UNITED STATES
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FORM
CURRENT REPORT
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| Item 7.01. | Regulation FD Disclosure. |
On November 13, 2023, Milestone Pharmaceuticals Inc. (“Milestone” or the “Company”) provided an updated 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 November 11, 2023, the Company issued a press release announcing positive Phase 2 data that show etripamil nasal spray resulted in rapid and statistically superior ventricular rate reduction and improved symptom relief in patients with atrial fibrillation with rapid ventricular rate compared to placebo. A copy of the press release is attached hereto as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated herein by reference.
| Item 9.01. | Financial Statements and Exhibits |
(d) Exhibits.
| Exhibit No. | Description |
| 99.1 | Corporate Presentation, dated November 13, 2023. |
| 99.2 | Press release, dated November 11, 2023. |
| 104 | Cover Page Interactive Data File (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. | ||
| Date: November 13, 2023 | By: | /s/ Amit Hasija |
| Amit Hasija | ||
| Chief Financial Officer Principal Financial Officer | ||
Exhibit 99.1
Company Overview CONFIDENTIAL Atrial Fibrillation Program Update November 2023
Forward Looking Statement 2 Milestone - Atrial Fibrillation Program 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,’’ ‘‘expec t,’ ’ ‘‘goal,’’ ‘‘intend,’’ ‘‘may,’’ ‘‘objective,’’ ‘‘plan,’’ ‘‘predict,’’ ‘‘positioned,’’ ‘‘potential,’’ ‘‘project,’’ ‘‘seek,’’ ‘‘should,’’ ‘‘target,’’ ‘‘will,’’ ‘‘would’’ (as well as other words or expressions refe ren cing 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 da te 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 design, progress, timing, scope and results of the etripamil clinical trials in PSVT and AFib - RVR, (ii) the potential efficacy, safety and tolerability of etripamil , (iii) the potential of etripamil to deliver a clinically meaningful benefit to patients with PSVT in the home - setting environment and to empower patients to tak e control of their condition as well as provide value to the healthcare system, (iv) the possibility that data could fulfill the efficacy requirement for an NDA submission w ith the FDA for etripamil , (v) plans relating to commercializing etripamil , if approved, including the geographic areas of focus and sales strategy and (vi) the potential market size and the rate and d egr ee of market acceptance of etripamil and any future product candidates and the implementation of Milestone's business model and strategic plans for its business, etripamil and any future product candidates. 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, including the lengthy and uncertain regulatory approval process, uncertainties related to the timing of initiation, enrollment, complet ion and evaluation of clinical trials, including the RAPID and ReVeRA trials, and whether the clinical trials will validate the safety and efficacy of etripamil for PSVT, AFib - RVR, or other indications, among others, as well as risks related to pandemics and public health emergencies, including those related to COVID - 19, and risks related the sufficiency of our capital resources and our ability to raise additional capital. These and other risks are set forth in Milestone's filings with the U.S. Securities and Exchange Commission, including in its annual report on Form 10 - K for the year e nded December 31, 2021, 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 resp ect ive 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 ob tai ned 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 informatio n o r statements made in this Presentation relating to or based on such internal estimates and research. Etripamil is an investigational new drug, which is not approved for commercial distribution in the United States.
Recent Progress and Key Upcoming Events 3 Milestone - Atrial Fibrillation Program Overview NDA submission for PSVT – October 2023 1 2 3 Initial data in AFib - RVR (NODE - 303 study) presented – May 2023 4 Operating runway to mid - 2025 via RTW financing – March 2023 7 AFib - RVR Ph2 ( ReVeRA study) data presented at AHA – November 2023 6 RAPID Study published in The Lancet – July 2023 Leadership Hired in Med. Affairs, Marketing, Market Access – 2022/2023 FDA Guidance (pre - IND meeting) on AFib - RVR Phase 3 Study – Mid 2023 5
KOL View on Currently Available Approaches / Unmet Need in AFib 4 • Regardless of rate - or rhythm - control strategy, break - through episodes of AFib - RVR are frequent, symptomatic, highly burdensome, and disruptive • Current treatment of acute attacks in the emergency department are burdensome and costly • Expensive and inefficient use of healthcare system resources • What would be helpful, and is currently missing, is a simple, fast - acting treatment, that could: ─ be self - administered at - home ─ reduce burden of episodes, and reduce trips to ED and calls to physicians Milestone - Atrial Fibrillation Program Overview Source: Milestone Pharmaceuticals Virtual Key Opinion Leader Event on Etripamil for the Treatment of AFib - RVR, May 22, 2023; htt ps://investors.milestonepharma.com/events - and - presentations KOL = Key Opinion Leader; AFib - RVR = Atrial Fibrillation with Rapid Ventricular Rate; ED = Emergency Department
Clinical Pipeline Advancement for Etripamil 5 Milestone - Atrial Fibrillation Program Overview PSVT AFib - RVR Phase 1 Phase 2 Phase 3 NDA Filing / Approval Pharmacology of L - type calcium channel blockers drives broad clinical utility Rapid conversion to sinus rhythm PSVT = Paroxysmal Supraventricular Tachycardia ; AFib - RVR = Atrial Fibrillation with Rapid Ventricular Rate; NDA = New Drug Application Acute control of rapid ventricular rate
Experience and Successful Progress in PSVT Program Applied to AFib - RVR Program 6 Milestone - Atrial Fibrillation Program Overview • Track - record of etripamil NS development in PSVT • Conducted multi - national PSVT development program in at - home setting with tachycardia - symptom prompted, self - administration of etripamil NS • We demonstrated: Rapid conversion of PSVT with etripamil NS 70 mg Optimized efficacy with repeat - dose regimen Symptomatic improvement Appropriate Safety & Tolerability Profile shown for approach of symptom - prompted, at - home self - administration • Resulted in NDA submission AFib - RVR = Atrial Fibrillation with Rapid Ventricular Rate; NS = nasal spray; NDA = New Drug Application; PSVT = Paroxysmal Supraventricular Tachycardia ;
ReVeRA - Phase 2 Proof of Concept Trial of Etripamil in AFib - RVR in the Emergency Department Setting 7 Milestone - Atrial Fibrillation Program Overview Patient presents to ED with episode of AFib - RVR Dosing & Assessment Efficacy Analysis 1. Baseline ECG for ≥ 10 min 2. Administer double blind study drug 70 mg etripamil : Placebo (1:1) 3. Monitor in - patient for 1 hour 4. Six - hour remote cardiac monitor 5. Complete safety 24 hours post dose Inclusion: • Atrial Fibrillation ≥ 1 hour • Ventricular Rate (VR) ≥ 110 bpm Select Exclusions: • Treated with antiarrhythmic drugs • Hemodynamically unstable • Heart failure Primary: Maximum reduction in VR within 60 min N=50: 90% powered to detect 20 bpm difference in max reduction, α=0.05 • Time to VR reduction • Duration of VR reductions • <100 bpm, ≥ 10% reduction, ≥ 20% reduction • Patient satisfaction with treatment (TSQM - 9) 1 2 3 Assessing Etripamil Ventricular Rate Reduction – How Much; How Fast; How Long AFib - RVR = Atrial Fibrillation with Rapid Ventricular Rate; TSQM - 9, Treatment Satisfaction Questionnaire for Medication; ED = Emerge ncy Department
ReVeRA was designed to demonstrate: 8 Milestone - Atrial Fibrillation Program Overview 1 Reduction = reduction from VR baseline. 2 Treatment Satisfaction Questionnaire for Medication - 9, a validated patient reported outcome tool. AFib - RVR = atrial fibrillatio n with rapid VR, VR = ventricular rate. • Sized to detect 20 - bpm reduction 1 vs placebo (in - line with HCP expectations as clinically meaningful, and similar to IV CCBs); assumed 90% power, α=0.05. Target N= 50. Sizing of the Study • Reduction in VR; as measured by difference in maximum reduction from baseline per study - arm over 60 min window Primary Endpoint • Achievement of responses of VR <100 bpm, or ≥20% reduction, or ≥10% reduction Amount of Reduction Secondary Measures • Time course plots, Time to VR reduction or to achieve responder status • Duration of VR <100 bpm, or ≥20% reduction, or ≥10% reduction Speed of Action Duration of Action • Measurements of Satisfaction of Effectiveness and Relief of Symptoms utilizing the TSQM - 9 2 Symptomatic Relief • Adverse event collection and ECG monitoring Safety & Tolerability
ReVeRA Patient Characteristics (Safety Population) 1 9 Milestone - Atrial Fibrillation Program Overview Characteristic Placebo n=29 Etripamil n=27 Total N=56 Age, years Mean (SD) 64.59 ± 10.53 64.63 ± 10.61 64.6 (10.47) Median (range) 66.00 (35.00, 83.00) 64.00 (45.00, 88.00) 65 (35.00, 88.00) Site Location Canada 14 (48.3%) 12 (44.4%) 26 (46%) The Netherlands 15 (51.7%) 15 (55.6%) 30 (54%) Sex, female, n (%) 11 (37.9%) 11 (40.7%) 22 (39.3) Baseline Systolic Blood Pressure (mmHg) Mean ± SD (median) 125.59 ± 17.34 (124.00) 130.00 ± 19.78 (126.00) 127.71 ± 18.52 (124.50) Type of AF Paroxysmal 22 (75.9%) 20 (74.1%) 42 (75%) Persistent 5 (17.2%) 5 (18.5%) 10 (17.9%) Permanent 2 (6.9%) 2 (7.4%) 4 (7.1%) Baseline Medications, 2 n (%) Any beta - blocker (BB) 10 (34.5%) 13 (44.8%) 23 (41.1%) Any NDHP CCB 3 (10.3%) 4 (14.8%) 7 (12.5%) Any BB or NDHP CCB 13 (44.8%) 15 (55.6%) 28 (50%) Any Class IC or III antiarrhythmic drug 5 (17.2%) 8 (29.6%) 13 (23.2%) Anticoagulant, oral 16 (55.1%) 16 (59.3%) 32 (57.1%) 1 Safety Population (all randomized patients receiving study drug). 2 Baseline = medications started at least 1 day prior to study drug administration. BB = Beta blocker, NDHP = non - dihydropyridine, CCB = calcium channel blocker, Pop = population, SD = standard deviation
10 Milestone - Atrial Fibrillation Program Overview 1 Efficacy Population (all randomized patients receiving study drug remaining in atrial fibrillation with adequately diagnostic ECG recordings for at le ast 60 min post drug). Maximum VR reductions determined based on 5 - min moving average of VR. 2 By ANCOVA. bpm ± SEM. bpm = beats per minute. CI = confidence interval. SD = standard deviation. VR = ventricular rate. ReVeRA Primary Endpoint – Maximum Reduction in VR (60 min) P RIMARY E NDPOINT : Maximum Reduction in VR from Baseline Placebo NS, 1 N=25 Etripamil NS, 70 mg, 1 N=24 Baseline Ventricular Rate (SD) 135.54 (13.93) 130.33 (15.28) Mean (95% CI), bpm - 5.06 ( - 7.44, - 2.67) - 34.97 ( - 45.13, - 24.87) Difference in means (95% CI), bpm -- - 29.91 ( - 40.31, - 19.52) p - value 2 -- <0.0001 Primary Endpoint achieved with high degree of statistical significance
-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 ReVeRA – Mean VR Change from Baseline (60 min) 1 ReVeRA Data Show Substantial & Rapid Reduction in VR for the Etripamil Group Note: Data plotted on time course are not those directly used for calculation of Primary Endpoint (by pre - specified plan). X - axi s: 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. B pm = beats per minute. CI = confidence interval. SEM = standard error of the mean, VR = ventricular rate. P RIMARY E NDPOINT : Maximum Reduction in VR from Baseline Placebo NS, N=25 1 Etripamil NS, 70 mg, N=24 1 Mean (95% CI), bpm - 5.06 ( - 7.44, - 2.67) - 34.97 ( - 45.13, - 24.87) Difference in means (95% CI), bpm -- - 29.91 ( - 40.31, - 19.52) p - value 2 -- <0.0001 Milestone - Atrial Fibrillation Program Overview 11
12 Milestone - Atrial Fibrillation Program Overview 1 mITT Population (all randomized patients receiving study drug) . 2 From t - test of difference between the a reas under the curves (AUC) of plots of absolute mean heart rate . X - axis: of plot: time following drug administration; Y - axis of plot: 5 - min moving average, bpm ± SEM. B pm = beats per minute; CI = confidence interval. SEM = standard error of the mean. Separation of Curves: d ifference between areas under the curves over 180 min p < 0.00001 2 ReVeRA Data Show Lasting Duration of Etripamil Effect, up to 150 min ReVeRA – Mean VR Change from Baseline (180 min) 1 Placebo 29 28 26 25 25 25 25 Etripamil 27 27 26 26 26 26 26 No. at risk 1 -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
13 Milestone - Atrial Fibrillation Program Overview 13 13
ReVeRA : TSQM - 9 PRO 1 Assessment & Results 14 Milestone - Atrial Fibrillation Program Overview Placebo 2 N=25 Etripamil 2 N=24 p value 3 Effectiveness Domain Scores, mean (SD) 36.67 (21.64) 62.69 (21.59) p<0.0001 • TSQM - 9 PRO 1 includes an Effectiveness Domain • Domain includes three questions, each answered on 7 - point anchored scale • The domain score is calculated from its three question scores ― Domain score is on a 0 to 100 - point scale ― Domain score of 50/100 corresponds to a 4/7 = “Somewhat Satisfied” 1 2 3 4 5 6 7 Extremely Dissatisfied Very Dissatisfied Dissatisfied Somewhat Satisfied Satisfied Very Satisfied Extremely Satisfied 1 Treatment Satisfaction Questionnaire for Medication - 9, a validated Patient - Reported Outcome tool. 2 Efficacy Population (all randomized patients receiving study drug remaining in atrial fibrillation with adequately diagnostic ECG recordings for at least 60 min post drug) . 3 From t - test Delta = 1.55 units on Relief of Symptoms ReVeRA Data Show Significant Improvement in Patient Reported Relief of Symptoms
Milestone - Atrial Fibrillation Program Overview 15 Patients with ≥1 of most common adverse events (≥5%) 1 Placebo (N= 29) 2 Etripamil (N=27) 2 Nasal Discomfort 11 (37.9%) 16 (59.3%) Rhinorrhea 1 (3.4%) 9 (33.3%) Increased Lacrimation 5 (17.2%) 8 (29.6%) Throat Irritation -- 5 (18.5%) Dizziness 3 (10.3%) 3 (11.1%) Bradyarrhythmia -- 2 (7.4%) 3 Epistaxis -- 2 (7.4%) Nasal Congestion 1 (3.4%) 2 (7.4%) Nasopharyngitis -- 2 (7.4%) Nasal Congestion 1 (3.4%) 2 (7.4%) Oropharyngeal Pain -- 2 (7.4%) Paresthesia 2 (6.9%) 1 (3.7%) Intracardiac Thrombus 2 (6.9%) -- ReVeRA Study - Most Common Adverse Events (≥5% frequency) 1 Treatment - emergent adverse events, MeDRA terms. 2 Safety Population (all randomized patients receiving study drug). 3 Two patients each with 1 event of bradyarrhythmia.
ReVeRA Study - Summary of Serious Adverse Events • One etripamil patient experienced 2 SAEs classified as related to study drug • Transient severe bradycardia and syncope, assessed as due to hyper - vagotonia • O ccurred in a patient with a history of vagal events • F ully resolved with placing the patient supine and without sequelae • Two placebo patients experienced 4 SAEs • Patient - 1: Intracardiac thrombus, peripheral artery occlusion • Patient - 2: Myocardial ischemia, atrial fibrillation 16 Milestone - Atrial Fibrillation Program Overview SAE = Serious Adverse Event.
ReVeRA demonstrated: 17 Milestone - Atrial Fibrillation Program Overview 1 Reduction from baseline. 2 Treatment Satisfaction Questionnaire for Medication - 9. AFib - RVR = atrial fibrillation with rapid VR, VR = ventricular rate • Goal: 20 bpm VR reduction 1 vs placebo • ReVeRA: - 30 bpm vs placebo; - 35 bpm absolute in etripamil arm Primary Endpoint: Treatment Effect Size • Goal: p ≤ 0.05 • ReVeRA : p < 0.0001 Primary Endpoint: Statistical Significance • Goal: quick on - set • ReVeRA : quick on - set. Median time to maximum reduction: 13 min in etripamil arm. Rapid achievement of responder status ( eg , VR <100 bpm) Speed of Action • Goal: at least 30 min (for the 1 dose in this study) • ReVeRA : ~150 min Duration of Action • Goal: positive trends, show feasibility of TSQM - 9 2 in AFib - RVR patients • ReVeRA : Improvement in satisfaction of effectiveness (p<0.0001) & symptom - relief (p=0.0002), and scores apparently exceeding minimally - important - difference benchmarks. Symptomatic Relief • Goal: findings aligned with PSVT program experience • ReVeRA : goals met (with monitored drug administration) Safety & Tolerability
FDA Pre - IND Guidance for Path to Approval in AFib - RVR 1 • Single study with self - administered etripamil and in an at - home setting, to gain a labelled indication via supplemental NDA ( sNDA ) • Can utilize the safety database from PSVT • Primary analysis to be on ITT population (all patients who receive drug) • Reduction in VR may be primary endpoint • Patient benefit on symptoms, via patient reported outcome (PRO), must be Key Secondary Endpoint: • p < 0.05 to gain approval • Key recommendation: use of anchored 7 - point scale; FDA gave latitude on specific PRO • FDA expectation of 1 - unit improvement in Target population (with verified AFib - RVR) 18 Milestone - Atrial Fibrillation Program Overview 1) We expect to have additional discussion with FDA regarding the proposed design of our Phase 3 pivotal trial, including whe the r the proposed Phase 3 pivotal trial will support registration of etripamil for the treatment of AFib - RVR. AFib - RVR = atrial fibrillation with rapid VR. VR = ventricular rate.
Proposed Phase 3 Registrational Study in AFib - RVR 1 • Key Inclusion Criteria: history of symptomatic episodes of AFib - RVR • Patients self - administer drug at - home for perceived episodes of AFib - RVR • Dose: etripamil NS 70 mg, repeat - dose regimen • Target Population = patients with verified AFib - RVR • ITT Population = patients self - administering study drug for perceived AFib - RVR • Primary endpoint = change from baseline to nadir VR, same as ReVeRA ; etripamil vs placebo • Key secondary = PRO similar to TSQM Effectiveness Domain or Relief of Symptoms Question • Estimated study size: N ≈ 150 - 200 total events, based on 2 : PRO delta of 1.2 units, 90% power, p < 0.05 19 Milestone - Atrial Fibrillation Program Overview 1 We expect to have additional discussion with FDA regarding the proposed design of our Phase 3 pivotal trial, including whethe r t he proposed trial will support registration of etripamil for the treatment of AFib - RVR. 2 Sizing assumptions also include standard deviation = 1.6 & Target/ITT population ratio of 0.70. AFib - RVR = atrial fibrillation with rapid ventricular rate; ITT = intention to treat; NS = nasal spray; TSQM = Treatment Satisfaction Questionnaire for Medication pati ent reported outcome tool.
AFib - RVR Program Timeline Projections 20 • FDA Confirmation of Ph3 Protocol: 1Q 2024 • Study Start: Mid 2024 • Top - Line Data: Mid 2026 Milestone - Atrial Fibrillation Program Overview
Market Opportunity for Etripamil in AFib - RVR
KOL View on Currently Available Approaches / Unmet Need in AFib 22 • Regardless of rate - or rhythm - control strategy, break - through episodes of AFib - RVR are frequent, symptomatic, highly burdensome, and disruptive • Current treatment of acute attacks in the emergency department are burdensome and costly • Expensive and inefficient use of healthcare system resources • What would be helpful, and is currently missing, is a simple, fast - acting treatment, that could: ─ be self - administered at - home ─ reduce burden of episodes, and reduce trips to ED and calls to physicians Milestone - Atrial Fibrillation Program Overview Source: Milestone Pharmaceuticals Virtual Key Opinion Leader Event on Etripamil for the Treatment of AFib - RVR, May 22, 2023; htt ps://investors.milestonepharma.com/events - and - presentations KOL = Key Opinion Leader; AFib - RVR = Atrial Fibrillation with Rapid Ventricular Rate; ED = Emergency Department
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 El ectrophysiologists . 5. Estimate of TAM (~40% - 60% of prevalence) based 2019 market research with patients conducted by BluePrint Research Group, ( n=247) 23 Milestone - Atrial Fibrillation Program Overview PSVT Atrial Fibrillation Total Patients (2030) 2.6 Million 3 10 Million 1 Discharged ED Visits & Hospital Admissions (2016) 2 145 Thousand 785 Thousand Target Addressable Market (2030) Patient Population 1.0 - 1.6 Million 5 ~3 - 4 Million 4 Atrial Fibrillation 10 Million 1 785 Thousand AFib - RVR ~3 - 4 Million 4
Peak US Market Opportunity for Etripamil in AFib - RVR AFib - RVR = Atrial Fibrillation with Rapid Ventricular Rate 1. Colilla et al., Am. J. Cardiol . 2013, 112(8), 1142 - 1147; Miyasaka et al., Circulation, 2006, 114, 119 - 125; 10M estimate reflects the midpoint of published estimates (~8M to ~12M by 2025 or 2030 ) 2. Quantitative Survey conducted by Triangle Insights, May 2021, N=250 Clinical Cardiologists, Interventional Cardiologists, and El ectrophysiologists 24 Milestone - Atrial Fibrillation Program Overview Prevalent AFib Patients 1 (~10M) Lone Episode (1M) Permanent (3M) ~40% of 3M (1.2M) Symptomatic AFib with RVR ~3.3M ( ~33% of prevalence) Persistent (3M) ~40% of 3M (1.2M) ~40% 2 ~30% 2 ~30% 2 ~30% of 3M (0.9M) Patient Segments Share Experiencing > 1 Symptomatic AFib with RVR Episode Requiring Treatment* per Year 2 Target Addressable Market *Treatment was defined as either seeking treatment at the emergency department or outpatient clinic or via self - administration of treatments at home or other unsupervised setting Market research suggests a target addressable market of ~3 - 4 million patients for AFib - RVR by 2030 Paroxysmal (4M) ~25% 2 ~30 - 40% ~10 million patients 1 US Prevalence (2030) ~3 - 4 million patients Addressable Market Peak Share Episodes/Pt Episodes/ Yr Peak Net Sales
Peak US Market Opportunity for Etripamil in PSVT and AFib - RVR Sources: 1. Rehorn et al. Journal of Cardiovascular Electrophysiology. 2021 Aug; 32(8): 2199 - 2206. doi : 10.1111/jce.15109. ; 2. 2019 market research with patients conducted by BluePrint Research Group, ( n=247); 3. 2020 market research with healthcare providers conducted by Triangle Insights Group, (n=250) 25 Milestone - Atrial Fibrillation Program Overview ~2.6 million patients 1 US Prevalence (2030) ~40 - 60% 2 ~1.0 - 1.6 million patients ~500k - 800k patients 4 - 6/year Addressable Market Peak Share Episodes/Pt Episodes/ Yr ~50% 3 2030 Peak Net Sales ~10 million patients ~30 - 40% ~3 - 4 million patients ~2.5 - 4.0 million episodes/year PSVT AFib - RVR AF – RVR = Atrial Fibrillation with Rapid Ventricular Rate; TAM = Target Addressable Market Avg of 5 / yr 2 Market Research Suggests a TAM of 4+ Million Patients across both PSVT and AFib - RVR Indications
Finances – as of September 30, 2023 Cash and short - term investments of $75.7M Synthetic Royalty Financing of $75M available upon approval (1) Cash as of September 30, 2023 together with synthetic royalty financing expected to fund operations into mid - 2025 (1) In March 2023, Milestone announced a $125.0M strategic with RTW Investments. The financings consists of $50.0M in convertible no tes issued in March 2023, and a commitment $75.0M in non - dilutive royalty funding if etripamil is approved by the FDA. (2) Common shares as of August 10, 2023. Pre - funded warrants as of June 30, 2023. 26 Milestone - Atrial Fibrillation Program Overview Equity - 43.1M in shares and pre - funded warrants outstanding • 33.5M common shares • 9.6M pre - funded warrants (2)
Strategic Approach to Value Creation • 2024 – Financially prudent commercial build to prepare for launch • 2025 – Staged entry following market access to demonstrate PSVT market potential • 2026 – Deliver phase 3 data in AFib - RV – Fully access cardiology market for PSVT with additional reps/resources • 2027+ – Expand revenue with AFib - RVR label and additional investments/ commercial spend post break even 27 Milestone - Atrial Fibrillation Program Overview
Milestone Pharma - Targeting Significant Unmet Need for Patient Management of Common Heart Conditions PSVT = Paroxysmal Supraventricular Tachycardia; AFib - RVR = Atrial Fibrillation with Rapid Ventricular Rate; NDA = New Drug Application 28 Milestone - Atrial Fibrillation Program Overview Targeting Common Arrhythmias Empowering Patients to Treat Themselves Positioned for Success • Etripamil : novel calcium channel blocker • Fast - acting, well - tolerated, portable, on - demand • Shift from Emergency Department to patient self - management • PSVT • AFib - RVR • High burden on patients and on the healthcare system • Positive Phase 3 results in PSVT • NDA submission Oct 2023 • AFib - RVR program expands market » Phase 2 data Nov 2023 • Experienced leadership driving commercialization
Appendix
TSQM - 9: Effectiveness Domain Questions 1. How satisfied or dissatisfied are you with the ability of the medication or treat your condition? 2. How satisfied or dissatisfied are you with the way the medication relieves your symptoms? 3. How satisfied or dissatisfied are you with the amount of time it takes the medication to start working? 30 Milestone - Atrial Fibrillation Program Overview 1 2 3 4 5 6 7 Extremely Dissatisfied Very Dissatisfied Dissatisfied Somewhat Satisfied Satisfied Very Satisfied Extremely Satisfied Answer scale for each question:
Time from Drug Administration to ≥20% and ≥10% Reductions from Baseline Ventricular Rate 31 Milestone - Atrial Fibrillation Program Overview ≥ 20% reduction ≥ 10% reduction Difference in achievement of % reduction, p - value 1, 2 <0.0001 <0.0001 Median time to achieve % reduction from baseline VR Placebo: not achieved Etripamil : 14 min Placebo: not achieved Etripamil : 4 min 1 Efficacy Population is comprised of all randomized patients receiving study drug who remained in atrial fibrillation with ade qu ately diagnostic ECG recordings for at least 60 min post drug. 2 B y chi - square test.
Exhibit 99.2
Milestone Pharmaceuticals Presents Positive Results from ReVeRA Phase 2 Study of Etripamil in AFib-RVR at the American Heart Association Scientific Sessions 2023
| · | Etripamil, an investigational drug, showed statistically significant reduction in ventricular rate by 30 beats per minute for episodes of atrial fibrillation with rapid ventricular rate (p < 0.0001) compared to placebo |
| · | Results also showed statistically significant rapid and sustained reductions in ventricular rate and improvement in patient reported symptoms |
| · | Safety and tolerability data were generally consistent with data from studies evaluating etripamil in PSVT |
| · | Results support further clinical development in a Phase 3 clinical trial evaluating patient-administered etripamil for management of AFib-RVR |
MONTREAL and CHARLOTTE, N.C., November 11, 2023 /PRNewswire/ -- Milestone Pharmaceuticals Inc. (Nasdaq: MIST) today announced positive Phase 2 data that show etripamil nasal spray resulted in rapid and statistically superior ventricular rate reduction and improved symptom-relief in patients with atrial fibrillation with rapid ventricular rate (AFib-RVR) compared to placebo. Safety and tolerability reported in the 56-patient safety population is generally consistent with that observed in Milestone’s much larger Phase 3 paroxysmal supraventricular tachycardia (PSVT) program. The results were presented as a Featured Science presentation at the American Heart Association (AHA) Scientific Sessions 2023 and simultaneously published in Circulation: Arrhythmia and Electrophysiology. These data support further development of self-administered etripamil for the treatment of AFib-RVR.
Incidence of atrial fibrillation (AFib) in the United States is expected to grow to approximately 10 million by 2025 and up to about 12 million by 2030.1,2,3 Patients with AFib-RVR continue to face a significant unmet need for symptom relief. They can experience the burden of symptomatic acute attacks and our market research indicates 30-40 percent of patients with AFib experience one or more symptomatic episodes of rapid ventricular rate (RVR) per year requiring treatment.
“Breakthrough episodes of rapid ventricular rate in patients with AFib are frequent and often symptomatic and may result in increasing burdens in patients’ everyday lives and disruptions to the healthcare system. Today, there is an unmet need for a portable, fast-acting treatment solution that can be easily administered by patients when they experience a sudden episode,” said A. John Camm, M.D., lead investigator, British Heart Foundation Emeritus Professor of Clinical Cardiology, The Cardiology Clinical Academic Group, Molecular and Clinical Sciences Research Institute, St. George’s University of London, London, UK. “The results presented and published today from the ReVeRA Phase 2 study are encouraging for patients and healthcare providers who are seeking a treatment solution that delivers significant symptom relief and helps reduce potential visits to the emergency department.”
“The results from the ReVeRA study are promising and demonstrate the potential of etripamil nasal spray to rapidly reduce heart rate and provide symptomatic benefit to patients suffering from AFib-RVR,” said David Bharucha, MD, PhD, Chief Medical Officer, Milestone Pharmaceuticals. “We believe our recent NDA submission for etripamil for the potential treatment of PSVT, as well as FDA guidance received on AFib-RVR, provide a strong foundation for the continued clinical development of patient-administered etripamil with a Phase 3 study in AFib-RVR.”
Randomized, Controlled Study of the Efficacy and Safety of Etripamil Nasal Spray: Findings from Phase 2 ReVeRA-201 Study (AHA Featured Science Session)
The randomized, controlled Phase 2 ReVeRA study treated 56 patients aged 18 years and older presenting in an emergency department or hospital with AFib with a ventricular rate of 110 or more beats per minute (bpm) prior to receiving either etripamil nasal spray or placebo. The study was designed to assess the reduction in ventricular rate (primary endpoint), the time to achieve maximum reduction in ventricular rate, the duration of effect, and patient satisfaction with treatment using the Treatment Satisfaction Questionnaire 9 (TSQM-9) patient reported outcome (PRO) tool (secondary endpoints).
Data from the ReVeRA trial showed that delivery of etripamil nasal spray significantly and rapidly reduced ventricular rate, consistent with the drug’s pharmacologic profile. The study achieved its primary endpoint with high statistical significance with patients experiencing a mean ventricular rate reduction of 29.91 bpm (95% confidence interval: -40.31, -19.52; p < 0.0001) in the etripamil arm compared to placebo. The absolute maximum reduction in rate was 35 bpm in the etripamil arm, compared with 5 bpm in the placebo arm. The median time to maximum reduction in ventricular rate was 13 minutes in the etripamil arm, and time course graphs of mean ventricular rate reduction illustrate onset of etripamil within minutes after drug administration and lasting approximately 150 minutes compared to placebo.
A greater number of patients receiving etripamil achieved a ventricular rate of less than 100 bpm (58.3%) than those receiving placebo (4%). Furthermore, 67% of patients receiving etripamil achieved at least 20% reductions in ventricular rate and 96% achieved at least 10% reductions in ventricular rate in the first 60 minutes compared to 0% and 20% on placebo, respectively. Using the TSQM-9, compared to placebo, patients treated with etripamil demonstrated significant improvements in two satisfaction ratings: effectiveness (p < 0.0001) and relief of symptoms (p = 0.0002).
Serious adverse events (SAEs) occurring in the 24 hours after drug were rare, with two occurring in one patient in the etripamil arm (3.7%) and four occurring in two patients in the placebo arm (6.9%). The SAEs in the etripamil arm were transient severe bradycardia and syncope, assessed as due to hyper-vagotonia, which occurred in a patient with a history of vagal events, and fully resolved by placing the patient supine and without sequelae. The most common (≥ 5%) adverse events were mild or moderate in intensity and included nasal discomfort and congestion, rhinorrhea (“runny nose”), and dizziness.
Investor and Analyst Call and Webcast
The Company will host an investor and analyst call and webcast on Monday, November 13, 2023, at 8:00 a.m. Eastern Time. The event will feature a review of the ReVeRA data, an overview of AFib-RVR and current treatment landscape, characteristics of etripamil, and commentary on next steps for Milestone's clinical development program for etripamil. To join the live call by phone, dial (877) 870-4263 (domestic) or (412) 317-0790 (international) and ask to be connected to the Milestone Pharmaceuticals call. To access the live or recorded webcast and accompanying slides, please visit the News & Events section of Milestone's investor relations website at investors.milestonepharma.com.
About Atrial Fibrillation with Rapid Ventricular Rate
An estimated five million Americans suffer from atrial fibrillation (AFib), a common arrhythmia marked by an irregular, disruptive and often rapid heartbeat. The incidence of AFib is expected to grow to approximately 10 million by 2025 and up to about 12 million by 2030.1,2,3 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.
About Etripamil
Etripamil is Milestone's lead investigational product. It is a novel calcium channel blocker nasal spray under clinical development for elevated and often highly symptomatic heart-rate attacks associated with PSVT and AFib-RVR. It is designed to be a rapid-response therapy that is self-administered by the patient, without the need for direct medical oversight. If approved, etripamil is intended to provide health care providers with a new treatment option to enable on demand care and patient self-management. If approved, the portable treatment, studied as self-administered, may provide patients with active management and a greater sense of control over their condition. CARDAMYST™, the conditionally approved brand name for etripamil nasal spray, is well studied with a robust clinical trial program that includes a completed Phase 3 clinical-stage program for the treatment of PSVT and Phase 2 proof-of-concept trial for the treatment of patients with AFib-RVR.
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 recently submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for etripamil for treatment of an abnormal heart rhythm, paroxysmal supraventricular tachycardia or PSVT. Find out more at www.milestonepharma.com.
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" 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 the anticipated growth of incidence of AFib and AFib-RVR by 2030; the ability of etripamil to provide patients with a treatment solution that delivers significant symptom relief and helps reduce potential visits to the emergency department; the ability of etripamil nasal spray to rapidly reduce heart rate and provide symptomatic benefit to patients suffering from AFib-RVR; the continued ability of etripamil provided superior time to conversion to normal heart rhythm compared to placebo; the timing of the anticipated launch of etripamil; the success of the NDA submission for etripamil nasal spray and the timing of the FDA’s approval of the NDA; and timing of the Phase 2 proof-of-concept trial of etripamil for the treatment of patients with AFib-RVR. 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, including the lengthy and uncertain regulatory approval process; 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 and 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, including in its annual report on Form 10-K for the year ended December 31, 2022, and its Quarterly Report on Form 10-Q for the quarter ended June 30, 2023 under the caption "Risk Factors," as such discussion may be updated from time to time by subsequent filings, we may make with the U.S. Securities and Exchange Commission. 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:
Kim Fox, Vice President, Communications
kfox@milestonepharma.com
704-803-9295
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1 Colilla S, Crow A, Petkun W, Singer DE, Simon T, Liu X. Estimates of current and future incidence and prevalence of atrial fibrillation in the U.S. adult population. Am J Cardiol. 2013;112:1142–1147.
2 Miyasaka Y, Barnes ME, Gersh BJ, et al. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation. 2006;114:199–225.
3 Benjamin, E. J., Muntner, P., et al. American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee (2019). Heart Disease and Stroke Statistics-2019 Update: A Report From the American Heart Association. Circulation, 139(10), e56–e528.