The bispecific antibody ALG.APV-527 has a tumor-binding part and immunomodulatory part in the same molecule. The immunomodulatory part of ALG.APV-527 recognizes and activates 4-1BB, which has the ability to stimulate the immune cells (antitumor-specific T cells) involved in tumor control, making 4-1BB a particularly compelling target for cancer immunotherapy. The tumor-binding part of ALG.APV-527 targets the tumor-associated antigen 5T4. 5T4 is a protein expressed in multiple tumor types, as well as in certain types of aggressive tumor cells (tumor-initiating cells), but at low levels or not at all in normal tissue, making 5T4 a compelling target molecule for cancer therapy.
Preclinical data for ALG.APV-527 has been presented at several scientific conferences. Data shows that ALG.APV-527 has the potential to selectively stimulate and strengthen the T cell response in the tumor without stimulating the immune system in the rest of the body. Data shows that ALG.APV-527 is localized to 5T4 positive tumors and selectively stimulates and enhances the tumor-directed immune responses of the T cells and NK cells. Additionally, data shows that the 5T4 antigen is expressed by a wide range of tumor types. The findings support its overall potential to evoke an effective tumor-targeting immune response with fewer adverse events.
Alligator and Aptevo are advancing ALG.APV-527 into Phase 1 clinical development. The companies will continue to explore licensing opportunities as ALG.APV-527 moves into clinical development.
Preclinical data for ALG.APV-527 was presented in June 2020 at PEGS Virtual Interactive Global Summit. The data show that ALG.APV-527 selectively enhances the function of activated T cells and NK cells in the presence of the tumor antigen 5T4, as shown in vitro, and potently rejects tumors in an in vivo animal model. As earlier presented, ALG.APV-527 has the potential to selectively stimulate and strengthen the T cell response in the tumor without stimulating the immune system in the rest of the body. The findings support ALG.APV-527’s overall potential to evoke an effective tumor-directed immune response with less side effects.
On September 19, 2022, Alligator Bioscience and Aptevo Therapeutics announced that the FDA had issued a “May Proceed” notification for the ALG.APV-527 IND application. This allows the companies to initiate clinical trials for the treatment of 5T4-expressing tumor antigens in multiple solid tumor types.
In July 2017, Aptevo Therapeutics and Alligator Bioscience signed an agreement regarding the co-development of ALG.APV-527. The antibody is based on Alligator’s original bispecific drug candidate ATOR-1016. Under the agreement, the companies will equally own and finance the development of the drug candidate through Phase 2 clinical trials.