ASNase-PEG is an early development stage biotherapeutic project. Polaris is developing a PEGylated version of L-asparaginase (ASNase) for use as an anticancer agent with the goal of reducing systemic toxicity and increasing activity against solid tumors.
Asparagine is an amino acid that is crucial for tumor cell metabolism and growth. Normal cells are able to synthesize asparagine from metabolic precursors while some cancers are deficient in one of the enzymes required for the synthesis of this amino acid and thus become dependent upon exogenous asparagine for survival. Therefore depleting asparagine from the blood can control tumor growth without damage to normal cells. Depletion of asparagine can be accomplished with ASNase, an enzyme that catalyzes the deamidation of L-asparagine to L-aspartic acid and ammonia.
Elspar, Erwinase, and Oncaspar are marketed ASNase-based drugs that have been approved for the treatment of acute lymphoblastic leukemia (ALL). Clinical toxicity has been observed with these drugs and it is suspected that this may partially be attributed to concomitant glutaminase activity of this enzyme. However, it has also been hypothesized that the glutaminase activity may be necessary for the clinical efficacy of these drugs.