Codexis Doses First Patient in PKU Trial; Triggers $4 Million Milestone Payment

Rare Daily Staff

Codexis said it began dosing patients in a first-in-human dose-escalation trial with CDX-6114, its orally-administered enzyme therapeutic being developed for the management of phenylketonuria, or PKU, a metabolic disorder that can cause cognitive and behavioral disabilities.

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.

PKU results 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 and seizures. People 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. There are an estimated 50,000 people with PKU in the developed world.

CDX-6114 is an orally dosed, GI-stable therapeutic enzyme developed to compensate for the missing natural enzyme.

The early-stage 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 the study, which will support the future development of the drug candidate. The company expects to report topline results from the 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,” said John Nicols, president and CEO of Codexis. “CDX-6114 is the first biotherapeutic discovered using our CodeEvolver protein engineering platform to enter human studies. 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.”

July 9, 2018
John Nicols, president and CEO of Codexis