- Oral PL8177 is gut restricted in rats, dogs and
humans
- Bioinformatics data shows positive effects on enterocytes
and infiltrating immune cells
CRANBURY, N.J., March 2,
2023 /PRNewswire/ -- Palatin Technologies, Inc. (NYSE
American: PTN), a biopharmaceutical company
developing first-in-class medicines based on molecules
that modulate the activity of the melanocortin receptor system,
today announced Frontiers in Immunology published a
manuscript, "A novel oral formulation of the melanocortin-1
receptor agonist PL8177 resolves inflammation in preclinical
studies of inflammatory bowel disease and is gut restricted in
rats, dogs and humans," summarizing data demonstrating
oral PL8177 provides therapeutic effects in inflammatory bowel
disease and pharmacokinetic data from a clinical study showing
PL8177 remains restricted to the gut.
Palatin research scientists conducted multiple studies in rat
models of inflammatory bowel disease to assess the
immunopharmacology of PL8177. Key findings included maintenance of
intact colon structure and barrier, reduced immune cell
infiltration, and increased enterocytes with PL8177 treatment.
Genomic data show that oral PL8177 treatment causes relative cell
populations and key gene expression levels to move closer to
healthy controls. Compared with vehicle, PL8177 treated colon
samples show positive effects on immune marker genes and diverse,
well known immune-related pathways.
Data from pharmacokinetic studies demonstrated that in rats and
dogs, orally administered PL8177 was detected at higher amounts in
the colon vs upper GI tract. [14C]-PL8177 was detected
in the feces but not in the plasma and urine in humans suggesting
that [14C]-PL8177 was released from the polymer
formulation within the GI tract, where it is expected to exert its
therapeutic effect.
"These promising results demonstrate the potential value of
targeting the melanocortin-1 receptor ("MC1r") for treating
inflammatory bowel disease," said Carl
Spana, Ph.D., President and CEO of Palatin. "This data adds
to the robust body of preclinical and clinical safety,
tolerability, efficacy, and mechanism of action data for PL8177 and
provides support for our oral PL8177 Phase 2 clinical trial for
patients with ulcerative colitis ("UC"), which is currently
enrolling patients."
Dr. Spana further commented, "In preparation for human dosing in
the clinic, oral PL8177 demonstrated an excellent safety profile
with zero observed safety or tolerability issues in both rats and
dogs. Because PL8177 is a peptide, restricted to the gut, and is
not systemically absorbed, it is anticipated the ongoing Phase 2
clinical trial for patients with UC will demonstrate the same
excellent safety and tolerability profile."
The authors on the paper were John
Dodd, Carl Spana,
Robert Jordan, Marie Makhlina, Keith
Barnett, Alison Orb, Priyanka
Dhingra, and Paul Kayne of
Palatin, and Ad Roffel from Consulting and Advisory Services,
Clinical Pharmacology, ICON plc, Groningen, Netherlands. The citation may be found at the
following
link: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1083333.
Drugs targeting the melanocortin system have emerged as
promising therapeutics for several conditions, including
inflammatory diseases, obesity and sexual dysfunction, with several
already FDA approved. As illustrated in the publication,
melanocortins are peptides that have anti-inflammatory and
pro-resolving effects. Many of these effects are mediated by the
melanocortin-1 receptor as reported in several experimental
settings. As such, MC1r can be a viable target for the development
of new therapies that mimic endogenous pro-resolving mediators.
Palatin has multiple MC1r agonist candidates in pre-clinical and
clinical development.
Palatin is conducting a Phase 2 multi-center, randomized,
double-blind, placebo-controlled, adaptive design, clinical study
of PL8177, with once daily (QD) oral dosing in adult patients with
active UC. The study is designed to enroll up to 28 adult patients
with active UC from approximately 22 sites. All subjects who meet
the eligibility criteria will be randomized to receive either
placebo or oral PL8177.
The PL8177-205 interim assessment is expected to occur in the
first half of calendar year 2023, with final topline data
anticipated in the second half of calendar year 2023. Additional
trial information, including inclusion and exclusion criteria, can
be found at https://clinicaltrials.gov/ via the identifier
NCT05466890.
About PL8177
PL8177 is a synthetic cyclic heptapeptide with demonstrated
efficacy in multiple animal inflammatory bowel disease models.
PL8177 is a potent, selective agonist at the human melanocortin-1
receptor, with sub-nanomolar affinity binding and EC50
functional values. Palatin data demonstrates that the oral
formulation of PL8177 was protected from degradation in the stomach
and small intestine and delivered to the large intestine and colon
over an extended period. In addition, orally administered PL8177
had a significant effect on resolving inflammation in a rat bowel
inflammation model.
PL8177 in oral formulations has demonstrated repeated, robust
efficacy in ulcerative colitis disease models. MC1r is found on
epithelial cells and resident macrophages of the colon which are
accessible from the lumen of the colon. Orally administered PL8177
is not systemically absorbed. PL8177 has the potential for
excellent efficacy without safety concerns.
About Ulcerative Colitis
Ulcerative colitis is a chronic disease of the large intestine
(colon), with inflammation and ulcerations that can cause
significant abdominal pain, persistent diarrhea, loss of appetite
and other symptoms. An estimated 1 million individuals in
the United States are affected by
ulcerative colitis, with over 350,000 diagnosed with
moderate-to-severe disease. Existing treatments are not effective
in a substantial portion of patients with moderate-to-severe
ulcerative colitis, with certain severe cases resulting in surgical
removal of the colon.
About Melanocortin Receptor Agonists and Inflammation
The melanocortin receptor ("MCr") system has effects on
inflammation, immune system responses, metabolism, food intake, and
sexual function. There are five melanocortin receptors, MC1r
through MC5r. Modulation of these receptors, through use of
receptor-specific agonists, which activate receptor function, or
receptor-specific antagonists, which block receptor function, can
have medically significant pharmacological effects. Many tissues
and immune cells located throughout the body, including the gut,
kidney and eye, express melanocortin receptors, empowering our
opportunity to directly activate natural pathways to resolve
disease inflammation.
About Palatin
Palatin is a biopharmaceutical company developing first-in-class
medicines based on molecules that modulate the activity of the
melanocortin receptor systems, with targeted, receptor-specific
product candidates for the treatment of diseases with significant
unmet medical need and
commercial potential. Palatin's strategy
is to develop products and then form
marketing collaborations with industry leaders to maximize their
commercial potential. For additional information regarding Palatin,
please visit Palatin's website at www.Palatin.com and follow
Palatin on Twitter at @PalatinTech.
Forward-looking Statements
Statements in this press release that are not historical facts,
including statements about future expectations of Palatin, such as
statements about PL8177 clinical trials and results, are
"forward-looking statements" within the meaning of Section 27A of
the Securities Act of 1933, Section 21E of the Securities Exchange
Act of 1934 and as that term is defined
in the Private Securities Litigation Reform Act of 1995. Palatin
intends that such forward-looking statements be subject to the
safe harbors created thereby. Such forward-looking statements
involve known and unknown risks, uncertainties and other
factors that could cause Palatin's actual results to be materially different from its historical
results or from any results expressed or implied by such
forward-looking statements. Palatin's actual results may differ
materially from those discussed in the forward-looking statements
for reasons including, but not limited to, results of clinical
trials, regulatory actions by the FDA and other regulatory and the
need for regulatory approvals, Palatin's ability to fund
development of its technology and establish and successfully
complete clinical trials, the length of time and cost required to
complete clinical trials and submit applications for regulatory
approvals, products developed by competing pharmaceutical,
biopharmaceutical and biotechnology companies, commercial
acceptance of Palatin's products, and other factors discussed in
Palatin's periodic filings with the Securities and Exchange
Commission. Palatin is not responsible for updating for events that
occur after the date of this press release.
Palatin Technologies® is a registered trademarks of Palatin
Technologies, Inc.
View original content to download
multimedia:https://www.prnewswire.com/news-releases/frontiers-in-immunology-publishes-pre-clinical-study-of-palatins-oral-formulation-of-pl8177-demonstrating-therapeutic-effects-in-inflammatory-bowel-disease-301760623.html
SOURCE Palatin Technologies, Inc.