TOULOUSE, France & LAKELAND, Fla.--(BUSINESS WIRE)--Regulatory News:
CERENIS Therapeutics (Paris:CEREN) (FR0012616852 – CEREN – PEA-PME eligible), an international biopharmaceutical company dedicated to the discovery and development of HDL-based innovative therapies for treating cardiovascular and metabolic diseases, as well as new HDL-based vectors for targeted drug delivery in the field of oncology, announces the approval and the upcoming launch of the second Phase I study to assess the daily administration of increasing doses of CER-209 over a 28-day period in patients with a high risk of developing Non-Alcoholic Steato-Hepatitis (NASH) and/or Non-Alcoholic Fatty Liver Disease (NAFLD).
Moreover, during the second annual H.C. Wainwright NASH Investor Conference in New York on March 19, 2018, Jean-Louis Dasseux will discuss the scientific aspects and clinical strategy of CER-209.
Jean-Louis Dasseux, founder and CEO of Cerenis, commented: “We are eager to validate CER-209’s safety and tolerance profile via the multiple dose Phase I study whose results are expected in Q4 2018. As well as the standard tolerance, safety and pharmacokinetic parameters examined in this study, the first pharmacodynamic data regarding CER-209’s mechanism of action should confirm our drug candidate’s therapeutic potential. CER-209, by activating the natural metabolic pathways mediated by the P2Y13 receptor, promotes HDL recognition and lipid elimination by the liver. It is precisely this objective of reducing hepatic fat that the Phase II study – the next stage in CER-209’s clinical development – will evaluate. This will represent a major milestone in the development of this treatment that aims to address NASH and NAFLD, which are among the leading causes of cirrhosis in the United States, and associated cardiovascular diseases that represent the main cause of death among patients with liver steatosis”.
Daily administration of repeated and increasing doses of CER-209 over
a 28-day period in patients with a high risk of NAFLD/NASH
The
regulatory authorities have given their approval to initiate the
enrollment of subjects that will begin by end-March 2018. The primary
endpoints concern safety and tolerance following the administration of
multiple doses of CER-209. Pharmacokinetic and pharmacodynamic endpoints
will also be studied in order to define the optimal dose for the next
studies.
The subjects included in the study have large waist circumferences and high triglyceride levels, parameters associated with a high risk of subsequently developing metabolic diseases such as NAFLD and NASH.
The protocol for this randomized, double blind and placebo controlled trial foresees the enrollment of 6 cohorts of subjects. Multiple doses of CER-209 will be administered in 6 cohorts of 5 subjects each. Daily doses of 10, 30, and 60 mg of CER-209 will be given for 28 days. In all cohorts 4 subjects will receive active drug.
First clinical assessment of the mechanism of action associated with
the P2Y13 receptor
The profile of the study’s subjects will
enable assessment of two parameters associated with the mechanism of
action of CER-209:
- Changes in the level of lipids in the liver, measured using magnetic resonance imaging (MRI-PDFF);
- The rate of fecal elimination of cholesterol and bile acids.
Positive efficacy signals, demonstrating improvement in these parameters, would enable validation of previous findings, and would strengthen CER-209’s therapeutic potential, already highlighted in preclinical studies.
The mechanism of action of CER-209, an agonist of the P2Y13 receptor
In
preclinical models, CER-209 results in a marked reduction in
steatohepatitis as determined by a reduction in the levels of
cholesterol, triglycerides and fatty acids in the liver compared with
the placebo, as well as a reduction in atherosclerosis. Furthermore,
CER-209 produces significant decreases in liver enzymes (ALT and AST) in
the plasma. These effects suggest the restoration of liver integrity and
indicate CER-209’s strong potential for treating NAFLD and NASH while
reducing the risks associated with cardiovascular disease.
About CERENIS: www.cerenis.com
CERENIS
Therapeutics is an international biopharmaceutical company dedicated to
the discovery and development of innovative lipid metabolism therapies
for the treatment of cardiovascular and metabolic diseases. HDL is the
primary mediator of the reverse lipid transport, or RLT, the only
natural pathway by which excess lipids is removed from arteries and is
transported to the liver for elimination from the body.
CERENIS is developing a portfolio of lipid metabolism therapies, including HDL mimetics for patients with genetic HDL deficiency, as well as drugs which increase HDL for patients with a low number of HDL particles to treat atherosclerosis and associated metabolic diseases including Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steato-Hepatitis (NASH). Capitalizing on its expertise, Cerenis is developing the first HDL-based targeting drug delivery platform dedicated to the oncology field (immuno-oncology and chemotherapy).
CERENIS is well positioned to become one of the leaders in the HDL therapeutic market, with a broad portfolio of programs in development.
About CER-001
CER-001 is an engineered complex of
recombinant human apoA-I, the major structural protein of HDL, and
phospholipids. It has been designed to mimic the structure and function
of natural, nascent HDL, also known as pre-beta HDL. Its mechanism of
action is to increase apoA-I and the number of HDL particles
transiently, to stimulate the removal of excess cholesterol and other
lipids from tissues including the arterial wall and to transport them to
the liver for elimination through a process called Reverse Lipid
Transport. SAMBA, the clinical Phase 2 study in patients with
hypoalphalipoproteinemia due to genetic defects, has provided important
data demonstrating the efficacy of CER-001 in regressing atherosclerosis
in several distinct vascular beds, and leading to the TANGO study. The
totality of the data to date indicates that CER-001 performs all of the
functions of natural pre-beta HDL particles and has the potential to be
the best-in-class HDL mimetic on the market.
About CER-209
CER-209 is the first drug candidate in the
category of oral P2Y13 receptor agonists. The P2Y13 receptor is a member
of the P2Y receptor family, well-known receptors including the P2Y12
receptor which is the target of successful drugs such as the
anti-platelet agent Clopidogrel (Plavix®). CER-209 is a specific agonist
of P2Y13 receptor and does not interact with the P2Y12 receptor. In
preclinical studies CER-209 promotes HDL recognition by the liver and
increase the activity of Reverse Lipid Transport (RLT), and thus has an
impact on atherosclerosis regression as well as liver fat. Thus the
favorable metabolic effects of CER-209 in the liver offers a new
mechanism for the treatment of non-alcoholic fatty liver disease (NAFLD)
and non-alcoholic steato-hepatitis (NASH).
About HDL targeting Drug Delivery
HDL particles, loaded with
an active agent, hold the promise to target and selectively kill
malignant cells while sparing healthy ones. A wide variety of drugs can
be embedded in these particles targeting markers specific to cancer
cells and bring these potent drugs to their intended site of action,
with lowered systemic toxicity. Cerenis intends to develop the first
HDL-based targeting drug delivery platform dedicated to the oncology
market, including immuno-oncology and chemotherapy.
Financial Agenda:
Cash position and revenue for Q1 2018
April
19th, 2018