Pulmazole (itraconazole inhaled) / Pulmatrix, Cipla - LARVOL DELTA

Study to Evaluate Itraconazole Administered as Inhaled Dry Powder in Adults With Asthma and ABPA (clinicaltrials.gov) - P2 | N=8 | Terminated | Sponsor: Pulmatrix Inc. | Active, not recruiting ➔ Terminated; Low enrollment

Trial termination • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Study to Evaluate Itraconazole Administered as Inhaled Dry Powder in Adults With Asthma and ABPA (clinicaltrials.gov) - P2 | N=8 | Active, not recruiting | Sponsor: Pulmatrix Inc. | Recruiting ➔ Active, not recruiting | N=30 ➔ 8 | Trial completion date: Jul 2024 ➔ Feb 2024 | Trial primary completion date: Jul 2024 ➔ Feb 2024

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Study to Evaluate Itraconazole Administered as Inhaled Dry Powder in Adults With Asthma and Allergic Bronchopulmonary Aspergillosis (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Pulmatrix Inc. | Trial completion date: Apr 2024 ➔ Jul 2024 | Trial primary completion date: Apr 2024 ➔ Jul 2024

Trial completion date • Trial primary completion date • Allergic Bronchopulmonary Aspergillosis • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Pulmatrix Announces Third Quarter 2023 Financial Results and Provides Corporate Update (PRNewswire) - "PUR1900 (itraconazole, administered as a dry powder for inhalation using iSPERSE™) has been in a Phase 2 trial for the treatment of ABPA in patients with asthma (NCT05667662)....Pulmatrix currently anticipates topline data from this study in the second half of 2024....Pulmatrix plans to pursue partnership opportunities to advance PUR1800 into a potential Phase 2 clinical trial....Research and development expenses decreased approximately $1.3 million to $4.0 million for the three months ended September 30, 2023 compared to $5.3 million for the three months ended September 30, 2022. The decrease was primarily due to decreased spend of $0.7 million in costs related to the Company's PUR3100 program, $0.4 million in costs related to the Company's PUR1900 program, $0.1 million in costs related to the Company's PUR1800 program and $0.1 million of employment and operating costs."

Commercial • New P2 trial • P2 data • Allergic Bronchopulmonary Aspergillosis • Chronic Obstructive Pulmonary Disease

Pulmatrix Announces Publication on Physiologically Based Pharmacokinetic Modelling of Potential Drug-Drug Interactions with PUR1900, Orally Inhaled Itraconazole (PRNewswire) - P1 | N=58 | NCT03479411 | Sponsor: Pulmatrix Inc. | "Pulmatrix is currently enrolling patients in a Phase 2 study of PUR1900 in adults with ABPA and Asthma....'We are pleased to publish the drug-drug interaction modeling study on PUR1900 in the AAPS Journal. This study demonstrates the risk of DDI with PUR1900 (inhaled itraconazole) is lower than with oral itraconazole and PUR1900 may be safely administered even in patients taking drugs contraindicated with oral itraconazole."

Enrollment status • P1 data • PK/PD data • Allergic Bronchopulmonary Aspergillosis • Asthma • Respiratory Diseases

Pulmatrix Announces Second Quarter 2023 Financial Results and Provides Corporate Update (PRNewswire) - "PUR1900; PUR1900 is currently in a Phase 2 trial for the treatment of ABPA in patients with asthma....Pulmatrix anticipates topline data from this study in the third quarter of 2024....Research and development expenses decreased approximately $0.2 million to $4.2 million for the three months ended June 30, 2023 compared to $4.3 million for the three months ended June 30, 2022. The decrease was primarily due to decreased spend of $0.8 million in costs related to the Company's PUR3100 program and $0.1 million in costs related to the Company's PUR1800 program, partially offset by increases in spending of $0.5 million in costs related to the Company's PUR1900 program and $0.2 million of employment and operating costs."

Commercial • Allergic Bronchopulmonary Aspergillosis • Asthma • CNS Disorders • Infectious Disease • Migraine • Pain • Pulmonary Disease • Respiratory Diseases

Evaluation of the Potential for Drug-Drug Interactions with Inhaled Itraconazole Using Physiologically Based Pharmacokinetic Modelling, Based on Phase 1 Clinical Data. (PubMed, AAPS J) - P1 | "This project used physiologically based pharmacokinetic (PBPK) modeling to assess the DDI potential of inhaled PUR1900, using midazolam as a "victim drug." The basic and mechanistic static models evaluated the DDI potential of PUR1900, assuming 5 mg of midazolam coadministration at steady-state itraconazole exposure. The low systemic exposure of itraconazole when administered as PUR1900 results in minimal to no CYP3A4 inhibition, reducing the concern of drug-drug interactions. As the risk of CYP3A4 DDI is predicted to be significantly lower when itraconazole is administered via oral inhalation as PUR1900, it is likely that PUR1900 can be safely used for the treatment of pulmonary fungal infections in patients taking pharmaceuticals currently contraindicated with oral itraconazole."

Clinical data • Journal • P1 data • PK/PD data • Allergic Bronchopulmonary Aspergillosis • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Pulmatrix Announces First Quarter 2023 Financial Results and Provides Corporate Update (PRNewswire) - "Research and development expenses decreased $0.2 million to $3.9 million for the three months ended March 31, 2023 compared to $4.1 million for the three months ended March 31, 2022....The decrease was primarily due to decreased spend of...$0.3 million in costs related to the Company's PUR1800 program, partially offset by increased spend of $0.6 million in costs related to the Company's PUR1900 program."

Commercial • Allergic Bronchopulmonary Aspergillosis • Asthma • Chronic Obstructive Pulmonary Disease

Pulmatrix Announces Year-End and Q4 Financial 2022 Results and Provides Corporate Update (PRNewswire) - "$35.6 million in cash and cash equivalents at the end of 2022 providing cash runway into Q2 2024....Pulmatrix began dosing patients for its Phase 2b study of PUR1900....Pulmatrix expects to report topline data from this study in mid-2024.....Research and development expense was $18.2 million for the year ended December 31, 2022, as compared to $15.4 million for the year ended December 31, 2021; an increase of $2.8 million. The increase was primarily due to an increased spend of $2.9 million in costs related to the Company's PUR1900 program and $2.6 million of employment and operating costs, partially offset by decreased spend of $2.7 million in costs primarily related to Pulmatrix's PUR1800 program."

Commercial • P2b data • Allergic Bronchopulmonary Aspergillosis • Asthma • Respiratory Diseases

Pulmatrix Announces First Patient Dosed in Phase 2b Study of PUR1900 for Treatment of Allergic Bronchopulmonary Aspergillosis (ABPA) in Subjects with Asthma (PRNewswire) - "Pulmatrix...today announced the first patient dosed in a Phase 2b trial evaluating safety and efficacy of PUR1900 in subjects with Allergic Bronchopulmonary Aspergillosis (ABPA) and asthma. PUR1900 is the company's iSPERSE-enabled dry powder formulation of itraconazole, developed for inhaled pulmonary delivery....'Initiating this study this quarter as planned, allows us to maintain our momentum towards expected proof-of-concept data by mid-2024.'"

P2b data • Trial status • Allergic Bronchopulmonary Aspergillosis • Asthma • Respiratory Diseases

Study to Evaluate Itraconazole Administered as Inhaled Dry Powder in Adults With Asthma and Allergic Bronchopulmonary Aspergillosis (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Pulmatrix Inc.

New P2 trial • Allergic Bronchopulmonary Aspergillosis • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Pulmatrix Announces Resolution of Contract Dispute with Cipla (Pulmatrix Press Release) - "Pulmatrix...today announced that it has completed an amendment to Pulmatrix's agreement with Cipla Technologies, LLC ('Cipla') for the development and commercialization of Pulmazole. The completion of the amendment resolves Pulmatrix's previously disclosed dispute with Cipla regarding the continued funding of the development costs for Pulmazole. Pursuant to the 2nd Amendment Cipla will continue to reimburse Pulmatrix for 50% of all third-party costs for the development of Pulmazole, provided Cipla will only be required to reimburse Pulmatrix for 40% of Pulmatrix dedicated personnel and consulting costs ('direct costs')....The development milestones for Pulmatrix's planned Phase 2b clinical trial include the dosing of 25% of participants in the clinical trial by June 30, 2023, and the delivery of top-line data results to the joint steering committee for the program by June 30, 2024."

Corporate lawsuit • P2b data • Trial status • Asthma • Respiratory Diseases

Pulmatrix Reports Second Quarter 2021 Financial Results and Provides Business Update (PRNewswire) - "Completed enrollment in ongoing Phase 1b clinical study of PUR1800 in acute exacerbations in COPD (AECOPD)....Top-line data is expected in Q1 2022: From 6-month rat...toxicology results demonstrate no progression of 28-day findings, suggesting potential for chronic dosing of PUR1800 in indications beyond AECOPD including, but not limited to, steroid resistant asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF)....Revenue for the second quarter of 2021 was $2.2 million, compared to $3.5 million for the same period in 2020. The revenue for the second quarter of 2021 was the result of the collaboration and licensing agreements with Cipla and JJEI. Research and development expense was $4.5 million in the second quarter of 2021...The increase year–over-year was primarily attributable to increased preclinical and manufacturing costs...decreased spend on the Pulmazole clinical trial."

Commercial • Enrollment closed • P1 data • Preclinical • Asthma • Chronic Obstructive Pulmonary Disease • Idiopathic Pulmonary Fibrosis • Respiratory Diseases

Pulmatrix Reports First Quarter 2021 Financial Results and Provides Business Update (PRNewswire) - "On May 10, 2021, we sent a letter to Cipla Technologies LLC ('Cipla') notifying Cipla that it is in material breach of our Development and Commercialization Agreement (the 'Cipla Agreement'), dated April 15, 2019, due to Cipla's anticipatory breach of its obligation under the Cipla Agreement to fund 50% of the development costs for Pulmazole...Pulmatrix intends to advance Pulmazole clinically to Ph2b....Research and development expense was $3.9 million in the first quarter of 2021 compared to $5.3 million for the same period in 2020. The decrease year–over-year was primarily attributable to decreased costs associated with the PUR1800 program and clinical study costs incurred for the Phase 2 Pulmazole study..."

Commercial • Licensing / partnership • Chronic Obstructive Pulmonary Disease • Respiratory Diseases

Allergic Diseases Caused by Aspergillus Species in Patients with Cystic Fibrosis. (PubMed, Antibiotics (Basel)) - "Oral corticosteroids are used to manage aspects of the inflammatory response and antifungal agents are used to reduce fungal burden and lower the exposure to fungal antigens. As the appreciation for the severity of fungal infections has grown, new therapies have emerged that aim to improve treatment and outcomes for patients with CF."

Clinical • Journal • Review • Allergic Bronchopulmonary Aspergillosis • Allergy • Asthma • Chronic Obstructive Pulmonary Disease • Cystic Fibrosis • Fibrosis • Genetic Disorders • Idiopathic Pulmonary Fibrosis • Immunology • Infectious Disease • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Respiratory Diseases

Pulmatrix Reports 2020 Financial Results and Provides Business Update (PRNewswire) - "PUR1800: Initiated the Phase 1b clinical study of PUR1800, dosing 4 of 15 patients to date....Pulmazole: Successfully completed a Type C Meeting with the U.S. FDA for the further clinical development of Pulmazole. Based on feedback from the Type C Meeting, and in accordance with our collaboration with Cipla, Pulmatrix intends to initiate a Phase 2b clinical study of Pulmazole in allergic bronchopulmonary aspergillosis (ABPA) in Q1 2022, dependent on assessment of COVID-19 impact on patient safety and study operations."

Trial initiation date • Trial status • Asthma • Chronic Obstructive Pulmonary Disease • Respiratory Diseases

Pulmatrix Reports Third Quarter 2020 Financial Results and Business Updates (PRNewswire) - "Pulmatrix anticipates initiating its Phase 1b study evaluating PUR1800, its iSPERSE enabled narrow spectrum kinase inhibitor (NSKI), in patients with stable COPD in the first half of 2021...Net loss was $10.6 million for the third quarter of 2020 and $3.6 million for the third quarter of 2019. The net loss for the third quarter 2020 was primarily due to warrant inducement expense of $9.3 million and manufacturing costs for the upcoming PUR1800 Phase 1b clinical study and the recently terminated Pulmazole Phase 2 study. The net loss for the third quarter of 2019 was due to spend on the Pulmazole Phase 2 study."

Commercial • New P1 trial • Asthma • Chronic Obstructive Pulmonary Disease • Respiratory Diseases

Pulmatrix Reports Progress on Product Pipeline (PRNewswire) - "Together with our partner Cipla Technologies LLC, we decided to end our Phase 2 clinical study of Pulmazole for the treatment of asthma patients with ABPA...the study was initially put on hold as the pandemic spread in 2Q 2020...we decided to stop the study and intend to start a new larger Phase 2b study designed with a longer treatment duration and key phase 3 enabling efficacy endpoints...We plan to have a Type-C meeting with the FDA in Q1 2021 to inform our final clinical design and timelines. We plan to commence the new Phase 2b study when the risk of...ongoing COVID-19 pandemic is reduced to an acceptable level."

FDA event • New P2b trial • Trial termination • Asthma • Respiratory Diseases

Study in Adult Asthmatic Patients With Allergic Bronchopulmonary Aspergillosis (clinicaltrials.gov) - P2; N=7; Terminated; Sponsor: Pulmatrix Inc.; N=64 ➔ 7; Suspended ➔ Terminated; COVID-19 Pandemic

Clinical • Enrollment change • Trial termination • Asthma • Respiratory Diseases

Study in Adult Asthmatic Patients With Allergic Bronchopulmonary Aspergillosis (clinicaltrials.gov) - P2; N=64; Suspended; Sponsor: Pulmatrix Inc.; Recruiting ➔ Suspended

Clinical • Trial suspension • Asthma • Respiratory Diseases

Pulmazole inhaled itraconazole for ABPA gets fast track designation - "A co-lead investigator of the Phase 2 study, William J Calhoun...'Approximately half of ABPA patients do not respond to first line treatment with oral steroids which carry risks of dependence and complications from long-term use. While effective, second-line oral antifungals are limited in their use due to safety and tolerability concerns. Pulmazole, which is being tested as an inhaled antifungal, has shown promising Phase 1/1b study results enabling approximately 50-fold higher lung delivery at 1/10th the dosing of oral itraconazole. I believe Pulmazole has the potential to shift the standard care for ABPA by addressing the underlying cause of inflammatory responses while avoiding the significant limitations in efficacy and safety associated with oral steroid and antifungal standard of care treatment.'"

Media quote

A phase 1/1b study of PUR1900, an inhaled formulation of itraconazole, in healthy volunteers and asthmatics to study safety, tolerability and pharmacokinetics. (PubMed, Br J Clin Pharmacol) - "PUR1900 was safe and well-tolerated under the study conditions. Compared to oral dosing, PUR1900 achieved higher lung and lower plasma exposure. The pharmacokinetic profile of PUR1900 suggests the potential to improve upon the efficacy and safety profile observed with oral itraconazole."

Clinical • Journal • P1 data • PK/PD data

THE DEVELOPMENT OF AN INHALED PUR1900 FORMULATION ENGINEERED TO ACHIEVE HIGH LUNG AND LOW SYSTEMIC EXPOSURE (ERS 2019) - No abstract available.

Study in Adult Asthmatic Patients With Allergic Bronchopulmonary Aspergillosis (clinicaltrials.gov) - P2; N=64; Recruiting; Sponsor: Pulmatrix Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

Study in Adult Asthmatic Patients With Allergic Bronchopulmonary Aspergillosis (clinicaltrials.gov) - P2; N=64; Not yet recruiting; Sponsor: Pulmatrix Inc.

New P2 trial