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PULMATRIX Corporate Overview November
2017 NASDAQ: PULM Exhibit 99.1
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obtaining, or we will be unable to obtain, FDA or other regulatory approvals for our products, unable to establish collaborations, or that our products will not be commercially viable, among other risks. A discussion of these and other factors,
including risks and uncertainties with respect to the Company, is set forth in the Company's filings with the Securities and Exchange Commission (SEC), including the Company's Annual Report on Form 10-K and its quarterly reports on Form
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Three Study Readouts in 2018-2019 with
Products Exceeding $6B in Estimated Revenue Potential ABPA = Allergic Bronchopulmonary Aspergillosis CF = Cystic Fibrosis NOTE - PUR1800 is iSPERSE re-formulation of in-licensed NSKI RV1162 from Janssen LEAD PROGRAM iSPERSE Pulmazole
Anti-Fungal PUR1800 is an iSPERSE formulation of a narrow spectrum kinase inhibitor (NSKI) for AECOPD Acute exacerbation treatment paradigm, vs prevention, leads to faster and cost efficient development plan 1st to market (U.S. & E.U.) inhaled
non-steroidal anti-inflammatory NSKI anti-inflammatory target activity, safety and tolerability in stable COPD patients Phase 2a COPD data expected 4Q 2018 ~$4.3B U.S. and E.U. estimated revenue opportunity Second PROGRAM iSPERSE PUR1800
Kinase Inhibitor Pulmazole inhaled itraconazole for ABPA Reduced development risk as itraconazole (Sporanox) was originally approved 25 years ago - 505(b)(2) pathway may allow for accelerated development 1st to market (U.S. & E.U.) inhaled
anti-fungal Qualified Infectious Disease Product (QIDP) designation obtained in 2017 for CF and ABPA Expected Phase 1 data mid-2018 and 28-day biomarker data in ABPA patients mid-2019 ~$2.3B U.S. and E.U. estimated revenue opportunity Accretive
Factors Contributing to Probability of Success "De-risked" programs with 505(b)(2) Pulmazole and precedent NSKI data in COPD patients iSPERSE dry-powder delivery technology studied in patients demonstrating safety, tolerability
and drug enabling capabilities Underlying iSPERSE intellectual property carries well into 2030's with additional patent protection through specific drug development AECOPD = Acute Exacerbations in Chronic Obstructive Pulmonary Disease
LOE = Loss of Exclusivity
Product Indication 2018* 2019*
Milestone Pulmazole Anti-fungal Allergic Bronchopulmonary Aspergillosis (ABPA) in Severe Asthma Phase 1 Mid-2018 Phase 1b Mid-2019 PUR1800 NSKI Acute Exacerbations of COPD (AECOPD) Phase 2a 4Q 2018 PUR5700 NSKI Idiopathic Pulmonary Fibrosis (IPF)
Phase 1 (2019) PUR0200-US LAMA Chronic Obstructive Pulmonary Disease (COPD) Out-Licensed to Vectura for U.S. 09/2017 PUR0200-EU LAMA E.U. Out-Licensing Opportunity Robust Pipeline with Projected Near-Term Value Catalysts NSKI = Narrow Spectrum
Kinase Inhibitor LAMA = Long-Acting Muscarinic Antagonist *Estimated Milestones Phase 2 Ready (U.S.) Pre-Clinical Registration Trial Ready (E.U.) Phase 2a Phase 1 KEY: 2018-2019 Development Focus 28-Day Biomarker
iSPERSE Best-in-Class Engineered
Particles Enable Development and Patient Care Advantages PK = Pharmacokinetic iSPERSE enables the sickest patient to get the right dose every time iSPERSE Differentiation iSPERSE Advantages Small, dense, dispersible, respirable
particles Flow rate independent performance (consistent delivery of high drug loads) Scalable platform Broad IP portfolio into 2030s Can be used with most drugs, small molecule or biologic Can be used with virtually any device (i.e., metered-dose,
reservoir, or blister-based inhalers) Requires low inspiratory flow given high particle dispersibility and penetration deep into lung Can deliver large doses into lungs (tens of milligrams) with high lung delivery efficiency Avoids first-pass effect
and systemic side-effects with improved PK profile compared to oral delivery iSPERSE 1 m
Pulmazole - Inhaled Antifungal
Inhaled itraconazole to Treat Allergic Bronchopulmonary Aspergillosis (ABPA) in Asthmatics
Pulmazole Targets ABPA Patients'
Unmet Need for an Efficacious and Well Tolerated Antifungal Meaningful ABPA Disease Burden ABPA is caused by hypersensitivity to Aspergillus fumigatus and untreated may result in pulmonary fibrosis, respiratory failure and potentially death ~1.5% of
adult asthma patients (~300K in U.S.) suffer 1-3 exacerbations annually Severe asthma patients annually average 5 hospitalization days at ~$15K 40% of patients treated on steroids alone demonstrate partial or non-response Up to 45% of patients
experience recurrent relapses or steroid dependence when treated with steroids alone Pulmazole Anticipated Benefits Improved efficacy with consistent, and potentially greater, drug levels in the lung Improved safety & tolerability from lower
systemic exposure via inhalation Reduced steroid burden by reduction in fungal growth and antigen production Source: Shah. AAIR. 2016;8(4):282; Wark. JACI. 2003;111; 952; Salez. Chest. 1999;116(6):1665; GINA 2015; Patterson. Arch Intern Med. 1986:
146:916-8; Physician Interviews; ClearView Analysis. QOL = Quality of Life. MOA = Mechanism of Action UNMET NEED Reduce exacerbations & prevent development of progressive lung injury Minimize toxicity associated with systemic absorption by
delivering drug locally Optimize efficacy by delivering higher dose of drug directly to lung Reduce steroid use & minimize steroid toxicity
3rd Line 2nd Line ABPA-Asthma Overview
Treatment Flow Treatment Shortcomings Increase Disease Burden for ~300K U.S. ABPA- Asthma Patients Source: Shah. Allergy Asthma Immunol Res. 2016;8(4):282; Agarwal. Clinical & Experimental Allergy. 2013;43:850; Patterson. Proc Am Thorac Soc.
2010;7:237; Tracy. J. Fungi. 2016;2:17; Physician Interviews; ClearView Analysis. IgE = Immunoglobulin E Antibodies Description ABPA in asthmatics is caused by hypersensitivity to Aspergillus fumigatus Persistence of A. fumigatus leads to local
inflammation, mucus production and airway hyper- reactivity Untreated ABPA may result in pulmonary fibrosis, respiratory failure and potentially death Unmet Need with Current Treatments Physicians told Pulmatrix they seek a better anti-fungal
approach to reduce exacerbations and reduce steroid burden / dependence Oral itraconazole (Sporanox) use is limited by safety and tolerability issues 1st Line Follow-up: Chest Radiograph, Spirometry, Total Serum IgE Glucocorticoids (4 Months) Acute
ABPA Patient (Stage I) Remission (Stage II) Response Exacerbation (Stage III) Steroids (4 Months) & antifungal (6 Months) Long Term Therapy: Azoles, Glucocorticoids, Omalizumab, Methylprednisolone Pulses, Nebulized Amphotericin
Treatment-Dependent (Stage IV)
Reducing Fungal Burden Plays an
Important Role in ABPA Treatment Pulmazole expected to reduce fungal burden and attenuate inflammatory response DC = dendritic cell; AM = alveolar macrophage Moss (2014) Eur Resp J 43:1487-1500 Antifungals Steroids Omalizumab Oral antifungals,
including itraconazole, are limited by poor pharmacokinetics and safety concerns associated with high plasma concentrations ABPA diagnosis: High IgE (>1000IU/mL) Skin prick positive to Aspergillus Eosinophilia (>500 cells L) Antibodies
to Aspergillus antigens Growing fungus in the airway activates a Th2 lymphocyte response Resulting eosinophilic inflammation and IgE production drive airway obstruction and clinical symptoms Steroids are immunosuppressive and may exacerbate fungal
growth or antigen production Antifungals inhibit fungal growth, improve fungal clearance and reduce antigen production Act to reduce inflammation, improve clinical outcomes and may be steroid sparing
Literature Indicates Antifungals
Improve Exacerbations Literature and Physicians Confirm the Importance of Antifungals in ABPA Treatment Physicians View Antifungals as Clinically Effective* Experts interviewed indicated antifungal agents reduce exacerbations and chronic steroid use
Physicians attribute results to reduction in ABPA patients' fungal burden Physicians interviewed currently use antifungals in ~50% of patients itraconazole is currently used in majority of patients receiving antifungal therapy Antifungal
agents have been shown to reduce exacerbations, improve lung function and reduce steroid use in ABPA Physicians consider antifungals as add-ons to steroids, although use is limited by a lack of robust data and known safety risks 1999, Salez et al.
itraconazole improved pulmonary function, and decreased total IgE, exacerbations, and steroid use in a cohort of 14 patients 2000, Stevens et al. itraconazole improved pulmonary function, and decreased steroid use and total IgE in a randomized
double-blind trial with 55 patients 2003, Wark et al. itraconazole decreased total IgE and the exacerbation frequency in a randomized, double-blind trial with 29 patients 2012 Chishimba et al. A review indicated that vori./posaconazole improved QOL,
and reduced steroid use and exacerbations in 20 patients 2016, Ram et al. Nebulized amphotericin B reduced exacerbations compared to nebulized budesonide in a study in 21 patients Source: Chishimba. Journal of Asthma. 2012; 49(4):423; Stevens.
NEJM.2000;342(11):757; Wark. J Allergy Clin Immuno. 2003;111; 952; Salez.Chest. 1999; 116(6):1665; Ram. Journal of Asthma. 2016:517; Physician Interviews; ClearView Analysis. QOL = Quality of Life *Based on certain physicians interviewed by
Lower Plasma Concentration of
Pulmazole at ~1/10 Oral Sporanox Dose >5X Greater Lung Concentration of Pulmazole at ~1/10 Oral Sporanox Dose Pulmazole: Anticipated Efficacy & Safety Benefits vs Oral itraconazole (Sporanox) In preclinical dog studies, Pulmazole reverses the
systemic to lung exposure ratio observed with oral Sporanox Data indicates potential for efficacy and tolerability advantages with Pulmazole compared to the preferred ABPA-Asthma oral antifungal treatment (Sporanox) Pulmazole 0.5 mg/kg Sporanox 5
mg/kg NOTE: Dosing reflects estimated Pulmazole lung dose vs. Sporanox oral dose Pulmazole 0.5 mg/kg Sporanox 5 mg/kg 11
Survival Pulmazole Compared to Oral
Sporanox and Placebo Pulmazole: Inhaled itraconazole Improved Survival in an Immunosuppressed Guinea Pig Model In a lethal model with aspergillus infected immunosuppressed guinea pigs, Pulmazole achieved ~90% survival vs 30% with oral Sporanox at 14
days Data re-asserts potential efficacy advantages for Pulmazole compared to the preferred ABPA-Asthma oral antifungal treatment (Sporanox) Pulmazole 1 mg/kg Sporanox 10 mg/kg NOTE: Dosing reflects estimated Pulmazole lung dose vs. Sporanox oral
Part 1: Single Ascending Dose
Healthy volunteers (n=6/cohort) Part 2: Multiple Ascending Dose Healthy volunteers (n=6/cohort) Part 3: Single Dose Crossover Asthmatics (n=12) Pulmazole: Phase 1/1b Clinical Development Plan Pulmazole (25 mg) Pulmazole (10 mg) Pulmazole (5 mg)
Pulmazole (20 mg) Pulmazole (10 mg) Pulmazole (20 mg) Sporanox (200 mg; oral) Phase 1: Safety, Tolerability and PK Study in Healthy Volunteers and Asthmatics Randomized, double-blind, placebo controlled study (1:2 randomization; n=8/8, 16, 16)
Exploratory endpoints: Biomarker IgE plasma concentrations Sputum and plasma eosinophils IgG specific to A. fumigatus antigens in plasma Aspergillus burden in sputum Clinical / radiographic (e.g. pulmonary function/CXR) Phase 1b: 28-day Safety,
Tolerability and Biomarker Study in Asthmatic ABPA Patients Pulmazole (10 mg) Pulmazole (20 mg) Placebo ABPA Patients Safety Tolerability 2018 2019 1Q 2Q 3Q 4Q 1Q 2Q 3Q Phase 1 Data Phase 1b Start Phase 1 Start Phase 1b Data Dose to be confirmed
upon completion of phase 1/1b
Pulmazole - Commercial
1st Line Antifungal Usage More than
Doubles Pulmazole: Efficacy and Safety Advantages Drive Prescriber Preference The Pulmazole Advantage Pulmazole Converts Majority of Oral Azole ABPA Market Patients Receiving Pulmazole Total Antifungal Therapy Pivotal Trial Design Oral Prednisone +
Placebo vs. Oral Prednisone + Pulmazole 4-month treatment following patients for 8 additional months Target Product Profile Primary Endpoint: 50% improvement in exacerbation number or rate Secondary Endpoints: FEV1 Unmet Need in ABPA-Asthma Frequent
exacerbations due to poor disease management Dependence on oral steroids as primary treatment option Safety / tolerability issues with both oral steroids and oral antifungals Pulmazole Value Drivers Inhaled delivery minimizes systemic exposure to
improve side-effect profile iSPERSE lung delivery enables high drug concentrations to lung with potential efficacy benefit itraconazole MOA and effectiveness in ABPA-Asthma is established Source: Physician Interviews; Payer Interviews; ClearView
Pulmazole: Payers Anticipate
Biologic Pricing with Minimal Access Restrictions Source: Chishimba. Journal of Asthma. 2012;49(4):423; Stevens. NEJM. 2000;342(11):757; Payer Interviews; ClearView Analysis. Red Book; Payer Interviews; Source: Payer Interviews; ClearView Analysis.
PA = Prior Authorization. Annual Gross Cost (U.S.) $100 K $10 K $30 K $70 K $50 K Anticipated Optimized Pricing Range Payer Tactics Overview Access Liberal Restricted Case-by-case Evaluation Restrict Beyond Trial Pop. Proof of Efficacy for Renewal
PA (e.g., Restrict to Trial Pop.) $50 K+ Access Liberal Restricted Case-by-case Evaluation Restrict Beyond Trial Pop. Proof of Efficacy for Renewal PA (e.g., Restrict to Trial Pop.) $30 - 50 K Access Liberal Restricted $5 - 30 K
Case-by-case Evaluation Restrict Beyond Trial Pop. Proof of Efficacy for Renewal PA (e.g., Restrict to Trial Pop.) Xolair is indicated for severe asthma poorly controlled by ICS with a reactivity to aeroallergen Annual Price: ~$40K Xolair Nucala is
indicated for patients with severe asthma and an eosinophilic phenotype Annual Price: ~$35K Nucala Cinqair is indicated for patients with severe asthma and an eosinophilic phenotype Annual Price: ~$25K Cinqair Pulmazole Pricing Potential Asthma
Biologic Price Analogues
Pulmazole: ABPA-Asthma Peak Revenue
Forecast at Loss of Exclusivity in 2033 Source: Physician Interviews; Payer Interviews; ClearView Analysis. * Also includes discount for patient compliance, patient persistence, and gross-to-net adjustment. U.S. Other Indications U.S. ABPA Asthma
E.U. ABPA Asthma US Patients at Peak Use (2033) 260 - 315 K ABPA patients 170 - 200 K diagnosed and treated 120 - 140 K inhaled antifungal eligible Pulmazole Penetration (2033) 80 - 95 K treated with Pulmazole (~67% of
eligible patients) Pricing Potential & Market Access (2033) 2033 Pricing: ~$55 K per year ($40 K at launch) 80% market access Peak US Net Sales* $1.3 Billion Pulmazole U.S. 2033 Forecast & Assumptions Pulmazole U.S. & E.U. 2033
Pulmazole Profile Meets Need for a
More Effective / Well Tolerated Antifungal and Drives Value Source: Physician Interviews; Payer Interviews; ClearView Analysis Pulmazole Clinicians told Pulmatrix they need safe and effective treatments that reduce the burden of exacerbations and
steroid-use High Unmet Need Prescribers indicate Pulmazole would penetrate 67% of addressable ABPA-Asthma market Physician Demand Clinical trial landscape survey identified limited competition (Pulmocide) for Pulmazole in ABPA-Asthma Limited
Competition Significant opportunity to expand Pulmazole to other indications beyond ABPA-Asthma Meaningful Upside Value Payers indicated favorable market access with minimal use restrictions at respiratory biologic pricing Potential for Favorable
PUR1800 - iSPERSE Narrow
Spectrum Kinase Inhibitor (NSKI) Novel Anti-inflammatory to Treat Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD)
PUR1800: Broad Efficacy Potential
and Significant Unmet Need in AECOPD Source: Aaron SD et al. N Engl J Med. 2003; 348(26): 2618-25. CDC Behavioral Risk Factor Surveillance System, 2013. Celli BR et al. Eur Respir J 2007; 29: 1224-1238. Chronic obstructive pulmonary disease
(COPD): Fact sheet. (2014, May). Chronic obstructive pulmonary disease (COPD): Fact sheet. (2014, May). Hurst JR et al. N Engl J Med 2010; 363(12): 1128-38. Soriano JB et al. Chest, 2013; 143(3): 694-702. Wise RA, et al. Chronic Obstr Pulm Dis
(Miami). 2017; 4(1): 7-20 Meaningful AECOPD Disease Burden ~16M COPD patients in the U.S. 77% experience at least one exacerbation ~18M moderate-to-severe AECOPD episodes annually > 20% corticosteroid treatment failure rate in moderate-to-severe
AECOPD patients Steroids Lack Consistent Efficacy Across Different AECOPD Phenotypes Environmental (Eosinophilic) Bacterial Viral Bacterial and Viral Anticipated Benefits of PUR1800 Inhaled Narrow Spectrum Kinase Inhibitor (P38, Syk and Src) Treat
Steroid-Resistant Inflammation that underlies COPD Treat Inflammation from Infections that trigger AECOPD where steroids are ineffective Inhalation directly to site of inflammation for fast onset and lower systemic exposure