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Cellectar Biosciences an oncology-focused, clinical stage biotechnology company, and Avicenna Oncology, a precision medicine company based in Basel, Switzerland have agreed to collaborate  on the development of new phospholipid drug conjugates or PDCs combining Cellectar’s patented phospholipid ether delivery platform with Avicenna’s novel, potent, cytotoxic payloads (potent anti-cancer small molecules).[1]

Cellectar’s product candidates are built upon the company’s patented cancer cell-targeting delivery and retention platform of optimized phospholipid ether-drug conjugates. The phospholipid ether (PLE) carrier platform is purposely designed to be coupled with a variety of payloads to facilitate both therapeutic and diagnostic applications.

The basis for selective tumor targeting of Cellectar’s PDC compounds lies in the differences between the plasma membranes of cancer cells compared to those of normal cells. Cancer cell membranes are highly enriched in lipid rafts, which are glycolipoprotein microdomains of the plasma membrane of cells that contain high concentrations of cholesterol and sphingolipids, and serve to organize cell surface and intracellular signaling molecules. To date, PDCs have been tested in more than 80 different xenograft models of cancer.

Portals of Entry
In vitro studies using fluorescent PDCs (including Cellectar’s CLR 1501 and CLR 1502) suggest that lipid rafts serve as portals of entry for PDCs. In addition, the disruption of the lipid raft architecture significantly reduces the uptake of our PLEs into cancer cells. These, and other, experiments have also demonstrated the selective uptake and prolonged retention in cancer cells versus non-cancerous cells. This selectivity of the company’s compounds for cancer cells is attributed to the high affinity of the PLE carrier for cholesterol and the abundance of cholesterol-rich lipid rafts in cancer cells as compared to non-cancer cells.  Finally, Cellectar’s PDCs are transported into the cytoplasm via clathrin-independent endocytosis.

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Illustration 1.0: Selective uptake and retention of PDCs in malignant cells and tumors. Courtesy: © 2017 Cellectar Biosciences. Used with permission.

New payloads
“We believe the combination of our targeted PDC delivery with Avicenna’s proprietary payloads has tremendous potential for the development of selective therapeutics for patients suffering with cancer,” noted Jim Caruso, president and CEO of Cellectar Biosciences.  “

This collaboration further validates the utility of our PDC delivery platform to provide targeted treatment of various resistant cancers, expands and accelerates our conjugate program research and potentially increases our novel, small molecule PDC pipeline,” Caruso added.

Under the terms of the research collaboration, Avicenna will provide their novel payloads to Cellectar, which will leverage its expertise in chemical conjugation to link the molecules to its phospholipid ether (PDC platform).

Cellectar will oversee the in vitro and in vivo testing of these molecules alongside an antibody-drug conjugate or ADC with the same payload. Both companies will have the option to advance the development of any of the newly phospholipid conjugated molecules (PDCs). Financial terms of the collaboration have not been disclosed.

“There remains a significant unmet medical need for providing patients with new generations of targeted treatments with improved therapeutic index. Combining Cellectar’s PDC platform with our payloads is a very promising approach that could potentially overcome some of the disadvantages presently seen with ADCs,” said Zaki Sellam, MSc, MBA, founder and CEO of Avicenna Oncology.

“In line with our common vision, we are very excited to combine our collective expertise to potentially provide new treatment options for patients.”

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