INSPIRE: A Phase 3 Open-Label, Multicenter Study to Evaluate the Safety and Tolerability of LIQ861 in Pulmonary Arterial Hypertension (PAH)

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1 INSPIRE: A Phase 3 Open-Label, Multicenter Study to Evaluate the Safety and Tolerability of LIQ861 in Pulmonary Arterial Hypertension (PAH) N. S. Hill; J. P. Feldman; S. Sahay; D. J. Levine; R. F. Roscigno; T. A. Vaughn; T. M. Bull Presenter: N.S. Hill April 3,

2 Relevant financial relationship disclosure statement INSPIRE: A Phase 3 Open-Label, Multicenter Study to Evaluate the Safety and Tolerability of LIQ861 in Pulmonary Arterial Hypertension (PAH) Presenter: N.S Hill, MD I will discuss investigational use of the following drugs/devices: LIQ861 Dry Powder Inhalation of Treprostinil The following relevant financial relationships exist related to this presentation: N. S. Hill: Consultant - Liquidia Technologies Grant/Research Support Institution - Actelion, Bayer, Gilead, Liquidia Technologies, Reata, United Therapeutics Scientific Medical Advisor - Liquidia Technologies 2

3 PAH is a rare, progressive disease that results in right heart failure Multiple pathways are involved in pathogenesis Abnormal changes in arteries of the lungs increase pressure in pulmonary arteries that leads to remodeling of the right ventricle Prostacyclin is essential to normal lung function Continually released by lungs to bind local receptors Vasodilates the pulmonary arteries Relaxes smooth muscle Inhibits platelet aggregation PAH Patient Prostacyclin Deficiency PAH Treatment Prostacyclin Analogs Goal of prostacyclin therapy is to maximize a patient s exposure to the highest tolerable level of drug Source: Channick Advances in Pulmonary Hypertension Spring,

4 Current prostacyclin-based products have clear tradeoffs Infusion = (Continuous IV or SubQ) Effective, but systemic toxicities & site pain, limitations on lifestyle Poses potential for risk of infection Oral = Convenient, but toxicities and limited symptom relief Increased GI side effects Up-titration can be challenging given side effects Nebulized = Local delivery, but provides limited dose range Due to throat, airway irritation, cough Inconvenient; requires assembly, cleaning and time to dose Source: Decision Resources, Pulmonary Hypertension Disease landscape & Forecast, November 2018; Recent advances in targeting the prostacyclin pathway in pulmonary arterial hypertension, November

5 LIQ861 applies PRINT technology to treprostinil using proven DPI device Uniform particles within the respirable range (<5.0 microns) LIQ861 Dry Powder Formulation RS00 Model 8 Dry Powder Inhaler LIQ861 particles are between 1-2 µm wide with trefoil shape Compact, disposable inhaler previously approved by FDA and EMEA to be used in asthma products Source: Liquidia Technologies data on file 5

6 Phase 1 pharmacokinetics n=57 healthy volunteers LIQ861 Mean Concentration Over Time Single, ascending dose Dose proportional response No dose-limiting toxicities up to 150 mcg Approx. Capsule (TRE fill wt.) Approx. Emitted Dose (mcg) Breaths Sources: Ph 1 study design: 57 subjects enrolled; 43 on LIQ861, 14 on placebo; each cohort = 8 subjects in 3:1 ratio (LIQ861:placebo) randomized, placebo-controlled; Royal M, Roscigno R, et al. Preclinical and Phase 1 Clinical Characterization of LIQ861, a New Dry Powder Formulation of Treprostinil [poster]. In: PVRI Annual World Congress; 2018 January 21-24; Singapore, Asia. 6

7 Phase 3: INSPIRE Study Design Day 0 Week 2 Month 1 Month 2 Month 4 WHO Group I (PAH) NYHA Class II, III and IV N > 100 Add-On LIQ861 <2 non-pgi oral PAH Rx Tyvaso Transitions Stable Doses > 3 mo. Treatment phase for Primary Endpoint Continued treatment up to 30 months Initiate 25 mcg capsule strength dose Increase in 25 mcg increments weekly to tolerance and symptom relief Initiate with comparable dose of LIQ861 Titrate in 25 mcg incremental doses to tolerance and symptom relief Primary Endpoint Incidence of TEAEs and SAEs at 2 months Exploratory Endpoints Sustained use after transition (Tyvaso transitions) 6 minute walk distance NT probnp NYHA functional class Quality of life questionnaire / Patient satisfaction with LIQ861 Sources: PGI prostacyclin; TEAEs treatment-emergent adverse events; SAEs serious adverse events Tyvaso is a registered trademark of United Therapeutics Corp. 7

8 Summary of Demographics and Baseline Characteristics No. Subjects (% of Study) at 2-month timepoint LIQ861 Add-Ons (N=65) Transitions (N=44) Overall (N=109) Sex Age at Screening (years) Female 51 (78.5%) 39 (88.6%) 90 (82.6%) Male 14 (21.5%) 5 (11.4%) 19 (17.4%) Mean ± SD 55 ± ± ± 13.9 BMI (kg/m²) Mean ± SD 29.5 ± ± ± 7.7 NYHA Functional Class at Screening Class II 36 (55.4%) 36 (81.8%) 72 (66.1%) Class III 29 (44.6%) 8 (18.2%) 37 (33.9%) 8

9 Most patients remained on LIQ861 through 2-months of treatment Preliminary data Sustained Therapy at 2 Months LIQ861 Tyvaso Add-ons Transitions Overall Total Patients Started Withdrawn < 2 Months Sustained at 2 Months % Patients Sustained 90.8% 95.5% 92.7% Patients withdrew due to: Adverse Events, Patient Choice, Investigator Decision, Lost to Follow Up 9

10 15 Serious Adverse Events (SAEs) unrelated to LIQ861 Respiratory, Thoracic and Mediastinal disorders Injury Acute pulmonary embolism Shortness of breath Fracture lower leg Infections Parainfluenza virus Viral illness Sepsis Hospital acquired pneumonia Nervous System disorders Gastrointestinal bleed Hypertensive urgency Fluid overload Gastrointestinal disorders Vascular disorders Possible seizure Syncope 10

11 Treatment Emergent Adverse Events (TEAEs) observed were consistent with inhaled prostacyclins and mild to moderate in severity TEAEs at Month 2 in 4% of Patients Receiving LIQ861 No. (%) Subjects LIQ861 Add-ons Tyvaso Transitions Overall No. of Events No. of Events No. of Events No. (%) No. (%) Mld Mod Sev Subjects Mld Mod Sev Subjects Mld Mod Sev Cough 30 (46.2%) (13.6%) (33.0%) Headache 11 (16.9%) (20.5%) (18.3%) Throat irritation 11 (16.9%) (9.1%) (13.8%) Dizziness 7 (10.8%) (9.1%) (10.1%) Diarrhoea 7 (10.8%) (4.5%) (8.3%) Oropharyngeal pain 5 (7.7%) (2.3%) (5.5%) Nausea 4 (6.2%) (4.5%) (5.5%) Dyspnea 3 (4.6%) (6.8%) (5.5%) Flushing 5 (7.7%) (2.3%) (5.5%) Chest discomfort 4 (6.2%) (2.3%) (4.6%)

12 TEAEs are those expected with prostacyclin therapy Add-On Patients (n=65) Transition Patients (n=44) Dyspnea Dizziness Diarrhea Flushing Nausea Pts w/ TEAES at 2-Months Pts w/ TEAES at 2-weeks Dyspnea Dizziness Diarrhea Flushing Nausea Pts w/ TEAES at 2-Months Pts w/ TEAES at 2-weeks Headache Headache Chest discomfort Chest discomfort Oropharyngeal pain Oropharyngeal pain Throat irritation Throat irritation Cough Cough Patients Patients 12

13 LIQ861 maintained 6MWD in Add-on and Transition Patients Six Minute Walk Distance Max Median Median 6MWD meters Add-On Patients Transition Patients Min 0 Baseline n=63 Week 2 n=61 Month 1 n=60 Month 2 n=57 0 Baseline n=44 Week 2 n=44 Month 1 n=44 Month 2 n=37 4 months would be minimum time required to fully assess 13

14 All domains from MLHFQ improved at 2 months Minnesota Living With Heart Failure Questionnaire (MLHFQ) Median Score Add-On Patients n=63, n= Transition Pts n=44, n= All Patients n=107, n=99 MLHFQ is a patientoriented measure of the adverse effects of heart failure on a patient s physical and emotional aspects of life A five (5) point change is the minimal clinically important difference Overall Score (Day 1) Overall Score (Month 2) Note: A decrease in MLHFQ score is considered an improvement; 14

15 LIQ861 met primary endpoint in pivotal Phase 3 INSPIRE study A convenient, safe, well tolerated option for inhaled prostacyclin therapy No study drug-related SAEs TEAEs expected and mostly mild in nature Most TEAEs occurred during first 2-weeks 93% of patients completed 2 months 6MWD maintained for at least 2 mos MLWHF Questionnaire registered improvements in both physical and emotional domains Serious Adverse Events (SAEs); Treatment Emergent Adverse Events (TEAEs) 15

16 Liquidia Technologies would like to thank our Patients and Principal Investigators *INSPIRE Steering Committee 16