Science Science

Science

The Challenge

Current medications fail to sufficiently penetrate solid tumors.

Cancer treatments are frequently ineffective and can cause significant harm to the patient. Even targeted and optimized drug delivery technologies (such as nanoparticles) are currently only able to deliver less that 1% of the administered dose to a solid tumor. This negatively impacts the therapeutic efficacy and toxicity profile of an anti-cancer drug.

Labelled anti-cancer drug is distributed evenly everywhere except the cancer tissue:

anti-cancer drug

Lack of penetration of a labelled chemotherapeutic drug (FAM-doxorubicin) into a metastatic foci. From a clinically relevant pancreatic cancer mouse model (genetically engineered KPC model) – provided by Dr. Ken Olive, Columbia University

Technology

Novel technology hijacks body’s own transport system to deliver anti-cancer drugs deep into the tumor

The CendR technology under development by DrugCendR increases drug penetration into solid tumors. The company’s lead compound CEND-1 (iRGD in scientific literature) seeks out tumors and activates the CendR transport pathway in them (and not elsewhere in the body). As a result, small cellular vesicles capture a drug co-administered with CEND-1 from the blood stream and transport it deep into tumor tissue. This technology has been extensively validated in animal studies and shown to be efficacious against a variety of tumor types and with a variety of different anti-cancer therapeutics. In addition to increasing the anti-cancer efficacy, this approach can be used to decrease the toxicity of the anti-cancer agents. The cancer-specific mechanism of action of CEND-1 is well understood, increasing the confidence in the technology and its potential to translate into a clinical breakthrough.

CEND-1 administration induces the formation of transport vesicles in a tumor:

bubbles

An electron micrograph illustrating the CEND-1 induced transport system in process. Reprinted with permission from ACS Nano, 2017, 11, pp 9567–9569. Copyright 2019 American Chemical Society.

Key Publications

Clinical-stage molecular mimicry agent validated has been validated in more than 150 publications.

Internal:

Ruoslahti E. Tumor penetrating peptides for improved drug delivery. Adv Drug Deliv Rev. 2017Feb;110-111:3-12.

Teesalu et al. Tumor-penetrating peptides. Front Oncol. 2013 Aug 27;3:216.

Sugahara KN, Teesalu T, Karmali PP, Kotamraju VR, Agemy L, Greenwald DR, Ruoslahti E. Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs. Science. 2010 May 21;328(5981):1031-5.

External / Independent publications:

Akashi et al. Anticancer effects of gemcitabine are enhanced by co-administered iRGD peptide in murine pancreatic cancer model that overexpressed neuropilin-1. Br J Cancer. 2014 Mar 18;110(6):1481-7.

Song et al., Methoxypoly(ethylene glycol)-block-poly(L-glutamic acid)-loaded cisplatin and a combination with iRGD for the treatment of non-small-cell lung cancers. Macromol Biosci. 2012 Nov;12(11):1514-23.

Sha et al,, Tumor-penetrating peptide fused EGFR single-domain antibody enhances cancer drug penetration into 3D multicellular spheroids and facilitates effective gastric cancer therapy. J Control Release. 2015 Feb 28;200:188-200.

Schmithals et al. Improving drug penetrability with iRGD leverages the therapeutic response to sorafenib and doxorubicin in hepatocellular carcinoma. Cancer Res. 2015 Aug 1;75(15):3147-54.

Shin et al. Enhancement of the tumor penetration of monoclonal antibody by fusion of a neuropilin-targeting peptidecimproves the antitumor efficacy. Mol Cancer Ther. 2014 Mar;13(3):651-61.

Zhang,et al. A novel strategy to improve the therapeutic efficacy of gemcitabine for non-small cell lung cancer by the tumor-penetrating peptide iRGD. PLoS One. 2015; 10(6): e0129865.

Cun et al. A novel strategy through combining iRGD peptide with tumor-Mmcroenvironment-responsive and multistage nanoparticles for deep tumor penetration. ACS Appl Mater Interfaces. 2015 Dec 16;7(49):27458-66.

Deng et al.. Inducing optimal antitumor Immune response through coadministering iRGD with pirarubicin loaded nanostructured lipid carriers for breast cancer therapy. Mol Pharm. 2017 Jan 3;14(1):296-309.

Liu et al. iRGD-mediated core-shell nanoparticles loading carmustine and O6-benzylguanine for glioma therapy. J Drug Target. 2017 Mar;25(3):235-246.

Song et al. Development of a multi-target peptide for potentiating chemotherapy by modulating tumor microenvironment. Biomaterials. 2016 Nov;108:44-56.

Zhang et al.. iRGD in a murine model of human NSCLC. Oncol Lett. 2016 Nov;12(5):3241-3249.

Liu X. et al., et al. Tumor-penetrating peptide enhances transcytosis of silicasome-based chemo- therapy for pancreatic cancer. J Clin Invest. 2017 May 1;127(5):2007-2018.