Full Press Release Details
October 2016 NASDAQ: PULM Engineering
the Future for Inhaled Therapeutics Exhibit 99.1
Disclaimers & Forward Looking
Statements This presentation contains forward-looking statements. Forward-looking statements may be identified by the use of forward-looking terms such as "anticipates," "assumes," "believes," "can,"
"could," "estimates," "expects," "forecasts," "guides," "intends," "is confident that," "may," "plans," "seeks,"
"projects," "targets," and "would" or the negative of such terms or other variations on such terms or comparable terminology. These statements are not guarantees of future performance, are based on current
expectations of future events and are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements, including risks that we will not have sufficient working capital, that
we will have delays in obtaining, or we will be unable to obtain, FDA or other regulatory approvals for our products, that we will be 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 most recently filed
Annual Report on Form 10-K and its subsequently filed quarterly reports on Form 10-Q. Investors and security holders are urged to read these documents free of charge on the SEC's website at http://www.sec.gov. Forward-looking statements
contained in this presentation are made as of this date, and the Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise.
Pulmatrix Snapshot Proprietary
iSPERSETM Technology Engineered dry powder particles enable highly efficient lung delivery independent of inhalation flow rate Strong IP provides protection into 2030s De-risked Strategy Outsourced manufacture, off-the-shelf inhalation device,
505(b)2 ANDA route to registration High Value Pipeline Products targeted at major diseases including COPD and asthma and unmet needs in rare pulmonary diseases like cystic fibrosis (CF) Experienced Team Founded by Drs. Robert Langer (MIT) and David
Edwards (Harvard) Management Team/Board with a history of Respiratory biotech success (AIR/Alkermes, Civitas, Sunovion, Pearl Therapeutics) Growth Opportunities iSPERSETM technology suited for virtually any drug class Additional 505(b)2 and
in-license molecules can expand pipeline
Pulmatrix Pipeline: iSPERSETM Pulmonary
Therapeutics Product Class Indication Development Phase Data Readout Next Study Start Addressable Market PUR0200 LAMA COPD (Mylan Collaboration) EU Bioequivalence/ Phase 2 Q2 2017 Pivotal Registration Study 2H 2018 $7.9B WW by 20191 PUR1900
Anti-fungal Cystic Fibrosis Phase 1/1A Phase 2 POC Q4 2018 20k patients2 ABPA Asthma >5MM patients3 PUR1500 Anti-fibrotic IPF Preclinical 140K US patients Q4 2017 Q4 2017 Cowen & Co. Therapeutic Categories Outlook, Feb 2014 Clearview
Healthcare Partners, Physician Interviews Denning et al. Med Mycol. 2013 May;51(4):361-70
Pulmatrix Team: A History of Biotech
Success Terry McGuire BOD Investor (AIR, Cubist, Ironwood) Robert Clarke, PhD CEO (12+ years) (AIR, Alkermes) Steve Gillis, PhD BOD Investor (Immunex, Bluebird) Michael Higgins BOD-Audit Chair (Genzyme) Scott Rocklage, PhD BOD Investor (Cubist,
Pearl) Board of Directors Management David Hava, PhD CSO (9+ years) (Harvard) Bill Duke, MBA CFO (18 months) (Genzyme, Valeritas) Mark Iwicki Chairman (Civitas, Sepracor) Matthew L. Sherman BOD (Madrigal Pharma, Wyeth)
Pulmatrix: Respiratory Focused Market
Opportunity Global Respiratory Market = $33 BB by 20191 Cowen & Co. Therapeutic Categories Outlook, Feb 2014 GBI Research, 2013 Radiant Insights, 2016 GlobalData.com Pulmatrix: Seeking to unlock the full potential of inhaled drugs COPD $11.3B2
Cystic Fibrosis $695M3 IPF High unmet need
Pulmonary Platform + Product = High
Value Exit Transactions Pearl Therapeutics Civitas Therapeutics Prosonix Insmed Indication COPD Parkinson's Disease COPD Non-tuberculous Myco-bacterium Drug PT003 (LABA/LAMA) CVT-301 (L-Dopa) PSX1001 (Fluticasone propionate) Arikayce
(Antibiotic) Development Stage Phase II Phase II Pre-clinical Phase III Value ($MM) Acquired (AZ/2013): $560 MM/ $1.2B total Acquired (Acorda/2014): $525MM cash Acquired (Circassia/2015): $157MM cash NASDAQ: INSM $900+MM
Delivering on Company Milestones Report
Positive PUR0200 data for EU PUR0200 clinical data complete towards pivotal PK match FDA Orphan Status for PUR1900 PUR1900 Phase I/IA data in hand 3Q2016 4Q2016 1Q2017 2Q2017 3Q2017 4Q2017 PUR1900 Data presented At NACFC PUR0200 first patient in
PUR1900 EMA submission PUR1900 first patient in Past Milestones Projected Milestones
iSPERSETM Platform: Small, dense,
dispersible, and respirable salt-containing particles Variable formulation concepts to achieve product advantages (particle size, formulation, etc.) Clinically validated advantages over conventional technologies Broad novel IP portfolio into 2030s
iSPERSETM Technology Platform: Engineered for Exceptional Performance Multiple Platform Advantages: Highly efficient delivery allows for reduced effective doses Flow rate independence assures that even the sickest patients get their inhaled dose
High drug loads (up to 85%) support delivery of higher doses by inhalation Tailored formulations allow disease-specific dose control Platform supports multiple device formats
Pulmatrix iSPERSETM Strategy:
Derisking the Platform Outsource GMP Manufacture: Fully integrated Pulmatrix R&D team expert in formulation/aerosol science In house spray drying capability from bench top to Size 1 scale (non-GMP) Expertly scale product concepts from early
feasibility to kg scale (Size 1) Transfer CMC methods to CMO for GMP manufacture (Size 1 and up) Commercially Available, Approved Device: 510K-approved/CE-marked capsule-based inhaler Device technology for two approved inhalation products Readily
available off-the-shelf from Italian manufacturer at commercial scale Easy to use, discrete device provides patient cues
PUR0200 Inhaled Long Acting
Muscarinic Antagonist (LAMA)
PUR0200: Bronchodilator for COPD
Indication Overview 64MM COPD patients WW; 3rd leading cause of death in the U.S.1 Once daily long acting muscarinic antagonist (LAMA) is the first line therapy for moderate to severe COPD patients (50%) Product Overview Branded generic iSPERSETM
version of a once daily LAMA bronchodilator (Spiriva HandiHaler) Marketed reference product generated annual worldwide sales of 3.6B (2015)2 Additional label claim expansion to asthma has the potential to continue to increase future revenues
Product Development Strategy Focused on capital efficient development in EU and US Pursuing European PK Bioequivalence Regulatory pathway Existing data sets will be used to enable U.S. development pathway - 505(b)2 Cowen & Co. Therapeutic
Categories Outlook 2015 Boehringer Ingelheim 2015 Annual Report
European Development of PK
Bioequivalent Orally Inhaled Drugs European regulations provide guidance for the development of orally inhaled products by a step-wise equivalence approach Product approval based on matching PK of test product with reference Single dose PK studies
as basis for approval --> No Phase 1/2/3 paradigm Acceptance if 90% confidence interval (CI) for test : reference is within acceptance range (80-125%) Precedent PK equivalence approvals for ICS-LABA combination products Lung deposition similar?
Approval Systemic exposure (PK) similar?
PUR0200 Clinical Data: PK
Bioequivalent Targets PUR0200 formulations Trial Design: Single dose PK study in healthy volunteers (n=42) Seven period cross-over design 5 PUR0200 formulations 2 periods of reference product administration Trial Goals: Define relationship between
PUR0200 formulation parameters and PK Establish formulation strength, lung dose and particle size to achieve equivalence to reference Successful Proof of Concept (7/2016) Dose dependent and proportional increases in exposure PUR0200 PK modulated by
changing particle size and lung dose PK of multiple PUR0200 formulations align with reference product PK Key criteria to demonstrating PK bioequivalence established Targets BE range Data: Cmax
PUR0200: Improved Product Profile
for US Low Mid High Shows a matching patient benefit of iSPERSETM PUR0200 vs marketed product at 80% lower dose of inhaled active pharmaceutical ingredient (API) Reduced API could translate to improved cost of goods and side effect profile Clinical
PD Data in COPD Patients Hava et al. 2015. European Respiratory Journal 46: PA4365
PUR0200: Next Steps in Partnership
and Development EU PK Bioequivalence Path Actively negotiating partnership rights Preferred development path identified with target of next clinical trial FPI Q2 2017 PK Bioequivalent product anticipated to be registered in EU by 2019 US 505(b)2
Path Pulmatrix actively talking to potential partners about the US rights Goal is to partner the program and initiate 505(b)2 development in next 6-12 months Pre-IND meeting will be sought to gain FDA opinion of lower effective dose profile and
additional required clinical data for approval Based on precedents, Pulmatrix expects at least one Phase 2 and one 12-week Phase 3 safety trial will be required; will evaluate alternate streamlined approach Anticipated NDA submission in
PUR1900 Addressing Pulmonary Fungal
Infections in Patients with Cystic Fibrosis and Severe Asthma
PUR1900: Inhaled Antifungal for CF
Indication Overview CF is a fatal genetic disease of the lungs/GI tract that affects 70K patients WW; median survival of patients is 39.3 years1. Patient populations suffer from copious, static mucus leaving patients susceptible to fungal infections
caused by fungal spore inhalation As patient survival improves, probability of fungal infection increases Product Overview Inhaled formulation of itraconazole (ITRA) to treat pulmonary fungal infections granted FDA orphan drug status in August 2016
Oral ITRA is first line therapy to treat Aspergillus infection with significant systemic side effects and subthreshold therapeutic levels in lung Superior PK profile when delivered by inhalation PUR1900 offers multiple promising advantages over
current oral therapy High drug concentration at the site of infection Initial indications suggest improved safety and tolerability profile with potential for improved efficacy https://www.cff.org Denning et al. Med
Mycol. 2013 May;51(4):361-70
PUR1900: Fungal Infections in Cystic
Fibrosis Source: Chotirmall. Int J Biochem Cell Biol. 2014;1(52):161 Moss. Semin Respir Crit Care Med. 2015;36(2):207 Physician Interviews; ClearView Analysis. A combination of the host's underlying immune state as well as pathogen-driven
factors ultimately determine the prevalence and overall clinical implications of fungal infections Disease Pathophysiology Disease Overview Healthy Diseased Description Patho-physiology Signs and Symptoms Impaired mucociliary clearance assists
entrapment and growth Fungal colonization can lead to inflammation and airway remodeling Common symptoms include increased exacerbations and worsening lung function Misdiagnosis can lead to prolonged illness Two types of fungal infections in cystic
fibrosis Aspergillus bronchitis (AB) Allergic bronchopulmonary aspergillosis (ABPA)
PUR1900: Disease Prevalence of
Fungal Infections in CF AB: Aspergillus bronchitis. ABPA: Allergic bronchopulmonary aspergillosis. % % % % % % Percent of All U.S. CF Patients Overview of Disease Prevalence by Key Patient Segment ABPA Aspergillus Bronchitis c Aspergillus Bronchitis
Two recent studies from the UK estimated the prevalence of AB in CF patients to be about 30%, suggesting about ~9 K AB patients in the US. However, physicians have consistently reported that AB patients represent about 20% of the CF population ABPA
Published data typically cite the ABPA population to be between 5 and 18% of the broader CF population However, KOLs suggested that 15% represents a more accurate estimate of ABPA prevalence in the CF population Sources: Baxter. J Allergy Clin
Immunol. 2013;132(3): 560 Armstead. PLoS One. 2014;9(6):e98502 Physician Interviews; ClearView Analysis.
Patient Referral Pathway Infectious
Disease Specialist Pulmonologist Key Diagnostic Tools Clinical Presentation Wheezing, bloody sputum, shortness of breath, and overall deteriorating lung function are common manifestations In select instances, infectious disease specialists are
consulted when clinical symptomology or serological findings are consistent with abnormal and / or aggressive pathogens Sputum Sample Sputum cultures support a diagnosis of Aspergillus colonization - PCR and genotyping are seeing increased
utilization Imaging Longitudinal imaging studies may inform the degree of fungi-associated inflammation and overall airway deterioration Immunological Markers Used to differentiate clinical phenotypes. IgE and IgG antibodies are often elevated in
ABPA and Aspergillus bronchitis, respectively PUR1900: Treating CF Patients with Fungal Infections
Relieves high treatment burden of
oral antifungal therapy and improve outcomes Inhalation delivery provides improved safety and (potentially superior) efficacy at a much lower total dose of drug Targeted delivery achieves high therapeutic dose directly to the site of infection
avoiding GI/systemic exposure PUR1900: Inhaled Itraconazole Itraconazole Inhibits Fungal Cell Wall Synthesis Commonly used to treat Aspergillus related illness Superior PK profile when delivered by inhalation Well understood mechanism of action Why
Itraconazole: PUR1900 Anticipated Advantages vs. Oral Antifungals:
PUR1900 Achieves High Lung and Low
Plasma Exposure Once daily aerosol dosing of PUR1900 achieves 3x lung concentration over oral dosing at 25% the dose in pre-clinical evaluation Significantly lower systemic exposure with PUR1900 after both single and repeat doses Low level of
systemic accumulation with PUR1900 relative to oral dosing PUR1900 Sporanox
Superior Efficacy Compared to Oral
Treatment of Immunosuppressed Guinea Pigs Treatment with PUR1900 beginning one day after infection provides greater protection than oral dosing
PUR1900: Cystic Fibrosis Product
Profile Physicians highlighted that ~85% of treated AB patients would likely be prescribed an inhaled antifungal, largely due to current dissatisfaction with available agents Source: Physician Interviews; ClearView Analysis. ABPA: Allergic
bronchopulmonary aspergillosis. AB: Aspergillus bronchitis. Physicians estimated that ~80% and ~85% of treated ABPA and Aspergillus bronchitis patients would receive PUR1900, respectively. ~75% ~80% Of the treated ABPA patients, physicians suggested
that ~80% would receive an inhaled antifungal Driven by increased physician willingness to utilize an inhaled antifungal in combination with steroids as first-line therapy given PUR1900's favorable profile Key Details ABPA Aspergillus
Bronchitis Segment Product Uptake Treated ABPA Population Diagnosed ABPA Population PUR1900 Utilization ~75% ~85% 65% Treated AB Population Diagnosed AB Population PUR1900 Utilization
PUR1900: Product Profile Feedback