Slide 1: Topline Results of Phase 2b Study of TPIP in PAH Patients
Topline Results of Phase 2b Study of TPIP in PAH Patients June 10, 2025 TPIP: Treprostinil Palmitil Inhalation Powder | PAH: pulmonary arterial hypertension 11
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation contains forward-looking statements that involve substantial risks and uncertainties. “Forward-looking statements,” as that term is defined in the Private Securities Litigation Reform Act of 1995, are statements that are not historical facts and involve a
Slide 3: Speakers Agenda Slides
Speakers Agenda Slides 1 Opening Remarks 5 Will Lewis Chair & CEO 2 Study Results 7-16 3 Closing Remarks 17 4 Q&A Session 18 Gene Sullivan Chief Product Strategy Officer 3
Slide 4: Opening Remarks
Opening Remarks Will Lewis | Chair & CEO 4
Slide 5: Phase 2b Study of TPIP for PAH is a Clear Success
Phase 2b Study of TPIP for PAH is a Clear Success • 35%* placebo-adjusted PVR reduction from baseline • 35.5-meter placebo-adjusted 6MWD improvement from baseline • Efficacy endpoints measured ~24-hours after prior dose; included milder, heavily pre-treated patients • Results illustrate a competitiv
Slide 6: Study Results
Study Results Gene Sullivan| Chief Product Strategy Officer 6
Slide 7: TPIP Designed with the Patient Experience in Mind
TPIP Designed with the Patient Experience in Mind Challenges of Conventional Prostanoids Potential Advantages of TPIP • Rapid systemic metabolism • Inert formula limits adverse airway effects • Systemic & local adverse effects • Local delivery minimizes systemic exposure • Short duration in the lung
Slide 8: TPIP Designed to Provide Long-Acting Vasodilation with Once-Daily Administration
TPIP Designed to Provide Long-Acting Vasodilation with Once-Daily Administration Randomized, Double-Blind, Multi-Center, Placebo-Controlled Phase 2b PAH Study Primary Analysis: Data Included in this Presentation Treatment period 4 weeks 4 weeks 16 weeks Primary Endpoint 3-week titration • Change fro
Slide 9: Baseline Characteristics Reasonably Well-Balanced Across Study Arms
Baseline Characteristics Reasonably Well-Balanced Across Study Arms TPIP (N=69) Placebo (N=33) Total (N=102) Age: Mean, years (SD) 48.1 (15.00) 46.9 (15.22) 47.7 (15.00) Age < 65 years, % (n) 75.4 (52) 87.9 (29) 79.4 (81) Sex: Female, % (n) 84.1 (58) 78.8 (26) 82.4 (84) BMI: Mean, kg/m2 (SD) 26.746
Slide 10: TPIP Generally Well-Tolerated with a Low Discontinuation Rate
TPIP Generally Well-Tolerated with a Low Discontinuation Rate TPIP (N=69) Placebo (N=33) Total (N=102) TPIP Dose Titration, % (n)* Participants Titrated to at least 480 μg 84.1 (58) 84.8 (28) 75% Titrated to max dose of 640 μg 75.4 (52) 81.8 (27) Participants Completed the Study, % (n) Completed 89.
Slide 11: PVR: Highly Statistically Significant Primary Endpoint Achieved with Once-Daily Therapy
PVR: Highly Statistically Significant Primary Endpoint Achieved with Once-Daily Therapy (P<0.001*) TPIP (N=69) Placebo (N=33) Week 16 n Week 16 n Primary Endpoint Pulmonary Vascular Resistance PVR at Baseline: 35% Mean PVR, Wood Units (SD) 9.588 (5.0072) 69 11.069 (5.9400) 33 PVR at Week 16: * Mean
Slide 12: Exercise Capacity: TPIP Showed a Clear Improvement in 6MWD
Exercise Capacity: TPIP Showed a Clear Improvement in 6MWD (P=0.003*) TPIP (N=69) Placebo (N=33) Week 16 n Week 16 n Secondary Endpoint All Efficacy Endpoints 6-Minute Walk Distance Measured ~24 Hours After Dose 35.5 6MWD at Baseline (m): Mean (SD) 348.48 (79.791) 69 371.06 (60.571) 33 6MWD at Week
Slide 13: Cardiac Stress: TPIP Showed a Meaningful Reduction in NT-proBNP
Cardiac Stress: TPIP Showed a Meaningful Reduction in NT-proBNP (P<0.001*) TPIP (N=69) Placebo (N=33) Week 16 n Week 16 n Secondary Endpoint NT-proBNP Concentration All Efficacy Endpoints Measured ~24 Hours After Dose Concentration at Baseline (pg/mL): 60% Mean 785.58 69 798.91 33 Concentration at W
Slide 14: WHO Functional Class: More Patients on TPIP Achieved an Improvement in Functional Class
WHO Functional Class: More Patients on TPIP Achieved an Improvement in Functional Class TPIP (N=69) Placebo (N=33) Week 16 n Week 16 n Exploratory Endpoint WHO Functional Class Shift, % FC Improvement FC Improvement* at Week 16: 30.4 21 15.2 5 Week 16 vs. Baseline FC II Improvement to FC I 13.0 9 6.
Slide 15: Cardiac Index: TPIP Showed an Increase Compared to Placebo
Cardiac Index: TPIP Showed an Increase Compared to Placebo (P=0.006*) TPIP (N=69) Placebo (N=33) Week 16 n Week 16 n Exploratory Endpoint Cardiac Index, L/min/m2 TPIP Cardiac Index at Baseline: Cardiac Index 15% Mean 2.641 69 2.691 33 Cardiac Index at Week 16: Mean 3.070 62 2.777 33 LS Mean Ratio to
Slide 16: Safety: Most Common TPIP TEAEs were Consistent with Known Profile of Inhaled Treprostinil
Safety: Most Common TPIP TEAEs were Consistent with Known Profile of Inhaled Treprostinil TPIP (N=69) Placebo (N=33) Week 16 n Week 16 n Safety TEAEs, % TPIP Any TEAE 88.4 61 75.8 25 Serious TEAE 7.2 5 3.0 1 Incidence Severe TEAE 5.8 4 3.0 1 TEAE Leading to Treatment Discontinuation 5.8 4 0 0 of Cou
Slide 17: Closing Remarks
Closing Remarks 1 Goal of TPIP: once-daily therapy that combines the continuity of parenteral treatment with the localization and convenience of inhaled therapy 2 Plan to advance TPIP to Phase 3 before the end of 2025 for PH-ILD and in early 2026 for PAH 3 Potential to realize stronger efficacy with
Slide 18: Q&A Session
Q&A Session Thank you to the patients and investigators who participated in this study! Will Lewis Gene Sullivan Martina Flammer Sara Bonstein Chair & CEO Chief Product Strategy Officer Chief Medical Officer Chief Financial Officer 18
Slide 19: insmed
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