AVENUE THERAPEUTICS, INC. ⎸ NASDAQ: ATXI
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: us obtaining regulatory approval from the U.S. Food and Drug Administration for our product candidate; 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 Quarterly Report on Form 10-Q for the three and nine months ended September 30, 2020 (“Form 10 - Q”) and other periodic reports filed from time to time with the Securities and Exchange Commission. 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 Form 10 -Q and other periodic reports to better understand the risks and uncertainties inherent in our business. AVENUE THERAPEUTICS ⎸ 2
Value Proposition 1. Contingent acquisition agreement with InvaGen would provide substantial profit to shareholders upon 2 nd stage closing* 2. Shareholders may also have upside from Contingent Value Rights (CVRs) based on IV tramadol sales under InvaGen deal 3. Strong IP position on our proprietary dosing regimen expected to protect exclusivity in the U.S. into the mid 2030’s *In October 2020, InvaGen communicated to us that it believes a Material Adverse Effect (as defined in the SPMA) has occurred due to the impact of the COVID-19 pandemic on potential commercialization and projected sales of IV Tramadol, which means it is possible InvaGen could attempt to avoid its obligation to consummate the second stage closing under the SPMA. We disagree with InvaGen’s assertion that a Material Adverse Effect has occurred and we have advised InvaGen of this position. AVENUE THERAPEUTICS ⎸ 3
IV Tramadol Update • Complete Response Letter received Oct 2020 and comments were focused on: 1. Safety for the intended population 2. Terminal sterilization validation • Avenue has scheduled a meeting with the FDA in the 4 th quarter 2020 AVENUE THERAPEUTICS ⎸ 4
Why IV Tramadol? Uniquely Positioned to Address a Clear and Significant Need for New Therapies for Post-operative Pain Amidst Opioid Crisis • Dual MOA delivers opioid efficacy with less abuse potential and risk of dependence • If approved, IV Tramadol will be the only intravenous Schedule IV opioid in the U.S. • Provides convenient bridge to widely prescribed oral tramadol, which has established efficacy and safety • Fills in the gap in acute care space between IV acetaminophen/NSAIDS and conventional narcotics Broad Applicability with Potential to Replace Conventional Narcotics in Wide Range of Patients • A new option for patients with contraindications to NSAIDS, those who can’t tolerate strong narcotics, and those unwilling to take strong narcotics, etc. AVENUE THERAPEUTICS ⎸ 5
Unique Dual Mechanism of Action Among IV Analgesics IV TRAMADOL Opioid INHIBITOR OF OPIOID AGONIST Efficacy NOREPINEPHRINE & Blocking pain signal with Less SEROTONIN RE-UPTAKE transmission at both the spinal Blocking pain signal transmission Abuse and brain levels at the spinal level Potential Schedule IV versus Conventional Narcotics (Schedule II) Note: Schedule IV means a low potential for abuse and low risk of dependence. Schedule II drugs have a high potential for abuse, with use potentially leading to severe psychological or physical dependence. Source: https://www.dea.gov/druginfo/ds.shtml AVENUE THERAPEUTICS ⎸ 6
What is the Unmet Need in Post-op Pain Care? Current Post-Op Pain Management Paradigm IV Opioids IV Acetaminophen IV NSAIDS Schedule II SEVERE M ILD M ODERATE M ODERATELY SEVERE Common Limitations & Contraindications Hepatic Impairment Bleeding Risk Strong Sedation Gap in acute care Slowed Healing Respiratory space between IV Process Depression acetaminophen/ GI Side Effects Constipation NSAIDS and narcotics. Renal Impairment Risk of Dependence ~200M ~10M ~45M doses/year doses/year doses/year AVENUE THERAPEUTICS ⎸ 7
Potential Paradigm: Simplified IV “Analgesic Ladder” Post -2020 Systemic Pharmacotherapy to Remain the Mainstay of Post-surgical Pain Management Strong conventional opioids IV morphine/ hydromorphone Atypical opioid + IV tramadol + Non-opioid Non-opioid Non-opioid analgesics analgesics analgesics IV acetaminophen IV acetaminophen IV acetaminophen (+ IV NSAIDs) (+ IV NSAIDs) (+ IV NSAIDs) STEP 1 STEP 2 STEP 3 Source: Can Fam Physician. 2010 Jun; 56(6): 514 – 517; Avenue research AVENUE THERAPEUTICS ⎸ 8
Oral Tramadol is Widely Prescribed in the U.S. Oral Tramadol Usage Has Increased During the Opioid Crisis Schedule II Usage Has Decreased Significantly, Less so in the IV Setting ~5 Year Period 1,2 +7% 1.2 41.8M 41.2M 39.2M 39.6M 39.6M 37.3M 1 (-3%) 0.8 Index Change 0.6 (-27%) 0.4 2013: FDA Announces Guidance 2016: FDA Announces Action Plan Against 0.2 Opioid Epidemic and Issues More and Labelling Changes to Abuse Deterrent Opioids Restrictive Guidance on Use of Opioids 0 2012 2013 2014 2015 2016 2017 Tramadol IV Schedule II Oral and Others Schedule II Source: Symphony Health Solutions; Note: 1. Decline shown as of 9/30/2017 2. Constraints at Pfizer’s McPherson site have affected IV product supply since November 2017 AVENUE THERAPEUTICS ⎸ 9
IV Tramadol Favorably Suited for Multi-modal Pain Management Future Post-Op Pain Management Paradigm IV Tramadol IV Opioids IV Acetaminophen IV NSAIDS Schedule IV Schedule II SEVERE M ILD M ODERATE M ODERATELY SEVERE Common Limitations & Contraindications Hepatic Impairment Bleeding Risk Strong Sedation Nausea/Dizziness Slowed Healing Process Respiratory Depression History of Seizure GI Side Effects Constipation Concomitant use of Serotonergic Drugs Renal Impairment Risk of Dependence Effective pain relief in place of Schedule II intravenous narcotics IV Tramadol to avoid use of conventional opioid; Step-down therapy to oral Tramadol AVENUE THERAPEUTICS ⎸ 10
2 Phase 3 Trials – Completed in 2Q2019 Soft Tissue Model Orthopedic Model (Bunionectomy) (Abdominoplasty) 405 Patients 360 Patients IV tramadol IV tramadol IV tramadol Placebo Placebo Morphine 25 mg 50 mg 50 mg (n=135) (n=135) (n=135) (n=135) (n=135) (n=90) PRIMARY ENDPOINT PRIMARY ENDPOINT Sum of Pain Intensity Differences (SPID) through Sum of Pain Intensity Differences (SPID) through 48 hours post first dose 24 hours post first dose Safety Study (n=250) AVENUE THERAPEUTICS ⎸ 11
Abdominoplasty Study Results IV Tramadol 50 mg Achieved Primary Endpoint and All Key Secondary Endpoints in this soft-tissue model • P<0.001 for the primary endpoint SPID24 of SPID24 (Sum of Pain Intensity 0 Difference over 24 hours) -10 • Key secondary endpoints included: -20 SPID24 LSMean (SE) Placebo IV Tramadol IV Morphine • PGA -30 50 mg 4 mg • SPID48 -40 • Total consumption of rescue -50 medicine -60 -70 • Similar efficacy benefit to IV -80 morphine 4 mg, a standard-of-care p-value < 0.001 -90 IV opioid p-value is comparing IV tramadol to placebo. AVENUE THERAPEUTICS ⎸ 12
Bunionectomy Study Results IV Tramadol 50 mg Achieved Primary Endpoint and All Key Secondary Endpoints in this orthopedic model • P=0.005 for the primary endpoint of SPID48 (Sum of Pain Intensity 0 SPID48 LSMean (SE) Difference from Placebo Difference over 48 hours) Tramadol 25 mg • Key secondary endpoints included: -10 Tramadol • SPID24 50 mg • Total consumption of rescue -20 medicine • Patient Global Assessment (PGA) -30 • Rapid onset of efficacy p-value vs Placebo • Statistically significant pain 0.005 -40 reduction seen as early as 30 minutes after dosing AVENUE THERAPEUTICS ⎸ 13
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