X4 Pharmaceuticals Announces Presentation of Positive Data – About Your Online Magazine

Robust reductions in serum IgM at low and medium doses suggest the best-in-class potential for
therapy with mavorixafor plus ibrutinib in patients with double Waldenström mutation;
increases in hemoglobin levels suggest a reduction in the burden of cancer in the bone marrow

At 6 months, patients had achieved mean IgM level reductions of 60%-75%, with
one patient achieved normal IgM and two out of four patients (50%) had >50% reduction
in baseline IgM

e-Poster now available online; pre-recorded presentation by lead author, Dr. Steven Treon
available to EHA conference attendees

Conference call and webcast today at 7:00 am EDT with X4 management and
poster co-author Dr. Christian Buske

BOSTON, June 11, 2021 (GLOBE NEWSWIRE) – X4 Pharmaceuticals, Inc. (Nasdaq: XFOR), a leader in the discovery and development of new targeted therapies for diseases resulting from CXCR4 pathway dysfunction, today announced positive preliminary efficacy and safety data from its ongoing Phase 1b clinical trial of its lead candidate mavorixafor in combination with ibrutinib, in patients with Waldenström’s macroglobulinemia with MYD88 and CXCR4 mutations. These data are included in a poster published today at the Annual Congress of the European Hematology Association (EHA).

“We are delighted to present this exciting first look at data from our ongoing Phase 1b study in Waldenström’s dual mutation patients,” said Diego Cadavid, M.D., Medical Director, X4 Pharmaceuticals. “Although we are still in the low and mid-dose ranges of mavorixafor, we are already seeing robust reductions in IgM levels – an important sign of clinical response – showing the potential benefit of mavorixafor in combination with ibrutinib. Combination therapy is demonstrating good tolerability and promising results in additional pharmacodynamic parameters, including increases in total hemoglobin and leukocyte mobilization. We expect to present long-term data and an expanded dataset from this trial by the end of the year. ”

“Although ibrutinib has significantly advanced in the treatment of Waldenström’s macroglobulinemia, we note that there remains an unmet clinical need for patients with concurrent CXCR4 and MYD88 mutations,” said Steven Treon, MD, Ph.D., FACP, FRCP, Director of Bing Center for Waldenström’s Macroglobulinemia at the Dana-Farber Cancer Institute, Professor of Medicine at Harvard Medical School and lead author of the poster. “I am encouraged by the preliminary safety and efficacy data from the ongoing combination trial of ibrutinib and mavorixafor in this difficult-to-treat patient population and look forward to continuing this important research.”

Key highlights of low and medium dose phase 1b preliminary results

  • As of April 15, 2021, 8 patients had been enrolled in the Phase 1b clinical trial with a mean treatment duration of 156 days; the data presented are mainly from patients in Cohort A who received low and medium doses of mavorixafor plus ibrutinib; 4 patients were treated for more than six 28-day cycles.
  • Mavorixa for monitored exposures with sustained and dose-dependent increases in WBC counts, confirming target involvement and mavorixa for mechanism of action.
  • All patients (100%) experienced reductions in serum IgM and none of the patients’ disease progressed during treatment.
  • At 6 months, mavorixafor plus ibrutinib showed signs of significant reductions in IgM versus comparable, previously published data from ibrutinib monotherapy in dual mutation patients:
    • Patients achieved median reductions of 60%-75% in serum IgM levels normalized to baseline; this compares with published ibrutinib monotherapy reductions of 38%-45% in patients with double mutation.
    • 2 of 4 patients (50%) had >50% reduction in serum IgM from baseline; Comparable reductions were reported in only 28% -38% of double mutation patients on ibrutinib monotherapy.
    • One patient achieved IgM levels within the normal range, a key criterion for a complete response.
  • All patients with below-normal hemoglobin levels at baseline had increases during treatment, with a median change in hemoglobin of >20 g/L approaching normal levels and suggesting a reduction in the cancer burden in the bone marrow.
  • Exposures to Mavorixafor and ibrutinib were consistent with previous single-agent studies, suggesting that there are no drug interactions.
  • The data suggest that mavorixafor plus ibrutinib is well tolerated, with no serious adverse events reported.
  • Enrollment of patients and dose escalation to the highest dose of mavorixa for the dose (600 mg) continues.

The e-poster (EP784) titled: “Preliminary clinical data from a phase 1b study of Mavorixafor and Ibrutinib in patients with Waldenström’s macroglobulinemia with MYD88 and CXCR4 mutations” is now available on X4 corporate website. Conference attendees can access an audio presentation by Dr. Treon on Congress website.

The X4 will host a conference call and webcast at 7:00 am ET today that will include presentations from senior X4 executives and a “Fireside Chat” and Q&A with poster co-author Christian Buske, MD, Director of the Experimental Cancer Research Institute and Assistant Physician, Senior Consultant, University Hospital Ulm, and Founder and Coordinator of the Waldenström European Consortium for Macroglobulinemia.

Conference calling can be accessed by dialing (866) 721-7655 (domestic) or (409) 216-0009 (international), followed by the conference ID: 4492859. The live webcast will be accessible from the Events & Presentations page of the company’s website at investors.x4pharma.com. The conference call slideshow will be made available after the event concludes and the webcast replay will be available approximately two hours after the event concludes on the X4 website.

This Phase 1b clinical trial is being conducted with support from AbbVie Inc. and The Leukemia & Lymphoma Society’s Therapy Acceleration Program® (LLS TAP).

About Waldenström Macroglobulinemia and Associated CXCR4 Mutations
Waldenström’s macroglobulinemia is a rare B-cell lymphoproliferative disorder characterized by increased immunoglobulin M (IgM). More than 90% of patients with Waldenström have acquired mutations in the MYD88 gene, with a subset (30%-40%) also having mutations in the CXCR4 chemokine receptor. The presence of the CXCR4 mutation is associated with a higher cancer burden, higher serum IgM levels, and an increased risk of developing a serious, emerging condition called symptomatic hyperviscosity syndrome. Importantly, the presence of CXCR4 mutations has been shown to negatively impact patients’ response to ibrutinib (a BTK inhibitor), as manifested by delayed response, lower depth of response, and/or shorter progression-free survival.

About Mavorixafor and the Phase1b Clinical Trial in Waldenström’s Macroglobulinemia
Mavorixafor is an oral small molecule antagonist of the CXCR4 receptor with a demonstrated ability to inhibit the binding of its ligand, CXCL12; this inhibition of CXCR4 has been shown to sensitize Waldenström cells with the MYD88 and CXCR4 mutations to BTK antagonists such as ibrutinib. The ongoing Phase 1b, open, multicenter, single-arm study (NCT04274738) examines intra-patient dose escalation, safety, pharmacokinetics and pharmacodynamics of mavorixafor in combination with ibrutinib in patients diagnosed with Waldenström’s macroglobulinemia and confirmed MYD88 and CXCR4 gene mutations. In the study, patients are started on once-daily oral doses of ibrutinib 420 mg and mavorixa 200 mg (low dose); in Cohort A, patients are escalated to 400 mg mavorixafor (intermediate dose) after 28 days if fewer than two dose-limiting toxicities are seen at the low dose; in Cohort B, patients go from 200 mg to 400 mg and finally to 600 mg (high dose) after each dose level is considered tolerable. Patients are followed for adverse events and change from baseline in serum IgM and hemoglobin, pharmacokinetics, and pharmacodynamic markers, including peripheral white blood cell (white blood cell) counts.

About X4 Pharmaceuticals
X4 Pharmaceuticals is an advanced clinical biopharmaceutical company and a leader in the discovery and development of new therapies for the treatment of diseases resulting from CXCR4 pathway dysfunction, with a focus on rare diseases and those with limited treatment options. The company’s lead candidate, mavorixafor, is a first-in-class, small-molecule CXCR4 chemokine receptor antagonist, being developed as a once-daily oral therapy. X4 believes that inhibition of the CXCR4 receptor creates the potential for mavorixafor to provide therapeutic benefits in a wide variety of diseases, including primary immunodeficiencies and certain cancers. The efficacy and safety of once-daily mavorixafor is being evaluated in a global Phase 3 clinical trial in patients with WHIM syndrome and in two Phase 1b clinical trials – in combination with ibrutinib in patients with Waldenström’s macroglobulinemia and how monotherapy in patients with severe congenital neutropenia (SCN). X4 continues to leverage its knowledge of CXCR4 biology at its corporate headquarters in Boston, Massachusetts and at its research facilities in Vienna, Austria, and is discovering and developing additional candidate products. For more information please visit www.x4pharma.com.

Forward Looking Statements
This press release contains forward-looking statements as to the meaning of the Private Securities Litigation Reform Act of 1995, as amended. These statements can be identified by the words “may”, “will”, “could”, “would”, “should”, “expect”, “plan”, “anticipate”, “intend”, “believe”, “estimate, ”“Forecast”,“project”,“potential”,“continue”,“target”or other similar terms or expressions that relate to the expectations, strategy, plans or intentions of X4. Forward-looking statements include, without limitation, statements regarding the clinical development of mavorixafor for the treatment of Waldenström’s macroglobulinemia and primary immunodeficiencies, the potential benefits of mavorixafor in the treatment of Waldenström’s macroglobulinemia or any other indication, and the availability and timing of future data from the ongoing clinical trial of mavorixafor X4 for the treatment of Waldenström’s macroglobulinemia. Any forward-looking statements in this press release are based on management’s current expectations and beliefs. Actual events or results may differ m materially from those expressed or implied by any forward-looking statements contained herein, including, without limitation, the risk that trials and studies may be delayed ​​and may not have satisfactory results, the risk that initial or interim results of a trial The clinician may not anticipate the final trial results or the results of future trials, the potential adverse effects arising from the testing or use of mavorixafor or other candidate products, and other risks and uncertainties, including those described in the section entitled “Risk Factors” in the Report X4’s Quarterly on Form 10-Q filed with the Securities and Exchange Commission (SEC) on May 6, 2021, 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.

Investors and media:
Daniel Ferry
Managing Director
LifeSci Advisors
(617) 430-7576

Monica Rouco Molina
Senior Account Executive
LifeScience Communications

Paula Fonseca