United Therapeutics Corporation · NASDAQ:UTHR
United Therapeutics — Investor Presentation (January 2021)
50 slides from United Therapeutics's investor presentation, January 2021
Slide 1: Tyvaso INCREASE Trial Results
TYVASO INCREASE TRIAL RESULTS January 2021
Slide 2: Safe Harbor Statement
INCREASE TRIAL RESULTS SAFE HARBOR STATEMENT Remarks today concerning There can be no assurance The discussions This presentation United Therapeutics may include forward- that the actual results, events or during this presentation could include certain and any related discussions or statements looki
Slide 3: Agenda
INCREASE TRIAL RESULTS AGENDA DEWEY STEADMAN Introduction Head of Investor Relations, United Therapeutics Corporation STEVEN D. NATHAN, MD INCREASE Trial Results INCREASE Study Investigator Director of the Advanced Lung Disease Program and Director of the Lung Transplant Program at Inova Fairfax Hos
Slide 4: Steven D. Nathan, MD
INCREASE TRIAL RESULTS STEVEN D. NATHAN, MD Steven D. Nathan, MD Dr. Nathan is board certified in pulmonary diseases, critical care medicine and internal medicine. The author of more than 380 publications, Dr. Nathan has written original research manuscripts, abstracts, reviews, book chapters, and a
Slide 5: Background
Background 5
Slide 6: WSPH Classification of Pulmonary Hypertension
WSPH Classification of Pulmonary Hypertension Pulmonary Hypertension* Resting mean pulmonary artery pressure (mPAP) >20 mmHg with an accompanying pulmonary vascular resistance (PVR) ≥3 Wood Units on right heart catheterization (RHC)1 Group 1 Group 2 Group 3 Group 4 Group 5 Pulmonary Arterial Pulmona
Slide 7: Pulmonary Hypertension due to Interstitial Lung Disease (PH-ILD)
Pulmonary Hypertension due to Interstitial Lung Disease (PH-ILD) Kaplan-Meier Survival Estimates in Patients with PH Associated with Chronic Fibrosing Idiopathic Interstitial Pneumonias and Idiopathic PAH – Data from the COMPERA Registry3 100 ¡ Interstitial lung disease (ILD) IPAH (N=798) encompasse
Slide 8: Epidemiology of PH-ILD
Epidemiology of PH-ILD ¡ Prevalence of ILD (US population-based study):1 Annually Annually 80.9 cases per 100,000 67.2 cases per 100,000 31.5 new cases per 100,000 26.1 new cases per 100,000 ¡ Precise prevalence of PH in patients with ILD is difficult to establish. – Most of the studies are from cas
Slide 9: Pathophysiology of PH-ILD
Pathophysiology of PH-ILD ¡ The mechanisms underlying the development of Potential Mechanisms of Remodeling in ILD and PH3 PH-ILD are complex, overlapping, and incompletely understood.1 ¡ Various factors contribute to PH development, including:2 – Hypoxemia – Vascular remodeling – Fibrogenesis – Dis
Slide 10: PH-ILD Study Outcomes
PH-ILD Study Outcomes Previous clinical trials have not conclusively demonstrated efficacy for pulmonary vasodilator therapy in PH-ILD Proposed Treatment Results STEP-IPF study did not achieve 20% change in 6MWD, but did suggest increased quality of life and SILDENAFIL decreased shortness of breath’
Slide 11: Current Management and Treatment Considerations
Current Management and Treatment Considerations Suspect Clinical, functional or imaging results suggestive of concomitant PH Support Echocardiogram Confirm Right heart catheterization There are currently no approved therapies for Stratify Group 1 versus group 3 PH PH-ILD. Limited CLD Severe CLD Obst
Slide 12: INCREASE
INCREASE A Multicenter, Randomized, Double-Blinded, Placebo- Controlled Trial to Evaluate the Safety and Efficacy of Inhaled Treprostinil in Patients with Pulmonary Hypertension due to Interstitial Lung Disease 12
Slide 13: INCREASE – Study Design and Inclusion Criteria
INCREASE – Study Design and Inclusion Criteria Phase 3, multicenter, randomized (1:1), double-blind, placebo-controlled, 16-week, parallel-group (inhaled treprostinil / placebo) study (NCT02630316) Key Inclusion Criteria Key Exclusion Criteria ¡ Confirmed diagnosis of Group 3 PH based on CT within 6
Slide 14: Eligible Study Population
INCREASE Eligible Study Population Group 3 PH due Included in INCREASE study enrollment to Lung Disease Alveolar Interstitial Lung Mixed Restrictive & Sleep-Disordered Chronic Exposure Developmental COPD Hypoventilation Disease (ILD) Obstructive Breathing Disorders to High Altitude Lung Diseases Idi
Slide 15: Study Assessments
Study Assessments Primary Endpoint Secondary Endpoints ¡ Change in 6MWD measured at peak exposure from ¡ Change in NT-proBNP from Baseline to Week 16 Baseline to Week 16 ¡ Time to clinical worsening - time of randomization until – 6-minute walk test (6MWT) performed at peak study discontinuation pla
Slide 16: Study Assessments
Study Assessments Exploratory Endpoints Additional Safety Endpoints ¡ Change in Quality of Life (SGRQ) ¡ Adverse events (AEs) ¡ Change in peak distance saturation product (DSP) ¡ Supplemental Oxygenation Requirements ¡ Change in peak 6MWD from Baseline to Weeks 4 ¡ Pulse oximetry and 8 ¡ Changes in
Slide 17: INCREASE – Study Procedures
INCREASE – Study Procedures Timeline of Study Endpoint Assessments Treatment Phase Week 4 Week 8 Week 12 Week 15 Week 16 Inhaled treprostinil (6 mcg/breath) 4 times daily* N=163 Screening Randomization 1:1 ≤ 30 days Placebo 4 times daily* N=163 Primary endpoint measure - 6MWD at peak exposure from B
Slide 18: Baseline Characteristics of Study Population
Baseline Characteristics of Study Population Inhaled Treprostinil Placebo N=163 N=163 Age Mean (SD) 65.6 (12.7) 67.4 (11.2) Sex, n (%) Male 78 (47.9%) 95 (58.3%) Female 85 (52.1%) 68 (41.7%) Time since PH-ILD Diagnosis, years Mean (SD) 0.54 (1.16) 0.54 (1.31) Etiology of PH-ILD, n (%) Idiopathic int
Slide 19: Baseline Assessments of Study Population
Baseline Assessments of Study Population TYVASO Placebo n=163 n=163 6MWD, meters Mean (range) 254.1 (100-538) 265.1 (30-505) Median 256 260 PVR, WU Mean (range) 6.369 (3.11-18.05) 6.013 (3.06-17.62) Median 5.57 5.06 NT-proBNP, pg/mL Mean (range) 1857.53 (10.2-21942) 1808.86 (23-16297) Median 550.5 4
Slide 20: Baseline Assessments of Study Population (Continued)
Baseline Assessments of Study Population (Continued) Inhaled Treprostinil Placebo Pulmonary Function Tests N=163 N=163 FEV1 % Predicted Mean (range) 63.9 (23, 120) 65 (22, 145) Median 63 63 FVC % Predicted Mean (range) 62.5 (24, 130) 63.8 (20, 134) Median 60 61 TLC % Predicted Mean (range) 62.9 (25,
Slide 21: Screening, Randomization, and Follow-Up
Screening, Randomization, and Follow-Up 462 patients were screened for eligibility 136 patients screen failed 326 underwent randomization 163 assigned to receive TYVASO 163 assigned to receive placebo 40 prematurely discontinued treatment 38 prematurely discontinued treatment with TYVASO for the fol
Slide 22: 6MWD Results Through Week 16
6MWD Results Through Week 16 — Mixed Model Repeated Measurement 40 35 At Week 16, inhaled we . = 30 P=0.002 treprostinil patients £ = 24.13 had a placebo- g 25 a a corrected difference [iy é from Baseline in peak iam 2 6MWD of 31.12 meters He 5 49 P=0.34 (95% Cl: 16.85, 45.39; P<0.001). Rep 5 0 Week
Slide 23: 6MWD Results Through Week 16
6MWD Results Through Week 16 Inhaled treprostinil Placebo Observed MMRM MCMC At Week 16, inhaled treprostinil patients 30 148 132 125 121 had a placebo- 25 corrected difference Change from Baseline (m) 20 from Baseline in peak 15 6MWD of 31.12 meters 10 5 (95% CI: 16.85, 45.39; P<0.001). 131 121 120
Slide 24: Subgroup Analyses of Peak 6MWD at Week 16
Subgroup Analyses of Peak 6MWD at Week 16 – MMRM Analysis INHALED TREPROSTINIL PLACEBO SUBGROUP LS MEAN DIFFERENCE (95% CI) # PATIENTS # PATIENTS OVERALL 121 120 31.1 (16.9, 45.4) AGE GROUP <65 years 48 32 27.0 (-2.2, 56.1) 65 to 80 years 63 78 32.9 (15.2, 50.5) ≥80 years 10 10 28.3 (-16.2, 72.9) SE
Slide 25: Secondary and Exploratory Endpoints
Secondary and Exploratory Endpoints Significant differences were observed with inhaled treprostinil, including: – Improvements in NT-proBNP – Reduction in time to clinical worsening – Improvements in peak 6MWD at Week 12 – Improvements in trough 6MWD at Week 15 No significant differences in patient-
Slide 26: NT-proBNP Results by Study Visit
NT-proBNP Results by Study Visit 0.74 (0.62, 0.88) 0.58 (0.47, 0.72) Estimated Difference (95% CI) P<0.001 P<0.001 3000 2737.45 2500 2347.6 2118.75 2106.05 Median (IQR) NT-proBNP (pg/mL) 1915.35 1957.75 2000 Inhaled treprostinil resulted 1500 in a 42% reduction in NT- proBNP when compared to placebo
Slide 27: Kaplan-Meier Plot of Time to First Clinical Worsening Event
Kaplan-Meier Plot of Time to First Clinical Worsening Event 100 75 Clinical worsening occurred in a 37 patients (22.7%) in the treprostinil group as compared with 54 patients Patients without an event (%) (33.1%) in the placebo group 25 (hazard ratio, 0.61; 95% Cl, 0.40 to 0.92; P = 0.04 by the P=0.
Slide 28: Summary of Clinical Worsening Events
Summary of Clinical Worsening Events Inhaled Treprostinil Placebo Occurrence of Clinical Worsening P-Value N=163 N=163 Any Events 37 (22.7%) 54 (33.1%) 0.04 (1) Hospitalization due to cardiopulmonary indication 18 (11%) 24 (14.7%) Decrease in 6MWD >15% from Baseline 13 (8%) 26 (16%) Death (all cause
Slide 29: Kaplan-Meier Plot of Time to Exacerbation of Underlying Lung Disease
Kaplan-Meier Plot of Time to Exacerbation of Underlying Lung Disease 100 = 75 § Inhaled treprostinil resulted in 3 a 34% reduction in risk of Fy exacerbation of underlying = : g © lung disease compared to £ placebo (P=0.03). 2 2 : ae 2 os 26.4% inhaled treprostinil and & ‘ 38.7% placebo patients hal
Slide 30: Safety
Safety Treatment was well tolerated – Safety profile was consistent with previous studies of inhaled treprostinil – Most treatment-related AEs were mild to moderate in intensity 10% of inhaled treprostinil and 8% of placebo patients prematurely discontinued treatment due to an AE Serious AEs occurre
Slide 31: Summary of Adverse Events
Summary of Adverse Events Inhaled Treprostinil Placebo Most Frequently Occurring AEs* N=163 N=163 n (%) n (%) Cough 71 (43.6%) 54 (33.1%) Headache 45 (27.6%) 32 (19.6%) Dyspnea† 41 (25.2%) 51 (31.3%) Dizziness 30 (18.4%) 23 (14.1%) Nausea 25 (15.3%) 26 (16%) Fatigue 23 (14.1%) 23 (14.1%) Diarrhea 22
Slide 32: FVC Results by Study Visit
FVC Results by Study Visit § Inhaled treprostinil resulted in placebo-corrected improvements in FVC of 28.47 mL and 44.40 mL at Weeks 8 and 16, respectively. § Percent predicted FVC at Week 8 (1.79%; P=0.01) and Week 16 (1.80%; P=0.03). LS Mean Change in FVC (mL) by Week LS Mean Change in FVC % Pred
Slide 33: Subgroup Analysis of FVC
Subgroup Analysis of FVC Contrast: Inhaled treprostinil - Placebo PH-ILD Estimated Difference Etiology Variable Visit Treatment LS Mean (95% CI) P-value Inhaled treprostinil (n=58) 9.27 46.48 Week 8 FVC Placebo (n=71) -37.21 (-32.55, 125.51) 0.25 (mL) Inhaled treprostinil (n=52) 22.16 108.18 Week 16
Slide 34: Additional Safety Endpoints
Additional Safety Endpoints No clinically relevant treatment-related changes in pulse oximetry or supplemental oxygen use in either group over the study period. No deleterious effect of inhaled treprostinil on any PFT parameter during the study. Median improvement in percent predicted FVC at Week 16
Slide 35: Conclusions
Conclusions ¡ INCREASE is the largest and most comprehensive study of this patient group to date. ¡ Patients experienced significant improvements in exercise capacity (6MWD) as early as 8 weeks, with effects sustained throughout the 16-week treatment period. ¡ Patients demonstrated improvements in o
Slide 36: Thank you to all INCREASE investigators and study personnel
Thank you to all INCREASE investigators and study personnel! INCREASE TRIAL RESULTS INCREASE • Roblee Allen, MD, University of California, Davis Medical • Micah Fisher, MD, The Emory Clinic • Colleen A. McEvoy, MD, Washington University • Lewis Gilmer Satterwhite, MD, Leslie Spikes, MD, University C
Slide 37: Tyvaso PH-ILD Commercial Strategy
TYVASO PH-ILD COMMERCIAL STRATEGY
Slide 38: Our Focus
INCREASE TRIAL RESULTS OUR FOCUS DEVELOPING NOVEL, LIFE-EXTENDING TECHNOLOGIES FOR PATIENTS IN TWO CORE AREAS: 1 2 PAH(1) ILD(2) (1) PAH = Pulmonary Arterial Hypertension. (2) ILD = Interstitial Lung Disease. 38 JANUARY 2021
Slide 39: Tyvaso Portfolio Positioned to Advance Our Growth
INCREASE TRIAL RESULTS TYVASO PORTFOLIO POSITIONED ®(1) TO ADVANCE OUR GROWTH 45K PAH NO APPROVED RX Pulmonary Arterial 30K PH-ILD Hypertension Pulmonary Hypertension associated with Interstitial Lung Disease INCREASE STUDY ESTIMATED NO DISEASE-MODIFYING RX US PATIENT POPULATION(1) NO APPROVED RX 10
Slide 40: Epidemiology of PH-ILD
v2 INCREASE TRIAL RESULTS EPIDEMIOLOGY OF PH-ILD PREVALENCE OF PH IN US S ILD ADVANCES, A PATIENTS WITH ILD(1): FREQUENCY OF PH CONTINUES TO RISE, BEYOND 50%(2) 230K ILD ~US PATIENT POPULATION(1) ILD F REQUENCY OF P H - IL D >50% » Precise prevalence of PH in patients with ILD is difficult 15% to es
Slide 41: PH Significantly Impacts ILD Patient Outcomes
INCREASE TRIAL RESULTS PH SIGNIFICANTLY IMPACTS ILD PATIENT OUTCOMES 1 PH changes the trajectory of patient prognosis and may impact ILD treatment choices2 PH REDUCES SURVIVAL IN PATIENTS WITH IPF, A SUBSET OF ILD3 PH REDUCES SURVIVAL IN PATIENTS WITH ILD/IPF mPAP≤25 mm Hg mPAP>25 mm Hg » Based on a
Slide 42: Identification of PH-ILD Patients
INCREASE TRIAL RESULTS IDENTIFICATION OF PH-ILD PATIENTS SUSPECT SUPPORT CONFIRM SUSPECT PH-ILD WHEN A PATIENT SUPPORT A SUSPICION OF CONFIRM PH-ILD WITH: PRESENTS WITH: PH-ILD WITH: » Right heart catheterization2 » Signs and symptoms out of proportion » Echocardiogram1,2,5 » Hemodynamic definition6
Slide 43: Physicians Are Eager for Tyvaso in PH-ILD
INCREASE TRIAL RESULTS PHYSICIANS ARE EAGER FOR TYVASO IN PH-ILD Surveys indicate physicians would use Tyvaso for most of their PH-ILD patients1 » INCREASE data will have a positive impact1 » INCREASE data suggests PH-ILD treatment will be augmented with a new, safe, effective » HCPs are motivated t
Slide 44: Majority of ILD Treaters Are Not PAH Treaters
INCREASE TRIAL RESULTS MAJORITY OF ILD TREATERS ARE NOT PAH TREATERS US PRESCRIBER UNIVERSE UNIQUE ILD TREATERS IN US DECILE 1-2 ~3,000 ~55K Patients PAH ~1,300 ILD 2,300 4,700 PHYSICIANS PHYSICIANS DECILE 3-10 ~1,700 ~160K Patients PAH PH-ILD • Higher decile for PAH vs ILD • Higher decile PH-ILD vs
Slide 45: Expanding Our Commercial/Medical Organization for PH-ILD
INCREASE TRIAL RESULTS EXPANDING OUR COMMERCIAL/MEDICAL ORGANIZATION FOR PH-ILD ~40% EXPANSION RESTRUCTURED SALES HIRING IS COMPLETE IN FIELD-BASED STAFF ORGANIZATION WITH INCLUDING SALES, MEDICAL THREE TEAMS: SCIENCE LIAISONS, AND NURSE SPECIALISTS A Orenitram and Tyvaso in PAH ® ~40% B Remodulin®
Slide 46: Planning for Rapid Tyvaso PH-ILD Uptake
INCREASE TRIAL RESULTS PLANNING FOR RAPID TYVASO PH-ILD UPTAKE If approved for PH-ILD, we expect to double the number of Tyvaso® patients within ~18 months of launch 6,000 # OF PATIENTS ON TYVASO OUR GOAL: 1 3,000 THE NUMBER TYVASO PATIENTS TODAY April 2021 2H/2022 PDUFA (1) 2x goal assumes an April
Slide 47: Key Summary Points
INCREASE TRIAL RESULTS KEY SUMMARY POINTS ADDRESSABLE MARKET PHYSICIANS INDICATE OF >30K PATIENTS INCREASE DATA IMPACTFUL >30K WITH NO APPROVED AND PLAN TO USE TYVASO THERAPIES FOR PH-ILD PATIENTS EFFORTS UNDERWAY TO ~ 40% UT STAFF EXPANSION INCREASE AWARENESS EXPANSION TO SUPPORT LAUNCH ON PH IMPAC
Slide 48: Key 2021 Catalysts
INCREASE TRIAL RESULTS KEY 2021 CATALYSTS Implantable Remunity INCREASE System Tyvaso DPI for Remodulin (1) Commercial sNDA PDUFA Date Commercial Anticipated Launch April 2021 Launch NDA PDUFA (1) FDA requires that certain conditions of Medtronic’s PMA approval of the Implantable System for Remoduli
Slide 49: Q&A
INCREASE TRIAL RESULTS Q&A MICHAEL BENKOWITZ STEVEN D. NATHAN, MD President and Chief Operating Officer United Therapeutics Corporation INCREASE Study Investigator Director of the Advanced Lung Disease Program and Director of the Lung Transplant Program at Inova Fairfax Hospital in Falls Church, VA
Slide 50: United Therapeutics
United Therapeutics POR A~ Fe wa® N c oO R
United Therapeutics — Investor Presentation (January 2021) on 6ix