Harmony Biosciences Holdings, Inc. · NASDAQ:HRMY
Harmony Biosciences — Investor Day (October 2024)
94 slides from Harmony Biosciences's investor day presentation, Oct 1, 2024
Slide 1: Investor Day 2024
Copyright © 2024 Harmony Biosciences. All rights reserved. INVESTOR DAY 2024 October 1, 2024 | New York City
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation includes forward‐looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements other than statements of historical facts contained in these materials or elsewhere, including statements regarding Harmony Bios
Slide 3: Agenda: Opening Remarks, Franchises, Panel, Q&A
OPENING REMARKS SLEEP/WAKE FRANCHISE NEUROBEHAVIORAL FRANCHISE EPILEPSY FRANCHISE CLOSING REMARKS MANAGEMENT PANEL DISCUSSION Q&A JEFFREY M. DAYNO, MD President & Chief Executive Officer Harmony Biosciences
Slide 4: Innovative Patient-Focused Catalyst-Rich Profitable Biotech
INNOVATIVE PATIENT-FOCUSED CATALYST-RICH PROFITABLE BIOTECH
Slide 5: Newrology
Slide 6: Development Pipeline January 2023
Development Pipeline January 2023 6 October 1, 2024 Harmony Biosciences | Investor Day Primarily focused on sleep/wake and pitolisant PRODUCT / INDICATION PRE-IND PHASE 1 PHASE 2 PHASE 3 REGULATORY FILING MARKETED PRODUCT Sleep/Wake WAKIX® EDS in Narcolepsy (Adults) Cataplexy in Narcolepsy (Adults)
Slide 7: Transformation of Harmony's Pipeline
Transformation of Harmony’s Pipeline 7 October 1, 2024 Harmony Biosciences | Investor Day PRODUCT / INDICATION PRE-IND PHASE 1 PHASE 2 PHASE 3 REGULATORY FILING MARKETED PRODUCT Sleep/Wake WAKIX® EDS in Narcolepsy (Adults) Cataplexy in Narcolepsy (Adults) EDS in Narcolepsy (Pediatric) Pitolisant Idi
Slide 8: Innovation driving growth of the portfolio
Innovation driving growth of the portfolio • Compelling data; conviction in IH - sNDA on track for Q4 2024 • Next-generation formulations of pitolisant to extend franchise beyond 2040 • Potential best-in-class orexin-2 agonist (BP1.15205) • ZYN-002: innovative synthetic cannabidiol (CBD) • Pivotal P
Slide 9: Anticipated Delivery on Catalyst-Rich Pipeline
Anticipated Delivery on Catalyst-Rich Pipeline 9 October 1, 2024 Harmony Biosciences | Investor Day One or more new product or indication launches each year over the next 5 years KEY TAKEAWAY Idiopathic Hypersomnia Pediatric Narcolepsy Pitolisant-GR Fragile X syndrome Pitolisant-HD in 2028 Dravet sy
Slide 10: Newrology: Building a Leading CNS Company
Our CNS expertise and proven commercial model will be efficiently scaled to successfully launch multiple rare CNS indications Newrology: Building a Leading CNS Company 10 October 1, 2024 Harmony Biosciences | Investor Day OUR FOUNDATION & PATH TO SUCCESS Strong/durable revenue growth for WAKIX® in n
Slide 11: Delivering on a Promise to Patients
Delivering on a Promise to Patients 11 October 1, 2024 Harmony Biosciences | Investor Day To become the leading patient-focused CNS company delivering innovative treatments to patients living with unmet medical needs Our Vision Potential to deliver innovative treatments to hundreds of thousands of p
Slide 12: Driving Shareholder Value
Driving Shareholder Value 12 October 1, 2024 Harmony Biosciences | Investor Day 5 Anticipate 1 or more new product or indication launches each year over next 5 years $1B+ Proven commercial product and growing $3B+ Establishing leadership position in CNS 13 Development programs; 4 in Phase 3 by year
Slide 13: See taped. “Po (WA Bee
See taped. “Po (WA Bee
Slide 14: Sleep/Wake Franchise: Jeffrey Dierks
JEFFREY DIERKS, MBA Chief Commercial Officer Harmony Biosciences OPENING REMARKS SLEEP/WAKE FRANCHISE NEUROBEHAVIORAL FRANCHISE EPILEPSY FRANCHISE CLOSING REMARKS MANAGEMENT PANEL DISCUSSION Q&A
Slide 15: WAKIX One of the Most Successful Rare/Orphan Launches
WAKIX® Is One of the Most Successful Rare/Orphan Launches With Demonstrated Durable Revenue Generation DURABLE SALES GROWTH INTO YEAR FIVE ON THE MARKET WITH CAGR of ~45% REITERATES 2024 GUIDANCE: $700–$720M WAKIX Net Revenue Growth 2020–2024 $160 $305 $438 $582 $700– $720 $0 $200 $400 $600 $800 $1,
Slide 16: Strong Durable Growth in Patients on WAKIX
Average Number of Patients on WAKIX Since Launch1 Meaningfully Differentiated Product Profile Key Driver in Strong Durable Growth in Patients on WAKIX® ~700 ~2,500 ~3,800 ~4,900 ~6,150 ~7,000 0 2,000 4,000 6,000 8,000 10,000 Nov-Dec 2019 2020 2021 2022 2023 2024 Guidance ~Average # of Patients on WA
Slide 17: Unique Prescriber Dynamics Support Continued WAKIX Growth
Unique Prescriber Dynamics Support Continued WAKIX® Growth, Opportunity for Next-Gen Pitolisant Assets in Narcolepsy 17 October 1, 2024 Harmony Biosciences | Investor Day ~4,000 Enrolled in oxybate REMS ~5,000 Not enrolled in oxybate REMS Depth of prescribing Breadth of prescribing WAKIX growth ~9,0
Slide 18: Core Attributes of WAKIX Align with Unmet Needs in Narcolepsy
* Based on FDA-approved adult narcolepsy product labeling | Source: Harmony ATU, July 2018 (n=286); Versta Research, Know Narcolepsy Survey (“Know Narcolepsy”), October 2018; Unmet needs listed in descending order of importance stated by combined HCP and patient audience responses. Core Attributes o
Slide 19: Unique Commercial Model Supporting WAKIX Growth
Unique Commercial Model Supporting WAKIX® Growth; Scalable For Next-Gen Formulations and Harmony Pipeline Assets 19 October 1, 2024 Harmony Biosciences | Investor Day Scalable, data-driven unique commercial model positioned to be leveraged for future Harmony pipeline KEY TAKEAWAY Patient Engagement
Slide 20: The Pitolisant Franchise: Patient-Centric Drug Development
The Pitolisant Franchise: Patient-Centric Drug Development Building Our Leadership Position in Sleep/Wake 20 Non-scheduled Gastro-resistant coating EDS and Cataplexy No titration Fatigue indication Higher dose, enhanced efficacy Non-scheduled EDS and Cataplexy Non-scheduled EDS and Cataplexy Gastro-
Slide 21: Physician Perceptions of Pitolisant-HD Profile
Physician Perceptions of Product Profile Favorability vs. WAKIX Rationale EDS / Cataplexy Enhanced efficacy viewed as the greatest differentiator Improvement in Fatigue Unique indication seen as value driver for select HCPs Overall Pitolisant-HD: Viewed as a Superior Product Compared to WAKIX® , Ant
Slide 22: Favorable Market Access Outlook for Pitolisant-HD
Favorable Market Access Landscape Outlook for Pitolisant-HD Pre- and Post-WAKIX® LOE 22 October 1, 2024 Harmony Biosciences | Investor Day 1 ~Approximate Patient Counts • Anticipated access to pitolisant-HD without restrictions Pre-WAKIX LOE • Anticipated access to pitolisant-HD for majority of pati
Slide 23: Pitolisant Franchise Poised to Drive Growth to Mid-2040s
Pitolisant Franchise Poised to Drive Durable Patient and Revenue Growth to the Mid-2040s • Two meaningfully differentiated product profiles building off WAKIX with PDUFAs prior to LOE • Provisional patents filed out to 2044 to extend durable patient and net revenue growth • Pursuing other indication
Slide 24: Kumar Budur, Chief Medical & Scientific Officer
KUMAR BUDUR, MD, MS Chief Medical & Scientific Officer Harmony Biosciences OPENING REMARKS SLEEP/WAKE FRANCHISE NEUROBEHAVIORAL FRANCHISE EPILEPSY FRANCHISE CLOSING REMARKS MANAGEMENT PANEL DISCUSSION Q&A
Slide 25: Why Are We Developing Pitolisant-HD?
Why Are We Developing Pitolisant-HD? 25 October 1, 2024 Harmony Biosciences | Investor Day 75% 7 to 8 out of 10 patients continue to experience EDS despite being on treatment1 Better Efficacy at Higher Exposure of Pitolisant Addresses an Important Unmet Medical Need for Patients with Narcolepsy2 1.
Slide 26: Phase 1b Safety Study
Phase 1b Safety Study • Randomized, double-blind, placebo-controlled • N = 15 subjects per cohort • Assessing safety, tolerability, pharmacokinetics • Effect on QT interval Primary Objective Safety and tolerability of pitolisant after 14-day multiple oral doses ranging from 60 mg/day to 180 mg/day i
Slide 27: Pitolisant High-Dose: Differentiated Profile
Pitolisant High-Dose (HD): Differentiated Profile 27 October 1, 2024 Harmony Biosciences | Investor Day Proof Points/Development Plans Differentiated Features Higher Dose Up to 2x compared to WAKIX® • Better efficacy in EDS/cataplexy • Higher POS for fatigue Optimized PK Profile Pilot PK study • Hig
Slide 28: Pitolisant-HD: Path to PDUFA
Pitolisant-HD: Path to PDUFA 28 October 1, 2024 Harmony Biosciences | Investor Day 2024 2025 2026 2027 2028 Formulation optimization/CMC/Phase 1 Topline data/ NDA submission Regulatory review/ PDUFA Phase 3 registration study On-track for PDUFA in 2028 KEY TAKEAWAY
Slide 29: Idiopathic Hypersomnia: Building Strong Benefit/Risk Proposition
Idiopathic Hypersomnia: Building Strong Benefit/Risk Proposition 29 October 1, 2024 Harmony Biosciences | Investor Day IH: DISORDER WITH HIGH UNMET NEED ESTABLISHED SAFETY Non-scheduled and simple dosing regimen FAVORABLE BENEFIT/RISK PROFILE COMPELLING TOTALITY OF DATA FROM INTUNE STUDY a Phase 3 p
Slide 30: Pitolisant Study Design in IH: INTUNE Study
Pitolisant Study Design in IH: INTUNE Study 30 October 1, 2024 Harmony Biosciences | Investor Day Long-term Extension Study UP TO 28 DAYS -28D through -1D Titration + Dose Optimization Stable Dose 2 WEEKS Weeks 7–8 6 WEEKS Titration: Weeks 1–3 | Optimization: Weeks 4–6 Responders Randomized Pitolisa
Slide 31: Strong and Durable Improvement in EDS in IH (ESS)
Strong and Durable Improvement in EDS in Patients With IH (As Measured by ESS) 31 October 1, 2024 Harmony Biosciences | Investor Day 0 2 4 6 8 10 12 14 16 18 0 31 60 91 121 152 182 213 244 274 305 335 366 397 425 456 Mean ( ±SD) ESS Score NORMAL ESS RANGE -1 8 22 56 84 OLE 22 OLE 202 OLE 382 LONG-TE
Slide 32: Randomized Withdrawal Period Results
OPEN-LABEL PHASE DAYS 0–56 LONG-TERM EXTENSION DAYS 84–466 Durability and persistence of response 0 2 4 6 8 10 12 14 16 18 0 31 60 91 121 152 182 213 244 274 305 335 366 397 425 456 Mean ( ±SD) ESS Score Day Randomized Withdrawal Period 32 October 1, 2024 Harmony Biosciences | Investor Day -1 8 22 5
Slide 33: Improvement in EDS in IH (ESS) Long-Term Extension
OPEN-LABEL PHASE DAYS 0–56 0 2 4 6 8 10 12 14 16 18 0 31 60 91 121 152 182 213 244 274 305 335 366 397 425 456 Mean ( ±SD) ESS Score Day Strong and Durable Improvement in EDS in Patients With IH (As Measured by ESS) 33 October 1, 2024 Harmony Biosciences | Investor Day -1 8 22 56 84 OLE 22 OLE 202 O
Slide 34: Strong and Durable Improvement in Symptoms of IH (IHSS)
Strong and Durable Improvement in Symptoms of IH (As Measured by IHSS) 34 October 1, 2024 Harmony Biosciences | Investor Day 0 5 10 15 20 25 30 35 40 0 31 60 91 121 152 182 213 244 274 305 335 366 397 425 456 Mean ( ±SD) IHSS Score -1 56 84 OLE 22 Day OLE 202 OLE 382 Day DESIRABLE RANGE NE W DATA Th
Slide 35: Improvement in Sleep Inertia (SIQ)
Strong and Durable Improvement in Sleep Inertia (As Measured by SIQ) 35 October 1, 2024 Harmony Biosciences | Investor Day 0 10 20 30 40 50 60 70 80 0 31 60 91 121 152 182 213 244 274 305 335 366 397 425 456 Mean ( ±SD) SIQ Score -1 56 84 OLE 22 Day OLE 202 OLE 382 Day NE W DATA The mean SIQ Score d
Slide 36: Pitolisant Use in IH: A French Study
Pitolisant Use in Idiopathic Hypersomnia: A French Study A real-world independent database analysis (SOMNOBANK) conducted by Yves Dauvilliers 36 October 1, 2024 Harmony Biosciences | Investor Day N=64 patients with idiopathic hypersomnia treated with pitolisant between 2010–2024 314 total clinical v
Slide 37: SOMNOBANK Real World Database Results
n=9, then converted to pitolisant as mono tx n=9, then converted to pitolisant with other txs n=15, continued pitolisant as mono tx n=6, combined pitolisant with other txs n=9, discontinued pitolisant, started other n=6, lost to follow-up SOMNOBANK Real World Database Results patients in database 37
Slide 38: Bioprojet Compassionate Use Study: ESS Total Score
Bioprojet Compassionate Use (ATU) Study: ESS Total Score 38 Harmony Biosciences | Investor Day Characteristic ESS Score at Baseline n 61 Mean (SD) 16.2 (3.80) Mean of Post-Baseline ESS Scores n 27 Mean (SD) 12.3 (4.67) Change from Baseline ESS Score to Mean of Post-Baseline ESS Scores n 26 Mean (SD)
Slide 39: Voice of the Patient Report
Voice of the Patient Report: Highlights Patient Burden and the Need for Non-Stimulant Treatments • Externally Led Patient-Focused Drug Development Initiative; April 2024 • Attended by FDA, Advocacy and other stakeholders • Need for more research and awareness • Desire for non-stimulant treatments •
Slide 40: Pitolisant: Strong Case for Approval
Pitolisant: Strong Case for Approval Proposed in the sNDA submission for IH 40 October 1, 2024 Harmony Biosciences | Investor Day TOTALITY OF DATA FROM THE PHASE 3 INTUNE STUDY Open-label, randomized withdrawal and long-term extension REAL WORLD AND CLINICAL EXPERIENCE DATA BENEFIT / RISK PROFILE No
Slide 41: BP1.15205: Potential Best-in-Class Orexin Agonist
BP1.15205: Potential Best-in-Class Orexin 2 (OX2R) Agonist 41 October 1, 2024 Harmony Biosciences | Investor Day Next wave of innovation in Sleep/Wake TEIJIN Tokyo-based Pharma, innovator (TPM-1116) COLLABORATION WITH PROF. YANAGISAWA Discovered orexin receptors and implications on sleep/wake UNIQUE
Slide 42: Discovery of BP1.15205: Novel Chemical Scaffolding
BP1.15205 Discovery of BP1.15205: Novel Chemical Scaffolding • Differentiated structure compared to the usual pyrrolidine sulfonamide and bicyclic moieties • Distinct scaffolding from known ligands with drug-like properties • Confers unique properties and potential clinical benefits • Efficient and
Slide 43: In Vitro Pharmacology
In Vitro Pharmacology • Highly potent compound which has shown concentration-dependent hOX2R agonistic activity • Minimal inter-species difference in the agonistic activity between hOX2R, mOX2R and mkOX2R • Greater than 600-fold selectivity for hOX2R over hOX1R • Very high selectivity (>1,000) over
Slide 44: BP1.15205: Most Potent OX2R Agonist
Select DMPK parameters HRMY/BP1 BP1.15205 Centessa2 ORX750 Eisai3 E2086 Takeda4 TAK-861 Takeda5 TAK-925 Takeda4 TAK-994 Alkermes6 2680 Jazz JZP441 Potency (hOX2R, EC50) 0.015 nM 0.11 nM 2.3 nM 2.5 nM 5.5 nM 19 nM Not reported Not reported Selectivity for hOX2R vs hOX1R > 600x 9800x > 2000x 3000x > 5
Slide 45: BP1.15205 Clinical Potential
BP1.15205 Clinical Potential: Novel Chemical Structure, High Potency / Good Selectivity and PK Profile 45 October 1, 2024 Harmony Biosciences | Investor Day High potency with potential efficacy in various sleep disorders and other indications Potent on-target effects Potentially better AE profile Hi
Slide 46: Sleep/Wake Franchise Catalysts
Q4 2024 – sNDA submission for pitolisant in IH; anticipated PDUFA Q2/Q3 2025 Mid-2025 – IND submission for OX2R agonist (BP1.15205) 2026 – PDUFA for pitolisant-GR in narcolepsy 2028 – PDUFA for pitolisant-HD in narcolepsy Sleep/Wake Franchise Catalysts
Slide 47: Fireside Chat
KUMAR BUDUR, MD, MS Chief Medical & Scientific Officer Harmony Biosciences BRUCE CORSER, MD, FAASM President and Medical Director Intrepid Research and Sleep Management Institute F I R E S I D E C H A T
Slide 48: Neurobehavioral
N E U R O B E H A V I O R A L
Slide 49: Neurobehavioral Franchise: Addressing a High Unmet Medical Need
Neurobehavioral Franchise: Addressing a High Unmet Medical Need 49 October 1, 2024 Harmony Biosciences | Investor Day ACQUISITION OF ZYNERBA BROUGHT IN ZYN-002 Innovative product profile; purely synthetic cannabidiol (CBD) LEAD PROGRAM IN FRAGILE X SYNDROME (FXS) • Currently in Phase 3 pivotal study
Slide 50: Carrie Buchanan, MD
CARRIE BUCHANAN, MD Developmental-Behavioral Pediatrician Greenwood Genetic Center OPENING REMARKS SLEEP/WAKE FRANCHISE NEUROBEHAVIORAL FRANCHISE EPILEPSY FRANCHISE CLOSING REMARKS MANAGEMENT PANEL DISCUSSION Q&A
Slide 51: Fragile X Syndrome and the Endocannabinoid System
Carrie Buchanan, MD Fragile X Program Director Greenwood Genetic Center Oct. 1, 2024 Fragile X Syndrome The Endogenous Cannabinoid System and the Role of CBD in Fragile X Syndrome
Slide 52: Fragile X Syndrome Genetics
• X-linked, genetic condition – DNA (gene)→ mRNA → Protein – FMR1 → FMR1 mRNA → FMRP – The gene (FMR1) is shut off by methylation, so the gene product (FMRP) is not made • Caused by a CGG repeat expansion >200 repeats in the promoter region of FMR1 • Full mutation results in hypermethylation and sil
Slide 53: FMRP Function
Carries mRNA from the nucleus to areas of the cell where proteins are made (translation) Largely repressive effect on translation (meaning, an absence of FMRP causes an over-production/abundance of many proteins) Absence leads to dysregulation of several proteins involved in neuron formation and syn
Slide 54: Fragile X Syndrome Overview
• Neurodevelopmental disorder • Males are more frequently affected than females, and often with higher severity (XX in females is protective) • Most common cause of inherited intellectual disability (low IQ) • Large impact on behavior and functional abilities – Daily living skills, communication, an
Slide 55: Fragile X Syndrome Behavioral Phenotype
Phenotype = observable symptoms resulting from genotype (genetics) • poor eye contact • social avoidance • preference for solitary activities • excessive shyness • anxiety (social anxiety, generalized anxiety, specific phobias) • hand flapping/stimming • hand biting • aggression • irritability • att
Slide 56: Endocannabinoid System
• Major role in neuronal (brain) development and function: – Facilitates synaptic homeostasis (balance of excitatory and inhibitory neurotransmitters) – Neuronal plasticity (neural growth/reorganization) • Two parts (neurotransmitters and receptor): – Two endocannabinoids = neurotransmitters • 2-AG
Slide 57: Normal Endocannabinoid System
Normal Endocannabinoid System When the FMR1 gene functions normally, FMRP is produced at adequate levels ▪ 2-AG is produced normally and released and binds to the CB1 receptor ▪ This inhibits glutamate release ▪ Glutamate is excitatory so may produce symptoms like social avoidance, anxiety, and irri
Slide 58: Endocannabinoid Dysfunction in FXS
Endocannabinoid Dysfunction in FXS When the FMR1 gene function is abnormal in FXS, FMRP production is decreased or absent 2-AG production and release increases ▪ This causes the CB1 receptor to become desensitized and internalized ▪ Normal inhibition of glutamate doesn’t occur ▪ Excitatory glutamate
Slide 59: Proposed Mechanism of Cannabidiol in FXS
Proposed Mechanism of Cannabidiol in Fragile X Syndrome in the ECS CBD works to bring the endocannabinoid system closer to normal function ▪ 2-AG production is still increased ▪ FMRP production is still decreased or absent ▪ CBD can modulate the CB1 receptor ▪ Normal inhibition of glutamate is resto
Slide 60: Role of Endocannabinoid System and CBD Therapy in FXS
Role of Endocannabinoid System and Cannabidiol Therapy in FXS Published in the Journal of Neurodevelopmental Disorders • “…Multiple lines of evidence suggest a central role for the endocannabinoid system (ECS) in the neuronal development and cognitive function and in the pathogenesis of fragile X sy
Slide 61: CONNECT-FX Data Published
CONNECT-FX Data Published in the Journal of Neurodevelopmental Disorders • “…ZYN002 was well tolerated in patients with FXS and demonstrated evidence of efficacy with a favorable benefit risk relationship in patients with ≥ 90% methylation of the FMR1 gene, in whom gene silencing is most likely, and
Slide 62: Variable Methylation in the FMR1 Gene
Variable Methylation in the FMR1 Gene • Healthy individuals: No methylation → normal expression and production of FMRP → normal function of the ECS • Fragile X syndrome – Full mutation (over 200 CGG repeats) → full methylation (>90%) of the promoter region → complete silencing of the gene → absence
Slide 63: CONNECT-FX Key Learnings: Complete Methylation
CONNECT-FX Trial Key Learnings: Results with complete methylation of FMR1 gene Consistent Improvements Observed with ZYN002 vs. Placebo in Patients with Complete Methylation PRIMARY ENDPOINT CAREGIVER-REPORTED BEHAVIOR CHANGE CLINICIAN-REPORTED BEHAVIOR IMPROVEMENTS CLINICALLY MEANINGFUL BEHAVIOR IM
Slide 64: Open-Label Extension: Sustained Improvement
Open-Label Extension Patients on ZYN002 Sustained Improvement in Patients With Complete Methylation of FMR1a a. Patients matching primary efficacy population in RECONNECT. b. ZYN2-CL-016 (CONNECT-FX). c. Least square mean ± SE; reduction equals improvement. Change in ABC-CFXS Social Avoidance CONNEC
Slide 65: Design Optimized from CONNECT-FX Trial
Design Optimized from CONNECT-FX Trial 65 More patient and family friendly Extending trial to 18 weeks Increased dosing option for individuals >50 kg Successful completion of Phase 3 pivotal trial expected to satisfy requirements for an NDA submission in the U.S. and a marketing authorization applic
Slide 66: Kumar Budur, Chief Medical & Scientific Officer
KUMAR BUDUR, MD, MS Chief Medical & Scientific Officer Harmony Biosciences OPENING REMARKS SLEEP/WAKE FRANCHISE NEUROBEHAVIORAL FRANCHISE EPILEPSY FRANCHISE CLOSING REMARKS MANAGEMENT PANEL DISCUSSION Q&A
Slide 67: The History of ZYN-002
The History of ZYN-002 67 October 1, 2024 Harmony Biosciences | Investor Day More Than 15 Years of Research, Dedication, and Expertise CONNECT FX Trial The company was founded by a pharmacologist and transdermal expert at the University of Kentucky College of Pharmacy FAB-C 1 st Trial in FXS Preclin
Slide 68: ZYN-002: Unique Product Attributes
ZYN-002: Unique Product Attributes 68 October 1, 2024 Harmony Biosciences | Investor Day • Unique product profile • Established safety and tolerability profile: Exposure for over 7 years in FXS patients — maintenance of effect and high persistence with treatment KEY TAKEAWAY E P I D E R M I S C I R
Slide 69: Enrolling Pivotal Phase 3 Trial in Fragile X Syndrome
Double-Blind, Placebo-Controlled Study: Enrolling Pivotal Phase 3 Trial in Fragile X Syndrome 69 October 1, 2024 Harmony Biosciences | Investor Day 16 weeks Males and females 3 to 29 years old Moderate-to-Severe FXS ZYN-002 (n~100; 801 ) 250 mg daily (≤30 kg) 500 mg daily (>30 kg) 750 mg daily (>50
Slide 70: ZYN-002: Primary and Key Secondary Objectives
ZYN-002: Primary and Key Secondary Objectives 70 October 1, 2024 Harmony Biosciences | Investor Day Primary Objective Change from baseline to end of treatment in ABC-CFXS Social Avoidance subscale in patients who have complete (100%) methylation of their FMR1 gene Selected Key Secondary Objectives C
Slide 71: FXS: Total Addressable Market
FXS: Total Addressable Market 71 October 1, 2024 Harmony Biosciences | Investor Day • There are currently no approved therapies for the treatment of FXS • Behavioral symptoms, especially social avoidance and irritability, significantly impact the patient and their family/ caregivers • Patients with
Slide 72: Neurobehavioral Franchise Catalysts
Mid-25 – topline data in FXS 2H 25 – Initiate 22q pivotal Phase 3 trial 2026 – PDUFA for FXS Neurobehavioral Franchise Catalysts
Slide 73: Epilepsy
EP] L E PASwys
Slide 74: Epilepsy Franchise: Meaningful Treatment Options for Unmet Needs
Epilepsy Franchise: Deliver Meaningful Treatment Options to Patients with Serious Unmet Medical Needs 74 October 1, 2024 Harmony Biosciences | Investor Day ACQUISITION OF EPYGENIX EPX-100 AND EPX-200 EPX-100: Innovative approach to treatment of Development Epileptic Encephalopathies (DEEs) based on
Slide 75: Scott C. Baraban, PhD
SCOTT C. BARABAN, PhD Professor of Neurological Surgery University of California, San Francisco OPENING REMARKS SLEEP/WAKE FRANCHISE NEUROBEHAVIORAL FRANCHISE EPILEPSY FRANCHISE CLOSING REMARKS MANAGEMENT PANEL DISCUSSION Q&A
Slide 76: References for Rare Epilepsy Drug Discovery Using Zebrafish
References for Presentation of Rare Epilepsy Drug Discovery using Zebrafish By Scott C. Baraban, PhD • Loscher and Schmidt, Epilepsia (2011) • Barbaban et al. Nature Communications (2013) • Dindo and Baraban, eNeuro (2016) • Griffin et al. Frontiers in Pharmacology (2018) • Griffen et al. Brain Comm
Slide 77: Kumar Budur, Chief Medical & Scientific Officer
KUMAR BUDUR, MD, MS Chief Medical & Scientific Officer Harmony Biosciences OPENING REMARKS SLEEP/WAKE FRANCHISE NEUROBEHAVIORAL FRANCHISE EPILEPSY FRANCHISE CLOSING REMARKS MANAGEMENT PANEL DISCUSSION Q&A
Slide 78: EPX-100 (Clemizole HCl): Overview and Clinical Development
EPX-100 (Clemizole HCl): Overview and Clinical Development Programs 78 October 1, 2024 Harmony Biosciences | Investor Day • Established MoA; potential for favorable risk/benefit profile in DEEs • On track for topline data in DS and LGS in 2026 • EPX-100 granted ODD and RPDD for both DS and LGS KEY T
Slide 79: EPX-100: Generally Safe and Well Tolerated
1 10 100 Mean Concentration 0 6 12 18 24 (ng/mL) Nominal Time (h) 20 40 80 EPX-100: Generally Safe and Well Tolerated 79 October 1, 2024 Harmony Biosciences | Investor Day * One subject on placebo and 2 subjects on EPX-100; mild, transient and self-limiting with no intervention; no symptoms reported
Slide 80: EPX-100: Safety Compared to Select Approved Drugs
EPX-100: Preliminary Safety and Tolerability Data Compared to Select Approved Drugs in DS and LGS 80 October 1, 2024 Harmony Biosciences | Investor Day Epidiolex1 Fintepla2 EPX-1003 Decreased appetite 16–22% 8% 0% Diarrhea 9–20% 6% 16% Somnolence 23–25% 11% 12% LFT monitoring Required n/a n/a REMS (
Slide 81: ARGUS Study Design in Dravet Syndrome
Phase 3 Study in DS: ARGUS Study Design 81 October 1, 2024 Harmony Biosciences | Investor Day 12 WEEKS MAINTENANCE 4 WEEKS TITRATION 4 WEEKS OBSERVATIONAL UP TO 156 WEEKS OPEN-LABEL EXTENSION Screening/ Baseline 4-week Dose Titration Period 12-week Maintenance Period Placebo Phone call 2 weeks post
Slide 82: ARGUS Study: Primary and Key Secondary Objectives
ARGUS Study: Primary and Key Secondary Objectives 82 October 1, 2024 Harmony Biosciences | Investor Day • Well-established study design and endpoints • Study designed to address the requirements for both US and EU regulatory authorities KEY TAKEAWAY Primary Objective To evaluate the efficacy of EPX-
Slide 83: ARGUS Study: Status Update
ARGUS Study: Status Update 83 October 1, 2024 Harmony Biosciences | Investor Day Generally safe and well tolerated (data from double-blind and open-label extension study) Most common TEAEs occurring in >5 subjects were pyrexia, URTI, seizure, somnolence and nasopharyngitis Actively recruiting patien
Slide 84: Dravet Syndrome: Total Addressable Market
Dravet Syndrome: Total Addressable Market 84 October 1, 2024 Harmony Biosciences | Investor Day • Severe refractory epilepsy not controlled even with polypharmacy • Extreme co-morbidity/ mortality if not effectively treated • Recognized need for improved treatment options ~7K ~8.6K 5–6K ~5K PRICING
Slide 85: EPX-100 in LGS: Phase 3 Study Design
EPX-100 in Lennox Gastaut Syndrome (LGS): Phase 3 Study Design 85 October 1, 2024 Harmony Biosciences | Investor Day 12 WEEKS DOUBLE-BLIND MAINTENANCE 4 WEEKS DOUBLE-BLIND TITRATION 4 WEEKS SEIZURE OBSERVATIONAL UP TO 3 YEARS OPEN-LABEL EXTENSION Screening/ Baseline 4-week Dose Titration Period 12-w
Slide 86: LGS Study: Primary and Key Secondary Objectives
LGS Study: Primary and Key Secondary Objectives 86 October 1, 2024 Harmony Biosciences | Investor Day • Well-established study design and endpoints • Study designed to address the requirements for both US and EU regulatory authorities KEY TAKEAWAY Primary Objective To evaluate the efficacy of EPX-10
Slide 87: LGS: Total Addressable Market
LGS: Total Addressable Market 87 October 1, 2024 Harmony Biosciences | Investor Day • Severe refractory epilepsy not controlled even with polypharmacy • Extreme co-morbidity/ mortality if not effectively treated • Recognized need for improved treatment options ~44K ~48K 35K ~35K PRICING BENCHMARK: F
Slide 88: Epilepsy Franchise Catalysts
Q4 2024 – Initiate LGS pivotal Phase 3 trial 2H 2026 – topline data in DS 2H 2026 – topline data in LGS 2027/2028 – PDUFA for DS 2027/2028 – PDUFA for LGS Epilepsy Franchise Catalysts
Slide 89: Closing Remarks: Jeffrey M. Dayno
JEFFREY M. DAYNO, MD President and Chief Executive Officer Harmony Biosciences OPENING REMARKS SLEEP/WAKE FRANCHISE NEUROBEHAVIORAL FRANCHISE EPILEPSY FRANCHISE CLOSING REMARKS MANAGEMENT PANEL DISCUSSION Q&A
Slide 90: Commitment to Patients and Value to Shareholders
90 October 1, 2024 Harmony Biosciences | Investor Day Commitment to patients Addressing unmet medical needs Delivering meaningful treatment options Helping patients thrive DELIVER ON PROMISE TO PATIENTS Innovative Catalyst-rich pipeline Profitable biotech company Meaningful investment opportunity DE
Slide 91: ym iS. Graeme s Ie N
ym iS. Graeme s Ie N \ P\ A Noa OL
Slide 92: Management Panel Discussion
SANDIP KAPADIA, CPA, MBA CFO & Chief Administration Officer Harmony Biosciences JEFFREY M. DAYNO, MD President & CEO Harmony Biosciences JEFFREY DIERKS, MBA Chief Commercial Officer Harmony Biosciences KUMAR BUDUR, MD, MS Chief Medical & Scientific Officer Harmony Biosciences
Slide 93: Innovative, Catalyst-Rich, Profitable Biotech Company
5 Anticipate 1 or more new product or indication launches each year over next 5 years Harmony is an innovative, catalyst-rich, profitable biotech company 93 October 1, 2024 Harmony Biosciences | Investor Day $1B+ Proven commercial product and growing $3B+ Establishing leadership position in CNS 13 D
Slide 94: company/harmonybiosciences/ @harmonybio harmony_biosciences w w w . h a r m o n y
company/harmonybiosciences/ @harmonybio harmony_biosciences w w w . h a r m o n y b i o s c i e n c e s . c o m
Harmony Biosciences Holdings — Investor Day (October 2024) on 6ix