AVENUE THERAPEUTICS, INC. NASDAQ: ATXI JANUARY 2018
Forward Looking Statements Statements 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. AVENUE THERAPEUTICS 2
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 widely prescribed If approved, IV Tramadol will be the only intravenous Schedule IV opioid in the U.S. Significant Need in Moderate-to-Moderately Severe Post-Operative Pain Gap in acute care space between IV acetaminophen/nsaids and conventional narcotics IV Tramadol could spare use of conventional opioids and step down to oral Tramadol In light of the current opioid epidemic, our recent market research of prescribers and payors indicate potentially very rapid uptake of our product once approved Multiple Near-Term Milestones to Drive Shareholder Value 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 and NDA filing by year-end 2019 Strong Corporate Position Robust patent portfolio on methods of administration covers IV Tramadol into 2036 Efficient approach executed by experienced management AVENUE THERAPEUTICS 3
Unique Dual Mechanism of Action Among IV Analgesics IV TRAMADOL OPIOID AGONIST Blocking pain signal transmission at both the spinal and brain levels Opioid Efficacy with Less Abuse Potential INHIBITOR OF NOREPINEPHRINE & SEROTONIN RE-UPTAKE Blocking pain signal transmission at the spinal level Schedule IV versus Conventional Narcotics (Schedule II) AVENUE THERAPEUTICS 4
MILLIONS Tramadol: Widely Prescribed Globally Oral Tramadol is Schedule IV and Widely Prescribed in the U.S. Approved in 1995 and labeled for moderate to moderately severe pain Approximately 40.0 million prescriptions annually Accounts for ~20% of all opioid prescriptions TRAMADOL TRx TRx Count 50 40 30 20 10 0 40 42 44 41 40 37 24 27 29 31 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 AVENUE THERAPEUTICS 5
Tramadol: Widely Prescribed Globally IV Formulation is Available and Widely Used Outside the U.S. Accounts for ~10% of IV analgesic use in the post-op setting in E.U. IV Tramadol Use Post-op All other Analgesics AVENUE THERAPEUTICS 6
Benefits of an Intravenous Formulation Convenience in the postsurgical/ acute care setting Suitable for patients who cannot take oral meds IV TRAMADOL Potentially faster onset of action than oral tramadol Smooth transition from IV to Oral tramadol spares use of conventional narcotics AVENUE THERAPEUTICS 7
What is the Unmet Need in Post-op Pain Care? Current Post-Op Pain Management Paradigm IV Acetaminophen IV NSAIDS IV Opioids Schedule II M I L D M O D E R AT E M O D E R AT E LY S E V E R E S E V E R E Hepatic Impairment Common Limitations & Contraindications Bleeding Risk Slowed Healing Process GI Side Effects Renal Impairment Gap in acute care space between IV acetaminophen/ NSAIDS and narcotics. Strong Sedation Respiratory Depression Constipation Risk of Dependence AVENUE THERAPEUTICS 8
IV Tramadol Ideally Suited for Wide Range of Patients Future Post-Op Pain Management Paradigm IV Acetaminophen IV NSAIDS IV Tramadol IV Opioids Schedule IV Schedule II M I L D M O D E R AT E M O D E R AT E LY S E V E R E S E V E R E Hepatic Impairment Common Limitations & Contraindications Bleeding Risk Nausea/Dizziness Strong Sedation Slowed Healing Process GI Side Effects Renal Impairment History of Seizure Concomitant use of Serotonergic Drugs Respiratory Depression Constipation Risk of Dependence IV Tramadol to avoid use of conventional opioid; Step-down therapy to oral Tramadol AVENUE THERAPEUTICS 9
Opioid Crisis Puts Pressure on the Use of Conventional Narcotics Healthcare Providers are Increasing Efforts to Reduce Strong Opioid Medicine Utilization 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) AVENUE THERAPEUTICS 10
Substantial Physician Demand for New Treatment Options IV to Oral Tramadol is Positioned to Help Reduce Conventional Opioid Usage Degree of Unmet Need AVENUE THERAPEUTICS 11
Positive Feedback from a Survey of 30 U.S. Anesthesiologists* Overall Impression Favorable initial impression of tramadol as a potential new IV analgesic 77% Patients taking Switch to IV tramadol Add IV tramadol IV morphine 40% 41% IV NSAIDS 26% 37% IV acetaminophen 24% 35% *Survey conducted through LEERINK and available upon request AVENUE THERAPEUTICS 12
Many Patients Could Benefit from IV Tramadol IV TRAMADOL is a better option when strong opioids are not desirable Contraindicated for NSAIDS Cannot Tolerate Strong Narcotics Elderly at Risk for Respiratory Depression Obese Patients with Sleep Apnea For the other patients: Why use a conventional (Schedule II) opioid when IV tramadol might be adequate for pain control? AVENUE THERAPEUTICS 13
Simplified Intravenous Analgesic Ladder Post-2020 Systemic Pharmacotherapy to Remain the Mainstay of Post-surgical Pain Management Strong conventional opioids IV morphine/ hydromorphone Non-opioid analgesics IV acetaminophen (+ IV NSAIDs) Atypical opioid IV tramadol + Non-opioid analgesics IV acetaminophen (+ IV NSAIDs) + Non-opioid analgesics IV acetaminophen (+ IV NSAIDs) STEP 1 STEP 2 STEP 3 AVENUE THERAPEUTICS 14
History of Safety and Efficacy in Europe Good head-to-head safety/tolerability vs. Standard-of-care opioids Positive respiratory safety history Opioid Efficacy Tramadol and morphine were compared in a double-blind, randomized study of 150 female patients after gynecologic surgery. Oxygen saturation, a surrogate for respiratory function, was monitored continuously by pulse oximetry for at least 30 min after each injection. In 13.3% of the morphine group (but in none of the tramadol group) transcutaneous pulse oxygen saturation decreased to less than 86%. Authors concluded that both drugs produced acceptable analgesia, and they underline tramadol s safety for postoperative pain relief. (http://www.ncbi.nlm.nih.gov/pubmed/1554117) 48 patients after total hip or knee replacement were randomly distributed into tramadol, meperidine or saline. The conclusion of the study was that meperidine and tramadol produced comparable analgesia. But meperidine induced sedation and respiratory depression while tramadol did not. (http://www.ncbi.nlm.nih.gov/pubmed/8738073) AVENUE THERAPEUTICS 15
Phase 3 Program Overview Orthopedic Model (Bunionectomy) Soft Tissue Model (Abdominoplasty) 405 Patients 360 Patients IV tramadol 50 mg IV tramadol 25 mg Placebo IV tramadol 50 mg Placebo Morphine (n=135) (n=135) (n=135) (n=135) (n=135) (n=90) P R I M ARY E N D P O I N T Sum of Pain Intensity Differences (SPID) through 48 hours post first dose P R I M ARY E N D P O I N T Sum of Pain Intensity Differences (SPID) through 24 hours post first dose Safety Study (n=250) AVENUE THERAPEUTICS 16
Novel Dosing Regimen Maximizes Efficacy and Tolerability IV tramadol 50 mg is infused intravenously over 15 minutes at Hours 0, 2, 4, and once every 4 hours thereafter Similar C max and AUC to that of 100 mg oral tramadol given every 6 hours at steady state AVENUE THERAPEUTICS 17
Mean Tramadol Plasma Concentration vs. Time Curve for IV 50 mg, Oral 100 mg Tramadol (ng/ml) 800 700 600 500 400 300 200 100 0 0 4 8 13 17 22 26 31 35 40 44 48 Time (hr) IV tramadol Oral tramadol AVENUE THERAPEUTICS 18
Strong Patent Portfolio 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 AVENUE THERAPEUTICS 19
A Prior Success Story IV acetaminophen Cadence Pharmaceuticals - OFIRMEV Licensed drug from Bristol-Myers Squibb in 2006 upfront fee of $25 million and $15 million milestone upon FDA approval FDA approval in November 2010 and launched in January 2011 List price of $14.75 per vial as of 2013 Royalties in mid-teens to mid-twenties Acquired on February 11, 2014 for $1.3 billion by Mallinckrodt Expected authorized generic launch in December 2020 Sales: 120 100 80 60 40 20 0 $111M $50M $12M 2011 2012 2013 Sales (in $ Millions) AVENUE THERAPEUTICS 20
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 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% IV acetaminophen Units All others Sales AVENUE THERAPEUTICS 21
Financial Highlights Market capitalization Outstanding shares Cash position (As of 9/30/17) ~$40 million ~10 million $26 million AVENUE THERAPEUTICS 22
Upcoming Milestones Initiated Phase III bunionectomy study 3Q 2017 Initiated 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 AVENUE THERAPEUTICS 23
AVENUE THERAPEUTICS, INC. NASDAQ: ATXI JANUARY 2018