application (NDA) for once-daily, oral mavorixafor to treat individuals aged 12 and older with WHIM (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis) syndrome, a rare, primary immunodeficiency. The FDA granted Priority Review of the mavorixafor NDA, establishing a goal of six months review from the date of acceptance and assigning a Prescription Drug User Fee Act (PDUFA) target action date of April 30, 2024. The FDA has notified X4 that it does not currently plan to hold an advisory committee meeting to review the filing.Due to mavorixafor’s Rare Pediatric Disease designation for WHIM syndrome in the U.S., X4 is eligible to receive a Priority Review Voucher (PRV) that can be used to obtain priority review for a subsequent application or can be sold to another drug sponsor, should mavorixafor be approved by the FDA for WHIM syndrome.In anticipation of a potential second quarter 2024 U.S. launch of mavorixafor in WHIM syndrome, X4 has continued to build out its go-to market organization, with key hires across commercial and medical functions, increased interactions with key stakeholders and rare disease patient advocacy organizations, and has launched a disease-awareness campaign called What If It’s WHIM? aimed at furthering the understanding of WHIM syndrome and educating patients and physicians on the importance and benefits of early diagnosis. Advancing Mavorixafor in Chronic Neutropenic Disorders: Following an earlier presentation of preliminary data from the first 3 participants in the company’s ongoing Phase 2 trial evaluating the safety and efficacy of mavorixafor in certain chronic neutropenic disorders, the company anticipates presenting additional longer-term treatment data on these participants in a poster session at the upcoming 65th Annual Meeting of the American Society of Hematology (ASH), taking place December 9-12, 2023 in San Diego, CA.In addition, X4 plans to present efficacy and safety data from at least 15 of the currently enrolled participants in the Phase 2 chronic neutropenia trial during the first half of 2024.The design of a planned pivotal, global Phase 3 clinical trial evaluating the safety and efficacy of mavorixafor in the treatment of people 12 years and older with idiopathic or congenital neutropenia is now complete and incorporates FDA input. X4 anticipates initiation of this Phase 3 trial in the first half of 2024. Other Recent Corporate Highlights: Management Team Strengthened with Addition of New Chief Medical Officer: In August 2023, X4 announced the appointment of Christophe Arbet-Engels, MD, PhD, as its new Chief Medical Officer. Dr. Arbet-Engels brings more than 25 years of experience to the company in strategic global drug discovery, development, and commercialization, as well as expertise in rare and orphan diseases.Completed a $115 million Debt Facility with Hercules Capital: In August 2023, X4 announced an expanded $115 million debt facility with Hercules Capital, with an initial drawdown of $22.5 million at closing.Expanded Company Board of Directors: In October 2023, X4 announced the addition of industry veteran R. Keith Woods to its Board of Directors bringing significant sales and commercial strategy experience most recently at argenx, where he helped build a global enterprise focused on developing treatments for rare autoimmune diseases and successfully launch the company’s flagship product, Vyvgart®. Third-Quarter 2023 Results Cash, Cash Equivalents, Restricted Cash, and Short-Term Marketable Securities: X4 had $142.7 million in cash, cash equivalents, restricted cash, and marketable securities as of September 30, 2023. X4 believes it has sufficient funds to support company operations into 2025 and notes that this projected runway does not include additional potential drawdowns from its debt facility nor the potential monetization of a Priority Review Voucher the company would expect to receive should mavorixafor be approved for WHIM syndrome in the U.S.Research and Development (R&D) Expenses were $19.1 million for the third quarter ended September 30, 2023 as compared to $14.1 million for the comparable period in 2022. R&D expenses for the third quarter ended September 30, 2023 included $1.3 million of certain non-cash expenses.Selling, General, and Administrative Expenses (SG&A) were $8.1 million for the third quarter ended September 30, 2023 as compared to $6.0 million for the comparable period in 2022. SG&A expenses for the third quarter ended September 30, 2023 included $1.1 million of certain non-cash expenses.Net Loss: X4 reported a net loss of $2.3 million for the third quarter ended September 30, 2023, as compared to $21.6 million for the comparable period in 2022. Net losses in the current period include a non-cash gain of $25.2 million related to the company’s Class C warrant liability, which is adjusted to fair value each reporting period. Net losses also included $2.4 million of stock-based compensation expense. Conference Call and Webcast The company will host a conference call and webcast today at 8:30 a.m. ET. The conference call can be accessed by dialing 1-877-451-6152 from the United States or 1-201-389-0879 internationally, followed by the conference ID: 13741400. The live webcast will be accessible through the investor relations section of X4 Pharmaceuticals’ website at www.x4pharma.com. Following the completion of the call, a webcast replay will be available on the website. About X4 Pharmaceuticals X4 Pharmaceuticals is a late-stage clinical biopharmaceutical company driven to improve the lives of people with rare diseases of the immune system. Our lead clinical candidate is mavorixafor, a small molecule antagonist of chemokine receptor CXCR4 that is being developed as an oral, once-daily therapy across a variety of immunodeficiencies, including WHIM (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis) syndrome and certain chronic neutropenic disorders. Following successful completion of a global, pivotal, Phase 3 clinical trial, we are seeking U.S. regulatory approval of oral, once-daily mavorixafor for the treatment of people aged 12 years and older with WHIM syndrome. We are also currently planning a Phase 3 clinical program evaluating mavorixafor in certain chronic neutropenic disorders. We continue to leverage our insights into CXCR4 and immune system biology at our corporate headquarters in Boston, Massachusetts and at our research center of excellence in Vienna, Austria. For more information, please visit our website at www.x4pharma.com. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of applicable securities laws, including the Private Securities Litigation Reform Act of 1995, as amended. These statements may be identified by the words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target,” or other similar terms or expressions that concern X4's expectations, strategy, plans, or intentions. Forward-looking statements include, without limitation, statements regarding the timing and potential impact of FDA acceptance and priority review of X4’s NDA for mavorixafor for the treatment of individuals with WHIM syndrome; the commercial launch of mavorixafor, if approved; the clinical development and therapeutic potential of mavorixafor for the treatment of WHIM syndrome, chronic neutropenic disorders, and other potential indications; expectations regarding timing for reporting data from ongoing clinical studies or the initiation of future clinical trials, including the timing of reporting additional data from X4’s ongoing Phase 2 trial of mavorixafor in certain chronic neutropenic disorders and the timing of commencing a Phase 3 trial; expectations regarding the commercial potential of mavorixafor; and X4’s financial position, potential cash runway, and ability to execute on the next phase of its strategy. Any forward-looking statements in this press release are based on management's current expectations and beliefs. Actual events or results may differ materially from those expressed or implied by any forward-looking statements contained herein, including, without limitation, risks of obtaining and maintaining regulatory approvals, including, but not limited to, potential regulatory delays or rejections or the risk that the FDA will require additional trials or data; uncertainties inherent in the initiation and completion of clinical trials and clinical development; the risk that trials and studies may not have satisfactory outcomes; the risk that the outcomes of earlier clinical trials will not be predictive of later clinical trial results; the risks related to X4’s ability to raise additional capital; the impacts of general macroeconomic and geopolitical conditions, rising inflation, and uncertain credit and financial markets on X4’s business, clinical trials, and financial position; and other risks and uncertainties, including those described in the section entitled “Risk Factors” in X4’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on August 10, 2023, and in other filings X4 makes with the SEC from time to time. X4 undertakes no obligation to update the information contained in this press release to reflect new events or circumstances, except as required by law. X4 PHARMACEUTICALS, INC. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS(in thousands, except per share amounts)(unaudited) Three Months Ended Nine Months Ended September 30, September 30, 2023 2022 2023 2022 Operating expenses: Research and development$19,081 $14,110 $56,745 $42,044 Selling, general and administrative 8,133 6,044 25,578 20,457 Gain on sale of non-financial asset — — — (509)Total operating expenses 27,214 20,154 82,323 61,992 Loss from operations (27,214) (20,154) (82,323) (61,992)Other expense, net 24,935 (1,445) 331 (2,757)Loss before provision for income taxes (2,279) (21,599) (81,992) (64,749)Provision for income taxes 26 (13) 45 14 Net loss (2,305) (21,586) (82,037) (64,763)Deemed dividend due to Class B warrant price reset — (287) — (2,546)Net loss attributable to common stockholders$(2,305) $(21,873) $(82,037) $(67,309)Net loss per share attributable to common stockholders- basic and diluted$(0.01) $(0.26) $(0.48) $(1.32)Weighted average common shares outstanding-basic and diluted 196,988 83,211 170,751 50,976 X4 PHARMACEUTICALS, INC. CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS(in thousands)(unaudited) Nine Months Ended September 30, 2023 2022 Net loss$(82,037) $(64,763)Adjustments to reconcile net loss to net cash used in operating activities 7,570 6,493 Changes in operating assets and liabilities 5,702 261 Net cash used in operating activities (68,765) (58,009)Net cash used in investing activities (10,050) (69)Net cash provided by financing activities 88,419 56,586 Impact of foreign exchange on cash, cash equivalents and restricted cash (28) (468)Net increase (decrease) in cash, cash equivalents and restricted cash 9,576 (1,960)Cash, cash equivalents and restricted cash at beginning of period 123,028 83,108 Cash, cash equivalents and restricted cash at end of period$132,604 $81,148 X4 PHARMACEUTICALS, INC. CONDENSED CONSOLIDATED BALANCE SHEETS(in thousands)(unaudited) September 30, 2023 December 31, 2022Current assets: Cash and cash equivalents$131,581 $121,718Marketable securities 10,102 —Research and development incentive receivable 393 1,152Prepaid expenses and other current assets 5,796 5,807Total current assets 147,872 128,677Property and equipment, net 772 1,104Goodwill 17,351 17,351Right-of-use assets 6,054 7,229Other assets 1,244 1,225Total assets$173,293 $155,586Current liabilities: Accounts payable$8,132 $7,777Accrued expenses 16,184 12,034Current portion of lease liability 1,116 1,198Current portion of long-term debt — 1,315Total current liabilities 25,432 22,324Long-term debt, including accretion, net of discount 54,322 32,304Lease liabilities 2,848 3,603Warrant liability 22,014 23,131Other liabilities 1,083 173Total liabilities 105,699 81,535Total stockholders' equity 67,594 74,051Total liabilities and stockholders' equity$173,293 $155,586 Contacts:Daniel Ferry (investors)Managing Director, LifeSci Advisorsdaniel@lifesciadvisors.com (617) 430-7576 Brett Whelan (media)LifeSci Communicationsbwhelan@lifescicomms.com

BOSTON, July 01, 2022 (GLOBE NEWSWIRE) -- X4 Pharmaceuticals, Inc. (Nasdaq: XFOR), a leader in the discovery and development of novel CXCR4-targeted small molecule therapeutics to benefit patients with diseases of the immune system, today announced that, on June 30, 2022 the Compensation Committee of X4’s Board of Directors issued inducement awards to new employees under the X4 Pharmaceuticals, Inc. 2019 Inducement Equity Incentive Plan (the “2019 Inducement Plan”). The 2019 Inducement Plan is used exclusively for the grant of equity awards to individuals who were not previously an employee of X4. The inducement awards consist of options to purchase an aggregate of 21,000 shares of X4’s common stock. These stock awards were granted as an inducement material to the new employees entering into employment with X4 in accordance with Nasdaq Listing Rule 5635(c)(4). The options have a ten-year term and an exercise price of $0.96 per share, which is equal to the closing price of X4’s common stock on June 30, 2022. Each option will vest over a four-year period, with 25% of the shares vesting after 12 months and the remaining shares vesting monthly over the following 36 months, subject to the employee’s continued employment with X4 on such vesting dates. The options are subject to the terms and conditions of the 2019 Inducement Plan and the terms and conditions of an award agreement covering the grant. About X4 Pharmaceuticals, Inc. X4 Pharmaceuticals is a late-stage clinical biopharmaceutical company leading the discovery and development of novel therapies for people with immune system dysfunction. The company’s lead candidate is mavorixafor, a first-in-class, small molecule antagonist of chemokine receptor CXCR4 that is being developed as a once-daily oral therapy. Due to mavorixafor’s ability to antagonize CXCR4 and improve the healthy maturation and trafficking of white blood cells, X4 believes that mavorixafor has the potential to provide therapeutic benefit across a wide variety of diseases, including primary immunodeficiencies (PIDs) and certain types of cancer. Mavorixafor has already demonstrated clinical potential in a Phase 2 trial in people with WHIM syndrome, a rare PID. Its efficacy and safety continue to be evaluated in a global Phase 3 clinical trial in WHIM (fully enrolled) and in two Phase 1b clinical trials – one, as monotherapy in people with Severe Congenital Neutropenia (SCN) and other chronic neutropenia conditions, and another in combination with ibrutinib in people with Waldenström’s macroglobulinemia, a rare B-cell lymphoma. X4 is continuing to leverage its insights into CXCR4 biology at its corporate headquarters in Boston, Massachusetts and at its research facility in Vienna, Austria, to discover and develop additional product candidates. For more information, please visit Investors and Media: Daniel Ferry Managing Director LifeSci Advisors daniel@lifesciadvisors.com (617) 430-7576 Mónica Rouco Molina Senior Account Executive LifeSci Communications mroucomolina@lifescicomms.com