Cancer cells, 3D illustration

Advanced Solid Tumors – Certepetide

Solid tumors are abnormal masses of tissue that usually do not contain cysts or liquid areas. Many solid tumors are characterized by a dense extracellular matrix (ECM), creating a physical barrier against penetration, which may limit adequate anti-cancer drug delivery. The ECM is a non-cellular meshwork of crosslinked macromolecules that form a dense desmoplastic stroma, which is fibrous connective tissue that surrounds tumor cells. This complex stroma, together with the formation of new leaky blood vessels, creates a tumor microenvironment in favor of tumor growth and invasiveness. Thus, the presence of the ECM, poor vascularity of the tumor, and high interstitial tumor pressure may result in only a small fraction of an administered anti-cancer drug reaching the tumor. Because of this, many solid tumors fail standard-of-care (SoC) chemotherapies and are often not well addressed by available immunotherapies.

Lisata aims to address the key limitations that enable effective treatment of advanced and/or metastatic solid tumors by targeting and penetrating the dense desmoplastic stroma and by reducing the immuno-suppressive tumor microenvironment that limits immune response to cancer. In addition, Lisata is focused on depleting certain immuno-suppressive cell types, such as regulatory T-cells (Tregs) and increasing the number of cytotoxic T cells (cancer-fighting immune cells) with the goal of mitigating the metastatic cascade.

Our Approach: Certepetide for the Treatment of Advanced Solid Tumors 

Lisata’s CendR Platform® technology is designed to enable more effective tumor-targeted, tissue penetrating delivery of anti-cancer drugs to solid tumors. Lisata’s lead investigational drug, certepetide, for the treatment of advanced solid tumors is a product of the CendR Platform®.

What is certepetide?

Certepetide is an investigational drug that is intended to selectively target and enhance the uptake of anti-cancer drugs into solid tumors. It targets specific alpha-v integrins (i.e., receptors) that are selectively expressed and upregulated on tumor endothelial cells and tumor cells themselves, but not healthy tissue. Certepetide is a cyclic peptide that, once bound to these integrins, is cleaved by proteases expressed in the tumor microenvironment. Of the two linear peptides that are a result of this cleavage, one is a “CendR fragment”, which then binds selectively to a second nearby receptor, called neuropilin-1 (NRP-1), also upregulated on tumors, to activate a novel uptake pathway that allows anti-cancer drugs to be transported into solid tumors more efficiently and selectively.

In preclinical models, certepetide has also shown the ability to modify the tumor microenvironment, thereby making tumors more susceptible to immunotherapies and inhibiting the metastatic cascade (i.e., the spread of cancer to other parts of the body). Lisata and its development collaborators have amassed significant non-clinical data demonstrating enhanced delivery of a range of existing and emerging anti-cancer therapies, including chemotherapeutics, immunotherapies, and RNA-based therapeutics. To date, certepetide has also demonstrated favorable safety, tolerability, and activity in completed and ongoing clinical trials designed to test its ability to enhance delivery of standard-of-care chemotherapy for pancreatic cancer. Currently, certepetide is the subject of multiple ongoing or planned Phase 1b/2a and 2b clinical studies being conducted globally in several solid tumor types in combination with a variety of anti-cancer regimens.

On December 30, 2023, the Oncology & Cancer Case Reports Journal published a case report entitled, “Certepetide Potentiates Complete Response in Metastatic Gastroesophageal Adenocarcinoma,” co-authored by Kristen K. Buck, M.D., Executive Vice President of R&D and Chief Medical Officer of Lisata, which details a patient with metastatic gastroesophageal adenocarcinoma who achieved a complete response when given certepetide in combination with standard-of-care FOLFIRINOX + pembrolizumab. The subject initially underwent months of SoC treatments and achieved a partial response. Upon subsequent addition of certepetide to such SoC therapeutic regimen, the subject achieved a complete response, confirmed both radiographically and surgically.

On July 5, 2022, The Lancet Gastroenterology and Hepatology published encouraging data from a Phase 1 study of certepetide in combination with SoC gemcitabine and nab-paclitaxel for the treatment of first-line, metastatic pancreatic ductal adenocarcinoma (mPDAC). The publication details the results of an open- label, multi-center, Phase 1 trial, highlighting that certepetide in combination with SoC had an acceptable safety profile with no dose-limiting toxicities and improved overall survival by 55% and progression free survival by 76% vs. historical SoC results. The objectives of the study were to determine the safety, tolerability, pharmacokinetics, and preliminary efficacy of certepetide in combination with gemcitabine and nab-paclitaxel in patients with mPDAC.

Investigational Clinical Trials of Certepetide in a Range of Advanced Solid Cancer Tumors

Clinical trials are essential for determining the efficacy of experimental cancer treatments. Certepetide is being considered as a potential treatment option for a range of advanced solid tumors in several ongoing clinical trials. Lisata is committed to conducting this important research in order to determine the efficacy of certepetide and to improve patient care for all those suffering from metastatic pancreatic cancer and other difficult-to-treat advanced solid tumors.


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