Morristown, New Jersey-based Capsugel, a provider of empty two-piece hard capsules and an innovator of drug delivery systems, and Pulmatrix, of Lexington, Massachusetts — a clinical-stage biopharmaceutical company and developer of inhaled therapies for treating pulmonary fibrosis and other pulmonary diseases with its patented iSPERSE technology, are collaborating to develop novel therapeutics to treat serious pulmonary diseases.
Terms of the agreement grant Capsugel exclusive rights to manufacture both clinical trial quantity and commercial volume batches of Pulmatrix’s iSPERSE-based inhaled therapeutic drug candidates currently under development by Pulmatrix and the company’s present and potential development partners. Capsugel will combine iSPERSE technology development with advances in its proprietary spray drying process, along with scaling-up expertise and commercial manufacturing capabilities at its Bend Research facility in Bend, Oregon, with Pulmatrix’s iSPERSE.
A $25 million-plus expansion of the Bend works received in 2014-2015 included installation of a commercial-scale spray dryer in its research and development facility to enhance commercial manufacturing capabilities for spray-dried dispersions at Bend, equipping it with the largest integrated pharmaceutical spray drying technology capability of any firm in North America. Capsugel is also investing to expand its late-stage inhalation offering to include full current good manufacturing practice (cGMP) analytical services and large-scale encapsulation for dry powder inhaler (DPI) applications.
Spray-dried dispersion technology helps enhance bioavailability of therapeutic compounds with low solubility and Bend’s high-capacity pharmaceutical spray dryer (PSD) can be used for scale-up, quality-by-design studies, and production of appropriate toxicology study supplies. Capsugel notes in a release that the technology can provide faster and more agile development activities, as well as reduced cost and more flexible use of active pharmaceutical ingredients (API), and also allows scale-up aspects of quality-by-design to be integrated earlier into development for spray-dried products.
“This strategic partnership with Pulmatrix puts our companies at the forefront of bringing unique inhalation products to the market to deliver better patient outcomes,” says Dan Dobry, head of Alliance Strategy at Bend Research, a division of Capsugel Dosage Form Solutions business unit, in a release.
“We look forward to working with Pulmatrix to help advance its pipeline of proprietary and partnered products utilizing our spray dry technology and infrastructure, and to jointly explore opportunities to collaborate with the broader pharmaceutical industry to develop next-generation inhalation therapies.”
Capsugel and Pulmatrix are both leaders in development of spray drying as an enabling technology to address the limitations of conventional lactose blending DPI and metered dose inhaler (MDI) technologies. Capsugel’s Dosage Form Solutions (DFS) business utilizes an array of proprietary technologies and specialized manufacturing capabilities to overcome a number of product development challenges, including bioavailability enhancement, modified release, abuse deterrence, biotherapeutic processing, and inhalation formulation.
Pulmatrix’s iSPERSE (inhaled small particles easily respirable and emitted) is a proprietary new platform for inhaled drug delivery based on a combination of properties: density, high drug load, engineered particles with highly efficient dispersibility, dose reproducibility, flow-rate independence, and delivery to the airways. The company notes that dry powder technologies offer several commercial advantages over nebulized liquid formulations, including ease of use, speed of dosing, improved portability, and proprietary iSPERSE technology is backed by a strong intellectual property estate extending into the 2030’s.
The first drug candidates from the iSPERSE platform are Pulmatrix’s dry powder (DP) iCALM therapies for use with hand held dry powder inhalers (DPIs). The iSPERSE platform enables Pulmatrix to optimize its DP iCALM therapies to be highly dispersible with a high drug payload to powder volume ratio, allowing for efficient and reproducible delivery of iCALM doses across a wide range of potential patient populations, including patients with compromised lung function.
High iSPERSE powder dispersibility facilitates use of commercially available or proprietary simple and passive capsule or blister-based dry powder inhaler (DPI) devices. Several products leveraging the iSPERSE platform currently under development include PUR1500, an iSPERSE formulation incorporating a kinase inhibitor with established anti-angiogenesis activity for treatment of idiopathic pulmonary fibrosis (IPF), which affects approximately 128,100 people in the United States, with about 48,000 new cases diagnosed annually.
A progressive and generally fatal disease, IPF is characterized by scarring of the lungs, causing an irreversible loss of the tissue’s ability to transport oxygen. PUR1500 intends to suppress the fibrotic pathway at the site of disease in the lung interstitium.
Other therapies in the Pulmatrix pipeline include a lead clinical stage bronchodilator (PUR0200) that delivers an iSPERSE formulation incorporating a marketed long-acting muscarinic antagonist (LAMA) in clinical development for treating chronic obstructive pulmonary disease (COPD) that exemplifies the highly efficient delivery that iSPERSE can achieve; an inhaled anti-infective iSPERSE formulation incorporating a large, complex anti-fungal compound that can be administered at high therapeutic dose to the lung while minimizing systemic side effects (PUR1900) for cystic fibrosis (CF), and a pipeline of products for treating rare pulmonary diseases, CF and idiopathic pulmonary fibrosis.
Pulmatrix says the high degree of aerosol efficiency and particle density engineered in its DP iSPERSE technology can be tailored to advantageously deliver a wide range of drugs via inhalation for both local and systemic drug delivery application, and moreover iSPERSE’s properties result in 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 use of simple and convenient inhaler devices.
For example, iSPERSE facilitates efficient airway delivery of higher drug loads in smaller masses of inhaled powder, since the iSPERSE powders are small in geometric size and relatively dense, yet highly dispersible and relatively flow-rate independent with high emitted doses achieved even at low flow rates. These qualities contrast with conventional DP technologies that rely on lactose blending or use of low-density particles in order to facilitate dispersibility.
Pulmatrix explains that iSPERSE uses proprietary salt-containing formulations rather than lactose blending to enable DP delivery. iSPERSE powders can contain as little as 20 percent or less of salts and other excipients, as contrasted with lactose blend DPs that typically consist of greater than 80-90 percent lactose blends, which have poor delivery efficiency, typically delivering less than 20 percent of the drug to the lungs. Additionally, they point out that lactose blends are also highly dependent on flow rate, resulting in significant variability with respect to emitted dose and aerodynamic size.
By contrast, low energy required for dispersion coupled with capacity for high drug loading, as well as potential for inclusion of multiple drugs in iSPERSE compositions, facilitates delivery of low potency or large-molecule drugs to a comprehensive patient population across a wide range of inhalation flow rates.
With completion of comprehensive proof-of-concept validation of the iSPERSE platform along with extensive initial patent filings, Pulmatrix is now advancing a select number of proprietary iSPERSE drug candidates as well as actively pursuing iSPERSE partnerships with pharmaceutical companies to create novel therapeutics such as the Capsugel collaboration.
“This collaboration provides us with access to Capsugel’s spray dry technology, scale-up capabilities, and state-of-the-art equipment to support our growing pipeline of internal and partnered development programs,” says Pulmatrix CEO Robert Clarke, PhD, in the joint release.
“In the near term, Capsugel will fulfill manufacturing needs for our planned clinical trial activities in cystic fibrosis and, longer term, will enable us to manufacture iSPERSE-based products at commercial scale,” comments Pulmatrix’s chief scientific officer, David Hava, PhD. “With this partnership, we can achieve these goals cost-effectively and without the risk or required capital to build and maintain these essential capabilities.”