Our
Pipeline

Pipeline

Pulmatrix is developing
transformational inhaled
therapies for patients
with pulmonary disease,
both rare and common

PUR1800
NSKI

INDICATION: Acute Exacerbations in Chronic Obstructive Pulmonary Disease (AECOPD)

PUR3100
DHE

INDICATION: Acute Migraine

PULMAZOLE*
Anti-fungal
(Cipla Partnership)

INDICATION: Allergic Bronchopulmonary Aspergillosis (ABPA)
in Patients witrh Asthma

FEND*
(NasoCalm)

Pulmatrix licensed NasoCalm formulations (PUR003 and PUR006), now re-branded as FEND, to Sensory Cloud in April 2020

1. Out-license to Sensory Cloud
POC - Proof of Concept

PUR3100

PUR3100

PUR3100 is orally inhaled dihydroergotamine (DHE) engineered with iSPERSE™ for the acute treatment of migraine

  • PUR3100 will be studied as an orally-inhaled acute migraine therapy. The Phase 1 study start is anticipated in Q2 2022 with data expected in Q3 2022
  • The Ph1/Ph2 study will evaluate PUR3100 safety and pharmacokinetics, as well as effectiveness of different doses in the treatment of acute migraine. The study results are expected to enable Phase 3 efficacy trials

As an orally inhaled DHE therapy, PUR3100 has potential advantages:

Fast pain relief within 15 to 30 minutes

Fast acting pain relief (15 to 30 min)
—Fast onset of action through early Tmax with sustained target engagement1

Efficacy when taken any time during a migraine

Effective when taken at any time during a migraine
—Migraine upon awakening and rescue for breakthrough migraine

Long-lasting relief

Long lasting relief
—24+ hour headache relief through sustained target engagement2,3

Ease of dosing

Ease of dosing
—Oral inhalation therapy vs intranasal, with a convenient device and administration

Minimal impact on regular daily activities

Minimal impact on patient’s regular activities
—Absence of nausea, lethargy, medication overuse, and dysgeusia4

In a Phase 3 trial, inhaled DHE (MAP0004, Allergan) showed significant pain freedom by 30 min but was denied FDA approval due to manufacturing/device issues. Formulated with iSPERSE™, PUR3100 mitigates the manufacturing/device issues with MAP0004.

In a pharmacokinetic study in dogs
PUR3100 SHOWED
similar plasma
concentrations
to MAP0004
In a pharmacokinetic study in dogs PUR3100 SHOWED similar plasma concentrations to MAP0004

PUR3100 has the potential to deliver significant pain
freedom at 15 to 30 min
vs ~1 hour for triptan and ~2 hours for
calcitonin gene-related peptide (CGRP)2,5

PUR3100 has the potential to deliver significant pain freedom at 15 to 30 min vs ~1 hour for triptan and ~2 hours  for calcitonin gene-related peptide (CGRP)

FAST FACTS:
MIGRAINE AND THE ONGOING NEED FOR ACUTE TREATMENT OPTIONS

  • >38 million people in the US suffer from migraine attacks; migraine sufferers typically experience 1 to 2 migraines each month and account for 1.2 million emergency room visits each year6
  • Migraines account for 150 million lost work days in the US each year6
  • 75% of patients with diagnosed migraine cannot obtain relief from current Rx medications and go untreated, leaving 19 million people in the US without effective Rx migraine relief6
  • Of the 5 million people currently on Rx therapy, 50% require acute care for breakthrough pain and up to 79% are seeking better treatment options6

What do migraine
sufferers want?

  • Fast pain relief within
    15 to 30 minutes
  • Efficacy when
    taken any time
    during a migraine
  • Long-lasting relief
  • Ease of dosing
  • Minimal impact on
    regular daily activities

PULMATRiX is currently developing PUR3100 to
meet acute treatment needs in migraine.

PULMATRiX is currently developing PUR3100 to meet acute treatment needs in migraine.

PulmazolE

Pulmazole is the antifungal itraconazole, engineered
with iSPERSE to overcome issues with oral administration

Itraconazole is available as an oral formulation, Sporanox®, which may negatively impact efficacy due to poor lung exposure and create tolerability and safety issues due to high plasma exposure.7,8

Pipeline ChartPipeline Chart

Pulmazole™ is currently in a Phase 2 trial for
the treatment of ABPA in patients with asthma.

Learn more at clintrials.gov

FAST FACTS:
ABPA and the Unmet Need for Additional Treatment Options

ABPA is an exaggerated response of the immune system to the fungus Aspergillus
in patients with asthma and cystic fibrosis10

Current standard of care
includes oral steroids
followed by add-on oral
antifungal treatment when
response is inadequate10

~50% of patients with ABPA have inadequate response to steroids alone. ~20% become dependent upon steroids and are at risk for long-term steroid complications

Current antifungals
are hindered by oral
delivery
which may
adversely affect
efficacy and safety14

Pulmazole is the first inhaled antifungal candidate
designed to overcome the limitations of oral antifungals
and also potentially reduce steroid burden.

Advancing Treatment in

A
llergic
B
roncho
-

p
ulmonary
A
spergillosis
(ABPA)

Aspergillus spp. are spore forming molds that cause significant morbidity and mortality in a number of different patient populations, with A. fumigatus the predominant species causing disease. Pulmonary A. fumigatus infections manifest as a range of diseases depending on the host’s immune state and underlying lung disease.15

In patients with asthma, fungal colonization and infection can result in ABPA. ABPA is a complex hypersensitivity reaction that occurs in the response to colonization of the airways with Aspergillus fumigatus, typically in patients with asthma or cystic fibrosis (CF). The immunological response to fungal antigens in the airway results in T-helper type 2 (Th2) cell activation and inflammatory cell recruitment to the airways, the most significant of which are eosinophils. Activation of both mast cells and eosinophils results in the release of mediators that induce bronchoconstriction.16

The diagnostic criteria for ABPA include both obligatory and supportive criteria in addition to having either asthma or CF. High levels of serum IgE (>1000 U/mL) and a positive hypersensitivity skin test or increased IgE antibody to Aspergillus are required criteria together with at least two additional supportive features: eosinophilia (>500 cells/μL), immunoglobulin G specific to Aspergillus antigens, and/or radiographic findings.17

ABPA LungABPA Lung

ABPA is characterized clinically by wheezing, dyspnea, mucus production and productive cough, and bronchoconstriction. Repeated episodes of mucus production, bronchial obstruction and inflammation may lead to bronchiectasis, and in severe cases, pulmonary fibrosis, which collectively result in a progressive loss of lung function.

PULMATRiX is developing Pulmazole, a dry powder iSPERSE
inhaled antifungal formulation for the treatment of ABPA.

Learn more about Pulmazole

PUR1800

PUR1800

PUR1800 is a Narrow Spectrum Kinase Inhibitor (NSKI) engineered with
iSPERSE that is currently being investigated for the treatment of
acute exacerbations in chronic obstructive pulmonary disease (AECOPD).
PUR1800 targets p38 MAP kinases (p38MAPK), Src kinases, and Syk kinases.18

These kinases play a critical role in chronic inflammation and airway remodeling.19-21

AECOPD Lung Remodeling ProcessAECOPD Lung Remodeling Process

By targeting these kinases,
PUR1800 is designed TO19-21

1. Block steroid resistant inflammation induced by a variety of stimuli including cytokines and free radical stressors such as cigarette smoke

2. Suppress inflammation associated with infection

3. Treat airway remodeling

FAST FACTS:
AECOPD and The Unmet Need for
Additional Treatment Options

There are ~18M moderate-to-severe cases of AECOPD in the US each year withThere are ~18M moderate-to-severe cases of AECOPD in the US each year with
due to infection-induced inflammation,here the standard of care (steroids) has limited efficacydue to infection-induced inflammation,here the standard of care (steroids) has limited efficacy

PUR1800, engineered with iSPERSE™, has the potential to deliver up to 3 times the effective lung dose when compared to a lactose blend formulation, improving delivery while reducing the potential for unwanted side effects.

ADVANCING TREATMENT IN AECOPD

Majority of COPD Exacerbations Are Secondary to Viral or Bacterial Infections 9

Acute exacerbations of COPD 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.24

COPD patients continue to suffer uncontrolled symptoms and exacerbations despite treatment with combination products which may contain inhaled corticosteroids, long acting muscarinic antagonists, and long acting ß-agonists. Depending on the severity, the management of AECOPD includes oral steroids and may include additional bronchodilators and antibiotics.25

Exacerbations often result in incomplete recovery and result in significantly increased morbidity and mortality. Hospitalization may be required for severe exacerbations.26 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.27,28

PULMATRiX is developing PUR1800 for the treatment of AECOPD.

Learn more about PUR1800

EXPANDED ACCESS STATEMENT

PULMATRiX is a clinical stage biopharmaceutical company developing innovative inhaled therapies to address serious pulmonary disease using its patented iSPERSE™ technology. PULMATRiX is currently developing PUR1900 (Pulmazole™), an investigational product intended for the treatment of allergic bronchopulmonary aspergillosis (ABPA). Currently there is no approved therapy for ABPA, and patients with ABPA are treated with corticosteroids to counter the inflammatory response to the Aspergillus fungus that lives in the lungs of these patients. Some patients with ABPA also receive systemic antifungal therapy, such as itraconazole. Although these therapies are effective in some patients with ABPA, the use of corticosteroids and systemic antifungals is limited by the potential for serious side effects. PUR1900 is a dry powder iSPERSE™ inhaled formulation of itraconazole.

A crucial step in the development of investigational products is to conduct clinical trials. Therapeutic products being studied in clinical trials have unknown benefits and unknown risks that will not be understood until the clinical trials are complete. If results from the clinical trials are favorable, they will be submitted to FDA and other regulatory bodies for review of the drug’s safety and efficacy in order to seek approval for the product. Obtaining regulatory approval for a new medicine is the best way to bring rapid access to the greatest number of patients who may benefit.

Sometimes patients may be able to access investigational products outside of a clinical trial. In the United States, this is possible through an expanded access program, also referred to as “compassionate use.” Use of the investigational product in an expanded access program is usually separate from the development program for that product, or at best an adjunct to the carefully designed, controlled, and monitored clinical studies conducted to demonstrate safety and efficacy of the product.

It is very important to systematically obtain information about the safety and tolerability of investigational products in a controlled manner. Currently a safety and tolerability study of PUR1900 is being conducted in patients with stable asthma and ABPA. Data on safety and tolerability of PUR1900 in these patients are not yet available. In the absence of these data, PULMATRiX is not accepting expanded access requests at this time. As information from our clinical trials become available, PULMATRiX will reevaluate this policy and publish any changes to this policy if appropriate.

If you have questions about this policy, or would like information about how to enroll in PUR1900 clinical studies, please contact PULMATRiX at info@pulmatrix.com. You can also obtain information about the current study at https://clinicaltrials.gov.

References: 1. Tepper SJ, Kori SH, Goadsby PJ. MAP004, orally inhaled dihydroergotamine for acute treatment of migraine: efficacy of early and late treatments. Mayo Clin Proc. 2011;86(10):948-955. 2. Aurora SK, Winner P, Freeman SC, et al. Onabotulinumtoxin A for treatment of chronic migraine: pooled analyses of the 56-week PREEMPT clinical program. Headache. 2011;51(9):1358-1373. 3. Winner P, Ricalde O, Le Force B. A double-blind study of subcutaneous dihydroergotamine vs subcutaneous sumatriptan in the treatment of acute migraine. Arch Neurol. 1996;53(2):180-184. 4. Saper JR, Silberstein S, Dodick D, et al. DHE in the pharmacotherapy of migraine: potential for a larger role. Headache. 2006;46(suppl 4):S212-S220. 5. Aurora SK, Rozen TD, Kori SH, et al. A randomized, double-blind, placebo-controlled study of MAP0004 in adult patients with migraine. Headache. 2009;available at: https://doi.org/10.1111/j.1526-4610.2009.01453.x. 6. Migraine Research Foundation. Available at: https://migraineresearchfoundation.org. Accessed November 24, 2020. 7. Agarwal R, Dhooria S, Singh Sehgal I, et al. A randomized trial of itraconazole versus prednisolone in acute-stage ABPA complicating asthma. CHEST. 2018.doi: 10.1016/ j.chest.2018.01.005. 8. Lestner JM, Roberts SA, Moore CB, et al. Toxicodynamics of itraconazole: implications for therapeutic drug monitoring. Clin Infec Dis. 2009;49:928-930. 9. Data on file. PULMATRiX: Lexington, MA. 10. Greenberger PA, Bush RK, Demain JG, et al. Allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol Pract. 2014; 2(6): 703–708. 11. Agarwal R, Aggarwal AN, Dhooria S, et al. A randomised trial of glucocorticoids in acute-stage allergic bronchopulmonary aspergillosis complicating asthma. Eur Respir J. 2016;47:385-387. 12. Shah A, Panjabi C. Allergic bronchopulmonary aspergillosis: a perplexing clinical entity. Allergy Asthma Immunol Res. 2016;8(4):282-297. 13. Patterson R, Greenberger PA, Halwig JM, et al. Allergic bronchopulmonary aspergillosis: natural history and classification of early disease by serologic and roentgenographic studies. Arch Intern Med. 1986;146(5)916-918. 14. Denning DW, Ribaud P, Milpied N, et al. Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis. Clin Infec Dis. 2002;34:563-571. 15. Kousha M, Tadi R, and Soubani AO. Pulmonary aspergillosis: a clinical review. Eur Respir Rev. 2011;20(121):156-174. 16. Patterson K, Strek ME. Allergic bronchopulmonary aspergillosis. Proc Am Thorac Soc. 2010;7(3):237-244. 17. Agarwal R, Chakrabarti A, Shah A, et al. Allergic bronchopulmonary aspergillosis: review of literature and proposal of new diagnostic and classification criteria. Clin Exp Allergy. 2013;43(8):850-873. 18. Curran AK, Charron C, Russel P, et al. PUR1800 (RV1162), a novel narrow spectrum kinase inhibitor, but not fluticasone, reduces TNFα-induced cytokine release by primary bronchial epithelial cells from healthy volunteers and COPD patients. Presented at: ERS International Congress; Paris, FRA: September 2018. 19. Barnes PJ. Kinases as novel therapeutic targets in asthma and chronic obstructive pulmonary disease. Pharmacol Rev. 2016;68:788-815. 20. Geraghty P, Hardigan A, Foronjy RF. Cigarette smoke activated the proto-oncogene c-Src to promote airway inflammation and lung tissue destruction. Am J Respir Cell Mol Biol. 2013;50(3):559-570. 21. Angata T, Ishii T, Motegi T, et al. Loss of siglec-14 reduces the risk of chronic obstructive pulmonary disease exacerbation. Cell Mol Life Sci. 2013;70(17):3199-3210. 22. Hurst JR, Vestbo J, Anzueto A, et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med. 2010;363:1128-1138. 23. Barnes PJ. Corticosteroid resistance in patients with asthma and chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2013;131(3):636-645. 24. Singh D, Agusti A, Anzueto A, et al. Global strategy for the diagnosis, management and prevention of chronic obstructive lung disease: the GOLD science committee report 2019. Eur Respir J. 2019;53(5):1900164. 25. Anzueto A. Primary care management of chronic obstructive pulmonary disease to reduce exacerbations and their consequences. Am J Med Sci. 2010;340(4):309-318. 26. Ko FW, Chan KP, Hui DS, et al. Acute exacerbation of COPD. Respirology. 2016;21:1152-1165. 27. Celli BR and Barnes PJ. Exacerbations of chronic obstructive pulmonary disease. Eur Respir J. 2007;29:1224-1238. 28. Seemungal TAR, Donaldson GC, Bhowmik A, et al. Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease. Am J Resp Crit Care Med. 2000;161:1608-1613.