The goal of the PB003a project is to develop an anti–cancer drug specifically targeting αVβ8 integrin, with markedly superior properties to anti-αVβ8 antibodies currently in preclinical and early clinical development (e.g., PF-06940434 molecule, Pfizer).
Integrin αVβ8 plays a key role in the inhibition by regulatory T cells (Treg) of lymphocyte cytotoxicity against tumor cells. While the mechanism of action of competing drug candidates is to block αVβ8 activity to reduce immunosuppression in the tumor environment, the PB003a project aims to develop a much more aggressive drug candidate that will kill αVβ8-mediated Treg cells. Since αVβ8 is also expressed on cells of various tumor types (including lung, colorectal, head and neck, and breast), PB003a will also directly induce the killing of tumor cells by cytotoxic lymphocytes, resulting in a much more effective anti-cancer therapy. To achieve this, drug candidate PB003a will be developed in the form of a so-called bi-functional therapeutic molecule (bifunctional fusion protein, BFP), in which a conventional antibody will be fused to ULBP2, a natural immunoligand of the NKG2D receptor present on most cytotoxic NK and T cells in the tumor environment. This unique therapeutic format will not only show a qualitative advantage over conventional antibodies, it will also lead to the recruitment of significantly more cytotoxic cells. In addition, we are working on alternative formats, including afucosylated, fully human anti- αVβ8 antibodies that are far more efficient in inducing immune-cell mediated killing of target cells than conventional antibodies.
The objective of the PB003A project is to develop a lead candidate and characterize it in in vitro and in vivo studies suitable for admitting the candidate to Phase 0 clinical trials. The implementation of the Phase 0 study, as the first phase of clinical development for immuno-oncology projects, is in line with Pure Biologics’ “smart clinical development” strategy of capturing valuable pharmacodynamic data directly in patients at an early clinical stage, in order to reduce the risk of failure of later, expensive phases of clinical trials, and significantly increase the value of the project in a more cost-effective manner compared to conventional clinical development based on phases 1-3, with the benefit of future commercialization of the project.
In the reported third quarter of 2023, the project’s main activities focused on continuing the search for potential drug-candidate antibodies that can induce killing of αVβ8-expressing tumor cells and regulatory immuno-suppressive regulatory T cells.
PROJECT DATA SHEET
Title: Development of an immunoligand-based therapy harnessing the immune system to fight cancer
Program: Smart Growth Operational Programme for 2014-2020
Value: PLN 39 905 405.00
Contribution of European Funds: PLN 30 130 439.00
Start: 1st February 2019
End: 31st December 2023