8-K - MIST - Equibles

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d) of theSecurities Exchange Act of 1934

Date of Report (Date of earliest event reported):

December12, 2025

MILESTONE

PHARMACEUTICALS INC.

(Exact name of registrant as specified in its charter)

Québec	001-38899	Not<br> applicable
(state or other jurisdiction of incorporation)	(Commission File Number)	(I.R.S. Employer Identification No.)
1111<br> Dr. Frederik-Philips Boulevard,
---	---
Suite<br> 420
Montréal,<br> Québec CA	H4M<br> 2X6
(Address of principal executive offices)	(Zip Code)

Registrant's telephone number, including area code:

(514

)

336-0444

(Former name or former address, if changed since last report.)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

¨ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

¨ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

¨ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

¨ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

Title of each class	Trading Symbol(s)	Name of each exchange on which<br><br> registered
Common<br> Shares	MIST	The<br> Nasdaq Stock Market LLC

Indicate by check mark whether the registrant is an emerging growth company as defined in as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b–2 of the Securities Exchange Act of 1934 (§ 240.12b–2 of this chapter).

Emerging growth company ¨

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ¨

Item 7.01.	Regulation FD Disclosure.

On December 15, 2025, Milestone Pharmaceuticals Inc. (“Milestone” or the “Company”) provided a corporate presentation that may be used in connection with presentations at conferences and investor meetings. The full text of the Company’s corporate presentation is filed as Exhibit 99.1 hereto, and incorporated herein by reference, and may also be accessed through the “Investors & Media” section of the Company’s website at www.milestonepharma.com.

The Company intends to use its website as a means of disclosing material non-public information and for complying with its disclosure obligations under Regulation FD. Such disclosures will be included on its website in the “Investors & Media” section. Accordingly, investors should monitor such portions of its website, in addition to following press releases, filings with the U.S. Securities Exchange Commission (the “SEC”) and public conference calls and webcasts.

The information furnished under this Item 7.01, including Exhibit 99.1, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, or subject to the liabilities of that section or Sections 11 and 12(a)(2) of the Securities Act of 1933, or the Securities Act. The information in this Item 7.01, including Exhibit 99.1, shall not be deemed incorporated by reference into any other filing with the SEC, made by the Company, whether made before or after the date hereof, regardless of any general incorporation language in such filing.

Item 8.01	Other Events

On December 12, 2025, the Company issued a press release announcing that the U.S. Food and Drug Administration has approved the Company’s New Drug Application for CARDAMYST (etripamil) nasal spray for the management of paroxysmal supraventricular tachycardia (PSVT). A copy of the press release is filed herewith as Exhibit 99.2 to this Current Report on Form 8-K and incorporated herein by reference.

Item 9.01	Financial Statements and Exhibits

(d) Exhibits.

Exhibit Number	Description of Exhibit
99.1	Corporate Presentation,<br> dated December 15, 2025
99.2	Press Release dated December 12,<br> 2025
104	Cover Page Interactive<br> Data (embedded within the Inline XBRL document)

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

MILESTONE PHARMACEUTICALS INC.
By:	/s/Amit Hasija
	Amit Hasija
	Chief Financial Officer
Dated: December 15, 2025

Exhibit 99.1

FDA Approval Investor Call December 15, 2025

Forward Looking Statements 2 Milestone 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,’’ ‘ ‘de sign,’’ ‘‘due,’’ ‘‘estimate,’’ ‘‘expect,’’ ‘‘goal,’’ ‘‘intend,’’ ‘‘may,’’ ‘‘objective,’’ ‘‘plan,’’ ‘‘predict,’’ ‘‘positioned,’’ ‘‘potential,’’ ‘‘project,’’ ‘‘seek,’’ ‘‘ sho uld,’’ ‘‘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 - look ing 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 a dmissions, (c) empower patients to treat symptomatic attacks; (iii) plans relating to commercializing CARDAMYST, including timing, the geographic ar eas 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 and idates; (v) the projected use of CARDAMYST in the future; (vi) anticipated commercial and Medicare coverage of CARDAMYST; (vii) the implementation of M ile stone’s business model and strategic plans for its business, etripamil and any future product candidates; (viii) Milestone’s expected cash run way ; (ix) potential royalty payments and potential royalty funding; (x) Milestone’s expectations regarding patient reach and market access; and any other st atements not related to historical facts. Important factors that could cause actual results to differ materially from those in the forward - looking state ments include, but are not limited to, the risks inherent in biopharmaceutical product development and clinical trials; whether our future interactions wit h the FDA will have satisfactory outcomes; uncertainties related to the timing of initiation, enrollment, completion, evaluation and results of o ur clinical trials; risks and uncertainty related to the complexity inherent in cleaning, verifying and analyzing trial data; and whether the clinical tria ls will validate the safety and efficacy of etripamil for PSVT or other indications, among others, general economic, political, and market conditions, includ ing deteriorating market conditions due to investor concerns regarding inflation, international tariffs, Russian hostilities in Ukraine and ongoing di spu tes in the Middle East and overall fluctuations in the financial markets in the United States and abroad; risks related to pandemics and public health e mer gencies; and risks related the sufficiency of Milestone's capital resources and its ability to raise additional capital in the current economic climate. The se 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 th e 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 l aw, Milestone assumes no obligation to update any forward - looking statements contained herein to reflect any change in expectations, even as new informat ion becomes available.

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

CARDAMYST is indicated for the conversion of acute symptomatic episodes of paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm in adults . 4 Milestone 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

Fast Relief to More Patients with Persistent Effects to 5 Hours Efficacy Data from RAPID 5 Milestone 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 20 56 32 25 22 21

Kaplan - Meier probability of conversion, (%) Fast Relief to More Patients Efficacy Data from RAPID 6 Milestone 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 20 56 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

CARDAMYST Was Well Tolerated, With Most Adverse Events Localized to the Nasal Administration Site 7 Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 Placebo n = 223 % CARDAMYST 2x70 mg ‡ n=86 % CARDAMYST 70 mg n=235 % 6 23 28 Nasal discomfort 1 12 14 Nasal congestion 2 10 12 Rhinorrhea 1 6 7 Throat irritation 1 7 6 Epistaxis † 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.

Our Vision for Commercial Success of CARDAMYST Key: ED = Emergency Department; CCB = Calcium Channel Blocker; HCP = Healthcare Provider Citations: Internal market research 8 Milestone 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

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

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 F atigue Anxiety / Loss of control Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025

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 supraventricula r tachycardia, Circulation. 2016;133:e471 – e505 11 Milestone 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

CARDAMYST is a Novel CCB Designed to Treat PSVT Episodes Safely and Quickly CCB = Calcium Channel Blocker; MOA = Mechanism of Action 12 Milestone 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 d ata in PSVT Label provides strong basis for communicating efficacy, safety, and tolerability Empowering patients to self - treat symptomatic attacks

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

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. 14 Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 140,000 – 525,000 Emergency Department Visits per Year 3 ~100,000 Ablations Performed per Year 2 650,000 to 1M Patients Treated per Year 2 40,000 – 120,000 In - Patient Admissions per Year 3 ~2M+ Patients Diagnosed with PSVT 1

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 C ost offsets driven by l ower HRU Familiar and trusted MOA Robust clinical data 100% s hare of voice Lower rebate pressure

~2 million 1 Diagnosed Population with PSVT Milestone can Potentially Reach Half of Annually - Treated Patients by Calling on ~10,000 Prescribers with ~60 Sales Reps 2 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 18 Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 Each figure represents 5,000 patients with PSVT ~1 million 3 Annually Treated Population with PSVT managed by ~40,000 healthcare providers ~500,000 4 Annually Treated Population with PSVT managed by ~10,000 healthcare providers

~2 million 1 Diagnosed Population with PSVT Milestone can Potentially Reach Half of Annually - Treated Patients by Calling on ~10,000 Prescribers with ~60 Sales Reps 2 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 19 Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 Each figure represents 5,000 patients with PSVT ~1 million 3 Annually Treated Population with PSVT managed by ~40,000 healthcare providers ~500,000 4 Annually Treated Population with PSVT managed by ~10,000 healthcare providers ~8,000 4 Clinical/Interventional Cardiologists managing ~330,000 patients with PSVT ~1,500 4 Electrophysiologists managing ~130,000 patients with PSVT ~500 4 Primary Care Physicians managing ~40,000 patients with PSVT ~10,000 healthcare providers Targets for ~60 sales reps

Versatility of CARDAMYST Leads to Multiple Use Cases in PSVT Citations: Internal Market Research 20 Milestone 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

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 21 Milestone 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%

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 an d Utilization Project (HCUP) NIS 2019 and CMS hospitalization payments, 2021); 5. Jiang S et al. J Manag Care Spec Pharm. 2022 Nov;28(11):1 321 - 1330; 6. Chew DS et al. Circ Arrhythm Electrophysiol . 2022 Feb;15(2);. 7. Assumed to be equivalent to ED visits 22 Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 Cost PSVT Treatment $1,649 WAC per Rx $500 - $1,000 Net Sales per Rx Commercial: $2,500 Emergency Department Visits 3,5 Medicare: $3,500 Commercial: $39,935 Inpatient Visits 1,2,3,4 Medicare: $14,956 Commercial: $2,500 Outpatient Hospital Visits 7 Medicare: $3,500 Commercial: $35,000 Ablations 1,2,6 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

Key Brand Performance Indicators for Planned Launch Year • New to Brand Prescriptions ( NBRx ) • Prescription Growth (week over week) 23 Milestone 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:

Factors Supporting Launch Year Uptake of CARDAMYST Citations: Internal Market Research and Data on File 24 Milestone 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

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

Conclusion 26 Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025

Q&A Milestone Pharmaceuticals Approval Call for CARDAMYST | December 15, 2025 27 Joe Oliveto David Bharucha Lorenz Muller Amit Hasija

Thank you

Exhibit 99.2

Milestone Receives FDA Approval of CARDAMYST™(etripamil) as First and Only Self-Administered Nasal Spray for Adults with Paroxysmal Supraventricular Tachycardia (PSVT)

- First FDAapproved treatment in 30+ years for more than 2 million Americans with PSVT

- Novel nasalspray designed to rapidly resolve episodes of PSVT and restore sinus rhythm

- FDA approvalin PSVT enables development of AFib-RVR under sNDA pathway

- Milestonewell-capitalized to launch and commercialize CARDAMYST with existing capital and royalty financing

- Conferencecall and webcast December 15, 8:00 a.m. ET

MONTREAL and CHARLOTTE, N.C., December 12, 2025 (GLOBE NEWSWIRE) -- Milestone^®^ Pharmaceuticals Inc. (Nasdaq: MIST) today announced that the U.S. Food and Drug Administration (FDA) approved its first commercial product, CARDAMYST™ (etripamil) nasal spray, a prescription medication for the conversion of acute symptomatic episodes of paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm in adults. This approval marks the first time that more than two million Americans with PSVT will have a rapid-acting treatment option they can self-administer outside the emergency department or other healthcare setting. CARDAMYST is expected to be available in retail pharmacies in the first quarter of 2026.

CARDAMYST nasal spray is a novel and rapid-acting calcium channel blocker delivered when needed to treat often highly symptomatic and unpredictable episodes of PSVT. With CARDAMYST, adults with PSVT can be prepared wherever and whenever episodes occur, providing them with active management and a greater sense of control of their condition.

“CARDAMYST is a novel at-the-ready treatment option that addresses the unpredictable impact of PSVT by offering patients the freedom to manage episodes anytime and anywhere,” said Joseph Oliveto, President and Chief Executive Officer of Milestone Pharmaceuticals. “The FDA approval of CARDAMYST is a watershed moment for Milestone and a gratifying event for our team members, patients, clinical investigators, and health care providers who participated in the development program, all of whom I sincerely thank for their dedication, counsel, and collaboration toward this important achievement.”

“Some people with PSVT have endured years of anxiety, fearing their next episode and the stress and disruption of emergency department visits,” said James Ip, M.D., FACC, FHRS, an etripamil investigator. “CARDAMYST will give many of them the ability to administer a medication themselves that can quickly stop their PSVT episode and potentially avoid a hospital trip or a call to emergency services.”

CARDAMYST Clinical Data

The FDA approval of CARDAMYST is supported by a robust clinical trial program based on safety data from more than 1,800 participants and more than 2,000 episodes of PSVT. This includes the successful Phase 3 RAPID trial, a global, randomized, double-blind comparison of CARDAMYST vs. placebo, published in The Lancet in 2023. In clinical studies, participants using CARDAMYST were two times more likely to convert symptomatic PSVT to sinus rhythm and did so more than three times faster compared with placebo. The RAPID trial achieved its primary endpoint with 64% of those who self-administered CARDAMYST (N=99) converting from supraventricular tachycardia (SVT) to sinus rhythm within 30 minutes compared to 31% on placebo (N=85) (HR = 2.62; p<0.001). At one hour, the benefit was demonstrated in 73% of participants. In addition, significant reductions in time to conversion in those who took CARDAMYST were evident early and durable, with a median time to conversion of 17 minutes (95% CI: 13.4, 26.5) for those treated with CARDAMYST vs. 54 minutes (95% CI: 38.7, 87.3) for those treated with placebo.

A consistent safety profile and treatment effects were observed across all subgroups, including participants concurrently on beta blockers or calcium channel blockers. The most frequent adverse events occurring in ≥5% of participants in randomized clinical trials were mild-to-moderate and transient in nature, including local-site nasal discomfort, nasal congestion, rhinorrhea, throat irritation, and epistaxis. Less than 2% of trial participants discontinued therapy due to adverse events.

For more safety information about CARDAMYST, please see Important Safety Information below. For the latest information about the product availability, please see https://milestonepharma.com/.

PSVT, also called SVT, is characterized by episodes of abnormally fast heart rate. Most people with PSVT experience multiple sustained episodes that require treatment on an annual basis. Until now, successful treatment options typically required IV administration in healthcare settings, creating stress and costs for patients and their insurers. CARDAMYST offers a new approach to treat episodes of PSVT, enabling adults to self-administer the medication at the onset of symptoms. For more information, please visit SVTHearttoHeart.com.

“Our goal is that CARDAMYST will become a trusted and essential solution for healthcare providers and their patients,” said Lorenz Muller, Chief Commercial Officer of Milestone. “Our team is focused on making CARDAMYST available to adults with PSVT as quickly as possible, including actively working to secure insurance coverage and begin the distribution of the product through retail pharmacies.”

Annette Greene, CARDAMYST clinical trial participant and administrator of the Supraventricular Tachycardia Group on Facebook, with more than 30,000 members, said, “Adults with SVT have been waiting a long time for the day when they can confidently self-administer CARDAMYST to treat their SVT episodes. It is very exciting that the day has become a reality.”

Regarding future R&D, Milestone is poised to enter a Phase 3 program in atrial fibrillation with rapid ventricular rate (AFib-RVR), particularly on the strength of the successful ReVeRA Phase 2 trial in AFib-RVR, results of which were published in Circulation: Arrhythmia and Electrophysiology. Incorporating FDA’s guidance, Milestone has developed a Phase 3 registrational program to evaluate self-administered etripamil as a potential treatment for patients with AFib-RVR. When completed, the Company will be following a supplemental New Drug Application (sNDA) regulatory approval pathway for a potential second indication for etripamil in AFib-RVR. As such, Milestone will leverage the approved PSVT indication and the PSVT program data, along with a single pivotal Phase 3 study in patients with AFib-RVR.

About Paroxysmal Supraventricular Tachycardia

An estimated two million people in the United States are currently diagnosed with PSVT, a type of arrhythmia or abnormal heart rhythm. PSVT is characterized by episodes of sudden onset rapid heartbeats often exceeding 150 to 200 beats per minute. The heart rate spike is unpredictable and may last several hours. The rapid heart rate often causes disabling severe palpitations, shortness of breath, chest discomfort, dizziness or lightheadedness, and distress, forcing people with PSVT to limit their daily activities. The uncertainty of when an episode of PSVT will strike or how long it will persist can provoke anxiety and negatively impact the day-to-day life between episodes of people with PSVT. The impact and morbidity from an attack can be especially detrimental in people with underlying cardiovascular or medical conditions, such as heart failure, obstructive coronary disease, or dehydration. Many health care providers are dissatisfied with the lack of effective treatment options with people with PSVT, often requiring prolonged, burdensome, and costly trips to the emergency department or even invasive cardiac ablation procedures.

About Atrial Fibrillation with Rapid VentricularRate

An estimated ten million Americans suffer from atrial fibrillation (AFib), a common arrhythmia marked by an irregular, disruptive and often rapid heartbeat. A subset of patients with AFib experience episodes of abnormally high heart rate most often accompanied by palpitations, shortness of breath, dizziness, and weakness. While these episodes, known as AFib-RVR, may be treated by oral calcium channel blockers and/or beta blockers, patients frequently seek acute care in the emergency department to address symptoms. In 2016, nearly 800,000 patients were admitted to the emergency department due to AFib symptoms where treatment includes medically supervised intravenous administration of calcium channel blockers or beta blockers, or electrical cardioversion. With little available data for AFib-RVR, Milestone’s initial market research indicates that 30% to 40% of patients with AFib experience one or more symptomatic episodes of RVR per year that require treatment, suggesting a target addressable market of approximately three to four million patients in 2030 for etripamil in patients with AFib-RVR.

Indication

CARDAMYST is indicated for the conversion of acute symptomatic episodes of paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm in adults.

IMPORTANT SAFETYINFORMATION FOR CARDAMYST (etripamil)

What is CARDAMYST?:

CARDAMYST is a prescription medicine used to help restore normal heart rhythm in adults who have symptoms of sudden episodes of fast heartbeat called paroxysmal supraventricular tachycardia (PSVT).

It is not known if CARDAMYST is safe and effective in children.

Do not useCARDAMYST if you:

·	are allergic to CARDAMYST or any of its ingredients. See the Patient Information for a complete list of<br>ingredients in CARDAMYST.
·	have limitations in activities due to heart failure (moderate to severe heart failure).
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·	have Wolff-Parkinson-White (WPW) syndrome, Lown-Ganong-Levine syndrome, or an abnormal heart rhythm pattern<br>called pre-excitation (delta wave) on an electrocardiogram (ECG).
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·	have sick sinus syndrome without a permanent pacemaker.
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·	have second degree or higher atrioventricular (AV) block.
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Before using CARDAMYST,tell your healthcare provider about all of your medical conditions, including if you:

·	have a history of fainting.
·	have low blood pressure.
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·	are pregnant or plan to become pregnant. It is not known if CARDAMYST will harm your unborn baby.
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·	are breastfeeding or plan to breastfeed. It is not known if CARDAMYST passes into your breast milk. You<br>should stop breastfeeding for 12 hours after treatment with CARDAMYST. During this time, pump and throw away your breast milk. Talk to<br>your healthcare provider about the best way to feed your baby after using CARDAMYST.
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Tell your healthcareprovider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

What are the possibleside effects of CARDAMYST?

CARDAMYST may causeserious side effects, including:

Fainting due to CARDAMYST effects on blood pressure, heart rate, and electrical activity of the heart.<br>CARDAMYST may cause dizziness and fainting, especially in people with a history of fainting and certain heart problems, or people with<br>a history of fainting during an episode of PSVT. Use CARDAMYST while sitting in a safe area where you will not fall if you become dizzy<br>or lightheaded. Lie down if you feel dizzy or lightheaded after using CARDAMYST. If fainting occurs after using CARDAMYST, caregivers<br>should place you on your back and seek medical help.

The most common sideeffects of CARDAMYST include:

·	nasal<br> discomfort	·	throat<br> irritation
·	nasal<br> congestion	·	nosebleed
·	runny<br> nose

These are not all of the possible side effects for CARDAMYST. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Please see the full Prescribing Information https://milestonepharma.com/etripamilprescribinginformation.pdf for CARDAMYST.

Milestone Well-Capitalized to Launch and Commercialize CARDAMYST

Milestone is well-capitalized to launch and commercialize CARDAMYST with existing capital and royalty financing. As of September 30, 2025, Milestone had cash, cash equivalents, and short-term investments of $82.6 million. In addition in March 2023, Milestone entered into the Royalty Purchase Agreement with RTW Investments, LP and certain of its affiliates (RTW), pursuant to which RTW agreed to purchase, following the FDA approval (subject to certain conditions) of etripamil on or prior to September 30, 2025 (Approval Date), the right to receive a tiered royalty payments on the annual net product sales of etripamil in the United States, in exchange for a purchase price of $75.0 million. On July 10, 2025, Milestone amended its Royalty Purchase Agreement (the Amendment) to provide for a three-month extension of the Approval Date.

Pursuant to the Amendment, in order to receive the $75.0 million purchase price, Milestone must receive marketing approval of etripamil from the FDA on or prior to December 31, 2025, and satisfy the other customary closing conditions. Milestone anticipates that the FDA approval announced today will satisfy the requirements for Milestone to receive the $75.0 million purchase price.

Conference Call and Live Webcast

Milestone management will host a conference call and live audio webcast with slides at 8:00 a.m. ET on Monday, December 15, 2025, to discuss the FDA approval of CARDAMYST. To access the call, please dial 1-877-407-0792 (domestic) or 1-201-689-8263 (international) and refer to conference ID 13756738, or click on Call me™ link and request a return call. The Call me™ link will be made active 15 minutes prior to scheduled start time. The webcast and slides can be accessed live on this link and also on the “News & Events” page of the Milestone Corporate Website at https://milestonepharma.com/. The archived webcast will also be available on Milestone's website following the call.

About Milestone Pharmaceuticals

Milestone Pharmaceuticals Inc. (Nasdaq: MIST) is a biopharmaceutical company developing and commercializing innovative cardiovascular medicines to benefit people living with certain heart conditions. Milestone’s lead product is CARDAMYST™ (etripamil) nasal spray, a novel calcium channel blocker, which is FDA approved for the conversion of acute symptomatic episodes of paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm in adults. Etripamil is also in development for the treatment of symptomatic episodic attacks associated with AFib-RVR.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “believe,” “continue,” “could,” “demonstrate,” “designed,” “develop,” “estimate,” “expect,” “may,” “pending,” “plan,” “potential,” “progress,” “will”, “intend” and similar expressions (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 press release. 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 press release include statements regarding: expectations on the timing of CARDAMYST for PSVT being available to patients in retail pharmacies; CARDAMYST’s potential as a novel treatment option to help patients with PSVT; Milestone’s ability to make CARDAMYST quickly available to PSVT patients following FDA approval; the success of Milestone’s launch infrastructure; the timing of patient enrollment in the Phase 3 study of etripamil for AFib-RVR and expectations regarding the Phase 3 study in patients with AFib-RVR; and 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, 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, 2025 and its quarterly report on Form 10-Q for the quarter ended September 30, 2025, in each case under the caption “Risk Factors,” as such discussions may be updated from time to time by subsequent filings Milestone may 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.

Contact:

Investor Relations

Kevin Gardner, kgardner@lifesciadvisors.com

Media Relations

Rebecca Novak, rnovak@milestonepharma.com