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LARKSPUR, Calif.--( BUSINESS WIRE )--Aulos Bioscience, an immuno-oncology company working to revolutionize cancer care through development of potentially best-in-class IL-2 therapeutics, today shared positive results from its Phase 1/2 dose escalation and cohort expansion study of AU-007. The data will be presented in a poster session at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting in Houston, Texas. Preliminary Phase 2 data reveal that a combination of AU-007 and low-dose, subcutaneous aldesleukin is clinically active in melanoma, a finding consistent with Phase 1 data demonstrating clinical activity in a range of patients whose tumors had progressed through prior checkpoint inhibitors. Data from all 77 patients show durable reductions in immunosuppressive Treg cells – a result unprecedented in the IL-2 class – with a correlation between longer progression-free survival outcomes as Treg reduction deepens. “ We believe these data represent preliminary clinical proof of concept for our unique monoclonal antibody, AU-007, and we are confident in its emerging profile as a potential best-in-class therapeutic,” said Aron Knickerbocker, Aulos Bioscience’s president and chief executive officer . “ We look forward to presenting a fuller and more mature set of Phase 2 data for melanoma, renal cell carcinoma and non-small cell lung cancer in the first half of next year.” Key findings from preliminary results of the Phase 1/2 dose escalation and cohort expansion study of AU-007, with data available on 77 patients as of the data cutoff date of September 28, 2024, are as follows: A tolerable and manageable safety profile was observed 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 Grade 1 or 2 except for: Grade 3 anemia in one patient who entered the study with Grade 2 anemia, had rapid disease progression and received only two doses of the study drug. Grade 4 cytokine release syndrome (CRS) in one patient that resolved with steroids, IV fluids and brief vascular pressor support, and did not require tocilizumab. This patient was noted retrospectively to have subclinical elevated IL-6 (5x upper limit of normal) serum levels, likely due to an active case of gout at baseline. Transient Grade 3 elevated lipase in one patient that was not associated with clinical symptoms and resolved without intervention. Transient (3-7 days) Grade 3 or 4 lymphopenias in six patients. The lymphopenias 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. Strong evidence of anti-tumor activity was observed in heavily pre-treated patients, particularly in melanoma. Two patients with melanoma refractory to prior anti-CTLA-4 and anti-PD-1 therapy were treated with AU-007 every two weeks (Q2W) and one administration of low-dose, subcutaneous aldesleukin (recombinant human IL-2), and experienced deep and durable tumor shrinkages of 48% and 100% in target lesions. One patient in dose escalation with acral melanoma that progressed rapidly on prior anti-PD-1 therapy received AU-007 Q2W and one loading dose of subcutaneous aldesleukin. This patient remained on AU-007 therapy for 11 months with disease control. Anti-tumor activity was also observed in heavily pre-treated patients with renal cell carcinoma (RCC), bladder cancer, head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC) whose tumors had progressed through checkpoint inhibitors. AU-007 and low-dose, subcutaneous aldesleukin continues to demonstrate a unique pharmacodynamic (PD) profile in the IL-2 class. A decrease in Tregs appears to be a critical determinant of observed efficacy, with greater median decreases observed in patients receiving one loading dose of low-dose, subcutaneous aldesleukin compared to low-dose, subcutaneous aldesleukin administered Q2W. Based on the Treg reduction levels and other PD findings, the company has made the decision to use the loading dose rather than the Q2W schedule of subcutaneous aldesleukin going forward. Greater decreases in Tregs on treatment is associated with longer progression-free survival (PFS) across the Phase 1 and Phase 2 portions of the AU-007 trial. Patients with a Treg cell reduction greater than the median of 43% had longer PFS outcomes than those with a Treg cell reduction less than the median of 43%. The Phase 2 expansion cohorts evaluating AU-007 and low-dose, subcutaneous aldesleukin continue to enroll patients, with a focus on melanoma and non-small cell lung cancer. An additional Phase 2 cohort will evaluate AU-007 and low-dose, subcutaneous aldesleukin combined with avelumab (checkpoint inhibitor; anti-PD-L1) in NSCLC. The company anticipates presenting updated clinical data in the first half of 2025. The poster, “ A phase 1/2 dose escalation and cohort expansion study of AU-007, a human monoclonal antibody (mAb) that binds to IL-2 and inhibits CD25 binding, plus low-dose aldesleukin in advanced solid tumors,” (Abstract 685) is available to meeting registrants as an electronic poster on the SITC 2024 virtual meeting platform. It will be presented in a poster session on Friday, November 8, 2024, 9:00 a.m.-7:00 p.m. CST in Exhibit Halls AB. The poster presentation 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. 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 human antibody designed by leveraging artificial intelligence 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 .

AU-007 demonstrates continued distinction in IL-2 class, with unique pro Treg reduction and correlated longer PFS outcomes, coupled with increases in tumor-killing Teffs Phase 2 clinical efficacy and safety data to be presented before end of year LARKSPUR, Calif.--(BUSINESS WIRE)--Aulos Bioscience, an immuno-oncology company working to revolutionize cancer care through development of potentially best-in-class IL-2 therapeutics, today shared data and analyses used to determine dose selection for Phase 2 expansion cohorts in a Phase 1/2 clinical trial of its lead candidate, AU-007. The data and evaluations of pharmacodynamics, pharmacokinetics, safety and clinical efficacy were presented as a poster at the 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain. The results continue to affirm AU-007’s unique pro interleukin-2 (IL-2) therapeutics, showing regulatory T cell (Treg) reduction, and demonstrating that deeper drops in peripheral Treg counts were associated with longer progression-free survival (PFS) outcomes in patients from the Phase 1 and Phase 2 portions of the AU-007 trial, across a range of dose levels, tumor types and lines of therapy. Additionally, increases in interferon-gamma and effector T cells (Teffs) were observed with escalating subcutaneously administered aldesleukin (recombinant human IL-2) dose levels. “These data point to a correlation between deeper reductions in Tregs and better clinical outcomes, which differentiates AU-007 from all other IL-2 therapeutics in development,” said Aron Knickerbocker, Aulos Bioscience’s president and chief executive officer . “We’re also excited about AU-007’s ability to increase Teffs and natural killer cells. These findings, combined with a mild and tolerable safety profile, further validate our belief in AU-007’s potential as a best-in-class IL-2 therapeutic for solid tumor cancers. We look forward to presenting new Phase 2 clinical efficacy and safety data, particularly in melanoma and renal cell carcinoma, later this year.” Created by Biolojic Design, AU-007 is the first human IgG1 monoclonal antibody designed by leveraging artificial intelligence to enter a human clinical trial. The antibody’s novel mechanism of action is to bind precisely to IL-2 instead of IL-2 receptors. By binding only to the portion of IL-2 that binds to CD25, AU-007 prevents IL-2 from binding to high-affinity IL-2 receptors on Tregs, vasculature and eosinophils, and redirects IL-2 to medium-affinity receptors on Teffs and natural killer (NK) cells. This allows Teffs and NK cells to expand and kill tumor cells. Safety data presented at the EORTC-NCI-AACR Symposium demonstrate manageable toxicity for AU-007 and low-dose, subcutaneous aldesleukin, with no vascular leak syndrome or pulmonary edema at all dose levels evaluated. Additionally, the AU-007 pharmacokinetic data show characteristics typical of an IgG1-LALA monoclonal antibody, with no evidence of neutralizing anti-drug antibody (ADA) activity and an approximate half-life of more than 15 days. No clear trends were observed in safety or efficacy data to determine if a single loading dose or multiple loading doses of aldesleukin would lead to better outcomes, and clinical investigation is ongoing in the Phase 2 dose expansion cohorts to determine the optimal dosing schedule. Based on these results, researchers will evaluate dosing regimens of 9 mg/kg for AU-007 every two weeks (Q2W) and 135K IU/kg subcutaneous aldesleukin administered either on a single loading dose schedule or a Q2W multiple dose schedule in the Phase 2 expansion cohorts. The Phase 2 expansion portion of the trial is currently ongoing in renal cell carcinoma (RCC), melanoma and non-small cell lung cancer (NSCLC) evaluating these two dosing regimens. The poster, “PB452: Determination of the phase 2 dose of AU-007, an AI-designed human monoclonal antibody that redirects IL-2 to T effector cells,” (Abstract 464) is available to meeting registrants as an electronic poster on the EORTC-NCI-AACR Symposium’s online platform . It will be presented live in the poster session “New therapies in immuno oncology” on Friday, October 25, 2024, 9:00 a.m.-3:00 p.m. CEST in the Exhibition Hall. The poster presentation 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 . For patients and health professionals in Australia, please visit . 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. 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 human antibody designed by leveraging artificial intelligence 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 , X ( @AulosBioscience ) and LinkedIn . Contacts Contact: info@aulosbio.com Media inquiries: Mike Beyer, Sam Brown Inc. / 312-961-2502 / mikebeyer@sambrown.com