Milestone Pharmaceuticals Inc. · NASDAQ:MIST
Milestone Pharmaceuticals — Investor Presentation (November 2021)
39 slides from Milestone Pharmaceuticals's investor presentation, Nov 12, 2021
Slide 1: Corporate Overview November 2021
Joseph Oliveto President & CEO Corporate Overview November 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,’’ ‘‘design,’’
Slide 3: Milestone Corporate Overview
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 guid
Slide 4: PSVT & Atrial Fibrillation Populations in the US
PSVT Atrial Fibrillation 2.6 Million3 10 Million1 145 Thousand 785 Thousand 1.0-1.6 Million5 ~3-4 Million4 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
Slide 5: Atrial Arrhythmias with a Common Patient Burden
Atrial Arrhythmias 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 Typically 150 -
Slide 6: Role of L-Type Calcium Channel Blockers
Role of 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 tachycardia and return th
Slide 7: Potential Paradigm-Changing Treatment to Empower Patient Control of their Condition
Potential Paradigm-Changing Treatment to Empower Patient Control of their Condition • Time consuming • Anxiety provoking • Costly 7 Milestone Corporate Overview Drawbacks with the current standard of care in the Emergency Department (ED) • Often results in a hospital admission • Experienced by patie
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 (IC50) 11 nM Metabolism Rapid: Esterase-mediated • Clinically-validated mechanism − Calcium channel blockers (CCBs) prolong refractoriness and slow conduction ove
Slide 9: Clinical Program Overview for Etripamil
Clinical Program Overview for Etripamil 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 Enrolling Enrolling/ Complete Electrophysi
Slide 10: Development Plan for Etripamil
Development Plan for Etripamil 10 Milestone Corporate Overview AFib-RVR = Atrial Fibrillation with Rapid Ventricular Rate; POC = Proof of Concept 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 Expa
Slide 11: NODE-301 Study Design
NODE-301 Study Design 11 Milestone Corporate Overview NODE-301 patients taking etripamil had no serious adverse events Test Dose Randomization Event Primary Efficacy Analysis 70 mg dose of etripamil Administer in office while in sinus rhythm for safety evaluation (N=431) Randomized 2:1 70 mg etripam
Slide 12: NODE-301 Kaplan-Meier Plot of Conversion to Sinus Rhythm
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: Data on Fi
Slide 13: NODE-301 Safety Analysis
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 erro
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 Analysis
Slide 16: ReVeRA – Proof of Concept for AFib with Rapid Ventricular Rate
ReVeRA – Proof of Concept for AFib with Rapid Ventricular Rate 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 Enrolling Enrollin
Slide 17: The ReVeRA Trial
The ReVeRA Trial 17 Milestone Corporate Overview Reduction of Ventricular Rate in Patients with Atrial 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; AFib-RVR = Atrial Fibrillation with
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) Payers • Sel
Slide 20: New Data Enhances Understanding of Burden of PSVT
New Data Enhances Understanding of Burden of PSVT Analysis of Prospective Patient Reported Outcomes Longitudinal Data • Phase 1: Baseline Survey (medical and SVT episode history) • Phase 2: Longitudinal Weekly Surveys (episode survey if experienced an episode, QoL survey if not) 5,277 surveys comple
Slide 21: Peak US Market Opportunity for Etripamil in PSVT
Peak US Market Opportunity for Etripamil in PSVT *Patient stated severity of SVT episode (mild, moderate, or severe) Sources: Internal estimates based on market and outcomes research, Milestone Pharmaceuticals. 1. Rehorn et al. Journal of Cardiovascular Electrophysiology. 2021 Aug; 32(8): 2199-2206.
Slide 22: Peak US Market Opportunity for Etripamil in AFib-RVR
AFib-RVR = Atrial Fibrillation with Rapid Ventricular Rate *Reflects the midpoint of published estimates (~8M to ~12M by 2025 or 2030) 1. Colilla et al., Am. J. Cardiol. 2013, 112(8), 1142-1147; Miyasaka et al., Circulation, 2006, 114, 119-125; Colilla et al., Am. J. Cardiol. 2013, 112(8), 1142-1147
Slide 23: Peak US Market Opportunity for Etripamil in PSVT and AFib-RVR
Peak US Market Opportunity for Etripamil in PSVT and AFib-RVR 23 Milestone Corporate Overview ~2.6 million patients US Prevalence (2030) ~40-60% ~1.0-1.6 million patients ~500k-800k patients 4-6/year Addressable Market Peak Share Episodes/Pt Episodes/Yr ~50% 2030 Peak Net Sales ~10 million patients
Slide 24: Finances – as of September 30, 2021
Finances – as of September 30, 2021 Cash, cash equivalents and short-term investments of $126.4M Cash funds operations past guidance for top-line data and into mid-2023 24 Milestone Corporate Overview Equity - 42.2Min shares and pre-funded warrants outstanding • 29.9M common shares • 12.3M pre-funde
Slide 25: Thank you
Milestone Thank you
Slide 26: Etripamil Phase 1 Pharmacology PR Prolongation
Etripamil Phase 1 Pharmacology PR Prolongation Used to Select Doses for Phase 2 Error bars indicate standard error of the mean 26 20 40 60 80 100 120 140 placebo 8 4 6 2 10 12 14 16 18 20 0 Target PR threshold PR Interval Prolongation (%) Etripamil Dose (mg) Milestone Corporate Overview
Slide 27: Etripamil Nasal Spray Pharmacological Results (NODE-102)
Etripamil Nasal Spray Pharmacological Results (NODE-102) 27 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 Etripamil
Slide 28: Phase 2 Study Design
Placebo n=20 Objectives: Demonstrate superiority of etripamil over placebo in terminating SVT and dose ranging trend analysis Etripamil 140mg n=21 15 min Etripamil 105mg n=20 0 min -5 min Phase 2a/b Study Design EP = electrophysiology, SVT = supraventricular tachycardia, PSVT = Paroxysmal Supraventr
Slide 29: Phase 2 Primary Endpoint
Phase 2 Primary Endpoint 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 29 Etripamil three highest doses demonstrated 75-95% conversion rates which are statistically significant compared
Slide 30: Phase 2 Time to Conversion
Phase 2 Time to Conversion 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 30 Milestone Corporate Overview 70mg etripamil dose showed rapid time to conversion (median < 3 min) Kaplan Meier
Slide 31: Phase 2 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 31 Milestone Corporate Overview 1 2 1 Baseline is defined as the average of the 20-min and 10-m
Slide 32: NODE-301 Efficacy – Time to Conversion over 45 Minutes
NODE-301 Efficacy– Time to Conversion over 45 Minutes 32 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 (po
Slide 33: 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) 33 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 to
Slide 34: PRO Analyses Provide A Clearer Picture of Burden of PSVT
PRO Analyses Provide A Clearer Picture of Burden of PSVT than Market Research Alone 34 Milestone Corporate Overview Sources: Internal estimates based on market and outcomes research, Milestone Pharmaceuticals. 1. PSVT patient market research conducted by Triangle Insights Group, 2018 (n=250). 2. PSV
Slide 35: 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 36: 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 diagnosis (currently 2-3 years) can be reduced to <6 months 2) Calculated as the difference between PSVT prevalence o
Slide 37: 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 37 Clinical Cardiologists Primary Care Physicians Electro- physiologists % of PSVT patie
Slide 38: Estimating Prevalence, Incidence, and Annually Treated Patients Using Longitudinal 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 for commercially insured (Truven) and Med
Slide 39: 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 427.0 So
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