Immuno-oncology company Aulos Bioscience has revealed interim results from an ongoing Phase I/II trial of monoclonal antibody AU-007 in solid tumours.
The data indicate that AU-007 is well tolerated in patients with unresectable locally advanced or metastatic cancer and there are early signs of anti-tumour activity.
AU-007 is a human IgG1 monoclonal antibody designed using artificial intelligence to harness the power of interleukin-2 (IL-2) to eradicate solid tumours.
“These new interim data support our belief that AU-007 offers a novel mechanism of action among IL-2 therapeutics in development, as demonstrated by AU-007’s pharmacodynamic and safety profile to date,” said Aron Knickerbocker, Aulos Bioscience’s Chief Executive Officer.
“In addition, we are further encouraged that, since the data cut-off date, we are seeing early signs of anti-tumour activity in patients, which is consistent with preclinical findings that demonstrate AU-007’s unique ability to bind to IL-2 and redirect it from regulatory T cells, which suppress the immune system, to effector T cells and natural killer cells that can kill tumour cells.”
The Phase I/II trial
AU-007 is the first computationally designed human monoclonal antibody in a human clinical trial. Created by Biolojic Design, the antibody binds with to IL-2, preventing IL-2 from binding to the CD25 subunit contained in trimeric IL-2 receptors expressed on immunosuppressive regulatory T cells (Tregs), vascular and pulmonary endothelium, and eosinophils.
While AU-007 prevents IL-2 from attaching to Tregs, it doesn’t affect IL-2’s ability to bind to dimeric IL-2 receptors expressed on effector T cells (Teff) and natural killer (NK) cells. This allows Teff and NK cells to expand and kill tumour cells.
In the Phase I/II trial, three of the four tumour evaluable patients had a best response of stable disease, and two patients continue treatment as of the data cut-off date.
In addition, all seven patients with available pharmacodynamic data demonstrate overall decreasing Tregs (percentage change and absolute) and eosinophils. This finding is in stark contrast to data from other IL-2 therapeutics, which show increases in Tregs that cannot be controlled and may result in immune suppression instead of activation.
Initial pharmacokinetic data from the AU-007 trial also demonstrate continued dose proportional serum concentrations of the compound, with characteristics similar to IgG1 therapeutic human monoclonal antibodies. This indicates the antibody is behaving predictably and has a half-life that will allow for dosing every two weeks.