Cerenis Therapeutics: Final Results of TARGET PHASE II Study Demonstrate the Ability of CER-001, an HDL Mimetic, to Target Tumor in Patients with Esophageal Cancer

  • Primary objective met: clinically meaningful targeting of esophageal tumor tissue by labeled CER-001, as evidenced by radioactive tumor labeling as measured by PET/CT
  • 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, FL, USA I December 17, 2018 I 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 the TARGET study has been completed on schedule and that the results are now available.

  • The final 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. A calculated 50% signal increase in the tumor SUV (standardized uptake value) mean was recorded after 24h (3.016; p=0.0048) and 72h (2.806; p=0.0289) compared with 1h (2.058).
  • The sustained radioactive labeling of the tumor, seen in all 9 patients analyzed, was observed over the last two predefined post-dose time points (24h to 72h), and supports using HDL mimetics for the efficient and targeted delivery of therapeutic agents.
  • These results are very encouraging knowing that esophageal cancer is often refractory to the standard of care for this devastating condition.

Full results will be detailed and presented at future medical conferences.

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, was labeled with Zirconium-89 for serial PET/CT1 imaging in patients. It has been previously demonstrated that CER-001 has the same structure and function as a natural pre-beta HDL. It was therefore reasoned that labeled CER-001 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.

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 stage T2 according to the TNM classification4.

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 Center (AMC).

Dr. Jean-Louis Dasseux, Founder and CEO of Cerenis, comments: “These results 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 such as chemotherapeutics, nucleic acids (siRNA, antisense oligonucleotides, immunostimulants) or peptide antigens. It further reinforces our intent to leverage our know-how and our proprietary intellectual property for 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. These results are very encouraging and open many opportunities.”

Professor Dr. Hanneke Van Laarhoven, MD, PhD, concludes: “TARGET 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.”

About CERENIS: www.cerenis.com
Founded in 2005, Cerenis Therapeutics is an international biopharmaceutical company dedicated to the discovery and development of HDL-based innovative therapies. CERENIS’ expertise has translated into a rich portfolio of programs for the treatment of cardiovascular disease and associated metabolic diseases such as NAFLD and NASH as well as a HDL targeted drug delivery platform in oncology, more specifically in 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 and several products in clinical phases.

About CER-001
CER-001 is a bio-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. In animal models regression of atherosclerosis was demonstrated in several distinct vascular beds.

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. CERENIS intends to develop an HDL-based targeted drug delivery platform dedicated to the oncology market, including immuno-oncology and chemotherapy.

1 PECT/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, a positron 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 or biochemical 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.
2 J Nucl Med August 1, 2015 vol. 56 no. 8 1272-1277
3 Front. Pharmacol. 7, 466 (2016).
4 TNM 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 of metastases.
5 Nature Reviews Materials volume 1, Article number: 16014 (2016)

SOURCE: Cerenis Therapeutics

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