Pulmatrix Announces Positive Top-Line Preliminary Results from Part 3 of the 3-Part Phase 1/1b Clinical Trial of Pulmazole - an Inhaled Dry-Powder iSPERSE™ Formulation of Itraconazole

Single dose of Pulmazole safe and well tolerated in subjects with asthma

PK analysis of sputum samples demonstrated ~50-fold higher lung exposure following inhalation of Pulmazole compared to oral Sporanox® despite inhaling only one tenth the dose of itraconazole (20 mg) contained in a dose of oral Sporanox (200 mg)

Total systemic exposure was ~85-fold lower following inhalation of 20 mg Pulmazole compared to 200 mg of oral Sporanox

All objectives from Part 3 successfully met, on track to initiate a Phase 2 study in asthmatic patients with allergic bronchopulmonary aspergillosis (ABPA) in 2018

LEXINGTON, Mass. /PRNewswire/ -- Pulmatrix, Inc. (NASDAQ: PULM) announced today that all dosing and follow up visits have been completed for Part 3 of the ongoing first-in-human study of Pulmazole (PUR1900) - an inhaled iSPERSE^TM formulation of the anti-fungal drug itraconazole for the treatment of allergic bronchopulmonary aspergillosis (ABPA) in patients with asthma. Pulmazole was safe and well tolerated administered as a single-dose of 20 mg inhaled itraconazole in asthmatic subjects. Based on review of the top-line preliminary data, the study successfully achieved all objectives. The company previously reported positive top line data from Part 1 and 2 of the study in normal healthy volunteers. With these encouraging Phase 1/1b results from Part 3 now also in hand, Pulmatrix plans to initiate a Phase 2 trial in ABPA patients in Q4 2018.

In the pharmacokinetic analysis of the data available, maximum sputum itraconazole concentrations were approximately 50-fold higher following inhalation dosing of 20 mg of Pulmazole compared to oral Sporanox dosing of 200 mg. Additionally, high lung exposure following inhalation of a single dose of 20 mg Pulmazole was maintained over a 24-hour period, whereas sputum concentrations of itraconazole decreased between 2 hours and 6 hours after a single 200 mg oral Sporanox dose. Following inhalation of 20 mg of Pulmazole, total systemic exposure over 24 hours (AUC_0-24h) and maximum plasma concentration (C_max) were approximately 85-fold and 250-fold lower compared to AUC_0-24hand C_max following 200 mg of oral Sporanox, respectively.

Dave Singh, MD, Professor of Clinical Pharmacology and Respiratory Medicine at the University of Manchester and principal investigator on Part 3 of the study commented, "These data in asthmatics are very promising regarding the future potential of Pulmazole as a therapy for patients with ABPA, a disease with significant unmet medical need. Demonstration of significantly higher levels in the lung as well as significantly lower systemic exposure following inhalation of Pulmazole suggests that Pulmazole has the potential to dramatically improve upon the known safety and efficacy of Sporanox."

The main objectives of the study in Part 3 were to evaluate the safety, tolerability, and pharmacokinetics of Pulmazole administered as a single-dose in mild-to-moderate asthmatics. Subjects were administered either a single dose of oral itraconazole (Sporanox; 200 mg itraconazole) or Pulmazole (20 mg itraconazole) in a crossover study design, to compare relative levels of itraconazole in both the blood and sputum after being administered by either route.

Part 3 of the study was planned to include 16 asthmatic subjects. A total of 17 asthmatic subjects (including one replacement subject) were dosed. The preliminary data reviewed suggests that Pulmazole was safe and well tolerated. All study drug-related adverse events (AEs) were characterized as mild, and no moderate, severe or serious study drug-related AEs were reported. The most common AEs in Part 3 following administration of Pulmazole were mild and transient headache, and the infrequent occurrence of a mild cough.

"These preliminary safety, tolerability and pharmacokinetic results from Part 3 in subjects with asthma strongly corroborate and further extend the positive findings we observed in normal healthy volunteers," commented Jim Roach, MD, Chief Medical Officer of Pulmatrix. "Notably, itraconazole levels in the sputum of asthmatic subjects were much higher following inhaled versus oral administration, despite administering much lower doses of itraconazole via the inhaled route. This further supports the potential of Pulmazole to improve upon the efficacy observed with oral Sporanox in patients with ABPA. We believe we have now generated the requisite data to advance to initiation of a Phase 2 study in patients with asthma and ABPA and are planning for study initiation in the fourth quarter of this year.  We look forward to submitting the Phase 1/1b study results in the next several weeks for presentation at a major scientific conference later this year."

About ABPA

ABPA is a disease that occurs most often in patients with underlying asthma or cystic fibrosis, and it is characterized by an exaggerated allergic hypersensitivity response of the immune system to the fungus Aspergillus colonizing and growing in the airways. Oral itraconazole (Sporanox®) is currently used as an adjunctive treatment to corticosteroids in ABPA patients. However, its use is limited by poor bioavailability, variable pharmacokinetics, and toxicity concerns related primarily to the risk of gastrointestinal and cardiac side effects, as well as extensive drug-drug interactions.  The Pulmatrix Pulmazole program is the first inhaled dry powder version of itraconazole known to the company to be advanced into clinical development, with the goal of improving upon the known safety and efficacy profile associated with oral Sporanox by delivering the drug directly to the lung. 

FORWARD-LOOKING STATEMENTS

Certain statements in this press release that are forward-looking and not statements of historical fact are forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. The Company cautions that such statements involve risks and uncertainties that may materially affect the Company's results of operations. Such forward-looking statements are based on the beliefs of management as well as assumptions made by and information currently available to management. Actual results could differ materially from those contemplated by the forward-looking statements as a result of certain factors, including but not limited to the ability to establish that potential products are efficacious or safe in preclinical or clinical trials; the ability to establish or maintain collaborations on the development of therapeutic candidates; the ability to obtain appropriate or necessary governmental approvals to market potential products; the ability to obtain future funding for developmental products and working capital and to obtain such funding on commercially reasonable terms; the Company's ability to manufacture product candidates on a commercial scale or in collaborations with third parties; changes in the size and nature of competitors; the ability to retain key executives and scientists; and the ability to secure and enforce legal rights related to the Company's products, including patent protection. A discussion of these and other factors, including risks and uncertainties with respect to the Company, is set forth in the Company's filings with the Securities and Exchange Commission, including its annual report on Form 10-K filed by the Company with the Securities and Exchange Commission on March 13, 2018, as may be supplemented or amended by the Company's Quarterly Reports on Form 10-Q. The Company disclaims any intention or obligation to revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

SOURCE Pulmatrix, Inc.