MONROVIA, Calif., Nov. 13, 2016 /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 preliminary data from XmAb5871-03, an ongoing,
open-label, pilot Phase 2 study of XmAb5871 in patients with active
IgG4- RD. Data show that 82% of patients achieved an initial
response to therapy within two weeks of their first dose. The data
are being presented by John H.
Stone, M.D., MPH, director of rheumatology at Massachusetts
General Hospital, at the American College of Rheumatology (ACR)
2016 Annual Meeting in the Miscellaneous Rheumatic and Inflammatory
Disease session on Sunday, November 13,
2016 (today) at 2:45 p.m.
EST.
"We are very encouraged by the rapid initial response in IgG4-RD
disease activity observed in this preliminary data set, in which
nine of the 11 patients evaluated for IgG4-RD Responder Index (RI)
post-treatment achieved a response within two weeks of their first
dose, with responses typically deepening over time," said
Paul Foster, M.D., chief medical
officer of Xencor. "We expect to report complete study results in
2017."
"I am impressed by the steady 'dialing down' of the inflammatory
response that XmAb5871 seems to exert in IgG4-RD and believe it is
a promising potential therapy," said Dr. John H. Stone, the principal investigator of the
study. "We are learning a lot about how to study this disease
in the context of this small trial."
As of a data cutoff of October 31,
2016, 12 patients with active IgG4-RD have been enrolled and
dosed with XmAb5871 (median number of infusions = 7, range 1-12).
Patients had a median IgG4-RD RI of 10 (range 2-30) with a median
of four organs involved (range 1-10) at the time of study entry.
Organ site involvement occurring at a frequency of greater than or
equal to 50% included lymph nodes, submandibular glands, parotid
glands and lacrimal glands.
Preliminary Safety Data:
Every other week intravenous administration of XmAb5871 has been
well tolerated. As of October 31,
2016, no serious adverse events (AEs) have been reported.
Treatment related AEs have occurred in five patients (42%).
Treatment-related AEs that occurred in more than one patient were
abdominal pain/discomfort in three patients (25%), occurring as
part of Grade 1 (mild) infusion-related gastrointestinal symptoms
(nausea and/or vomiting and/or diarrhea) during the first infusion,
and Grade 1 (mild) headache in two patients (16.7%). One patient
discontinued the study as the result of an AE. The patient
developed a Grade 2 (moderate) hypersensitivity reaction with rash
and arthritis, commonly referred to as serum sickness, following
the fifth infusion. The event resolved quickly without the need for
medical management. This patient was subsequently found to have
developed anti-drug antibodies.
Preliminary Efficacy Data:
Eleven of the 12 patients dosed with XmAb5871 have had at least
one IgG4-RD RI performed following dosing as of the data cutoff
date. Nine of 11 patients (82%) have had an initial response to
XmAb5871 therapy of at least a three-point reduction in the IgG4-RD
RI within two weeks of the first dose. Five patients attained
disease remission (an IgG4-RD RI of 0) during the study. Two
patients entering the study on corticosteroids have been able to
taper and discontinue steroid use during the study.
In addition to the patient with early study termination due to
an AE, two other patients have discontinued treatment prior to
receipt of all 12 planned infusions. One patient had a response to
therapy (IgG4-RD RI reduction of six points), but lost response
following the sixth infusion, at which point this patient
discontinued treatment. One patient had no response to therapy as
defined by a greater than or equal to two-point decrease in the
IgG4-RD RI. This patient had an atypical presentation of larynx
involvement as the only organ involved. The patient discontinued
the study after six infusions. Neither of these two patients have
responded to subsequent rituximab treatment.
The slide presentation will be available at 3:00 p.m. Eastern Time today on the 'Investors'
page of Xencor's website under 'Events and Presentations' at
www.xencor.com.
Conference Call Information
Xencor management will
host a conference call and webcast today at 6:00 p.m. Eastern Time to discuss data presented
today. The live call may be accessed by dialing (877) 359-9508 for
domestic callers or (224) 357-2393 for international callers, and
providing the conference ID number 16658995. A live webcast of the
conference call will be available online from the investors section
of the Xencor website at www.xencor.com. The webcast will be
archived on the Company's website for 30 days.
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, 10 candidates engineered
with Xencor's XmAb® technology are in clinical development
internally and with partners. Xencor's internal programs include:
XmAb5871 in Phase 2 development for the treatment of IgG4-Related
Disease, and also for the treatment of Systemic Lupus
Erythematosus; XmAb7195 in Phase 1 development for the treatment of
asthma and allergic diseases; XmAb14045 in Phase 1 development for
acute myeloid leukemia; and XmAb13676 for B-cell malignancies and
XmAb18087 for the treatment of neuroendocrine tumors, both in
pre-clinical development. 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, Novo Nordisk 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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