Summary of X4 Pharmaceuticals FY Conference Call Company Overview - **Company**: X4 Pharmaceuticals (NasdaqCM:XFOR) - **Focus**: Specializes in rare hematology diseases, particularly chronic neutropenia and WHIM syndrome [4][5] Key Points Management Transition - New management team joined X4 Pharmaceuticals three months prior, focusing on restructuring and financing [2] - Raised nearly $240 million to fund the phase 3 trial for chronic neutropenia [2] Lead Compound: Mavorixafor - **Indications**: Approved for WHIM syndrome, now targeting chronic neutropenia [9] - **Mechanism of Action**: Antagonizes CXCR4, facilitating the release of neutrophils from bone marrow into the bloodstream [7] - **Administration**: Oral agent, providing a competitive advantage over G-CSF, which requires injections and can cause discomfort [8] Market Opportunity - Estimated patient population for chronic neutropenia is approximately 15,000, significantly larger than the WHIM indication [5][12] - Current management of chronic neutropenia is inconsistent, with 40-45% of patients receiving G-CSF and 60% managed through other means [10][11] Clinical Trials - **Phase 2 Study**: Demonstrated that mavorixafor can increase ANC levels and can be safely combined with G-CSF [13][14] - **Phase 3 Study**: Double-blinded, placebo-controlled trial with 176 patients, focusing on ANC increase and reduction in infection rates [17][20] - Expected to complete enrollment by Q3 2026, with top-line data anticipated in the second half of 2027 [25] Competitive Landscape - Main competitor is G-CSF; no direct oral competitors currently exist [28] - Focus on generating combination data with G-CSF in the ongoing study [28] Commercialization Strategy - Plans to target a similar prescriber base as previous experiences with CTI and Bendeka [27] - Anticipates a premium pricing environment typical for rare diseases, though specific pricing strategies are still under development [27] Future Milestones - Completion of patient enrollment in the phase 3 trial is a critical upcoming milestone [29] - Ongoing efforts to better communicate market opportunities to investors [29] Collaborations - Strong relationship with Norjin for European rights, while focusing on the US market for commercialization [31] Additional Insights - The WHIM data collected from previous trials is being used to inform assumptions for the larger chronic neutropenia trial [9] - The company is restructuring to enhance trial enrollment efforts, particularly in the US [23][24]

Core Insights - X4 Pharmaceuticals will participate in the Guggenheim Second Annual Healthcare Innovation Conference from November 10-12, 2025, in Boston [1] - The management team will hold a fireside chat on November 10th at 8:30 a.m. ET and will be available for one-on-one meetings with investors [1] - A webcast of the fireside chat will be available on the company's website, with a replay accessible for 30 days post-event [2] Company Overview - X4 Pharmaceuticals focuses on developing and commercializing innovative therapies for patients with rare hematology diseases and significant unmet needs [3] - The company has developed mavorixafor, an orally available CXCR4 antagonist, currently marketed in the U.S. as XOLREMDI for its first indication [3] - X4 is conducting a global pivotal Phase 3 clinical trial (4WARD) for mavorixafor in patients with certain chronic neutropenic disorders [3]

Core Viewpoint - X4 Pharmaceuticals has successfully closed a public offering of 52,844,000 shares, raising approximately $155.3 million to support its operations and development of therapies for rare hematology diseases [1][2]. Group 1: Offering Details - The public offering price was set at $2.90 per share, with an additional option for underwriters to purchase up to 6,984,000 shares [1]. - Pre-funded warrants were also offered at a price of $2.899, allowing the purchase of up to 700,000 shares at an exercise price of $0.001 per share [1]. - After the offering, the total shares outstanding increased to 79,214,708 [1]. Group 2: Underwriters and Registration - Leerink Partners, Stifel, and Guggenheim Securities served as joint bookrunning managers for the offering [2]. - A shelf registration statement for these securities was filed with the SEC on August 14, 2023, and became effective on August 24, 2023 [3]. Group 3: Company Overview - X4 Pharmaceuticals focuses on developing innovative therapies for patients with rare hematology diseases, particularly through its CXCR4 antagonist, mavorixafor [5]. - The company is currently marketing mavorixafor in the U.S. under the brand name XOLREMDI® and is conducting a pivotal Phase 3 clinical trial for chronic neutropenic disorders [5].

Core Viewpoint - X4 Pharmaceuticals has announced a public offering of 45,860,000 shares of common stock priced at $2.90 per share, aiming to raise approximately $135 million to fund the development of its drug mavorixafor and for general corporate purposes [1][2]. Group 1: Offering Details - The public offering includes pre-funded warrants for up to 700,000 shares at a price of $2.899 each, with an exercise price of $0.001 per share [1]. - The offering is expected to close on October 27, 2025, pending customary closing conditions [1]. - Underwriters have a 30-day option to purchase an additional 6,984,000 shares at the public offering price [1]. Group 2: Use of Proceeds - The net proceeds from the offering will be used to fund the pivotal Phase 3 development of mavorixafor for chronic neutropenic disorders, along with general administrative expenses, capital expenditures, and working capital [2]. Group 3: Company Background - X4 Pharmaceuticals focuses on developing therapies for rare hematology diseases, with mavorixafor being an orally available CXCR4 antagonist currently marketed in the U.S. as XOLREMDI® [5]. - The company is conducting a global Phase 3 clinical trial (4WARD) for mavorixafor in patients with chronic neutropenic disorders [5].

Core Viewpoint - X4 Pharmaceuticals successfully closed an upsized private placement, raising $85 million to support the development of therapies for rare immune diseases, particularly focusing on mavorixafor for chronic neutropenia and WHIM commercialization [1][2]. Group 1: Financing Details - The private placement included 11,040,776 shares of common stock and pre-funded warrants for 48,852,772 shares, increasing from an initially announced $60 million offering to accommodate an additional investor [1]. - The offering was led by Coastlands Capital, with participation from notable investors such as Empery Asset Management, Bain Capital Life Sciences, and New Enterprise Associates [1]. Group 2: Use of Proceeds - The net proceeds from the financing will be utilized for the continued development of mavorixafor, aiming for additional approval in chronic neutropenia and supporting the commercialization of WHIM [2]. Group 3: Company Overview - X4 Pharmaceuticals focuses on developing innovative therapies for rare immune diseases, leveraging expertise in CXCR4 biology [4]. - The company has successfully marketed mavorixafor in the U.S. under the name XOLREMDI and is conducting a pivotal Phase 3 clinical trial (4WARD) for chronic neutropenic disorders [4].

Core Viewpoint - X4 Pharmaceuticals has announced a $60 million PIPE financing led by Coastlands Capital, with a new management team appointed to enhance the company's strategic direction and operational capabilities in the life sciences sector [1][2][3]. Financing Details - The PIPE financing is expected to yield gross proceeds of approximately $60 million, with the closing anticipated around August 13, 2025, subject to customary conditions [1]. - X4 will issue 11,040,776 shares of common stock at a purchase price of $1.42 per share, or pre-funded warrants for up to 31,234,731 shares at $1.419 each [5]. - The net proceeds will be utilized for the continued development of mavorixafor for chronic neutropenia and the commercialization of WHIM [6]. Management Changes - Paula Ragan, PhD, and Adam Mostafa have stepped down from their roles as President and CFO, respectively, with Dr. Adam Craig appointed as Executive Chairman, John Volpone as President, and David Kirske as CFO [2][7]. - The new management team brings extensive experience from CTI BioPharma, with a focus on operational turnarounds and strategic leadership in life sciences [2][7][8]. Strategic Focus - Dr. Adam Craig expressed enthusiasm for establishing a leading hematology company by unlocking the commercial potential of mavorixafor, with a clear pathway for potential approval in treating chronic neutropenia [3]. - The company is currently conducting a pivotal Phase 3 clinical trial (4WARD) for mavorixafor, which is crucial for its future growth and market positioning [3][10].

Core Insights - X4 Pharmaceuticals presented positive data from its Phase 2 trial of mavorixafor for chronic neutropenia at the European Hematology Association Congress, indicating significant increases in circulating neutrophils and the potential to reduce G-CSF usage [1][2][3] Group 1: Clinical Trial Results - The Phase 2 trial was a six-month open-label study involving 23 participants with chronic neutropenia, assessing mavorixafor as a monotherapy and in combination with G-CSF [2][7] - Results showed that mavorixafor monotherapy durably increased mean absolute neutrophil count (ANC) from baseline, with severe chronic neutropenia patients achieving nearly three-fold increases in ANC levels [4][11] - 89% of participants and investigators opted to reduce or discontinue G-CSF while maintaining normal ANC levels, suggesting a potential transition to mavorixafor as an oral treatment option [4][11] Group 2: Ongoing and Future Trials - X4 is conducting a pivotal Phase 3 trial (4WARD) to evaluate mavorixafor's efficacy and safety in chronic neutropenia, aiming to enroll 150 participants and assess annualized infection rates and ANC response over 52 weeks [5][8] - The Phase 3 trial is expected to fully enroll in the third or fourth quarter of 2025, building on the encouraging Phase 2 results [2][5] Group 3: Mechanism and Background - Chronic neutropenia is characterized by low neutrophil levels, increasing infection risk and reducing quality of life; mavorixafor acts as a CXCR4 antagonist, mobilizing neutrophils from the bone marrow [6][9] - The Phase 1b/Phase 2 trial was designed to assess the safety and tolerability of mavorixafor, with the Phase 2 portion focusing on its impact on neutropenia over six months [7][8]

Core Viewpoint - X4 Pharmaceuticals has received Fast Track designation from the FDA for mavorixafor, an oral CXCR4 antagonist, aimed at treating chronic neutropenia (CN), highlighting the company's commitment to addressing unmet medical needs in rare diseases of the immune system [1][2]. Company Overview - X4 Pharmaceuticals focuses on developing innovative therapies for rare immune system diseases, with mavorixafor being a key product currently marketed in the U.S. as XOLREMDI [6]. - The company is headquartered in Boston, Massachusetts, and is leveraging its expertise in CXCR4 and immune system biology to advance its therapeutic offerings [6]. Product Development - Mavorixafor is undergoing a global pivotal Phase 3 clinical trial (4WARD) to evaluate its efficacy, safety, and tolerability in patients with chronic neutropenia [5]. - The trial aims to enroll 150 participants and has a primary endpoint based on annualized infection rate and positive absolute neutrophil count (ANC) response [5]. Regulatory Milestones - The FDA's Fast Track designation facilitates more frequent communication with the agency and may lead to accelerated approval or priority review if certain criteria are met [2][3]. - Mavorixafor previously received Fast Track designation for the treatment of WHIM syndrome, which was approved by the FDA in April 2024 [1][2]. Market Context - Currently, the only FDA-approved treatment for chronic neutropenia is injectable human recombinant granulocyte-colony stimulating factor (G-CSF), which has significant side effects and risks associated with long-term use [2]. - Mavorixafor is positioned to offer a better balance of disease control and treatment burden compared to G-CSF, potentially benefiting patients with certain primary CN conditions [2].

Core Insights - X4 Pharmaceuticals announced the acceptance of two abstracts for presentation at the 30th Annual Congress of the European Hematology Association, highlighting positive results from a Phase 2 trial of mavorixafor for chronic neutropenia [1][2] - Mavorixafor is positioned as a potential first oral treatment for chronic neutropenia in over 30 years, with ongoing Phase 3 trials supporting its efficacy and safety [2][8] Company Overview - X4 Pharmaceuticals focuses on developing therapies for rare immune system diseases, with mavorixafor being a key product currently marketed in the U.S. as XOLREMDI® [9] - The company is headquartered in Boston, Massachusetts, and is actively pursuing additional indications for mavorixafor [9] Clinical Trial Details - The Phase 2 trial was a six-month open-label study involving 23 participants with various forms of chronic neutropenia, assessing the safety and efficacy of mavorixafor [3][7] - The ongoing pivotal Phase 3 trial, named 4WARD, aims to evaluate mavorixafor's efficacy and safety in a larger cohort of 150 participants with chronic neutropenia [8] Research Findings - The Phase 2 study demonstrated meaningful increases in functional neutrophils, with many participants able to reduce their G-CSF dosing when treated with mavorixafor [1][6] - Mavorixafor acts as a CXCR4 antagonist, mobilizing neutrophils from the bone marrow into the bloodstream, which is crucial for managing chronic neutropenia [5][6]

Financial Data and Key Metrics Changes - The company ended 2024 with just under $103 million in cash and cash equivalents, which is expected to support operations into the first half of 2026 [24] - Net revenues from XOLREMDI were reported at $1.4 million for the fourth quarter and $2.6 million for the full year 2024 [25] - R&D expenditures totaled $21.7 million for the fourth quarter and $81.6 million for the full year, while SG&A expenses were $15.1 million and $61.5 million respectively [25] - The net loss for the fourth quarter was $39.8 million, and for the full year, it was $37.5 million, reflecting a one-time sale of a priority review voucher for $105 million in May of the previous year [25][26] Business Line Data and Key Metrics Changes - XOLREMDI sales topped $2.5 million for the 7.5 months since its launch in mid-May 2024 [10] - The company has successfully engaged with top-tier immunologists and hematologists, which is expected to continue to increase patient finding and shorten the time to prescription [11] Market Data and Key Metrics Changes - The company has made significant progress in expanding the global reach of mavorixafor, with the EMA accepting the submitted MAA for review, potentially leading to approval as early as Q1 2026 [12] - The company entered into a partnership with Norgine for commercialization in Europe, Australia, and New Zealand, receiving EUR 28.5 million upfront and potential milestone payments of up to EUR 226 million [13] Company Strategy and Development Direction - The company aims to maximize the opportunity for mavorixafor in chronic neutropenia, which is viewed as a larger market opportunity [22] - A strategic restructuring is expected to decrease annual spending by about $30 million to $35 million, implemented to sharpen focus on chronic neutropenia [22] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the engagement with regulatory agencies, indicating a supportive environment for the trial design [32][34] - The company is focused on building awareness and education around WHIM syndrome and chronic neutropenia, with plans to pivot efforts towards the patient community [86] Other Important Information - The company has initiated a peer-to-peer speaker program to enhance physician education regarding WHIM syndrome [7] - The 4WARD trial for chronic neutropenia has been activated at about 90% of targeted sites worldwide, with expectations for full enrollment by Q3 or Q4 of this year [22] Q&A Session Summary Question: Regulatory conversation regarding ANC threshold - Management indicated that the FDA is supportive of the trial design focusing on moderate to severe patients, and the change in ANC threshold is not expected to impact trial pace [32][33] Question: Inventory and discounting trends - The company noted that inventory reflects stocking up in Q4, and there are no current trends in discounting as they have a tight distribution channel [43][49] Question: Patient numbers and price increase for XOLREMDI - Management did not disclose patient numbers but confirmed a 7% price increase for the new year [54][56] Question: Commercialization experiences since launch - The company has successfully engaged physicians and identified additional patients, with ongoing efforts to build demand through conferences and education [70][71] Question: Expected patient numbers for WHIM and CN - Management reiterated the guidance of approximately 1,000 diagnosed WHIM patients in the U.S. and about 50,000 total chronic neutropenia patients, targeting the refractory severe end of that population [78]