New Phase 1 Dose Escalation Data Show Well-Tolerated Safety Profile and Anti-Tumor Activity for Aulos Bioscience’s AU-007 at Society for Immunotherapy of Cancer (SITC) Annual Meeting

Preliminary evidence of anti-tumor activity observed in heavily pre-treated patients, including those whose tumors progressed through checkpoint inhibitors

Further development of AU-007 to continue in combination with low-dose aldesleukin, with Phase 2 expansion cohorts planned in melanoma, renal cell carcinoma and non-small cell lung cancer

LARKSPUR, Calif.–(BUSINESS WIRE)–Aulos Bioscience, an immuno-oncology company working to revolutionize cancer care through the development of best-in-class IL-2 therapeutics, today shared new data from its Phase 1/2 clinical trial of AU-007 at the 38th Society for Immunotherapy of Cancer (SITC) Annual Meeting in San Diego, California. The data, from Phase 1 dose escalation cohorts, continue to indicate that AU-007 is well tolerated as a monotherapy treatment or in a combination therapy regimen with low-dose, subcutaneous aldesleukin (recombinant human IL-2). The data also demonstrate early evidence of anti-tumor activity in patients with several solid tumor cancer types.

“These encouraging new data support AU-007’s distinct advantages in the IL-2 class,” said Aron Knickerbocker, Aulos Bioscience’s chief executive officer. “AU-007 continues to be well tolerated by patients, with no pulmonary or generalized edema, no vasculature leakage, and no dose-limiting toxicity to date. We are particularly encouraged by the initial signs of clinical efficacy that have been seen even during dose escalation, which show that heavily pre-treated patients are benefiting from a treatment regimen of AU-007 dosed in combination with low doses of aldesleukin. At this point, we are observing the greatest anti-tumor activity in patients with tumors known to be sensitive to immune-modulating drugs. Tumor shrinkage has been observed in patients with melanoma, bladder, kidney and lung cancers. These data support our decision to focus our Phase 2 expansion cohorts in melanoma, renal cell carcinoma and non-small cell lung cancer. We look forward to presenting clinical data from the Phase 2 expansion cohorts next year.”

Created by Biolojic Design, AU-007 is the first human IgG1 monoclonal antibody designed using artificial intelligence to be tested in a clinical trial. Unique among interleukin-2 (IL-2) therapeutics in development, the antibody’s computational design allows it to bind precisely to the portion of IL-2 that binds to CD25. Consequently, AU-007 prevents IL-2 from binding to high-affinity IL-2 receptors on regulatory T cells (Tregs), vasculature, pulmonary tissue and eosinophils, and redirects IL-2 to medium-affinity receptors on effector T cells (Teffs) and natural killer (NK) cells. This novel mechanism of action allows Teffs and NK cells to expand and kill tumor cells.

The Phase 1 data presented at SITC is based on 42 patients who received study treatment as of October 13, 2023. AU-007 alone or in combination with aldesleukin was generally well tolerated as administered in the following cohorts:

• Arm 1A as a monotherapy treatment up to 12 mg/kg
• Arm 1B with 4.5 mg/kg of AU-007 and escalating aldesleukin (up to 270K IU/kg) given only once on Day 1
• Arm 1C with 4.5 mg/kg of AU-007 in combination with aldesleukin (up to 135K IU/kg) also given every two weeks

All drug-related adverse events were Grade 1 or 2, with the exception of three transient Grade 3 or 4 lymphopenias that were not associated with adverse outcomes in patients receiving AU-007 and aldesleukin. Transient lymphopenia is a known effect of IL-2 treatment. No patients were discontinued for a drug-related adverse event and no dose-limiting toxicities were observed.

Additionally, preliminary evidence of anti-tumor activity was observed in heavily pre-treated patients, including in patients with melanoma, renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC) whose tumors had progressed through checkpoint inhibitors. Of note, CT scans of a patient with melanoma, who had progressed on anti-CTLA-4 and anti-PD-1 therapy without a response, show a 40% decrease in target tumor lesions, with shrinkage beginning at eight weeks and shrinking further at weeks 16 and 24. The patient continues on the study. Scans of a second patient with RCC, whose tumors had progressed through prior anti-PD-1 therapy, show 20% shrinkage in target tumor lesions beginning at eight weeks, and the patient continues on the study. Across the Phase 1 dose escalation cohorts, nine of 33 (27%) tumor evaluable patients had a best response of stable disease, and 16 patients continue treatment as of the data cutoff date.

As previously reported in October, new pharmacodynamic data from the Phase 1 dose escalation study show favorable trends toward decreasing Tregs with concordant increases in the CD8 Teff:Treg ratio, initial interferon-gamma increases, and absolute eosinophil decreases. These findings are consistent with the novel mechanism of action of AU-007 redirecting IL-2 away from the cells that express high-affinity IL-2 receptors that contain CD25, which include Tregs, vascular endothelial cells and eosinophils, and toward CD8 Teff cells and NK cells that can elicit anti-tumor immune effects.

The Phase 1/2 clinical trial of AU-007 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. The trial is currently enrolling patients at multiple locations in the United States and Australia. The company anticipates transitioning to the Phase 2 portion of the AU-007 study by late 2023 or early 2024, with Phase 2 dose expansion cohorts planned in melanoma, RCC and NSCLC.

The poster presentation is 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 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 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 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 Apple Tree Partners (ATP) and is led by pioneers in the field of artificial intelligence, antibody development and cancer immunotherapies. For more information, visit www.aulosbio.com, X (Twitter) at @AulosBioscience and LinkedIn.

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Media inquiries: Mike Beyer, Sam Brown Inc. / 312-961-2502 / [email protected]