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1094 Favorable preclinical efficacy and safety profile of AVB-001 a novel IL-2 cell-based immunotherapy that eradicates ovarian cancer in mouse tumor models and supports first in human clinical development
  1. Guillaume Carmona1,
  2. Amanda Nash2,
  3. Ryan Newman1,
  4. Jake Schladenhauffen1,
  5. Maria Jarvis2,
  6. Samira Aghlara-Fotovat2,
  7. Sudip Mukherjee2,
  8. Andrea Hernandez2,
  9. Andrew Hecht2,
  10. Peter Rios3,
  11. Shirin Nouraein2,
  12. Rahul Sheth4,
  13. Weiyi Peng5,
  14. Jose Oberholzer3,
  15. Amir Jazaeri4 and
  16. Omid Veiseh2
  1. 1Avenge Bio, Natick, MA, USA
  2. 2Rice University, Houston, TX, USA
  3. 3Celltrans, Chicago, IL, USA
  4. 4University of Texas MD Anderson Cancer, Houston, TX, USA
  5. 5University of Houston, Houston, TX, USA


Background Aldesleukin, recombinant human IL-2 has been approved by the FDA for the treatment of melanoma and renal cancer. However, effective cytokine therapy is limited by its short half-life in circulation and the severe adverse effects associated with high systemic exposure when administered iv. To overcome these limitations, Avenge Bio has developed a localized cytokine delivery LOCOcyteTM platform comprised of polymer encapsulated epithelial cells that produce potent immune effector molecules for loco-regional delivery with temporal regulation. AVB-001 is engineered to produce native IL-2, for the treatment of ovarian cancer.

Methods Safety, PK and PD testing of AVB-001 using a combination of rodent and NHP animal models.

Results Tumor-adjacent local administration of AVB-001 demonstrated that mIL-2 local concentration (intraperitoneal space) was 100x higher than the systemic concentration (blood) demonstrating the ability of the LOCOcyteTM platform to deliver native cytokines in vivo and create a high locoregional concentration of cytokines with limited peripheral exposure. Additional studies in mice demonstrated dose-dependent levels of IL-2 in the IP cavity in mice. Treatment of solid tumors using a single administration of AVB-001 demonstrated complete responses as monotherapy and provided sustained eradication of peritoneal tumors in ID8 ovarian cancer mouse model. Our data in mice confirmed that AVB-001 leads to a local increase in activation and proliferation of cytotoxic T-cells within the IP space in comparison to sham mice. In addition, in MC38 colorectal cancer rechallenge model it was observed that a single local administration of AVB-001 leads to complete tumor eradication as a single agent and was accompanied by systemic antitumor immune responses. A single administration of AVB-001 in NHP led to therapeutic levels of IL-2 in the IP cavity and produced local and systemic T-cell biomarker profiles that predict efficacy. In safety assessments of AVB-001, no signs of cytokine storm and vascular leak syndrome and no evidence of adverse pathologic effects on local or systemic tissue were observed with administration of AVB-001 expressing up to 16.7 μg hIL-2/kg in mice and 12.8 μg hIL-2/kg in NHP giving a sufficient safety window for the planning of our first clinical study.

Conclusions It was demonstrated that the AVB-001 is dose adjustable, safe and efficacious in preclinical animal models. Avenge Bio aims to pursue a Phase 1 First in Human study of AVB-001 in ovarian cancer patients. The LOCOcyteTM platform enables delivery of a diverse set of cytokines alone or in combination which is presently being explored.

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