Syntimmune announces Breakthrough Results of FcRn Inhibition

syntimmune

Preclinical In Vivo Models Demonstrate Blockade of
FcRn-Albumin Interactions May Have Application in Protecting the Liver
from Hepatotoxins

SYNT002 Program to Commence IND-Enabling Studies in 2017

NEW YORK–(BUSINESS WIRE)–Syntimmune, Inc., a clinical-stage biotechnology company and the leader
in FcRn biology, today announced the peer-reviewed publication of
research findings for SYNT002, the Company’s second most advanced
pipeline program and lead monoclonal antibody therapy targeting
albumin-FcRn interactions. SYNT002 is in active preclinical development
by Syntimmune for a number of indications and is expected to enter
IND-enabling studies in 2017. The study, led by Syntimmune scientific
founder Dr. Richard Blumberg in collaboration with multiple members of
the Company’s Scientific Advisory Board, appears in the journal Proceedings
of the National Academy of Sciences
(doi: 10.1073/pnas.1618291114
PNAS March 20, 2017). These research findings demonstrate that
inhibition of FcRn (neonatal Fc receptor) provides protection against
toxin-induced liver injury and causes removal of toxins from circulation
via a newly described mechanism that is engaged by SYNT002. Among the
key results are:

  • While FcRn in the liver maintains albumin homeostasis, inhibition of
    albumin-FcRn binding caused clearance of albumin from the circulation
    via transport into the bile.
  • Using acetaminophen poisoning as a preclinical model of an
    albumin-bound hepatotoxin, FcRn inhibition was shown to increase
    albumin-mediated transport of acetaminophen out of the circulation and
    into the bile where it is excreted from the body, protecting the liver
    and other organs from this toxin.
  • In addition to inducing sequestration of albumin-bound toxins in bile,
    FcRn blockade caused albumin accumulation within hepatocytes, exerting
    important anti-oxidant effects to protect liver cells from
    acetaminophen damage.
  • Multiple therapeutic modalities, including SYNT002 and a peptide
    mimetic inhibitor of FcRn, engaged this mechanism to provide robust
    protection from acetaminophen-induced liver toxicity.

“There are two important aspects of this research. First, FcRn is shown
to be critical for directing albumin into the blood, allowing albumin’s
normal functions for health,” stated David E. Cohen, Chief of Division
of Gastroenterology and Hepatology at Weill Cornell Medicine and
NewYork-Presbyterian/Weill Cornell Medical Center. “Second, this article
also underscores a broad therapeutic opportunity. Substances such as
acetaminophen can literally act as hitchhikers by attaching to albumin,
and this allows them to build up toxic levels in the body. I find it a
very exciting possibility that we may be able to decrease these toxic
levels by selectively inhibiting FcRn so that albumin and the toxin it
is carrying can be shunted out of the bloodstream and into the bile. I
look forward to the continued progress of this promising research.”

“Syntimmune has built a commanding intellectual property (IP) estate
covering therapeutic blockade of FcRn-albumin interactions, including
key IP licensed from Brigham and Women’s Hospital. The findings
published this week in PNAS bring together over a decade of research on
modulation of FcRn-albumin interactions. The results of this study
support the high potential of SYNT002 and related molecules to treat a
wide range of conditions involving exo- and endo-toxins that bind to
albumin. These include toxins associated with renal disease and
drug-induced liver injury, as well as certain severe metabolic diseases
and many forms of chemical poisoning. In addition to promoting liver
clearance of albumin-bound toxins, we envision an opportunity to also
effect the clearance of toxins through the kidney by extrapolation from
these innovative studies,” stated David de Graaf, Ph.D., Syntimmune’s
President and Chief Executive Officer. “The immediate goal for our
SYNT002 program is to progress our lead molecule to the IND stage in
important indications where this novel mechanism of action has potential
to transform therapy. We are excited with the progress of this program,
which could have a far-reaching impact on human health by providing a
powerful and non-invasive means to clear the body of toxins.”

Laurence Blumberg, M.D., Founder and COO of Syntimmune, commented,
“Syntimmune continues to advance its clinical-stage lead program,
SYNT001, a biologic that precisely blocks FcRn-IgG interactions and is
being developed for the treatment of IgG-mediated autoimmune diseases.
Based on the activity and safety profile demonstrated by SYNT001 in
Phase 1, we have initiated a broad Phase 1b/2a development campaign that
includes multiple independent Phase 1b/2a studies of SYNT001 across a
range of prioritized indications that provide compelling clinical and
commercial opportunities.”

About Syntimmune

Founded in 2013, Syntimmune is advancing novel therapies based on its
leading position in the biology of the neonatal Fc receptor (FcRn). As a
core part of a central common pathway that enables abnormal IgG
responses, FcRn is a well-validated target for the treatment of
IgG-mediated autoimmune diseases. Syntimmune’s lead candidate, SYNT001,
is a biologic that specifically blocks FcRn-IgG interactions and is
being studied in multiple 1b/2a trials for the treatment of IgG-mediated
autoimmune diseases. In addition to SYNT001, Syntimmune is developing
two earlier-stage therapeutic programs, including SYNT002, which target
other unique aspects of FcRn biology. The Syntimmune team has
world-class experience in the field of FcRn biology and has successfully
pioneered and advanced biologics targeting FcRn, including approved
therapies currently on the market. Since its founding, the Company has
received a total of $28 million in funding commitments from leading life
sciences investors, led by Apple Tree Partners. For more information on
Syntimmune, please visit the Company’s website at www.syntimmune.com.
Contacts

Burns McClellan
Justin Jackson, 212-213-0006 ext. 327
jjackson@burnsmc.com