Preliminary results show durable anti-tumor activity in multiple solid tumor types among heavily pre-treated patients, including patients whose tumors have progressed through checkpoint inhibitors

The results confirm the ability of AU-007, a human IgG1 monoclonal antibody designed using artificial intelligence, to harness the power of interleukin-2 (IL-2) to reduce solid tumors, and support ongoing and planned Phase 2 expansion cohorts in combination with low-dose aldesleukin in melanoma, renal cell carcinoma and non-small cell lung cancer

Aulos Bioscience, an immuno-oncology company working to revolutionize cancer care through the development of best-in-class IL-2 therapeutics, today shared interim results from its Phase 1/2 trial of AU-007, the first human monoclonal antibody designed using artificial intelligence to be tested in a clinical trial. The data will be presented in a poster session at the American Society of Clinical Oncology (ASCO) 2024 Annual Meeting in Chicago, Illinois.

“The level and scope of anti-tumor activity we’re seeing across solid tumor types are remarkable so early in clinical development, particularly the partial responses and metabolic complete response. The durability of the tumor reductions seen in several patients suggests the formation of immune memory of the cancerous cells. These results validate our long-held belief that AU-007 could widen the therapeutic window of IL-2 by redirecting IL-2 toward CD8+ T and natural killer cells that can kill tumor cells and away from immunosuppressive regulatory T cells and the vasculature,” said Aron Knickerbocker, Aulos Bioscience’s chief executive officer. “While other developmental IL-2 therapies focus on changing IL-2 itself, AU-007 is a human antibody that is a well-established therapeutic modality. This provides sources of advantage and differentiation. As we treat patients in earlier lines of therapy, we are confident AU-007 is emerging as a potential best-in-class regimen.”

Key findings from the updated results of the AU-007 Phase 1/ 2 study, with data available on 59 patients as of the data cutoff date of April 9, 2024, are as follows.

Well-tolerated safety profile:

• No evidence of vascular leak syndrome or pulmonary edema reported at all dose levels evaluated.
• All drug-related adverse events were Grade 1 or 2 except for:
  • One patient with Grade 4 CRS that resolved quickly with steroids. This patient was noted retrospectively to have subclinical elevated IL-6 serum levels at baseline.
  • Five patients experienced transient (3-7 days) Grade 3 or 4 lymphopenias that were not associated with adverse outcomes. Transient lymphopenia is a known effect of IL-2 treatment as lymphocytes traffic out of blood and into tissue.
  • One patient with Grade 3 anemia who entered the study with Grade 2 anemia.

Profound and durable tumor shrinkage observed in multiple tumor types:

• A patient with large-volume metastatic melanoma whose tumors had progressed through anti-PD-1 and anti-CTLA-4 checkpoint inhibitors was treated with AU-007 (9 mg/kg) and one 135K IU/kg low dose of IL-2 and experienced 76% shrinkage (unconfirmed partial response) in target lesions at 8 weeks.
• Another patient with metastatic melanoma whose tumors had also progressed through anti-PD-1 and anti-CTLA-4 checkpoint inhibitors was treated with AU-007 (4.5 mg/kg) and one 15K IU/kg low dose of IL-2 and achieved 48% shrinkage in target lesions.
• A patient with head and neck cancer whose tumors had progressed through an anti-PD-1 checkpoint inhibitor was treated with AU-007 (4.5 mg/kg) and 45K IU/kg IL-2 dose every two weeks and experienced 32% shrinkage (confirmed partial response) in a cervical bone metastasis, as well as reduced pain and improved motor function in an affected hand.
• A patient with bladder cancer whose tumors had progressed through an anti-PD-L1 checkpoint inhibitor was treated with AU-007 (4.5 mg/kg) and one 45K IU/kg IL-2 dose and achieved a durable metabolic complete response.
• Additional tumor shrinkages were observed in patients with widespread large-volume disease in renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC) and MSI-stable (MSS) colorectal cancer.

Unique pharmacodynamic (PD) and pharmacokinetic (PK) profiles in the IL-2 class:

• Decreases in peripheral regulatory T cells (Tregs) and increases in CD8/Treg ratios demonstrate AU-007’s ability to redirect IL-2 and prevent the negative feedback loop to Tregs. AU-007 and low-dose aldesleukin also substantially increases peripheral natural killer (NK) cells.
• AU-007 PK demonstrates dose-proportionality over the dose range tested and no signs of neutralizing anti-drug antibodies (ADAs) activity, and a half life of 15+ days.

The Phase 2 expansion cohorts of the AU-007 study are continuing to enroll patients with a focus on melanoma and RCC. The company anticipates presenting updated clinical data in the second half of 2024. Additional Phase 2 expansion cohorts are planned to evaluate AU-007 and aldesleukin in second-line PD-L1+ NSCLC, with and without the PD-L1 antibody avelumab.

The poster, “Updated results of a phase 1/2 study of AU-007, a monoclonal antibody (mAb) that binds to IL-2 and inhibits CD25 binding, in patients with advanced solid tumors,” (Abstract 2527) is available to meeting registrants as an electronic poster on the ASCO online meeting platform and will be presented live in the poster session “Developmental Therapeutics—Immunotherapy” on Saturday, June 1, 2024, 9:00 a.m. to 12:00 p.m. CDT.

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 using 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 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 (@AulosBioscience) and LinkedIn.

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