Pulmatrix has been awarded $5.7 million by DARPA for preclinical development of its inhaled cationic airway lining modulator (iCALM) technology for the treatment of airborne biothreats including anthrax, tularemia, and influenza.
The funding will be used to support formulation development and preclinical studies with lead iCALM drug candidates. The aim is to develop field-deployable drug/device combinations against infections for both military personnel and civilians.
“The milestones of this work are focused on demonstrating the efficacy of iCALM in making multiple viral pathogens less infectious to the warfighter and civilians,” comments Robert Clarke, Ph.D., vp research. "The outcome will demonstrate two utilities of the technology, pathogen independence and the ability to disrupt the induction of infection.
"In addition, advanced formulation work supported by this grant will allow the development and characterization of an optimized lead formulation well suited to the rigors of a field device in terms of ease of inhalation and climate tolerance.”
Pulmatrix’ iCALM technology exploits a pathogen-independent approach that is designed to harness the natural defenses in the body’s airways to prevent and treat infections and acute exacerbations associated with chronic or progressive respiratory diseases.
The multifactorial mechanism of action occurs at two levels, Pulmatrix suggests. At the biophysical level iCALM therapies activate the assembly of endogenous proteins in the airway lining fluid into 3-D matrices, resulting in enhanced barrier function in the lung to reduce the penetration of pathogens into the lung tissue. These changes in the rheological properties of the airway, in addition, lead to a reduction in the formation and exhalation of infectious bioaerosols. At the biological level iCALM therapy stimulates host defense mechanisms in the lung that prevent infection, enhance the clearance of pathogens, and reduce airway inflammation.
Pulmatrix hopes the host-targeting mechanisms of action of iCALM therapies will also mean the approach is less susceptible to pathogen mutation and the emergence of pathogen resistance than pathogen-targeted therapies.
The firm claims iCALM therapies could have potential utility against a range of chronic and acute respiratory diseases and infections including COPD, asthma, cystic fibrosis, influenza, ILI, rhinovirus, ventilator-associated pneumonia, and RSV, in both compromised and healthy individuals. The firm has established a preclinical data package demonstrating treatment efficacy, prophylaxis, and transmission control in multiple animal species, with respect to viral and bacterial diseases as well as the reduction of inflammation in acute models of lung injury.
A liquid iCALM formulation PUR003 has already completed two trials in healthy normal volunteers. One of these demonstrated the effectiveness, safety, and tolerability of the PUR003 iCALM formulation in an experimental influenza infection model in healthy volunteers.The candidate is currently being evaluated in a blinded, placebo-controlled crossover trial in asthma patients. Phase I trials of a dry powder iCALM are expected to start during early 2011.
In November 2009, Pulmatrix was awarded a $2.2 million grant by the NIAID to develop novel influenza therapeutics for the treatment of seasonal and pandemic influenza. “The DARPA award and the 2009 NIAID grant we received are validation of the value and utility of braod-spectrum inhaled therapeutics that can treat both bacterial and viral infections, the one-size-fits-many approach,” concludes Robert Connelly, Pulmatrix CEO.