Interim data from an ongoing trial support overall mechanism of action of AU-007, a computationally designed human monoclonal antibody, in decreasing Tregs while increasing effector T cells and NK cells

Clinical efficacy and safety data from Phase 1 dose escalation cohorts to be presented before end of year

LARKSPUR, CA, USA I October 14, 2023 I Aulos Bioscience, an immuno-oncology company working to revolutionize cancer care through the development of potentially best-in-class IL-2 therapeutics, today presented new pharmacodynamic data from the ongoing Phase 1 dose escalation portion of its Phase 1/2 clinical trial of AU-007, the first human monoclonal antibody designed using artificial intelligence to be tested in a clinical trial. The data were shared in a poster presentation at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston, Massachusetts.

The study evaluated AU-007 as a monotherapy treatment or in a combination therapy regimen with low-dose subcutaneous Proleukin® (aldesleukin; recombinant human IL-2). The data demonstrate that AU-007 redirects interleukin-2 (IL-2) from regulatory T cells (Tregs) toward effector T cells (Teffs) and natural killer (NK) cells, which can kill tumor cells. The data also show a reduction in eosinophils, which at high cell counts can be associated with toxicity in the lungs.

“We believe AU-007 may be therapeutically effective in solid tumor cancers, and the cell types of interest in this study are trending in the right directions,” said Aron Knickerbocker, Aulos Bioscience’s chief executive officer. “These data continue to demonstrate favorable and unique pharmacodynamic effects in the IL-2 class. When AU-007 is administered to patients as monotherapy or in combination with low doses of Proleukin, the data show a decrease in immunosuppressive Tregs and increases in the numbers of Teffs and NK cells, both of which are cell types capable of killing tumor cells. To our knowledge, no other IL-2 therapy has shown such a profile of immune cell changes and the resulting change in the ratio of effector to suppressor immune cells. We also observed immune activation as assessed by interferon-gamma levels, which tend to increase following AU-007 with Proleukin. We will share the results of further pharmacodynamic investigations of AU-007 in combination with higher doses of Proleukin in the future. We also look forward to presenting new clinical efficacy and safety data from the Phase 1 dose escalation cohorts later this year.”

Created by Biolojic Design, AU-007 is a human IgG1 monoclonal antibody designed using artificial intelligence to harness the power of IL-2 to eradicate solid tumors. The antibody’s novel mechanism of action lies in its ability 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 and eosinophils and redirects IL-2 to medium-affinity receptors on NK cells and effector T cells. This allows effector T cells and NK cells to expand and kill tumor cells.

The Phase 1 dose escalation study presented at the AACR-NCI-EORTC International Conference shows that AU-007 redirected IL-2 from Tregs toward effector T cells and NK cells and expanded those cells with and without low doses of Proleukin, which is consistent with the antibody’s mechanism of action. This overall effect increased with time on Proleukin given every two weeks with AU-007, or with higher dose levels of Proleukin. These changes were observed across a broad range of cancer types and were not associated with any drug-related events. Additionally, AU-007 treatment led to decreases in eosinophils and increases in interferon-gamma with and without Proleukin, which supports the antibody’s proposed activity.

The Phase 1/2 clinical trial of AU-007 is a two-part, open label, first-in-human study evaluating the safety, tolerability, immunogenicity and clinical activity of AU-007 in patients with unresectable locally advanced or metastatic cancer. The trial is currently enrolling patients at multiple site locations in the United States and Australia. The company anticipates transitioning to the Phase 2 portion of the AU-007 study by year-end.

The poster presentation is available on the Aulos Bioscience website in the Abstracts and Publications section.

About AU-007
AU-007 is a computationally designed, human IgG1 monoclonal antibody 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 leverages 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 vasculature and pulmonary endothelium, which may significantly reduce the vascular leak syndrome and pulmonary edema associated with high-dose IL-2 therapy.

About Aulos
Aulos Bioscience is an immuno-oncology company working to revolutionize cancer patient care through best-in-class IL-2 therapeutics that direct patients’ immune systems toward killing tumor cells. Matching world-class machine learning from co-founder Biolojic Design with an in-depth understanding of the immune system, Aulos’ initial clinical candidate, AU-007, is a computationally designed human antibody that harnesses the power of IL-2 to induce tumor killing while limiting the immunosuppression and toxicities typically associated with this validated pathway. The company was founded by Biolojic Design and Apple Tree Partners (ATP) and is led by pioneers in the field of artificial intelligence, antibody development and cancer immunotherapies. For more information, visit, X (Twitter) at @AulosBioscience and LinkedIn.

SOURCE: Aulos Bioscience