Aptevo - Model ALG.APV-527 -Bispecific Antibody
ALG.APV-527 is a bispecific antibody candidate targeting 4-1BB x 5T4 and is intended for tumor-directed treatment of solid cancers. It was built using Aptevo’s ADAPTIR™ bispecific technology platform and combines binding domains sourced from Alligator Biosciences’ ALLIGATOR-GOLD® human scFv library.
Co-developed by Aptevo Therapeutics and Alligator Biosciences under a collaboration agreement signed in 2017, ALG.APV-527 is currently in preclinical development. The companies made a joint decision in late 2019 to postpone submission of a CTA (Clinical Trial Authorization) planned for Q4 2019 and have instead initiated discussions with potential partners for the upcoming clinical development of ALG.APV-527.
ALG.APV-527 is designed to simultaneously target the tumor antigen, 5T4, and the co-stimulatory receptor 4-1BB 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.
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.
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, these 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
- Was well tolerated in a dose-range finding pilot toxicology study with no major changes in liver enzyme levels, cytokine levels or immune cell populations observed
- Had an extended serum half-life of 5-7 days when administered by intravenous infusion in a preclinical toxicology study
- Augments CD8 T cell proliferation and activation in a 5T4-dependent fashion
- Induces NK cell proliferation and enhances the NK cell cytotoxic profile, but only in the presence of 5T4
- Inhibits tumor growth in a human xenograft colon carcinoma model expressing the tumor antigen 5T4