Pulmatrix Demonstrates iSPERSE Capabilities for Inhaled Dry Powder Delivery of Antibiotics and Antibodies

LEXINGTON, Mass.--Pulmatrix, a biotechnology company developing breakthrough therapies for respiratory diseases, today announced that its iSPERSE™ inhaled drug delivery platform demonstrated the capability to formulate a wide range of drugs for inhaled administration, including antibiotics, antibodies and other macromolecules. These preclinical data highlight the ability of iSPERSE formulations to efficiently deliver stable, consistent and therapeutically-relevant drug doses across a broad range of flow rates, offering the potential of improved drug efficacy and safety for patients having both normal and lower or impaired lung function. These results were presented in posters entitled "Formulation Characterization of a Novel Levofloxacin Pulmonary Dry Powder Drug Delivery Technology" and "Development of an iSPERSE™ Based Platform for the Delivery of Macromolecules via Dry Powder Formulations" at Respiratory Drug Delivery 2012, which is being held May 13-17, 2012, in Phoenix, AZ.

"These data show the significant potential of iSPERSE for pulmonary delivery across a diverse range of therapies, at higher drug loads with flow rate independence and enhanced delivery efficiency," said Robert Clarke, PhD, Chief Scientific Officer and Vice President of Research and Development at Pulmatrix. "This combination of traits differentiates iSPERSE from existing approaches by enabling the possibility of therapeutic dose delivery in lower total inhaled powder masses."

In two series of in vitro and preclinical studies, two iSPERSE formulations were evaluated: one containing levofloxacin, a potent fluoroquinolone antibiotic, and the other containing immunoglobulin G ((IgG), from Bovine serum), which was selected as a model antibody macromolecule. These studies highlight the potential of iSPERSE therapies to deliver significant benefits to patients. For example, in patients with cystic fibrosis (CF) there is a need for alternative pulmonary therapies for lung infections due to the shortcomings of the two FDA approved nebulized antibiotics, such as decreased efficacy over long-term use, drug intolerance and new emerging pathogens. Additionally, nebulized therapies have documented disadvantages, including high cost and inconvenient, time-consuming administration. The IgG studies support the utility of iSPERSE for respiratory drug delivery of antibodies to treat diseases of the lung, such as asthma, by increasing local macromolecule concentration, reducing systemic drug exposure and providing a non-invasive delivery means.

Highlights from the data presented at Respiratory Drug Delivery 2012 include:

iSPERSE formulations were created containing levofloxacin that yielded powders that were composed of small, relatively dense and dispersible particles, potentially allowing for the delivery of large masses across a range of inspiratory flow rates via a simple, passive dry powder inhaler leading to faster and more convenient administration.
Optimized iSPERSE levofloxacin showed flow rate independent performance in terms of dose and particle size distribution which could enable iSPERSE applicability across a broad range of patient populations, expanding applications beyond patients with normal lung function to also include those having lower or impaired lung function, including pediatric, elderly and those with compromised lung function. Optimized iSPERSE levofloxacin behaved flow rate independently between flow rates of 20 and 60 LPM, maintaining consistent dose delivery when tested via actuation from a capsule-based passive dry powder inhaler. The capsule emitted powder mass (CEPM) of optimized iSPERSE levofloxacin remained greater than 97% and thus primarily unchanged as a function of flow rate between 20 and 60 LPM and was still greater than 87% at 15 LPM, while the volume mean diameter (VMD) increased only slightly at lower flow rates.
iSPERSE formulations were created containing IgG, using a commercially available spray dryer, which were stable physically and chemically, and achieved iSPERSE powder properties of small size and relatively high density. The dense nature of these particles facilitates the delivery of a high payload to the lungs with a simple inhaler, which is highly desirable for macromolecules, and establishes the potential of iSPERSE as an alternative delivery route for macromolecules for respiratory disease. In contrast, spray drying of IgG alone did not yield stable powders suitable for inhaled dry powder delivery.
The lead IgG iSPERSE formulation, which had an IgG loading of greater than 25% and showed good stability, demonstrated consistent emitted mass from capsule and particle size across a wide range of therapeutically-relevant flow rates (15-60 LPM). This consistency of dose delivery across a broad range of flow rates offers the potential to use a simple, passive inhaler to achieve improved drug efficacy and safety for patients having both normal and lower or impaired lung function.
Pulmatrix is now advancing a number of proprietary iSPERSE drug formulation candidates including small molecules, combinations and biologics in a variety of therapeutic areas, including chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), asthma, idiopathic pulmonary fibrosis (IPF) and bronchiectasis, as well as pursuing partnerships for iSPERSE.

About iSPERSE

iSPERSE is a novel dry powder delivery platform developed by Pulmatrix for use in the formulation of drugs for administration via inhalation for local or systemic applications. iSPERSE uses a delivery matrix containing proprietary cationic salt formulations to create a robust and flexible platform that can accommodate low or high drug loads in highly dispersible particles, yielding drug delivery capabilities not feasible with conventional dry powder technologies that rely on the use of lactose blending or low-density particles. The properties of iSPERSE have meaningful therapeutic and patient benefits, including the potential for single formulations with multiple drugs, effective inhaled drug delivery to patients with normal or impaired lung function, and the use of simple and convenient inhaler devices. iSPERSE offers the potential of a strong safety profile, as, in addition to drug and drug molecules, iSPERSE dry powders comprise exclusively generally regarded as safe (GRAS) salts and small quantities of additional, safe excipients if needed. iSPERSE powders are made via a straightforward, proven one-step spray-drying process capable of high and consistent yields.

About Pulmatrix

Pulmatrix, Inc. is a clinical stage biotechnology company developing two novel pulmonary drug platforms, iCALM™ and iSPERSE™, for the prevention, treatment and control of respiratory diseases. iCALM (inhaled cationic airway lining modulators) are first-of-a-kind inhaled therapies to prevent and treat acute exacerbations and improve lung function in patients with chronic respiratory diseases, such as COPD, asthma, cystic fibrosis, idiopathic pulmonary fibrosis (IPF) and bronchiectasis, while also treating and preventing respiratory infections including influenza, ventilator acquired pneumonia (VAP) and respiratory syncytial virus (RSV). iSPERSE (inhaled small particles easily respirable and emittable) is a proprietary dry powder pulmonary drug delivery platform, comprised of small, dense particles with unique capabilities to support efficient, reproducible lung delivery of a broad spectrum of drug classes from small molecule to macromolecule including double- and triple-combination therapies. Pulmatrix's lead iCALM clinical candidate, PUR118, is in two on-going Phase 1b studies in patients with COPD. The Company is pursuing both proprietary and partnered applications for iCALM and iSPERSE. For additional information about Pulmatrix, please visit http://www.pulmatrix.com.

iCALM™ and iSPERSE™ are trademarks of Pulmatrix, Inc.

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