Pulmatrix Announces Positive Final Results from the Phase 1/1b Clinical Trial of Pulmazole - an Inhaled Dry-Powder iSPERSE™ Formulation of Itraconazole

LEXINGTON, Mass., Nov. 21, 2018 /PRNewswire/ -- Pulmatrix, Inc. (NASDAQ: PULM) announced the results of the completed 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.

The company previously reported positive top line data from Parts 1 and 2 of the study in normal healthy volunteers, and from Part 3 in asthmatic subjects.  With the final results now in hand, which both extend and confirm the previously reported positive top line data, Pulmatrix plans to initiate a Phase 2 trial in asthmatic patients with ABPA patients in Q4 2018.

Pulmazole appeared to be safe and well tolerated in normal healthy subjects in Parts 1 and 2 at doses up to 35 mg, the maximal dose tested, over 14 days of administration.  Single doses of Pulmazole 20 mg and oral Sporanox 200 mg appeared to be safe and well tolerated in asthmatic subjects.  The most common adverse event (AE) reported was mild cough during dosing, which resolved spontaneously in seconds to minutes.  No subject experienced an AE leading to withdrawal.

Sustained low-level systemic exposure after single and multiple doses over 24 hours post-dose is indicative of high and sustained lung exposure and supports once daily dosing.  Very low systemic exposure for itraconazole was observed across all doses, with 106- to 400-fold lower itraconazole exposure after 14 days of 10 to 35 mg Pulmazole compared to expected values following administration of oral Sporanox^® 200 mg twice daily.  In asthmatics, adjusted geometric mean AUC_0-t was 66-fold lower after a single 20 mg inhaled Pulmazole dose compared to a single 200 mg oral Sporanox^® dose.  Geometric mean sputum itraconazole C_max was ~70-fold higher following 20 mg inhaled Pulmazole versus 200 mg oral Sporanox^® (4530 ng/mL compared to 65.4 ng/mL). 

David Denning, MD, Professor of Infectious Diseases in Global Health and the Director of the National Aspergillosis Centre, Manchester, UK and co-chair of the Pulmazole Clinical Advisory Board, commented that "Itraconazole's track record of greater than twenty-five years of usage and demonstrated patient benefits for allergic fungal disease tells its own story.  Direct delivery of itraconazole into the lungs to increase exposure in the lung where the disease is manifest, while minimizing systemic exposure and associated side effects clearly offers the potential to improve upon both the efficacy and safety observed with oral itraconazole."   

Jim Roach, MD, Chief Medical Officer of Pulmatrix remarked, "With the phase 1 study results now firmly in hand, we remain very enthusiastic about the potential for Pulmazole to address the significant limitations associated with oral itraconazole, and more importantly, to address the significant unmet medical need that patients with asthma and ABPA currently face.  We believe that these results strongly support the further advancement of Pulmazole into Phase 2 and look forward to getting our next study underway next month."   

The Phase 1/1b study included 58 patients in a 3-part open-label study in healthy adults (Parts 1 and 2) and in adults with mild to moderate, stable asthma (Part 3). The main objectives of Part 1 single ascending dose and Part 2 multiple ascending dose were to evaluate the safety, tolerability, and pharmacokinetics (PK) of Pulmazole administered either as a single-dose or multiple-doses administered daily over 14 days in normal healthy volunteers. The main objective in Part 3 was to evaluate the safety, tolerability, and pharmacokinetics (PK) of Pulmazole administered as a single-dose in mild-to-moderate asthmatics, and an additional exploratory objective in Part 3 was to characterize the concentrations of itraconazole in induced sputum following single doses of inhaled Pulmazole and oral Sporanox® solution in subjects with mild to moderate stable asthma. 

The maximum dose of Pulmazole administered in this study was 35 mg itraconazole. A total of 23 subjects were dosed across 4 cohorts (5 mg, 10 mg, 25 mg, and 35 mg itraconazole) in Part 1, and a total of 18 subjects were dosed across 3 cohorts (10 mg, 20 mg, and 35 mg itraconazole) in Part 2.  In Part 3, subjects were administered as 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 were dosed.

A copy of the poster presented at the American College of Allergy, Asthma, and Immunology in Seattle, Washington on November 17, 2018 is available on the Pulmatrix website. 

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.

About Pulmatrix          
Pulmatrix is a clinical stage biopharmaceutical company developing innovative inhaled therapies to address serious pulmonary disease using its patented iSPERSE™ technology. The Company's proprietary product pipeline is focused on advancing treatments for serious lung diseases, including Pulmazole, an inhaled anti-fungal for patients with allergic bronchopulmonary aspergillosis ("ABPA"), and PUR1800, a narrow spectrum kinase inhibitor for patients with obstructive lung diseases including asthma and chronic obstructive pulmonary disease ("COPD"). Pulmatrix's product candidates are based on iSPERSE™, its proprietary engineered dry powder delivery platform, which seeks to improve therapeutic delivery to the lungs by maximizing local concentrations and reducing systemic side effects to improve patient outcomes.

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.

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