- PBI-4050 monotherapy and combination with nintedanib
demonstrated promising results in the treatment of Idiopathic
Pulmonary Fibrosis (IPF)
- Data on PBI-4050 regulation of proteins involved in human
lung fibrosis
- Plasminogen administration shown to reduce acute lung injury
(ALI) in an acute pancreatitis model
- PBI-4425 shown to reduce pulmonary emphysema in a
scleroderma mouse model
LAVAL, QC, May 23, 2017 /CNW Telbec/ - Prometic Life
Sciences Inc. (TSX: PLI) (OTCQX: PFSCF) ("Prometic" or
the "Corporation") presented new data at the 2017 American
Thoracic Society (ATS) International Conference in Washington, D.C. The data presented included
results from a Phase 2 clinical trial evaluating PBI-4050 in
patients with idiopathic pulmonary fibrosis ("IPF"), and the
benefits of plasminogen administration in reducing lung injury in a
gold standard animal model of ALI/ARDS associated with acute
pancreatitis.
PBI-4050 Phase 2 clinical data
During an oral presentation, Joseph
Parker, M.D., senior director, clinical development at
Prometic, explained that the lung function in 25 IPF patients
receiving either PBI-4050 alone or PBI-4050 in combination with
nintedanib remained stable as measured by the difference between
the Forced Vital Capacity (FVC) at baseline and following 12 weeks
of treatment (∆FVC of -12 ml and +2 ml, respectively). This
contrasted significantly with the patients who received the
PBI-4050 and pirfenidone combination treatment. In these patients,
FVC declined significantly (n=15, ∆FVC of -102 ml). An apparent
drug-drug interaction between pirfenidone and PBI-4050 resulted in
a reduction of the therapeutic effect of each drug. PBI-4050's
absorption was reduced by over 50%, and stimulation of the
metabolism of pirfenidone by PBI-4050 may have led to a
sub-therapeutic level of pirfenidone. PBI-4050 + nintedanib
provided a statistically significant benefit over PBI-4050 +
pirfenidone (∆FVC of +2 ml vs. -102 ml respectively, p=0.0376).
There was no statistical difference between PBI-4050 + nintedanib
and PBI-4050 alone. PBI-4050 alone trended favorably compared to
PBI-4050 + pirfenidone (∆FVC of -12 ml vs. -102 ml, p=0.1359).
Change after 12 weeks
of therapy
|
PBI-4050
Monotherapy
(n=9)
|
PBI-4050 +
Nintedanib
(n=16)
|
PBI-4050 +
Pirfenidone
(n=15)
|
∆FVC (ml)
|
-12 ml*
|
+2 ml**
|
-102 ml
|
*p = 0.1359 vs. PBI-4050 + Pirfenidone; n.s. vs. PBI-4050 +
Nintedanib
** p = 0.0376 vs. PBI-4050 + Pirfenidone
"PBI-4050 presented a highly compelling safety and tolerability
profile throughout all clinical trials," said Dr. Parker.
"Because PBI-4050 was well-tolerated and appeared to demonstrate a
dose response relationship in the Phase 2 study, the planned
pivotal Phase 2/3 trial will include three arms – two dose levels
of PBI-4050 and placebo."
Last month, Prometic confirmed the U.S. Food and Drug
Administration's (FDA) concurrence that only the combination of
PBI-4050 and nintedanib would be required in the placebo-controlled
Phase 2/3 clinical trial. Prometic also intends to initiate a
second Phase 2/3 placebo-controlled trial in which IPF patients who
failed to tolerate either nintedanib or pirfenidone would be
randomized to receive either PBI-4050 or placebo (PBI-4050
Monotherapy). Prometic plans to initiate both studies in the second
half of 2017.
PBI-4050 and effect on biomarkers in lung fibrosis
Martin Leduc, Ph.D., scientist at
Prometic, presented data on the differentiating effect of PBI-4050
when compared to pirfenidone and nintedanib on
biomarkers.
Abnormally activated small airway epithelial cells and
interstitial fibroblasts are the principal effector cells in the
pathogenesis of lung fibrosis. These cells produce a variety of
proteins (biomarkers) involved in activities related to
myofibroblast activation, inflammation and extracellular matrix
accumulation and remodeling that all contribute to the pulmonary
fibrosis process.
Plasminogen as potential treatment for Acute Lung Injury
(ALI)
Data were presented by Lyne Gagnon, Ph.D., vice president of
research and development at Prometic, on the efficacy of Prometic's
plasminogen in significantly reducing the lesions in the lung in
the gold standard mouse model of acute pancreatitis. In this model,
the circulating level of plasminogen was reduced, resulting in
fibrin and fibrinous material being deposited in the lung.
Prometic's plasminogen treatment restored the plasminogen level in
the animals and cleared the lung of fibrin deposits. Pathological
lesions in the lungs of non-treated animals were similar to those
seen in the lungs of human patients who develop ALI following acute
pancreatitis.
PBI-4425
PBI-4425, an analogue of PBI-4050, expected to enter clinical
trials later this year, was shown to significantly reduce pulmonary
emphysema and cutaneous hyperplasia in the tight-skin (TSK) mouse
model for scleroderma. TSK animals develop cutaneous hyperplasia,
cardiac hypertrophy, pulmonary emphysema and autoimmunity against
scleroderma target autoantigens. The treatment of scleroderma is
one of the indications potentially earmarked for PBI-4425.
Posters and oral presentation
- Phase 2, Open label, Single arm, Exploratory, Observational
study to evaluate the safety and tolerability of PBI-4050 in
patients with Idiopathic Pulmonary Fibrosis (IPF)
- PBI-4050 Reduces Expression of Fibrosis Biomarkers in the
BioMAP SAEMyoF Primary Human Small Airway Epithelial Cells and Lung
Myofibroblasts System
- Plasminogen Reduces Acute Lung Injury in an Acute Pancreatitis
Model
- PBI-4425, a Novel First-in-class Anti-inflammatory/Antifibrotic
Compound, Reduces Pulmonary Emphysema and Cutaneous Hyperplasia in
Tight-skin (FBN1) Mouse
- PBI-4425, a Novel First-in-class
Anti-inflammatory/Anti-fibrotic Compound, Inhibits Collagen I and
CTGF Production in Human Fibroblasts, and Reduces Lung Fibrosis in
the Bleomycin-Induced Lung Fibrosis Model
- Oral Treatment with PBI-4050 Reduces Acute Lung Injury in an
Acute Pancreatitis Model
About acute lung injury (ALI) and acute respiratory distress
syndrome (ARDS)
Acute lung injury (ALI) and acute respiratory distress syndrome
(ARDS) are life-threatening conditions resulting in respiratory
failure in critically ill patients. ALI is the term used to
describe the pulmonary response to a broad range of injuries
occurring either directly to the lung or as a consequence of injury
or inflammation at other sites of the body, such as acute
pancreatitis, severe burns, trauma or sepsis. ARDS represents the
most severe subset of this condition. ALI and ARDS affect
approximately 190,000 patients every year in the U.S., and are
associated with a high mortality rate varying between 30% and
60%.
Prometic has previously disclosed that ALI and ARDS are two
examples of acute critical care conditions it intends to pursue
with its plasminogen product once it receives regulatory approval
for use in congenital plasminogen deficiency, expected later this
year.
About PBI-4050 & PBI-4425
PBI-4050 and PBI-4425 are Prometic's orally active lead drug
candidates targeting fibrosis. PBI-4050 is entering Phase 2/3
clinical trials after demonstrating efficacy and excellent safety
profiles in three Phase 2 open label clinical trials. Prometic
plans to initiate the next phase of clinical trials for PBI-4425 in
the first quarter of 2018. Fibrosis is a complex process by which
continuing inflammation causes vital organs to lose their function
as normal tissue is replaced by fibrotic scar tissue. The
proof-of-concept data generated to-date with PBI-4050 confirms its
anti-fibrotic activity in several key organs including the kidneys,
the heart, the lungs and the liver. PBI-4050 has on-going clinical
trials in patients with metabolic syndrome and type 2 diabetes,
cystic fibrosis with related diabetes and Alström Syndrome. The
planned Phase 2/3 clinical trials scheduled to commence this year
target patients with idiopathic pulmonary fibrosis (IPF) and
chronic kidney disease (CKD). Twenty-six million patients in the
U.S. alone are believed to suffer from CKD. Patients with severe
CKD (stages 3 and 4) suffer from a progressive loss of their renal
function leading to end-stage renal disease and the need for
dialysis or kidney transplant. Cardiovascular complications are the
most common cause of death in dialysis patients.
About Plasminogen
Plasminogen is a naturally occurring protein that is synthesized
by the liver and circulates in the blood. Activated plasminogen,
plasmin, is a fundamental component of the fibrinolytic system and
is the main enzyme involved in the lysis of blood clots and
clearance of extravasated fibrin. Plasminogen is therefore vital in
wound healing, cell migration, tissue remodeling, angiogenesis and
embryogenesis.
About Prometic Life Sciences
Inc.
Prometic Life Sciences Inc. (www.prometic.com) is a
long-established biopharmaceutical company with globally recognized
expertise in bioseparations, plasma-derived therapeutics and
small-molecule drug development. Prometic offers its
state-of-the-art technologies for large-scale purification of
biologics, drug development, proteomics and the elimination of
pathogens to a growing number of industry leaders. The company uses
its own affinity technology, which provides for highly efficient
extraction and purification of therapeutic proteins from human
plasma, to develop best-in-class therapeutics and orphan drugs.
Prometic is also active in developing its own novel small-molecule
therapeutic products targeting unmet medical needs in the fields of
fibrosis, anemia, neutropenia, cancer and autoimmune
diseases/inflammation as well as certain nephropathies.
Headquartered in Laval, Canada,
Prometic has R&D facilities in the U.K., the U.S. and
Canada, manufacturing facilities
in the U.K. and commercial activities in the U.S., Canada, Europe, Russia, Asia
and Australia.
Forward Looking Statements
This press release contains forward-looking statements about
Prometic's objectives, strategies and businesses that involve risks
and uncertainties. These statements are "forward-looking" because
they are based on our current expectations about the markets we
operate in and on various estimates and assumptions. Actual events
or results may differ materially from those anticipated in these
forward-looking statements if known or unknown risks affect our
business, or if our estimates or assumptions turn out to be
inaccurate. Such risks and assumptions include, but are not limited
to, Prometic's ability to develop, manufacture, and successfully
commercialize value-added pharmaceutical products, the availability
of funds and resources to pursue R&D projects, the successful
and timely completion of clinical studies, the ability of Prometic
to take advantage of business opportunities in the pharmaceutical
industry, uncertainties related to the regulatory process and
general changes in economic conditions. You will find a more
detailed assessment of the risks that could cause actual events or
results to materially differ from our current expectations in
Prometic's Annual Information Form for the year ended December 31, 2016, under the heading "Risk and
Uncertainties related to Prometic's business". As a result, we
cannot guarantee that any forward-looking statement will
materialize. We assume no obligation to update any forward-looking
statement even if new information becomes available, as a result of
future events or for any other reason, unless required by
applicable securities laws and regulations. All amounts are in
Canadian dollars unless indicated otherwise.
SOURCE ProMetic Life Sciences Inc.