Acasti Pharma Inc. (“Acasti or the “Company”) (NASDAQ: ACST –
TSX-V: ACST), a biopharmaceutical innovator focused on the
research, development and commercialization of its prescription
drug candidate CaPre® (omega-3 phospholipid) for the treatment of
severe hypertriglyceridemia (HTG), released some preliminary new
animal data today which provides additional insights into CaPre’s
potential mechanism of action in diabetes. In the Company’s Phase 2
studies in humans, a statistically significant reduction of
hemoglobin A1c (HbA1c) was seen in the 4 gram treatment arm of the
COLT study. This is the same dose that is currently being tested in
Acasti’s TRILOGY Phase 3 program in humans. This positive
HbA1c result In COLT was surprising at the time, and potentially
unique to CaPre, as other therapeutic OM3s had previously shown no
effect on glucose metabolism in a diabetic or pre-diabetic
population. The main objective for this new mechanistic diabetes
mouse study was to assess if CaPre acts on glucose and/or insulin
in some unique manner, and to compare results head-to-head with
icosapent ethyl (VASCEPA), a marketed omega-3 therapeutic, and
metformin, a widely prescribed diabetic medication. Acasti
collaborated with Professor André Marette, Ph.D. who conducted the
study. Dr. Marette, who is the Director of the Pfizer Chair to
study the pathogenesis of insulin resistance and cardiometabolic
diseases at the University Laval, Quebec, conducted the study for
Acasti in a widely used and well accepted animal model in
diet-induced obese C57BL6 mice to compare the mechanisms of action
of CaPre versus icosapent ethyl and metformin on insulin resistance
and type 2 diabetes. A second, still ongoing study will also
compare these same drugs in a fatty liver disease animal model. Dr.
Marette is a highly regarded researcher of cardiometabolic disease,
and he has published numerous papers in prestigious journals such
as Nature Medicine.
The preliminary findings obtained for the
diabetes mouse study showed that CaPre may promote insulin
secretion as seen by statistically significant results produced in
a standard glucose challenge test, thus suggesting a mechanism of
action different and unique when compared to metformin, which does
not promote insulin secretion. Furthermore, icosapent ethyl showed
no effect on insulin or any improvement in glucose metabolism or
management.
Key additional findings from this diabetic mouse
study are:
- CaPre increased insulin production in association with
increased c-peptide levels, suggesting that this effect is linked
to greater insulin secretion by ß cells. This was also associated
with a tendency for lower glucose responses during a glucose
challenge test. CaPre exhibited a dose response, where the higher
the dose the more insulin was secreted.
- Both CaPre and icosapent ethyl significantly increased plasma
18RS-HEPE, (a metabolite of EPA and a precursor of Resolvin E1) as
compared to the untreated control and metformin groups. Despite the
lower levels of EPA in CaPre’s composition, the actual levels of
18RS-HEPE reached in the blood were higher for CaPre than levels
produced by icosapent ethyl. Again, a dose response effect was seen
with CaPre. 18RS-HEPE and Resolvin E1 are both resolving mediators
of OM3s, and particularly EPA, and they are involved in the
resolution of inflammation that is triggered in many chronic
diseases including obesity and diabetes.
- Both high dose (HED or human equivalent dose of 4 grams/day),
and low dose (HED of 2 grams/day) of CaPre significantly increased
plasma levels of 17S-HDHA and PDX (two metabolites of DHA) as
compared to the untreated control group. The effects of high dose
CaPre on PDX was very robust and significant, and much greater than
those of icosapent ethyl, which showed virtually no response.
Research has shown that increased levels of PDX improves insulin
sensitivity in various models of insulin resistance and diabetes by
several mechanisms, including by limiting inflammation in metabolic
tissues, as well as by enhancing skeletal muscle IL-6 secretion,
AMP activated protein kinase (AMPK) activation and glucose uptake,
and by enhancing insulin's ability to suppress hepatic glucose
production, which is also elevated in diabetic patients.
Data from the diabetic mouse study are still being compiled and
finalized. The second study underway in a fatty liver/NASH
disease model, will further confirm the findings of the diabetes
study, and may potentially provide more insight into the mechanism
of action of CaPre on the plasma lipid profile, and in fatty liver
disease by further comparing the impact of CaPre on plasma TGs,
LDL-C and HDL-C, as well as on hepatic lipid accumulation versus
that of icosapent ethyl and metformin. Based on the findings from
both of these study phases, Acasti and Dr. Marette plan to submit
the data to a peer review journal for publication. Acasti may also
file additional patents covering unique aspects and applications of
this expanded understanding of CaPre’s mechanism of action.
Dr. Marette commented, “Our initial pre-clinical
studies with CaPre are very promising. The effect of CaPre on
insulin secretion may suggest preservation of beta-cell function
early in the development of type 2 diabetes. The robust increase in
plasma PDX levels with CaPre treatment is also of marked interest
given the pleiotropic action of this key anti-inflammatory and
pro-metabolic molecule. We have not seen this in previous studies
with other OM3s using similar pre-clinical models of diabetes.”
Pierre Lemieux, Ph.D., COO and CSO of Acasti,
added, “We are very pleased to collaborate with Dr. Marette. He has
been a leader in the omega-3 research field, and especially in
elucidating the importance and the role of resolvins and protectins
(PDX) in the management of inflammation related to insulin
resistance and glucose management in diabetes. These studies
may also further reinforce and explain some of the unique and
positive results reported in our Phase 2 human clinical trials.
Furthermore, based on this data, we now plan to expand our list of
exploratory markers to be evaluated in our TRILOGY Phase 3 program
to include the resolvins and protectins such as PDX and other
related pro-resolution molecules.”
About CaPre (omega-3
phospholipid)
Acasti’s prescription drug candidate, CaPre, is
a highly purified omega-3 phospholipid concentrate derived from
krill oil, and is being developed to treat severe
hypertriglyceridemia, a metabolic condition that contributes to
increased risk of cardiovascular disease and pancreatitis. Its
omega-3s, principally EPA and DHA, are either “free” or bound to
phospholipids, which allows for better absorption into the body.
Acasti believes that EPA and DHA are more efficiently transported
by phospholipids sourced from krill oil than the EPA and DHA
contained in fish oil that are transported either by triglycerides
(as in dietary supplements) or as ethyl esters in other
prescription omega-3 drugs, which must then undergo additional
digestion before they are ready for transport in the bloodstream.
Clinically, the phospholipids may not only improve the absorption,
distribution, and metabolism of omega-3s, but they may also
decrease the synthesis of LDL cholesterol in the liver, impede or
block cholesterol absorption, and stimulate lipid secretion from
bile. In two Phase 2 studies, CaPre achieved a statistically
significant reduction of triglycerides and non-HDL cholesterol
levels in patients across the dyslipidemia spectrum from patients
with mild to moderate hypertriglyceridemia (patients with TG blood
levels between 200mg/dl and 500mg/dl) to patients with severe
hypertriglyceridemia (those with TG levels above 500mg/dl).
Furthermore, in the Phase 2 studies, CaPre demonstrated the
potential to actually reduce LDL, or “bad cholesterol”, as well as
the potential to increase HDL, or “good cholesterol”, especially at
the therapeutic dose of 4 grams/day. The Phase 2 data also showed a
significant reduction of HbA1c at a 4 gram dose, suggesting that
due to its unique omega-3/phospholipid composition, CaPre may
actually improve long-term glucose metabolism. Acasti’s TRILOGY
Phase 3 program is currently underway.
About Acasti Pharma
Acasti Pharma is a biopharmaceutical innovator
advancing a potentially best-in-class cardiovascular drug, CaPre®
(omega-3 phospholipid), for the treatment of hypertriglyceridemia,
a chronic condition affecting an estimated one third of the U.S.
population. Since its founding in 2008, Acasti Pharma has focused
on addressing a critical market need for an effective, safe and
well-absorbing omega-3 therapeutic that can make a positive impact
on the major blood lipids associated with cardiovascular disease
risk. The company is developing CaPre in a Phase 3 clinical program
in patients with severe hypertriglyceridemia, a market that
includes 3 to 4 million patients in the U.S. The addressable market
may expand significantly if omega-3s demonstrate long-term
cardiovascular benefits in on-going third party outcomes studies.
Acasti may need to conduct at least one additional clinical trial
to support FDA approval of a supplemental New Drug Application to
expand CaPre’s indications to this segment. Acasti’s strategy is to
commercialize CaPre in the U.S. and the company is pursuing
development and distribution partnerships to market CaPre in major
countries around the world. For more information, visit
www.acastipharma.com.
Forward
Looking
Statements
Statements in this press release that are not
statements of historical or current fact constitute
“forward-looking information” within the meaning of Canadian
securities laws and “forward-looking statements” within the meaning
of U.S. federal securities laws (collectively, “forward-looking
statements”). Such forward-looking statements involve known and
unknown risks, uncertainties, and other unknown factors that could
cause the actual results of Acasti to be materially different from
historical results or from any future results expressed or implied
by such forward-looking statements. In addition to statements which
explicitly describe such risks and uncertainties, readers are urged
to consider statements labeled with the terms “believes,” “belief,”
“expects,” “intends,” “anticipates,” “potential,” “should,” “may,”
“will,” “plans,” “continue”, “targeted” or other similar
expressions to be uncertain and forward-looking. Readers are
cautioned not to place undue reliance on these forward-looking
statements, which speak only as of the date of this press release.
Forward-looking statements in this press release include, but are
not limited to, information or statements about Acasti’s strategy,
future operations, prospects and the plans of management; Acasti’s
ability to conduct all required clinical and non-clinical trials
for CaPre, including the timing and results of those trials; the
timing and the outcome of licensing negotiations; CaPre’s potential
to become the “best-in-class” cardiovascular drug for treating
severe Hypertriglyceridemia (HTG), Acasti’s ability to commercially
launch CaPre, CaPre’s potential to meet or exceed the target
primary endpoint of reducing triglycerides by 20% compared to
placebo, CaPre’s potential mechanism of action in diabetes, and
Acasti’s ability to fund its continued operations.
The forward-looking statements contained in this
press release are expressly qualified in their entirety by this
cautionary statement, the “Cautionary Note Regarding
Forward-Looking Information” section contained in Acasti’s latest
annual report on Form 20-F and most recent management’s discussion
and analysis (MD&A), which are available on SEDAR at
www.sedar.com, on EDGAR at www.sec.gov/edgar/shtml, and on the
investor section of Acasti’s website at www.acastipharma.com. All
forward-looking statements in this press release are made as of the
date of this press release. Acasti does not undertake to update any
such forward-looking statements whether as a result of new
information, future events or otherwise, except as required by law.
The forward-looking statements contained herein are also subject
generally to assumptions and risks and uncertainties that are
described from time to time in Acasti’s public securities filings
with the Securities and Exchange Commission and the Canadian
securities commissions, including Acasti’s latest annual report on
Form 20-F and most recent MD&A.
Neither NASDAQ, the TSX Venture Exchange nor its
Regulation Services Provider (as that term is defined in the
policies of the TSX Venture Exchange) accepts responsibility for
the adequacy or accuracy of this release.
Acasti
Contact:Jan
D’AlviseChief Executive OfficerTel: 450-686-4555Email:
info@acastipharma.comwww.acastipharma.com
Investor
Contact:Crescendo
Communications, LLCTel: 212-671-1020Email:
ACST@crescendo-ir.com
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