Pulmatrix Stock

Pulmatrix, Inc. (Pulmatrix) operates as a clinical-stage biotechnology company. The company focuses on the discovery and development of novel inhaled therapeutic products intended to prevent and treat respiratory and other diseases with significant unmet medical needs using its patented iSPERSE technology.

The company's proprietary product pipeline includes treatments for serious lung diseases, such as allergic bronchopulmonary aspergillosis (ABPA) and Chronic Obstructive Pulmonary Disease (COPD), and central nervous system (CNS) disorders, such as acute migraine. The company's product candidates are based on its proprietary engineered dry powder delivery platform, iSPERSE, which seeks to improve therapeutic delivery to the lungs by maximizing local concentrations and reducing systemic side effects to improve patient outcomes.

The company designs and develops inhaled therapeutic products based on its proprietary dry powder delivery technology, iSPERSE (inhaled Small Particles Easily Respirable and Emitted), which enables delivery of small or large molecule drugs to the lungs by inhalation for local or systemic applications. The iSPERSE powders are engineered to be small, dense particles with highly efficient dispersibility and delivery to airways. iSPERSE powders can be used with an array of dry powder inhaler technologies and can be formulated with a broad range of drug substances, including small molecules and biologics. The iSPERSE dry powder technology offers enhanced drug loading and delivery efficiency that outperforms traditional lactose-blend inhaled dry powder therapies.

Business Strategy

The company develops iSPERSE-based therapeutic candidates which target the prevention and treatment of a range of diseases, including CNS disorders and pulmonary diseases. These therapeutic candidates include PUR1900 for the treatment of ABPA in patients with asthma and in patients with cystic fibrosis (CF), PUR3100 for the treatment of acute migraine, and PUR1800 for the treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Each program is enabled by its unique iSPERSE formulation designed to achieve specific therapeutic objectives.

The key elements of the company's strategy are to conduct PUR1900 clinical trials focused on the development of an inhaled antifungal therapy to treat an allergic/hypersensitivity response to fungus in the lungs of patients with asthma and CF; pursue further clinical studies for PUR3100, an orally inhaled dihydroergotamine (DHE), including a Phase 2 clinical study for the treatment of acute migraine; continue to advance PUR1800, focusing on the development of an inhaled kinase inhibitor for the treatment of AECOPD; capitalize on its proprietary iSPERSE technology and its expertise in inhaled therapeutics and particle engineering to identify new product candidates for prevention and treatment of diseases with significant unmet medical needs; invest in protecting and expanding its intellectual property portfolio and file for additional patents to strengthen its intellectual property rights.

iSPERSE Technology

The company uses simple, safe excipients, including proprietary cationic salt formulations, to create a robust and flexible dry powder platform technology that can accommodate a wide range of drug loads in highly dispersible particles. The company's initial delivery platform emerged from development of iCALM (inhaled Cationic Airway Lining Modulators), a non-steroidal anti-inflammatory therapy. The high degree of aerosol efficiency and the density profile of the company's dry powder iCALM formulations provided the foundation for its development of iSPERSE in 2012, which uses other monovalent and divalent salts.

iSPERSE particles are engineered with a small, dense and dispersible profile to exceed the performance of traditional dry powder particles as the iSPERSE particles have the dispersibility advantages of porous engineered particles.

Therapeutic Candidates

PUR1900

The company is developing an iSPERSE inhaled formulation of the antifungal drug itraconazole for the prevention and treatment of fungal infections and allergic/hypersensitivity reactions to fungus in patients with severe lung disease, including those with asthma and CF. On January 28, 2020, PUR1900 received Fast Track designation from the FDA for the treatment of ABPA.

PUR1900 is the company's inhaled formulation of itraconazole, an antifungal drug commercially available as an oral drug that it is developing to treat and prevent pulmonary fungal infections. Development of PUR1900 is focused on treatment of Aspergillus.

PUR1900 is the company's inhaled formulation of itraconazole, an antifungal drug commercially available as an oral drug that it is developing to treat and prevent pulmonary fungal infections. Development of PUR1900 is focused on treatment of Aspergillus. colonization and infection in patients with asthma and CF. In a Phase 1/1b clinical trial, PUR1900 appeared to be safe and well tolerated in healthy normal volunteers (Parts 1 and 2) and in patients with asthma (Part 3). In Part 3 of the Phase 1/1b clinical study, following a single dose of PUR1900, the pharmacokinetics (PK) analysis of sputum samples demonstrated approximately 70-fold higher maximum lung concentration of itraconazole following inhalation of PUR1900 compared to oral Sporanox (Janssen Pharmaceuticals) despite inhaling only one-tenth the dose of itraconazole (20 mg) relative to the dose of oral Sporanox (200 mg).

On April 15, 2019, the company entered into a Development and Commercialization Agreement (the Cipla Agreement) with Cipla Technologies LLC (Cipla) for the co-development and commercialization, on a worldwide, except for the Cipla Territory defined below, exclusive basis, of PUR1900, the company's inhaled iSPERSE drug delivery system (the Product) enabled formulation of the antifungal drug, itraconazole, which is only available as an oral drug, for the treatment of all pulmonary indications, including ABPA in patients with asthma. The company entered into an amendment to the Cipla Agreement on November 8, 2021 (the Amendment), and all references to the Cipla Agreement herein refer to the Agreement as amended.

The new development plan, including the new Phase 2b clinical study, was approved by the partnership joint steering committee (JSC) on November 8, 2021. On February 6, 2023, the company announced the first patient dosed in the Phase 2b study and the study is on track with topline data anticipated in mid-2024.

Clinical Development

The company successfully completed a Phase 1/1b clinical study in 2018 which enabled it to initiate a Phase 2 clinical study in 2019. The Phase 2b study includes a 16-week dosing regimen and exploration of potential regulatory approval endpoints. The company dosed the first patient in this Phase 2b clinical study during the first quarter of 2023 with topline data expected in mid-2024.

PUR3100

In 2020, the company began developing PUR3100, the iSPERSE formulation of DHE, for the treatment of acute migraine. Over 38 million people suffer from migraine in the United States. DHE is only available as intravenous infusion or intranasal delivery. If approved for commercialization, PUR3100 should be the first orally inhaled dihydroergotamine (DHE) treatment for acute migraine and be an alternative to other acute therapies, such as oral and intravenous triptans that represent the majority of the annual migraine prescriptions in the United States. Given the oral inhaled route of delivery, PUR3100 could provide a rapid onset of migraine symptom relief with a favorable tolerability profile.

Non-Clinical Development

A total of three 14-day good laboratory practices (GLP) toxicology studies have been completed with PUR3100 to support single dose clinical studies. Preparations are underway for chronic toxicology to support long-term dosing and an eventual new drug application (NDA).

Clinical Development

The company has completed several interactions with the FDA and they have confirmed that, in addition to the Planned Phase 2 and Phase 3 studies, long-term safety should be assessed in a minimum of one hundred patients for six months of dosing and fifty patients for twelve months of dosing. The FDA also confirmed that it will be necessary to perform a safety study administering PUR3100 to otherwise healthy patients with asthma before a NDA is submitted.

On September 26, 2022, the company announced the completion of patient dosing in a Phase 1 clinical study, performed in Australia, designed to assess not only safety, tolerability, and pharmacokinetics of PUR3100 in humans, but also provide preliminary comparative bioavailability data to support the use of the 505(b)(2) pathway for marketing authorization.

The study design was a double-dummy, double-blinded trial to assess the safety, tolerability, and pharmacokinetics of three dose levels of single doses of inhaled PUR3100 with IV placebo, as compared to IV DHE (DHE mesylate injection) with inhaled placebo. Twenty-six healthy subjects were enrolled and each of the four groups contained at least six subjects. On January 4, 2023, the company announced topline results. PUR3100 was well-tolerated and there was a lower incidence of nausea in PUR3100 dose groups compared to IV DHE.

The company plans to open an IND in the second quarter of 2023 in order to conduct a randomized placebo-controlled Phase 2 clinical study in patients with migraine to assess the safety and effectiveness of two doses of PUR3100, in which the selection of the two doses has been informed by the initial Phase 1 clinical study. The company anticipates that this Phase 2 clinical study will initiate once financing or partnership arrangements have been made.

PUR1800

RV1162, the active ingredient of PUR1800, is a novel, potent anti-inflammatory that inhibits the phosphorylation of a narrow spectrum of kinases. In pre-clinical studies, RV1162 demonstrated direct anti-inflammatory activity in a model of viral induced respiratory inflammation. RV1162 also demonstrated a reduction in corticosteroid-resistant inflammatory responses in a model of cigarette smoke induced inflammation. These findings suggested that RV1162 has the potential to deliver effective anti-inflammatory outcomes in corticosteroid-resistant patients while also reducing the underlying source of inflammation in an exacerbation, such as a viral and/or bacterial respiratory infection.

Clinical studies conducted by RespiVert/Janssen with RV1162 formulated as a lactose blend for inhalation demonstrated that the molecule was well tolerated for up to 14 days of dosing in patients with COPD. Analysis of sputum collected from patients with COPD treated with RV1162 showed reduced levels of p38 phosphorylation in sputum cells and decreases in the number of neutrophils recovered in sputum after 12 days of dosing. These findings suggest that inhalation of RV1162 may confer anti-inflammatory benefits after a short dosing regimen. Long-term toxicology studies with RV1162 as a lactose blend suggested that this formulation was not suitable for chronic dosing.

Based upon the clinical results generated by RespiVert/Janssen for RV1162 and the anticipated benefits of an iSPERSE formulation of RV1162, the company entered into a License, Development and Commercialization Agreement with RespiVert Ltd. (RespiVert), a wholly owned subsidiary of Janssen Biotech, Inc. on June 9, 2017. RespiVert granted the company an exclusive, royalty-bearing license in a portfolio of narrow spectrum kinase inhibitor compounds (NSKI). The company subsequently formulated RV1162 into PUR1800 for development as a potential therapy for AECOPD.

The company conducted two 28-day GLP toxicology studies in rats and dogs. Results from the two GLP toxicology studies supported the potential for PUR1800 to improve lung exposure, with reduced lung accumulation, as compared to RV1162 as a lactose blend formulation, suggesting potential for chronic dosing.

On December 26, 2019, the company entered into a License, Development and Commercialization Agreement (the JJEI License Agreement) with Johnson & Johnson Enterprise Innovation, Inc. (JJEI). Under the JJEI License Agreement, the company granted JJEI an option to acquire the company's rights to an intellectual property portfolio of materials and technology related to NSKI and an exclusive, worldwide, royalty bearing license to PUR1800. As part of the agreement, Pulmatrix was to complete chronic toxicology studies in rats and dogs, with durations of six and nine months, respectively. The company was also to complete a Phase 1b clinical trial in stable COPD patients. JJEI had the right to execute its option for licensure (option period) any time up to three months following the later of receipt of the final report for the clinical study, or receipt of the audited draft reports for the toxicology study. JJEI terminated the JJEI License Agreement effective July 6, 2021, prior to delivery of any data from the ongoing toxicology studies and ongoing Phase1b clinical study.

All rights to the kinase inhibitor portfolio, including PUR1800 and PUR5700, reverted back to the company along with all data generated from the ongoing studies predominantly funded through proceeds from the terminated JJEI License Agreement.

Clinical Development

The clinical study, performed at the Medicines Evaluation Unit in Manchester, UK, was a randomized, three-way crossover double-blind study with 14 days of daily dosing which includes placebo and one of two doses of PUR1800, and included a 28 day follow up period after each treatment period. A total of 18 adults with stable COPD were enrolled. Safety and tolerability, as well as systemic PK were evaluated.

The company completed the Phase 1b safety, tolerability, and pharmacokinetics of PUR1800 for patients with stable moderate-severe COPD. Topline data was delivered in the first quarter of 2022 and presented at the American Academy of Allergy, Asthma and Immunology conference in the first quarter of 2023. PUR1800 was well tolerated and there were no observed safety signals. The PK data indicate that PUR1800 results in low and consistent systemic exposure when administered via oral inhalation. The topline data, along with the results from chronic toxicology studies, support the continued development of PUR1800 for the treatment of AECOPD and other inflammatory respiratory disease. These data will inform the design of a potential Phase 2 study in the treatment of AECOPD.

Intellectual Property

Patents and Patent Applications

The company protects its intellectual property by filing and advancing patent applications and maintaining granted patents on its iSPERSE platform technology and in-licensed kinase inhibitors, which includes claims to compositions of matter and methods of use for its PUR1900, PUR3100, PUR1800 and other programs, as well as manufacturing processes, devices and packaging relevant to its iSPERSE platform and product candidates.

As of December 31, 2022, the company's patent portfolio related to iSPERSE included approximately 137 granted patents, 19 of which are granted U.S. patents, with expiration dates from 2024 to 2037, and approximately 49 additional pending patent applications in the U.S. and other jurisdictions. The company's in-licensed portfolio related to kinase inhibitors included approximately 276 granted patents, 32 of which are granted U.S. patents, with expiration dates from 2029 to 2035, and approximately 26 additional pending patent applications in the U.S. and other jurisdictions. On March 1, 2022, the company filed a patent treaty application that discloses and claims certain formulations and methods of use relevant to its PUR3100 program.

Trade Secrets

The company also relies on trade secret protection of its confidential and proprietary information, including the iSPERSE technology.

Research and Development

For the year ended December 31, 2022, the company's research and development expenses were approximately $18.2 million.

Government Regulation

In the United States, the company must follow rules and regulations established by the United States Food and Drug Administration (FDA) requiring the presentation of data indicating that its products are safe and efficacious and are manufactured in accordance with current Good Manufacturing Practices (cGMP) regulations.

History

Pulmatrix, Inc. was founded in 2003.