Benzinga | Nov 22, 2021 08:23AM EST

Codexis Presents Pre-Clinical Data Highlighting Programs In Homocystinuria And Maple Syrup Urine Disease At ICIEM 2021

Codexis, Inc. (NASDAQ:CDXS), a leading enzyme engineering company enabling the promise of synthetic biology, today announced that two of the Company's wholly owned biotherapeutic programs, CDX-6512 for the treatment of homocystinuria (HCU) and enzymes for the treatment of maple syrup urine disease (MSUD), were the subject of oral presentations at the 14th International Congress of Inborn Errors of Metabolism (ICIEM) 2021 held in Sydney, Australia from November 21-24, 2021. The enzyme candidates are gastrointestinal (GI)-stable enzymes specifically engineered to be highly resistant to both the acidic conditions of the stomach and to proteases of the upper intestines, to effectively degrade methionine and leucine that is liberated from protein digestion. Elevated levels of these amino acids and their metabolites can lead to the variety of clinical manifestations of HCU and MSUD respectively.



"Our engineered enzymes have demonstrated the potential to be first-in-class oral enzyme therapeutics for patients with homocystinuria and maple syrup urine disease, who currently have limited therapeutic options and must adhere to a life-long, protein restricted diet," said John Nicols, Codexis President and CEO. "As we have demonstrated with our Phase 1 Phenylketonuria and Exocrine Pancreatic Insufficiency programs, and now through our HCU and MSUD programs, food constituent degrading enzymes designed to be stable to the conditions in the GI-tract hold exciting potential as treatments for inborn errors of metabolism and gastrointestinal conditions. We look forward to driving the clinical development of these programs and continuing to push the boundaries of what our enzymes can do to address patients' unmet needs."

Kristen Skvorak, PhD, Translational Scientist and Patient Ambassador at Codexis, presented 'Discovery of CDX-6512, a gastrointestinal-stable methionine-gamma-lyase as a potential orally-administered enzyme therapy for homocystinuria,' which demonstrated up to a 45% suppression in serum total homocysteine (p<0.001), at 4 hours post protein challenge in HCU mice treated with a single dose of CDX-6512, compared to vehicle. Similarly, a statistically significant, dose-dependent reduction in plasma methionine was observed following administration of CDX-6512 in healthy non-human primates receiving a peptone meal.

Dr. Skvorak also presented 'Discovery of a gastrointestinal-stable bacterial leucine decarboxylase as a potential orally-administered enzyme therapy for maple syrup urine disease,' which demonstrated an up to 45% suppression in blood leucine levels, measured as incremental area under the curve (iAUC), in whey-fed iMSUD mice with a single dose of leucine decarboxylase compared to vehicle (p<0.01). A dose-dependent reduction in the plasma leucine iAUC was also observed in healthy non-human primates receiving the engineered enzyme. This pivotal preclinical work has led to Codexis' elevation of our lead candidate, CDX-6210, for MSUD.