SEATTLE & LUND, Sweden—Aptevo Therapeutics Inc., a biotechnology company focused on developing novel immuno-oncology and hematology therapeutics, and Alligator Bioscience, a biotechnology company developing antibody-based pharmaceuticals for tumor-directed immunotherapy, announced in early May 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.
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
“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 Dr. Jane Gross, 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 potentially 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.