Immunomedics reports study results of antibody-SN-38 conjugates for targeted cancer chemotherapy

Apr 21 2010

Immunomedics, Inc. (Nasdaq:IMMU), a biopharmaceutical company focused on developing monoclonal antibodies to treat cancer and other serious diseases, reported today at the 101^st Annual Meeting of the American Association for Cancer Research (AACR) results from two studies aimed at improving the design of antibody-SN-38 conjugates for targeted cancer chemotherapy.

SN-38 is an active form of, and about three orders of magnitude more potent than, irinotecan or CPT-11, which has been approved for the treatment of metastatic colorectal cancer. CPT-11 has also shown clinical activity in lung, breast, and brain cancers. Due to its toxicity and poor solubility in water, SN-38 cannot be administered systemically to patients with cancer. Targeting drugs such as SN-38 to cancer cells using cancer-selective monoclonal antibodies could lower their toxicities to bystander tissues, thus potentially offering an attractive alternative as cancer therapeutic agents.

The first study reported at the AACR conference evaluated 4 linkers to connect SN-38 to labetuzumab or hRS7, two of the Company's proprietary humanized monoclonal antibodies. Stabilities of the antibody-SN-38 conjugates were examined in human or mouse serum. In vitro binding and cytotoxicities of the ADCs were studied using human colon cancer cells, and comparison of the therapeutic potentials of the conjugates was carried out in a human colon cancer model in mice. Overall, results indicated that a redesigned linker labeled as CL2A provides a practical approach for antibody-based targeted chemotherapy with SN-38.

Efficacies of antibody-SN-38 conjugates redesigned with CL2A were investigated in the second study. Five of the Company's humanized antibodies were conjugated to CL2A-SN-38: epratuzumab (anti-CD22), veltuzumab (anti-CD20), clivatuzumab (anti-mucin), labetuzumab (anti-CEACAM5) and hRS7 (anti-EGP-1, or TROP-2). In a mouse model of human pancreatic cancer, SN-38 conjugates of labetuzumab and hRS7 produced enhanced antitumor effects versus veltuzumab-SN-38 conjugate, which does not target pancreatic cancer, suggesting the binding abilities of labetuzumab and hRS7 were retained in both conjugates. Additionally, in a subcutaneous lymphoma model in mice, median survival time (MST) for untreated animals was only 7 days, while the tumor-specific epratuzumab-SN-38 conjugate in combination with veltuzumab increased MST 10-fold to more than 77 days.

Commenting, Cynthia L. Sullivan, President and CEO stated, "The redesigned CL2A linker developed by our scientists allows us to produce SN-38 conjugates that are soluble in water with excellent yields, as well as preservation of antibody binding and drug activity. These results portend well for the clinical development of these redesigned antibody-SN-38 conjugates for different cancer indications."

SOURCE Immunomedics, Inc.