ALG.APV-527
ALG.APV-527 is a bispecific antibody co-developed by Alligator and Aptevo Therapeutics since 2017. The antibody combines a tumor-binding domain (5T4) and an immunomodulatory domain (4-1BB) within a single molecule and is only active upon simultaneous binding to its target molecules.
Co-development with Aptevo Therapeutics Inc.
ALG.APV-527 is a bispecific antibody that targets the 4-1BB and 5T4 molecules and is expected to stimulate T cells and NK cells driving tumor specific immune attacks. 5T4 is a protein preferentially expressed on several tumor types including triple negative breast cancer and renal cell carcinoma. ALG.APV-527 requires simultaneous binding to 4-1BB and 5T4 to stimulate T cells and NK cells, thereby securing that it will only drive immune responses in the tumor and not elsewhere in the body, thus securing a favorable balance between efficacy and safety.
In July 2017, Aptevo Therapeutics Inc. and Alligator signed an agreement regarding the co-development of ALG.APV-527. Under the agreement, both companies will own and finance the development equally (50/50). The original molecules of the tumor-binding and immunomodulatory parts of ALG.APV-527 was developed using Alligator’s proprietary ALLIGATOR-GOLD® antibody library. The bispecific molecule was further developed and improved with the technology platform ADAPTIR™, which has been developed by the partner Aptevo Therapeutics Inc. By combining a tumor-binding and an immunomodulatory part in one and the same molecule, a drug candidate has been created whose effect is selectively targeted to the tumor and activates the anti-tumor-specific immune cells present there.
Project status
Phase 1 dose escalation completed
In recent years prior, preclinical data for ALG.APV-527 has been presented at several international conferences. In November 2022, consolidated preclinical data was published in the peer-reviewed journal Molecular Cancer Therapeutics.1 The data demonstrates that ALG.APV-527 effectively and selectively stimulates and strengthens the T cell response in the tumor, leading to tumor elimination. ALG.APV-527 also induces a tumor-specific immunologic memory in experimental disease models. Furthermore, the data shows that ALG.APV-527 has a good preclinical safety profile, with no signs of systemic immunostimulation or liver toxicity. Overall, the results support the potential of ALG.APV-527 to induce effective tumor-targeted immunostimulation with fewer adverse events.
In February 2023 the first patient in the study was dosed with ALG.APV-527 in a Phase 1 study assessing the safety and efficacy of ALG.APV-527 in up to 30 patients with solid tumor types over-expressing 5T4. In March 2024, the companies announced the first interim data from the Phase 1 study with more than half of the planned patients recruited. The data demonstrated an encouraging safety and pharmacokinetics profile for ALG.APV-527, as well early signs of clinical efficacy in heavily pretreated breast cancer patients. In Q4 2024, the companies reported Phase 1 data for the candidate which indicated that trial endpoints of adequate exposure, safety, tolerability and biological activity had been met.
1 Mol Cancer Ther. 2023 Jan 3;22(1):89-101. DOI: 10.1158/1535-7163.MCT-22-0395.