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FDA Approval Investor Call December 15, 2025
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Forward Looking Statements 2Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 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,’’ ‘‘due,’’ ‘‘estimate,’’ ‘‘expect,’’ ‘‘goal,’’ ‘‘intend,’’ ‘‘may,’’ ‘‘objective,’’ ‘‘plan,’’ ‘‘predict,’’ ‘‘positioned,’’ ‘‘potential,’’ ‘‘project,’’ ‘‘seek,’’ ‘‘ should,’’ ‘‘target,’’ ‘‘will,’’ ‘‘would’’ (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward -looking statements. These forward- looking statements are based on Milestone's expectations and assumptions as of the date of this Presentation. Each of these forward-looking statements involves risks and uncertainties. Actual results may differ materially from these forward-looking statements. Forward-looking statements contained in this Presentation include statements regarding: (i) potential protections afforded by U.S. patents; (ii) the potential of CARDAMYST to (a) deliver a new PSVT therapeutic option to market, (b) decrease costs for the healthcare system and reduce emergency department visits and hospita l admissions, (c) empower patients to treat symptomatic attacks; (iii) plans relating to commercializing CARDAMYST, including timing, the geographic areas of focus and sales strategy; (iv) the potential market size and the rate and degree of market acceptance of CARDAMYST (etripamil) and any future product c andidates; (v) the projected use of CARDAMYST in the future; (vi) anticipated commercial and Medicare coverage of CARDAMYST; (vii) the implementation of Milestone’s business model and strategic plans for its business, etripamil and any future product candidates; (viii) Milestone’s expected cash runway; (ix) potential royalty payments and potential royalty funding; (x) Milestone’s expectations regarding patient reach and market access; and any other statements not related to historical facts. Important factors that could cause actual results to differ materially from those in the forward-looking statements include, but are not limited to, the risks inherent in biopharmaceutical product development and clinical trials; whether our future interactions with the FDA will have satisfactory outcomes; uncertainties related to the timing of initiation, enrollment, completion, evaluation and results of our clinical trials; risks and uncertainty related to the complexity inherent in cleaning, verifying and analyzing trial data; and whether the clinical trials will validate the safety and efficacy of etripamil for PSVT or other indications, among others, general economic, political, and market conditions, including deteriorating market conditions due to investor concerns regarding inflation, international tariffs, Russian hostilities in Ukraine and ongoing disputes in the Middle East and overall fluctuations in the financial markets in the United States and abroad; risks related to pandemics and public health emergencies; and risks related the sufficiency of Milestone's capital resources and its ability to raise additional capital in the current economic climate. These and other risks are set forth in Milestone's filings with the U.S. Securities and Exchange Commission (“SEC”), including in its annual report on Form 10-K for the year ended December 31, 2024 and its subsequent quarterly report on form 10-Q for the quarters ended March 31, 2025, June 30, 2025 and September 30, 202 5, in each case, under the caption "Risk Factors,” as such discussion may be updated in future filings we make with the SEC. Except as required by law, Milestone assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.
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Call Agenda Presenters Introduction & CARDAMYST Label Highlights Joe Oliveto, President & Chief Executive Officer Clinical Perspective David Bharucha, MD, PhD, FACC, Chief Medical Officer Commercial Plans Lorenz Muller, Chief Commercial Officer Conclusion Joe Oliveto Q&A Joe Oliveto, David Bharucha, Lorenz Muller, Amit Hasija Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 3 Joe Oliveto David Bharucha Lorenz Muller Amit Hasija
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CARDAMYST is indicated for the conversion of acute symptomatic episodes of paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm in adults. 4Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 Indication & Usage: CARDAMYST is a calcium channel blocker indicated for the conversion of acute symptomatic episodes of paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm in adults https://milestonepharma.com/etripamilprescribinginformation.pdf
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Fast Relief to More Patients with Persistent Effects to 5 Hours Efficacy Data from RAPID 5Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 Key: CI = confidence interval; HR = hazard ratio; SR = sinus rhythm 1. Stambler BS, et al. Lancet. 2023;402(10396):118-128. # of subjects at risk Kaplan-Meier probability of conversion, (%) 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 230 240 250 260 270 280 290 300 Time Since Study Drug Administration (minutes) Placebo Conversion of PSVT to SR by 30 min: HR = 2.62 (95% CI: 1.659, 4.147); p<0.001 Placebo 99 26 18 18 17 16 Placebo 35 19 18 18 17 85 37 27 22 22 2056 32 25 22 21
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Kaplan-Meier probability of conversion, (%) Fast Relief to More Patients Efficacy Data from RAPID 6Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 Key: CI = confidence interval; HR = hazard ratio; SR = sinus rhythm 1. Stambler BS, et al. Lancet. 2023;402(10396):118-128. 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 230 240 250 260 270 280 290 300 Time Since Study Drug Administration (minutes) Placebo 99 26 18 18 17 16 Placebo 35 19 18 18 17 85 37 27 22 22 2056 32 25 22 21 Conversion of PSVT to SR by 30 min: HR = 2.62 (95% CI: 1.659, 4.147); p<0.001 0% 10% 20% 30% 40% 50% 60% 70% 0 5 10 15 20 25 30 64% Placebo 31% Time Since Study Drug Administration (minutes) Faster conversion with CARDAMYST by median time to conversion Greater likelihood of conversion with CARDAMYST within 30 minutes 2x >3x # of subjects at risk
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CARDAMYST Was Well Tolerated, With Most Adverse Events Localized to the Nasal Administration Site 7Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 CARDAMYST 70 mg n=235 % CARDAMYST 2x70 mg ‡ n=86 % Placebo n = 223 % Nasal discomfort 28 23 6 Nasal congestion 14 12 1 Rhinorrhea 12 10 2 Throat irritation 7 6 1 Epistaxis 6 7 1 †Adverse reactions that occurred within 24 hours of study drug administration for perceived PSVT in the double-blind, placebo-controlled studies, NODE-1, NODE-301 Part 1, NODE-301 Part 2 (RAPID), and NODE-301 Part 3 (RAPID Extension) that had an overall incidence of 5% or greater and an incidence in the pooled CARDAMYST group at least 1% greater than that of the pooled placebo group. ‡ 2x70 mg: first administration of 70-mg CARDAMYST followed by a repeat dose of 70 -mg CARDAMYST 10 minutes later if symptoms persisted. Most Frequent (≥5.0%) Adverse Reactions Observed in Randomized Controlled Studies† In clinical studies:* No instances of Mobitz type 2 second-degree or third- degree atrioventricular block were reported. Within 24 hours of CARDAMYST administration: 0.4% of patients experienced hypotension, 0.1% of patients experienced syncope. *Includes patients who received CARDAMYST in double-blind, randomized, placebo-controlled, and open-label studies (n=1753); 2.5% of patients discontinued CARDAMYST due to treatment-related adverse reactions.
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Our Vision for Commercial Success of CARDAMYST Key: ED = Emergency Department; CCB = Calcium Channel Blocker; HCP = Healthcare Provider Citations: Internal market research 8Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 Patients Empowerment Fast, reliable self-administration Less disruption, reliance on ED Less fear over when the next event will occur Prescribers Provides a solution Trusted CCB mechanism Robust clinical data Frees up HCP time and office resources Novel and cost-effective treatment Potential to reduce ED visits or hospital admissions Payers Efficiency Goal Easy to use Easy to prescribe Limit need to manage
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Presenters Introduction & CARDAMYST Label Highlights Joe Oliveto, President & Chief Executive Officer Clinical Perspective David Bharucha, MD, PhD, FACC, Chief Medical Officer Commercial Plans Lorenz Muller, Chief Commercial Officer Conclusion Joe Oliveto (Q&A) Joe Oliveto, David Bharucha, Lorenz Muller. Amit Hasija Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 9 Joe Oliveto David Bharucha Lorenz Muller Amit Hasija
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PSVT– An Atrial Arrhythmia with a Substantial Patient Burden PSVT = Paroxysmal Supraventricular Tachycardia; AV = Atrioventricular; AVNRT=AV Nodal Reentrant Tachycardia; AVRT=AV Reentrant Tachycardia 10 PSVT (mainly AVNRT and AVRT) Arrhythmias characterized by a sudden-onset, rapid heart rate 90% of PSVTs are AV-nodal dependent (CCB-sensitive) Commonly 150 - 250 bpm Common & Disabling Symptoms Include Heart palpitations Shortness of breath Light-headedness Chest pressure or pain Fatigue Anxiety / Loss of control Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025
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Chronic / Preventive Acute Many Current Treatments are Poorly Effective, Invasive, or Inconvenient BB = Beta Blocker; CCB = Calcium Channel Blocker; PiP = Pill in Pocket *Ablation is elected by only ~15% of eligible US PSVT patients (due to patient reluctance, availability issues). Citations: 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, Circulation. 2016;133:e471–e505 11Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 Most Patients Experience PSVT Problems Despite Chronic Rx or PiP Options Oral BBs and CCBs Catheter ablation* ED, Urgent Care visit or hospitalization “Pill in Pocket” = off label oral CCB or BB, or vagal maneuver
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CARDAMYST is a Novel CCB Designed to Treat PSVT Episodes Safely and Quickly CCB = Calcium Channel Blocker; MOA = Mechanism of Action 12Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 Short-acting CCB MOA very well understood and trusted New Chemical Entity (NCE) Patent protection until 2042 Portable, on-demand nasal spray Fast onset of action, well tolerated Robust clinical data in PSVT Label provides strong basis for communicating efficacy, safety, and tolerability Empowering patients to self-treat symptomatic attacks
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Presenters Introduction & CARDAMYST Label Highlights Joe Oliveto, President & Chief Executive Officer Clinical Perspective David Bharucha, MD, PhD, FACC, Chief Medical Officer Commercial Plans Lorenz Muller, Chief Commercial Officer Conclusion Joe Oliveto (Q&A) Joe Oliveto, David Bharucha, Lorenz Muller. Amit Hasija Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 13 Joe Oliveto David Bharucha Lorenz Muller Amit Hasija
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2M+ Patients Cost the Healthcare System at Least $5 Billion Annually Key: PSVT = Paroxysmal Supraventricular Tachycardia Citations: 1. Rehorn M, et al. J Cardiovasc Electrophysiol. 2021 Aug;32(8):2199-2206. 2. IQVIA Pharmetrics Plus 2019 Commercial claims for patients <65yo and Medicare LDS 5% for patients >65yo (ICD: I47.1) 3. Healthcare Utilization Project (HCUP) 2019, https://hcup-us.ahrq.gov/databases.jsp; accessed 12/2025; range reflects ED visits/IP admissions with PSVT as primary diagnosis code to ED visits/IP admissions with PSVT in any diagnostic position. 14Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 140,000 – 525,000 Emergency Department Visits per Year3 ~100,000 Ablations Performed per Year2 650,000 to 1M Patients Treated per Year2 40,000 – 120,000 In-Patient Admissions per Year3 ~2M+ Patients Diagnosed with PSVT1
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Accessible and Compelling Commercial Opportunity for CARDAMYST Key: MOA = Mechanism of Action; HRU = Healthcare Resource Utilization Citations: Internal Market Research and Longitudinal Analysis of Truven/Marketscan and Medicare claims data No anticipated branded competition Low barrier to prescribing Opportunity for strong demand generation & quality coverage Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 15 ~650k – 1M patients treated annually ~50% patients commercially insured Cost offsets driven by lower HRU Familiar and trusted MOA Robust clinical data 100% share of voice Lower rebate pressure
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~2 million1 Diagnosed Population with PSVT Milestone can Potentially Reach Half of Annually-Treated Patients by Calling on ~10,000 Prescribers with ~60 Sales Reps2 Citations: 1. Rehorn M, et al. J Cardiovasc Electrophysiol. 2021 Aug;32(8):2199-2206. 2. Milestone Data on File 16Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 Each figure represents 5,000 patients with PSVT
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~2 million1 Diagnosed Population with PSVT Milestone can Potentially Reach Half of Annually-Treated Patients by Calling on ~10,000 Prescribers with ~60 Sales Reps2 Citations: 1. Rehorn M, et al. J Cardiovasc Electrophysiol. 2021 Aug;32(8):2199-2206. 2. Milestone Data on File. 3. IQVIA Pharmetrics Plus 2019 Commercial claims for patients <65yo and Medicare LDS 5% for patients >65yo (ICD: I47.1) 17Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 Each figure represents 5,000 patients with PSVT ~1 million3 Annually Treated Population with PSVT managed by ~40,000 healthcare providers
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~2 million1 Diagnosed Population with PSVT Milestone can Potentially Reach Half of Annually-Treated Patients by Calling on ~10,000 Prescribers with ~60 Sales Reps2 Citations: 1. Rehorn M, et al. J Cardiovasc Electrophysiol. 2021 Aug;32(8):2199-2206. 2. Milestone Data on File. 3. IQVIA Pharmetrics Plus 2019 Commercial claims for patients <65yo and Medicare LDS 5% for patients >65yo (ICD: I47.1). 4. Milestone Data on File 18Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 Each figure represents 5,000 patients with PSVT ~1 million3 Annually Treated Population with PSVT managed by ~40,000 healthcare providers ~500,0004 Annually Treated Population with PSVT managed by ~10,000 healthcare providers
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~2 million1 Diagnosed Population with PSVT Milestone can Potentially Reach Half of Annually-Treated Patients by Calling on ~10,000 Prescribers with ~60 Sales Reps2 Citations: 1. Rehorn M, et al. J Cardiovasc Electrophysiol. 2021 Aug;32(8):2199-2206. 2. Milestone Data on File. 3. IQVIA Pharmetrics Plus 2019 Commercial claims for patients <65yo and Medicare LDS 5% for patients >65yo (ICD: I47.1). 4. Milestone Data on File 19Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 Each figure represents 5,000 patients with PSVT ~1 million3 Annually Treated Population with PSVT managed by ~40,000 healthcare providers ~500,0004 Annually Treated Population with PSVT managed by ~10,000 healthcare providers ~8,0004 Clinical/Interventional Cardiologists managing ~330,000 patients with PSVT ~1,5004 Electrophysiologists managing ~130,000 patients with PSVT ~5004 Primary Care Physicians managing ~40,000 patients with PSVT ~10,000 healthcare providers Targets for ~60 sales reps
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Versatility of CARDAMYST Leads to Multiple Use Cases in PSVT Citations: Internal Market Research 20Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 Diagnosis Off-Label Chronic Oral Rx Off-Label “Pill in Pocket” Rx No Treatment Catheter Ablation ← Add ← Switch ← Add ← Switch ← Add ← Bridge ← Alternative Attack of PSVT Emergency Department “Tough it out” Very frequent and/or severe Not infrequent and moderate/severe Infrequent or mild Target Addressable Market
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Cardiologists Expect to Prescribe CARDAMYST to the Majority of Unablated Patients with PSVT Citation: Quantitative market research conducted by Triangle Insights Group (n=250 cardiologists), June-September 2020; Estimated number of unique patients with annual claims for PSVT from Truven MarketScan data, 2008-2016 analyzed by Precision Xtract, 2019 21Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 Cardiologists’ Stated Adoption of CARDAMYST per Segment Current Management of PSVT Pill-in-Pocket 64% Chronic Meds Alone 43% No Current Treatment 53% Impact of Expected Cardiologist Adoption of CARDAMYST Pill-in- Pocket 34% Chronic Medications Alone 37% No Treatment 17% Ablation 12% 46% 12% 21% 8% 12%
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Market Access Strategy: Accessibility and Affordability 1. Data on file (Trinity); 2. Sacks NC et al. Am J Cardiol. 2020 Jan 15;125(2):215-221; 3. Deshmukh A et al. Heart Rhythm O2. 2022 Aug 4;3(5):577-586; 4. Data on File (Healthcare Cost and Utilization Project (HCUP) NIS 2019 and CMS hospitalization payments, 2021); 5. Jiang S et al. J Manag Care Spec Pharm. 2022 Nov;28(11):1321-1330; 6. Chew DS et al. Circ Arrhythm Electrophysiol. 2022 Feb;15(2);. 7. Assumed to be equivalent to ED visits 22Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 PSVT Treatment Cost $1,649 WAC per Rx $500-$1,000 Net Sales per Rx Emergency Department Visits3,5 Commercial: $2,500 Medicare: $3,500 Inpatient Visits1,2,3,4 Commercial: $39,935 Medicare: $14,956 Outpatient Hospital Visits7 Commercial: $2,500 Medicare: $3,500 Ablations1,2,6 Commercial: $35,000 Medicare: $15,000 Healthcare Providers Patients Coverage with Low Need to Control Not actively managing PSVT Rational pricing supports coverage Potential for cost offsets Easy to Prescribe Contract for quality coverage Reimbursement support services Prior Auth/denial conversion support Accessible and Affordable Retail distribution Copay mitigation for commercial Patient support services Payers
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Key Brand Performance Indicators for Planned Launch Year • New to Brand Prescriptions (NBRx) • Prescription Growth (week over week) 23Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 • % Target Lives Covered (emphasis on commercial) • % of Targets with Quality Coverage Drive HCP Awareness & Adoption Establish & Maintain Broad, Quality Access & Affordability Strategic Objective:
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Factors Supporting Launch Year Uptake of CARDAMYST Citations: Internal Market Research and Data on File 24Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 • Initial sales force covers 50% of potential annually treated patients • Patients seeking treatment weekly • HCP familiarity and evidence-based approach • Accessibility through retail distribution • Fit-for-purpose HCP and patient support programs • No anticipated branded competition • Potential healthcare cost offsets facilitates coverage Scripts Written Scripts Filled
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Presenters Introduction & CARDAMYST Label Highlights Joe Oliveto, President & Chief Executive Officer Clinical Perspective David Bharucha, MD, PhD, FACC, Chief Medical Officer Commercial Plans Lorenz Muller, Chief Commercial Officer Conclusion Joe Oliveto (Q&A) Joe Oliveto, David Bharucha, Lorenz Muller. Amit Hasija Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 25 Joe Oliveto David Bharucha Lorenz Muller Amit Hasija
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Conclusion 26Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025
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Q&A Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 27 Joe Oliveto David Bharucha Lorenz Muller Amit Hasija
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Thank you