Data show trend in decreasing Tregs, presenting unique profile among current IL-2 therapeutics

Adding Phase 1/2 clinical trial sites in the U.S. following recent IND application clearance

LARKSPUR, CA, USA I November 10, 2022 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 early data from its Phase 1/2 study of AU-007. AU-007 is a human monoclonal antibody computationally designed by Biolojic Design to harness the power of interleukin-2 (IL-2) and eradicate solid tumors. Data were presented in a poster presentation at the 37th Society for Immunotherapy of Cancer (SITC) Annual Meeting in Boston, Massachusetts.

Initial pharmacokinetic data from the first three patients administered AU-007 as a monotherapy demonstrate characteristics similar to other IgG1 therapeutic human monoclonal antibodies. Further, the data are consistent with the novel mechanism of action of the antibody. AU-007 binds IL-2 with high specificity and picomolar affinity, and completely inhibits IL-2’s binding to the CD25 subunit contained in trimeric IL-2 receptors expressed on immunosuppressive T regulatory cells (Tregs), vascular and pulmonary endothelium, and eosinophils. It does this without hindering IL-2’s binding to dimeric IL-2 receptors that contain CD122 and CD132 and are expressed on T effector and NK cells. Both T effector and NK cells are cell types that can kill tumor cells.

The early clinical data with AU-007 show trends toward decreasing Tregs with corresponding increases in the CD8/Treg ratio, initial interferon-gamma increases, and decreasing absolute eosinophils. The initial clinical findings are consistent with the preclinical in vivo and in vitro data from mice with syngeneic tumors, human peripheral blood mononuclear cells and cynomolgus monkeys treated with AU-007. In contrast, reported clinical data and preclinical data from other IL-2 therapeutics demonstrate that all other agents assessed substantially increase Tregs due to the negative feedback loop that such other approaches elicit and cannot control, likely contributing to disappointing clinical efficacy findings with second-generation IL-2 agents. Among the three evaluable patients treated with monotherapy AU-007, there has been only one drug-related toxicity, a case of Grade 1 diarrhea in a single patient. Two of the three patients have stable disease and continue on study treatment, with tumor shrinkage seen in one patient with metastatic non-small lung cancer treated with 1.5 mg/kg of monotherapy AU-007 every two weeks.

“With this very early data from our Phase 1/2 study, we are encouraged to see that in the initial three patients, AU-007 appears to be safe and well-tolerated to date,” said Aron Knickerbocker, Aulos Bioscience’s chief executive officer. “At this early stage, we are also pleased to see an overall trend of decreasing immunosuppressive Tregs, which is consistent with what we found in our preclinical studies. The promise of AU-007 in eradicating solid tumors lies in this highly differentiated mechanism of action, which breaks the negative feedback loop to Tregs, and is completely unlike that of any other IL-2 therapy in development. We continue to believe that AU-007 has significant potential sources of efficacy and safety competitive advantages in the class due to its unique ability to redirect IL-2 to T effector and NK cells and away from immunosuppressive Tregs, vasculature and pulmonary endothelium. We are grateful to the patients and investigators in Australia who are taking part in our clinical trial, and we are excited to add trial sites in the United States following the clearance of our IND application by the FDA two weeks ago.”

The company’s Phase 1/2 clinical trial (NCT05267626) is an 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. Phase 1 consists of three dose escalation arms evaluating AU-007 either as a monotherapy, in combination with a single loading dose of recombinant human IL-2 (aldesleukin), or with both AU-007 and aldesleukin administered once every two weeks. The aldesleukin will be administered subcutaneously, at much lower doses and much less frequently than the approved regimen of intravenously administered aldesleukin. The Phase 2 portion of the trial will evaluate a dosing regimen selected from dose escalation for expansion in specified tumor types to further define the safety and initial efficacy of AU-007.

In October, the U.S. Food and Drug Administration (FDA) cleared the company’s Investigational New Drug (IND) application for AU-007, allowing expansion of the Phase 1/2 study in the United States. Dosing of patients in the U.S. is anticipated to begin by year-end. The trial is currently enrolling patients in Australia.

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 T effector cells, from binding to trimeric receptors on T regulatory cells while still allowing IL-2 to bind and expand T effector 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 trimeric 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 ATP with $40 million in Series A funding from ATP and is led by pioneers in the field of artificial intelligence, antibody development and cancer immunotherapies. For more information, visit

SOURCE: Aulos Bioscience