The global Phase 3 RAPID clinical trial of Etripamil nasal spray in patients with paroxysmal supraventricular tachycardia (PSVT) has achieved positive results

● The RAPID trial met the protocol endpoint, with a conversion rate of 64.
3% within 30 minutes of self-administered etripamil in PSVT patients and 31.
2% in the placebo group (HR=2.
62, p<0.
001)

● Safety and tolerability data are consistent with previous studies to support out-of-hospital self-administration of Etripamil in patients with PSVT

● Pooled analysis showed that self-administration of etripamil in patients with PSVT significantly reduced the number of additional medical interventions and emergency department visits

● Milestone plans to submit a new drug application to the U.
S.
FDA by mid-2023

On October 17, 2022, Milestone Pharmaceuticals (NASDAQ: MIST), a biopharmaceutical company focused on the development and commercialization of innovative cardiovascular drugs, announced positive efficacy and safety data
from its global Phase 3 RAPID clinical trial of etripamil.
Etripamil is an investigational calcium channel blocker for the treatment of patients with
paroxysmal supraventricular tachycardia (PSVT).

Bruce Stambler, MD, director of the Arrhythmia Research and Education Center at the Piedmont Heart Institute in Atlanta, Georgia, said: "PSVT has an unpredictable and devastating disease burden for patients, and current interventions are limited to expensive and complex emergency care modalities
.

I am very encouraged by the results of the RAPID trial, which shows that patients using etripamil significantly more converted to normal sinus rhythm and did not experience serious adverse events
without the need for medical supervision, compared with placebo patients.
These trial data further confirm the potential of etripamil to bring clinical benefits to patients and provide important and valuable treatments for treating physicians
.
”

Mr.
Joseph Oliveto, President and Chief Executive Officer of Milestone, said, "Today is an important milestone for Milestone and PSVT patients, and if etripamil is approved, we believe etripamil will empower patients to self-control their condition and provide value
to the healthcare system by reducing emergency room visits, among other reasons.

We look forward to working with the U.
S.
Food and Drug Administration (FDA) to bring about the early development of a pioneering treatment for self-management of this disease
.
" On behalf of Milestone, I would like to thank all the patients, caregivers and physicians
who participated in the RAPID trial.
”

RAPID is a multicenter, randomized, double-blind, placebo-controlled trial enrolling 706 patients
in clinical centers in North America and Europe.
Patients were randomly assigned to etripamil or placebo nasal spray at
a ratio of 1:1 without medical supervision.
To maximize the therapeutic potential of etripamil, patients who did not have relief in symptoms within 10 minutes were instructed to repeat the study drug
on their own 。 The RAPID trial met the protocol endpoint, with a conversion rate of 64.
3% within 30 minutes of self-administered etripamil in PSVT patients and 31.
2% in the placebo group (HR=2.
62, p<0.
001); In addition, the transition time was significantly shorter in the etripamil group compared with placebo (three times faster in the Etripamil group than in the placebo group) and continued throughout the observation period
.

The safety and tolerability data are consistent with previous studies to support out-of-hospital self-administration of etripamil
in patients with PSVT.
The most common randomized treatment period adverse event (RTEAE), which occurs within 24 hours of study drug administration (AE), is associated with
the site of nasal administration.
Overall, most reported RTAE were mild (68%) to moderate (31%), no serious adverse events associated with etripamil were reported, and to date, the etripamil overall PSVT clinical program has included more than 1600 patients receiving etripamil (dose ≥ 70 mg).

A pooled analysis of NODE-301 and RAID studies showed that self-administration of etripamil in patients with PSVT significantly reduced the number of
additional medical interventions and emergency department visits.

Full results of the RAPID Global Phase 3 clinical trial are scheduled to be presented at a future medical conference and presented to a peer-reviewed medical journal
.

As previously disclosed, Milestone believes that the results of the RAPID trial and the completed NODE-301 trial data can meet the efficacy requirements
of the new drug application for the treatment of PSVT patients with etripamil.
The company will continue to recruit patients in the open-label NODE-303 safety trial and communicate with the drug regulatory agency, and expects to submit a new drug application
by mid-2023.

About paroxysmal supraventricular tachycardia (PSVT)

Paroxysmal supraventricular tachycardia (PSVT) is a condition that affects approximately 2 million Americans and is characterized by intermittent episodes
in which the heartbeat starts and stops suddenly.
Episodes of supraventricular tachycardia (SVT) are often associated
with symptoms such as palpitations, sweating, chest tightness or pain, shortness of breath, sudden fatigue, dizziness or lightheadedness, fainting, and anxiety.
Certain intravenous drugs, including adenosine, β-blockers, and calcium channel blockers, have long been used in the acute treatment
of PSVT.
But these medications must be used under medical supervision, usually in an emergency room or other acute care situation
.

About Etripamil

Etripamil is a new chemical entity that is Milestone's primary research product
.
It is a novel calcium channel blocker designed to provide a fast-acting therapy
for patients with episodic cardiovascular disease.
As a patient-administered nasal spray, Etripamil has the potential to transform the current patient experience from emergency to out-of-hospital care
.
Milestone is conducting a comprehensive development program for etripamil and is currently conducting a Phase 3 trial for the treatment of paroxysmal supraventricular tachycardia (PSVT) and a Phase 2 proof-of-concept trial
for the treatment of rapid ventricular rate atrial fibrillation (AFib-RVR).