Exhibit 99.1
Corporate Overview December 2019 Joseph Oliveto Chief Executive Officer
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,’’ ‘‘believe,’’ ‘‘contemplate,’’ ‘‘continue,’’ ‘‘could,’’ ‘‘design,’’ ‘‘due,’’ ‘‘estimate,’’ ‘‘expect,’’ ‘‘goal,’’ ‘‘intend,’’ ‘‘may,’’ ‘‘objective,’’ ‘‘plan,’’ ‘‘predict,’’ ‘‘positioned,’’ ‘‘potential,’’ ‘‘seek,’’ ‘‘should,’’ ‘‘target,’’ ‘‘will,’’ ‘‘would’’ and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. These forward-looking statements include, but are not limited to, statements about the initiation, timing, progress and results of our current and future clinical trials of etripamil, including our Phase 3 clinical trials of etripamil for the treatment of paroxysmal supraventricular tachycardia (“PSVT”), and of our research and development programs and clinical pipeline; our plans to develop and commercialize etripamil and any future product candidates; the expected benefits of using etripamil to treat PSVT; our expectations regarding the potential market size and the rate and degree of market acceptance of etripamil and any future product candidates and the implementation of our business model and strategic plans for our business, etripamil and any future product candidates. Such forward-looking statements are subject to inherent uncertainties, risks and assumptions that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, our dependence on the success of our Phase 3 clinical trials of etripamil for PSVT, the risks inherent in biopharmaceutical product development and clinical trials, including the lengthy and uncertain regulatory approval process, uncertainties related to the timing of initiation, enrollment and completion of clinical trials, and whether the clinical trials will validate the safety and efficacy of etripamil for PSVT or other indications, among others. These and other risks and uncertainties are described more fully in our annual and other periodic filings with the Securities and Exchange Commission (the "SEC"), including under the heading “Risk Factors” in our Quarterly Report on Form 10-Q filed with the SEC on November 13, 2019. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. We undertake no obligation to update or revise any forward-looking statements, whether as a result of new information, the occurrence of certain events or otherwise. This Presentation contains trademarks, trade names and service marks of other companies, which are the property of their respective owners. Certain information contained in this Presentation and statements made orally during this Presentation relate to or is based on studies, publications, surveys and other data obtained from third-party sources and the Company’s own internal estimates and research. While the Company believes these third-party studies, publications, surveys and other data to be reliable as of the date of the Presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, no independent sources has evaluated the reasonableness or accuracy of the Company’s internal estimates or research and no reliance should be made on any information or statements made in this Presentation relating to or based on such internal estimates and research. Milestone Corporate Overview 2
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 PSVT in > 25 years New Chemical Entity with proprietary IP protection until 2036 Pipeline opportunities beyond the lead indication $95M Initial Public Offering - May 13, 2019 Cash & equivalents of $136.5M (Sept. 30, 2019) – expected runway into Q3, 2021 PSVT = Paroxysmal Supraventricular Tachycardia Milestone Corporate Overview 3
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
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 pain, shortness of breath sudden onset of fatigue lightheadedness or dizziness fainting or anxiety PSVT episode 37% frequency (per yr.) 15% 11% ✓ ✓ ✓ <2 2 to 5 6 to 1112 to 24>25 episodes episodes episodes episodes episodes AVNRT = Atrioventricular Nodal Re-entrant Tachycardia AVRT = Atrioventricular Re-entrant Tachycardia bpm = beats per minute Sources: Internal estimates based on market research Milestone Corporate Overview 5 12% 25%
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 the management of adult patients with supraventricular tachycardia: executive summary: a report of the ACC/AHA Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation. 2016;133:e471–e505 Milestone Corporate Overview 6 Chronic / preventive • Chronic oral medication with modest efficacy and unpleasant side effects • 4-7 episodes/year despite preventive medications • Catheter ablation • ~80K ablations/year • Only ~10% of patients opt for ablation Acute • IV adenosine or DC cardioversion in the ED • >150K ED visits/hospital admissions per year • Many patients endure episodes when they occur Current acute treatment options are invasive, inconvenient, anxiety-provoking and/or costly
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 first approved treatment to be used by patients whenever and wherever an episode of PSVT occurs
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 spray Short half-life • • 0 20 40 60 • Minutes after Dose Error bars indicate standard error of the mean AV = Atrio-ventricular Milestone Corporate Overview 8 Etripamil Plasma Levels (ng/ml) 140 mg 60 mg 14 mg Etripamil ClassNovel CCB Potency (IC50) 11 nM MetabolismRapid: Esterase-mediated A paradigm-changing approach for treating PSVT
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 clinical utility
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 Tachycardia Milestone Corporate Overview 10 Endpoint: conversion to sinus rhythm within 15 minutes >80% power to show a 50% absolute difference vs. placebo Objectives: Demonstrate superiority of etripamil over placebo in terminating SVT and dose ranging trend analysis
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 successfully converted at T=15min # patients converted at 15 min 7/20 13/20 20/23 15/20 20/21 p-value 0.1128 0.0006 0.0248 <.0001 65% 35% Etripamil three highest doses demonstrated 75-95% conversion rates which are statistically significant compared to placebo
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 baseline. 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 12 Etripamil 70 mg showed no drop in blood pressure
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; however these were transient • Etripamil 70 mg demonstrated the best efficacy/safety profile to take into Phase 3 Source: Adapted from 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 13
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 scheme 2:1 etripamil : placebo Milestone Corporate Overview 14 Follow up visit Primary endpoint PSVT conversion to SR (adjudicated) N = 150 events; >90% power, α=0.01 PSVT Episode Event Driven Trial: only PSVT adjudicated events count for efficacy Objective: Superiority of etripamil over placebo in terminating PSVT events in the outpatient setting
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 Population and Safety Database Open-label global safety trial •Removed the in-office safety test dose that is currently required in the NODE-301 study NODE-303 Single pivotal efficacy study to support NDA submission •Once target of 150 adjudicated events reached, collection of blinded data from patients who have not experienced an event to continue as separate dataset called “NODE-301B” NODE-301
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 Overview 16
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% of patients have ≥ 1 ED visit per year* • • *Estimates are for patients in year after initial diagnosis; rates drop by 13-29% in years following their initial diagnosis Sources: Internal estimates based on market research and longitudinal analysis of Truven/Marketscan and Medicare claims data Milestone Corporate Overview 17 Unmet Need • Strongly negative experience associated with adenosine in ED • Significant anxiety/fear of ablation • Patients indicate “significant impact” on QOL
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 Paroxysmal Supraventricular Tachycardia (PSVT) in the US in Patients Under 65 Years of Age; Abstract and Oral Presentation at the International Academy of Cardiology Annual Scientific Sessions 2018, 23rd World Congress on Heart Disease; Precision Xtract, Boston, MA, USA; and 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 Medicare covered patients using PSVT code 427.0 or I47.1 for up to a 9-year interval between 2008 and 2016 inclusive. Milestone Corporate Overview 18 Total annual US healthcare expenditures of ~$3B
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 patients managed acutely) ✓ 2+ PSVT codes required in the outpatient setting (additional unique patients managed chronically) 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 Medicare covered patients using PSVT code 427.0 or I47.1 for up to a 9-year interval between 2008 and 2016 inclusive. Milestone Corporate Overview 19 Prevalent PSVT Patients Incident PSVT Patients Annually Treated PSVT Patients Age Group Year 1 Year 2 Year 3 Year 4 Year 5 Total Age < 65 271,024 196,653 169,988 155,966 145,485 939,116 Age 65+ 377,493 220,596 209,358 188,925 166,286 1,162,658 All Ages 648,518 417,249 379,346 344,891 311,771 2,101,775
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 427.0 Weaknesses Data only from patients presenting to healthcare settings acutely, with the episode confirmed on ECG during the encounter PSVT episodes were only adjudicated during the first healthcare encounter with a PSVT or PSVT-related code in PREEMPT Non-representative, small, and non-contemporary population (MESA) • • • • • • Source: Orejarena LA, Vidaillet H Jr, DeStefano F, Nordstrom DL, Vierkant RA, Smith, PN, Hayes JJ. Paroxysmal supraventricular tachycardia in the general population. J Am Coll Cardiol. 1998;31:150–157. Alan S. Go, MD; Mark A. Hlatky, MD; Taylor I. Liu, MD, PhD; Dongjie Fan, MSPH; Elisha A. Garcia, BS; Sue Hee Sung, MPH; Matthew D. Solomon, MD, PhD. Contemporary Burden and Correlates of Symptomatic Paroxysmal Supraventricular Tachycardia. J Am Heart Assoc. 2018;7:e008759. DOI: 10.1161/JAHA.118.008759. Milestone Corporate Overview 20 PREEMPT Study
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 Marketscan® Commercial Research Database (<65y) and the Medicare Limited Dataset (≥65y), with demographic, enrollment and claims data for commercially insured (Truven) and Medicare covered patients using PSVT code 427.0 or I47.1 HRU = Healthcare Resource Utilization Milestone Corporate Overview 21 Prevalence of Healthcare Utilization for PSVT 2014 Inpatient and Outpatient ablations* Non cardiac ablation PSVT encounter Total Hospitalizations with PSVT Emergency Department Visits with PSVT Outpatient Hospital Visits with PSVT Outpatient Other Office visits HRU 79,347103,865 51,048 260,207 503,269 1,174,087 Cost ($) $24,071$8,860 $1,003 $853 $195 $123 Total ($) $1.9B$920M $51M $221M $98M $144M $3.3B
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 diagnosis, respectively Source: Sacks, N et al.; “Healthcare Resource Use and Expenditures in Patients under 65 Years of Age and Newly Diagnosed with Paroxysmal Supraventricular Tachycardia (PSVT) in the United States”; Podium presentation at the International Academy of Cardiology, Annual Scientific Sessions 2018; 23rd World Congress on Heart Disease; July 2018 Milestone Corporate Overview 22 $9,028 $6,510 $6,103 In the year following diagnosis, total spending more than tripled for PSVT 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 $5,000 $0 PSVT Pre/Baseline Matched Control non-PSVT related PSVT Other Cardiac Arrhythmias Source: Sacks, N et al.; “Healthcare Resource Use and Expenditures in Patients under 65 Years of Age and Newly Diagnosed with Paroxysmal Supraventricular Tachycardia (PSVT) in the United States”; Podium presentation at the International Academy of Cardiology, Annual Scientific Sessions 2018; 23rd World Congress on Heart Disease; July 2018 Milestone Corporate Overview 23 $6,764 for PSVT and other cardiac arrhythmias healthcare services •Of that amount, $9,039 was tied t treatment with a PSVT diagnosis code Total spending $14,075 $5,036 increase post diagnosis (68%) of the total $9,039 was for PSVT or for $406 $9,028 $6,103
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 $40,000 $60,000 $10,000 t as ations $5,000 $0 Pre/Baseline Ablations Total cost increase (excluding ablations) * Includes ablations in unspecified outpatient settings Source: Sacks, N et al.; “Healthcare Resource Use and Expenditures in Patients under 65 Years of Age and Newly Diagnosed with Paroxysmal Supraventricular Tachycardia (PSVT) in the United States”; Podium presentation at the International Academy of Cardiology, Annual Scientific Sessions 2018; 23rd World Congress on Heart Disease; July 2018 Milestone Corporate Overview 24 Ablation Rates by setting All settings*0.14 Outpatient Hospital0.12 Inpatient0.02 $30,512 $33,572 $16,139 23% of the average patient cos increase w spent on abl $4,700 $9,028
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 Addressable Market 65% patients on chronic medications for PSVT 40% patients with ≥1 ED visits for PSVT/yr* *Estimates are for patients in year after initial diagnosis; rates drop by 13-29% in years following their initial diagnosis Sources: Internal estimates based on market research Milestone Corporate Overview 25 Percent of Patients 12% 25% 11%15% Market research suggests TAM for PSVT of >800k patients
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 Moderate 3-4 episodes lasting ~15min with a peak heart rate of ~170 bpm Moderate High 5-6 episodes per year in a ~70-year-old patient who has been diagnosed with hypertension Moderate Moderate 2-3 episodes per year causing moderate anxiety and fatigue Moderate Moderate ~6 episodes per year with <2min duration causing mild fatigue and a peak heart rate of ~130 bmp Low Low Low Low <1 episodes per year with moderate heart palpitations Sources: Internal market research Milestone Corporate Overview 26 Episode Burden High Moderate Low Patients with PSVT present with a large range of episode and quality of life burdens
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 Corporate Overview 27 Episode Burden ModerateHigh ModerateModerateCardiologistsEpisodic Use ModerateModerate High Moderate Low Patients experiencing moderate episode burden are the anticipated target user of etripamil
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 Option • Self-management of acute episodes • Less need for chronic medications • Avoidance of 50-75% of ED visits/hospital admissions • Better risk/reward profile • Expected to have significant adoption in unablated patients • Alternative to ablation • Bridge to ablation • Reduction in ED/hospital admissions • Deferral of ablation satisfaction Potential for high receptivity to the etripamil profile across stakeholders
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 Pharmaceuticals, Inc. Milestone Corporate Overview 29 Physician Reaction to Phase 2 Target Product Profile (TPP) for Etripamil Overall Receptivity from MIST Quantitative Survey (n=353) “On a scale of 1-7, where 1 = not at all favorable and 7 = extremely favorable, please rate your receptivity to Product X.” All HCPs (n=353) Reaction to TPP from MIST Qualitative Survey (n=30) • Potential for a fast onset of action and high conversion rates within 30 to 60 minutes of administration noted to be significantly better than current approaches (vagal maneuvers, pill-in-the-pocket) • HCPs familiar with and comfortable prescribing CCBs to the PSVT population • May require additional tests to rule out potential contraindications Potential Utilization from MIST Quantitative Survey (n=353) “Of PVST patients not contraindicated to Product X, please estimate the share that would be prescribed Product X.” Cards (n=253) EPs (n=50) PCPs (n=50) 54% 47% 58%
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, Cards: 54% Avg (mean) Adoption, EPs: 47% 40% 20% 0% 1 2 3 4 5 6 7 “On a scale of 1-7, where 1 = not at all favorable and 7 = extremely favorable, please rate your receptivity to Product X.” 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 Pharmaceuticals, Inc. Milestone Corporate Overview 30 HCP Estimate of Share of Patients Prescribed Etripamil (%)
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, Cards: 54% Avg (mean) Adoption, EPs: 47% 40% 20% 0% 1 2 3 4 5 6 7 “On a scale of 1-7, where 1 = not at all favorable and 7 = extremely favorable, please rate your receptivity to Product X.” 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 Pharmaceuticals, Inc. Milestone Corporate Overview 30 HCP Estimate of Share of Patients Prescribed Etripamil (%)
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 Group Qualitative (n=20) Market Research with PSVT Patients, April – June 2017 MIST = Milestone Pharmaceuticals, Inc. Milestone Corporate Overview 32 PSVT Patient Reaction to Phase 2 Target Product Profile (TPP) for Etripamil Overall Receptivity from MIST Qualitative Survey (n=20) “On a scale of 1-7, where 1 = not at all favorable and 7 = extremely favorable, please rate your receptivity to Product X.” • Patients had highest receptivity to etripamil of all 1Avg (mean): ~6.3 7• Important because MIST anticipates patient-driven Reaction to TPP from MIST Qualitative Survey (n=20) • Estimated that patients would potentially have avoided ~50-75% of all Emergency Department visits (reduces anxiety of the next event, allowing patients to perform activities that are limited without a reliable • Minority of patients indicated an aversion to administering medications intranasally Expected Usage Rate by Patients from MIST Qualitative Survey (n=20) “Please estimate the share of your PSVT episodes for which you would use Product X.” $60 OOPMIST would expect approximately 3-4 annual etripamil doses Tier 2 or Tier 3 out of pocket (OOP) costs 40% 60% 85%
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 Physicians Electro-physiologists % of PSVT patients managed ~60% ~30% ~10% Long-term Use Add to or Replace Primary Target Medium-term Use Defer Ablation Secondary Target Short-term Use Bridge to Ablation Majority of PSVT patients managed by CV specialists, leading to commercial efficiencies
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) Calculated as the difference between PSVT prevalence of 2M and annual treatment rate of ~600k from IBM Marketscan® Commercial Research Database (<65y) and the Medicare Limited Dataset (≥65y), 2008-2016 analyzed by Precision Xtract, 2019 2) Estimated number of unique patients with annual claims for PSVT from IBM Marketscan® Commercial Research Database (<65y) and the Medicare Limited Dataset (≥65y), 2008-2016 analyzed by Precision Xtract, 2019. Milestone Corporate Overview 34 Core Market Expanded Market ~600k/year2 Diagnosed, Annually Treated PSVT Patients ~1.4 Million1 Diagnosed, Untreated PSVT Patients Undiagnosed PSVT Patients
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 publications, and Medical Affairs initiatives patient education − Phase 2 proof of concept endpoint in atrial fibrillation • 24.5M shares outstanding Milestone Corporate Overview 35
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 Rapid Ventricular Rate Milestone Corporate Overview 36
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 PSVT in > 25 years New Chemical Entity with proprietary IP protection until 2036 Pipeline opportunities beyond the lead indication $95M Initial Public Offering - May 13, 2019 Cash & equivalents of $136.5M (Sept. 30, 2019) – expected runway into Q3, 2021 PSVT = Paroxysmal Supraventricular Tachycardia Milestone Corporate Overview 37
Thank you Subtitle
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
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 Tachycardia to Sinus Rhythm; J Am Coll Cardiol. 2018;72(5):489–97 Milestone Corporate Overview 40 Cumulative Conversion Rate (%) Etripamil 7K0amplganvMs.epielar cpelobtoshpo=w0.in0g00ti3m*e to conversion Placebo PlaceboEtripamil 35 mg Etripamil 70 mgEtripamil 105 mg Etripamil 140 mg 70mg etripamil dose showed rapid time to conversion (median < 3 min)
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 baseline. 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 41 Etripamil 70 mg showed no drop in blood pressure
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 and Medicare claims data Milestone Corporate Overview 42 Number of annual PSVT ablations 80,000 Ratio of etripamil-treated patients : ablation x 3.5 Total expected etripamil patients/year 280,000 Etripamil expected doses/patient/year x 3 Etripamil doses/year 840,000