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Avenue Therapeutics, Inc. Nasdaq: ATXI December 2017
Avenue Therapeutics, Inc.Nasdaq: ATXI
December 2017
Forward Looking StatementsStatements in this presentation that are not descriptions of historical facts are forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. We have attempted to identify forward-looking statements by terminology including “anticipates,” “believes,” “can,” “continue,” “could,” “estimates,”“expects,” “intends,” “may,” “plans,” “potential,” “predicts,” “should,” or “will” or the negative of these terms or other comparable terminology. Forward-looking statements are based on management’s current expectations and are subject to risks and uncertainties that could negatively affect our business, operating results, financial condition and stock price. Factors that could cause actual results to differ materially from those currently anticipated are risks relating to: our growth strategy; results of research and development activities; uncertainties relating to preclinical and clinical testing; our dependence on third party suppliers; our ability to obtain, perform under and maintain financing and strategic agreements and relationships; our ability to attract, integrate, and retain key personnel; the early stage of products under development; our need for substantial funds; government regulation; patent and intellectual property matters; competition; as well as other risks described in the “Risk Factors” section of our Registration Statement on Form S-1 initially filed with the Securities and Exchange Commission on April 28, 2017 as subsequently amended to date (our “Registration Statement”). We expressly disclaim any obligation or undertaking to update or revise any statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances after the date of this presentation. You should read carefully our “Special Cautionary Notice Regarding Forward-looking Statements” and the factors described in the “Risk Factors” sections of our Registration Statement to better understand the risks and uncertainties inherent in our business. 2
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Developing IV Tramadol to Address Significant Unmet Need in Postoperative Pain
New Formulation of Established Analgesic to Reduce Use of Conventional Opioids• Double MOA delivers opioid efficacy with less abuse potential and risk of dependence• Oral formulation has established efficacy and safety profile and is frequently prescribed• If approved, IV Tramadol will be the only intravenous Schedule IV opioid available in the U.S.
Significant Unmet Need in Moderate-to-Moderately Severe Post-Operative Pain • Gap in acute care space between IV acetaminophen/NSAIDS and conventioal narcotics• IV Tramadol could spare use of conventional opioids and step down to oral Tramadol
Multiple Near-Term Milestones• Topline data for pivotal Phase 3 trial in patients undergoing bunionectomy expected 2Q18• Initiation of pivotal Phase 3 trial in patients following abdominoplasty expected 3Q18;
topline data expected 2Q19
Strong Corporate Position • Robust patent portfolio on methods of administration covers IV Tramadol into 2036• Efficient approach executed by experienced management
What is Tramadol?
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Not a Typical OpioidDual Mechanisms of Action
5
Inhibitor of
Re-uptake of
Norepinephrine
and
Serotonin
Opioid
Agonist
Opioid Efficacy with Less Abuse Potential
Oral Tramadol in the U.S.Schedule IV and widely prescribed
• Approved in 1995 and labeled for “moderate to moderately severe” pain
• Prescriptions increased from 24.5 million in 2007 to over 40.0 million in 2012
• Accounts for ~20% of all opioid prescriptions
6
0
10
20
30
40
50
20
07
20
08
20
09
20
10
20
11
20
12
20
13
20
14
20
15
20
16
Mill
ion
s
Tramadol TRxTRx…
Source: Symphony Health
Stable Prescription Volume
Widely Used Outside the U.S.
Accounts for ~10% of IV analgesic use in the post-op setting in E.U.
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IV Tramadol UsePost-op
All otherAnalgesics
Source: IMS Health
IV Tramadol – Addressing Unmet Needs in Acute Post-operative Pain
Management
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“Opioid Crisis”
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• Release of the CDC guidelines:
“When opioids are used for acute pain,
clinicians should prescribe the lowest effective dose of immediate-release opioids and should prescribe no greater quantity than needed for the expected duration of pain severe enough to require opioids. Three days or less will often
be sufficient; more than seven days will rarely be needed. ”
• DEA has proposed a 20% reduction in the manufacture of opioids for 2018
• CVS/other pharmacies limiting opioid (new) prescriptions to 7 days and the daily dosage (mg)
Increasing efforts to reduce “strong” opioid utilization due to overdose deaths
Mild to Moderate
Hepatic Impairment
Mild to Moderately Severe
Bleeding Risk
Slowed Healing Process
GI Side Effects
Renal Impairment
Moderate to Severe
Strong Sedation
Respiratory Depression
Constipation
Risk of Dependence
Current Post-Op Pain Management Paradigm
IV Acetaminophen IV NSAIDS IV Opioids
Common Limitations & Contraindications
Pain Levels
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What is an Unmet Need in Acute Pain Today?
Mild to Moderate
Hepatic Impairment
Mild to Moderately
Severe
Bleeding Risk
Slowed Healing
Process
GI Side Effects
Renal Impairment
Moderate to Severe
Strong Sedation
Respiratory
Depression
Constipation
Risk of Dependence
Future Post-Op Pain Management Paradigm
IV Acetaminophen IV NSAIDS IV Opioids
Pain Levels
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Moderate to
Moderately Severe
Nausea/Dizziness
History of Seizure
Concomitant use of
Serotonergic Drugs
Common Limitations & Contraindications
IV Tramadol
IV Tramadol is Ideally Suited for a Wide Range of Patients
IV Tramadol to Displace Strong Opioids
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Degree of Unmet Need
Positioned to Help Reduce Conventional Opioid Usage
Commercial Opportunity
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Advantages of IV Tramadol
• Oral tramadol has established efficacy and safety and physicians are familiar with it
• Less addiction potential than widely prescribed narcotics in the hospital
• Easily fitted into multi-modal pain management to avoid conventional opioids
• Available “step-down” therapy
• Patients can transition from IV to oral tramadol and avoid conventional opioids
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Key Analogue for IV Tramadol
• Revenues for Ofirmev® (IV acetaminophen) are ~$300 MM per year
• Ofirmev accounts for ~30% of the total dollar market on approximately 3 to 4% of the unit volume
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Share (2015)
Source: IMS Health and Mallinckrodt Pharmaceuticals
0%
20%
40%
60%
80%
100%
Units Sales
IV acetaminophen All others
Targeted Patient Groups
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IV Tramadol
Elderly at risk for
respiratory depression
Obese patients
with sleep apnea
Contra-indicated
for NSAIDS
Cannot tolerate strong
narcotics
Results from a Survey of 30 U.S. Anesthesiologists*
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*Survey conducted through LEERINK and available upon request
Patients taking Switch to IV tramadol Add IV tramadol
IV morphine 40% 41%
IV NSAIDS 26% 37%
IV acetaminophen 24% 35%
Overall Impression
Favorable initial impression of tramadol as a potential new IV analgesic 77%
IV Tramadol Strengths/Opportunities
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▪ Differentiated product – dual
mechanism
▪ Schedule IV DEA status
▪ Tramadol has an established
efficacy and safety profile
▪ Opioid efficacy
▪ Positive respiratory safety history
▪ Head-to-head safety/tolerability vs.
morphine
▪ Reliable PK/PD
▪ Transition/step-down to oral
tramadol
Product Profile Strengths Market Opportunities
▪ Moderate pain
▪ Ambulatory surgery (ASC) –
favorable reimbursement
▪ At-risk populations: patients at
risk for sedation/respiratory
depression, suffering from
COPD, sleep apnea, etc.
▪ Patients contraindicated to
NSAID therapy/concerns with
bleeding
▪ Patients and physicians who
desire to use drugs with less
addiction potential
Intellectual Property
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Novel Dosing Regimen
• IV tramadol 50 mg is infused intravenously over 15 minutes at Hours 0, 2, 4, and once every 4 hours thereafter
• This dosing regimen, intended to maximize the efficacy and tolerability profile of IV tramadol, provides a similar Cmax and AUC to that of 100 mg oral tramadol given every 6 hours at steady state
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Mean Tramadol Plasma Concentration vs. Time Curve for IV 50 mg, Oral 100 mg
21Source: Study AVE-901-101
Strong Patent Portfolio on Methods of Administration
•U.S. Patents No. 8,895,622, No. 9,561,195 and No. 9,566,253
• Expires in 2032
•U.S. Patent No. 9,693,949
• Expires in 2036
• Further Patent Applications are contemplated
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Regulatory Filing Strategy
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Phase 3 Program
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Orthopedic Model (Bunionectomy)
405 Patients
IV tramadol50 mg
IV tramadol25 mg Placebo
Soft Tissue Model (Abdominoplasty)
360 Patients
IV tramadol 50 mg
Placebo Morphine
Safety Study 250 Patients
Clinical Development Plan Summary
Study Design Outcomes
Orthopedic Model -Bunionectomy
• 405 patients will be randomized in this Phase 3, double-blind, three-arm (IV tramadol 50 mg, 25 mg, placebo) study in a 1:1:1 ratio.
• The primary measure of efficacy is the Sum of Pain Intensity Differences (SPID) through 48 hours post first dose.
Soft Tissue Model - Abdominoplasty
• 360 patients will be randomized in this Phase 3, double-blind, three-arm (IV tramadol 50 mg, placebo, IV morphine) study in a 3:3:2 ratio.
• The primary measure of efficacy is the Sum of Pain Intensity Differences (SPID) through 24 hours post first dose.
• The purpose of the morphine arm is to compare tolerability of IV tramadol to standard-of-care.
Safety Study • 250 patients will be enrolled into this open-label, single-arm, all-comer study to assess safety of IV tramadol in the post-operative setting.
• The study will ensure that we have a total exposure of 500 patients to IV tramadol 50 mg for the NDA submission.
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Detailed Calendar of Events
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Initiated Phase III bunionectomy study 3Q 2017 ✓
Initiate Safety study 4Q 2017
Topline data from Phase III bunionectomy study 2Q 2018
Initiate Phase III abdominoplasty study 3Q 2018
Topline data from Phase III abdominoplasty study 2Q 2019
Complete Safety study 2Q 2019
Submit NDA Year-end 2019
Corporate & Financial Overview
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Corporate Overview
• Fortress Biotech, Inc. (“Fortress”) provides an efficient way for its subsidiary companies to develop/commercialize products.
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Avenue Therapeutics, Inc. (NASDAQ: ATXI), a Fortress Biotech Company, is a specialty pharmaceutical company that acquires/in-licenses, develops and commercializes products principally for use in the acute/hospital setting.
Financial Information
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Market capitalization (As of 11/1/17) $50 million
Outstanding shares ~10 million
Cash position (As of 9/30/17) $26 million
Investment Highlights
• Offers a novel MOA for IV pain meds • Fills gap between IV acetaminophen/NSAIDS and IV conventional narcotics
• De-risked asset • Tramadol is a known analgesic
• The only IV Schedule IV opioid in the U.S. if approved • Low potential for abuse and low risk of dependence
• Long patent life • Dosing regimen patent does not expire until 2036
• Major inflection point in 2Q2018 • Phase III bunionectomy topline results
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Lucy Lu, M.D.
President and Chief Executive Officer
Avenue Therapeutics, Inc.
2 Gansevoort St., 9th Floor
New York, NY 10014
Tel: 781-652-4500/Email: [email protected]
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Avenue Therapeutics, Inc.
Appendix
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Why Hasn’t it Been Developed in the U.S.?
• The opioid crisis reached “boiling point” in 2010s and created a real need for a lesser-scheduled opioid
• Difficult to obtain patents once tramadol became generic in the U.S.
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