AU-007 Shows Strong Anti-Tumor Activity in Advanced Solid Cancers at SITC Meeting

Aulos Bioscience, an immuno-oncology company based in Larkspur, California, has announced promising results from its Phase 1/2 clinical trial of AU-007, an innovative IL-2 therapeutic. The findings will be presented at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting in Houston, Texas.

The Phase 2 trial data indicates that combining AU-007 with low-dose, subcutaneous aldesleukin shows clinical activity in melanoma. This result aligns with Phase 1 data that demonstrated AU-007's clinical efficacy across various patients whose tumors had previously progressed despite checkpoint inhibitor treatments. Across all 77 patients involved in the study, there were significant and lasting reductions in immunosuppressive Treg cells, a novel outcome within the IL-2 class, correlating with improved progression-free survival as Treg reduction increased.

Aron Knickerbocker, President and CEO of Aulos Bioscience, stated that these results support the clinical proof of concept for AU-007. He expressed confidence in its potential as a leading therapeutic and anticipates presenting more comprehensive Phase 2 data for melanoma, renal cell carcinoma, and non-small cell lung cancer in the coming year.

Key findings from the Phase 1/2 trial, which included data from 77 patients as of September 28, 2024, are as follows:

1. **Safety and Tolerability**: The safety profile was manageable and tolerable across various doses in Phase 1. There were no dose-limiting toxicities observed. Most side effects were minor (Grade 1 or 2), except for:
- Grade 3 anemia in one patient with pre-existing anemia, progressing rapidly, and receiving only two doses of the study drug.
- Grade 4 cytokine release syndrome (CRS) in one patient, which was managed with steroids, IV fluids, and brief vascular pressor support, without the need for tocilizumab. This patient had elevated IL-6 levels, likely due to gout.
- Transient Grade 3 elevated lipase in one patient, which resolved without symptoms or intervention.
- Transient Grade 3 or 4 lymphopenias in six patients, which resolved within 3-7 days without adverse outcomes. This is consistent with IL-2 treatment effects as lymphocytes move from blood to tissue.

2. **Anti-Tumor Activity**: There was strong evidence of anti-tumor activity, particularly in heavily pre-treated melanoma patients:
- Two melanoma patients, resistant to prior anti-CTLA-4 and anti-PD-1 therapies, showed significant tumor shrinkage of 48% and 100% following treatment with AU-007 and low-dose aldesleukin.
- One patient with acral melanoma, progressing on prior anti-PD-1 therapy, maintained disease control for 11 months on AU-007 and low-dose aldesleukin.

In addition to melanoma, anti-tumor activity was observed in patients with renal cell carcinoma, bladder cancer, head and neck squamous cell carcinoma, and non-small cell lung cancer who had previously failed checkpoint inhibitors.

AU-007 combined with low-dose, subcutaneous aldesleukin continues to exhibit a unique pharmacodynamic profile within the IL-2 class. A decrease in Treg cells is pivotal in determining efficacy, with greater reductions observed when a loading dose of aldesleukin is used rather than a bi-weekly schedule. This finding has prompted Aulos Bioscience to adopt the loading dose approach moving forward. Greater Treg cell reductions correlate with longer progression-free survival across both Phase 1 and Phase 2 trial segments.

The trial continues to enroll patients, focusing on melanoma and non-small cell lung cancer, with an additional Phase 2 cohort evaluating AU-007 combined with avelumab in non-small cell lung cancer. The company expects to present updated clinical data in the first half of 2025.

The detailed findings will be available to attendees of the SITC 2024 virtual meeting platform and presented during a poster session on November 8, 2024. Further information about the AU-007 clinical trial program can be found on ClinicalTrials.gov under identifier NCT05267626.