Zevra Therapeutics, Inc. · NASDAQ:ZVRA
Zevra Therapeutics — Kempharm — Investor Presentation (January 2017)
33 slides from Zevra Therapeutics's investor presentation, Jan 9, 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 FDA
Slide 4: Ligand Activated Therapy (LAT) Platform Technology
Ligand Activated Therapy (LAT) Platform Technology ax ©” aD ax © ( ( —_ —— Approved Drug 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 liga
Slide 5: KemPharm Prodrug Product Pipeline
KemPharm Prodrug Product Pipeline category Candidate Product Parent Drug Development Status Next Milestone Potential NDA Submission ADHD KP415 aie ia Clinical Efficacy Data 2018 KP201/IR Hydrocodone Clinical IN HAL Data 2018'with Priority Review 7 POC in ER 2019 with KPS11/ER | Hydromorphone Clinica
Slide 6: Attention-Deficit/Hyperactivity Disorder: KP415
Attention-Deficit/Hyperactivity Disorder: KP415 For the Treatment of ADHD
Slide 7: KP415 Product Overview
KP415 Product Overview + Prodrug of d-methylphenidate with extended release properties + Potential KP415 features and benefits o Earlier onset of action eo Once-daily dosing o Active metabolism may offer more predictable therapeutic effect o Reduced abuse potential o Patient-friendly dosage form = S
Slide 8: ADHD and ER Methylphenidate Market
ADHD and ER Methylphenidate Market >$15 billion ADHD market with prescriptions growing at ~5% year-over-year + Methylphenidate accounted for approximately 19.7 million TRx’s and $4.2 billion in sales in 2015 *« KemPharm believes ADHD key opinion leaders have significant interest in an ER methylpheni
Slide 9: Clinical Study Results of KP415.101 — Oral PK in Humans
Clinical Study Results of KP415.101 — Oral PK in Humans 9 8 -*-KP415 (d-MPH), 32 mg G7 -+-Concerta (d-MPH), 36 mg £6 r= & <5 & 8 4 53 2 o 2 3 1 ie) ie) 4 8 12 16 20 24 Time (hours) KP415, 32 mg Concerta®, 36 mg Earner N "Mean(sp) | “ Mean (SD) Note: The 32 mg dose of KP415 was Crnex (ngimL) 24 8.20(
Slide 10: Predicted Oral Exposure for Commercial Dosage Strength
Predicted Oral Exposure for Commercial Dosage Strength 10 —e-KP415 (d-MPH), 40 mg extrap. ~«-Concerta (d-MPH), 36 mg Concentration (ng/mL) SCANWHOADTANDO ie) 4 8 12 16 20 24 Time (hours) Note: KP416 (40 mg) plasma concentrations were extrapolated by KemPharm from data for the 32 mg dose administered
Slide 11: KP415 Reduced IN and IV Pharmacokinetics in Rats
KP415 Reduced IN and IV Pharmacokinetics in Rats Intranasal PK Curves Intravenous PK Curves AUC %Cmax AUC %Cmax KP415/MPH 7% 5% KP415/MPH 27% 25% 2500 300 250 MPH-HCI 7 eMIPH-HCI z ne KP aS Bio KP AIS oo = eo 000 = i bo 8 8 a 50 oO — = 0 0 02 04 06 08 1 0 05 1 15 2 Time [h] Time fh] Dose Dose Refere
Slide 12: KP415 Clinical Update and Development Timeline
KP415 Clinical Update and Development Timeline * Completion of a Pre-Investigational New Drug (Pre-IND) review of KP415 announced on July 14, 2016 + KP415 IND acceptance announced on October 11, 2016 + Results from KP415 Phase 1 proof-of-concept trial announced on December 14, 2016 + KP415 efficacy
Slide 13: Pain: KP201/IR (APAP-free)
Pain: KP201/IR (APAP-free) For the Short-Term Treatment of Acute Pain
Slide 14: KP201/IR (APAP-free) Product Overview
KP201/IR (APAP-free) Product Overview + IR formulation of benzhydrocodone without APAP + Potentially the first IR hydrocodone-related/APAP free product in the U.S. + An abuse-deterrent opioid that offers comparable efficacy to Vicodin, Norco and Lortab, but with the potential safety advantage of hav
Slide 15: KP201/IR (KP201 API) Intranasal PK Trial
KP201/IR (KP201 API) Intranasal PK Trial + KP201/IR (KP201 API or benzhydrocodone) compared to hydrocodone bitartrate (HB) after intranasal administration for drug exposure levels, safety and drug likability in single-center, randomized, double-blind trial (n=51) + Significant differences observed i
Slide 16: Intranasal Administration of Benzhydrocodone API (KP201) and Hydrocodone Bitartrate API
Intranasal Administration of Benzhydrocodone API (KP201) and Hydrocodone Bitartrate API (Study A03) 40 ~*-Hydrocodone Bitartrate (IN) ~*-Benzhydrocodone (IN) 2 36 HC Concentration (ng/mL) N 8 10 ie) te) 1 2 3 4 Time (hours) Benzhydrocodone, Hydrocodone Bitartrate, | Benzhydrocodone vs PK Parameter N
Slide 17: Intranasal Benzhydrocodone and Hydrocodone Bitartrate — Drug Liking Scores
Intranasal Administration of Benzhydrocodone and Hydrocodone Bitartrate — Drug Liking Scores (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 BenzhydrocodonevsH
Slide 18: Differences Observed in Drug Liking and Ease of Insufflation
Differences Observed in Drug Liking and Ease of Insufflation of KP201 (API) vs. Hydrocodone (API) LS Mean Hydrocodone Parameter KP201 (API) Bitartrate Drug Liking E,,.x 67.5 73.2 0.004 Ease of Insufflation* 78.5 65.8 0.0004 4. Higher score indicates increased difficulty with insufflation Study A03:
Slide 19: KP201/IR Clinical Update and Development Timeline
KP201/IR Clinical Update and Development Timeline * Completed KP201/IR End-of-Phase 1 (EOP1) meeting with the FDA on June 23, 2016 « Licensing agreement with Acura Pharmaceuticals for Aversion® abuse- deterrent technology announced on October 18, 2016 + KP201/IR IND acceptance announced on November
Slide 20: Pain: KP511/ER and KP511/IR
Pain: KP511/ER and KP511/IR For the Treatment of Severe Pain
Slide 21: KP511/ER and IR: Product Overview
KP511/ER and IR: Product Overview + KP511 is a prodrug of hydromorphone o KP511/ER is designed as an Extended Release (ER) formulation o KP511/IR is designed as an Immediate Release (IR) formulation + Potential KP511 abuse-deterrent features based on clinical and preclinical trials o Significantly r
Slide 22: Hydromorphone Market
Hydromorphone Market + Nearly a $280 million combined ER and IR hydromorphone market in 2015 + Almost 3.2 million total prescriptions in 2015 + Hydromorphone prescribers: o ~3,500 branded prescribers eo ~140,000 generic prescribers + The top 4 specialties make up over 50% of the prescription base +
Slide 23: KP511 (API) Intranasal PK and Pilot HAL Studies
KP511 (API) Intranasal PK and Pilot HAL Studies + KP511 API compared to molar-equivalent dose of hydromorphone (HM) API after intranasal administration for drug exposure levels, safety and drug likability in single-center, randomized, double-blind trial (n=26) + Significant differences observed incl
Slide 24: Study KP511.A01 — Intranasal Pharmacokinetics
Study KP511.A01 — Intranasal Pharmacokinetics 9 a8 £ Zi 2 —»-KP511 (HM) ic 6 —*-HM (HM) B 5 54 2 93 is) §2 o 21 ie) ; ; ; 1 ie) 1 2 3 4 Time (hours) KP511, 16.1 mg HM-HCI8mg Earner N “"Mean(sp) | Mean (SD) Note: 16.1 mg of KP511 are equivalent to 8 mg of HM‘HCI with respect to Cree (ngimL) 26 -346(1
Slide 25: Differences Observed in Drug Liking, Feeling High and Take Drug Again
Differences Observed in Drug Liking, Feeling High and Take Drug Again of KP511 (API) vs. Hydromorphone (API) LS Mean Hydromorphone Parameter KP511 (API) (API) Drug Liking En, 67.2 78.7 0.0017 Feeling High E,,., 44.8 68.2 0.0002 Take Drug Again 62.7 74.1 0.0094 (12 hours)? 4. Mean Take Drug Again sco
Slide 26: KP511 Potential Oral Overdose Protection
KP511 Potential Oral Overdose Protection asses, HM-HCI extrapolated ——HM-HCI (HM) —KP511 (HM) AUC (h‘ngimL) 0 4 8 12 16 20 24 28 32 36 40 44 52 56 60 64 HM Dose (mg/kg) Note: HM-HCI refers to hydromorphone hydrochloride Studies conducted in rats me ..)—rtrti‘i‘_i™OO OU
Slide 27: KP511 Clinical Update and Development Timeline
KP511 Clinical Update and Development Timeline «+ KP511/ER IND acceptance announced on March 28, 2016 and “Fast Track” designation was announced on May 10, 2016 + Results from KP511 API Phase 1 proof-of-concept trial announced on June 28, 2016 + Results from intranasal PK and pilot HAL studies of KP
Slide 28: Central Nervous System Disorders: KP303
Central Nervous System Disorders: KP303 For the Treatment of Schizophrenia and Other CNS Disorders
Slide 29: KP303 Product Overview
KP303 Product Overview * Prodrug of quetiapine (Seroquel®) * Quetiapine is heavily metabolized by CYP450 in the liver + High interpatient variability (due to differences in hepatic enzymes) + KP303 has been observed to have significantly higher oral bioavailability in rats compared to quetiapine + P
Slide 30: KP303 Oral PK Profile in Rats
KP303 Oral PK Profile in Rats Quetiapine 200 180 160 140 120 100 —*QTP:2 HCl —*-KP303 ie) r ; ; : ; T ; 1 ie) 0.5 1 1.5 2 25 3 3.5 4 KP303 vs QTP-2HCI PK Parameter Mean Diff Cree (ng/mL) +90% AUCo.«n (h*ngimL) +68% Note: KP303 (N=22) and QTP-2 HCl (N=28) were administered at equimolar doses of 6.92
Slide 31: KemPharm Expected News Flow
KemPharm Expected News Flow Product Even Date KP511 (API) Intranasal PK and Pilot HAL Study Data 1Q 2017 KP415 Initiate Efficacy Trials 2H 2017 KP201/IR Intranasal HAL Study Data 2H 2017 KP415 Efficacy Trial Results 1H 2018 KP415 NDA Submission 2018 KP201/IR NDA Submission with Priority Review 2018
Slide 32: Q3 2016 Financial Update
Q3 2016 Financial Update Total cash, cash equivalents, restricted cash, marketable securities and long-term investments of $92.0M as of September 30, 2016 o Represents a decrease of $10.6M from June 30, 2016 Q3 2016 net loss of ($13.4M), or ($0.92) per basic and diluted share vs. Q3 2015 net loss of
Slide 33: For additional information please contact
K Pharm For additional information please contact: jdrumm@tiberend.com