Oral Enzyme Therapy at Codexis

Oral Enzyme Therapy

Engineered enzymes for oral enzyme therapies

We use our propietary CodeEvolver® technology platform to engineer enzymes that are highly stable to the harsh conditions of the gastrointestinal (GI) tract, including the low pH of the stomach and the protease-rich upper intestines. Our engineered enzymes are active within the GI tract, where they degrade substrates that originate from diet or enteric recycling. Highly stable and active recombinant oral enzyme replacement therapies potentially can provide many benefits to patients, including reducing dosing burden as compared to animal-derived products, easing dietary restrictions, and improving quality of life.

Oral enzyme therapy programs

Our lead oral enzyme replacement therapy candidates include our partnered enzymes CDX-7108 for the potential treatment of exocrine pancreatic insufficiency and CDX-6114 for the potential treatment of phenylketonuria. Both are being tested in Phase 1 clinical trials.

Our wholly owned, engineered, and orally administered replacement enzymes include potential treatments for two inborn errors of metabolism - homocystinuria and maple syrup urine disease - plus an oral enzyme candidate for potential treatment of celiac disease.

Exocrine pancreatic insufficiency (EPI)

EPI is a disorder affecting ~190,000 patients in the US arising from a range of primary conditions including chronic pancreatitis, cystic fibrosis, and pancreatic cancer, impacting the ability of the pancreas to produce digestive enzymes. Existing pancreatic enzyme replacement therapies (PERTs) are derived from porcine pancreas and are limited by activity of the lipase enzyme, and patients may need 5 or more pills per meal. The high pill burden leads to poor compliance, which exacerbates the disease morbidity. As a potential alternative to porcine-derived PERT, we have engineered a recombinant lipase enzyme, CDX-7108, with very high activity and stability throughout the gastrointestinal tract. In a minipig model of EPI, CDX-7108 showed similar efficacy to porcine PERT at a >10-fold lower dose by mass. We are developing CDX-7108 in collaboration with Nestlé Health Science with the goal of offering patients a highly efficacious oral treatment option with a less burdensome dosing schedule.

Phenylketonuria (PKU)

PKU is an inborn error of metabolism that affects around 50,000 patients in the developed world. PKU patients are deficient in the enzyme phenylalanine hydroxylase (PAH), which is responsible for metabolizing the amino acid phenylalanine. If not managed, phenylalanine accumulates to toxic levels in the brain, causing serious neurological problems including intellectual disability, seizures, and cognitive and behavioral problems. A strict, life-long diet restricting protein intake is the primary treatment option for PKU patients to avoid buildup of toxic levels of phenylalanine. CDX-6114 is a recombinant enzyme that we engineered to be taken orally with meals to degrade phenylalanine in the small intestines to potentially help PKU patients maintain healthy phenylalanine levels. Our partner, Nestlé Health Science, is testing CDX-6114 in clinical trials in PKU patients.

Oral enzyme clinical development pipeline

Program Indication IND-enabling studies Phase 1 Phase 2 Phase 3 Partner
CDX-7108 Exocrine pancreatic insufficiency
IND-enabling studies Phase complete
Phase 1 Phase in progress
Phase 2 Phase not started
Phase 3 Phase not started
CDX-6114 Phenylketonuria
IND-enabling studies Phase in progress
Phase 1 Phase not started
Phase 2 Phase not started
Phase 3 Phase not started

1 Co-development by Nestlé Health Science and Codexis

2 Nestlé Health Science licensed CDX-6114 for world-wide development

There are many steps to a healthier future.

Join us on our journey.