UNITED
STATES
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
FORM
10-K
(Mark
One)
For
the fiscal year ended December 31, 2025
or
For
the transition period from ___________ to __________
Commission
file number: 001-36199
PULMATRIX,
INC.
(Exact
name of registrant as specified in its charter)
(Address of principal executive offices) (Zip Code)
(888)355-4440
Registrant’s
telephone number, including area code
Securities
registered pursuant to Section 12(b) of the Exchange Act:
Title of each class Trading Symbol(s) Name of each exchange on which registered
Common Stock, par value $0.0001 per share PULM The Nasdaq Stock Market LLC
Securities
registered pursuant to Section 12(g) of the Exchange Act: None
Indicate
by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☐ No ☒
Indicate
by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Exchange Act. Yes ☐
No ☒
Indicate
by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange
Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2)
has been subject to such filing requirements for the past 90 days. Yes ☒ No ☐
Indicate
by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule
405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant
was required to submit such files). Yes ☒ No ☐
Indicate
by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting
company or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer”,
“smaller reporting company” and “emerging growth company” in Rule 12b-2 of the Exchange Act.
Large accelerated filer ☐ Accelerated filer ☐
Non-accelerated filer ☒ Smaller reporting company ☒
Emerging growth company ☐
If
an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying
with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act ☐
Indicate
by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness
of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered
public accounting firm that prepared or issued its audit report. Yes ☐ No ☒
If
securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant
included in the filing reflect the correction of an error to previously issued financial statements. ☐
Indicate
by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation
received by any of the registrant’s executive officers during the relevant recovery period pursuant to §240.10D-1(b). ☐
Indicate
by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes ☐ No ☒
The
aggregate market value of the registrant’s voting and non-voting common equity held by non-affiliates computed by reference to
the price at which the common equity was last sold, as of June 30, 2025, the last business day of registrant’s most recently completed
second fiscal quarter, was $25,200,594.
As
of February 23, 2026, the registrant had 3,652,285 shares of common stock, par value $0.0001 per share, issued and outstanding.
DOCUMENTS
INCORPORATED BY REFERENCE
None.
PULMATRIX,
INC.
TABLE
OF CONTENTS
Page No.
Forward-Looking Statements 1
PART I
Item 1. Business. 2
Item 1A. Risk Factors. 20
Item 1B. Unresolved Staff Comments. 54
Item 1C. Cybersecurity. 54
Item 2. Properties. 55
Item 3. Legal Proceedings. 55
Item 4. Mine Safety Disclosures. 55
PART II
Item 6. Reserved. 56
Item 7A. Quantitative and Qualitative Disclosures About Market Risk. 64
Item 8. Financial Statements and Supplementary Data. 64
Item 9A. Controls and Procedures. 65
Item 9B. Other Information. 66
Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections. 66
PART III
Item 10. Directors, Executive Officers and Corporate Governance. 67
Item 11. Executive Compensation. 74
Item 14. Principal Accountant Fees and Services. 77
PART IV
Item 15. Exhibits, Financial Statement Schedules. 79
Signatures 84
PART
I
Forward-Looking
Statements
This
Annual Report on Form 10-K contains forward-looking statements. All statements other than statements of historical fact contained herein,
including statements regarding our business plans or strategies, projected or anticipated benefits or other consequences of our plans
or strategies, projected or anticipated benefits from acquisitions to be made by us, or projections involving anticipated revenues, earnings,
or other aspects of our operating results, are forward-looking statements. Words such as “anticipates,” “assumes,”
“believes,” “can,” “could,” “estimates,” “expects,” “forecasts,”
“guides,” “intends,” “is confident that,” “may,” “plans,” “seeks,”
“projects,” “targets,” and “would,” and their opposites and similar expressions, as well as statements
in future tense, are intended to identify forward-looking statements. Forward-looking statements should not be read as a guarantee of
future performance or results and may not be accurate indications of when such performance or results will actually be achieved. Forward-looking
statements are based on information we have when those statements are made or our management’s good faith belief as of that time
with respect to future events and are subject to risks and uncertainties that could cause actual performance or results to differ materially
from those expressed in or suggested by the forward-looking statements. Important factors that could cause such differences include,
but are not limited to:
● adverse market and economic conditions;
● loss of one or more key executives; and
For
a more detailed discussion of the risks that may affect our business and that could cause our actual results to differ from those projected
in these forward-looking statements, see the risk factors and uncertainties described under the heading “Risk Factors” in
Part I, Item 1A of this Annual Report on Form 10-K. The forward-looking statements contained in this Annual Report on Form 10-K are expressly
qualified in their entirety by this cautionary statement. We do not undertake any obligation to update any forward-looking statement
to reflect events or circumstances after the date on which any such statement is made or to reflect the occurrence of unanticipated events,
except as required by law.
Unless
otherwise stated, references in this Annual Report on Form 10-K to “us,” “we,” “our,” or “Company”
refer to Pulmatrix, Inc., a Delaware corporation, and its subsidiaries, Pulmatrix Operating Company, Inc. and PCL Merger Sub, Inc., both
Delaware corporations.
“iSPERSETM”
is one of our trademarks used in this Annual Report on Form 10-K. Other trademarks appearing in this report are the property of their
respective holders. Solely for convenience, these and other trademarks, trade names and service marks referred to in this report appear
without the ®, TM and SM symbols, but those references are not intended to indicate, in any way, we or the owners of such
trademarks will not assert, to the fullest extent under applicable law, their rights to these trademarks and trade names.
ITEM 1. BUSINESS.
Overview
We
are a biopharmaceutical company that has focused on the development of novel inhaled therapeutic products intended to prevent and treat
migraine and respiratory diseases with important unmet medical needs using our patented iSPERSETM technology. Our proprietary
product pipeline includes treatments for central nervous system (“CNS”) disorders such as acute migraine and serious lung
diseases such as Chronic Obstructive Pulmonary Disease (“COPD”) and allergic bronchopulmonary aspergillosis (“ABPA”).
Our product candidates are based on our proprietary engineered dry powder delivery platform, iSPERSETM, which seeks to
improve therapeutic delivery to the lungs by optimizing pharmacokinetics and reducing systemic side effects to improve patient outcomes.
We
design and develop inhaled therapeutic products based on our proprietary dry powder delivery technology, iSPERSETM, which
enables delivery of small or large molecule drugs to the lungs by inhalation for local or systemic applications. The iSPERSETM
powders are engineered to be small, dense particles with highly efficient dispersibility and delivery to airways. iSPERSETM
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. We believe the iSPERSETM dry powder technology offers enhanced drug loading
and delivery efficiency that outperforms traditional lactose-blend inhaled dry powder therapies.
We
were incorporated in 2013 as a Delaware corporation.
After
a comprehensive review of strategic alternatives, including identifying and reviewing potential candidates for a strategic transaction,
on November 13, 2024, we entered into the Agreement and Plan of Merger and Reorganization, as amended by Amendment No. 1 (“Amendment
No. 1”) thereto on April 7, 2025 (as amended by Amendment No. 1, the “Merger Agreement”), pursuant to which, among
other matters, PCL Merger Sub, Inc., our direct wholly owned subsidiary, will merge with and into Cullgen Inc. (“Cullgen”),
with Cullgen surviving as our wholly owned subsidiary and the surviving corporation of the merger (the “Merger”). The Merger
Agreement was unanimously approved by our board of directors, which resolved to recommend approval of the Merger Agreement to our stockholders.
On
June 16, 2025, we held a special meeting in lieu of the annual meeting of Pulmatrix stockholders, at which special meeting our stockholders
approved the Merger and related proposals. The Closing is subject to other customary closing conditions, including Nasdaq’s approval
of the listing of the shares of Pulmatrix common stock to be issued in connection with the Merger and approval from the China Securities
Regulatory Commission (“CSRC”) pursuant to the Trial Administrative Measures of Overseas Securities Offering and Listing
by Domestic Enterprises (the “Trial Measures”), No. 1 to No. 6 Supporting Guidance Rules, the Notice on Administration Arrangements
for the Filing of Overseas Listings by Domestic Enterprises and the relevant CSRC Answers to Reporter Questions on the official website
of the CSRC. These regulations established a filing-based regime to regulate overseas offerings and listings by Chinese domestic companies.
As of the date of this filing, we have not yet received approval from the CSRC to complete the Merger. As previously disclosed, on August
1, 2025, we and Cullgen, as provided for in the Merger Agreement, mutually agreed to extend the “End Date”, a term defined
in the Merger Agreement, by 60 days from August 13, 2025, to October 12, 2025. The Merger Agreement does not have a defined term and
does not terminate on the “End Date”. The “End Date” is simply the date at which certain termination options
become available to either party.
On
December 17, 2025, the Company, Cullgen and PLC Merger Sub, Inc. (collectively, the “Parties”) entered into a mutual waiver
agreement (the “Waiver Agreement”), pursuant to which the Parties agreed to mutually waive compliance with Section 5.4 of
the Merger Agreement, which such provision imposes restrictions on each party during the Pre-Closing Period (as defined in the Merger
Agreement). Except as expressly waived pursuant to the Waiver Agreement, the Merger Agreement continues to remain in full force and effect
in all respects, and no other provision of the Merger Agreement has otherwise been amended, waived, or modified.
If
the Merger is completed, the business of Cullgen will continue as the business of the combined company. We are currently seeking opportunities
to monetize iSPERSETM and our existing clinical assets.
Our
future operations are highly dependent on the success of the Merger and there can be no assurances that the Merger will be successfully
consummated. There can be no assurance that the strategic review process or any transaction relating to a specific asset, including the
Merger and any asset sale, will result in us pursuing such a transaction, or that any transactions, if pursued, will be completed on
terms favorable to us and our stockholders in the existing Pulmatrix entity or any possible entity that results from a combination of
entities. If the strategic review process is unsuccessful, and if the Merger is not consummated, the Pulmatrix board of directors may
decide to pursue a dissolution and liquidation of the Company.
Business
Strategy
Our
goal has been to develop breakthrough therapeutic products that are safe, convenient, and more effective than the existing therapeutic
products for respiratory and other diseases where iSPERSETM properties are advantageous.
Our
current pipeline of clinical assets is aligned to this goal and includes iSPERSETM-based therapeutic candidates, which target the
prevention and treatment of a range of diseases, including CNS disorders and pulmonary diseases. These therapeutic candidates include
PUR3100 for the treatment of acute migraine, PUR1800 for the treatment of acute exacerbations of chronic obstructive pulmonary disease
(“AECOPD”), and PUR1900 for the treatment of ABPA in patients with asthma and in patients with cystic fibrosis. Each program
is enabled by its unique iSPERSETM formulation designed to achieve specific therapeutic objectives.
In
connection with the Merger, we are exploring opportunities to monetize these clinical assets and have paused the development of these
product candidates. Continued development of these candidates, if that were to occur, would be contingent on securing additional funding
and would require significant expenditures to advance. Thereafter, if development of such product candidates were to be continued and
successfully advanced (of which there can be no assurance), it would be necessary to seek and obtain marketing approval to commercialize
such product candidates, which could be expected to require the expenditure of significant additional resources and expenses related
to regulatory, product sales, medical affairs, marketing, manufacturing and distribution.
Contingent
on securing additional funding and continuing development of these candidates, we would expect to continue to incur substantial expenses
and operating losses for at least the next several years, as we would:
iSPERSETM
Technology
We
use 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. Our initial delivery platform emerged from development
of iCALMTM (inhaled Cationic Airway Lining Modulators), a non-steroidal anti-inflammatory therapy. The high degree of
aerosol efficiency and the density profile of our dry powder iCALMTM formulations provided the foundation for our development
of iSPERSETM in 2012, which uses other monovalent and divalent salts.
iSPERSETM
particles are engineered with a small, dense and dispersible profile to exceed the performance of traditional dry powder particles
as the iSPERSETM particles have the dispersibility advantages of porous engineered particles. We believe this
results in superior drug delivery compared to traditional oral and injectable forms of treatment for certain diseases. Unlike lactose-blended
carrier formulations or low-density particles which disperse poorly, we believe that the iSPERSETM technology
platform offers several potential benefits, achieved through the following technological innovations:
iSPERSETM
particles can be engineered to include concentrations from less than one percent (1%) to greater than eighty percent (80%)
active pharmaceutical ingredients (“APIs”), which allows flexibility for dosing both high potency and high-drug load therapeutics.
● Superior flow rate independent lung delivery without carriers.
The
iSPERSETM technology enables pulmonary delivery independent of lactose or other carriers, which results in significantly
greater lung dose at a matched nominal dose of conventional lactose-based formulations. iSPERSETM formulations
are dispersible across a range of flow rates with consistent emitted dose and particle size. Performance across flow rates provides reliable
dose delivery across patient populations and reduces patient-to-patient variability.
● Delivery of macromolecules and biologics.
iSPERSETM
powders can be used with an array of dry powder inhaler technologies and can be formulated with a broad range of therapeutic
compounds ranging from small molecules to proteins for both local and systemic drug delivery applications.
● Homogenous combinations of multiple drugs.
iSPERSETM
creates homogenous particles including excipients and API, which allow for the consistent delivery of multiple APIs in a product.
We have successfully formulated iSPERSETM-based products with dual and triple API combinations.
● Strong safety profile.
Current
iSPERSETM products and planned clinical-stage products to be formulated in iSPERSETM are
supported by robust preclinical safety profiles. iSPERSETM excipients include those with inhalation precedent
and those that are generally regarded as safe by other routes of administration.
Therapeutic
Candidates
PUR3100
PUR3100 is still an investigational drug candidate and not authorized for commercialization, but we
are currently exploring other opportunities to monetize PUR3100.
In
2020, we developed PUR3100, the iSPERSETM formulation of DHE, for the treatment of acute migraine. Currently DHE is only
available as subcutaneous, intravenous infusion or intranasal delivery. If approved for commercialization, PUR3100 has the opportunity
to be the first orally inhaled DHE treatment for acute migraine and an alternative to other acute therapies. Given the oral inhaled route
of delivery, PUR3100 is anticipated to provide rapid relief from migraine symptoms and provide a favorable tolerability profile.
Competition
and Market Opportunities
The
American Migraine Foundation estimates that at least 39 million people in the United States and 1 billion people worldwide live with
migraine, but because many people are not diagnosed or do not receive the treatment they need, the actual number may be higher. Current
treatments for migraine include oral, intranasal, IV or subcutaneous formulations of triptans, DHE, and calcitonin gene-related peptide
(“CGRP”) antagonists (gepants). Studies show that people with migraines are underdiagnosed, undertreated, and experience
substantial decreases in functioning and productivity, which translates into diminished quality of life for individuals and financial
burdens to patients, healthcare systems, and employers. All current treatments are limited by incomplete efficacy and/or intolerability.
Therefore, development of additional treatments for acute migraine is warranted.
DHE
has been shown to be effective in the treatment of migraine and, in particular, hard to treat migraines, such as menstrual migraine,
migraine upon awakening, and severe migraine. Utilization of DHE has been limited due to its poor oral bioavailability, requiring IV,
subcutaneous or intranasal dosing. IV dosing generally requires administration in a healthcare setting and may result in nausea and vomiting.
Hence, its use has generally been limited to patients with intractable or medication-overuse migraine. In May 2025, the FDA approved Brekiya (Amneal Pharmaceuticals, Inc.), a subcutaneous DHE autoinjector for acute treatment
of migraine with or without aura and cluster headaches in adults. Intranasal dosing with DHE, including
Migranal (Bausch Health US LLC), approved in December 1997, and Trudhesa (Impel NeuroPharma, Inc.), approved by the FDA in September
2021, have been poorly adopted due to incomplete efficacy and intolerability of nasal inhalation in patients during a migraine.
There
is precedent for an orally inhaled DHE therapy. MAP Pharmaceuticals, Inc. developed MAP0004, also known as Levadex or Semprana, a liquid
suspension formulation of DHE, designed to be dosed via a breath-actuated pMDI inhalation device. Their published data indicate a safe
and well tolerated formulation with rapid onset and long-lasting efficacy that compared favorably to existing treatments. Development
of MAP0004 led to a new drug application (“NDA”) but was halted after multiple complete response letters from the FDA citing
Chemistry, Manufacturing and Controls (“CMC”) issues related to dose uniformity and stability issues. Regardless of the failure
of MAP0004, the efficacy and tolerability of the formulation reported by MAP Pharmaceuticals provides proof of concept for an orally
inhaled DHE formulation. PUR3100, the iSPERSETM formulation planned by Pulmatrix, is anticipated to deliver DHE
to the lung with efficacy and tolerability that compares favorably with MAP0004, while avoiding the device-related issues of MAP0004
by delivering PUR3100 as an iSPERSETM dry powder.
We
believe that an iSPERSE formulation of DHE can provide the positive rapid onset and long-lasting efficacy seen in the MAP0004 data by
enabling a similar pharmacokinetic profile while eliminating the manufacturing and device issues which led to the MAP0004 FDA complete
response letters.
Aspeya,
Inc. (“Aspeya”), a subsidiary of Philip Morris International, Inc. and formerly known as Vectura Fertin Pharma, Inc., is
developing a drug-device combination product for the pulmonary delivery of an inhaled dry-powder formulation of DHE for the acute treatment
of migraines in adults. Aspeya completed a Phase 1 clinical trial in New Zealand in 2024, later announcing the treatment was assessed
safe, well-tolerated and supporting further clinical development. Aspeya later completed a Phase 1 clinical trial in 2025 (NCT07226362),
with results pending. To the best of our knowledge, there are no other orally inhaled DHE formulations currently in development or on
the market.
Migranal,
Trudhesa and Atzumi are currently FDA approved intranasal formulations of DHE. While Migranal and Trudhesa are nasal liquid sprays, Atzumi
is a nasal powder formulation. Satsuma Pharmaceuticals, a subsidiary of Shin Nippon Biomedical Laboratories (“Satsuma”),
gained FDA approval during 2025 for Atzumi for acute treatment of migraine.
Non-Clinical
Development
A
total of three 14-day GLP toxicology studies have been completed with PUR3100 to support single-dose clinical studies. We are planning
to conduct a chronic toxicology study to support long-term dosing. Based on discussions with the FDA, this would complete the non-clinical
requirements to support an NDA.
Clinical
Development
All U.S. clinical development is currently on hold
while we work to license or monetize this asset.
Our
interactions with the FDA have indicated that, as part of 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 an NDA is submitted.
On
September 26, 2022, we announced the completion of patient dosing in a Phase 1 clinical study, performed in Australia. 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. This study may also provide
preliminary comparative bioavailability data to support the use of the 505(b)(2) pathway for marketing authorization. Twenty-six healthy
subjects were enrolled and each of the four groups contained at least six subjects.
On
January 4, 2023, we announced topline results. We presented the Phase 1 study data at the American Headache Society 65th Annual Meeting
in June 2023. The study showed that PUR3100 achieved peak exposures in the targeted therapeutic range and time to maximum concentration
occurred at five minutes after dosing at all dosing levels. The PUR3100 dose groups also showed a lower incidence of nausea and no vomiting
compared to observations of nausea and vomiting in the IV administered DHE dose group.
Based
on the rapid systemic exposure in the therapeutic range and the improved side effect profile relative to IV dosing, we believe the PUR3100
formulation of DHE may differentiate from approved DHE products or those known to be in development. If effectiveness is demonstrated,
PUR3100 may offer the convenience of being self-administered with a pharmacokinetic profile that may potentially provide rapid onset
of action.
In
September 2023, we announced that the FDA accepted the PUR3100 IND and the receipt of a “study may proceed” letter for the
clinical study: “A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Single Event Study to Evaluate the Safety,
Tolerability, and Efficacy of PUR3100 (Dihydroergotamine Mesylate Inhalation Powder) in the Acute Treatment of Migraine”. We anticipate
that this Phase 2 clinical study will initiate once financing or partnership arrangements have been made.
On
May 15, 2024, we announced publication of, “Safety, tolerability, and pharmacokinetics of a single orally inhaled dose of PUR3100,
a dry powder formulation of dihydroergotamine versus intravenous dihydroergotamine: A Phase 1 randomized, double-blind study in healthy
adults” in the peer-reviewed publication Headache: The Journal of Head and Face Pain.
We
believe that in this trial, PUR3100 demonstrated the potential for rapid pain relief and improved DHE tolerability versus IV DHE. With
a Tmax of 5 minutes and a Cmax in the therapeutic window for all doses tested, we believe that PUR3100 has the
potential to address an unmet need for acute migraine sufferers and we are pursuing different options to advance PUR3100 into a Phase
2 clinical trial to further investigate its promising profile in treating acute migraine.
The
completed Phase 1 study demonstrated optimal pharmacokinetics and improved tolerability of PUR3100 compared to IV DHE. All doses of PUR3100
were generally well tolerated with a lower incidence of nausea (21% vs. 86%), vomiting (0% vs. 29%), and headache (16% vs. 57%) compared
to IV DHE. The PK profile of PUR3100 versus IV DHE was characterized by a similar mean time to Cmax (5 vs. 5.5 min), with
reduced AUC0–2h (1120–4320 vs. 6340 ng*h/mL), and a lower Cmax (3620–14,400 vs. 45,000 ng/mL).
All doses of PUR3100 were associated with mean Cmax above the minimum level required to achieve efficacy (1000 pg/mL).
PUR1800
PUR1800 is still an investigational drug candidate and not authorized for commercialization, but we
are currently exploring other opportunities to monetize PUR1800.
PUR1800
is a Narrow Spectrum Kinase Inhibitor, engineered with our iSPERSETM technology, with a target indication for the treatment of
acute exacerbations in chronic obstructive pulmonary disease (AECOPD). PUR1800 targets p38 MAP kinases (p38MAPK), Src kinases, and Syk
kinases. These kinases play a critical role in chronic inflammation and airway remodeling.
Reduced
responsiveness to corticosteroids represents an important barrier to effective treatment of COPD and AECOPD and provides a clear rationale
to seek novel medicines to treat these respiratory diseases. In addition, current treatments generally fail to treat the underlying source
of the AECOPD, in particular when a viral or bacterial infection is the cause, which occurs in approximately 80% of exacerbations. 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 iSPERSETM
formulation of RV1162, we 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 us an exclusive, royalty-bearing license in a portfolio
of narrow spectrum kinase inhibitor compounds (“NSKI”). We subsequently formulated RV1162 into PUR1800 for development as
a potential therapy for AECOPD. In January 2026, we provided RespiVert notice that, pursuant to our agreement, we are exercising our
option to abandon the prosecution of certain individual RespiVert patents. We do not consider these patents to be necessary to support
PUR1800 at this time.
Competition
and Market Opportunities
There
are 18 million moderate-to-severe episodes of AECOPD in the US each year. AECOPD 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. 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.
Steroids
are standard of care for moderate-to-severe acute exacerbations, which occur across all patient severity types. We believe a substantial
unmet need exists in AECOPD for those patients with underlying infection and/or steroid resistance. Acumapimod (BCT-197) is an oral p38
MAP kinase inhibitor being developed by Mereo BioPharma. BCT-197 completed Phase 2 development as first-line therapy for severe AECOPD.
In April 2019, Mereo BioPharma announced completion of an end of Phase 2 meeting with the FDA and stated the company is continuing discussions
with potential partners for BCT-197. We are not aware of any further progress in either clinical development or partnership efforts on
this product. A generic version of roflumilast, a phosphodiesterase inhibitor approved by the FDA for use in managing COPD exacerbations,
became available in 2022.
Non-Clinical
Development
We
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.
Toxicology
studies in rats and dogs, with durations of six and nine months respectively, are complete. The data from both studies demonstrated
that PUR1800 is safe and well tolerated with chronic dosing, with little to no progression of findings from 28-day studies. We
believe that this indicates potential for chronic dosing of PUR1800, enabling us to explore PUR1800 therapy for chronic respiratory
diseases such as steroid resistant asthma, COPD, or idiopathic pulmonary fibrosis. While the program is currently in development for
treatment of acute exacerbation of COPD, these positive toxicology study results could expand potential indications and value of the
program. In 2024, Pulmatrix published an abstract titled “Ex vivo evaluation of the potential for Narrow Spectrum Kinase
inhibitors as a treatment for Idiopathic Pulmonary Fibrosis”.
Clinical
Development
All clinical development is currently on hold while
we work to license or monetize this asset.
We
completed a Phase 1b safety, tolerability, and pharmacokinetics of PUR1800 in patients with stable moderate-severe COPD. Topline data
were 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.
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 included 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 pharmacokinetics
(“PK”) were evaluated.
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 diseases. These data will inform the
design of a potential Phase 2 study in the treatment of AECOPD.
PUR1900
PUR1900 is still an investigational drug candidate and not authorized for commercialization, but we
are currently exploring other opportunities to monetize PUR1900 within the United States.
PUR1900
is our iSPERSETM inhaled formulation of itraconazole, an antifungal drug commercially available as an oral drug. We
developed PUR1900 for the prevention and potential 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. Aspergillus colonization and infections are likely underdiagnosed and
occur frequently in patients of all ages. Colonization and infection with Aspergillus can lead to clinical disease with
differing severities and complications depending on the immune status of the host. Invasive aspergillosis is a frequently fatal
disease that occurs in patients that are typically immune suppressed as a result of treatment for hematologic cancers or
immunosuppression prior to solid organ transplantation. In patients with asthma and CF, Aspergillus can cause chronic
infections that may be associated with worsening disease and larger declines in lung function than patients without infection. A
subset of patients with asthma and CF with Aspergillus colonization and/or infection develop ABPA, which is a complex
hypersensitivity reaction to fungal antigens. ABPA is a disease resulting in mucus production, wheezing, pulmonary infiltrates,
worsening bronchiectasis, and fibrosis of the lung.
In
patients with both asthma and CF, ABPA is commonly treated with oral steroids to treat inflammation and with oral antifungals to reduce
fungal infection. The inhalation administration of a drug affords direct delivery of the drug to the infected parts of the lung, maximizing
the dose to the affected sites and minimizing systemic exposure to the rest of the body where it could cause dose-limiting side effects.
Therefore, treatment of lung infections by direct administration of anti-infective products to the lung may improve both the safety and
efficacy of treatment compared to systemic administration by other routes, as well as improving patient convenience as compared to oral
and injectable forms of the treatment. We believe that local lung delivery by inhalation of our iSPERSETM formulation
could provide convenient, effective and safe management of the debilitating and often life-threatening lung infections that are not currently
addressed by inhaled therapies.
Competition
and Market Opportunities
Current
treatments of pulmonary fungal infections highlight the limitations of oral or intravenous anti-infective treatments for lung infections.
Itraconazole is one of the most commonly prescribed therapies for treating Aspergillus infections in patients with asthma and
CF. Itraconazole is available commercially as Sporanox® in both a capsule and oral solution form. Itraconazole is metabolized
in the liver by CYP3A4 and coadministration with a large number of drugs is contraindicated due to the potential for severe drug-drug
interactions.
We
have demonstrated that PUR1900 achieves higher local lung itraconazole concentrations with lower systemic exposure relative to oral dosing,
thus allowing for the potential to improve upon both the efficacy and safety profiles observed with oral itraconazole. Furthermore, administration
by inhalation reduces the exposure of the drug in the rest of the body, which may be beneficial in reducing systemic side effects and
the risk of potentially toxic drug-drug interactions.
There
is precedent for both dry powder and nebulized inhaled anti-infective therapy to address specific pulmonary infections in patients which
demonstrates potential utility of inhaled drug delivery and market opportunity. Mylan currently markets TOBI Podhaler for treatment of
Pseudomonas aeruginosa infection in the United States and Teva markets inhaled colistin, Colobreathe, for the same infection in
Europe. Insmed currently markets Amikacin Liposome Inhalation Suspension (Arikayce) in the United States for the treatment of lung disease
caused by a group of bacteria, Mycobacterium avium complex in a limited population of patients with the disease who do not respond
to conventional treatment (refractory disease). There are currently no products specifically approved for treatment of ABPA, however,
there are several inhaled antifungal agents currently under development for the treatment of invasive aspergillosis or ABPA. Treatments
under development for invasive aspergillosis include PC945, a novel azole antifungal being developed by Pulmocide as a liquid for nebulization
prior to the termination of their Opera-T Phase 3 study with Opelconazole based on an interim analysis data. In addition, a dry powder
formulation of voriconazole was previously being developed by TFF Pharmaceuticals prior to announcing dissolution in 2025. In principle,
development of an orally inhaled antifungal for the treatment of invasive aspergillosis could also be effective for ABPA but would require
additional clinical studies in the target patient population. Zambon has also developed a dry powder formulation of voriconazole for
the treatment of ABPA and completed a Phase 1 study in the third quarter of 2020. However, no additional development has since been reported.
Regeneron Pharmaceuticals completed a clinical trial in 2024 with dupilumab (NCT04442269) for the treatment of ABPA in asthma. This trial
focused on prevention of exacerbations in individuals with at least one or more severe respiratory exacerbations. In 2025, Regeneron
announced dupilumab significantly improved lung function and substantially reduced severe exacerbations while enhancing quality of life
in patients with ABPA during the treatment period.
New
methods to detect Aspergillus infection in sputum have improved the sensitivity of diagnosis and clinical appreciation for these
infections. Pulmonary Aspergillus infections affect approximately 14 million patients worldwide according to the Global Action
Fund for Fungal Infections (Improving Outcomes for Patients with Fungal Infections across the World: A Road Map for the Next Decade).
The majority of these cases occur in patients with asthma who have allergic disease and also include invasive Aspergillus infections
that are associated with a high rate of mortality in immunocompromised patients. We believe that PUR1900 compares favorably to the products
discussed above and has the potential to generate substantial value based on treating and preventing pulmonary fungal infections in multiple
patient populations.
Clinical
Development
All clinical development is currently on hold while
our partner, Cipla, has completed a Phase 2 trial and is approved to proceed to a Phase 3 trial, both in India.
We
completed a Phase 1/1b clinical study in 2018, wherein 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). Lung exposure, as measured by sputum induction and
analysis, was approximately 50-fold higher and plasma exposure was approximately 85-fold lower following inhalation of 20 mg of PUR1900
compared to 200 mg of oral Sporanox®. All endpoints from the Phase 1/1b clinical study were successfully met.
Successful
completion of the Phase 1/1b clinical study enabled us to initiate a Phase 2 clinical study in 2019, entitled: “A Randomized, Double-Blind,
Multicenter, Placebo-Controlled, Phase 2 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Itraconazole Administered
as a Dry Powder for Inhalation (PUR1900) in Adult Asthmatic Patients with ABPA.” This clinical study was terminated in July 2020
due to the impact of the COVID-19 pandemic on patient enrollment and clinical study conduct. The completion of a 6-month inhalation toxicology
study in dogs in 2020 enabled the conduct of a new Phase 2b clinical study.
The
new Phase 2b study included a 16-week dosing regimen and exploration of potential regulatory approval endpoints. We dosed the first patient
during the first quarter of 2023. In January 2024, pursuant to the Third Amendment (as defined herein), we announced plans to stop patient
enrollment at 8 subjects in this study, effective immediately, and to terminate the study as soon as reasonably possible between the
date of the Third Amendment and July 30, 2024. We completed all Phase 2b wind down activities in the third quarter of 2024. As such,
we no longer bear further financial responsibility for the commercialization and development with respect to the Product in the Cipla
Territory, with such commercialization and development expenses of the Product in the Cipla Territory to be borne at Cipla’s sole
cost and expense after January 6, 2024.
Business
Development
PUR3100
We
are currently exploring opportunities to monetize PUR3100.
In
September 2023, we announced the FDA’s acceptance of an IND application for PUR3100 and receipt of a “study may proceed”
letter for a Phase 2 study. The IND includes a Phase 2 clinical protocol where safety and preliminary efficacy of PUR3100 will be investigated
in patients with acute migraine.
PUR1800
We
are currently exploring opportunities to monetize PUR1800.
We
completed a Phase 1b safety, tolerability, and pharmacokinetics clinical study of PUR1800 for subjects with stable moderate-severe COPD
and received topline data from the Phase 1b clinical study in the first quarter of 2022. We analyzed data from the completed Phase 1b
clinical study of PUR1800 for AECOPD and presented study results at the American Academy of Allergy, Asthma & Immunology (AAAAI)
conference in the first quarter of 2023. The results indicated PUR1800 was safe and well tolerated with no observed safety signals. 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 diseases.
PUR1900
We
are currently exploring opportunities to monetize PUR1900 within the United States.
On
April 15, 2019, we entered into a Development and Commercialization Agreement (the “Cipla Agreement”) with Cipla for the
co-development and commercialization, on a worldwide, except for the Cipla Territory defined below, exclusive basis, of PUR1900, our
inhaled iSPERSETM 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. We entered into an amendment to the Cipla Agreement on November 8, 2021 (the “Second Amendment”) and a subsequent
amendment on January 6, 2024 (the “Third Amendment”). All references to the Cipla Agreement herein refer to the Cipla Agreement,
as amended. The Cipla Agreement will remain in effect in perpetuity, unless otherwise earlier terminated in accordance with its terms.
Pursuant
to the Third Amendment, all development and commercialization activities with respect to the Product in all markets other than the United
States (the “Cipla Territory”) will be conducted exclusively by Cipla at Cipla’s sole cost and expense, and Cipla shall
be entitled to all profits from the sale of the Product in the Cipla Territory, except that we will receive 2% royalties on any potential
future net sales by Cipla outside the United States.
Also
pursuant to the Third Amendment, we and Cipla stopped patient enrollment for the ongoing Phase 2b clinical study. We agreed that during
the period commencing on January 6, 2024 and ending July 30, 2024 (the “Wind Down Period”), we would complete all Phase 2b
activities, assign or license all patents to Cipla and their registration with the appropriate authorities in the Cipla Territory, complete
a physical and demonstrable technology transfer and secure all data from the Phase 2b study for inclusion in the safety database for
the Cipla Territory.
For
the duration of the Wind Down Period, we and Cipla were each responsible for 60% and 40%, respectively, of our Direct Costs. We shared
all other development costs with Cipla that are not Direct Costs, such as the cost of clinical research organizations, manufacturing
costs and other third-party costs, on a 50/50 basis. Reimbursements from Cipla to us for these costs were subject to a maximum reimbursement
amount as approved by the joint steering committee.
We
completed all Phase 2b wind down activities in the third quarter of 2024. As such, we no longer bear further financial responsibility
for the commercialization and development with respect to the Product in the Cipla Territory, with such commercialization and development
expenses of the Product in the Cipla Territory to be borne at Cipla’s sole cost and expense after January 6, 2024.
Our
partner Cipla has continued clinical development outside the United States and India’s Central Drug Standard Control Organization
has accepted Cipla’s Phase 2 clinical trial results for inhaled itraconazole dry powder formulation and approved the company’s
proposal to proceed with Phase 3 trials. Should Cipla successfully market PUR1900 outside the United States, Pulmatrix will receive 2%
royalties on any potential future net sales by Cipla outside the United States. Within the United States, we and Cipla will seek to monetize
PUR1900 for indications where an orally inhaled antifungal may provide a therapeutic benefit or fulfill an unmet medical need.
Intellectual
Property
Patents
and Patent Applications
We
protect our intellectual property by filing and advancing patent applications and maintaining granted patents on our iSPERSETM
platform technology and in-licensed kinase inhibitors, which includes claims to compositions of matter and methods of use for
our PUR3100, PUR1800, PUR1900 and other programs, as well as manufacturing processes, devices and packaging relevant to our iSPERSETM
platform and product candidates.
The
status of our patent portfolio changes frequently in the ordinary course of patent prosecution. As of December 31, 2025, our patent portfolio
related to iSPERSETM included approximately 149 granted patents, 18 of which are granted US patents, with expiration
dates from 2026 to 2043, and approximately 48 additional pending patent applications in the US and other jurisdictions. Our in-licensed
portfolio related to kinase inhibitors included approximately 284 granted patents, 33 of which are granted US patents, with expiration
dates from 2029 to 2035, and approximately 11 additional pending patent applications in the US and other jurisdictions. We have national
phase applications pending in Australia, Brazil, Canada, China, Europe, Israel, India, Japan, Korea, Mexico, New Zealand, Russia, Hong
Kong and the United States that cover certain formulations and methods of use relevant to our PUR3100 program.
There
can be no assurance that the patent applications will be granted. The term of individual patents depends upon the legal term of the patents
in the countries in which they are obtained. In most countries in which we file, the patent term is 20 years from the earliest date of
filing a non-provisional patent application. In the United States, the patent term of a patent that covers a FDA-approved drug may also
be eligible for patent term extension, which permits patent term restoration as compensation for the patent term lost during the FDA
regulatory review process. The length of the patent term extension is related to the length of time the drug is under regulatory review.
Patent term extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval and only