Codexis Doses First Subjects in Phase 1a Trial; Triggers Milestone

Codexis, Inc. recently announced it has dosed the first subjects in a first-in-human Phase 1a dose-escalation trial with CDX-6114, its orally administered enzyme therapeutic being developed for the management of phenylketonuria (PKU). The initiation of the trial triggers a $4-million milestone payment to Codexis from Nestlé Health Science under their strategic collaboration announced in October 2017.

This randomized, double-blind, placebo-controlled Phase 1a trial is intended to evaluate the safety and tolerability of CDX-6114 in up to 32 healthy volunteers, with up to four cohorts receiving a single dose of CDX-6114 at increasingly higher dose levels. Codexis also expects to generate valuable pharmacology data from this study, which will support the future development of the drug candidate. The company expects to report topline results from the Phase 1a trial in the fourth quarter of 2018.

“Initiation of this clinical trial is a major milestone in the development of CDX-6114 for the management of the orphan metabolic disorder PKU. CDX-6114 is the first biotherapeutic discovered using our CodeEvolver protein engineering platform to enter human studies,” said Codexis President and CEO John Nicols. “Commencement of this clinical trial further validates our biotherapeutics strategy as PKU is the lead program in our pipeline, which focuses generally on the discovery and development of novel enzyme drug candidates for the treatment of rare diseases.”

“PKU is caused by the deficiency or absence of the natural enzyme for the metabolism of phenylalanine, and can lead to intellectual disability, seizures, and cognitive and behavioral disabilities,” he added. “Physicians have been able to test for PKU for more than 50 years, yet treatment options have been limited primarily to dietary management. CDX-6114 is an orally dosed, GI-stable therapeutic enzyme developed to compensate for the missing natural enzyme.”

PKU is an inborn metabolic disorder resulting from a mutation in the gene for the enzyme that converts the essential amino acid phenylalanine, present in almost all dietary protein, into tyrosine. As a result of this deficiency, phenylalanine builds up to levels that are toxic in the brain, causing serious neurological symptoms including intellectual disability, seizures and cognitive and behavioral disabilities. To avoid phenylalanine toxicity and the most severe disease symptoms, individuals with PKU must follow a strict, life-long diet that is low in phenylalanine and supplement their diet with a synthetic phenylalanine-free formula to provide sufficient nutrients. Maintaining a strict, life-long diet is a challenge for individuals with PKU. There are an estimated 50,000 people with PKU in the developed world.

Codexis is a leading protein engineering company that applies its proprietary CodeEvolver technology to develop proteins for a variety of applications, including as biocatalysts for the commercial manufacture of pharmaceuticals, fine chemicals and industrial enzymes, and enzymes as biotherapeutics and for use in molecular diagnostics. Codexis’ proven technology enables improvements in protein performance, meeting customer needs for rapid, cost-effective and sustainable manufacturing in multiple commercial-scale implementations of biocatalytic processes. For more information, see