Milestone Pharmaceuticals Inc. · NASDAQ:MIST
Milestone Pharmaceuticals — Investor Presentation (December 2019)
42 slides from Milestone Pharmaceuticals's investor presentation, Dec 17, 2019
Slide 1: Corporate Overview December 2019
Corporate Overview December 2019 Joseph Oliveto Chief Executive Officer
Slide 2: Disclaimers
Disclaimers This Presentation contains forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, as amended. In some cases, you can identify forward-looking statements by terminology such as ‘‘aim,’’ ‘‘anticipate,’’ ‘‘assume,
Slide 3: Milestone (Nasdaq: MIST) - Corporate Highlights
Milestone (Nasdaq: MIST) - Corporate Highlights • • • • • • • • Phase 3 Cardiovascular Company with data read out anticipated in middle 1H, 2020 PSVT is a robust market represented by ~2M patients in US Paradigm-changing approach enabling patient self-management Potentially first new drug therapy in
Slide 4: Management Team
Management Team Joseph Oliveto Chief Executive Officer Amit Hasija Chief Financial Officer Francis Plat, MD Chief Medical Officer Lorenz Muller Chief Commercial Officer Algene Biotechnologies Philippe Douville, PhD Chief Scientific Officer / Founder Milestone Corporate Overview 4
Slide 5: Paroxysmal Supraventricular Tachycardia (PSVT)
Paroxysmal Supraventricular Tachycardia (PSVT) AVNRT AVRT Short Circuit • PSVT is a rapid heart rate condition that starts and stops without warning Heart rates >200 bpm are not uncommon Symptoms include • Retrograde impulse– Fast pathway Slow pathway • ✓ ✓ ✓ palpitations sweating chest pressure or
Slide 6: Current Standard of Care for PSVT
Current Standard of Care for PSVT PSVT = Paroxysmal Supraventricular Tachycardia DC = Direct Current ED = Emergency Department Sources: Internal estimates based on market research and longitudinal analysis of Truven/Marketscan and Medicare claims data; Page RL et al, 2015 ACC/AHA/HRS guideline for t
Slide 7: A Paradigm-Changing Approach
A Paradigm-Changing Approach Non-invasive Convenient Empowering • Avoidance of ED visits/ hospital admissions • Less need for chronic medications • Alternative or bridge to ablation procedure PSVT = Paroxysmal Supraventricular Tachycardia Milestone Corporate Overview 7 Opportunity to develop the fir
Slide 8: Etripamil
Etripamil • • Rapid onset (Tmax < 5 min) Transient plasma levels 240 220 200 180 160 140 120 100 80 60 40 20 0 • Clinically-validated mechanism − Etripamil, Calcium Channel Blockers (CCBs), terminate PSVT through AV node modulation Rapid onset of action Convenient patient self-administered nasal spr
Slide 9: Etripamil Clinical Pipeline
Etripamil Clinical Pipeline Preclinical Phase 1 Phase 2 Phase 3 Rapid conversion to sinus rhythm PSVT Temporary control of rapid ventricular rate Atrial Fibrillation Acute relief of angina symptoms Angina Milestone Corporate Overview 9 Pharmacology of L-type calcium channel blockers drives broad cli
Slide 10: Phase 2a/b Study Design
Phase 2a/b Study Design -5 min 0 min 15 min Placebo n=20 Etripamil 140mg n=21 PSVT patients with scheduled cardiac ablation (EP lab) SVT Induced Etripamil 105mg n=20 Etripamil 70mg n=23 Etripamil 35mg n=20 EP = electrophysiology, SVT = supraventricular tachycardia, PSVT = Paroxysmal Supraventricular
Slide 11: Phase 2 Primary Endpoint
Phase 2 Primary Endpoint 87% 95% 100% 80% 60% 40% 20% 0% 75% Placebo35mg 70mg 105mg140mg 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 Milestone Corporate Overview 11 % patients successf
Slide 12: Phase 2 Mean Systolic Blood Pressure Effects
Phase 2 Mean Systolic Blood Pressure Effects 1 2 1 Baseline is defined as the average of the 20-min and 10-min pre-dose measurements. 2 Time 0 is defined as the average of the measurements during supraventricular tachycardia between 5 and 0 min before study drug administration. *p < 0.05 versus base
Slide 13: Phase 2a/b Clinical Conclusions
Phase 2a/b Clinical Conclusions • Etripamil at 70, 105 and 140 mg is significantly better than terminating PSVT placebo in • Median time to conversion <3 min with etripamil 70 mg • 70 mg dose showed no mean blood pressure (BP) drop • Most frequent side effect was nasal irritation or nasal congestion
Slide 14: Pivotal Phase 3 Study Design
Pivotal Phase 3 Study Design Randomization; up to 500 patients Placebo ~33% of events Test Dose Active drug while not in PSVT Etripamil 70mg ~67% of events Documented diagnosis of PSVT History of longer episodes SR = Sinus Rhythm; PSVT = Paroxysmal Supraventricular Tachycardia; Study randomization s
Slide 15: FDA Provided a Clear Regulatory Path for Etripamil in PSVT
FDA Provided a Clear Regulatory Path for Etripamil in PSVT Milestone Corporate Overview 15 •Program enrolling broad patient population including elderly and those on concomitant medications (e.g. calcium channel blockers and beta blockers) •Total NDA safety data set of ≤ 1,500 unique patient events
Slide 16: Etripamil PSVT Phase 3 Development Plan
Etripamil PSVT Phase 3 Development Plan Primary Utility 2018 2019 2020 2021 Pivotal Efficacy & Safety Data NODE-301 Safety & Supportive Efficacy NODE-301B NODE-302 Open-Label Extension Safety NODE-303 Open-Label Safety Safety PSVT = Paroxysmal Supraventricular Tachycardia Milestone Corporate Overvie
Slide 17: 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 patients 40%
Slide 18: Current US PSVT Market
Current US PSVT Market Current Management Ablation ~10% • • • • • Prevalence ~2M diagnosed PSVT patients ~300K ~600K >150K newly diagnosed per year patients treated per year ED/hospital visits per year No Rx ~25% Chronic Therapy ~65% ~80K ablations per year Source: Sacks, N.C. et al; Prevalence of P
Slide 19: Estimating Prevalence, Incidence, and Annually Treated Patients Using Longitudinal Claims Data
Estimating Prevalence, Incidence, and Annually Treated Patients Using Longitudinal Claims Data • Analyzed commercial and Medicare claims data over a 9-year period, where patients were required to have 5 years of continuous enrollment ✓ 1+ PSVT code required in the ED or inpatient setting (unique pat
Slide 20: Published Disease Data Likely Under-Reports Burden of PSVT
Published Disease Data Likely Under-Reports Burden of PSVT MESA Study 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
Slide 21: Healthcare Cost and Utilization for PSVT
Healthcare Cost and Utilization for PSVT with PSVT *Ablations are for patients with a PSVT diagnosis in the same year. Mean costs for inpatient and outpatient ablations reflect claims with ablation procedure code and inpatient and outpatient hospital settings. Source: Data on file from IBM Marketsca
Slide 22: Post-Diagnosis Total Healthcare Spending for Newly-Diagnosed PSVT Patients
Post-Diagnosis Total Healthcare Spending for Newly-Diagnosed PSVT Patients <65 Years Old Relative to Matched Controls Average Total Costs $35,000 $29,867 $30,000 $25,000 $20,000 $15,000 $10,000 $5,000 $0 Dx-1 * Dx+1 * PSVT Matched Control * Dx-1 and Dx+1 refer to 12 months prior to and following dia
Slide 23: Components of Spending in Newly-Diagnosed Patients
Components of Spending in Newly-Diagnosed Patients <65 for PSVT and Other Cardiac Arrhythmias Healthcare Services $35,000 • The majority of the increase in spending following diagnosis was $29,867 $30,000 $20,839 $25,000 o $20,000 spending increase $15,000 other cardiac arrhythmias $6,510 $10,000 $5
Slide 24: Mean Cost per PSVT Ablation
Mean Cost per PSVT Ablation and Contribution to Average per Patient Cost Increase in Year after Diagnosis in Patients <65 Years Old Mean Cost per ablation $30,000 $25,000 Outpatient Hospital 87% of total ablations $20,000 Inpatient 13% of total ablations $49,947 $15,000 All Settings* per $0 $20,000
Slide 25: Target Addressable Market for PSVT
Target Addressable Market for PSVT Total Number of Episodes in the First 12 Months After Diagnosis 37% 50% 40% 30% 20% 10% 0% <2 episodes 2 to 5 episodes6 to 11 episodes 12 to 24 episodes >25 episodes Episode Frequency (n=256 US patients) 40% patients with multiple episodes >10min/yr* TAM – Target A
Slide 26: Examples of PSVT Patient Profiles
Examples of PSVT Patient Profiles Episode Burden Symptomology/QoL Example Patient Profiles Symptomatology/QOL 3-4 episodes per year with severe palpitations, dizziness, and a peak heart rate of >200 bpm High High 16 episodes per year causing faint severity and a peak heart rate of ~130 bmp High Mode
Slide 27: Etripamil Use Case and Target Prescriber
Etripamil Use Case and Target Prescriber Episode Burden Symptomology/QoL HCP Etripamil Use Case Symptomatology/QOL High High Electrophysiologists Bridge to Ablation High Moderate Low Low Cardiologists/ Primary Care Physicians Rescue Therapy Low Low Sources: Internal market research Milestone Corpora
Slide 28: Etripamil – Addressing Market Needs
Etripamil – Addressing Market Needs Etripamil– a Better Treatme • Improvement in patient Cards = Cardiologists, EPs = Electrophysiologists, PCPs = Primary Care Physicians Sources: Internal market research Milestone Corporate Overview 28 Patients Physicians (Cards, EPs, PCPs) Payors Future with nt Op
Slide 29: MIST Healthcare Practitioner (HCP) Survey Results
MIST Healthcare Practitioner (HCP) Survey Results 1 7 Avg (mean): 5.6 Source: Triangle Insights Group Qualitative (n=30) and Quantitative (n=353) Market Research with General Cardiologists, Electrophysiologists, and Primary Care Physicians, November 2018 through April 2019. MIST = Milestone Pharmace
Slide 30: Variability in Response for Cardiologist Stated Adoption
Variability in Response for Cardiologist Stated Adoption Favorability Score by MIST Quantitative Demand Survey – Cards and EPs Physician Favorability Score v. Estimated Adoption Share Note – many dots reflect more than 1 response (n=303) Cards (n=253) EPs (n=50) 100% 80% 60% Avg (mean) Adoption, Car
Slide 31: Variability in Response for Cardiologist Stated Adoption
Variability in Response for Cardiologist Stated Adoption Favorability Score by MIST Quantitative Demand Survey – Cards and EPs Physician Favorability Score v. Estimated Adoption Share Note – many dots reflect more than 1 response (n=303) Cards (n=253) EPs (n=50) 100% 80% 60% Avg (mean) Adoption, Car
Slide 32: MIST Patient Survey Results
MIST Patient Survey Results stakeholders surveyed by MIST N=20 market dynamic • Expect etripamil to provide ‘peace of mind’ in between episodes and a sense of control over disease at-home therapy) per patient based on patient stated usage rates at potential $30 OOP $10 OOP Source: Triangle Insights
Slide 33: PSVT Patient Management and Call Point Targeting
PSVT Patient Management and Call Point Targeting Chronic Medications • • Targeted sales force to reach majority of available opportunity Significant overlap with most common CV portfolio call points Source: Internal market research Milestone Corporate Overview 33 Clinical Cardiologists Primary Care
Slide 34: Core Market for PSVT with Potential for Expansion
Core Market for PSVT with Potential for Expansion Opportunity to Address Increase speed and rates of diagnosis through wearable technology Target PSVT Market • • Re-engage in healthcare system through targeted DTC promotion • • MIST specialty sales force Partner majority of PCP promotion Source: 1)
Slide 35: Finances
Finances • Cash and equivalents of $136.5M (as of September 30, 2019) • IPO (May 2019) net proceeds of approx. $86M • Runway expected into Q3, 2021 − − − Phase 3 pivotal efficacy trial (NODE-301) data Significant progression of Phase 3 safety study (NODE-303) Continued PSVT market development via pu
Slide 36: Etripamil Development Plan
Etripamil Development Plan 2021 2018 2019 2020 Data NODE-301: Efficacy & Safety NODE-301B Phase 3 PSVT Program NODE-302: Open-Label Extension NODE-303: Open-Label Safety Pipeline Expansion (Phase 2) Afib - RVR Angina PSVT = Paroxysmal Supraventricular Tachycardia Afib-RVR = Atrial Fibrillation with
Slide 37: Milestone (Nasdaq: MIST) - Corporate Highlights
Milestone (Nasdaq: MIST) - Corporate Highlights • • • • • • • • Phase 3 Cardiovascular Company with data read out anticipated in middle 1H, 2020 PSVT is a robust market represented by ~2M patients in US Paradigm-changing approach enabling patient self-management Potentially first new drug therapy in
Slide 38: Thank you
Milestone Thank you
Slide 39: Etripamil Phase 1 Pharmacology
Etripamil Phase 1 Pharmacology PR Prolongation Used to Select Doses for Phase 2 20 18 16 14 12 10 8 6 4 2 0 placebo 20 40 60 80 Etripamil 100 Dose (mg) 120 140 Error bars indicate standard error of the mean Milestone Corporate Overview 39 PR Interval Prolongation (%) Target PR threshold
Slide 40: Phase 2 Time to Conversion
Phase 2 Time to Conversion 100 Etripamil 70mg 80 60 40 20 0 10 15 0 5 Time Since Study Drug Administration (min) *Hazard Ratio and 95% Confidence Intervals etripamil 70mg vs. placebo; 4.99 (2.09, 11.93) Source: Stambler, B.S. et al.; Etripamil Nasal Spray for Rapid Conversion of Supraventricular Tac
Slide 41: Phase 2 Mean Systolic Blood Pressure Effects
Phase 2 Mean Systolic Blood Pressure Effects * * * * * * * * * 1 2 1 Baseline is defined as the average of the 20-min and 10-min pre-dose measurements. 2 Time 0 is defined as the average of the measurements during supraventricular tachycardia between 5 and 0 min before study drug administration. *p
Slide 42: Potential Commercial Opportunity for Etripamil in PSVT
Potential Commercial Opportunity for Etripamil in PSVT 400,000 Etripamil patients (50% of TAM) ~2M diagnosed PSVT patients (4 yr. prevalence) 800,000 TAM (40% of 2M) TAM – Target Addressable Market Sources: Internal estimates based on market research and longitudinal analysis of Truven/Marketscan an
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