X4 Pharmaceuticals to Have Strong Presence at ASH 2021 with Seven Accepted Abstracts Highlighting New Clinical and Scientific Data; Company Reports Third Quarter Financial Results
Data continue to support mavorixafor’s potential to benefit patients with WHIM syndrome, chronic neutropenia, and Waldenström’s macroglobulinemia
Discovery of new prevalent WHIM variant further validates the company’s
Company to host an Investor Day on
Conference call today at
“This has been an amazing quarter of progress for all of us at X4, as we completed enrollment in the Phase 3 trial of mavorixafor in its first indication of WHIM syndrome and are now looking ahead to sharing a broad array of clinical and scientific data in the fourth quarter that further support the potential of mavorixafor across multiple additional therapeutic areas,” said
Key Takeaways from ASH Abstracts Published Today
WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome:
- Mavorixafor continues to show durable increases in neutrophils and lymphocytes, sustained improvements in infections and warts, and good tolerability in the ongoing Phase 2 open-label extension trial in WHIM syndrome.
- Patient interviews revealed that study participants experienced good tolerability and beneficial treatment effects when dosed with mavorixafor.
- Broader understanding of the clinical spectrum of WHIM syndrome and genotype/phenotype correlations have enabled assessment of novel CXCR4 variants for disease-correlation, including a newly discovered missense mutation (p.D84H) that is relatively frequent in the general population.
- The D84H mutation is the first mutation identified outside of the C-terminus of the CXCR4 receptor showing gain-of-function signaling and disease phenotype; the frequency of the D84H mutation derived from broad population genomic databases robustly supports current estimates of
U.S. WHIM prevalence of 1,000 to 3,500 or more. - This and other related research will be shared at the Investor Day on
December 16 .
- The D84H mutation is the first mutation identified outside of the C-terminus of the CXCR4 receptor showing gain-of-function signaling and disease phenotype; the frequency of the D84H mutation derived from broad population genomic databases robustly supports current estimates of
- Analyses of insurance claim databases using artificial intelligence indicate that the
U.S. population of WHIM patients may be much larger than currently reported in the literature.- Results showed that there may be as many as 3,700 WHIM patients based on WHIM-like phenotypes described.
- Data are consistent with novel genetic variant discoveries and genotype-phenotype correlations, building further confidence in estimates of potentially treatable WHIM patients in the
U.S.
- The company’s global Phase 3 clinical trial in WHIM syndrome (now fully enrolled) is the first double-blind, placebo-controlled, randomized trial in this patient population and the only one exploring an oral therapy. All enrolled patients had severe neutropenia and more than half are pediatric patients, illustrative of the severity and early onset of the disease. Top-line data from the trial are expected in the fourth quarter of 2022.
Chronic neutropenia and other indications:
- Mavorixafor alone or in combination with other therapies is the first oral treatment to acutely and chronically increase total peripheral white blood cells (WBCs) 1.5- to 3-fold across all disease populations examined (WHIM syndrome, Waldenström’s macroglobulinemia, clear cell renal cell carcinoma, and healthy volunteers).
- Further, mavorixafor's ability to increase circulating WBCs (neutrophils, lymphocytes, and monocytes) across various disease states and in healthy individuals supports its potential utility in the treatment of patients with immunodeficiency, regardless of the presence or absence of CXCR4 mutations.
- A Phase 1b trial in chronic neutropenia populations is ongoing to assess the potential of mavorixafor to treat broader neutropenias by increasing neutrophil counts, as well as other white blood cell types; initial data from this trial are expected to be presented in an ASH poster presentation and at the Investor Day on
December 16 .
Waldenström’s macroglobulinemia (WM):
- Additional preliminary clinical data are presented from the ongoing Phase 1b dose-escalation trial assessing the tolerability and efficacy, including clinical response rates, of mavorixafor in combination with ibrutinib in diagnosed WM patients with both MYD88 and CXCR4 mutations.
- As of the abstract cutoff date of
June 15, 2021 , the overall response rate (minor response or better) for evaluable patients was 100% (N=8), with 4 of 8 patients achieving a major response (corresponding to >50% reduction in serum IgM) and 1 of 8 patients achieving very good partial response (corresponding to >90% reduction in serum IgM). - Additional clinical data are expected to be presented in an ASH poster presentation and at the Investor Day on
December 16 .
Abstracts Accepted for Presentation and Publication at ASH
Preliminary Clinical Response Data from a Phase 1b Study of Mavorixafor in Combination with Ibrutinib in Patients with Waldenström’s Macroglobulinemia with MYD88 and CXCR4 Mutations | Poster Presentation on |
Mavorixafor, an Oral CXCR4 Antagonist, for Treatment of Patients with WHIM Syndrome: Results from the Long-Term Extension of the Open-Label Phase 2 Study | Poster Presentation on |
Poster Presentation on |
|
Comprehensive in Vitro Characterization of CXCR4WHIM variants to Decipher Genotype–Phenotype Correlations in WHIM Syndrome | Poster Presentation on |
Characterization of a Novel Missense CXCR4 Mutation in a Patient With WHIM-like Syndrome | Abstract Publication only |
Application of an Artificial Intelligence/Machine Learning Model for Estimating Potential US Prevalence of WHIM Syndrome, a Rare Immunodeficiency, From Insurance Claims Data | Abstract Publication only |
Global Phase 3, Randomized, Placebo-Controlled Trial With Open-Label Extension Evaluating the Oral CXCR4 Antagonist Mavorixafor in Patients With WHIM Syndrome (4WHIM): Trial Design and Enrollment | Abstract Publication only |
Following the ASH meeting, the company will be hosting an investor event on the morning of
Third Quarter and Recent Highlights
- X4 achieved a major milestone in early October, completing enrollment in the ongoing pivotal Phase 3 clinical trial (4WHIM) of mavorixafor in the treatment of patients with WHIM syndrome. Thirty-one adult and pediatric patients have been enrolled in the 4WHIM trial, which was originally designed to enroll 18-28 patients.
- The company recently announced the appointment of
Françoise de Craecker to the company’s Board of Directors and the recent hiring ofKarolyn Park to the newly created role of Vice President,U.S. Commercial, significantly strengthening the company’s depth and breadth of commercial leadership experience in the strategic marketing of rare disease therapeutics. - The company announced the promotion of
Mary DiBiase , Ph.D. to the newly created position of Chief Operating Officer, reflecting her long-standing contributions to the company and the advancement of mavorixafor into global late-stage clinical development.
Third Quarter 2021 Financial Results
- Cash, Cash Equivalents & Restricted Cash: X4 had
$77.7 million in cash, cash equivalents, and restricted cash as ofSeptember 30, 2021 . The company continues to expect 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 third quarter endedSeptember 30, 2021 , as compared to$11.4 million for the comparable period in 2020. R&D expenses include$0.6 million and$1.0 million of certain non-cash expenses for the quarters endedSeptember 30, 2021 and 2020, respectively. - General and Administrative Expenses were
$5.9 million for the third quarter endedSeptember 30, 2021 , as compared to$5.6 million for the comparable period in 2020. G&A expenses include$0.9 million and$1.2 million of certain non-cash expenses for the quarters endedSeptember 30, 2021 and 2020, respectively. - Net Loss: X4 reported a net loss of
$20.2 million for the quarter endedSeptember 30, 2021 , as compared to a net loss of$17.4 million for the comparable period in 2020. Net losses include$1.5 million and$2.2 million of certain non-cash expenses for the quarters endedSeptember 30, 2021 and 2020, respectively.
Conference Call and Webcast
X4 will host a conference call and webcast today at
About
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of 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 clinical development and therapeutic potential of mavorixafor and X4’s other product candidates or programs; X4’s possible exploration of additional opportunities for mavorixafor; the anticipated achievement of upcoming clinical milestones; the expected availability, content, and timing of clinical trial data; anticipated regulatory filings and commercial plans; clinical trial design, and the company’s cash runway. 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, uncertainties inherent in the initiation and completion of preclinical studies and clinical trials and clinical development; the risk that trials and studies may be delayed, including, but not limited to, as a result of the effects of the ongoing COVID-19 pandemic or delayed patient enrollment, and may not have satisfactory outcomes; the risk that the outcomes of preclinical studies or earlier clinical trials will not be predictive of later clinical trial results; the risk that initial or interim results from a clinical trial may not be predictive of the final results of the trial or the results of future trials; the potential adverse effects arising from the testing or use of mavorixafor or other product candidates; risks related to X4’s ability to raise additional capital, 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
(Tables Follow)
CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS
(in thousands, except per share amounts)
(unaudited)
Three Months Ended | Nine Months Ended | ||||||||||||||||||
2021 | 2020 | 2021 | 2020 | ||||||||||||||||
License revenue | $ | — | $ | — | $ | — | $ | 3,000 | |||||||||||
Operating expenses: | |||||||||||||||||||
Research and development | 13,188 | 11,381 | 38,485 | 29,634 | |||||||||||||||
General and administrative | 5,931 | 5,599 | 17,567 | 15,585 | |||||||||||||||
Total operating expenses | 19,119 | 16,980 | 56,052 | 45,219 | |||||||||||||||
Loss from operations | (19,119 | ) | (16,980 | ) | (56,052 | ) | (42,219 | ) | |||||||||||
Other expense, net | (1,054 | ) | (469 | ) | (2,423 | ) | (1,364 | ) | |||||||||||
Loss before provision for income taxes | (20,173 | ) | (17,449 | ) | (58,475 | ) | (43,583 | ) | |||||||||||
Provision for income taxes | 2 | — | 14 | 148 | |||||||||||||||
Net loss | (20,175 | ) | (17,449 | ) | (58,489 | ) | (43,731 | ) | |||||||||||
Deemed dividend due to Class B warrant price reset | — | — | (8,239 | ) | — | ||||||||||||||
Net loss attributable to common stockholders | $ | (20,175 | ) | $ | (17,449 | ) | $ | (66,728 | ) | $ | (43,731 | ) | |||||||
Net loss per share attributable to common stockholders- basic and diluted | $ | (0.76 | ) | $ | (0.87 | ) | $ | (2.71 | ) | $ | (2.18 | ) | |||||||
Weighted average common shares outstanding-basic and diluted | 26,609 | 20,085 | 24,667 | 20,035 | |||||||||||||||
CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS
(in thousands)
(unaudited)
Nine months ended |
|||||||||
2021 | 2020 | ||||||||
Net loss | $ | (58,489 | ) | $ | (43,731 | ) | |||
Adjustments to reconcile net loss to net cash used in operating activities | 6,809 | 5,198 | |||||||
Changes in operating assets and liabilities | (172 | ) | (2,781 | ) | |||||
Net cash used in operating activities | (51,852 | ) | (41,314 | ) | |||||
Net cash used in investing activities | (602 | ) | (1,060 | ) | |||||
Net cash provided by financing activities | 49,675 | 4,765 | |||||||
Impact of foreign exchange on cash, cash equivalents and restricted cash | (203 | ) | 240 | ||||||
Net decrease in cash, cash equivalents and restricted cash | (2,982 | ) | (37,369 | ) | |||||
Cash, cash equivalents and restricted cash at beginning of period | 80,702 | 128,086 | |||||||
Cash, cash equivalents and restricted cash at end of period | $ | 77,720 | $ | 90,717 | |||||
CONSOLIDATED BALANCE SHEETS
(in thousands)
(unaudited)
Current assets: | |||||||
Cash and cash equivalents | $ | 76,393 | $ | 78,708 | |||
Research and development incentive receivable | 646 | 917 | |||||
Prepaid expenses and other current assets | 3,661 | 3,682 | |||||
Total current assets | 80,700 | 83,307 | |||||
Property and equipment, net | 1,632 | 1,237 | |||||
27,109 | 27,109 | ||||||
Right-of-use assets | 9,071 | 7,960 | |||||
Other assets | 2,005 | 3,258 | |||||
Total assets | $ | 120,517 | $ | 122,871 | |||
Current liabilities: | |||||||
Accounts payable | $ | 2,424 | $ | 3,144 | |||
Accrued expenses | 9,074 | 8,018 | |||||
Current portion of lease liability | 1,041 | 786 | |||||
Current portion of long-term debt | 693 | — | |||||
Total current liabilities | 13,232 | 11,948 | |||||
Long-term debt, including accretion, net of discount | 33,043 | 33,178 | |||||
Lease liabilities | 5,067 | 4,484 | |||||
Other liabilities | 496 | 462 | |||||
Total liabilities | 51,838 | 50,072 | |||||
Total stockholders' equity | 68,679 | 72,799 | |||||
Total liabilities and stockholders' equity | $ | 120,517 | $ | 122,871 | |||
Investors and Media:
Managing Director
daniel@lifesciadvisors.com
(617) 430-7576
Senior Account Executive
mroucomolina@lifescicomms.com
Source: X4 Pharmaceuticals