Primary objective met: clinically meaningful targeting of
esophageal tumor tissue by labeled CER-001
The sustained tumor labeling supports future use of HDL mimetics to
improve effective delivery of therapeutic agents
Results are consistent with preclinical studies using HDL mimetics
These encouraging results were observed in patients with esophageal
cancer, often refractory to standard therapy
No safety or tolerability issues were observed
TOULOUSE, France & LAKELAND, Mich.–(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, metabolic diseases, and HDL platform
technologies today announced that enrollment of all patients (ten) in
TARGET study has been completed on schedule. The preliminary results in
five patients are also now available.
The preliminary data analysis of TARGET demonstrates the ability of a
radioactive labeled HDL mimetic (CER-001) to target tumor in patients
with esophageal cancer as demonstrated visually and resulted in a
calculated 50% signal increase in the tumor after 24h and 72h compared
The sustained radioactive labeling of the tumor, seen in all 5
patients analyzed, was observed over the last two predefined post-dose
time points (24h to 72h), and supports using HDL mimetics to improve
effective targeted delivery of therapeutic agents.
These results are encouraging knowing that esophageal cancer is often
refractory to the standard of care for this devastating condition.
Full results will be communicated and presented at future medical
conferences. Given the uniformly favorable findings seen in all 5
patients, the final analysis results are not expected to differ from
this preliminary analysis.
TARGET is the first clinical study ever performed to assess labeled HDL
tumor uptake in cancer patients and in doing so, the first clinical
study to test the ability of HDL to target tumor in patients after
interacting with cellular HDL receptors.
In TARGET, CER-001, a pre-beta HDL mimetic, is labeled with Zirconium-89
for serial PET/CT1 imaging in patients. It has been
demonstrated that CER-001 has the same structure and function as a
natural pre-beta HDL and therefore could be used as a tumor imaging
product to target tumors via HDL receptors. A number of preclinical
studies have already validated the concept2,3,
showing that HDL nanoparticles can act as a specific drug delivery
platform targeting tumor cells or targeting immune cells.
Cerenis’ CER-001 is a recombinant human apoA-I pre-beta HDL mimetic.
CER-001 has been shown to be safe and well tolerated in multiple
previous clinical trials with more than 5,000 administrations among the
different studies and with repeated administrations of up to 18 months.
CER-001 is currently in a phase III clinical trial for patients with a
genetic HDL deficiency (“TANGO”).
The TARGET study is an investigator initiated single-center
observational trial enrolling adult subjects with a pathologically
proven diagnosis of primary esophageal carcinoma in situ. Patients were
all at least T2 staged according to the TNM classification4.
The investigators planned to include 10 patients, all of whom have now
The two principal investigators of the TARGET study are Professor Dr.
Erik Stroes, MD, PhD, Professor and Chair of the Department of Vascular
Medicine, Amsterdam Medical Center (AMC) and Professor Dr. Hanneke Van
Laarhoven, MD, PhD, Department of Medical Oncology, Amsterdam Medical
Dr. Jean-Louis Dasseux, Founder and CEO of Cerenis, comments: “These
preliminary data support our HDL drug delivery platform based on apoA-I,
Cargomer™ and HDL mimetics. It is an important milestone which helps
position the company as a leader in the field, as we are the first
company that has clinical data on HDL delivery, with a delivery vehicle
(CER-001) which has demonstrated safety and tolerability in humans.
TARGET is our first step for our platform in the clinic and this imaging
study in patients supports targeting cells which over-express HDL
receptors, such as tumor cells, in order to deliver active
pharmaceutical drugs. It further reinforces our intent to leverage our
know-how and our proprietary intellectual property to move forward into
immuno-oncology and chemotherapy.”
Professor Dr. Erik Stroes, comments: “The concept of targeted delivery
to cancer using nanoparticles is highly attractive. However, historical
nanoparticle platforms have failed to deliver on their promise (on
average, only 0.7% of the administered nanoparticle dose has been found
to be delivered to solid tumors5 which can lead to
undesirable systemic and toxic side effects). HDL is a naturally
occurring particle in humans, which can be loaded with exogenous
compounds, leading to a unique and safe local delivery strategy in
humans. Our data in TARGET suggest the potential for greatly enhanced
delivery to specific cellular targets. HDL interacts with a number of
HDL receptors including the scavenger receptor B-I (SR-BI), which is
highly expressed in certain cancers. Thus these preliminary results are
very encouraging and open many opportunities.”
Professor Dr. Hanneke Van Laarhoven, MD, PhD, concludes: “TARGET
preliminary data support CER-001 targeting particles promise to markedly
increase the amount of drug delivered to cancer cells in our patients.
The fact that a wide variety of drugs can be embedded in HDL
nanoparticles could increase efficacy compared to available drug
delivery technologies and open a new generation of drugs in oncology.
Targeted delivery also holds the promise of safer chemotherapeutic
regimens. Despite medical progress in the diagnosis and treatment of
esophageal cancer, 5-year overall survival rates remain poor,
underlining the critical need for novel treatment strategies. We believe
that the TARGET study results will offer new hope.”
1PECT/CT: Positron emission tomography–computed
tomography (better known as PET-CT or PET/CT) is a nuclear
medicine technique which combines, in a single gantry,
emission tomography (PET) scanner and an x-ray
computed tomography (CT) scanner, to acquire sequential
images from both devices in the same session, which are combined into a
single superposed (co-registered)
image. Thus, functional
imaging obtained by PET, which depicts the spatial
distribution of metabolic
activity in the body can be more precisely aligned or correlated with
anatomic imaging obtained by CT scanning. Two- and three-dimensional image
reconstruction may be rendered as a function of a common software
and control system.
2J Nucl Med August 1, 2015
vol. 56 no. 8 1272-1277
3Front. Pharmacol. 7,
4TNM classification: International
classification that reports on the stage of cancer progression. The
letter T is the tumor initial and corresponds to the size of the tumor;
the letter N (for Node) indicates whether or not lymph nodes have been
invaded; the letter M (for Metastasis) indicates the presence or absence
5Nature Reviews Materials volume
1, Article number: 16014 (2016)
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, metabolic
diseases, and HDL platform technologies. HDL is the primary mediator of
the reverse lipid transport, or RLT, the only natural pathway by which
excess lipids are removed from arteries and transported to the liver for
elimination from the body.
In addition to advancing HDL technologies for drug delivery, 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). CERENIS is well positioned to become one of the
leaders in the HDL therapeutic market, with a broad portfolio of
programs in development.
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. SAMBA, the clinical Phase II 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 with results expected at the end of 2018. 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.
The TARGET study is an investigator initiated single-center
observational trial enrolling 10 adult subjects with a pathologically
proven diagnosis of primary esophageal carcinoma in situ. Patients are
at least all T2 staged according to the TNM classification.
The aim of the TARGET study is to assess the concentrations of Zirconium
89 labeled CER-001 in tumor tissue at three time points after a single
administration (1, 24 and 72 hours). Recent pre-clinical studies have
demonstrated that reconstituted radio-labeled HDL nanoparticles may be
used to label tumors, with specificity for tumor associated macrophages.
Furthermore, in cancer patients, 89Zr-labeled HDL mimetic
CER-001 will allow for non-invasive evaluation of the potential of drug
delivery strategies in selected cancers. Success will pave the way for
loading of HDL nanoparticles with immune-oncology and chemotherapeutic
The investigational product is CER-001, a pre-beta HDL mimetic labeled
with Zirconium-89 for serial PET/CT imaging in patients. It has been
demonstrated that CER-001 pre-beta HDL mimetic could be used as a tumor
imaging product to validate that HDL specifically target tumors via HDL
receptors in patients. CER-001 has a very favorable safety and tolerance
profile as demonstrated in previous clinical trials.
About Targeted HDL 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.
Cargomer™, apo-AI multimeric nanoparticles, and HDL particles such as
CER-001 have the future potential to serve as carriers of multiple
anti-cancer drugs, antigens, interfering RNA (siRNA’s), and anti-sense
oligonucleotides (ASOs) opening the path for the Cerenis platform.
Cerenis intends to develop the first HDL-based targeting drug delivery
platform dedicated to the oncology market, including immuno-oncology and
Jean-Louis Dasseux, +33 (0)5 62 24 09 49
Emmanuel Huynh / Louis-Victor Delouvrier, +33 (0)1 44 71
Nicolas Merigeau, +33 (0)1 44 71 94 98