Zevra Therapeutics, Inc. · NASDAQ:ZVRA
Zevra Therapeutics — Kempharm — Investor Presentation (September 2017)
37 slides from Zevra Therapeutics's investor presentation, Sep 26, 2017
Slide 1: Management Presentation
K Pharm Management Presentation
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 our prodrug product candidates, the timing of and our ability to obtain
Slide 3: KemPharm Overview
KemPharm Overview + Specialty pharmaceutical company discovering and developing novel prodrugs + Leveraging our LAT™ Platform Technology to improve the attributes of approved drugsin large markets + Building a pipeline of product candidates for ADHD, pain and CNS disorders + Potentially utilizing FD
Slide 4: LAT (Ligand Activated Therapy) Platform Technology
LAT™ (Ligand Activated Therapy) Platform Technology Approved ona with Ligand Prodrugwith 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 create a prodrug o
Slide 5: KemPharm Clinical Product Pipeline
KemPharm Clinical Product Pipeline Potential Product Development Next Category, Candidate Parent Drug Status Milestone etn : Submission Methylphenidate = PK + Efficacy KP415 (ER) Clinical Data 2018 ADHD - KP484 Methylphenidate Clinical PK + Efficacy 2019 (ER) Data EEE aS SSS Hydrocodone/ NDA PDUFA A
Slide 6: Attention-Deficit/Hyperactivity Disorder: KP415 and KP484
Attention-Deficit/Hyperactivity Disorder: KP415 and KP484 For the Treatment of ADHD
Slide 7: ADHD and ER Methylphenidate Market
ADHD and ER Methylphenidate Market * ~$13 billion ADHD market with prescriptions growing at >5% year-over-year * Methylphenidate accounted for approximately 19.8 million TRx’s and $3.8 billion in sales in 2016 *« KemPharm believes ADHD key opinion leaders have significant interest in an ER methylphe
Slide 8: KP415: ADHD Market Dynamics
KP415: ADHD Market Dynamics * In 2016, the branded ADHD market was ~$6.4B and more than 95% of these branded products are extended release’ *« ADHD market has become more genericized, but many generics are priced closely to their branded comparator *« Recent ADHD new product launches have been based
Slide 9: KP415 Product Overview
KP415 Product Overview + Prodrug of d-methylphenidate (MPH) with intrinsic extended release properties, co-formulated with immediate release d-methylphenidate + Potential KP415 features and benefits o Early onset of action o Potential longer total duration than current MPH therapies o Active metabol
Slide 10: KP415 Single and Multiple Oral Dose PK
KP415 Single and Multiple Oral Dose PK Anticipated KP415 Commercial Formulation Anticipated KP415 Commercial Formulation Single Dose PK Steady State PK 25 25 20 20 z z Bis —* KP415, 12/56 mg * Bis —e KP415, 12/56 mg* § § = = Zao Zao 5 5 8 8 5 5 o o 0 2 4 6 8 10 12 14 16 18 2 2 2% 0 2 4 6 8 10 12 14
Slide 11: KP415 Steady State PK at Hours vs. Focalin XR
KP415 Steady State PK at 13 Hours vs. Focalin XR Anticipated KP415 Commercial Formulation Focalin XR, 40 mg Steady State PK Steady State PK eon —e-KP415, 12/56 mg (steady state)* 25 4 Focalin XR, 40 mg (steady state) = 2 5 = 5 Qs = Fy z 2 o 2° : é 5 } 6.7 ng/ml @ 13hours gr & 5 5.6ng/mL @ 12 hours 0
Slide 12: KP415 Steady State PK vs. Vyvanse
KP415 Steady State PK vs. Vyvanse’ Anticipated KP415 Commercial Formulation Vyvanse, 70 mg Steady State PK Steady State PK 25 90 ze 2 e+ KP415, 12/56 mg* Bao —# Vyvanse, 70 mg ig z ry § rn z° gi 2 # #50 2 5 g 940 E10 2 = B20 = En 5 £ $10 ° ° 02 4 6 8 2 4 16 18 20 2 2 02 4 6 8 2 4 16 18 20 2 2 Time (
Slide 13: KP484: Adult ADHD Market Dynamics
KP484: Adult ADHD Market Dynamics ° Over 4% of U.S. adults, or approximately 10.5 million adults have ADHD12 + If approved, KP484 would launch into the high growth adultADHD market eo The adultADHD market has grown at 11% YoY vs. 4% for the pediatric ADHD market for the last several years? o Adults
Slide 14: KP484 Product Overview
KP484 Product Overview + Prodrug of d-methylphenidate with extended release properties + Potential KP484 features and benefits o True once-daily dosing o Potentially longer duration than other super-extended release ADHD products o Active metabolism may offer more predictable therapeutic effect o Lo
Slide 15: KP484 Single and Predicted Multiple Oral Dose PK
KP484 Single and Predicted Multiple Oral Dose PK KP484- Oral PK, Single Dose KP484 - Predicted Oral PK, Steady State kP484, 60 mg kP484, 60 mg © 2 KP484, 60 mg —e-KP484, 60 mg o - uo d-MPH Concentration (ng/mL) d-MPH Concentration (ng/mL) ° ° 12 16 20 24 0 4 8 12 16 20 24 Time (hours) Time (hours) °
Slide 16: KP484 Single Oral Dose PK vs. Mydayis
KP484 Single Oral Dose PK vs. Mydayis' KP484 vs. Mydayis ~ AUC. 2, Normalized KP484 vs. Mydayis - C,., Normalized 7 7 é ~oKpae4 é ~oKpae4 —eMydayis —eMydayis 55 55 & & = = Za Za 5 5 <3 <3 § § a2 =2 1 1 o o 0 2 4 6 8 10 2 4 16 18 20 2 m4 0 2 4 6 8 10 2 4 16 18 2 2 2m Time (hours) Time (hours) Disclai
Slide 17: KP484 Steady State PK vs. Mydayis
KP484 Steady State PK vs. Mydayis’ KP484 vs Mydayis - AUC. 2, Normalized KP484 vs Mydayis ~C,,., Normalized 9 9 e+ KP484 (steady state) 4 —e— KP484 (steady state) = Mydayis (steady state) = Mydayis (steady state) 7 § § & &6 = = g g° 8 Sa — — & Bs 2 2 1 1 o o 0 2 4 6 8 1012 4 16 18 20 2 0 2 4 6 8 101
Slide 18: Data Indicates KP484 May Have No Food Effect
Data Indicates KP484 May Have No Food Effect 8 —e-KP484, 60 mg, fasted 7 a KP484, 60mg, fed 6 Concentration (ng/mL} ~ 0 4 8 12 16 20 24 28 32 36 Time (hours) Note: Subjects in the fed treatment arm received a single dose of KP484, 60 mg within 20 minutes following a standardized breakfast Mme rti‘i‘
Slide 19: KP415 Clinical Update and Development Timeline
KP415 Clinical Update and Development Timeline Completed End-of-Phase 1 Meeting on June 14, 2017 « FDAraised no objections to proposed KP415 clinical program o Single efficacy study + Data from multiple PK studies support potential efficacy of the prodrug and KP415 in both single dose and multiple d
Slide 20: KP484 Clinical Update and Development Timeline
KP484 Clinical Update and Development Timeline + KP484 IND filing announced on September 20, 2017, but clinical program already initiated under KP415’s IND + KP484 and KP415 are each expected to benefit from each other’s development program, with KP484/KP415 clinical studies completed to date includ
Slide 21: Abuse-Deterrent Opioid Prodrugs
Abuse-Deterrent Opioid Prodrugs For the Treatment of Pain
Slide 22: KemPharm's Abuse-Deterrent Opioid Prodrug Technology
KemPharm’s Abuse-Deterrent Opioid Prodrug Technology No Tamper Resistance Many Formulation- Based Abuse-Deterrent Opi Crushing or Physical Manipulation KemPharm’s Molecular Based Abuse-Deterrent ff Crushing or Physical with Dual Barrier Manipulation Technology Neutralization and/or Isolation Chemica
Slide 23: U.S. Opioid Epidemic Remains Uncontrolled
U.S. Opioid Epidemic Remains Uncontrolled Marked Increases in Prescription Opioid and Heroin Overdose Deaths in the USA 2000 to 2015 Overdose Deaths Involving Opioids, United States, 2000-2015 USA 2015 Overdose Any Opioid Deaths: . °52,404 Any Drug 33,091 Any Opioid Commonly Prescribed Opioids (patu
Slide 24: FDA Expanding Access to ADFs to Discourage Abuse
FDA Expanding Access to ADFs to Discourage Abuse Development of New Pain Treatments Abuse-deterrent Opioid Non-Opioid based formulations analgesics Cannabinoids; Inflammatory mediators; tf Pro-drugs lon channel blockers be Non-pharmacological treatments es.. Crush/extraction Surgical interventions;
Slide 25: Apadaz
Apadaz For Short-Term Treatment of Acute Pain
Slide 26: Apadaz Product Overview
Apadaz Product Overview + IR opioid fixed-dose combination product comprised of 6.67 mg benzhydrocodone HCI (a prodrug of hydrocodone equivalent to 7.5 mg hydrocodone bitartrate) and 325 mg APAP + Prodrug consists of hydrocodone plus benzoic acid + Molecular-Based Abuse-Deterrent Technology + Potent
Slide 27: Apadaz vs. Norco Bioequivalence (Study 102)
Apadaz vs. Norco Bioequivalence (Study 102) 20,000 500 far + 1%7.5/325 mg Norco (HC) 450 F 6000 =~ 1%6.67/325 mg KP201/APAP (HC) ao = 3 1%7.5/325 mg Norco (HM) - = 14,000 350 e 5 1x6.67/325 mg KP201/APAP (HM) 3 12,000 soo § 10,000 20 8 8 S 8,000 200g ry £ & 2 S 6,000 150 3 5 2 4,000 100 £ 3 2 £2,000
Slide 28: Differences Observed in Drug Liking, Feeling High and Take Drug Again
Differences Observed in Drug Liking, Feeling High and Take Drug Again of IN and Oral Apadaz vs. Norco (Study A02) LS Mean IN vs. Oral Parameter IN Norco Oral Norco P-value Drug Liking Enna 79.0 77.8 0.6881 Feeling High E,,., 59.1 60.4 0.8049 Take Drug Again (12 hrs) 72.1 74.0 0.6835 LS Mean IN vs. O
Slide 29: Oral and IN Drug Liking of Apadaz vs. Norco (Study A02)
Oral and IN Drug Liking of Apadaz vs. Norco (Study A02) Norco Drug Liking: Oral vs Intranasal Apadaz Drug Liking: Oral vs Intranasal 100 100 --8--2 Tablets - Snorted --a--2 Tablets - Snorted 90 —e— 2 Tablets - Oral 90 22 Tablets - Oral 2 e0 2 eo é é Fc) 5 10 3 3 4 4 8 60 3 60 2 2 50 50 a So 04 al °
Slide 30: IN PK of Apadaz API vs. Norco API (Study A03)
IN PK of Apadaz API’ vs. Norco API? (Study A03) 40 ~e-Hydrocodone Bitartrate (IN) a —*-Benzhydrocodone (IN) — 30 S & < 2g ge 20 2 o 2 oS 10 (s) iS) = te) ; ; ; 1 ie) 1 2 3 4 Time (hours) Benzhydrocodone, Hydrocodone Bitartrate, | Benzhydrocodone vs PK Parameter N 13.34 mg N 15mg Hydrocodone Bitartra
Slide 31: IN Drug Liking of Apadaz API vs. Norco API (Study A03)
IN Drug Liking of Apadaz API‘ vs. Norco API? (Study A03) 100 2 90 -e- Hydrocodone Bitartrate (IN) = —*Benzhydrocodone (IN) => 80 2 a mm 7) 4H § @ = z Neutral Liking o4 ; ; ; ] ie) 0.5 1 1.5 2 Time (hours) Parameter Benzhydrocodone HB — BenzhydrocodonevsHB Mean (SE) 13.34mg 15mg P value = 67.5(18) —
Slide 32: Differences Observed in IN Drug Liking and Ease of Insufflation
Differences Observed in IN Drug Liking and Ease of Insufflation of Apadaz API vs. Norco API (Study A03) LS Mean Parameter Apadaz API* Norco API? Drug Liking E,,3x 67.5 73.2 0.004 Ease of 78.5 65.8 0.0004 Insufflation? 1. Benzhydrocodone 2. Hydrocodone Bitartrate 3. Higher score indicates increased d
Slide 33: Apadaz NDA Resubmission Timeline
Apadaz NDA Resubmission Timeline + FDA acknowledged receipt of Apadaz NDA resubmission on August 23, 2017 + Items includedin NDA resubmission Revised label Updated tampering data Updated abuse liability assessment Updated CMC information to include blister packaging (18-tablet pack, comprising a 3-d
Slide 34: KemPharm Expected Milestones
KemPharm Expected Milestones Product Event Date Apadaz FDRR Resolution and NDA Resubmission 2017 v KP484 IND Filing 2017 v KP415 Initiate Pivotal Efficacy Study 2017 KP415/ KP484 IV Human Abuse Liability (HAL) Data 2018 Apadaz PDUFA Date 02/23/18 KP415 Pivotal Efficacy Study Results 2018 KP484 Initi
Slide 35: Q2 2017 Financial Update
Q2 2017 Financial Update * Total cash’ of $65.8 million as of June 30, 2017 o Used $6.6 million of cash during Q2 2017 * Q2 2017 net loss of $6.5 million, or $(0.44) per basic and diluted share vs. Q2 2016 net income of $9.8 million, or $0.59 per basic share and net loss of $(0.58) per diluted share
Slide 36: For additional information please contact
K Pharm For additional information please contact: jdrumm@tiberend.com
Slide 37: KP415 and KP484 Market Data Sources
Slides 8 and 13: KP415 and KP484 Market Data Sources 4. Symphony Heath, PHAST 2011-2016 2. Ronald C. Kessler etal. (April2006). The Prevalence and Correlates of Adult ADHD in the United States: Results From the National Comorbidty Survey Replication, American Journal of Psychiatry 163(6):71