When treating both respiratory and non-respiratory disease, even dispersion of inhaled therapeutics throughout the lung is a critical factor driving efficacy and safety.
Conventional dry powder technologies
rely on the use of lactose blending or
low-density particles to facilitate
To optimize dispersion of therapeutic particles,
the scientists and engineers at PULMATRiX have
developed a technological innovation, iSPERSE™.
iSPERSE™ makes possible a new generation of pulmonary-delivered
therapies to dramatically improve patient outcomes.
PULMATRiX is committed to the development and commercialization of novel and transformational medicines for patients all over the world, using our proprietary iSPERSE™ technology to optimally deliver both respiratory and non-respiratory therapies via the respiratory system. Our initial focus is on respiratory diseases.
Aspergillus spp. are spore forming molds that cause significant morbidity and mortality in a number of different patient populations, with A. fumigatus the predominant species causing disease. Pulmonary A. fumigatus infections manifest as a range of diseases depending on the host’s immune state and underlying lung disease.1
In patients with asthma, fungal colonization and infection can result in ABPA. ABPA is a complex hypersensitivity reaction that occurs in the response to colonization of the airways with Aspergillus fumigatus, typically in patients with asthma or cystic fibrosis (CF).2 The immunological response to fungal antigens in the airway results in T-helper type 2 (Th2) cell activation and inflammatory cell recruitment to the airways, the most significant of which are eosinophils. Activation of both mast cells and eosinophils results in the release of mediators that induce bronchoconstriction.2
The diagnostic criteria for ABPA include both obligatory and supportive criteria in addition to having either asthma or CF. High levels of serum IgE (>1000 U/mL) and a positive hypersensitivity skin test or increased IgE antibody to Aspergillus are required criteria together with at least two additional supportive features: eosinophilia (>500 cells/μL), immunoglobulin G specific to Aspergillus antigens, and/or radiographic findings.3
ABPA is characterized clinically by wheezing, dyspnea, mucus production and productive cough, and bronchoconstriction. Repeated episodes of mucus production, bronchial obstruction and inflammation may lead to bronchiectasis, and in severe cases, pulmonary fibrosis, which collectively result in a progressive loss of lung function.
PULMATRiX is developing Pulmazole™, a dry powder iSPERSE™
inhaled antifungal formulation for the treatment of ABPA.
Pulmazole™ can be delivered directly to the lung with high and sustained lung exposure and minimal systemic exposure, potentially improving the efficacy and reducing the side effect profile demonstrated by oral antifungal treatment.
Learn more about Pulmazole™
Acute exacerbations of COPD are sudden onset increases in symptoms, including increased dyspnea, sputum purulence and volume, and wheezing, coughing, and shortness of breath that require medical intervention and can lead to hospitalization.4
COPD patients continue to suffer uncontrolled symptoms and exacerbations despite treatment with combination products which may contain inhaled corticosteroids, long acting muscarinic antagonists, and long acting ß-agonists. Depending on the severity, the management of AECOPD includes oral steroids and may include additional bronchodilators and antibiotics.5
Exacerbations often result in incomplete recovery and result in significantly increased morbidity and mortality. Hospitalization may be required for severe exacerbations.6 The occurrence of an exacerbation greatly increases the likelihood of a further exacerbation within the following 6 months and creates a significant financial burden to healthcare systems.7,8
PULMATRiX is developing PUR1800 for the treatment of AECOPD.
PUR1800 is a Narrow Spectrum Kinase Inhibitor (NSKI) engineered with iSPERSE™, and targets p38 MAP kinases (p38MAPK), Src kinases, and Syk kinases,10 which play critical roles in chronic inflammation and airway remodeling in patients with COPD.11-13
Learn more about PUR1800
Small, dense, and dispersible particles for highly efficient delivery of respiratory and non-respiratory therapies via the respiratory system
References: 1. Kousha M, Tadi R, and Soubani AO. Pulmonary aspergillosis: a clinical review. Eur Respir Rev. 2011;20(121):156-174. 2. Patterson K, Strek ME. Allergic bronchopulmonary aspergillosis. Proc Am Thorac Soc. 2010;7(3):237-244. 3. Agarwal R, Chakrabarti A, Shah A, et al. Allergic bronchopulmonary aspergillosis: review of literature and proposal of new diagnostic and classification criteria. Clin Exp Allergy. 2013;43(8):850-873. 4. Singh D, Agusti A, Anzueto A, et al. Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Lung Disease: the GOLD science committee report 2019. Eur Respir J. 2019;53(5):1900164. 5. Anzenuto A. Primary care management of chronic obstructive pulmonary disease to reduce exacerbations and their consequences. Am J Med Sci. 2010;340(4):309-318. 6. Ko FW, et al. Acute exacerbation of COPD. Respirology. 2016;21:1152-1165. 7. Celli BR and Barnes PJ. Exacerbations of chronic obstructive pulmonary disease. Eur Respir J. 2007;29:1224–1238. 8. Seemungal TAR, Donaldson GC, Bhowmik A, et al. Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease. Am J Resp Crit Care Med. 2000;161:1608-1613. 9. Data on file. PULMATRiX: Lexington, MA. 10. Curran AK, Charron C, Russel P, et al. PUR1800 (RV1162), a novel narrow spectrum kinase inhibitor, but not fluticasone, reduces TNFα-induced cytokine release by primary bronchial epithelial cells from healthy volunteers and COPD patients. Presented at: ERS International Congress; Paris, FRA: September 2018. 11. Barnes PJ. Kinases as novel therapeutic targets in asthma and chronic obstructive pulmonary disease. Pharmacol Rev. 2016;68:788-815. 12. Geraghty P, Hardigan A, Foronjy RF. Cigarette smoke activated the proto-oncogene c-Src to promote airway inflammation and lung tissue destruction. Am J Respir Cell Mol Biol. 2013;50(3):559-570. 13. Angata T, Ishii T, Motegi T, et al. Loss of siglec-14 reduces the risk of chronic obstructive pulmonary disease exacerbation. Cell Mol Life Sci. 2013;70(17):3199-3210.