X4 Presents Data from Ongoing Phase 2 Study Demonstrating Promising Activity of X4P-001-RD in Patients with WHIM Syndrome

Pharmaceuticals, a clinical stage biotechnology company developing
novel CXCR4 allosteric antagonist drugs to improve immune cell
trafficking to treat cancer and rare disease, today announced the
presentation of clinical data demonstrating safety and promising
activity of X4P-001-RD
in patients with WHIM syndrome, a rare primary immunodeficiency disease.
The X4P-001-RD clinical data is from the ongoing open-label Phase 2
portion of a Phase 2/3 study in patients with WHIM syndrome, and the
presentation was made at the 23rd Congress of the European
Hematology Association (EHA) taking place on June 14-17, 2018 in
Stockholm, Sweden.

The interim results from the Phase 2 portion of the study demonstrated
promising activity of X4P-001-RD with dose-dependent increases in
absolute neutrophil and lymphocyte counts in patients with WHIM
syndrome. Most patients enrolled in the study to date had meaningful
increases in the levels of neutrophil and lymphocyte counts with daily
oral administration of X4P-001-RD. Measurement of circulating
neutrophils and lymphocytes are endpoints in the X4P-001-RD clinical
study because in WHIM syndrome patients, leukocytes are retained in the
patient’s bone marrow, causing severe chronic panleukopenia, including
neutropenia and lymphopenia. This results in inadequate immune
surveillance and function for WHIM syndrome patients.

X4P-001-RD was observed to be safe and well tolerated for durations up
to 400 days and including doses up to 400 mg daily. Based on this safety
profile, along with results of dose-dependent neutrophil and lymphocyte
activity, the recommended dose of X4P-001-RD in the future Phase 3 study
has been determined to be 400 mg once daily. X4 is completing the Phase
2 portion and plans to initiate the Phase 3 portion towards year end.

“In this study, X4P-001-RD showed consistent increases in neutrophils
and lymphocytes, the primary biomarker for response to therapy.
Increases in these biomarkers are an indication of an improvement in the
pathophysiology underlying WHIM syndrome. One exciting example of
improvement was a reduction in HPV-related warts following X4P-001-RD
therapy in one patient,” said David C. Dale, MD, Professor of Medicine
at the University of Washington, Seattle, WA and lead investigator of
the study. “These results are very encouraging and represent a milestone
in X4P-001-RD’s development as an oral therapy for WHIM syndrome

The poster presentation at EHA describes results from the first 8
patients with genetically confirmed WHIM syndrome who were enrolled in
the Phase 2 portion of the ongoing Phase 2/3 study (as of data cutoff
date of March 20, 2018) and include the following highlights:

“Our clinical program with X4P-001-RD in WHIM syndrome has made
significant progress, with the establishment of the recommended dose for
our future Phase 3 study in WHIM syndrome,” said Sudha Parasuraman, MD,
Chief Medical Officer of X4. “We look forward to moving expeditiously
toward starting the pivotal Phase 3 study.”

Details of the trial of X4P-001-RD in patients with WHIM syndrome can be
found on clinicaltrials.gov: https://clinicaltrials.gov/ct2/show/NCT03005327.

About WHIM Syndrome

syndrome is a primary immunodeficiency disease caused by a mutation
in the C-X-C
receptor type 4 (CXCR4) gene resulting in susceptibility to certain
types of infections. WHIM is an abbreviation for the characteristic
clinical symptoms of the syndrome: Warts, Hypogammaglobulinemia,
Infections, and Myelokathexis. Within the overall category of primary
immunodeficiencies, there are between 15,000 and 100,000 patients in the
US that are classified with primary immunodeficiency disease of unknown
origin – of which WHIM is one.1,2,3 WHIM syndrome is a rare
disorder and the precise prevalence or incidence of patients that have
the genetic mutation responsible for WHIM syndrome is unknown. Because
patients are highly susceptible to infections, WHIM syndrome is
associated with significant morbidity beginning in early childhood and
continuing throughout life. Current therapy is limited to treatment of
acute infections with antibiotics or prevention through the use of
intravenous immunoglobulin or G-CSF. There is no approved therapy for
the treatment of WHIM syndrome.

About X4P-001-RD for Primary Immunodeficiency Disease

an oral, small molecule inhibitor of CXCR4 is being developed for use as
a life-long treatment for patients with WHIM syndrome and other primary
genetic immunodeficiencies. X4P-001-RD is currently being studied in a
Phase 2/3 trial in patients with WHIM syndrome. Within the bone marrow,
a normally functioning CXCR4 receptor controls the release of
neutrophils and leukocytes into the blood stream, thereby ensuring
normal immune surveillance functions throughout the body. In patients
with WHIM syndrome, mutations to the CXCR4 gene cause aberrant signaling
leading to retention of neutrophils and leukocytes in the bone marrow
and inadequate immune surveillance and function.4,5 X4P-001-RD
is designed to normalize the signaling for the mutant CXCR4 receptor to
promote the release of neutrophils and leukocytes, thereby restoring
healthy immunity.

About X4 Pharmaceuticals

Pharmaceuticals is developing novel therapeutics designed to
improve immune cell trafficking to treat cancer and rare diseases. The
Company’s oral small molecule drug candidates antagonize the CXCR4 pathway,
which plays a central role in immune surveillance. X4’s most advanced
product candidate, X4P-001-RD, is in a Phase 2/3 study in patients with
WHIM syndrome, a rare genetic, primary immunodeficiency disease.
X4P-001-IO is currently under investigation in multiple clinical studies
in solid tumors. X4 was founded and is led by a team with deep product
development and commercialization expertise, including several former
members of the Genzyme leadership team, and is located in Cambridge, MA.
For more information, visit www.x4pharma.com.

1 Boyle JM, Buckley, RH, Population Prevalence of Diagnosed
Primary Immunodeficiency Diseases in the United States. J Clin
Immunol 2007;27:497–502.

2 Gathmann B, Grimbacher B, et al. The European
internet-based patient and research database for primary
immunodeficiencies: results 2006–2008. Clin Exp Immunol. 2009
Sep;157 Suppl 1:3-11.

3 Modell V, Gee B, et al. Global study of primary
immunodeficiency diseases (PI) — diagnosis, treatment, and economic
impact: an updated report from the Jeffrey Modell Foundation. Immunol
Res. 2011;51:61–70.

4 Hernandez PA, Gorlin RJ, Lukens JN, et al. Mutations in the
chemokine receptor gene CXCR4 are associated with WHIM syndrome, a
combined immunodeficiency disease. Nature Genetics 2003;34(1):70-74.

5 Gulino AV, Moratto D, Sozzani S, et al. Altered leukocyte
response to CXCL12 in patients with Warts Hypogammaglobulinemia,
Infections, Myelokathexis (WHIM) syndrome. Blood 2004;104(2):444-452.

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