12:00 AM
Jul 15, 2013
 |  BioCentury  |  Strategy

Triple advantage in COPD

Pearl gets AstraZeneca into LAMA/LABA race, plus COPD triple therapy

AstraZeneca plc's acquisition of Pearl Therapeutics Inc. gives the pharma an entry point into the LAMA/LABA race and a platform to build out other combination products. While the Pearl programs may be a couple of years behind competitors, AZ is betting that better stability and dosing consistency could result in products that are best in class.

On July 1, AstraZeneca completed its acquisition of Pearl for $560 million up front. The biotech's investors will be eligible for up to $450 million in development and regulatory milestones, plus up to $140 million in sales milestones. Investors had put in $167.5 million.

The pharma said the deal was driven by two primary assets. The first is PT003, a combination of glycopyrrolate and formoterol fumarate that is delivered via a hydrofluoroalkane metered-dose inhaler (MDI). Glycopyrrolate is a long-acting muscarinic antagonist (LAMA) and formoterol fumarate is a long-acting adrenergic receptor beta 2 agonist (LABA).

The second asset is Pearl's porous particle formulation technology. It is designed to increase product stability and dosing consistency - allowing for lower doses than other formulation technologies - as well as reduce the potential for drug-drug interactions in combination products.

The technology also may provide improved aerodynamics and a simplified manufacturing process.

Course correction

According to Pearl co-founder and CSO Sarvajna Dwivedi, the company had to rethink its formulation approach early on.

Founded in 2006, Pearl in-licensed the porous particle formulation technology from Nektar Therapeutics in 2007. But according to Dwivedi, Pearl soon found that Nektar's approach of trying to put drug inside the porous particles didn't work, as the drug crystals were either physically or chemically unstable.

Pearl spent the next year developing a co-suspension formulation for the porous particles. Rather than putting drug inside the particles, the company makes the phospholipid and calcium chloride microparticles free of drug, then puts porous particles into suspension and adds the crystallized form of drug. The porous particles provide a large surface area with which the drug crystals associate via van der Waals interactions.

"We simply suspended the particles in liquid, and we surprisingly found the drug crystals actually floated with these engineered light particles in the liquid," Dwivedi said. "You can call it a loose physical binding, but it is practically irreversible during production, during usage, during storage over time and when patients are delivering the drug."

The drug is released when the particle phospholipids interact with other phospholipids in the airway epithelium.

This porous particle-drug crystal interaction provides multiple benefits.

First, the drug crystals assume the characteristics of the porous particles, which are highly stable and uniformly dispersed in suspension in the propellant of a pressurized metered-dose...

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