OBJECTIVES
The aim of the PB004 project is to develop an anti-cancer therapeutic based on an anti-ROR1 antibody, with significantly improved therapeutic properties compared to Zilovertamb, an anti-ROR1 antibody currently in III phase of clinical development.
ROR1 is a cell surface molecule expressed in many types of cancer, involved in cancer cell survival, proliferation and migration, but absent in most normal healthy tissue, making it an excellent therapeutic target. PB004 has developed an anti-ROR1 antibody that binds to a specific epitope on the ROR1 molecule, and that has increased binding affinity to CD16 receptor expressed on Natural Killer (NK) cells. It induces cancer cell death by activating NK cells and leading to so called Antibody-Dependent Cell Cytotoxicity (ADCC). The developed antibody has great potential for the treatment of patients with ROR1-expressing cancers, especially lymphomas and leukaemias, such as mantle cell lymphoma (MCL) and chronic lymphocyte leukemia (CLL).
The project originally funded under POIR has been divided into two substantially separate phases [PHASE I and PHASE II].
In Phase II of the project, the Company is focused on conducting a Phase 0 study in cancer patients. The Phase 0 study in solid tumor patients will evaluate the mechanism of action of PBA-0405 in the complex microenvironment of human cancer. The planned study will include patients with head and neck cancer, soft tissue sarcoma and triple negative breast cancer and will use a panel of biomarkers to investigate different signs of PBA-0405 activity in cancer patients. The endpoint of the Phase II project is to demonstrate the efficacy of the investigational compound in human tumors in a Phase 0 clinical trial.
The subject of the funded Phase II project is R&D work in the area of innovative medical solutions and the implementation of innovations. Among other things, the Phase II project will include studies to assess the safety of the lead molecule using off-target binding and immunogenicity assays.
PROJECT PROGRESS
In the first quarter of 2025, activities in the project focused on completing the phase clinical trial of the PBA-0405 molecule. The last, eighth patient was recruited in February 2025, and the results were presented in early March. At the same time, the required stability testing of the medicinal product for clinical trials was carried out by Wuxi Biologics. Tests at the last scheduled time point (M18) showed that PB-0405 is stable and retains its activity over 18 months.
In total, among the 8 patients enrolled in the study, the pharmacodynamic effect at the injection sites of PBA-0405 and the control was analysable in 86 tumour tissue sections from 5 patients. The results of the phase 0 study allowed the following conclusions to be drawn:
1) ROR-1 was present in all tumours studied, which is a critical condition for the activity of PBA-0405, although the level of expression varied.
2) NK cells and macrophages, immune cells that induce antibody-dependent cytotoxicity (ADCC and ADCP), are present in all tumour samples tested, which is an absolute prerequisite for the activity of PBA-0405.
3) PBA-0405 induces the killing of tumour cells. An increase in the level of a biomarker indicating cell killing (CC3, activated caspase 3) was observed in 4 out of 5 patients. The level of the CC3 biomarker correlates with PBA-0405-induced activation of the immune system, observed by an increase in the expression of the interferon response gene ISG-15 in the same patients.
Thus, the primary endpoints of the study were achieved – it was confirmed that PBA-0405 leads to the killing of cancer cells in a ROR1-dependent manner, with the involvement of immune mechanisms. No obvious adverse events related to the administration of PBA-0405 were reported during the study. Obtaining a positive response, i.e. one that is consistent with expectations and confirms the intended mechanism of action of PBA-0405 in 4 out of 5 patients (80%), is a very promising result that allows us to plan further phases of clinical development with optimism. We are currently awaiting the final version of the biomarker study report and the final study report. Once approved, the phase 0 study will be formally completed.
PROJECT DATA SHEET
PHASE I
Title: Development of a bispecific antibody fragment for simultaneous cancer control and immune cell recruitment (BIKE)
Program: Smart Growth Operational Programme 2014-2020
Value: PLN 40,417,125.00
Contribution of European Funds: PLN 29 869 080,00
Start: July 1, 2019
End: December 30, 2023
PHASE II
Title: Development of a bispecific antibody fragment for simultaneous cancer control and immune cell recruitment (PHASE II)
Program: European Funds for Modern Economy Program 2021-2027 (FENG) within the scope of Action 01.01 SMART Pathways – R&D Module of the FENG Program
Value: PLN 5,848,000.00
Contribution of European Funds: PLN 2,924,000.00
Start: January 1, 2024
End: November 15, 2025
