Cerenis Therapeutics

Cerenis Reports Two Positive Phase II Studies for HDL Mimetic CER-001 at EAS

• CER-001 proven to enhance Reverse Lipid Transport, facilitating elimination of cholesterol from the body
• Statistically significant reduction in carotid artery Mean Vessel Wall Area in two distinct clinical populations, as measured by Magnetic Resonance Imaging
• CER-001 complementary to LDL-c-lowering treatment and may represent a new chronic therapy on top of standard of care for patients with Familial Hypercholesterolemia and Familial Primary Hypoalphalipoproteinemia
• CER-001 well tolerated

TOULOUSE, France and ANN ARBOR, Michigan, June 2nd 2014 - Cerenis Therapeutics, the biopharmaceutical company, today announced that two of its Phase II studies, SAMBA and MODE (Modifying Orphan Disease Evaluation), with CER-001, an engineered human apoA-I-containing pre-β HDL mimetic, met their primary clinical endpoints in patients with Familial Primary Hypoalphalipoproteinemia (FPHA) and Homozygous Familial Hypercholesterolemia (HoFH), respectively.

Data are being presented at the Late Breaker Session at the European Atherosclerosis Society (EAS) Meetings in Madrid, Spain on June 2, 2014.

For the EAS Interactive Programme and link to the abstracts, please visit: www.eas.kenes.com.

SAMBA clinical trial:
Proof-of-Mechanism data will be presented at the EAS from the SAMBA Phase II efficacy and safety trial in patients with Familial Primary Hypoalphalipoproteinemia (FPHA), a rare syndrome of severe HDL deficiency caused by mutations in the genes responsible for HDL synthesis /maturation and characterized by accelerated atherosclerosis.

This pharmacokinetic/pharmacodynamic trial, conducted by Principal Investigator, Erik S.G. Stroes, MD, PhD of the Department of Vascular Medicine at the Academic Medical Center (AMC) in Amsterdam, The Netherlands, enrolled 7 FPHA patients in an open-label single-arm active-treatment study and assessed the efficacy of infused CER-001 engineered human apoA-I-containing pre-β HDL particles in reconstituting the endogenous Reverse Lipid Transport in individuals who have defects in the natural HDL pathway and facilitate elimination of cholesterol from the body.

The data from patients receiving CER-001 treatment on top of optimized standard of care LDL-c-lowering therapy showed that CER-001 performed the four steps of the Reverse Lipid Transport pathway: CER-001 increased cholesterol mobilization and esterification in the HDL fraction, and one month of treatment with 9 doses of CER-001 resulted in a statistically significant reduction in carotid artery Mean Vessel Wall Area, as measured by Magnetic Resonance Imaging (3T-MRI). CER-001 was well-tolerated.

Specific data from the study will be presented on Monday June 2, 2014 at 3:45pm in Madrid.

Dr. Stroes commented, "The results of this study support the future use of CER-001 for chronic administration aiming to reduce the elevated cardiovascular risk in low HDL patients with a high unmet clinical need."

MODE clinical trial:
Cerenis also reported that data from the MODE (Modifying Orphan Drug Evaluation) trial, a Phase II efficacy and safety study in patients with Homozygous Familial Hypercholesterolemia (HoFH), a rare disease of markedly elevated LDL-cholesterol (bad cholesterol) levels caused by genetic defects in the LDL-receptor pathway and characterized by premature atherosclerosis. Data will also be presented as a late-breaking clinical trial at the EAS.

The open-label single-arm active-treatment study in 23 patients with homozygous FH met the prespecified primary clinical endpoint in the modified Intention to Treat population, demonstrating a statistically significant reduction in carotid artery Mean Vessel Wall Area, as measured by Magnetic Resonance Imaging (3T-MRI), after 6-months of bi-weekly CER-001 treatment on top of optimized LDL-c-lowering therapy, including apheresis. CER-001 was well-tolerated.

Specific data from the study will be presented on Monday June 2, 2014 at 4:00pm in Madrid.

Dr. Kees Hovingh, the Principal Investigator of the MODE study, commented, "These data indicate that HDL therapy is complementary to LDL-c-lowering treatment and may represent a new therapy for addressing the unmet medical need in FH patients."

John F. Paolini, MD, PhD, FACC, Chief Medical Officer of Cerenis, said, “CER-001 has been shown to offer an important benefit for patients suffering from accelerated cardiovascular disease caused by genetic defects at both ends of the spectrum of cholesterol homeostasis. The demonstrated safety profile observed in all studies performed thus far supports the use of CER-001 for chronic treatment in both these rare patient populations.”

Jean-Louis Dasseux, PhD, MBA, and CEO of Cerenis, concluded: “In all preclinical and clinical studies to date, CER-001 has been shown to perform the functions of natural HDL and the steps of the Reverse Lipid Transport Pathway leading to elimination of cholesterol from the body with a high degree of potency. The clinical benefit observed in these genetically challenged patients is further evidence supporting HDL therapy in the broader treatment of atherosclerosis. We are committed to continuing the development of CER-001 in these important rare disease clinical indications.”



About Cerenis Therapeutics
Cerenis Therapeutics is an international biopharmaceutical company dedicated to the discovery and development of novel HDL therapies for the treatment of cardiovascular and metabolic diseases. HDL is the primary facilitator of the reverse lipid transport, or RLT, pathway by which excess cholesterol is removed from arteries and is transported to the liver for elimination from the body. Cerenis is developing a portfolio of HDL therapies, including HDL mimetics for the rapid regression of atherosclerotic plaque in high-risk patients, and drugs which increase HDL for patients with low HDL. Cerenis is well-positioned to become the leader in the HDL therapeutic market with a broad portfolio of programs in development.

Since its inception in 2005, the company raised €117 M in equity with top tier investors: Sofinnova Partners, HealthCap, Alta Partners, EDF Ventures, Daiwa Corporate Investment, TVM Capital, Orbimed, IRDI/IXO Private Equity and the FSI (Fund for Strategic Investment). €10,7M was also provided by OSEO, the French agency for innovation, to support the development of CER-001.

About CER-001
CER-001 is an engineered complex of recombinant human apoA-I, the major structural protein of HDL, and charged 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.

Familial Primary Hypoalphalipoproteinemia (FPHA)
Hypoalphalipoproteinemia (“low HDL”), as a general term, has historically been defined clinically as an HDL-cholesterol (HDL-C) less than 40 mg/dL (1.0 mmol/L) in men, and less than 50 mg/dL (1.3 mmol/L) in women. A number of etiologies, often metabolic, can underlie a reduced circulating level of cholesterol in the HDL fraction, for example diabetes, Metabolic Syndrome, obesity, and lack of physical activity (thus called secondary hypoalphalipoproteinemia). In a very small percentage of the population, particularly amongst the patients with the very lowest HDL-C values, there are patients who have a genetic defect (thus called primary hypoalphalipoproteinemia) affecting either the constituent components of the pre-β particle, the process of pre-β particle synthesis, the steps leading to maturation into an alpha HDL particle, or the rates of catabolism – any of which alone or in combination can then result in an inherited condition of very low circulating HDL particle number.

Familial Primary Hypoalphalipoproteinemia (FPHA) includes patients with a range of individual mutations across the key genes involved in HDL particle production or maturation (apoA-I, ABCA1, LCAT) which are individually extremely rare (prevalence less than one in one million births in the homozygous form) but in both homozygous and heterozygous forms can act in an autosomal dominant manner to cause low apoA-I levels and low HDL particle numbers through either decreased production or increased clearance and premature destruction of HDL particles and ultimately result in accelerated atherosclerosis from a single final common pathophysiology of impaired Reverse Lipid Transport (RLT) and accumulation of cholesterol throughout the body, in particular, the vasculature. FPHA patients are at high risk of cardiovascular disease as a consequence of having inherited a virtually absent endogenous RLT system. Because of the specific characteristics and very limited available therapeutic approaches, FPHA remains an unmet medical need and a life-threatening condition.

Familial Hypercholesterolemia (FH)
Familial hypercholesterolemia (FH) is characterized by high cholesterol levels, specifically very high low-density lipoprotein (LDL) levels and early cardiovascular disease. Many patients have mutations in the LDLR gene that encodes the LDL receptor protein, which normally removes LDL from the circulation, or apolipoprotein B (ApoB), which is the part of LDL that binds with the receptor; mutations in other genes are rare. In homozygous familial hypercholesterolemia (HoFH), serum LDL-C levels may be elevated six-fold. Patients develop severe aortic stenosis and coronary heart disease by age 20 and normally do not respond adequately to drug or diet modification therapy. Although the existing therapies, including statins, cholesterol absorption inhibitors, and LDL apheresis, can significantly reduce circulating LDL-C, nevertheless, LDL-C still remains higher than that recommended by current treatment guidelines, and these patients continue to have cardiovascular events of MI, stroke, and death at an elevated rate. The prevalence of homozygous FH is approximately one in one million births.

For further information, please contact:

Cerenis Therapeutics:
Jean-Louis Dasseux, President and CEO
John F. Paolini, CMO
Tel: +33 5 62 24 09 49

Instinctif Partners
Melanie Toyne-Sewell
Tel: +44 20 7457 2029