On October 17, 2022 Patrys Limited (ASX: PAB, "Patrys" or the "Company"), a therapeutic antibody development company, reported that new preclinical data for its full-sized IgG antibody, PAT-DX3 (Press release, Patrys, OCT 17, 2022, View Source [SID1234622042]). Results from a new study support the potential to use deoxymabs to deliver small molecule therapeutics and gene editing technologies across the blood-brain barrier to treat various neurological targets and conditions.
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This study was conducted by a leading global contract research organisation which radioactively labelled both PAT-DX3 and a control antibody to monitor their relative uptake into various tissues over the course of four days. The study’s goal was to establish the distribution of PAT-DX3 in a range of different tissues to assist in the selection of future targets and payloads for future potential antibody drug conjugate (ADC) development programs.
The study found that the uptake into the brain (per cubic centimetre) of PAT-DX3 was 3–4 fold higher than that of a control antibody soon after injection, and this persisted for the duration of the study period. This compares favourably to antibodies that have been specifically engineered for enhanced blood-brain barrier crossing that have reported brain uptake values 2–3 fold higher than control antibodies1. The area under the curve (AUC) of PAT-DX3, a measurement of overall drug exposure, was approximately seven times greater for PAT-DX3 than it was for the control antibody in this study, with significant concentrations of antibody still in the brain after four days.
The ability of PAT-DX3 to cross the blood-brain barrier is consistent with current data which indicates that Patrys’ deoxymabs enter cells using the ENT2 transporter protein; a protein which is highly expressed in the neural vasculature. Elevated levels of PAT-DX3 were found in brain tissue but not in a range of other tissues including the lung, the liver and the thyroid adding further support to this proposed mechanism for crossing the blood-brain barrier. 1 Kouhi, A. et al. Brain Disposition of Antibody-Based Therapeutics: Dogma, Approaches and Perspectives. Int. J. Mol. Sci. 2021, 22, 6442. View Source
Patrys Chief Executive Officer and Managing Director, Dr. James Campbell said: "This is an important result that opens up a range of potential applications for Patrys and its development partners. PAT-DX3 appears to out-perform antibodies specifically developed by other companies for the delivery of payloads to brain tissue. Unlike deoxymabs, none of these other antibodies are able to deliver their payloads into the cell and the cell nucleus. These properties open up a range of applications for using deoxymabs to deliver small molecule therapeutics and gene editing technologies directed to various neurological targets and conditions. As we advance PAT-DX1 towards the first clinical trial in cancer patients in H2 CY2023, it is very exciting for Patrys to be able to identify additional applications for PAT-DX3 that may open up new development or partnering opportunities for the Company."