On October 23, 2024 Aulos Bioscience, an immuno-oncology company working to revolutionize cancer care through development of potentially best-in-class IL-2 therapeutics, reported data and analyses used to determine dose selection for Phase 2 expansion cohorts in a Phase 1/2 clinical trial of its lead candidate, AU-007 (Press release, Aulos Bioscience, OCT 23, 2024, View Source [SID1234647330]). The data and evaluations of pharmacodynamics, pharmacokinetics, safety and clinical efficacy were presented as a poster at the 36th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain.
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The results continue to affirm AU-007’s unique profile among interleukin-2 (IL-2) therapeutics, showing regulatory T cell (Treg) reduction, and demonstrating that deeper drops in peripheral Treg counts were associated with longer progression-free survival (PFS) outcomes in patients from the Phase 1 and Phase 2 portions of the AU-007 trial, across a range of dose levels, tumor types and lines of therapy. Additionally, increases in interferon-gamma and effector T cells (Teffs) were observed with escalating subcutaneously administered aldesleukin (recombinant human IL-2) dose levels.
"These data point to a correlation between deeper reductions in Tregs and better clinical outcomes, which differentiates AU-007 from all other IL-2 therapeutics in development," said Aron Knickerbocker, Aulos Bioscience’s president and chief executive officer. "We’re also excited about AU-007’s ability to increase Teffs and natural killer cells. These findings, combined with a mild and tolerable safety profile, further validate our belief in AU-007’s potential as a best-in-class IL-2 therapeutic for solid tumor cancers. We look forward to presenting new Phase 2 clinical efficacy and safety data, particularly in melanoma and renal cell carcinoma, later this year."
Created by Biolojic Design, AU-007 is the first human IgG1 monoclonal antibody designed by leveraging artificial intelligence to enter a human clinical trial. The antibody’s novel mechanism of action is to bind precisely to IL-2 instead of IL-2 receptors. By binding only to the portion of IL-2 that binds to CD25, AU-007 prevents IL-2 from binding to high-affinity IL-2 receptors on Tregs, vasculature and eosinophils, and redirects IL-2 to medium-affinity receptors on Teffs and natural killer (NK) cells. This allows Teffs and NK cells to expand and kill tumor cells.
Safety data presented at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium demonstrate manageable toxicity for AU-007 and low-dose, subcutaneous aldesleukin, with no vascular leak syndrome or pulmonary edema at all dose levels evaluated. Additionally, the AU-007 pharmacokinetic data show characteristics typical of an IgG1-LALA monoclonal antibody, with no evidence of neutralizing anti-drug antibody (ADA) activity and an approximate half-life of more than 15 days. No clear trends were observed in safety or efficacy data to determine if a single loading dose or multiple loading doses of aldesleukin would lead to better outcomes, and clinical investigation is ongoing in the Phase 2 dose expansion cohorts to determine the optimal dosing schedule.
Based on these results, researchers will evaluate dosing regimens of 9 mg/kg for AU-007 every two weeks (Q2W) and 135K IU/kg subcutaneous aldesleukin administered either on a single loading dose schedule or a Q2W multiple dose schedule in the Phase 2 expansion cohorts. The Phase 2 expansion portion of the trial is currently ongoing in renal cell carcinoma (RCC), melanoma and non-small cell lung cancer (NSCLC) evaluating these two dosing regimens.
The poster, "PB452: Determination of the phase 2 dose of AU-007, an AI-designed human monoclonal antibody that redirects IL-2 to T effector cells," (Abstract 464) is available to meeting registrants as an electronic poster on the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium’s online platform. It will be presented live in the poster session "New therapies in immuno oncology" on Friday, October 25, 2024, 9:00 a.m.-3:00 p.m. CEST in the Exhibition Hall.
The poster presentation is also available on the Aulos Bioscience website in the Abstracts and Publications section.
To learn more about the AU-007 clinical trial program, please visit ClinicalTrials.gov (identifier: NCT05267626). For patients and providers in the U.S., please visit www.solidtumorstudy.com. For patients and health professionals in Australia, please visit www.solidtumourstudy.com.
About AU-007
AU-007 is a human IgG1 monoclonal antibody designed by leveraging artificial intelligence that is highly selective to the CD25-binding portion of IL-2. With a mechanism of action unlike any other IL-2 therapeutic in development, AU-007 redirects IL-2 to reinforce anti-tumor immune effects. This is achieved by preventing IL-2, either exogenous or secreted by effector T cells, from binding to trimeric receptors on regulatory T cells while still allowing IL-2 to bind and expand effector T cells and NK cells. This prevents the negative feedback loop caused by other IL-2-based treatments and biases the immune system toward activation over suppression. AU-007 also prevents IL-2 from binding to CD25-containing receptors on eosinophils, as well as vasculature and pulmonary endothelium, which may significantly reduce the vascular leak syndrome and pulmonary edema associated with high-dose IL-2 therapy.