Milestone Pharmaceuticals Inc. · NASDAQ:MIST

Milestone Pharmaceuticals — Technical Presentation (April 2024)

18 slides from Milestone Pharmaceuticals's technical presentation, Apr 1, 2024

  1. Slide 1: NODE-303: Multi-Center, Multi-National, Open-Label Safety Study of Etripamil Nasal Spray for PSVT

    NODE-303: Multi-Center, Multi-National, Open-Label, Safety Study of Etripamil Nasal Spray for Patients With Paroxysmal Supraventricular Tachycardia James E. Ip, MD, FACC, FHRS Professor of Clinical Medicine Weill Cornell Medicine On behalf of: James E. Ip, MD; Benoit Coutu, MD; John H. Ip, MD; Peter

  2. Slide 2: Disclosures

    Disclosures James E. Ip, MD: • Received compensation as study investigator and steering committee member for Milestone Pharmaceuticals • Received honoraria/speaking/consulting fees for Abbott Medical, Boston Scientific, and Medtronic Inc. • Membership on advisory committee and/or steering committee

  3. Slide 3: Etripamil: Potential New Treatment for PSVT

    Etripamil: Potential New Treatment for PSVT • Novel, investigational, L-type channel calcium channel blocker • Formulated for intranasal spray with: – Rapid onset of action (Tmax ≤7 minutes) – Metabolism: inactivation by blood esterases • Developed to satisfy unmet need for self-administered therapy

  4. Slide 4: RAPID: Conversion of Adjudicated PSVT to NSR

    RAPID: Conversion of Adjudicated PSVT to NSR at 30 and 60 min 100% Test dose required: 90% Kaplan-Meier Probability of Conversion (%) 80% 73.5% • During Sinus Rhythm 70% 64.3% • Continuous ECG Monitoring 60% • Serial BP Measurements 50% 54.5% every 5 min 40% 30% 1.3% test dose failure in RAPID 31.2%

  5. Slide 5: NODE-303 Phase 3 Study Design

    Real-world design: NODE-303 Phase 3 Study Design • No test dose • No exclusion of AF/AFL history • Multiple episodes (up to four) Screening visit Treatment period End of study Outcome measures Key inclusion criteria Treated PSVT episode Follow-up visit Final visit Safety assessments ▪ Patients ≥18 y

  6. Slide 6: Patient Disposition and Analyses Populations

    Patient Disposition and Analyses Populations Patients screened Screen failure (n=226) (N=1342) Eligibility criteria not met (159) Sponsor decision (11) Withdrawal of consent by patient (13) Planned ablation (7) ECG of concern (3) COVID-19 (1) Physician decision (3) Other (33) Patients enrolled (N=11

  7. Slide 7: Demographics & Baseline Characteristics (Safety Population)

    Demographics & Baseline Characteristics (Safety Population) Mean (SD) or Patients for Categorical Variables, n (%) Age, y 54.9 (13.6) Sex, n (%) Female 344 (68.4) Male 159 (31.6) Region, n (%) North America 353 (70.2) South America 150 (29.8) Age at first PSVT diagnosis, y 47.7 (16.8) Time since fir

  8. Slide 8: Rhythms Captured on CMS During Perceived PSVT Episodes

    Rhythms Captured on CMS During Perceived PSVT Episodes • 503 patients treated 1054 episodes as perceived PSVT PSVT, 52.3% Sinus Rhythm/ – 220 pts treated 1 episode Sinus Tachycardia, 12.7% – 118 pts treated 2 episodes Atrial Fibrillation/ – 62 pts treated 3 episodes Atrial Flutter/ Atrial Tachycardi

  9. Slide 9: Conversion of PSVT to SR: All Episodes (Efficacy Population)

    Conversion of PSVT to SR: All Episodes (Efficacy Population) Secondary Efficacy Assessments KM Estimate of PSVT By 30 By 60 Conversion to Minutes Minutes Sinus Rhythm NODE-301 53.7 63.7 NODE-302 60.2 75.1 RAPID 64.3 73.5 NODE-303 60 69.9 Median time to conversion: 17.0 min (95% CI, 13.9–22.3) CI = c

  10. Slide 10: Additional Secondary Endpoints

    Additional Secondary Endpoints Kaplan-Meier Analyses of Confirmed PSVT to SR Conversion at 60 Minutes by Episode (Efficacy Population) Episode 1 Episode 2 Episode 3 Episode 4 All Episodes (n=312) (n=151) (n=71) (n=18) Kaplan-Meier Estimate of Patients Converted to 69.9 70.5 73.5 57.7 77.8 SR Within

  11. Slide 11: Overview of Treatment-Emergent Adverse Events (Safety Population)

    Overview of Treatment-Emergent Adverse Events (Safety Population) TEAE Category (Safety Population N=503) Events, n Patients, n (%) Any TEAE 997 301 (59.8) Severe 43 31 (6.2) Any TEAE 24 h 776 269 (53.5) Severe 22 16 (3.2) Serious TEAE 33 26 (5.2) Drug related 0 0 Leading to deatha 4 4 (0.8) Serious

  12. Slide 12: Summary of Drug-Related TEAEs Leading to Study Drug Discontinuation

    Summary of Drug-Related TEAEs Leading to Study Drug Discontinuation Drug-Related TEAEs* (N=503) System Organ Class Preferred Term No. of Events n (%) Any TEAE 24 12 (2.4) Gastrointestinal disorders 1 1 (0.2) Oral discomfort 1 1 (0.2) General disorders and administration site conditions 1 1 (0.2) Fac

  13. Slide 13: Most Common (≥5%) Treatment-Emergent Adverse Events

    Most Common (≥5%) Treatment-Emergent Adverse Events Within 24 h After Etripamil Administration (Safety Population) Single Dose (70 mg) Optional Repeat Dose (2 × 70 mg) Total Safety Population TEAE 24 h (N=428) (N=75) (N=503) System organ class Preferred term Events, n Patients, n (%) Events, n Patie

  14. Slide 14: TEAEs of Special Interest (Safety Population)

    TEAEs of Special Interest (Safety Population) Single Dose (70 mg) Repeat Dose (2 × 70 mg) Total Safety Population (N=428) (N=75) (N=503) System Organ Class Preferred Term Events, n Patients, n (%) No. of Events n (%) No. of Events n (%) Any AEs 20 15 (3.5) 3 3 (4.0) 23 18 (3.6) Cardiac disorders 6 3

  15. Slide 15: Downward Trend in Treatment-Emergent Adverse Events With Repeat Episodes

    Downward Trend in Treatment-Emergent Adverse Events Within 24 h With Repeat Episodes TEAE = treatment-emergent adverse event. 15

  16. Slide 16: NODE-303: Summary and Conclusions

    NODE-303: Summary and Conclusions • NODE-303 was the first study to evaluate treatment of multiple episodes of PSVT with single and optional repeat-dose etripamil, self-administered outside of the healthcare setting as prompted by PSVT symptoms, without a prior medically supervised test dose • The s

  17. Slide 17: NODE-303 Trial Sites and Investigators

    NODE-303 Trial Sites and Investigators UNITED STATES Tamas Balogh, Mount Airy, NC Mirel Sanchez, Miami, FL Raja Chehayeb, Greenfield Park, QC Fernando Colombo Berra, Buenos Aires Roger Damle, Littleton, CO Ronald Polinsky, Wyomissing, PA Sander Fernandez, Orlando, FL Jeffrey Sean Healey, East Hamilt

  18. Slide 18: NODE-303: Now published online

    NODE-303: Multi-Center, Multi-National, Open-Label, Safety Study of Etripamil Nasal Spray for Patients With Paroxysmal Supraventricular Tachycardia Now published online: James E. Ip, MD1; Benoit Coutu, MD2; John H. Ip, MD3; Peter A. Noseworthy, MD, MBA4; Maria L. Parody, MD5; Farhad Rafii, MD6; Samu

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