On August 3, 2021 X4 Pharmaceuticals, Inc. (Nasdaq: XFOR), a leader in the discovery and development of novel therapies targeting diseases of the immune system resulting from dysfunction of the CXCR4 pathway, reported financial results for the second quarter and six months ended June 30, 2021 (Press release, X4 Pharmaceuticals, AUG 3, 2021, View Source [SID1234585702]). The company also announced key enrollment milestone achievements for its lead product candidate, mavorixafor, a novel, oral small molecule currently being evaluated in a Phase 3 clinical trial (4WHIM) for patients with WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome and in two Phase 1b clinical trials for patients with Waldenström’s macroglobulinemia and Severe Congenital Neutropenia (SCN) and chronic neutropenia disorders, respectively.

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"We are very encouraged by the strong interest from both the physicians and patients participating in our mavorixafor clinical programs," said Paula Ragan, Ph.D., President and Chief Executive Officer of X4 Pharmaceuticals. "With enrollment nearly complete in the 52-week placebo-controlled Phase 3 trial in WHIM syndrome, our initial indication for mavorixafor, and continued supportive data coming from our ongoing open-label Phase 2 trial in WHIM, we are starting to ramp up our pre-commercial planning, as we now look forward to Phase 3 top-line data in the fourth quarter of 2022. In addition, we are making strong progress in our ongoing Phase 1b clinical trial in Waldenström’s and intend to announce preliminary high-dose data along with certain response measures from this trial in the fourth quarter of 2021 that we believe will build on the low- and mid-dose data we presented at EHA (Free EHA Whitepaper) this past June. Lastly, as enrollment continues in our ongoing Phase 1b trial in SCN, from which we expect the first data in the fourth quarter of 2021, we are exploring the potential broader use of mavorixafor across the larger chronic neutropenia landscape. We look forward to reporting on our continued progress with mavorixafor, presenting additional clinical, pre-clinical and prevalence data, and providing a variety of company updates later this year."

Mavorixafor Clinical Trial Updates

Phase 3 Trial in WHIM Syndrome (4WHIM):
The company reported that it has surpassed the 18-patient minimum enrollment needed for primary endpoint analyses, determination of clinical benefit, and U.S. regulatory filing (if supported by the Phase 3 data), having enrolled 23 patients to date in its ongoing Phase 3 trial in WHIM syndrome. Enrollment will be completed in the third quarter of 2021, allowing the remaining identified patients to complete screening and potential enrollment. Top-line data are expected to be announced in the fourth quarter of 2022.
The 4WHIM Phase 3 trial is a global, randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the safety and efficacy of mavorixafor in 18-28 genetically confirmed WHIM patients over the course of a 52-week study with open-label extension. The primary endpoint for the trial will compare the level of circulating neutrophils relative to a clinically meaningful threshold in response to treatment with mavorixafor versus placebo over 24-hour periods. Secondary endpoints will assess infection rates, wart burden, markers of immune system function, and quality of life, among others.
The company is planning to announce new data from the open-label extension of its ongoing Phase 2 clinical trial, as well as an update on patient prevalence, and new data from research into the genetics of WHIM that will detail new insights into genotype/phenotype correlations and the identification of a new WHIM variant.
Phase 1b Trial in Waldenström’s Macroglobulinemia (WM):
The company also announced today that it has surpassed enrollment of the minimum 12 patients (Cohorts A and B) required to determine optimal dosing of mavorixafor in combination with ibrutinib in the ongoing Phase 1b clinical trial. The company is continuing enrollment in the optional Cohort C (up to an additional 6 patients).
This ongoing Phase 1b, open-label, multicenter, single-arm study examines intra-patient dose escalation, safety, pharmacokinetics (PK), and pharmacodynamics (PD) of mavorixafor (200 mg, 400 mg, and 600 mg) in combination with ibrutinib (420 mg), both delivered orally once daily, in patients with Waldenström’s macroglobulinemia and confirmed MYD88 and CXCR4 mutations. Patients are followed for adverse events and change from baseline in IgM and hemoglobin, PK, and PD (including peripheral white blood cell counts), in addition to clinical response.
The company remains on track to announce additional dosing, efficacy, safety, and clinical response data from the ongoing trial in the fourth quarter of 2021, including patient data at the highest planned mavorixafor dose of 600 mg.
Phase 1b Trial in Severe Congenital Neutropenia (SCN):
Enrollment continues in this clinical trial, with initial data anticipated in the fourth quarter of 2021. The company expects that the initial data from this trial, in combination with additional data emerging from prior and ongoing studies that show chronic, sustained white blood cell increases across a number of patient groups treated with mavorixafor, will support the company’s exploration of opportunities for mavorixafor use across larger chronic neutropenic populations and more broadly in cellular immunodeficiencies.
Second Quarter Highlights and Upcoming Events

EHA 2021: In June, the company announced the presentation of positive data from its ongoing Phase 1b clinical trial of mavorixafor in combination with ibrutinib in Waldenström’s macroglobulinemia. Data showed robust decreases in serum IgM at low- and mid-doses of mavorixafor, suggesting best-in-class potential for this combination treatment; meaningful increases in hemoglobin levels suggested reduction in cancer burden in the bone marrow; and at 6 months, patients achieved median IgM level reductions of 60%-75%, with one patient achieving normal IgM; two of four patients (50%) had >50% reduction in serum IgM from baseline. The poster is available here; slides from the company’s associated analyst event are available here.
X4 management will be participating in the following upcoming investor conferences:
Canaccord Genuity Growth Conference – taking place virtually August 10-12, 2021
Citi Annual BioPharma Conference– taking place virtually September 8-10, 2021
Oppenheimer Fall Healthcare Life Science & Med Tech Summit – taking place virtually September 20-23, 2021
Cantor Fitzgerald Healthcare Conference – taking place virtually September 27-30, 2021
Second Quarter 2021 Financial Results

Cash, Cash Equivalents & Restricted Cash: X4 had $96.5 million in cash, cash equivalents, and restricted cash as of June 30, 2021. The company expects that its cash and cash equivalents will fund company operations into the fourth quarter of 2022.
Research and Development Expenses were $13.2 million for the second quarter ended June 30, 2021, as compared to $9.3 million for the comparable period in 2020. R&D expenses include $0.8 million and $0.5 million of certain non-cash expenses for the quarters ended June 30, 2021 and 2020, respectively.
General and Administrative Expenses were $5.8 million for the second quarter ended June 30, 2021, as compared to $5.3 million for the comparable period in 2020. G&A expenses include $1.0 million and $0.7 million of certain non-cash expenses for the quarters ended June 30, 2021 and 2020, respectively.
Net Loss: X4 reported a net loss of $19.6 million for the quarter ended June 30, 2021, as compared to a net loss of $15.1 million for the comparable period in 2020. Net losses include $1.8 million and $1.2 million of certain non-cash expenses for the quarters ended June 30, 2021 and 2020, respectively.
Conference Call and Webcast
X4 will host a conference call and webcast today at 8:30 a.m. ET to discuss these 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: 2236266. 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 company website.