On May 26, 2022 Aulos Bioscience, an immuno-oncology company working to revolutionize cancer care through the development of potentially best-in-class IL-2 therapeutics, reported a Trials in Progress poster that is being presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2022 Annual Meeting (Press release, Aulos Bioscience, MAY 26, 2022, View Source [SID1234615134]). The poster showcases the study design for the company’s first-in-human Phase 1/2 trial of AU-007 that is currently enrolling patients in Australia. AU-007 is a human monoclonal antibody computationally designed by Biolojic Design, with a highly differentiated approach to harnessing the power of interleukin-2 (IL-2) to eradicate solid tumors.
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"AU-007 stands apart with a mechanism of action that is entirely different from every other IL-2 therapeutic in development," said Aron Knickerbocker, Aulos Bioscience’s chief executive officer. "This Phase 1/2 study is the first time that a computationally designed human monoclonal antibody has been tested in humans. By addressing the IL-2 negative feedback loop, we believe AU-007 could potentially subdue immune suppression and prevent the toxic side effects of IL-2, leading to a novel treatment for solid tumor cancers."
The Trials in Progress poster describes how AU-007 can bind human IL-2 with picomolar affinity and precisely block IL-2’s binding to CD25, without hindering IL-2’s binding to CD132/CD122. Through this unique mechanism of action, AU-007 can transform the IL-2 negative feedback loop into a positive one, tipping the balance toward immune activation and away from immune suppression. Recently released preclinical data of murine models demonstrate that redirected IL-2 signaling by AU-007 can lead to significant tumor growth inhibition, and complete MC38 colorectal tumor elimination when AU-007 is dosed in combination with checkpoint inhibitors.
The company’s Phase 1/2 trial (NCT05267626) 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. Phase 1 consists of three dose escalation arms evaluating AU-007 either as a monotherapy, in combination with a single loading dose of aldesleukin, or with both AU-007 and aldesleukin administered once every two weeks. The Phase 2 portion of the trial evaluates a dosing regimen selected from dose escalation for expansion in specified tumor types to further define the safety and initial efficacy of AU-007. Dosing of patients commenced in May, and preliminary data from the Phase 1 portion of the clinical trial is expected by late 2022.
The Trials in Progress poster is available to meeting registrants as an e-poster on the ASCO (Free ASCO Whitepaper) Annual Meeting website and will be presented live in the Trials in Progress poster session "Developmental Therapeutics—Immunotherapy" on Sunday, June 5, 2022, 8:00 a.m. to 11:00 a.m. CDT.
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.