Immunooncology

 PB003G

In cancer, a balance between immune system effector and regulatory cells becomes disturbed. Project PB003G involves a novel approach to develop a drug based on a so-called bifunctional therapeutic molecule (BFP) that will synergistically activate immune cells and minimize immunosuppression in the tumor microenvironment.

OBJECTIVES

The goal of the PB003g project is to develop an anticancer drug that specifically targets the GARP-TGFβ1 protein complex, with significantly greater therapeutic efficacy than anti-GARP antibodies currently in early clinical development (e.g., ABBV-151 molecule, Abbvie, HLX60, Henlius and DS-1055, Daichii-Sankyo).

The accumulation of regulatory T (Treg) cells in the tumor microenvironment is associated with an unfavorable prognosis in various types of solid tumors. The GARP-TGFβ1 complex is highly expressed on various tumor cells (including lung, colorectal, breast, head and neck), as well as on regulatory T cells (Treg), and plays a key role in immunosuppression. While ABBV-151 aims to restore immune function by blocking the release of immunosuppressive TGFβ1 from its complex with GARP, DS-1055 recruits and activates NK cells to directly kill Treg and tumor cells. Project PB003g aims to develop a therapeutic molecule that targets Treg and tumor cells with GARP-TGFβ1 expression much more effectively than competing molecules. To achieve this, drug candidate PBA-0091 is being developed in the form of a so-called bifunctional therapeutic molecule (bifunctional fusion protein, BFP), in which a conventional antibody will be fused with ULBP2, a natural immunoligand of the NKG2D receptor present on most cytotoxic NK and T cells in the tumor environment. This unique therapeutic format developed by Pure Biologics will not only show a qualitative advantage over conventional antibodies, it will also lead to the recruitment of a much larger number of cytotoxic cells capable of killing cancer cells. In addition, we have developed an afucosylated fully human anti-GARP antibody, PBA-0111, that combines the blocking features of ABBV-151 with the killing power of DS-1055.

The goal of the PB003G project is to identify the best lead candidate for testing in a Phase 0 clinical study in cancer patients. 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 early clinical development. 

PROJECT PROGRESS

In the third quarter of 2023, the PB003G project focused on CMC and preclinical development of drug candidate PBA-0091 and selected back-up candidates, to prepare for Phase 0 clinical development in solid tumor cancer patients. 

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

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