NEWARK, Calif., Aug. 1, 2019 /PRNewswire/ -- Protagonist
Therapeutics, Inc. (Nasdaq:PTGX) today announced results from the
completed Phase 1 normal healthy volunteer (NHV) study of PN-943,
an oral, gut-restricted alpha-4-beta-7 integrin specific antagonist
in development for the potential treatment of inflammatory bowel
disease (IBD). Results of the first clinical study of PN-943 in a
randomized, double-blind, placebo-controlled, dose escalation study
in NHVs demonstrated that administration of PN-943 was safe and
well tolerated. The pharmacokinetic and pharmacodynamic findings
were consistent with the design of PN-943 as a gut-restricted
alpha-4-beta-7 integrin antagonist.
"These dose-finding results from the multiple ascending dose
(MAD) part of the Phase 1 study with two weeks of daily
administration of PN-943 are consistent with the previously
reported preclinical and Phase 1 single ascending dose (SAD) data
with PN-943," commented Samuel Saks,
M.D., Protagonist Chief Medical Officer. "The MAD data show the
additional benefit of sustained target engagement with repeated
dosing compared to the SAD results. These observations provide
additional confirmation of superior target engagement as compared
with our first generation antagonist PTG-100. We are very
encouraged by these findings and plan to initiate a Phase 2
ulcerative colitis study with PN-943 in early 2020."
PN-943 has been designed as a second generation oral,
gut-restricted, alpha-4-beta-7-integrin antagonist with superior
potency in comparison to the previous candidate PTG-100 that has
validated this novel approach based on our findings from the Phase
2 PROPEL trial in patients with ulcerative colitis (UC) with
PTG-100. In the MAD part of the Phase 1 study, PN-943 was
administered daily over 14 days. The new results from the MAD part
of the study are briefly described below and a complete
presentation of the Phase 1 study results is scheduled for the
American College of Gastroenterology Conference on Oct. 28, 2019, in San
Antonio.
A summary of results of target engagement as measured by maximum
blood receptor occupancy (%RO) and 24 hour area under the %RO curve
(AUC0-24) on day 14 in alpha-4-beta-7 positive CD4
positive memory T cells is provided below (mean ± standard
deviation).
Dose (mg)
|
PN-943 %RO
(max)
(n=8)
|
PTG-100
%RO*
(max)
(n=8)
|
PN-943 %RO
(AUC0-24)
(n=8)
|
PTG-100
%RO*
(AUC0-24)
(n=8)
|
100 mg
|
56 ± 8.8
|
26 ± 9.8
|
971 ± 179
|
384 ± 180
|
300 mg
|
80 ± 5.4
|
51 ± 7.0
|
1467 ± 145
|
930 ± 226
|
1000 mg
|
96 ± 1.0
|
74 ±
6.9#
|
1957 ± 372
|
1544 ±
144#
|
*Previously reported
results from Phase 1 trial of PTG-100 in healthy volunteers (table
above).
|
#
N=7
|
The Phase 2 PROPEL trial of PTG-100 in patients with ulcerative
colitis has previously demonstrated that pharmacodynamic responses
correlate with histologic remission and clinical efficacy responses
(see Sandborn, W. et al., PTG-100, an oral
gut-restricted peptide alpha-4-beta-7 antagonist, induces clinical
and histologic remission in patients with moderate to
severely active ulcerative colitis. United European
Gastroenterology Journal 2018; 6 (Supplement 1),
2018)
About PN-943
PN-943 is an oral, gut-restricted alpha-4-beta-7 integrin
specific antagonist peptide in clinical development for the
treatment of inflammatory bowel disease. PN-943 is designed to
offer the convenience of oral administration and the potential for
improved safety and tolerability compared to antibody therapeutics
administered by injection that target the alpha-4-beta-7 integrin
pathway.
About Protagonist Therapeutics, Inc.
Protagonist Therapeutics is a clinical stage biopharmaceutical
company that utilizes a proprietary technology platform to discover
and develop novel peptide-based drugs to transform existing
treatment paradigms for patients with significant unmet medical
needs. PTG-300 is an injectable hepcidin mimetic in development for
the treatment of iron overload anemia and related rare blood
diseases. PTG-300 is currently in a global Phase 2 study in
beta-thalassemia. PTG-200 is an oral, gut-restricted interleukin-23
receptor specific antagonist peptide in clinical development for
the potential treatment of inflammatory bowel disease. The Company
has a worldwide license and collaboration agreement with Janssen
Biotech for the clinical development of PTG-200 and a Phase 2 study
in Crohn's disease is expected in fourth quarter of 2019. PN-943 is
an oral, gut-restricted alpha-4-beta-7 integrin specific antagonist
peptide in clinical development for the potential treatment of
inflammatory bowel disease, with ulcerative colitis as the initial
intended indication.
Protagonist is headquartered in Newark, California. For further information,
please visit http://www.protagonist-inc.com.
Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements for
purposes of the safe harbor provisions of the Private Securities
Litigation Reform Act of 1995. Forward-looking statements include
statements regarding our intentions or current expectations
concerning, among other things, the availability of results of our
clinical trials. In some cases, you can identify these statements
by forward-looking words such as "anticipate," "believe," "may,"
"will," "expect," or the negative or plural of these words or
similar expressions. Forward-looking statements are not guarantees
of future performance and are subject to risks and uncertainties
that could cause actual results and events to differ materially
from those anticipated, including, but not limited to, our ability
to develop and commercialize our product candidates, our ability to
earn milestone payments under our collaboration agreement with
Janssen, our ability to use and expand our programs to build a
pipeline of product candidates, our ability to obtain and maintain
regulatory approval of our product candidates. Additional
information concerning these and other risk factors affecting our
business can be found in our periodic filings with the Securities
and Exchange Commission, including under the heading "Risk Factors"
contained in our Quarterly Report on Form 10-Q for the three months
ended March 31, 2019, filed with the
Securities and Exchange Commission. Forward-looking statements are
not guarantees of future performance, and our actual results of
operations, financial condition and liquidity, and the development
of the industry in which we operate, may differ materially from the
forward-looking statements contained in this press release. Any
forward-looking statements that we make in this press release speak
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SOURCE Protagonist Therapeutics, Inc.