On April 29, 2025 Aulos Bioscience, an immuno-oncology company working to revolutionize cancer care through development of its lead immune-activating antibody therapeutic, reported positive results from its Phase 1/2 dose escalation and cohort expansion study of its investigational candidate AU-007 (Press release, Aulos Bioscience, APR 29, 2025, View Source [SID1234652302]). The data were shared in a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, Illinois.
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The interim Phase 2 data demonstrate clear evidence of durable partial and complete tumor response in multiple cancer types, including patients with melanoma whose tumors had progressed through prior checkpoint inhibitors and who received a combination of AU-007 and low-dose, subcutaneous aldesleukin. Durable tumor shrinkages were also observed in patients with checkpoint inhibitor-resistant or progressed renal cell carcinoma (RCC) who received the same AU-007 and aldesleukin regimen. Additionally, AU-007 and low-dose, subcutaneous aldesleukin continues to demonstrate a unique pharmacodynamic (PD) profile in the interleukin-2 (IL-2) class, with regulatory T cells (Tregs) decreasing and CD8 effector T cells expanding at all AU-007 dose levels.
"We are very pleased with the clinical activity observed with AU-007 and low-dose, subcutaneous aldesleukin without a checkpoint inhibitor, as it accentuates our confidence in AU-007 as a potential best-in-class therapeutic for multiple cancers," said Aron Knickerbocker, Aulos Bioscience’s president and chief executive officer. "Deep and durable tumor shrinkages, including complete responses, are occurring in patients who were refractory to treatment and had achieved no responses from highly potent prior immuno-oncology regimens. Importantly, the results reinforce the previously reported observation that the CD8 effector T cell expansion and Treg reduction correlates with clinical efficacy. This key driver of Treg reduction coupled with CD8 effector T cell expansion and enhancement of the CD8/Treg ratio differentiates AU-007 from other IL-2 therapeutic programs. Today’s data support further evaluation of AU-007 and low-dose, subcutaneous aldesleukin as a second-line treatment for melanoma, where limited treatment options exist. Our new Phase 2 cohort augmenting this regimen with anti-PD-1 nivolumab is now enrolling patients and we look forward to presenting preliminary data later this year."
Key findings from interim results of the Phase 1/2 dose escalation and cohort expansion study of AU-007, with data available on 95 patients as of the data cutoff date of March 20, 2025, are as follows:
Continued tolerable and manageable safety profile was observed with AU-007 as a monotherapy and in combination with low-dose, subcutaneous aldesleukin at all doses evaluated in Phase 1 dose escalation.
No dose-limiting toxicity occurred throughout Phase 1 dose escalation.
Most drug-related adverse events were mild and transient Grade 1 or 2 events.
The most common treatment-related adverse events in patients who received AU-007 and low-dose, subcutaneous aldesleukin were Grade 1 or 2 fatigue (21%), pyrexia (21%), chills (19%) and infusion-related reaction (15%).
The incidence of Grade 3 or 4 treatment-related adverse events in patients who received AU-007 and low-dose, subcutaneous aldesleukin was cytokine release syndrome (1%), lymphopenia (8%) and anemia (3%). All events were transient and resolved, and there were no Grade 5 treatment-related adverse events.
Durable objective responses were observed in patients with multiple tumor types enrolled in the Phase 1 dose escalation and Phase 2 cohorts.
One patient with metastatic bladder cancer that progressed on an anti-PD-L1 treatment was treated with AU-007 every two weeks (Q2W) and one loading dose of low-dose, subcutaneous aldesleukin, has an ongoing metabolic complete response and continues on treatment for two years.
One patient with metastatic nasopharyngeal head and neck cancer that progressed on five prior systemic therapies received AU-007 and low-dose, subcutaneous aldesleukin Q2W. This patient experienced an unconfirmed complete response after 20 months and continues on treatment.
Three patients with melanoma refractory to either prior anti-CTLA-4 and anti-PD-1 or anti-PD-1 and anti-LAG-3 therapy were treated with AU-007 Q2W and one loading dose of low-dose, subcutaneous aldesleukin, and experienced deep and durable tumor shrinkages of 100% (complete response in all target lesions, continues on study for 13+ months), 58% (continues on study for 10+ months) and 48% (on study for 13 months).
One patient in dose escalation with acral melanoma that progressed rapidly on prior anti-PD-1 therapy received AU-007 and one loading dose of low-dose, subcutaneous aldesleukin. This patient remained on AU-007 therapy for 11 months with disease control.
The regimen of AU-007 and low-dose, subcutaneous aldesleukin exhibits distinct pharmacodynamic effects in the class and continues to drive durable decreases in Tregs, increases in CD8 T cells, and corresponding increases in CD8/Treg ratios.
A decrease in Tregs appears to be a critical determinant of observed efficacy, with Tregs decreasing in the periphery in the presence of AU-007 at all dose levels.
This finding supports AU-007’s overall mechanism of action to control and redirect endogenously produced IL-2 and exogenously administered IL-2 to reduce the Treg population and increase circulating CD8 effector T cell populations. Treg cells are highly immunosuppressive cells that can blunt the immune response to tumors and reduce the durability of responses and progression-free survival.
The Phase 2 expansion cohorts evaluating AU-007 and a single loading dose of low-dose, subcutaneous aldesleukin continue to enroll patients with advanced cutaneous melanoma who have failed prior checkpoint inhibitor therapy as well as patients with PD-L1+ non-small cell lung cancer (NSCLC) who have failed prior checkpoint inhibitor therapy.
An additional Phase 2 cohort is evaluating AU-007 and low-dose, subcutaneous aldesleukin combined with avelumab (checkpoint inhibitor with ADCC effector function; anti-PD-L1) in PD-L1+ NSCLC in patients who have failed prior checkpoint inhibitor therapy. As announced earlier this month, a new Phase 2 cohort evaluating AU-007 and a single subcutaneous loading dose of low-dose aldesleukin combined with nivolumab (checkpoint inhibitor; anti-PD-1) as a second-line treatment for cutaneous melanoma is enrolling patients who have not received a prior BRAF/MEK inhibitor. Aulos anticipates presenting preliminary clinical data from these two Phase 2 expansion cohorts in the second half of 2025.
The poster, "AU-007, a human monoclonal antibody (mAb) that binds to IL-2 and inhibits CD25 binding, plus low-dose aldesleukin, in advanced solid tumors: Phase 2 update," (Abstract CT178) is accessible to meeting registrants as an electronic poster on the AACR (Free AACR Whitepaper) 2025 virtual meeting platform. It is also available on the Aulos Bioscience website in the Abstracts and Publications section.
To learn more about the AU-007 clinical trial program, please visit ClinicalTrials.gov (identifier: NCT05267626). For patients and providers in the U.S., please visit www.solidtumorstudy.com. For patients and health professionals in Australia, please visit www.solidtumourstudy.com.
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.