MCPs for COPD and asthma

OXFORD, U.K.—Prosonix has signed a collaborative researchagreement with Imperial College London to accelerate the development of itsengineered multi-component particles (MCPs) as respiratory medicines, per anannouncement made by the partners last month.

The collaboration will result in Prosonix working closelywith Dr. Omar Usmani, an expert in respiratory diseases and inhaled drugdelivery at the college's National Heart and Lung Institute (NHLI). The workaims to develop a deeper understanding of how MCPs can be translated into newrespiratory medicines with significant clinical benefits compared to existingcombination formulations in chronic obstructive pulmonary disease (COPD) andasthma. A "rapid synergistic potentiation" has previously been reported for thesimultaneous administration of corticosteroids and beta-2 agonists.

Results from the collaboration are intended to acceleratethe development of Prosonix's PSX2000 MCP Series of novel combinationmedicines, with the aim of advancing one or more MCP candidates into formalpreclinical/proof-of-concept studies in 2013. The collaboration willinvestigate MCPs in in-vitro and in-vivo models of the lung. It will alsocompare key performance criteria, including synergistic effects in reducinginflammation and improving bronchodilation resulting from co-localization ofactive drug components with other combination formulations including marketedcombination products.

Prosonix's drug-particle engineering approach and expertisehas enabled the development of MCPs that combine two active respiratory drugmolecules consistently in a pre-determined ratio in each particle in theformulation, without the need for additional excipients.

"We use ultrasound to control nucleation, which is the firststep in crystallization," says Prosonix CEO David Hipkiss.

Traditionally, formulators were taught to make bigcrystals—on the order of 50 to 200 micron—then crush them. This provideseffective size control, but introduces entropy, Hipkiss notes.

"We use ultrasound to get controlled nucleation and crystalgrowth from solution without any further application of energy. As a result, weare able to put a fixed-dose combination —with no fancy excipient—into apressurized metered dose inhaler (pMDI) formulation that is uniform within eachdose, and from dose to dose using simple, multidose delivery devices," he says.

Excipient-free, drug-only MCPs engineered by Prosonix thatwill be evaluated in the project include inhaled corticosteroids withlong-acting beta-agonist (LABA) and LABAs with long-acting muscarinicantagonists, Hipkiss says.

"Our strong links with the world's leading academic researchgroups focused on respiratory medicine and inhaled drug delivery such as Dr.Omar Usmani's group at Imperial College's NHLI and Prof. Rob Price's team atthe University of Bath, alongside our own development team, will ensure thatProsonix retains a preeminent position in the field. We believe that ourparticle engineering technology is potentially transformational in enabling thedevelopment of novel inhaled combination therapies that deliver significantclinical benefits. Following the recent close of our $20.6 million financing,we believe we are very well placed now to drive the development of our uniqueMCPs into the clinic," he adds.

Usmani adds, "Co-localization of active components inrespiratory drug combinations in the lung may offer the potential for anenhanced clinical effect and therapeutic efficacy that is currently not fullyachieved with current combinations. We are extremely interested in Prosonix'sparticle engineering approach and MCPs to determine whether they candemonstrate clinical synergy and thus provide a novel and effective means ofdelivering respiratory combinations."

Prosonix is not a "vapor-ware" company, Hipkiss points out.Changes in its business model over the past 18 months have moved it from the"service world" to a processing mode in the respiratory space, he notes, withprocesses in place and at work. Its current development programs includePSX1001, a drug-only directly substitutable generic version of fluticasonepropionate, a potent inhaled corticosteroid monotherapy for asthma in metereddose inhaler (pMDI); PSX1002, a drug-only version of glycopyrrolate, along-acting muscarinic antagonist for chronic obstructive pulmonary disease inpMDI; and PSX2000 MCP Series, a potentially revolutionary approach tocombination therapy for respiratory diseases using MCPs.