INO-4995, is an ion channel regulator that inhibits sodium absorption and enhances chloride and fluid secretion in cystic fibrosis (CF) pulmonary epithelial cells. The underlying defect in CF is a genetic mutation that causes malfunction or absence of the cystic fibrosis transmembrane regulator (CFTR) resulting in the excretion of too little chloride and the absorption of too much sodium. This causes too little water to move out of the cell and leads to the thick and sticky mucus that characterizes the disease. INO-4995 is a small molecule prodrug (MW about 1370) that is analogue of an inositol signaling molecule. INO-4995 is rapidly taken up by the appropriate cell type where it is metabolized to the active drug with a long duration of action.
INO-4995 is one a handful of drugs in development that attacks the underlying defect in CF but is unique for the following reasons.
- Circumvents the genetic defect by correcting both sodium and chloride channels (ion channel modulator)
- Novel NCE that is an analog of a molecule normally “seen and used” by the cell
- Comparable or better dosing than current development candidates
- Selective for CF epithelial cells with a therapeutic index of 100-1000x over normal cells
- Long duration of action (greater than 24 hours after single dose)
- Good safety profile to date in animal models
- Can be used in combination with existing treatments
The forecast for a therapeutic drug for CF could exceed $500M by benchmarking other niche markets of genetic disorders using prevalence, penetration and price. There are 75,000 people worldwide afflicted with CF. Current palliative therapies cost $15-16K/year per patient. INO-4995 is unique among its competitors as it affects both sodium and chloride ion channel regulation and re-regulates water balance, has a long duration of action and is effective at low doses in a convenient inhaler formulation. As a result INO-4995 would be expected to have considerable therapeutic impact on the disease.
Status:
INO-4995 has completed a substantial amount of preclinical testing:
- A manufacturing route has been developed and process development is largely complete.
- A pulmonary formulation and components for a metered dose inhaler have been identified.
- A preliminary clinical trial strategy ex-US through a phase II trial in CF patients has been developed. The active drug of INO-4995 has received Orphan Drug Status. It is likely that INO-4995 will have follow-on utility in sinusitis and chronic bronchitis or COPD.
Approximately $4.5M has been spent on this program to date with NIH grant monies, angel investments and $1.5M derived from an award from the Cystic Fibrosis Foundation. These monies were used to discover a lead drug candidate, complete initial pharmacology studies and develop a manufacturing process and formulation approaches.
