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Cerenis receives EMA Orphan Drug Designation for CER-001 for the treatment of APoA-I and ABCA-1 deficiencies

TOULOUSE, France and ANN ARBOR, Michigan, USA, 3 September 2014 – Cerenis Therapeutics, the biopharmaceutical company developing CER-001, an engineered human apoA-I-containing pre-beta HDL mimetic, for the treatment of cardiovascular disease, announced today that it has received two separate Orphan Drug Designations from the European Medicines Agency (EMA) for the use of CER-001 in the treatment of patients with rare genetic defects in HDL synthesis/maturation pathways, specifically apoA-I deficiency and ABCA1 deficiency.

Inherited defects in the apoA-I gene or the ABCA1 gene in both homozygous and heterozygous forms can act in a dominant manner to cause Familial Primary HypoAlphalipoproteinemia (FPHA), a rare syndrome characterised by the absence of or a severe deficiency of HDL particles in the circulation. Due to either the impaired production/maturation or the premature destruction of HDL particles, the Reverse Lipid Transport (RLT) pathway, the body’s only natural mechanism for the elimination of cholesterol, is compromised. Patients experience a rapid accumulation of cholesterol, particularly in blood vessels, which often results in accelerated atherosclerosis and premature cardiovascular disease.

John J.P. Kastelein, MD, PhD, of the Department of Vascular Medicine at the Academic Medical Center in Amsterdam, The Netherlands, said: “These patients accumulate cholesterol and experience premature cardiovascular events despite essentially ‘normal’ levels of LDL-C or despite having been placed on optimized statin therapy. The mechanism of action of statins does not directly target this pathophysiology in these patients with FPHA; as a result the benefit derived from statins will be at best indirect and incomplete. There is no treatment currently available which can directly restore normal HDL levels or normal levels of apoA-I. Despite receiving the best standard of care, many patients have a persistent and extremely high risk of adverse cardiovascular events and premature death, underscoring the unmet medical need for novel therapies. An orphan designation opens up a pathway for CER-001 to be a potential new therapeutic strategy to add to currently available lipid lowering agents to address this elevated risk.”

Proof-of-mechanism data supporting the orphan designation application were obtained from the SAMBA Phase II efficacy and safety trial of CER-001 in patients with FPHA and were presented at the European Atherosclerosis Society in June 2014. The data from this trial showed that CER-001 reconstituted the RLT pathway in individuals who have defects in the natural HDL pathway and facilitated elimination of cholesterol from the body. Importantly, one month of treatment with 9 doses of CER-001, provided on top of optimized standard of care for LDL-c-lowering therapy, 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.

Erik S.G. Stroes, MD, PhD, Professor of Medicine, Head of the Department of Vascular Medicine at the Academic Medical Center in Amsterdam, The Netherlands, and Principal Investigator of the SAMBA trial, commented, “We observed that CER-001 stimulated cholesterol removal on all essential levels of the reverse cholesterol transport pathway, eventually resulting in increased cholesterol excretion into the faeces. More importantly, this increased lipid removal was accompanied by marked reductions in the vessel wall dimensions of atherosclerotic arteries in patients with genetically-determined low HDL cholesterol. This is in line with the observed reduction in vessel wall dimension in patients following 24 weeks of bi-weekly CER-001 infusion in patients with Familial Hypercholesterolemia in the MODE study. The results of these two studies 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.

John F. Paolini, MD, PhD, FACC, Chief Medical Officer of Cerenis, said, “CER-001 has now been shown in Phase II trials to provide benefit to patients suffering from accelerated cardiovascular disease caused by genetic defects at both ends of the spectrum of cholesterol homeostasis. The product has a good safety profile as observed in all studies performed thus far.”

Jean-Louis Dasseux, PhD, MBA, and Chief Executive Officer of Cerenis, concluded: “CER-001 has the potential to be an important therapy not only for patients with rare diseases, such as FPHA, for which there is currently no other therapeutic option, but also for larger patient populations such as post-ACS patients. These two orphan drug designations from the EMA validate our approach and will enable us to accelerate the development of CER-001 and provide this new treatment option to patients.”



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 Bpifrance. €10.7 M 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 heritable genetic defect in one of the key genes involved in HDL particle production or maturation (apoA-I, ABCA-1, LCAT), which are individually very 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 and accumulation of cholesterol throughout the body, in particular, the vasculature. FPHA caused by homozygous ABCA-1 deficiency is also known as Tangier’s disease. 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 of the disease and very limited available therapeutic approaches, FPHA remains an unmet medical need and a life-threatening condition.

Orphan Drug Designation
Orphan Drug Designation provides regulatory support for development activities for drugs that have the potential to provide significant benefit to patients suffering from rare, life-threatening diseases. The designation provides companies with access to protocol assistance and reduced regulatory fees, as well as tax incentives and market exclusivity following drug approval.
For further information, please contact:

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

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

Source: Cerenis