Syntimmune Announces Positive Preliminary Results from Clinical Proof-of-Concept Trial of SYNT001 in Pemphigus Vulgaris and Foliaceus

  • Favorable safety and tolerability profile consistent with Phase 1a data
  • SYNT001 treatment resulted in clinical improvement as measured by
    Pemphigus Disease Area Index (PDAI) score, with clinical effect
    persisting beyond the treatment period
  • Rapid reductions in total IgG and circulating immune complex (CIC)
    levels

BOSTON–(BUSINESS WIRE)–Syntimmune,
Inc
., a clinical-stage biotechnology company developing antibody
therapeutics targeting FcRn, today announced positive preliminary
results from its Phase 1b proof-of-concept trial of SYNT001 in patients
with pemphigus vulgaris and pemphigus foliaceus. The data showed
clinically meaningful benefit of SYNT001, with a favorable safety and
tolerability profile similar to that observed in the Phase 1a study.

“There remains a clear unmet need for a safe and fast-acting treatment
for patients with pemphigus, who face serious symptoms and complications
associated with their disease,” said Donna Culton, M.D., Ph.D., an
assistant professor at the University of North Carolina School of
Medicine. Culton presented preliminary results of the Phase 1b study at
the International Investigative Dermatology conference being held on May
16-19, 2018 in Orlando, FL. “These preliminary data demonstrate safety
as well as a rapid reduction in PDAI scores and lowering of IgG levels
with treatment of SYNT001, which support further studies of this drug as
a potential new therapeutic option,” Culton said.

Trial Design

SYNT001-103 is an ongoing, multi-center, open-label Phase 1b study
evaluating the safety and clinical effect of SYNT001 in patients with
active pemphigus vulgaris (PV) or pemphigus foliaceus (PF). SYNT001 will
be studied in three successive dosing cohorts, each treated with five
weekly doses of SYNT001 administered intravenously (IV), with dose
escalation between cohorts up to a maximum of 45 mg/kg. The study
observation period covers 16 weeks, including an active treatment period
from day 0-28 and follow-up through day 112. The primary endpoint of the
study is safety and tolerability. Secondary endpoints include PDAI,
total IgG, CIC and serum anti-desmoglein IgG (anti-DSG1 and anti-DSG3)
levels. The results reported in this press release include data from
seven patients (six with PV and one with PF) enrolled in the first
cohort who received five weekly infusions of 10 mg/kg SYNT001 and are in
varying stages of follow-up.

Results from First Cohort

Primary endpoint analysis revealed SYNT001 to be well tolerated in
treated patients, with all study drug-related adverse events (AEs)
characterized as mild or moderate. No severe or serious study
drug-related AEs were reported.

The secondary endpoint measures showed a reduction in mean PDAI score
from severe to moderate, with clinical effect persisting beyond the
treatment period. Rapid and clinically meaningful reductions in
pharmacodynamic biomarkers were observed in all patients. At nadir, mean
total IgG levels were reduced by 59% (day 30), mean CIC levels were
reduced by 50% (day 33), mean anti-DSG1 levels were reduced by 22% (day
14) and mean anti-DSG3 levels were reduced by 24% (day 33).

“We believe that effective reduction in PDAI scores at this lowest dose
indicates the potential for a greater magnitude and duration of response
at higher doses. In individual patients, we saw reductions of up to 67%
in total IgG, 71% in CIC, 65% in anti-DSG1 and 61% in anti-DSG3. These
results strengthen our conviction that reducing pathogenic
autoantibodies and blocking key inflammatory functions of FcRn may offer
an innovative approach to treat pemphigus and could give rise to
therapeutic benefits in a wide range of autoimmune diseases that are
similarly mediated,” said Jean-Paul Kress, M.D., president and CEO of
Syntimmune. “We see tremendous promise for SYNT001, which we are also
currently evaluating in an ongoing clinical proof-of-concept trial in
warm autoimmune hemolytic anemia. We look forward to initiating
additional studies in other indications and realizing the broad
potential of SYNT001.”

Syntimmune is conducting an additional ongoing Phase 1b trial of SYNT001
in warm autoimmune hemolytic anemia (WAIHA). Interim data for the WAIHA
trial are expected in the second half of 2018.

About SYNT001

Syntimmune is developing SYNT001, an investigational humanized IgG4
monoclonal antibody optimized to inhibit FcRn binding to IgG at both
neutral and acidic pH. Studies have shown that SYNT001 rapidly
facilitates clearance of IgG and IgG circulating immune complexes
(CICs), with the potential to block innate immune responses induced by
IgG and CIC, as well as inhibit T cell and B cell activation in response
to CIC. Additionally, studies suggest that SYNT001 accomplishes its
effects on IgG without destroying immune cells or impacting other types
of immunoglobulin. SYNT001 has the potential to exert a rapid
therapeutic effect in a wide range of IgG-mediated autoimmune diseases.

About Syntimmune

Founded in 2013, Syntimmune is a clinical-stage biotechnology company
developing differentiated drug candidates in a wide range of autoimmune
diseases. Drawing on the pioneering research of its scientific founders,
the company is advancing novel therapies based on its deep expertise in
the biology of the neonatal Fc receptor (FcRn) and its complex role in
the pathogenesis of IgG-mediated autoimmune diseases. Syntimmune’s lead
candidate, SYNT001, is a monoclonal antibody that specifically blocks
FcRn-IgG interactions and is being studied in multiple Phase 1b/2a
trials for the treatment of IgG-mediated autoimmune diseases. Syntimmune
is also developing SYNT002, which targets FcRn-albumin interactions to
facilitate the clearance of albumin-bound toxins. Headquartered in
Boston, Mass., Syntimmune has raised $78 million in private financing
from leading life sciences investors led by Apple Tree Partners.
Investors also include Partners Innovation Fund, FMB Research, and AFB
Fund. For more information on Syntimmune, please visit the company’s
website at www.syntimmune.com.

Forward-Looking Statements

This release contains “forward-looking statements” within the meaning of
the Private Securities Litigation Reform Act of 1995, including, but not
limited to, statements regarding Syntimmune’s development of its product
candidates, including SYNT001 and SYNT002, the timing of receipt and
announcement of data from its clinical trials and studies, and the
potential benefits to patients of the product candidates. Any
forward-looking statements in this press release are based on
management’s current expectations of future events and are subject to a
number of risks and uncertainties that could cause actual results to
differ materially and adversely from those set forth in or implied by
such forward-looking statements. All information in this press release
is as of the date of the release, and Syntimmune undertakes no duty to
update this information unless required by law.

Contacts

Syntimmune, Inc.
Adam Hansard, 617-206-3149
adam.hansard@syntimmune.com