AU-007 Showcases Unique IL-2 Class Profile with Promising Efficacy Data
Aulos Bioscience, a pioneering company in the field of immuno-oncology, recently presented significant data supporting the dose selection for its lead therapeutic candidate, AU-007, at the 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics held in Barcelona, Spain. This research is part of a Phase 1/2 clinical trial evaluating the efficacy and safety of AU-007, which is designed to enhance cancer treatment by harnessing the immune system.
The data presented affirm AU-007’s distinctive profile among interleukin-2 (IL-2) therapeutics, particularly highlighting its ability to effectively reduce regulatory T cells (Tregs). A notable finding is the correlation between deeper reductions in peripheral Treg counts and improved progression-free survival (PFS) outcomes among patients across various doses, tumor types, and lines of therapy. This suggests that AU-007 may provide a therapeutic advantage by improving immune response against tumors, a critical factor in cancer treatment.
Additionally, the results indicated an increase in tumor-killing effector T cells (Teffs) and interferon-gamma levels with escalating doses of subcutaneously administered aldesleukin, a recombinant form of human IL-2. The data suggests that AU-007 not only reduces Tregs, which are known to suppress immune responses, but also enhances the activity of Teffs and natural killer (NK) cells, essential players in the body’s ability to fight cancer.
Aron Knickerbocker, President and CEO of Aulos Bioscience, commented on the findings, stating, “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. 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.”
AU-007 is particularly noteworthy as it is the first human IgG1 monoclonal antibody designed with the aid of artificial intelligence to enter human clinical trials. Its novel mechanism of action involves binding specifically to IL-2 rather than IL-2 receptors, enabling it to selectively redirect IL-2 to medium-affinity receptors on Teffs and NK cells while preventing IL-2 from binding to high-affinity receptors on Tregs, vasculature, and eosinophils. This unique approach enhances the expansion and activation of Teffs and NK cells, thereby promoting tumor cell destruction.
During the symposium, safety data were also presented, showcasing that AU-007, when administered alongside low-dose aldesleukin, exhibited a manageable toxicity profile. Importantly, no cases of vascular leak syndrome or pulmonary edema were reported across all evaluated dose levels. Pharmacokinetic data indicated characteristics typical of an IgG1-LALA monoclonal antibody, revealing no evidence of neutralizing anti-drug antibody (ADA) activity and demonstrating an approximate half-life exceeding 15 days.
The clinical investigation is ongoing, with researchers assessing the optimal dosing schedule for AU-007 in the Phase 2 expansion cohorts. Proposed regimens include administering AU-007 at a dose of 9 mg/kg every two weeks, alongside 135K IU/kg of subcutaneous aldesleukin, which may be given as either a single loading dose or multiple doses every two weeks. The expansion cohorts are focused on evaluating these regimens in patients with renal cell carcinoma (RCC), melanoma, and non-small cell lung cancer (NSCLC).
The poster presentation titled “PB452: Determination of the phase 2 dose of AU-007, an AI-designed human monoclonal antibody that redirects IL-2 to T effector cells,” was made available for attendees of the symposium as an electronic poster and will also be featured in a live presentation during the session on “New therapies in immuno-oncology” on Friday, October 25, 2024.
In addition, the poster is accessible on the Aulos Bioscience website in the Abstracts and Publications section, allowing wider access to this critical research for those interested in the advancements of immuno-oncology and the potential of AU-007 to reshape cancer therapy.
Overall, the data presented by Aulos Bioscience at the symposium underscores the promising potential of AU-007 as a groundbreaking therapeutic option for patients with solid tumors. The ongoing studies aim to provide further insights into its efficacy and safety, with the hope of transforming the landscape of cancer treatment and improving patient outcomes.
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.
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 human antibody designed by leveraging artificial intelligence 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.
