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.