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Corporate Overview November 12, 2025 Investigational Product. Not approved for commercial use in any jurisdiction.
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Disclaimer This presentation discusses our intended promotional launch strategy for CARDAMYSTTM (etripamil) nasal spray, which has not yet been approved for commercial use in any jurisdiction. Any plans described herein remain subject to FDA approval of the NDA. Milestone Pharmaceuticals Corporate Overview 2
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Forward Looking Statements 3Milestone Pharmaceuticals Corporate Overview 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) the outcomes of future interactions with the FDA, including with regard to the new drug application for CARDAMYST; (ii) Milestone's ability to address the issues raised in the CRL on a timely basis, if at all; (iii) the outcome of the potential NDA resubmission; (iv) potential protections afforded by U.S. patents; (v) the design, progress, timing, scope and results of the etripamil clinical trial in AFib-RVR; (vi) the potential efficacy, safety and tolerability of etripamil for AFib-RVR; (vii) 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 hospital admissions, (c) empower patients to treat symptomatic attacks; (viii) plans relating to commercializing CARDAMYST, if approved, including timing, the geographic areas of focus and sales strategy; (ix) the potential market size and the rate and degree of market acceptance of CARDAMYST (etripamil) and any future product candidates; (x) the projected use of CARDAMYST in the future; (xi) anticipated commercial and Medicare coverage of CARDAMYST; (xii) the implementation of Milestone’s business model and strategic plans for its business, etripamil and any future product candidates; (xiii) Milestone’s expected cash runway; (xiii) potential royalty payments and potential royalty funding; 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; whether and when, if at all, our NDA for etripamil will be approved by the FDA; 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 Israel and Gaza 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 quarterly report on form 10-Q for the quarter ended March 31, 2025, 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. 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 Milestone's own internal estimates and research. While Milestone 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 Milestone'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.
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Milestone - 2025 Key: PSVT = Paroxysmal Supraventricular Tachycardia; AFib-RVR = Atrial Fibrillation with Rapid Ventricular Rate; CRL = Complete Response Letter; sNDA = supplemental New Drug Application 1 $75.0M in non-dilutive royalty funding if etripamil is approved by the FDA in 2025 2 March 25, 2025 – US Patent Office issued patent covering repeat dose regimen 4Milestone Pharmaceuticals Corporate Overview • CARDAMYST being developed to be first and only FDA-approved on-demand therapy for patients with PSVT • PDUFA target date Dec. 13, 2025, response to CRL accepted by FDA • Promotional launch plans set with quick start capability • $82.6M cash balance as of September 30, 2025 • $75M payment expected upon FDA approval from royalty financing1 • Exclusivity to 2042 via recently issued US patent2 • AFib-RVR represents larger potential target population than PSVT • Strong Phase 2 data published • Approval for PSVT, opens regulatory sNDA pathway for AFib-RVR • Phase 3 AFib-RVR is set up, study-start paused PSVT AFib-RVR Finances & Other
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Atrial Arrhythmias with a Common Patient Burden and Cardiac Target Key: PSVT = Paroxysmal Supraventricular Tachycardia; AFib-RVR = Atrial Fibrillation with Rapid Ventricular Rate; SA = Sino-Atrial; AV = Atrioventricular Sources: adapted from https://en.ecgpedia.org/index.php?title=Supraventricular_Rhythms, accessed 2/2021 5 AV Node SA Node Atrial Fibrillation (multiple atrial wavelets) AV Reentrant Tachycardia (AVRT) AV Nodal Reentrant Tachycardia (AVNRT) AV Node – gatekeeper of electrical signals to the ventricles Irregular rapid heart rate; episodes have sudden onset Commonly 100 - 175 bpm PSVT (AVNRT and AVRT) Arrhythmia characterized by a sudden-onset, rapid heart rate Commonly 150 - 250 bpm AFib-RVR (subset of AFib) Common Symptoms Include Heart palpitations Shortness of breath Light-headedness Chest pressure or pain Fatigue Anxiety / Loss-of-control Target = AV Node Milestone Pharmaceuticals Corporate Overview
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PSVT Characteristics and Patient Burden • Chronic condition with symptomatic attacks of elevated heart rate • Unpredictable onset, duration, severity, and frequency • Interferes with life activities • More common in women (~65%) • ~Half under 65 years of age • Mostly managed by Cardiology (~70%) • Current treatments are inconvenient, intrusive or ineffective • No new drug therapies approved since IV adenosine (1989) 6Milestone Pharmaceuticals Corporate Overview
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Most Patients Experience Attacks Despite Preventive Options Many Current Treatments for PSVT are Inconvenient, Intrusive, or Ineffective Key: BB = Beta Blocker; CCB = Calcium Channel Blocker; HCPs = Health Care Providers Citations: 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. Circulation. 2016;133:e471–e505 7 “Pill in Pocket” = off label oral CCB or BB, or Vagal maneuver • poor efficacy (low success and delayed) • used because many HCPs want to offer something to help patients self manage ED, Urgent Care Visit or Hospitalization • IV adenosine, IV CCB or DC cardioversion • time consuming • costly • stressful Oral BBs and CCBs • reduce episodes • only somewhat effective • require daily administration though need is for episodes • unwanted side effects Catheter ablation • often curative • risks associated with invasive procedure • only elected by ~15% patients Milestone Pharmaceuticals Corporate Overview Chronic / Preventive Acute
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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 11/2024; range reflects ED visits/IP admissions with PSVT as primary diagnosis code to ED visits/IP admissions with PSVT in any diagnostic position. 8Milestone Pharmaceuticals Corporate Overview 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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CARDAMYST is a Novel Investigational CCB Designed to Treat Episodes of PSVT and AFib-RVR Safely and Quickly Key: NCE = New Chemical Entity; CCB = Calcium Channel Blocker; MOA = Mechanism of Action 9Milestone Pharmaceuticals Corporate Overview New Chemical Entity Short-acting CCB MOA very well understood and trusted Patent Protection until 2042 Robust clinical data in PSVT Portable, on-demand nasal spray Fast onset of action, well tolerated Empowering patients to self-treat symptomatic attacks
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CARDAMYST Would Put Patients in Control of Their PSVT Citations: Internal market research 10Milestone Pharmaceuticals Corporate Overview Efficacy Convenience Safety Cost Quiet Mind Reduce worry between episodes with versatile on-demand treatment Active Living Allow a return to normal rhythm Patient Empowerment Empower in disease management and avoid unneeded healthcare visits Rapid & Reliable Relief Provide meaningful relief from episode symptoms and duration Investigational Product. Not approved for commercial use in any jurisdiction
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Well-Tolerated with a Favorable Safety Profile Safety Data from RAPID 1. Randomized-period treatment-emergent adverse events, those ≥5% or those specifically tracked as potentially representing lowered blood pressure. 2. Safety Population. 3. Six of eight rated as mild, two of eight rated as moderate, zero needing intervention.. Key: AV = Atrioventricular Citations: American Heart Association Scientific Sessions, Late-Breaking Clinical Trial Presentation, November 2022; and The Lancet (2023). 11Milestone Pharmaceuticals Corporate Overview Subject-reported AEs from the RAPID Study,1 n (%) Placebo2 n=120 Etripamil2 n=135 Nasal discomfort 6 (5.0) 31 (23.0) Nasal congestion 1 (0.8) 17 (12.6) Rhinorrhea 3 (2.5) 12 (8.9) Epistaxis 2 (1.7) 8 (5.9)3 Adverse Events were predominantly attributed to route of administration No syncope, pre-syncope, or 2nd/3rd degree AV block
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Fast Relief to More Patients Efficacy Data from RAPID 12Milestone Pharmaceuticals Corporate Overview 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 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 Time since study drug administration (minutes) Placebo 31% Etripamil 64% 85 67 60 56 49 44 37Placebo 78 64 58 53 45 40 36 3537 36 32 99 67 45 35 31 28 26Etripamil 79 55 40 33 29 27 23 2025 22 19 35 19 Number of subjects at risk 61% 81% Conversion of PSVT to SR by 30 min: HR = 2.62 (95% CI: 1.659, 4.147); p<0.001 55% 73% More Converted >2x patients converted to SR within 30 minutes of taking CARDAMYST vs placebo Kaplan-Meier probability of conversion, (%) Faster Conversion >3x faster conversion of PSVT to SR with CARDAMYST vs placebo Fewer ED Visits ~40% reduction in ED use for CARDAMYST vs placebo
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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 13Milestone Pharmaceuticals Corporate Overview 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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Versatility of CARDAMYST Leads to Multiple Use Cases in PSVT Citations: Internal Market Research 14Milestone Pharmaceuticals Corporate Overview Diagnosis Off-label Chronic Oral Rx Off-label “Pill in Pocket” Rx No Treatment Catheter Ablation ← Add ← Switch ← Add ← Switch ← Add ← Bridge ← Alternative CARDAMYST 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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Patients with PSVT are Primarily Treated by Cardiologists in the Outpatient Setting Citations: Internal Market Research 15 Clinical CardiologistsPrimary Care Physicians Electrophysiologists 10% 60%30% Milestone Pharmaceuticals Corporate Overview
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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 16Milestone Pharmaceuticals Corporate Overview 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% CARDAMYST 46% 12% 21% 8% 12%
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Electrophysiologists Have an Important Role to Play with CARDAMYST Key: KOL = Key Opinion Leader; P&T = Pharmacy & Therapeutics; PSVT = Paroxysmal Supraventricular Tachycardia; AFib-RVR = Atrial Fibrillation with Rapid Ventricular Rate; EPs = Electrophysiologists Citations: Internal Market Research 17 • KOLs in arrhythmias respected for their input onP&T and guidelines • Perform ~100,000 cardiac ablations annually in the U.S. • Treat ~10% of patients with PSVT Bridge to ablation between consultation and procedure (33%) Alternative to ablation for patients hesitant about procedure (24%) EPs report willingness to use CARDAMYST in majority of cases1 Milestone Pharmaceuticals Corporate Overview
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3-5 times per year Most Patients with a Diagnosis of PSVT Over Time Could Use CARDAMYST Multiple Times per Year Citations:. 1. Stambler BS, et al. Lancet 2023 Jul 8;402(10396):118-128.; Stambler BS. et al. CIRCEP. 2022 Dec;15(12):e010915. 2. Ip JE et al. JACC. 2024 May 21;83(20):2032-2034.; Ip JE et al. JAHA. 2023 Oct 3;12(19):e028227. 3. PSVT patient longitudinal study (n=247 US & UK), conducted by Blueprint Research Group, 2019-2020. 4. Quantitative market research (n=250 clinical cardiologists) conducted by Triangle Insights Group, 2020-2021. 18 Source Reported Frequency of use of CARDAMYST/yr Randomized Clinical Studies1 3-9 Open Label Studies2 2-4 Observational Study3 4-6 Market Research4 3-4 Projected use of CARDAMYST: ~1 per year Launch Year 1 ~1-2 per year Year 2 ~3-5 per year Year 3+ Milestone Pharmaceuticals Corporate Overview
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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 Corporate Overview 19 ~650k patients treated annually ~50% commercially- insured patients Cost offsets driven by lower HRU Familiar and trusted MOA Robust clinical data 100% share of voice Lower rebate pressure
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Priorities for Launching CARDAMYST 20Milestone Pharmaceuticals Corporate Overview Awareness and Demand Generation Sales Leadership Sales Rep hiring following potential approval Promotional launch shortly after rep hiring Access and HCP Experience Distribution Contracts Payer engagement (National Account Team) Reimbursement Support Programs Patient Experience and Affordability Contracting for Target Coverage Patient Support Services Copay Mitigation (Commercial)
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PSVT & AFib-RVR Populations in the US 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 January 2021. 3. Rehorn et al. Journal of Cardiovascular Electrophysiology. 2021 Aug; 32(8): 2199-2206. doi: 10.1111/jce.15109. Epub 2021 Jun 14. 2018 prevalence of 2M anticipated to grow at a CAGR of ~2% 4. Quantitative Survey conducted by Triangle Insights, May 2021, N=250 Clinical Cardiologists, Interventional Cardiologists, and Electrophysiologists. 5. Estimate of TAM (~40%- 60% of prevalence) based 2019 market research with patients conducted by BluePrint Research Group, (n=247) 21Milestone Pharmaceuticals Corporate Overview PSVT Atrial Fibrillation Total Patients (2030) 2.6 Million3 10 Million1 Discharged ED Visits & Hospital Admissions (2016)2 145 Thousand 785 Thousand Target Addressable Market (2030) Patient Population 1.0-1.6 Million5 ~3-4 Million4 Atrial Fibrillation 10 Million1 785 Thousand AFib-RVR ~3-4 Million4
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AFib-RVR – Acute Treatment Scenarios 22Milestone Pharmaceuticals Corporate Overview Acute AFib-RVR Attack Symptom Impact • Heart palpitations • Chest pressure/pain • Shortness of breath Need to treat early • Early symptom relief • Lessen urgent-care need • Prevent snow-ball effect, eg, ‘AFib-RVR begets AFib-RVR’ • Marked fatigue • Light-headedness • Anxiety Heart Rate Time (hrs) Patient 3: Self-administered, fast-acting Rx Patient 1: Acute oral drug, ‘pill-in-pocket’ Patient 2: Emergency Department, intravenous drug
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Potential Use Cases of Etripamil for AFib-RVR 1. Acute, stand-alone, portable treatment for rate control and symptom control 2. Acute treatment as a bridge (“precursor”) to the delayed effects of oral rate-control or anti-arrhythmic drug administration 3. Use peri-ablation 4. Non-invasive administration opens options for potential treatment without an IV line in emergency-department or ambulance setting Key: AFib-RVR = atrial fibrillation with rapid ventricular rate, Rx = treatment, IV = intravenous 23 A drug that is rapidly acting and self-administered outside of a medical setting could have characteristics that fulfill an unmet medical need Milestone Pharmaceuticals Corporate Overview
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ReVeRA - Phase 2 Trial of Etripamil in Patients Presenting Urgently with AFib-RVR Key: AFib-RVR = Atrial Fibrillation with Rapid Ventricular Rate; ED = Emergency Department; bpm = beats per minute; VR = Ventricular Rate 24Milestone Pharmaceuticals Corporate Overview Baseline ECG for ≥ 10 min Double-blind study drug single dose 70 mg etripamil : placebo (1:1) Monitor as in-patient for 1 hour Six-hour remote ECG monitor Safety visit 24 hours post dose Key Inclusion: • Atrial Fibrillation ≥ 1 hour • Ventricular Rate (VR) ≥ 110 bpm Select Exclusion: • Treated with IV antiarrhythmic drugs • Hemodynamically unstable • Severe heart failure Primary: Maximum reduction in VR within 60 min; • Objective ≥20 bpm max VR reduction • Sized: 50 patients; α=0.05; 90% power Secondary: • Time to VR reduction • Duration of VR reductions • Patient satisfaction with treatment symptom relief Assessing Ventricular Rate Reduction with Etripamil – How Much; How Fast; How Long Presents to Emergency Dept. with episode of AFib-RVR Dosing & Assessment Efficacy Analysis
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-40 -35 -30 -25 -20 -15 -10 -5 0 5 10 0 10 20 30 40 50 60 Change in Ventricular Rate (bpm) Time (minutes) Etripamil Placebo PRIMARY ENDPOINT: Maximum Reduction in VR from Baseline Placebo NS, N=251 Etripamil NS (70 mg) N=241 Mean, bpm -5.06 -34.97 Difference in means, bpm -- -29.91 p-value2 -- <0.0001 ReVeRA – Substantial & Rapid Reduction in VR with Etripamil Note: Data plotted on time course are not those directly used for calculation of Primary Endpoint (by pre-specified plan). X-axis: of plot: time following drug administration; Y-axis: 5-min moving average, bpm ±SEM. 1 Efficacy Population (all randomized patients receiving study drug remaining in atrial fibrillation with adequately diagnostic ECG recordings for at least 60 min post drug) 2 By ANCOVA. Source: American Heart Association Scientific Sessions, Featured Science Presentation, Nov. 2023; and Circulation: Arrhythmia & EP (Nov. 2023) 25 Key: NS = Nasal Spray; VR = ventricular rate; bpm = beats per minute Milestone Pharmaceuticals Corporate Overview
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ReVeRA – Mean Heart Rate Change from Baseline 26 1 mITT Population (all randomized patients receiving study drug, 5 min moving average ±SEM). Primary endpoint: VR max. reduction from baseline, 30 min., 29.91 bpm, p<0.0001. Difference between areas under the curves, 180 min., p<0.00001, by t -test. 2 including beta-blockers, calcium channel blockers, digoxin. VR = ventricular rate. Placebo 29 28 26 25 25 25 25 Etripamil 27 27 26 26 26 26 26 No. at risk1 -40 -35 -30 -25 -20 -15 -10 -5 0 5 10 0 30 60 90 120 150 180 Change in Ventricular Rate (bpm) Time (minutes) Etripamil Placebo Milestone Pharmaceuticals Corporate Overview • Data Show Significant, Lasting Duration of Effect of Etripamil NS, up to 180 min • Lower Use of Rescue Medication Approximately twice as many rescue meds (IV and oral AV-nodal agents2) were administered to patients on placebo vs. etripamil starting at 60 minutes
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1 Treatment Satisfaction Questionnaire for Medication-9, a validated Patient-Reported Outcome tool, Question #2; administered to Efficacy Population (all randomized patients receiving study drug remaining in atrial fibrillation with adequately diagnostic ECG recordings for at least 60 min post drug). P-value is from t-test. Delta is difference between mean responses; a delta of 1 or greater indicates a clinically meaningful difference. Source: American Heart Association Scientific Sessions, Featured Science Presentation, Nov. 2023; and Circulation: Arrhythmia & EP (Nov. 2023) 27Milestone Pharmaceuticals Corporate Overview Question: How satisfied or dissatisfied are you with the way the medication relieves your symptoms? 1 1 2 3 4 5 6 7 Extremely Dissatisfied Very Dissatisfied Dissatisfied Somewhat Satisfied Satisfied Very Satisfied Extremely Satisfied Delta = 1.55 units ReVeRA – Significant and Clinically Meaningful Difference in Satisfaction with Symptom Relief
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AFib-RVR Phase 3 Key: AFib-RVR = atrial fibrillation with rapid VR. sNDA = supplemental New Drug Application. PRO = patient reported outcome. VR = ventricular rate 28Milestone Pharmaceuticals Corporate Overview • Potential single-study, regulatory registration program via sNDA pathway • Study design, dosing, conduct & operations similar to PSVT Phase 3 Program ― Double-blind randomized; etripmail vs. placebo ― Patient self-administration outside the medical setting, prompted by symptoms ― Etripamil 70-mg repeat-dose regimen • Primary endpoint: Reduction in Ventricular Rate (VR) within 30 minutes; • Key Secondary endpoint: symptom relief measured via PRO; necessary for approval • Sizing: Estimate ≈ 150-200 total events, 90% power, p < 0.05 • Operationally: Ready to start
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Financials as of September 30, 2025 $82.6M Cash and short-term investments Equity: 101.6 M units1 - 85.2M common shares - 16.4M pre-funded warrants 1 Common shares as of November 12, 2025, and pre-funded warrants as of September 30, 2025 2 In March 2023, Milestone announced a $125.0M strategic financing with RTW Investments. The financing consists of $50.0M in convertible notes issued in March 2023, and a commitment of $75.0M in non-dilutive royalty funding if etripamil is approved by the FDA in 2025. 3 Series A warrants $1.50 exercise price, exercisable immediately and will expire 1 year from issuance, July 14, 2026. Net of underwriter’s discount 4 Series B warrants $1.875 exercise price, exercisable immediately and will expire 5 years from issuance, July 14, 2030. Forced exercise 10 consecutive trading days above $3.50. Net of underwriter’s discount 29 $265M in total potential funding for commercialization - $82.6M Cash and s-t investments - $75M Royalty payment upon approval2 - $49M Series A warrants3 - $59M Series B warrants4 Milestone Pharmaceuticals Corporate Overview
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Thank you
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Complete Response Letter (CRL) • No clinical concerns raised relating to safety or efficacy of etripamil • Focused on Chemistry, Manufacturing & Controls (CMC) with two key issues 1. Nitrosamine impurities based on new guidance issued after the NDA submission 2. Pre-Approval Inspection required for facility that performs release testing and which has undergone an ownership change during the review 31Milestone Pharmaceuticals Corporate Overview Key: NDA = New Drug Application • Generated data from in vitro studies and nitrosamine testing • Type A meeting with FDA occurred in June • Response to the CRL submitted to the NDA on June 13, 2025 • FDA accepted the response to the CRL as complete; PDUFA target date of December 13, 2025 Progress – completed actions and next steps CRL received March 27, 2025
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Strategic Financing with RTW To help fund commercialization of CARDAMYST in PSVT 32Milestone Pharmaceuticals Corporate Overview 1 VWAP – Volume Weighted Average Price as of 3/27/23 2 Rate can increase by 2.5% if certain annual net sales thresholds are not met 3 Annual net product sales of etripamil in the United States • 6-year term ending 2029 • Initial Conversion Price $5.23/share ― 50% premium to 30-day VWAP1 • 6% coupon — Payable quarterly, or at our option payable in kind (PIK) for first 3 years • Funded if FDA approves etripamil in PSVT by December 31, 2025 • Non-dilutive synthetic royalty • 7% Royalty2 up to $500M3 • 4% Royalty >$500-$800M • 1% Royalty >$800M $50M Convertible Notes $75M Synthetic Royalty