Alligator Bioscience AB and Aptevo Therapeutics announced the publication of a peer-reviewed article highlighting preclinical data that demonstrates a positive safety and anti-tumor activity profile in both in vitro and in vivo studies for ALG.APV-527, a novel second generation 4-1BB agonistic bispecific antibody that is designed to stimulate 4-1BB function only when co-engaged with the tumor-associated antigen 5T4. The publication in Molecular Cancer Therapeutics, a journal of the American Association for Cancer Research (AACR), includes data provided in the companies' investigational new drug (IND) application to the US Food and Drug Administration (FDA) supporting the advancement of ALG.APV-527 into the clinic for evaluation in the treatment of multiple solid tumor types. The article, entitled "The bispecific tumor antigen-conditional 4-1BB x 5T4 agonist, ALG.APV-527, mediates strong T cell activation and potent anti-tumor activity in preclinical studies", demonstrates how the design, epitope, and molecular properties of ALG.APV-527 translate into a potentially safe and potent anti-cancer therapeutic both in vitro and in vivo for the treatment of multiple solid tumor types.

The preclinical functional data presented demonstrate that ALG.APV-527 has the potential to activate key immune cell populations such as T cells and NK cells within the tumor microenvironment. Of particular importance is the favorable safety profile, where the preclinical data demonstrates a potentially wider therapeutic window for ALG.APV-527 compared to first generation 4-1BB agonists. In September 2022, the FDA issued a "may proceed" notification for the ALG.APV-527 IND.

Alligator and Aptevo are working rapidly to initiate a multi-center Phase 1 trial in the US to evaluate ALG.APV-527 in the treatment of multiple solid tumor types expressing the tumor antigen 5T4. ALG.APV-527 is an antibody with dual function: tumor-binding and 4-1BB immunomodulatory agonist effects. This has the potential to be clinically important because 4-1BB 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.

Preclinical results, presented at the Society of Immunotherapy Cancer's 2021 Annual Meeting, highlighted the differentiated design of the molecule that minimizes systemic immune activation, allowing for highly efficacious tumor-specific responses as demonstrated by potent activity in vitro models. Alligator and Aptevo are working rapidly to advance ALG.APV-527 into Phase 1 clinical development in the US.