Aulos Bioscience presented dose selection data from its Phase 1/2 clinical trial of AU-007, a novel IL-2 therapeutic, at the 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain. The data supports the selection of doses for Phase 2 expansion cohorts and highlights AU-007's unique profile among IL-2 therapeutics.
AU-007's Unique Mechanism of Action
AU-007, created by Biolojic Design, is a human IgG1 monoclonal antibody designed using artificial intelligence. It binds specifically to IL-2, preventing it from binding to high-affinity IL-2 receptors on regulatory T cells (Tregs), vasculature, and eosinophils. This redirection of IL-2 promotes binding to medium-affinity receptors on effector T cells (Teffs) and natural killer (NK) cells, enhancing their expansion and tumor-killing capabilities.
Clinical Trial Data and Findings
The Phase 1/2 trial data indicated that deeper reductions in peripheral Treg counts were associated with longer progression-free survival (PFS) across various dose levels, tumor types, and lines of therapy. Additionally, escalating doses of subcutaneous aldesleukin (recombinant human IL-2) led to increases in interferon-gamma and Teffs.
Aron Knickerbocker, Aulos Bioscience’s president and chief executive officer, stated, “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. We’re also excited about AU-007’s ability to increase Teffs and natural killer cells.”
Safety and Pharmacokinetics
Safety data presented at the symposium showed that AU-007 and low-dose aldesleukin had manageable toxicity, with no reports of vascular leak syndrome or pulmonary edema at any of the evaluated dose levels. Pharmacokinetic data indicated that AU-007 exhibits characteristics typical of an IgG1-LALA monoclonal antibody, with an approximate half-life exceeding 15 days and no evidence of neutralizing anti-drug antibody (ADA) activity.
Phase 2 Expansion Cohorts
Based on these findings, 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. These cohorts are currently enrolling patients with renal cell carcinoma (RCC), melanoma, and non-small cell lung cancer (NSCLC).
Ongoing Clinical Investigation
The Phase 2 expansion portion of the trial is ongoing to determine the optimal dosing schedule. The primary focus remains on evaluating the efficacy and safety of AU-007 in combination with aldesleukin in selected solid tumors.
More information about the AU-007 clinical trial program can be found at ClinicalTrials.gov (identifier: NCT05267626).
