Patrys Ltd (ASX:PAB) has fielded preclinical data that demonstrate the company’s full-sized IgG antibody, PAT-DX3, can effectively cross the blood-brain in healthy animals, opening potential new pathways to use deoxymabs to deliver small molecule therapeutics and gene editing technologies for various neurological conditions.
A 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 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.
Patrys demonstrated 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 that it maintained that advantage for the duration of the study.
Antibodies specifically engineered to cross the blood-brain barrier have reported brain uptake values 2–3 fold higher than control antibodies, meaning PAT-DX3 compares favourably to even purpose-built antibodies.
The PAT-DX3 advantage
Patrys’ treatment appears to have pharmacokinetic advantages above and beyond its ability to cross the blood-brain barrier, also demonstrating a much higher average drug exposure than control antibodies.
PAT-DX3’s area under the curve (AUC), a measurement of overall drug exposure, was about seven times greater than control, with ‘significant’ concentrations of antibody still in the brain after the trial ended at four days.
“This is an important result that opens up a range of potential applications for Patrys and its development partners,” Patrys CEO and managing director Dr James Campbell said.
“PAT-DX3 appears to outperform 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.”