Slide 1: Kempharm Management Presentation
Kempharm Management Presentation June 16, 2015
Slide 2: Cautionary Note Regarding Presentation Information
Cautionary Note Regarding Presentation Information This presentation contains forward-looking statements, including statements about our plans to develop and commercialize our product candidates, our planned clinical trials for KP201/APAP and our other prodrug product candidates, the timing of and o
Slide 3: KemPharm Overview
KemPharm Overview • Specialty pharmaceutical company discovering and developing novel prodrugs • Leverage LAT Platform Technology to improve the attributes of approved drugs in large markets o 505(b)(2) pathway reduces risk and expense o Composition-of-matter patent protection • KP201/APAP has the p
Slide 4: Management Team
Management Team Travis C. Mickle, PhD President and CEO Gordon K. Johnson COO and CFO Tracy M. Woody CCO Sven Guenther, PhD EVP of R&D Christopher M. Lauderback, PhD VP of Commercial Operations Christal M.M. Mickle, MA VP of Operations and Product Development New RIVER PHARMACEUTICALS WRHAMBRECT+CO
Slide 5: Ligand Activated Therapy (LAT) Platform Technology
Ligand Activated Therapy (LAT) Platform Technology LAT LAT LAT Approved Drug with Ligand Prodrug with Cleaved Drug through Sub-Optimal Improved Attributes Human Metabolic Properties Process 1) Select FDA-approved and widely prescribed drug for improvement 2) Chemically modify using a ligand to creat
Slide 6: Pipeline of Multiple Product Candidates
Pipeline of Multiple Product Candidates Selected KemPharm Prodrug Product Candidates Indication / Parent Drug Product Candidate Development Status Key Milestone Pain Hydrocodone (IR) KP201/APAP Clinical Trials NDA Filing – 2H 2015 Hydromorphone (ER) KP511/ER Preclinical Human POC Data – 2016 Oxycodo
Slide 7: Advancing Opioid Abuse-Deterrent Technology
Advancing Opioid Abuse-Deterrent Technology No Tamper Resistance Traditional Opioids Many Formulation- Crushing or Physical Based Abuse-Deterrent Extraction Manipulation Opioids KemPharm’s Molecular Neutralization Crushing or Physical Chemical Based Abuse-Deterrent Extraction and/or Manipulation Hyd
Slide 8: Opioid Abuse-Deterrent Landscape
Opioid Abuse-Deterrent Landscape KemPharm OxyContin TARGINIQ EMBEDA Hysingla Prodrugs Multiple ER ER ER ER Parent Drug IR/ER Opioids Oxycodone Oxycodone Morphine Hydrocodone Resists Physical Tampering ??? ? ? ? ? Resists Non-Oral Abuse ??? ? ? ? ? Molecular-Based Deterrence ? x x x x Prevents Common
Slide 9: KP201/APAP Overview
KP201/APAP Overview Treatment of Acute Moderate to Moderately Severe Pain 9
Slide 10: KP201/APAP Product Features
KP201/APAP Product Features Prodrug composed of hydrocodone and a generally regarded as safe (GRAS) ligand Molecular-Based Abuse-Deterrent Technology Composition-of-Matter Patent Protection Until 2031 No Generic Equivalent Product (Benzhydrocodone) Convenient Dosing Successfully completed bioequival
Slide 11: Bioequivalence Study KP201.102 (KP201/APAP vs. Norco)
Bioequivalence Study KP201.102 (KP201/APAP vs. Norco®) Hydrocodone/Hydromorphone Acetaminophen 20,000 500 4.5 1×7.5/325 mg Norco 1×7.5/325 mg Norco (HC) 450 4.0 1×6.67/325 mg 1×6.67/325 mg KP201/APAP KP201/APAP (HC) 400 [pg/mL] 3.5 15,000 1×7.5/325 mg Norco [µg/mL] [pg/mL] (HM) 350 3.0 1×6.67/325 mg
Slide 12: FDA Meeting Minutes
FDA Meeting Minutes At the End of Phase 1 Meeting on November 15, 2012, KemPharm asked: “Because KP201 lacks opioid antagonist activity, and based on the first Phase 1 trial, we believe that if the remaining pharmacokinetic studies demonstrate bioequivalence of KP201/Acetaminophen tablets to the RLD
Slide 13: Large Market Opportunity
Large Market Opportunity • Hydrocodone is associated with more drug abuse and diversion than any other licit or illicit opioid(1) • IR hydrocodone in combination with acetaminophen is the most frequently prescribed opioid in the U.S.(2) o IR hydrocodone/APAP products accounted for 127.4 million pres
Slide 14: The Epidemic of Hydrocodone Abuse in the United States
The Epidemic of Hydrocodone Abuse in the United States • IR hydrocodone causes the most emergency department visits among Rx opioids • No approved IR hydrocodone product has abuse-deterrent labeling Note: ED refers to emergency department. Rajdeep Gill, Pharm.D. Outpatient Drug Utilization Patterns
Slide 15: KP201/APAP Tamper Resistant Properties – In Vitro Studies
KP201/APAP Tamper Resistant Properties – In Vitro Studies • Extraction of API (KP201) only yields inactive prodrug • Hydrocodone not released through: o Physical manipulation (e.g., grinding) o Common solvent extraction (e.g., “alcohol dose dumping”, “cold water extraction”) • KP201 is chemically st
Slide 16: KP201 Solvent Hydrolysis Studies
KP201 Solvent Hydrolysis Studies Preliminary results suggest that KP201 remains intact and does not hydrolyze or break down into its components in commonly available solvents % Release of Hydrocodone Solvent Ambient Temperature At Boiling Point 0.5 hours 1 hour 4 hours 0.5 hours 1 hour 4 hours Water
Slide 17: KP201 Abuse-Deterrent Properties in Rat Studies
KP201 Abuse-Deterrent Properties in Rat Studies Intranasal Intravenous 500 4,000 HC·BT (2.0 mg/kg HC eq.) HC·BT (25.5 mg/kg HC eq.) KP201 (2.0 mg/kg HC eq.) KP201 (0.2 mg/kg HC eq.) 400 [ng/mL] [ng/mL] 3,000 300 2,000 Concentration 200 Concentration 1,000 Hydrocodone 100 Hydrocodone 0 0 0.0 0.2 0.4
Slide 18: Recently Completed KP201.A01 Human Abuse Liability Trial
Recently Completed KP201.A01 Human Abuse Liability Trial • Oral Human Abuse Liability Trial o Compared the drug likability, exposure levels and safety of KP201/APAP compared to Norco after oral administration o Single-center, randomized, double-blind, active- and placebo-controlled crossover trial (
Slide 19: Hydrocodone PK Curves
Hydrocodone PK Curves 250000 KP201/APAP (HC, 4 Tablets) KP201/APAP (HC, 8 Tablets) KP201/APAP (HC, 12 Tablets) 200000 Norco® (HC, 4 Tablets) [pg/mL] Norco® (HC, 8 Tablets) Norco® (HC, 12 Tablets) Concentration 150000 100000 50000 0 0 0.5 1 1.5 2 2.5 3 Time [hours] 19
Slide 20: Incidence of Hypoxia by Treatment
Incidence of Hypoxia by Treatment 4 Tablets 8 Tablets 12 Tablets 0 Tablets KP201/ ® KP201/ ® KP201/ ® Treatment Norco Norco Norco Placebo APAP APAP APAP N 64 65 65 65 65 67 Hypoxia (N) 1 1 3 9 13 21 1 (%) (1.6%) (1.5%) (4.6%) (13.8%) (20.0%) (31.3%) (1/5%) 20
Slide 21: LS Mean of Drug Liking Scores: Emax Score
LS Mean (SE) of Drug Liking Scores: Emax 100 90 80 Score 70 VAS 60 50 Placebo KP201/APAP 40 Norco® 30 20 10 0 High Dose Medium Dose Low Dose Placebo 21
Slide 22: Ongoing Human Abuse Liability and PK Trials
Ongoing Human Abuse Liability and PK Trials • Intranasal Human Abuse Liability Trial o Assesses the drug likability, exposure levels and safety of KP201/APAP compared to Norco after crushing and intranasal administration o Single-center, randomized, double-blind trial (n=40) o Data in 3Q 2015 • Intr
Slide 23: KP201/APAP Potential Abuse-Deterrent Label Claims
KP201/APAP Potential Abuse-Deterrent Label Claims FDA Guidance • The FDA outlines 3 types of studies that may translate into 4 categories of label claims • KemPharm’s abuse liability 1. Laboratory manipulation and extraction studies (Category 1) program is consistent with the FDA Guidance: 2. Pharma
Slide 24: KP201/APAP Commercial Strategy
KP201/APAP Commercial Strategy KemPharm has many potential avenues to commercialize KP201/APAP, including but not limited to, a collaboration or establishing a specialist U.S. sales force Collaboration Specialist U.S. Sales Force • Potential global / U.S.-based • Specialist sales force targeting dea
Slide 25: Federal and State Legislative Support of Abuse-Deterrence
Federal and State Legislative Support of Abuse-Deterrence • The problem of opioid abuse significantly impacts the federal and state governments o Rising crime o Healthcare costs o Increase utilization of government services • There are numerous bills introduced aimed at dealing with prescription abu
Slide 26: State Legislative Initiatives
State Legislative Initiatives WA ME MT ND OR MN NH* ID WI NY VT SD MA WY MI RI IA PA NE OH CT NV UT** NJ IL IN WV* DE CA CO** KS VA* MD MO KY NC OK TN** AZ AR SC NM* AL GA MS TX LA To be filed FL Introduced Passed by one or both Houses * Bill would require a study of AD inclusion on formularies Pass
Slide 27: KP201/APAP Milestones
KP201/APAP Milestones Human Bioequivalence Preclinical Abuse Deterrence / Tamper Resistance Oral Human Abuse Liability Trial Intranasal Human Abuse Liability Trial 3Q 2015 Intranasal PK Trial 3Q 2015 NDA Submission 2H 2015 NDA Approval (with priority review) As Early As Mid-2016 DEA Scheduling and P
Slide 28: KP511/ER Overview
KP511/ER Overview Treatment of Moderate to Severe Pain 28
Slide 29: KP511/ER Product Overview
KP511/ER Product Overview • KP511/ER is an ER formulation of KP511, a prodrug of hydromorphone • IR bioequivalent release of hydromorphone demonstrated in rats • Potential valuable properties based on preclinical data o Significantly reduced IN and IV bioavailability (abuse deterrence) o Highly tamp
Slide 30: KP511/ER Reduced Abuse Potential
KP511/ER Reduced Abuse Potential Intranasal PK Curves Intravenous PK Curves 1,200 HM (compiled) 60 HM KP511 (compiled) KP511 [ng/mL] 1,000 [ng/mL] 50 800 40 Concentration 600 Concentration 30 400 20 Hydromorphone 200 Hydromorphone 10 0 0 0 0.2 0.4 0.6 0.8 1 0 0.5 1 1.5 2 Time [h] Time [h] • 2.0 mg/k
Slide 31: KP511/ER Potential Oral Overdose Protection
KP511/ER Potential Oral Overdose Protection AUC 3,500 HM·HCl extrapolated 3,000 HM·HCl (HM) KP511 (HM) HM] 2,500 [h×ng/mL 2,000 AUC 1,500 1,000 500 0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 Dose [mg/kg HM] Note: HM refers to hydromorphone hydrochloride. Studies conducted in rats. 31
Slide 32: KP415 Overview
KP415 Overview Treatment for ADHD 32
Slide 33: KP415 Overview
KP415 Overview • Prodrug of methylphenidate • Branded formulations of methylphenidate (Concerta, Focalin and Ritalin) accounted for sales of $1.1 billion in 2014(1) • Potential features and benefits o Controlled release methylphenidate o Reduced abuse potential o Suitable for more patient compliant
Slide 34: KP415 Oral PK Profile in Rats
KP415 Oral PK Profile in Rats Oral PK Curves 140 %-t max MPH·HCl 100% 120 283% KP415 [ng/mL] 100 80 Concentration 60 Methylphenidate 40 20 0 0 1 2 3 4 Time [h] Note: MPH·HCI refers to methylphenidate hydrochloride. Studies conducted in rats. 34
Slide 35: KP415 Reduced Abuse Potential
KP415 Reduced Abuse Potential Intranasal PK Curves Intravenous PK Curves 2,500 350 MPH·HCl KP415 MPH·HCl KP415 300 2,000 [ng/mL] [ng/mL] 250 1,500 Concentration 200 Concentration 150 1,000 100 500 Methylphenidate Methylphenidate 50 0 0 0 0.2 0.4 0.6 0.8 1 0 0.5 1 1.5 2 Time [h] Time [h] %-AUC %-Cmax
Slide 36: KemPharm Expected News Flow
KemPharm Expected News Flow Product Event Date KP201/APAP Intranasal Human Abuse Liability Trial – Clinical Results 3Q 2015 KP201 (API) Intranasal PK Trial – Clinical Results 3Q 2015 KP201/APAP NDA Submission 2H 2015 KP201/APAP NDA Approval (Priority Review) As Early As Mid-2016 KP201/APAP DEA Sched
Slide 37: 1Q 2015 Update
1Q 2015 Update • Cash of $10.3 million as of March 31, 2015 • Net proceeds from IPO in April/May 2015 of $59.9 million, net of underwriting discounts and commissions • 1Q 2015 net loss was $6.0 million vs. $1.9 million for 1Q 2014 o Increase in net loss year-over-year primarily due to IPO expenses a
Slide 38: For additional information please contact
kempharm For additional information please contact: Gordon K. “Rusty” Johnson rjohnson@kempharm.com 319-665-2575