We designed a novel stabilized humanized asparaginase with clinically relevant pharmacokinetic properties that has significantly reduced toxicity, but similar anti-leukemic properties compared to the asparaginase formulations that are nowadays used in the clinic to treat pediatric and adult acute lymphoblastic leukemia (manuscript in preparation). This project aims to validate the safety and efficacy of our newly designed asparaginase in a dog model, a necessary step to enter clinical trials.

The primary objectives are:

- To demonstrate the low toxicity profile of our enzyme, head-to-head compared to the currently used first-line product Oncaspar. More specifically, we will prove the low immunogenicity of our product, and the reduced non-immunological toxicity including pancreatitis, thrombosis, hypertriglyceridemia, and liver dysfunction.

- To confirm the efficacy of our enzyme in the treatment of lymphoma and acute lymphoblastic leukemia.

The secondary objectives of this study include:

- To document pharmacokinetics and pharmacodynamics in a dog model. This will allow to better define initial treatment schedules and dose levels for the Phase I clinical study following the experiments proposed in this project.

- To document and optimize the production process of generating this enzyme in sufficient quantities and at high-quality for in vivo use in large clinical studies.