PB004 project focuses on the development of a biologic drug, a novel therapeutic molecule in the format of an afucosylated antibody, which is expected to stimulate the immune response of NK cells against tumor cells bearing the tumor antigen ROR-1, leading to their direct killing by an antibody-dependent cellular cytotoxicity (ADCC) mechanism. The PBA-0405 molecule is being developed for the treatment of solid tumors, including triple-negative breast cancer, as well as for the treatment of selected hematological malignancies, including chronic lymphocytic leukemia.
- PBA-0405 will be developed as a potential first-in-class molecule for the treatment of cancer patients based on an immunotherapeutic approach.
- The proposed therapy is envisioned for patients with leukemia and solid tumors whose cancer cells are characterized by overproduction of the ROR-1 protein.
- PBA-0405 was selected based on its efficacy parameter, i.e. the in vitro initiation of tumor cell killing by immune cells. This mechanism provides potentially significant therapeutic benefits. Secondary candidate parameters, such as stability and selectivity, also reached the required level.
- With the lead candidate selected, we are beginning preparations for the chemistry-manufacturing-control (CMC) stage, i.e. contracting these studies and producing the molecule on a larger scale, as well as preparing for preclinical studies.
- We expect the first results of PBA-0405’s anticancer efficacy studies in animal models to be available by the end of Q2 2023.
- We have already initiated activities leading to approval to initiate a Phase 0 clinical trial in 2023. The Phase 0 study is designed to determine preliminary local clinical efficacy in humans. Phase 0 is expected to be completed in Q2 2024.
- As part of further development, we assume that a clinical phase 1 trial, which could include hematologic cancer patients, could be initiated in late 2024.
- We have secured a total of approximately PLN 48 million in co-financing for the preclinical and clinical development of PB004 from non-dilutive grant sources.
- In early April 2023, we announced the nomination of lead candidate PBA-0091 for PB003G, the second project to be developed in parallel with PBA-0405.
Dr. Pieter Spee, Board Member and Chief Scientific Officer of Pure Biologics explains:
The nomination of a second lead candidate in the oncology area at short notice is a confirmation of our ambition to develop highly innovative oncology drugs. In line with our “me-better” approach to drug development, PBA-0405 has very clear competitive advantages against other potential drugs targeting ROR-1 that are at an advanced stage of clinical development. In in vitro tests, PBA-0405 has demonstrated selectivity and stability, as well as high efficiency in initiating ex vivo killing of tumor cells derived from the blood of patients with B-cell leukemia. The PB004 project is progressing on schedule to begin Phase 0 in cancer patients before the end of 2023. Our team has done an amazing job selecting a drug candidate with high potential for use in the treatment of both solid tumors and hematological malignancies, addressing an unmet medical need.
Dr. Filip Jeleń, co-founder, major shareholder and CEO of Pure Biologics comments:
According to the announced schedule, we have nominated a second lead candidate, this time in project PB004. Later this year, we aim to initiate Phase 0 clinical trials in both projects to determine the initial therapeutic efficacy of the drug candidates we are developing in the human cancer tumor setting. In parallel, we are intensifying contacts with potential partners. According to our discussions, we will need at least preliminary results of animal studies to carry out a possible transaction on terms that are reasonable from the point of view of the company and its shareholders. For both PB003G and PB004, we expect to obtain such results in late Q2/early Q3 2023.
The first studies in animal models with the proprietary molecules, determination of pharmacokinetic and pharmacodynamic (PK/PD) properties, and initiation of preclinical safety studies are planned for Q2 2023. The development of a manufacturing process for the drug candidate is scheduled to be contracted for the second half of 2023 (commencement of the CMC phase) and the filing of an eIND (exploratory IND, a form of application for clinical trial approval with the US FDA) and the start of a Phase 0 clinical trial (the first studies in humans after local administration of the investigational molecule to the tumor). Completion of the Phase 0 study is expected in Q2 2024.
In December 2022 Pure Biologics announced that it is accelerating development and focusing its activities on projects PB003A, PB003G and PB004, for which it has secured grant funding from the National Center for Research and Development and the Medical Research Agency in the total amount of approximately PLN 100 million. The Company’s plans are oriented – thanks to the synchronous development of the PB003 and PB004 projects – to accelerate the progress of work and optimize costs in the projects. In early April 2023. Pure Biologics announced the nomination of a lead candidate for the PB003G project.
We plan to carry out both projects in a novel approach involving a Phase 0 clinical trial, which may allow us to obtain the first information on the effectiveness of compounds in humans even two years sooner than in the case of the classic approach, based on Phase I and II clinical trials. At the same time, the data will be obtained at a financial outlay significantly lower than that of the aforementioned classical approach. In December 2022, we announced the conclusion of an agreement with the US company Presage Biosciences Inc. for the first human administration of molecules from the PB003G and PB004 projects in Phase 0. The study is scheduled to start in Q4 2023. We assume that the start of clinical Phase 1 could be possible in late 2024, and the trial in PB004 could include patients with hematological malignancies.