Xencor, Inc. (NASDAQ: XNCR), a clinical-stage biopharmaceutical
company developing engineered antibodies and cytokines for the
treatment of cancer and autoimmune diseases, today presented data
from multiple preclinical-stage XmAb® programs at the 38th Annual
Meeting of the Society for Immunotherapy of Cancer (SITC) in San
Diego.
“Xencor aims to stay on the leading edge of molecular
engineering, using and improving upon our XmAb technologies to
create molecules with enhanced functionality or new therapeutic
mechanisms. At SITC, we are presenting new preclinical data from
two research-stage programs—engineered, decoy-resistant IL18-Fc
fusions and our multi-valent NK cell engagers targeted to MICA and
MICB, which are tumor antigens upregulated in the tumor
microenvironment,” said John Desjarlais, Ph.D., executive vice
president and chief scientific officer at Xencor. “Later this year,
we expect to submit an investigational new drug application for
XmAb541, an XmAb 2+1 format CLDN6 x CD3 bispecific antibody that we
are developing for patients with ovarian cancer and other tumor
types. We are also developing additional CD3 and CD28 T cell
engaging bispecific antibodies against solid tumor targets.”
Posters will be available in the poster hall and virtually to
registrants of the SITC Annual Meeting. In the poster hall,
odd-numbered posters will be displayed on Friday, November 3, and
even-numbered posters will be displayed on Saturday, November 4.
Xencor’s posters will be archived under "Events &
Presentations" in the Investors section of the Company's website
located at www.xencor.com.
Clinical Trials in Progress
Abstract 764, “A Phase 1, first-in-human
(FIH), open-label, dose-finding and expansion study of XmAb808, a
B7H3 x CD28 bispecific antibody, in combination with pembrolizumab
in patients with advanced solid tumors”
Xencor is conducting a Phase 1 study of XmAb808 in patients with
advanced solid tumors. XmAb808 is a tumor-selective, co-stimulatory
XmAb 2+1 bispecific antibody designed to bind to the broadly
expressed tumor antigen B7-H3 and selectively to the CD28 T-cell
co-receptor only when bound to tumor cells, which was demonstrated
in vitro. Strong potentiation of checkpoint and CD3 cytotoxic
activity was also observed in vivo. XmAb808 is a wholly owned
Xencor program.
The clinical trials in progress poster reviews the design of
XmAb808 and the rationale of using CD28 bispecific antibodies to
expand the utility of checkpoint blockade and CD3 T cell engagers.
The poster also provides study objectives, key eligibility criteria
and study schema.
Preclinical Programs
Abstract 1060, “Optimally engineered
IL18-Fc fusion proteins balance potency and pharmacokinetics to
promote strong anti-tumor activity”
IL-18 is a proinflammatory cytokine that modulates both the
innate and adaptive immune responses. Preclinical studies of IL-18
have demonstrated its anti-tumor activity, including synergy with
immune checkpoint inhibitors and CAR-T therapies. In contrast with
other potent cytokines, IL-18 has been well tolerated in clinical
trials but demonstrated a lack of efficacy despite heavy dosing.
IL-18 induces a negative feedback loop with its high affinity
natural inhibitor, IL18BP, which was upregulated in early phase
clinical studies and may have limited IL-18’s clinical
performance.
Xencor engineered stabilized, potency-modulated IL-18 cytokines
fused to an XmAb heterodimeric Fc domain with Xtend™ Fc technology
for longer half-life (IL18-Fc). In addition, Xencor engineered
bispecific IL18-Fc cytokines targeted to PD-1, a checkpoint
receptor on T cells. Importantly, these molecules were engineered
to avoid binding IL18BP.
Xencor’s IL18-Fc fusions and PD1 x IL18-Fc bispecific inhibited
tumor growth in a dose- and potency-dependent manner, outperforming
a wild-type IL18-Fc fusion, in vivo. Further preclinical studies of
the engineered IL18-Fc fusions demonstrated pharmacodynamic
profiles similar to wild-type IL18-Fc. Notably, a set of surviving
tumor-engrafted mice, which had previously received engineered
IL18-Fc fusions, had no tumor growth upon rechallenge.
Abstract 1193, “Synergistic targeting of
multiple activating pathways with Natural Killer cell
Engagers”
Xencor’s XmAb natural killer cell engagers (NKEs) are
multifunctional antibodies that target multiple activating
receptors on the surface of NK cells and bind to tumor-associated
antigens.
MICA and MICB (MICA/B) are stress-induced tumor antigens
expressed in a range of cancers. MICA/B antigens are recognized by
NKG2D, an activating receptor on NK and CD8+ T cells. While
membrane-bound, MICA/B is immuno-stimulatory; however, the cleaved
and soluble form, found in the tumor microenvironment, prevents
NKG2D from recognizing tumor cells. Xencor engineered anti-MICA/B
antibodies with enhanced effector function in order to block the
cleavage of MICA/B antigens and promote NK cell engagement. These
antibodies increased MICA/B membrane surface density and led to
tumor cell killing with MICA/B binding to NKG2D on immune cells. To
enhance the anti-tumor activity, Xencor engineered multi-specific
NK cell-engaging antibodies that simultaneously target MICA/B
antigens and an orthogonal activating receptor on NK cells, NKp46.
These multi-specific NK cell-engaging antibodies demonstrated
enhanced functional activity compared to the antibodies targeting
only MICA/B.
About Xencor
Xencor is a clinical-stage biopharmaceutical company developing
engineered antibodies and cytokines for the treatment of patients
with cancer and autoimmune diseases. More than 20 candidates
engineered with Xencor's XmAb® technology are in clinical
development, and three XmAb medicines are marketed by partners.
Xencor's XmAb engineering technology enables small changes to a
protein's structure that result in new mechanisms of therapeutic
action. For more information, please visit www.xencor.com.
Forward-Looking Statements
Certain statements contained in this press release may
constitute forward-looking statements within the meaning of
applicable securities laws. Forward-looking statements include
statements that are not purely statements of historical fact, and
can generally be identified by the use of words such as
“potential,” “can,” “will,” “plan,” “may,” “could,” “would,”
“expect,” “anticipate,” “seek,” “look forward,” “believe,”
“committed,” “investigational,” and similar terms, or by express or
implied discussions relating to Xencor’s business, including, but
not limited to, statements regarding Xencor preclinical programs
and clinical trials, the quotations from Xencor's executive vice
president and chief scientific officer, and other statements that
are not purely statements of historical fact. Such statements are
made on the basis of the current beliefs, expectations, and
assumptions of the management of Xencor and are subject to
significant known and unknown risks, uncertainties and other
factors that may cause actual results, performance or achievements
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, including the ability of publicly
disclosed preliminary clinical trial data to support continued
clinical development and regulatory approval for specific
treatments, in each case as described in Xencor's public securities
filings. For a discussion of these and other factors, please refer
to Xencor's annual report on Form 10-K for the year ended December
31, 2022, as well as Xencor's subsequent filings with the
Securities and Exchange Commission. You are cautioned not to place
undue reliance on these forward-looking statements, which speak
only as of the date hereof. This caution is made under the safe
harbor provisions of the Private Securities Litigation Reform Act
of 1995, as amended to date. All forward-looking statements are
qualified in their entirety by this cautionary statement and Xencor
undertakes no obligation to revise or update this press release to
reflect events or circumstances after the date hereof, except as
required by law.
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For Investors: Charles Liles cliles@xencor.com 626-737-8118
For Media: Jason I. Spark Evoke Canale
jason.spark@evokegroup.com 619-849-6005
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