Milestone Pharmaceuticals Inc. · NASDAQ:MIST
Milestone Pharmaceuticals — Investor Presentation (June 2021)
34 slides from Milestone Pharmaceuticals's investor presentation, Jun 2, 2021
Slide 1: Corporate Overview June 2021
Joseph Oliveto President & CEO Corporate Overview June 2021
Slide 2: Disclaimers
Disclaimers 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,’’ ‘‘believe,’’ ‘‘contemplate,’’ ‘‘continue,’’ ‘‘could,’’ ‘‘desig
Slide 3: Milestone Corporate Highlights
3 Milestone Corporate Overview Phase 3 Cardiovascular Company Etripamil - novel calcium channel blocker (IP protection until 2036) Shift from the ED to patient self - management Targeting Large Areas of Unmet Need PSVT AFib - RVR Additional pipeline opportunities First Phase 3 study findings and FDA
Slide 4: PSVT & AFib-RVR Patient Populations
PSVT Atrial Fibrillation 2 Million 4 5 Million 1 (expected to grow to 7 - 12M by 2030 1,3 ) 145 Thousand 785 Thousand 0.8 – 1.2 Million 6 2 Million 5 Source(s): 1. Khavjou , et al., Projections of Cardiovascular Disease Prevalence and Costs: 2015 – 2035, American Heart Association, November 2016. 2.
Slide 5: Supraventricular Tachycardias with a Common Patient Burden
Supraventricular Tachycardias with a Common Patient Burden Sources: adapted from https://en.ecgpedia.org/index.php?title=Supraventricular_Rhythms , accessed 2/2021 5 Milestone Corporate Overview PSVT (AVNRT and AVRT) AFib - RVR (a subset of AFib ) Regular rapid heart rate Irregular rapid heart rate
Slide 6: Role of Intravenous L-Type Calcium Channel Blockers
Role of Intravenous L - Type Calcium Channel Blockers 6 Milestone Corporate Overview for PSVT for AFib - RVR Sino - Atrial Node Atrio - Ventricular (AV) Node IV CCBs like verapamil or diltiazem slow conduction over the AV node… …to reduce the ventricular rate while still in AFib …to break the tachyc
Slide 7: Potential Paradigm-Changing Treatment to Empower Patient Control
Potential Paradigm - Changing Treatment to Empower Patient Control of their Condition • Time consuming • Anxiety provoking • Costly 7 Milestone Corporate Overview Issues with the current standard of care in the Emergency Department (ED) • Often results in a hospital admission • Experienced by patien
Slide 8: Etripamil Nasal Spray is Designed to be Fast, Convenient, and Empowering
Etripamil Nasal Spray is Designed to be Fast, Convenient, and Empowering 8 Milestone Corporate Overview Etripamil Class Novel CCB Potency (IC 50 ) 11 nM Metabolism Rapid: Esterase - mediated • Clinically - validated mechanism − Calcium channel blockers (CCBs) slow conduction over the AV node • Rapid
Slide 9: Clinical Program for Etripamil
Clinical Program for Etripamil Enrolling Phase 2, Phase 3, and Safety 9 Milestone Corporate Overview NODE - 1 PSVT ReVeRA AFib - RVR NODE - 301 PSVT RAPID PSVT NODE - 303/302 PSVT Phase 2 Phase 2 Phase 3 Phase 3 Phase 3 Efficacy Efficacy POC Efficacy Efficacy Safety Published Enrolling Complete Enro
Slide 10: Development Plan for Etripamil
Development Plan for Etripamil 10 Milestone Corporate Overview NODE - 301: Efficacy & Safety RAPID NODE - 302: Open - Label Extension NODE - 303: Open - Label Safety 2019 2020 2021 Data ReVeRA : AFib – RVR Efficacy POC 2022 Expanded Access Program RAPID Phase 3 PSVT Program Pipeline Expansion (Phase
Slide 11: NODE-301 Study Design
NODE - 301 Study Design 11 Milestone Corporate Overview NODE - 301 patients on drug had no serious adverse events Test Dose Randomization Event Primary Efficacy Analysis 70 mg dose Administer in office while in sinus rhythm for safety evaluation 70 mg etripamil : placebo 2:1 (N=419) 1. Patient recog
Slide 12: NODE-301 Primary Endpoint
Primary Endpoint - over 5 hours Hazard Ratio = 1.09; p<0.12 NODE - 301 Kaplan - Meier Plot of Conversion to Sinus Rhythm 12 Milestone Corporate Overview Post hoc analysis - over 30 minutes Etripamil = 54% vs. Placebo = 35% HR = 1.87; p<0.02 Primary analysis – over 5 hours HR = 1.086; p<0.12 Source:
Slide 13: Randomized Treatment Emergent Adverse Events
Randomized Treatment Emergent Adverse Events (RTEAE) Etripamil N=138 (%) Placebo N=60 (%) Subjects with any RTEAE 53 (38.4) 12 (20.0) Maximum severity of RTEAE Mild 45 (32.6) 10 (16.7) Moderate 8 (5.8) 3 (3.3) Severe 0 (0.0) 0 (0.0) Most Common Adverse Events (>5%) Nasal discomfort 27 (19.6) 4 (6.7)
Slide 14: PK of Etripamil Repeat Administration
PK of Etripamil 30 mg Repeat Administration at T=10 min (Study MSP - 2017 - 1096) 14 0 10 20 30 40 50 60 70 80 90 100 0 10 20 30 40 50 60 Plasma Concentration (ng/ml) Time (minutes) 30mg 30mg Milestone Corporate Overview Repeat administration increases both Cmax and AUC N=7, Error bars are standard
Slide 15: RAPID Study Design
RAPID Study Design 1 includes ~30 events expected to be treated with the single dose double - blind study drug administration from NODE - 301 patients who experienced an event prior to the RAPID study being available 15 Milestone Corporate Overview Test Dose Randomization Event Primary Efficacy Anal
Slide 16: Clinical Program for Etripamil
Clinical Program for Etripamil Enrolling Phase 2, Phase 3, and Safety 16 Milestone Corporate Overview NODE - 1 PSVT ReVeRA AFib - RVR NODE - 301 PSVT RAPID PSVT NODE - 303/302 PSVT Phase 2 Phase 2 Phase 3 Phase 3 Phase 3 Efficacy Efficacy POC Efficacy Efficacy Safety Published Enrolling Complete Enr
Slide 17: The ReVeRA Trial
The ReVeRA Trial 17 Milestone Corporate Overview Re duction of Ve ntricular R ate in Patients with A trial Fibrillation CHADs 0 = No Heart Failure/No Hypertension/Age < 65/No Diabetes/No History of Stroke or TIA/No Coronary ischemic disease; OAC, oral anti - coagulant; RVR, Rapid Ventricular Rate; T
Slide 18: Commercial Opportunity
Milestone Commercial Opportunity
Slide 19: Etripamil – Addressing Market Needs in PSVT and AFib-RVR
Etripamil – Addressing Market Needs in PSVT and AFib - RVR Sources: Internal market research 19 Milestone Corporate Overview Future with Etripamil – a Potentially Better Treatment Option Potential for high receptivity to etripamil across stakeholders Patients Physicians (Cards, EPs, PCPs) Payors • S
Slide 20: Projected US Market for Etripamil in PSVT
12% 37% 25% 11% 15% 0% 10% 20% 30% 40% 50% <2 episodes 2 to 5 episodes 6 to 11 episodes 12 to 24 episodes >25 episodes Percent of Patients Projected US Market for Etripamil in PSVT 20 Milestone Corporate Overview Episode Frequency (n=256 US patients) 40% patients with ≥1 ED visits for PSVT/ yr * 40%
Slide 21: Projected US Market for Etripamil in AFib-RVR
1. Colilla et al., Am. J. Cardiol . 2013, 112(8), 1142 - 1147; 2. Zoni - Berisso et al., Clin. Epidemiol., 2014, 6, 213 - 220; Benjamin et al., Circulation, 2019, 139, e56 - e528; Go et al., JAMA, 2001, 285(18), 2370 - 2375; Turakhia et al., PLOS ONE, 2018, 13(4), e0195088; Kornej et al. Circ. Res.,
Slide 22: Projected US Market for Etripamil in Arrhythmias
Projected US Market for Etripamil in Arrhythmias (PSVT and AFib - RVR) 22 Milestone Corporate Overview ~ 2 million patients US Prevalence • 40 - 65% ~ 800k patients ~ 400k patients 3 - 5/year Addressable Market Peak Share Episodes/Pt Episodes/ Yr • 50% Peak Net Sales • 50% of events ~ 5 million pati
Slide 23: Finances – as of March 31, 2021
Finances – as of March 31, 2021 1 Proforma cash $149.9M 2 • $129.9M in Cash as of March 31, 2021 • $20M in Equity and Upfront cash from Ji Xing deal Cash funds operations past guidance for top - line data and into mid - 2023 1) Adjusted to reflect financing events through May 17, 2021; 2) $129.9M as
Slide 24: Thank you
Milestone Thank you
Slide 25: Etripamil Nasal Spray Pharmacological Results (NODE-102)
Etripamil Nasal Spray Pharmacological Results (NODE - 102) 25 Milestone Corporate Overview Anticipated therapeutic effect within 45 minutes; peak within 10 minutes -10% 0% 10% 20% 0 20 40 60 80 100 120 140 160 0 10 20 30 40 50 60 70 80 90 100 PR Interval – Mean change from baseline (%) Mean Etripami
Slide 26: Mean Systolic Blood Pressure Effects
Phase 2 Mean Systolic Blood Pressure Effects Source: Stambler, B.S. et al.; Etripamil Nasal Spray for Rapid Conversion of Supraventricular Tachycardia to Sinus Rhythm; J Am Coll Cardiol . 2018;72(5):489 – 97 26 Milestone Corporate Overview 1 2 1 Baseline is defined as the average of the 20 - min and
Slide 27: NODE-301 Efficacy – Time to Conversion over 60 Minutes
NODE - 301 Efficacy – Time to Conversion over 45 Minutes 27 0% 10% 20% 30% 40% 50% 60% 70% 0 5 10 15 20 25 30 35 40 45 % Converted to SR Time to Conversion (minutes) Placebo Etripamil 70mg 32% 14% 54% 35% Milestone Corporate Overview New Primary Endpoint Second Dose Option for RAPID HR 1.87, p=0.02
Slide 28: NODE-301 Conversion up to 5 Hours with Medical Intervention
NODE - 301 Conversion up to Hour 5 with Medical Intervention Patients Analyzed as Treatment Failures at 5 hours (post - hoc) 28 Milestone Corporate Overview Etripamil 70mg Placebo Subjects who convert following medical assistance are censored at 5 hours. Subjects who present missing data from time t
Slide 29: PSVT Patient Characteristics
PSVT Patient Characteristics • Age: teens to elderly • Gender: majority are female • Episode frequency and duration varies widely − Median 4 - 7 per year despite chronic medications − Almost 40% of patients have at least 2 episodes/year >10 min* • Cardiovascular comorbidities in about half of patien
Slide 30: Current US PSVT Market
• Prevalence ~2M diagnosed PSVT patients • ~300K newly diagnosed per year • ~600K patients treated per year • >150K ED/hospital visits per year • ~80K ablations per year No Rx ~25% Chronic Therapy ~65% Ablation ~10% Current US PSVT Market Source: Sacks, N.C. et al; Prevalence of Paroxysmal Supravent
Slide 31: Core PSVT Market is Addressable Now, with Potential for Expansion
Core PSVT Market is Addressable Now, with Potential for Expansion Source: 1) assumes annual incidence rate for PSVT of ~300k from longitudinal claims analysis and the average time to diagnosi s ( currently 2 - 3 years) can be reduced to <6 months 2) Calculated as the difference between PSVT prevalen
Slide 32: PSVT Patient Management and Call Point Targeting
PSVT Patient Management and Call Point Targeting • Targeted sales force to reach majority of available opportunity • Significant overlap with most common CV portfolio call points Source: Internal market research 32 Clinical Cardiologists Primary Care Physicians Electro - physiologists % of PSVT pati
Slide 33: Estimating Prevalence, Incidence, and Annually Treated Patients Using Claims Data
Estimating Prevalence, Incidence, and Annually Treated Patients Using Longitudinal Claims Data Source: Data on file from IBM Marketscan ® Commercial Research Database (<65y) and the Medicare Limited Dataset (≥65y), with demographic, enrollment and claims data f or commercially insured (Truven) and M
Slide 34: Published Disease Data Likely Under-Reports Burden of PSVT
Published Disease Data Likely Under - Reports Burden of PSVT Strengths • Provides important demographic and clinical characteristic data on patients with PSVT • Positive Predictive Values from PREEMPT useful • Less than 40% of incident cases in MESA would have been detected by PSVT ICD - 9 Code 427.
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