Full Press Release Details
December 2019 Joseph Oliveto Chief Executive Officer
Presentation contains forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation
Reform Act of 1995, as amended. In some cases, you can identify forward-looking statements by terminology such as aim,''
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that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology.
These forward-looking statements include, but are not limited to, statements about the initiation, timing, progress and results
of our current and future clinical trials of etripamil, including our Phase 3 clinical trials of etripamil for the treatment of
paroxysmal supraventricular tachycardia ("PSVT"), and of our research and development programs and clinical pipeline;
our plans to develop and commercialize etripamil and any future product candidates; the expected benefits of using etripamil to
treat PSVT; our expectations regarding the potential market size and the rate and degree of market acceptance of etripamil and
any future product candidates and the implementation of our business model and strategic plans for our business, etripamil and
any future product candidates. Such forward-looking statements are subject to inherent uncertainties, risks and assumptions that
are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, our dependence on
the success of our Phase 3 clinical trials of etripamil for PSVT, 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 and completion of clinical trials, and whether the clinical trials will validate the safety and efficacy of etripamil
for PSVT or other indications, among others. These and other risks and uncertainties are described more fully in our annual and
other periodic filings with the Securities and Exchange Commission (the "SEC"), including under the heading "Risk
Factors" in our Quarterly Report on Form 10-Q filed with the SEC on November 13, 2019. We may not actually achieve the plans,
intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking
statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking
statements we make. We undertake no obligation to update or revise any forward-looking statements, whether as a result of new
information, the occurrence of certain events or otherwise. This Presentation contains trademarks, trade names and service marks
of other companies, which are the property of their respective owners. Certain information contained in this Presentation and
statements made orally during this Presentation relate to or is based on studies, publications, surveys and other data obtained
from third-party sources and the Company's own internal estimates and research. While the Company 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 the Company's internal estimates
or research and no reliance should be made on any information or statements made in this Presentation relating to or based on
such internal estimates and research. Milestone Corporate Overview 2
MIST) - Corporate Highlights - - - - - - - - Phase 3 Cardiovascular Company with data
read out anticipated in middle 1H, 2020 PSVT is a robust market represented by ~2M patients in US Paradigm-changing approach enabling
patient self-management Potentially first new drug therapy in PSVT in > 25 years New Chemical Entity with proprietary IP protection
until 2036 Pipeline opportunities beyond the lead indication $95M Initial Public Offering - May 13, 2019 Cash & equivalents
of $136.5M (Sept. 30, 2019) - expected runway into Q3, 2021 PSVT = Paroxysmal Supraventricular Tachycardia Milestone Corporate
Joseph Oliveto Chief Executive Officer Amit Hasija Chief Financial Officer Francis Plat, MD Chief Medical Officer Lorenz Muller
Chief Commercial Officer Algene Biotechnologies Philippe Douville, PhD Chief Scientific Officer / Founder Milestone Corporate
Supraventricular Tachycardia (PSVT) AVNRT AVRT Short Circuit - PSVT is a rapid heart rate condition that starts and stops
without warning Heart rates >200 bpm are not uncommon Symptoms include - Retrograde impulse- Fast pathway Slow pathway
- palpitations sweating chest pressure or pain, shortness of breath sudden onset of fatigue lightheadedness
or dizziness fainting or anxiety PSVT episode 37% frequency (per yr.) 15% 11% <2 2 to 5 6 to 1112
to 24>25 episodes episodes episodes episodes episodes AVNRT = Atrioventricular Nodal Re-entrant Tachycardia AVRT = Atrioventricular
Re-entrant Tachycardia bpm = beats per minute Sources: Internal estimates based on market research Milestone Corporate Overview
Standard of Care for PSVT PSVT = Paroxysmal Supraventricular Tachycardia DC = Direct Current ED = Emergency Department Sources:
Internal estimates based on market research and longitudinal analysis of Truven/Marketscan and Medicare claims data; Page RL et
al, 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular tachycardia: executive summary: a report
of the ACC/AHA Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation. 2016;133:e471-e505
Milestone Corporate Overview 6 Chronic / preventive - Chronic oral medication with modest efficacy and unpleasant side effects
- 4-7 episodes/year despite preventive medications - Catheter ablation - ~80K ablations/year - Only ~10% of
patients opt for ablation Acute - IV adenosine or DC cardioversion in the ED - >150K ED visits/hospital admissions
per year - Many patients endure episodes when they occur Current acute treatment options are invasive, inconvenient, anxiety-provoking
A Paradigm-Changing Approach Non-invasive Convenient Empowering
- Avoidance of ED visits/ hospital admissions - Less need for chronic medications - Alternative or bridge to ablation
procedure PSVT = Paroxysmal Supraventricular Tachycardia Milestone Corporate Overview 7 Opportunity to develop the first approved
treatment to be used by patients whenever and wherever an episode of PSVT occurs
Etripamil - - Rapid onset (Tmax < 5 min) Transient
plasma levels 240 220 200 180 160 140 120 100 80 60 40 20 0 - Clinically-validated mechanism Etripamil, Calcium Channel
Blockers (CCBs), terminate PSVT through AV node modulation Rapid onset of action Convenient patient self-administered nasal spray
Short half-life - - 0 20 40 60 - Minutes after Dose Error bars indicate standard error of the mean AV = Atrio-ventricular
Milestone Corporate Overview 8 Etripamil Plasma Levels (ng/ml) 140 mg 60 mg 14 mg Etripamil ClassNovel CCB Potency (IC50) 11 nM
MetabolismRapid: Esterase-mediated A paradigm-changing approach for treating PSVT
Etripamil Clinical Pipeline Preclinical Phase 1 Phase 2 Phase
3 Rapid conversion to sinus rhythm PSVT Temporary control of rapid ventricular rate Atrial Fibrillation Acute relief of angina
symptoms Angina Milestone Corporate Overview 9 Pharmacology of L-type calcium channel blockers drives broad clinical utility
Phase 2a/b Study Design -5 min 0 min 15 min Placebo n=20 Etripamil
140mg n=21 PSVT patients with scheduled cardiac ablation (EP lab) SVT Induced Etripamil 105mg n=20 Etripamil 70mg n=23 Etripamil
35mg n=20 EP = electrophysiology, SVT = supraventricular tachycardia, PSVT = Paroxysmal Supraventricular Tachycardia Milestone
Corporate Overview 10 Endpoint: conversion to sinus rhythm within 15 minutes >80% power to show a 50% absolute difference vs.
placebo Objectives: Demonstrate superiority of etripamil over placebo in terminating SVT and dose ranging trend analysis
Phase 2 Primary Endpoint 87% 95% 100% 80% 60% 40% 20% 0% 75%
Placebo35mg 70mg 105mg140mg Source: Stambler, B.S. et al.; Etripamil Nasal Spray for Rapid Conversion of Supraventricular Tachycardia
to Sinus Rhythm; J Am Coll Cardiol. 2018;72(5):489-97 Milestone Corporate Overview 11 % patients successfully converted at
T=15min # patients converted at 15 min 7/20 13/20 20/23 15/20 20/21 p-value 0.1128 0.0006 0.0248 <.0001 65% 35% Etripamil three
highest doses demonstrated 75-95% conversion rates which are statistically significant compared to placebo
Phase 2 Mean Systolic Blood Pressure Effects 1 2 1 Baseline
is defined as the average of the 20-min and 10-min pre-dose measurements. 2 Time 0 is defined as the average of the measurements
during supraventricular tachycardia between 5 and 0 min before study drug administration. *p < 0.05 versus baseline. Source:
Stambler, B.S. et al.; Etripamil Nasal Spray for Rapid Conversion of Supraventricular Tachycardia to Sinus Rhythm; J Am Coll Cardiol.
2018;72(5):489-97 Milestone Corporate Overview 12 Etripamil 70 mg showed no drop in blood pressure
Phase 2a/b Clinical Conclusions - Etripamil at 70, 105
and 140 mg is significantly better than terminating PSVT placebo in - Median time to conversion <3 min with etripamil 70
mg - 70 mg dose showed no mean blood pressure (BP) drop - Most frequent side effect was nasal irritation or nasal congestion;
however these were transient - Etripamil 70 mg demonstrated the best efficacy/safety profile to take into Phase 3 Source:
Adapted from Stambler, B.S. et al.; Etripamil Nasal Spray for Rapid Conversion of Supraventricular Tachycardia to Sinus Rhythm;
J Am Coll Cardiol. 2018;72(5):489-97 Milestone Corporate Overview 13
Pivotal Phase 3 Study Design Randomization; up to 500 patients
Placebo ~33% of events Test Dose Active drug while not in PSVT Etripamil 70mg ~67% of events Documented diagnosis of PSVT History
of longer episodes SR = Sinus Rhythm; PSVT = Paroxysmal Supraventricular Tachycardia; Study randomization scheme 2:1 etripamil
: placebo Milestone Corporate Overview 14 Follow up visit Primary endpoint PSVT conversion to SR (adjudicated) N = 150 events;
>90% power, =0.01 PSVT Episode Event Driven Trial: only PSVT adjudicated events count for efficacy Objective: Superiority
of etripamil over placebo in terminating PSVT events in the outpatient setting
FDA Provided a Clear
Regulatory Path for Etripamil in PSVT Milestone Corporate Overview 15 -Program enrolling broad patient population including
elderly and those on concomitant medications (e.g. calcium channel blockers and beta blockers) -Total NDA safety data set