Milestone Pharmaceuticals Inc. · NASDAQ:MIST
Milestone Pharmaceuticals — Corporate Update (November 2023)
31 slides from Milestone Pharmaceuticals's corporate update, Nov 13, 2023
Slide 1: Atrial Fibrillation Program Update November 2023
Company Overview CONFIDENTIAL Atrial Fibrillation Program Update November 2023
Slide 2: Forward Looking Statement
Forward Looking Statement 2 Milestone - Atrial Fibrillation Program Overview The Presentation contains forward - looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, as amended. Words such as ‘‘aim,’’ ‘‘anticipate,’’ ‘‘assume,’’
Slide 3: Recent Progress and Key Upcoming Events
Recent Progress and Key Upcoming Events 3 Milestone - Atrial Fibrillation Program Overview NDA submission for PSVT – October 2023 1 2 3 Initial data in AFib - RVR (NODE - 303 study) presented – May 2023 4 Operating runway to mid - 2025 via RTW financing – March 2023 7 AFib - RVR Ph2 ( ReVeRA study)
Slide 4: KOL View on Currently Available Approaches / Unmet Need in AFib
KOL View on Currently Available Approaches / Unmet Need in AFib 4 • Regardless of rate - or rhythm - control strategy, break - through episodes of AFib - RVR are frequent, symptomatic, highly burdensome, and disruptive • Current treatment of acute attacks in the emergency department are burdensome a
Slide 5: Clinical Pipeline Advancement for Etripamil
Clinical Pipeline Advancement for Etripamil 5 Milestone - Atrial Fibrillation Program Overview PSVT AFib - RVR Phase 1 Phase 2 Phase 3 NDA Filing / Approval Pharmacology of L - type calcium channel blockers drives broad clinical utility Rapid conversion to sinus rhythm PSVT = Paroxysmal Supraventric
Slide 6: Experience and Successful Progress in PSVT Program Applied to AFib-RVR Program
Experience and Successful Progress in PSVT Program Applied to AFib - RVR Program 6 Milestone - Atrial Fibrillation Program Overview • Track - record of etripamil NS development in PSVT • Conducted multi - national PSVT development program in at - home setting with tachycardia - symptom prompted, sel
Slide 7: ReVeRA Phase 2 Proof of Concept Trial of Etripamil in AFib-RVR
ReVeRA - Phase 2 Proof of Concept Trial of Etripamil in AFib - RVR in the Emergency Department Setting 7 Milestone - Atrial Fibrillation Program Overview Patient presents to ED with episode of AFib - RVR Dosing & Assessment Efficacy Analysis 1. Baseline ECG for ≥ 10 min 2. Administer double blind st
Slide 8: ReVeRA was designed to demonstrate
ReVeRA was designed to demonstrate: 8 Milestone - Atrial Fibrillation Program Overview 1 Reduction = reduction from VR baseline. 2 Treatment Satisfaction Questionnaire for Medication - 9, a validated patient reported outcome tool. AFib - RVR = atrial fibrillatio n with rapid VR, VR = ventricular rat
Slide 9: ReVeRA Patient Characteristics (Safety Population)
ReVeRA Patient Characteristics (Safety Population) 1 9 Milestone - Atrial Fibrillation Program Overview Characteristic Placebo n=29 Etripamil n=27 Total N=56 Age, years Mean (SD) 64.59 ± 10.53 64.63 ± 10.61 64.6 (10.47) Median (range) 66.00 (35.00, 83.00) 64.00 (45.00, 88.00) 65 (35.00, 88.00) Site
Slide 10: ReVeRA Primary Endpoint – Maximum Reduction in VR (60 min)
10 Milestone - Atrial Fibrillation Program Overview 1 Efficacy Population (all randomized patients receiving study drug remaining in atrial fibrillation with adequately diagnostic ECG recordings for at le ast 60 min post drug). Maximum VR reductions determined based on 5 - min moving average of VR.
Slide 11: ReVeRA – Mean VR Change from Baseline (60 min)
-40 -35 -30 -25 -20 -15 -10 -5 0 5 10 0 10 20 30 40 50 60 Change in Ventricular Rate (bpm) Time (minutes) Etripamil Placebo ReVeRA – Mean VR Change from Baseline (60 min) 1 ReVeRA Data Show Substantial & Rapid Reduction in VR for the Etripamil Group Note: Data plotted on time course are not those di
Slide 12: ReVeRA – Mean VR Change from Baseline (180 min)
12 Milestone - Atrial Fibrillation Program Overview 1 mITT Population (all randomized patients receiving study drug) . 2 From t - test of difference between the a reas under the curves (AUC) of plots of absolute mean heart rate . X - axis: of plot: time following drug administration; Y - axis of plo
Slide 13: 13 Milestone - Atrial Fibrillation Program Overview 13 13
13 Milestone - Atrial Fibrillation Program Overview 13 13
Slide 14: ReVeRA: TSQM-PRO Assessment & Results
ReVeRA : TSQM - 9 PRO 1 Assessment & Results 14 Milestone - Atrial Fibrillation Program Overview Placebo 2 N=25 Etripamil 2 N=24 p value 3 Effectiveness Domain Scores, mean (SD) 36.67 (21.64) 62.69 (21.59) p<0.0001 • TSQM - 9 PRO 1 includes an Effectiveness Domain • Domain includes three questions,
Slide 15: ReVeRA Study - Most Common Adverse Events
Milestone - Atrial Fibrillation Program Overview 15 Patients with ≥1 of most common adverse events (≥5%) 1 Placebo (N= 29) 2 Etripamil (N=27) 2 Nasal Discomfort 11 (37.9%) 16 (59.3%) Rhinorrhea 1 (3.4%) 9 (33.3%) Increased Lacrimation 5 (17.2%) 8 (29.6%) Throat Irritation -- 5 (18.5%) Dizziness 3 (1
Slide 16: ReVeRA Study - Summary of Serious Adverse Events
ReVeRA Study - Summary of Serious Adverse Events • One etripamil patient experienced 2 SAEs classified as related to study drug • Transient severe bradycardia and syncope, assessed as due to hyper - vagotonia • O ccurred in a patient with a history of vagal events • F ully resolved with placing the
Slide 17: ReVeRA demonstrated
ReVeRA demonstrated: 17 Milestone - Atrial Fibrillation Program Overview 1 Reduction from baseline. 2 Treatment Satisfaction Questionnaire for Medication - 9. AFib - RVR = atrial fibrillation with rapid VR, VR = ventricular rate • Goal: 20 bpm VR reduction 1 vs placebo • ReVeRA: - 30 bpm vs placebo;
Slide 18: FDA Pre-IND Guidance for Path to Approval in AFib-RVR
FDA Pre - IND Guidance for Path to Approval in AFib - RVR 1 • Single study with self - administered etripamil and in an at - home setting, to gain a labelled indication via supplemental NDA ( sNDA ) • Can utilize the safety database from PSVT • Primary analysis to be on ITT population (all patients
Slide 19: Proposed Phase 3 Registrational Study in AFib-RVR
Proposed Phase 3 Registrational Study in AFib - RVR 1 • Key Inclusion Criteria: history of symptomatic episodes of AFib - RVR • Patients self - administer drug at - home for perceived episodes of AFib - RVR • Dose: etripamil NS 70 mg, repeat - dose regimen • Target Population = patients with verifie
Slide 20: AFib-RVR Program Timeline Projections
AFib - RVR Program Timeline Projections 20 • FDA Confirmation of Ph3 Protocol: 1Q 2024 • Study Start: Mid 2024 • Top - Line Data: Mid 2026 Milestone - Atrial Fibrillation Program Overview
Slide 21: Market Opportunity for Etripamil in AFib-RVR
Market Opportunity for Etripamil in AFib - RVR
Slide 22: KOL View on Currently Available Approaches / Unmet Need in AFib
KOL View on Currently Available Approaches / Unmet Need in AFib 22 • Regardless of rate - or rhythm - control strategy, break - through episodes of AFib - RVR are frequent, symptomatic, highly burdensome, and disruptive • Current treatment of acute attacks in the emergency department are burdensome
Slide 23: PSVT & AFib-RVR Populations in the US
PSVT & AFib - RVR Populations in the US Source(s): 1. Colilla et al., Am. J. Cardiol . 2013, 112(8), 1142 - 1147; Miyasaka et al., Circulation, 2006, 114, 119 - 125. American Heart Association 2 . HCUP ED & Admissions Data (2016), accessed January 2021. 3. Rehorn et al. Journal of Cardiovascular Ele
Slide 24: Peak US Market Opportunity for Etripamil in AFib-RVR
Peak US Market Opportunity for Etripamil in AFib - RVR AFib - RVR = Atrial Fibrillation with Rapid Ventricular Rate 1. Colilla et al., Am. J. Cardiol . 2013, 112(8), 1142 - 1147; Miyasaka et al., Circulation, 2006, 114, 119 - 125; 10M estimate reflects the midpoint of published estimates (~8M to ~12
Slide 25: Peak US Market Opportunity for Etripamil in PSVT and AFib-RVR
Peak US Market Opportunity for Etripamil in PSVT and AFib - RVR Sources: 1. Rehorn et al. Journal of Cardiovascular Electrophysiology. 2021 Aug; 32(8): 2199 - 2206. doi : 10.1111/jce.15109. ; 2. 2019 market research with patients conducted by BluePrint Research Group, ( n=247); 3. 2020 market resear
Slide 26: Finances – as of September 30, 2023
Finances – as of September 30, 2023 Cash and short - term investments of $75.7M Synthetic Royalty Financing of $75M available upon approval (1) Cash as of September 30, 2023 together with synthetic royalty financing expected to fund operations into mid - 2025 (1) In March 2023, Milestone announced a
Slide 27: Strategic Approach to Value Creation
Strategic Approach to Value Creation • 2024 – Financially prudent commercial build to prepare for launch • 2025 – Staged entry following market access to demonstrate PSVT market potential • 2026 – Deliver phase 3 data in AFib - RV – Fully access cardiology market for PSVT with additional reps/resour
Slide 28: Milestone Pharma - Targeting Significant Unmet Need for Patient Management of Common Heart Conditions
Milestone Pharma - Targeting Significant Unmet Need for Patient Management of Common Heart Conditions PSVT = Paroxysmal Supraventricular Tachycardia; AFib - RVR = Atrial Fibrillation with Rapid Ventricular Rate; NDA = New Drug Application 28 Milestone - Atrial Fibrillation Program Overview Targeting
Slide 29: Appendix
AA AAAd bs... Milestone Appendix
Slide 30: TSQM-9: Effectiveness Domain Questions
TSQM - 9: Effectiveness Domain Questions 1. How satisfied or dissatisfied are you with the ability of the medication or treat your condition? 2. How satisfied or dissatisfied are you with the way the medication relieves your symptoms? 3. How satisfied or dissatisfied are you with the amount of time
Slide 31: Time from Drug Administration to ≥20% and ≥10% Reductions from Baseline Ventricular Rate
Time from Drug Administration to ≥20% and ≥10% Reductions from Baseline Ventricular Rate 31 Milestone - Atrial Fibrillation Program Overview ≥ 20% reduction ≥ 10% reduction Difference in achievement of % reduction, p - value 1, 2 <0.0001 <0.0001 Median time to achieve % reduction from baseline VR Pl
Milestone Pharmaceuticals — Corporate Update (November 2023) on 6ix