Milestone Pharmaceuticals Announces Regulatory Guidance and Updated Clinical Development Plan for Etripamil in PSVT - Recently completed NODE-301 and ongoing NODE-301B studies can be used as two efficacy studies supporti

Milestone Pharmaceuticals

Announces Regulatory Guidance and

Updated Clinical Development

Plan for Etripamil in PSVT

- Recently completed NODE-301 and

ongoing NODE-301B studies can be used as two efficacy

studies supporting a future NDA submission (target p-values of <0.05)

NODE-301B, renamed the RAPID study, will reopen to enrollment and incorporate a repeat dosing

regimen; results anticipated in

late 2021/early 2022 -

million private placement expected to fund

planned operations into the second quarter of 2022 -

- Company to host conference

call today, July 23, 2020, at 8:30 a.m. ET -

and Charlotte, NC, July 23, 2020 - Milestone Pharmaceuticals Inc. (Nasdaq: MIST), a biopharmaceutical company

focused on the development and commercialization of innovative cardiovascular medicines, today announced a clinical and regulatory

update for its pivotal program with etripamil following recent interactions with the U.S. Food and Drug Administration (FDA). Etripamil

nasal spray is the Company's investigational novel short-acting calcium channel blocker for patients with paroxysmal supraventricular

"We are pleased with

the outcome of our recent interactions with the FDA, as they outline an efficient path to registration for etripamil which eliminates

the need to start a new Phase 3 study," said Joseph Oliveto, President and Chief Executive Officer of Milestone Pharmaceuticals.

"The FDA agreed with our plan to modify the ongoing NODE-301B study, now known as the RAPID study, to highlight the unique

pharmacology of etripamil, including a primary endpoint of time to conversion within 30 minutes. This study, together with our

recently completed NODE-301 study, which will also now use a 30 minute endpoint, will serve to fulfill the efficacy requirements

for a New Drug Application (NDA) for etripamil in PSVT."

Mr. Oliveto added, "In

addition to expanding the RAPID study, the modified design will direct patients to administer an additional dose of study drug

10 minutes after the first dose if they still experience signs and symptoms of a supraventricular tachycardia (SVT) episode. We

believe this dosing regimen provides a tailored approach to increase efficacy in patients with more persistent events and improve

the overall clinical utility of etripamil. We look forward to reopening enrollment in the RAPID study later this year, with results

anticipated in late 2021/early 2022."

The Company announced separately

today that it has entered into a securities purchase agreement with existing shareholder RTW Investments, LP for a $25 million

private placement. The Company believes that net proceeds from the private placement, together with its existing cash, cash equivalents

and short-term investments, will be sufficient to fund its planned operations into the second quarter of 2022. Commenting on the

agreement, Mr. Oliveto said, "We are pleased to have the strong, continued support of our largest shareholder, RTW, and to

be in a position to fund the RAPID study through to topline data readout."

Regulatory Updates and

Clinical Development Plan in Detail

The FDA indicated that two

studies, the RAPID study and the completed NODE-301 study, could fulfill the efficacy requirement for the Company's NDA for

etripamil in patients with PSVT. The Company proposed and the FDA agreed to the following program changes:

When employing the updated

SAP, results from NODE-301 show that 54% of etripamil patients vs. 35% of placebo patients converted within 30 minutes (HR 1.87,

p=0.02), which clinicians and cardiovascular thought leaders indicate is a clinically-meaningful outcome given the symptomatic

nature of SVT episodes and the lack of approved at-home treatments. Assuming a positive outcome in the RAPID study, this data could

serve to fulfill the efficacy requirement for the NDA.

Based on discussions with

the FDA regarding maximizing the treatment effect of etripamil, the RAPID study will allow for an optional repeat administration

of study drug (either 70 mg of etripamil or placebo) for patients who have not experienced symptom relief within 10 minutes of

the first study drug administration. This tailored regimen, which is similar to current PSVT treatment practices in the emergency

department setting, is enabled by the favorable safety data from the NODE-301 study. The Company expects that the repeat administration

could benefit a broader group of patients, including those with more persistent episodes. In the NODE-301 study, 32% of etripamil

patients and 14% of placebo patients converted to sinus rhythm within 10 minutes. The FDA agreed that the single and repeat administrations

of etripamil will be pooled and compared to placebo for the primary analysis, resulting in no increase in the sample size.

The Company expects to reopen

enrollment in the RAPID study later this year, with data anticipated in late 2021/early 2022.

Milestone will host a conference

call and webcast to discuss the regulatory guidance and updated clinical development plan today, July 23, 2020 at 8:30 a.m. ET.

To access the live call by phone, dial (800) 529-3311 (domestic) or (470) 495-9164 (international); the conference ID is 4085796.

A live audio webcast of the event may also be accessed through the "Investors" section of Milestone's website at www.milestonepharma.com.

A replay of the webcast will be available for 30 days following the event.

About Paroxysmal Supraventricular

Paroxysmal supraventricular tachycardia

(PSVT) is a rapid heart rate condition characterized by intermittent episodes of supraventricular tachycardia (SVT) that start

and stop suddenly and without warning. Episodes of SVT are often associated with symptoms including palpitations, sweating, chest

pressure or pain, shortness of breath, sudden onset of fatigue, lightheadedness or dizziness, fainting, and anxiety. Certain calcium

channel blockers have long been approved for the treatment of PSVT as well as other cardiac conditions; however, when approved

calcium channel blockers are used for the termination of SVT episodes, they must be administered intravenously under medical supervision,

usually in an emergency department or other acute care setting.

Etripamil, the Company's

lead investigational product, is designed to be a rapid response therapy for episodic cardiovascular conditions. The novel calcium

channel blocker is self-administered via a nasal spray which may shift the current treatment paradigm for many patients with PSVT

from the emergency department to the at-home setting. Milestone is conducting a comprehensive development program for etripamil,

with Phase 3 studies underway in PSVT, and plans to commence a Phase 2 proof-of-concept trial in atrial fibrillation patients with

rapid ventricular rate, with subsequent trials expected in other conditions where calcium channel blockers are used.

NODE-301 is a Phase 3, multicenter,

randomized (2:1), double-blind, placebo-controlled single administration study of etripamil nasal spray in patients with PSVT.

The study targeted a total of 150 adjudicated SVT events. Top line results were reported in March 2020. Despite early activity

at 30 minutes, a time period consistent with the relevant pharmacodynamic effect of etripamil, the study did not achieve its primary

endpoint of time to conversion of SVT to sinus rhythm (SR) compared to placebo over the pre-specified five hour period following

study drug administration (p=0.12). The small number of placebo patients and prolonged efficacy measurement period was found to

have confounded the statistical analysis of the results. The study did demonstrate statistically significant improvements in favor

of etripamil over placebo in the important secondary endpoint of patient reported treatment satisfaction, as well as a trend toward

a reduction in emergency department visits. The Company believes the safety and tolerability data from the NODE-301 study is supportive

of at- home use of etripamil, with adverse events consistent with those observed in prior trials.

About Milestone Pharmaceuticals

Milestone Pharmaceuticals

is a biopharmaceutical company focused on the development and commercialization of innovative cardiovascular medicines. Milestone

Pharmaceuticals operates in Canada and the United States. For more information, visit www.milestonepharma.com and follow the Company

on Twitter at @MilestonePharma.

Forward-Looking Statements

contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as

"may," "will," "expect," "plan," "anticipate," "estimate,"

"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 (i) the design, progress, timing, scope and results

of the RAPID study, (ii) potential clinical trials in other cardiac conditions and (iii) the possibility that data will