MONROVIA, Calif., June 16, 2017 /PRNewswire/ -- Xencor, Inc.
(NASDAQ: XNCR), a clinical-stage biopharmaceutical company
developing engineered monoclonal antibodies for the treatment of
autoimmune diseases, asthma and allergic diseases and cancer, today
announced interim data from an ongoing, open-label, pilot Phase 2
study of XmAb®5871 in patients with active IgG4-Related
Disease (IgG4-RD). Data show that 93% of patients achieved a
response to therapy, 12 of them within two weeks of their first
dose. The data were presented today by John
H. Stone, M.D., MPH, director of rheumatology at
Massachusetts General Hospital, at the Annual European Congress of
Rheumatology (EULAR 2017).
"We continue to be very encouraged by the rapid initial response
in IgG4-RD disease activity observed in this interim data set, in
which now 14 of 15 patients evaluated for IgG4-RD Responder Index
(RI) achieved a response, with initial responses typically
occurring after the first dose and deepening over time," said
Paul Foster, M.D., chief medical
officer of Xencor. "We expect to report final study results for
these 15 patients in 2017."
"The rapid clinical responses in many patients and the continued
decline in the inflammatory response indicate that XmAb5871 is
clearly a promising therapy for IgG4-RD," said Dr. John H. Stone, the principal investigator of the
study. "We have learned a lot about how to study this disease
in the context of this small trial."
As of a data cutoff of April 18,
2017, all 15 planned patients with active IgG4-RD have been
enrolled and dosed with XmAb5871 (median number of infusions = 12,
range 5-12). Patients had a median IgG4-RD RI of 12 (range 2-30)
with a median of five organs involved (range 1-10) at the time of
study entry. Organ site involvement occurring at a frequency of
greater than or equal to 45% included lymph nodes, submandibular
glands, parotid glands and lacrimal glands. In addition, 40% of
patients suffered from constitutional symptoms at time of study
entry.
Every other week intravenous administration of XmAb5871 has been
well tolerated. Adverse events (AEs) were consistent with that
previously reported, with all XmAb5871-related AEs graded as mild
or moderate and no AE reported in more than 2 patients. No severe
AEs deemed related to XmAb5871 were reported. One patient
discontinued the study as the result of an AE of a moderate
hypersensitivity reaction, as previously reported in November 2016.
Interim Efficacy Data:
As of April 18, 2017, 10 patients
have completed the study, 3 of whom discontinued early as reported
previously in November 2016, and 5
patients are ongoing. Fourteen of the 15 patients (93%) dosed with
XmAb5871 have had a response to XmAb5871 therapy of greater than or
equal to a two-point reduction in the IgG4-RD RI (protocol defined
response), 12 of them within two weeks of the first dose. At two
weeks following the last dose, five patients had an IgG4-RD RI of 0
and were on no corticosteroid therapy between months 2-6 (protocol
definition of remission). In addition, a sixth patient achieved
remission in the post-therapy follow-up period. All five of the
patients that either entered the study on corticosteroids or that
were administered corticosteroids at the beginning of the study
have been able to taper and discontinue corticosteroids within 2
months of the start of the study.
The early discontinuations included the patient with early study
termination due to an AE, one patient that had a response to
therapy (IgG4-RD RI reduction of six points), but lost response
following the sixth infusion, and one patient that had no response
to therapy as defined by a greater than or equal to two-point
decrease in the IgG4-RD RI. This latter patient had an atypical
presentation of larynx involvement as the only organ involved. The
patient discontinued the study after six infusions. Neither of the
two patients that discontinued early due to loss of response or
lack of response responded to subsequent rituximab treatment.
Interim Biomarker Data:
Circulating CD19+ plasmablast levels were elevated in
the majority of patients at baseline and levels were reduced
quickly following XmAb5871 treatment. XmAb5871 also reduced the
numbers of circulating SLAMF7+ CD4+ cytotoxic
T lymphocytes, an immune cell population potentially important in
IgG4-RD, in those patients with measurable levels at baseline.
The poster presentation is available on the 'Investors' page of
Xencor's website under 'Events and Presentations' at
www.xencor.com.
About XmAb®5871-03
XmAb5871-03 is an open-label, single-arm study of up to 15
patients with histopathologically proven IgG4-RD with active
disease as defined by disease activity in one or more organ systems
and an IgG4-RD RI of greater than or equal to three. Participants
will receive XmAb5871 by intravenous infusion every other week for
up to a total of 12 infusions. Primary and secondary objectives are
to evaluate the effect of every other week intravenous
administration of XmAb5871 on the IgG4-RD RI in patients with
active IgG4-RD and to evaluate the safety, tolerability,
pharmacokinetics and immunogenicity of XmAb5871 in patients with
active IgG4-RD over an up to six-month period. The primary endpoint
of the completed study will be the proportion of patients on Day
169 with an improvement of disease activity score as defined by a
decrease of IgG4-RD RI of greater than or equal to two points from
the Day 1 pre-dose disease activity score.
About XmAb®5871
XmAb®5871 is a first-in-class monoclonal antibody
that targets CD19 with its variable domain and that
uses Xencor's XmAb immune inhibitor Fc domain to target
FcγRIIb, a receptor that inhibits B-cell function. XmAb5871 is the
first drug candidate that Xencor is aware of that targets
FcγRIIb inhibition. Xencor has demonstrated in multiple
animal models and in initial human clinical trials that XmAb5871
inhibits B-cell function without destroying these important immune
cells, and demonstrated promising treatment effect in patients with
rheumatoid arthritis, as well as ex vivo results showing inhibition
of systemic lupus erythematosus (SLE) patient B-cell activation and
humoral immunity.
Complete data results from a Phase 1b/2a study of XmAb5871 in
patients with rheumatoid arthritis were presented at
the American College of Rheumatology 2015 Annual Meeting
as well as at the EULAR 2015 Annual Meeting. Ex vivo
studies of SLE patient B cells were published in Journal of
Immunology, 2011, 186(7):4223.
About IgG4-Related Disease
IgG4-Related Disease (IgG4-RD) is a rare fibro-inflammatory
autoimmune disorder that is estimated to impact up to 40,000
patients in the United
States. IgG4-RD affects multiple organ systems and is
characterized by a distinct microscopic appearance of diseased
organs, including the presence of IgG4-positive plasmablast cells.
This objective diagnostic criterion is atypical for autoimmune
diseases and offers advantages for accurately identifying patients.
There are currently no approved therapies for this newly recognized
disorder and corticosteroids are the current standard of care.
John H. Stone, M.D, MPH, director, clinical rheumatology at
Massachusetts General Hospital has developed and is validating
the IgG4-RD Responder Index (RI), a proposed instrument to assess
disease activity.
About Xencor's XmAb® Immune Inhibitor Technology
FcγRIIb (IIb), also called CD32b, is a receptor for Fc domains
on B cells and other immune cells. When engaged, the IIb receptor
blocks immune activation pathways and traffics bound soluble
antigens out of circulation. Xencor has discovered a series of Fc
domain variants with up to a 400-fold increase in binding affinity
to FcγRIIb derived from just two amino acid changes. These XmAb®
Immune Inhibitor Fc domains greatly heighten the properties of IIb
receptor engagement and have potential as building blocks for drug
candidates in autoimmune, allergic and inflammatory diseases.
About Xencor, Inc.
Xencor is a clinical-stage biopharmaceutical company developing
engineered monoclonal antibodies for the treatment of autoimmune
diseases, asthma and allergic diseases and cancer. Currently, 11
candidates engineered with Xencor's XmAb® technology are in
clinical development internally and with partners. Xencor's
internal programs include: XmAb®5871 in Phase 2 development for the
treatment of IgG4-Related Disease, and also for the treatment of
Systemic Lupus Erythematosus; XmAb®7195 in Phase 1 development for
the treatment of asthma and allergic diseases; XmAb®14045 in Phase
1 development for acute myeloid leukemia; XmAb®13676 in Phase 1
development for B-cell malignancies; XmAb®18087 in pre-clinical
development for the treatment of neuroendocrine tumors; and
XmAb®20717 in pre-clinical development for the treatment of
multiple cancers. Xencor's XmAb antibody engineering technology
enables small changes to the structure of monoclonal antibodies
resulting in new mechanisms of therapeutic action. Xencor
partners include Novartis, Amgen, MorphoSys, Merck, CSL/Janssen,
Alexion and Boehringer Ingelheim. For more information, please
visit www.xencor.com.
Forward Looking Statements:
Statements contained in this press release regarding matters
that are not historical facts are forward-looking statements within
the meaning of applicable securities laws, including the quotation
from Xencor's officer and any expectations relating to its
business, research and development programs, including ongoing
clinical trials of XmAb5871, and the immune inhibitory Fc domain
technology, partnering efforts or its capital requirements. Such
statements involve known and unknown risks, uncertainties and other
factors that may cause actual results, performance or achievements,
including those of the complete clinical trial of XmAb5871, and the
timing of events to be materially different from those implied by
such statements, and therefore these statements should not be read
as guarantees of future performance or results. Such risks include,
without limitation, the risks associated with the process of
discovering, developing, manufacturing and commercializing drugs
that are safe and effective for use as human therapeutics and other
risks described in Xencor's public securities filings.
All forward-looking statements are based
on Xencor's current information and belief as well as
assumptions made by Xencor. Readers are cautioned not to place
undue reliance on such statements and Xencor disclaims
any intention or obligation to update or revise any forward-looking
statements, whether as a result of new information, future events
or otherwise.
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SOURCE Xencor, Inc.