Article Text

Download PDFPDF

775 Initial results from dose escalation of a phase 1/2 first-in-human, open label study of AU-007, a monoclonal antibody that binds to IL-2 and prevents its binding to CD25, in patients with solid tumors
  1. James Vasselli1,
  2. Paul de Souza2,
  3. Sophia Frentzas3,
  4. Andrew Weickhardt4,
  5. Timothy Wyant1,
  6. Jenny Tang1,
  7. Lori Richards5,
  8. Aron Knickerbocker1,
  9. Inbar Amit6 and
  10. Yanay Ofran6
  1. 1Aulos Bioscience, San Francisco, CA, USA
  2. 2Southside Cancer Care, Campbelltown, Australia
  3. 3Monash Cancer Center, Melbourne, Australia
  4. 4Austin Health, Heidelberg, VT, Australia
  5. 5Aulos Biosciences, Oakland, CA, USA
  6. 6Biolojic Design, Rehovot, Israel


Background AU-007 is a computationally designed monoclonal antibody that binds IL-2 on its CD25 binding epitope. AU-007 bound IL-2 (A/IL-2) cannot bind to trimeric (CD25, CD122, CD132) IL-2 receptors (IL-2R) on Tregs and vascular endothelium, but leaving IL-2’s binding to dimeric IL-2Rs (CD122, CD132) on T effector and NK cells unhindered. Therefore AU-007 redirects endogenous or exogenous IL-2 (aldesleukin) towards T effector and NK cell activation, while diminishing Treg activation and vascular leak. Unique in the IL-2 field, AU-007 can bind and redirect endogenous IL-2 generated from A/IL-2 driven T cell expansion in vivo, converting a Treg-mediated autoinhibitory loop into an immune-stimulating loop. Additionally, A/IL-2 is expected to substantially prolong the 90-minute T1/2 of IL-2, potentially allowing the use of endogenous IL-2 (as A/IL-2) alone to initiate an anti-tumor response. In non-human primates, AU-007 bound IL-2 with a similar affinity to human IL-2 and increased IL-2 serum concentrations in a dose- dependent manner while demonstrating an excellent safety profile.

Methods Phase 1 of this Phase 1/2 study (NCT05267626) consists of 3 dose escalation arms. Each Arm begins with one 1+2 escalation cohort followed by 3+3 escalation cohorts. In Arm 1A, escalating doses of monotherapy AU-007 (Q2W) are evaluated in sequential cohorts. In Arm 1B, AU-007 (Q2W) is evaluated in combination with a single low-dose of aldesleukin with the first AU-007 dose. The AU-007 dose will be fixed with escalating aldesleukin doses in sequential cohorts. In Arm 1C, AU-007 is evaluated in combination with escalating low-doses of aldesleukin, both given Q2W. The AU-007 and aldesleukin dose and schedule for Phase 2 cohort expansion in selected solid tumor types will be based on safety, objective signs of efficacy and PD parameters including increases of IL-2 concentration (as A/IL-2), total lymphocytes, CD8+ T cells, IFN-γ, and soluble CD25.

Results As of July 2022, two patients enrolled into dose escalation Arm 1A, 1 patient on 0.5 mg/kg (First In Human starting dose) and one patient into the second cohort (1.5 mg/kg). AU-007 was well tolerated with no drug related adverse events in the ongoing dose escalation.

Conclusions At this early data cut, AU-007 monotherapy given 0.5 mg/kg Q2W or 1.5 mg/kg Q2W was safe and well tolerated. Data from additional patients are expected to be presented in the poster.

Trial Registration NCT05267626

Ethics Approval HREC: Monash Health Human Research Ethics Committee CT-2021-CTN-03938-1

All of the participants in this study gave informed consent before taking part in the study.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.