On May 8, 2018 Alligator Bioscience (Nasdaq Stockholm: ATORX), a biotechnology company developing antibody-based pharmaceuticals for tumor-directed immunotherapy, and Aptevo Therapeutics Inc. (Nasdaq: APVO), a biotechnology company focused on developing novel immuno-oncology and hematology therapeutics, reported the presentation of new preclinical data supporting ALG.APV-527 as a promising new immunotherapeutic candidate for the treatment of a variety of 5T4-expressing solid tumors (Press release, Alligator Bioscience, MAY 8, 2018, View Source [SID1234538677]).
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ALG.APV-527 is designed to simultaneously target 5T4 and the co-stimulatory receptor 4-1BB (CD137) to promote potent, tumor-directed immune T-cell activation. 5T4 is a well-defined tumor antigen expressed on many different types of malignancies including, non-small cell lung, renal, pancreas, prostate, breast, colorectal, gastric, ovarian and cervical cancers. Conversely, 5T4 has limited expression on normal tissues, making it an attractive target for cancer immunotherapy.
New ALG.APV-527 preclinical data show that ALG.APV-527 has the potential to selectively activate and enhance tumor specific T cell responses at the tumor site without triggering systemic immune activation. Notably, the preclinical in vitro and in vivo data show that ALG.APV-527:
Stimulates increased T cell activation in the presence of 5T4-expressing cells
Localizes to the site of 5T4 positive tumors in an in vivo melanoma tumor model
Inhibits tumor growth in a 5T4 expressing in vivo human colon carcinoma model
Has an extended, antibody-like serum half-life of 9 days in an experimental model
The data were recently presented at the PEGS Summit 2018 and American Association of Immunologists (AAI) annual meeting and will be presented next week at the Annual Meeting of Cancer Immunotherapy (CIMT) (Free CIMT Whitepaper).
"Taken together, the accumulating preclinical data package for ALG.APV-527 support its potential to provide effective tumor-directed immune activation with reduced systemic side effects. We are continuing to advance this candidate and look forward to commencing clinical development in 2019," said Christina Furebring, Senior Vice President Research at Alligator.
"Our collaboration with Alligator Bioscience continues to yield encouraging data supporting the advantages of this novel pathway for targeted immunotherapy of cancer," said Jane Gross, Ph.D., Chief Scientific Officer for Aptevo. "As a first-in-class molecule, ALG.APV-527 showcases the versatility of our ADAPTIR platform in generating bispecific antibodies with unique mechanisms of action and a therapeutic profile that is more consistent with traditional antibodies, including an extended half-life, desirable antibody-like manufacturing characteristics and increased potency and stability."
Aptevo and Alligator believe that the precise targeting of 4-1BB within the tumor microenvironment can overcome some of the limitations seen with other 4-1BB therapies. ALG.APV-527 employs a novel mechanism of action, 4-1BB x 5T4 binding, to direct the therapeutic immune response towards the tumor, thereby potentially reducing the harmful side effects of systemic immune stimulation while providing a strong tumor directed immune activation.
About ALG.APV-527
ALG.APV-527 is a bispecific antibody (4-1BB x 5T4) intended for tumor-directed treatment of solid cancers. ALG.APV-527 was built using Aptevo’s ADAPTIR bispecific platform and combines binding domains sourced from the ALLIGATOR-GOLD human scFV library. The ALG.APV-527 bispecific antibody consists of two parts, one part activating tumor-specific T cells through the co-stimulatory receptor 4-1BB, the other part binding to the 5T4 protein expressed on the surface of tumor cells. This enables the immune-activating effect of ALG.APV-527 to be directed specifically to the tumor and not against normal tissue.