Supernus Pharmaceuticals, Inc. · NASDAQ:SUPN

Supernus Pharmaceuticals — Investor Day (October 2023)

104 slides from Supernus Pharmaceuticals's investor day presentation, Oct 18, 2023

1. Slide 1: Supernus Pharmaceuticals R&D Day

   © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Supernus Pharmaceuticals R&D Day October 18, 2023 1

2. Slide 2: Introduction and Agenda

   © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Introduction and Agenda 2 Jack Khattar President and Chief Executive Officer

3. Slide 3: Safe Harbor Statement

   © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Safe Harbor Statement 3 This presentation and other matters discussed today or answers that may be given to questions asked include forward-looking statements within the meaning of the federal securities laws. These statements, among other t

4. Slide 4: Agenda

   © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. AGENDA Introduction Corporate Overview Product Candidates SPN-820 – Depression SPN-817 – Epilepsy SPN-443 – ADHD/CNS SPN-446 – Narcolepsy General Q&A and Closing Comments 4

5. Slide 5: Participants

   © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Participants 5 Supernus Pharmaceuticals Jack Khattar, MBA President and Chief Executive Officer Jonathan Rubin, M.D., MBA SVP, Research and Development, Chief Medical Officer Bryan Roecklein, Ph.D. SVP, Corporate Development Tim Dec SVP, Chi

6. Slide 6: Proven Commercial Execution & Growth Strategy

   © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023E 147 93 12 215 302 409 393 520 Total Revenues ($ Millions) 580 Proven Commercial Execution & Growth Strategy Total Portfolio Revenue Growth 667 Year-end 2018 inventory build by distribut

7. Slide 7: Robust CNS Pipeline to Drive Long-Term Growth

   © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Robust CNS Pipeline to Drive Long-Term Growth 7 Program Indications Discovery Preclinical Phase 1 Phase 2 Phase 3 NDA Market SPN-830 PD SPN-820 Depression SPN-817 Epilepsy SPN-443 ADHD/CNS SPN-446 Narcolepsy SPN-448 CNS PD = Parkinson’s Dise

8. Slide 8: Strategic Overview: Development Cost

   © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Development Cost Strategic Overview 8 Low High Short Long Low Risk High Time to Market Known Drugs New Delivery Clinically Validated Target Clinically Non-Validated Target First in Class New Chemical Entities Known Drugs New Indication New M

9. Slide 9: Strategic Overview: Market Value

   © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Market Value Strategic Overview 9 Low High Oxtellar XR® Trokendi XR ® Clinically Non-Validated Target Qelbree® Gocovri® SPN-820 SPN-817 SPN-443 SPN-446 SPN-448 Short Time to Market Long

10. Slide 10: Key Strategic Imperatives

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Market Value Strategic Overview 10 Low High Key Strategic Imperatives Multi-Billion Dollar Market Value Corporate Development Capitalize on our Strong R&D Capability Complete Development and Launch SPN-830 SPN-820 SPN-817 Build a Multi-Billi

11. Slide 11: Significant Experience & Capabilities in Drug Development

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Significant Experience & Capabilities in Drug Development 11 Discovery Concept Validation Safety CMC Drug Candidate Discovery Platform Design and synthesis of new compounds based on structure, function and disease pathways In vitro, PK, prec

12. Slide 12: Supernus Near-Term Milestones

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. 2023 2024 2025 2026 Supernus Near-Term Milestones Above timelines represent management’s estimates that are subject to several factors that are beyond our control and actual results may be significantly different from our estimates 12 SPN-83

13. Slide 13: Multi-Billion Dollar Market Value Growth Potential

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. 13 Multi-Billion Dollar Market Value Growth Potential of Existing Products Qelbree® and GOCOVRI® Innovative R&D Portfolio SPN-830 Novel Infusion Device for PD SPN-820 First in Class Novel MOA for Depression SPN-817 First in Class Novel MOA f

14. Slide 14: Supernus Pipeline

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Supernus Pipeline 14 Jonathan Rubin SVP, Research and Development, Chief Medical Officer

15. Slide 15: Qelbree Novel Non-Stimulant ADHD Product

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Qelbree® Novel Non-Stimulant ADHD Product 15

16. Slide 16: Co-administration of Qelbree with a Stimulant Provides Incremental Efficacy

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Co-administration of Qelbree with a Stimulant Provides Incremental Efficacy Phase IV, Open-Label, Flexible-Dose study in Children and Adolescents with ADHD Primary Objective: Safety and tolerability when administered with stimulants (methylp

17. Slide 17: Efficacy of Qelbree in Adults with ADHD and Mood Symptoms

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Efficacy of Qelbree in Adults with ADHD and Mood Symptoms 60% of adults with ADHD have comorbid depression and 57% have comorbid anxiety Viloxazine IR was approved in the EU for the treatment of depression Phase IV, Open-label, decentralized

18. Slide 18: SPN-830 Treatment of Hypomobility in Parkinson's Disease

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-830 Treatment of Hypomobility in Parkinson’s Disease 1818

19. Slide 19: SPN-830: Infusion Device Submission

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-830: Infusion Device Submission Continuous treatment of motor fluctuations (OFF episodes) in Parkinson’s disease (PD) patients that are not adequately controlled with oral levodopa and one or more adjunct PD medications. ‒ If approved, w

20. Slide 20: SPN-820 First in Class Intracellular Mechanism to Treat Depression

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-820 First in Class, Unique Intracellular Mechanism to Treat Depression 2020

21. Slide 21: Depression Market Update

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Depression Market Update 2121

22. Slide 22: Depression: One of the Largest Therapeutic Areas

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Depression – One of the Largest Therapeutic Areas with ~195M Prescriptions in the U.S. per Year 1. NIMH Health Statistics 2. NIMH Sequenced Treatment Alternatives to Relieve Depression (STAR*D Study) 2. Trials & Triumphs of Neuropsychiatry:

23. Slide 23: MDD vs. Treatment Resistant Depression

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Major Depressive Disorder (MDD) vs. Treatment Resistant Depression (TRD) 23 DSM-5 classification with specific clinical criteria Five or more symptoms during the same 2-week period, at least one of the symptoms is (1) depressed mood or (2) l

24. Slide 24: Multiple MOAs for Treating Depression

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Multiple MOAs for Treating Depression • “Depression Only” TRx, Integrated IQVIA NPA & NMTA • All trademarks are owned by their respective owners 24 Abbrev. Treatment Class/MOA/Description Depression TRx* % of Total Most Commonly Prescribed D

25. Slide 25: The Future: Faster Relief, Greater Tolerability, Neuroplasticity

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. The Future: Faster Relief, Greater Tolerability, and Improvement of Neuroplasticity for Long-Term Benefits Leading brand Trintellix® differentiates with efficacy, impact on DSST/Executive Function and lower sexual dysfunction side effects Ne

26. Slide 26: Market Needs: Ideal Product Profile

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Market Needs: Ideal Product Profile High effect size with good responder frequency Fast onset – one week or less No cognitive impairment No impact on sexual dysfunction Positive impact on neuroplasticity for prolonged effects Low to no disso

27. Slide 27: SPN-820

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-820 27 Vladimir Maletic, M.D., M.S. Clinical Professor Neuropsychiatry and Behavioral Science University of South Carolina, School of Medicine

28. Slide 28: A Rapid Acting Antidepressant with Novel MOA

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. A Rapid Acting Antidepressant with Novel MOA 2828 SPN-820

29. Slide 29: Evolution of Depression Treatment

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Evolution of Depression Treatment 1930s 1940s 1950s 1960s 1970s 1980s 1990s 2000s 2010s ECT MAOIs TCAs Trazodone SSRIs SNRIs rTMS DBS glutamate modulators Recently-developed treatments for TRD restore neuroplasticity and do so rapidly Monoam

30. Slide 30: Neuroplasticity Hypothesis of Depression

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Neuroplasticity Hypothesis of Depression Dysfunctional neuroplasticity underlies depression manifestation ‒ Inability of neuronal connections to undergo activity- and experience-dependent changes in strength; brain region and circuit specifi

31. Slide 31: Symptoms of Depression Reflect Disrupted Network Connectivity in MDD

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Symptoms of Depression Reflect Disrupted Network Connectivity in MDD 31 MDD = major depressive disorder; DMN = default mode network; sgACC = subgenual anterior cingulate cortex. Dunlop et al. Curr Psychiatry Rep. 2019;21:87. Mulders PC, et a

32. Slide 32: Dysfunctional Network Connectivity and Related Symptoms in TRD

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Dysfunctional Network Connectivity and Related Symptoms in TRD 32 Idlett-Ali SL, et al. Front Hum Neurosci. 2023;17:1125074.

33. Slide 33: Severely Depressed Subjects Have Decreased Synaptic Density

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Severely Depressed Subjects Have Decreased Synaptic Density Holmes SE, et al. Nat Comm. 2019; 10:1529 VT=volume of distribution; ACC=anterior cingulate cortex; HC=healthy control; PET=positron emission tomography; SV2A=synaptic vesicle glyco

34. Slide 34: Decreased Synaptic Density in Severe Depression is Statistically Significant

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Decreased Synaptic Density Between Healthy Controls and those with Severe Depression is Statistically Significant Holmes SE, et al. Nat Comm. 20 19; 10 :1529 PTSD=post-traumatic stress disorder; MDD=major depressive disorder; [11C]UCB-J =SV2

35. Slide 35: SPN-820 MOA Video

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-820 MOA Video 3535 Click Here to Watch SPN-820 MOA Video

36. Slide 36: mTORC1 Activation in a Physiological Manner

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. mTORC1 Activation in a Physiological Manner • Generally, equivalent increase in mTORC1 activation between NV-5138 and leucine in peripheral organs suggests low likelihood of peripheral side effects related to increased mTORC1 activation Seng

37. Slide 37: NV-5138 Shows Antidepressant Efficacy in Multiple Preclinical Models

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. NV-5138 Shows Antidepressant Efficacy in Multiple Preclinical Models Model Outcome Forced swim test Efficacious in standard antidepressant screening (behavioral despair) Novelty suppressed feeding test Anti-anxiety effects Female urine sniff

38. Slide 38: NV-5138 Normalizes Chronic Stress-Induced Behavioral Changes

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. NV-5138 Normalizes Chronic Stress-Induced Behavioral Changes Relevant to Depression Kato T, et al. J Clin Inv. 2019; 129(6):2542-2554 CUS=chronic unpredictable stress; NSFT=novelty suppressed feeding test; s=seconds • NV-5138 prevents chroni

39. Slide 39: NV-5138 Normalizes Decreases in Synaptic Plasticity-Related Proteins in PFC

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. NV-5138 Normalizes Chronic Stress-Induced Decreases in Synaptic Plasticity-Related Proteins in PFC Kato T, et al. J Clin Inv. 2019; 129(6):2542-2554 CUS=chronic unpredictable stress; NS=non-stress; NV=NV-5138, V=vehicle; PSD-95=post-synaptic

40. Slide 40: NV-5138 Induces Growth of New Dendritic Spines

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. NV-5138 Induces Growth of New Dendritic Spines Vehicle NV-5138 Stubby Thin Mushroom Kato T, et al. J Clin Inv. 2019; 129(6):2542-2554 40

41. Slide 41: NV-5138 Increases Dendritic Spine Density in PFC

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. µm=micron; mshrm=mushroom type spine; PFC=prefrontal cortex NV-5138 Increases Dendritic Spine Density in PFC Kato T, et al. J Clin Inv. 2019; 129(6):2542-2554 • NV-5138 specifically increases thin and mushroom type spines 24 hours after oral

42. Slide 42: NV-5138 Increases Excitatory Responses in PFC Neurons

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. NV-5138 Increases Excitatory Responses in PFC Neurons 24 hours After Oral Administration in Rats Kato T, et al. J Clin Inv. 2019; 129(6):2542-2554 5-HT=serotonin; EPSC=excitatory post-synaptic current; PFC=prefrontal cortex; ** p<0.01 Studen

43. Slide 43: A First in Class Antidepressant SPN-820

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. A First in Class Antidepressant SPN-820 A first in class, small molecule that increases mTORC1 mediated synaptic function intracellularly No synaptic receptor modulation 43 No synaptic receptor modulation Improved side effect profile vs. cur

44. Slide 44: SPN-820 Pharmacology

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-820 Pharmacology 4444

45. Slide 45: PK: Good Development Properties

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. PK: Good Development Properties Rapid absorption in animals across species ‒ Rapid uptake in the brain (PFC) ‒ No plasma protein binding One major metabolite identified, not active in mTORC1 activation assay Urine is primary route of excreti

46. Slide 46: Novel Intracellular Mechanism

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Novel Intracellular Mechanism Does not bind to or modulate any cell surface receptors ‒ Unlikely to have abuse potential given lack of binding to targets implicated in drug abuse Unlike leucine, NV-5138 is not incorporated into proteins duri

47. Slide 47: SPN-820 Phase Studies

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-820 Phase 1 Studies 4747

48. Slide 48: SPN-820 PK: Rapid Absorption & Once a Day

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-820 PK: Rapid Absorption & Once a Day Half-life: 10.7 hours in plasma and 11.7 in cerebrospinal fluid (CSF) Exposure in CSF is 10 times lower than plasma Confirmed rapid absorption: Tmax: 0.5-1.25 hours (Plasma), 4 hours (CSF) and renal

49. Slide 49: SPN-820 Phase Studies: Rapid Acting Antidepressant

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-820 Phase 1 Studies: Rapid Acting Antidepressant Rapid and sustained effect Improvement of core symptoms of depression with a single dose of 2400 mg/day at 4 and12 hours post-dose, with sustained effect to 72 hours, the last timepoint as

50. Slide 50: SPN-820 Phase Studies: Favorable Safety Profile

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-820 Phase 1 Studies: Favorable Safety Profile Total of 205 subjects in Phase 1 studies ‒ Single oral doses and two sequential oral doses of SPN-820 up to 3000mg/day were safe and well tolerated ‒ Maximal tolerated dose not achieved ‒ Mos

51. Slide 51: SPN-820: Proof of Concept in TRD Subjects

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-820: Proof of Concept in TRD Subjects Randomized, two-part, double-blind, placebo-controlled study of single ascending oral solution dose Primary endpoint: Changes from baseline to 24, 48, and 72 hours, post-dose in the MADRS rating Addi

52. Slide 52: SPN-820 POC Study: Rapid Acting & Sustained Efficacy

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-820 POC Study: Rapid Acting & Sustained Efficacy Efficacy with HAM-D6 shows early, large effect size, sustained to 72 hours after single dose. MADRS did not show efficacy with single dose but showed small effect on acute symptoms. 52 Eff

53. Slide 53: SPN-820: Dose Selection Based on PK

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-820: Phase 2 Dose Selection Based on PK NV-5138 CSF concentration: Day 7 after multiple doses of 800 mg and 1600 mg once daily for 7 days (at steady state) versus single dose of 2400 mg on Day 1 53

54. Slide 54: SPN-820: Dose Selection Based on Biomarkers

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-820: Phase 2 Dose Selection Based on Biomarkers 54 Biomarkers downstream of mTORC1 activation are increased in CSF at 800 and 1600 mg doses of NV-5138

55. Slide 55: SPN-820: Phase 2b Study

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Primary efficacy: MADRS Key secondary: CGI-S HAM-D6 Onset of effect Depression symptoms response and remission Individual disability Anxiety Rate of improvement Safety and tolerability SPN-820: Phase 2b Study 55 Multicenter, randomized, doub

56. Slide 56: SPN-820: Phase 2b Study Enrollment Status

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-820: Phase 2b Study Enrollment Status 1 Data updated as of 11 October 2023 56 Number of Subjects Overall Randomized 62 In-Screening1 37 In-Treatment1 6 Completed 44 Discontinued (%) 13 (21%) Discontinued due to AEs 2 (3%) 56

57. Slide 57: SPN-820: Planned New Phase Study in MDD

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-820: Planned New Phase 2 Study in MDD Optimize dosing and assess rapid onset ‒ Pulsatile dosing ‒ Efficacy in MDD ‒ Rapid onset Open–label study ‒ 40 subjects with MDD ‒ Rapid and sustained efficacy (2, 4, 8 and 72 hours after a single a

58. Slide 58: SPN-820: Summary of Attributes

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-820: Summary of Attributes Increases mTORC1-mediated synaptic function through a first in class, unique intracellular mechanism. Adjunctive therapy for patients with TRD An average effect size of 0.6 has been measured with a single dose

59. Slide 59: SPN-820 Q & A

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-820 Q & A 5959

60. Slide 60: SPN-817

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-817 60 Jonathan Rubin SVP, Research and Development, Chief Medical Officer

61. Slide 61: SPN-817 Novel Selective AChE Inhibitor for Focal Epilepsy

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-817 Novel, First in Class, Highly Selective Acetylcholinesterase (AChE) Inhibitor for Focal Epilepsy 6161

62. Slide 62: Refractory Epilepsy Results in Switching & Polypharmacy

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Refractory Epilepsy Results in Switching & Polypharmacy Generic ASM (e.g., NA+/Ca+ inhibitor, GABA), monotherapy Optimize dose (evaluate at 1-4, 8 weeks) Switch to a different ASM, monotherapy Combine two ASMs (branded / generic) Further com

63. Slide 63: Epilepsy: Debilitating Disease with Significant Unmet Need

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Epilepsy: Debilitating Disease with Significant Unmet Need • 1.2% of people in the U.S. have epilepsy (~3.4M people)1 • Focal seizures affect up to 61% of people with epilepsy1 • 40% of patients with epilepsy are drug resistant1 • 28.5M annu

64. Slide 64: SPN-817: Market Opportunity

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-817: Market Opportunity All drugs that treat Seizure Disorders1 166.5M TRx Epilepsy & Seizure Disorders2 28.5M TRx 1. IQVIA NPA, MAT April 2023 (includes non-seizure disorder indications as well) 2. IQVIA Integrated NPA + NMTA, MAT April

65. Slide 65: Need for Effective Pharmacological Treatments

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Despite a Competitive Market, There is a Need for Effective Pharmacological Treatments1 HCPs are aligned on treatment goals Reducing seizure frequency, improving QoL, achieving seizure freedom, and reducing severity of seizures are key. Trea

66. Slide 66: SPN-817: Only AChE Inhibitor in Development for Focal Seizures

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-817: Only AChE inhibitor in Development for Focal Seizures Ph 1 Ph 2 Ph 3 XEN-1101 (KCNQ) NBI-921352 (Nav1.6) JNJ-40411813 (mGlu2 PAM) EQU-001 (Undisclosed) SPN-817 (AChE) Darigabat (GABA PAM) BHV-7000 (KCNQ) ENX-101 (GABA PAM) OV329 (GA

67. Slide 67: SPN-817 Huperzine A Novel MOA

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-817 Huperzine A Novel MOA Reduce Neuronal Hyperactivity Decrease Excitation Block or Inhibit Na+ Channel Inhibit Glutamate Release / Other Increase Inhibition Activate Post-Synaptic GABA Receptors Inhibit GABA Reuptake or Breakdown Incre

68. Slide 68: SPN-817 Pharmacology

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-817 Pharmacology 6868

69. Slide 69: SPN-817: Novel MOA for the Treatment of Focal Seizures

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-817: Novel MOA for the Treatment of Focal Seizures Huperzine A is a potent, selective and reversible acetylcholinesterase (AChE) inhibitor, an enzyme that metabolizes acetylcholine (ACh) after synaptic release1,2 Inhibition of AChE incre

70. Slide 70: SPN-817 Preclinical Data: Refractory Seizures

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-817 Preclinical Data: Refractory Seizures 70 (ED50 in mg/kg) 22mA 32mA 44mA Phenytoin 9.4 >60 >60 Lamotrigine 4.4 >60 >60 Ethosuximide 86.9 167 >600 Valproic Acid 41.5 126 310 Levetiracetam (Keppra) 4.6 19.4 1,089 SPN-817 0.28 0.34 0.58-

71. Slide 71: SPN-817: Current MoA Hypothesis for Seizure Control

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-817: Current MoA Hypothesis for Seizure Control: Cholinergic Modulation of Neuronal Excitation Seizures are the result of the imbalance of the Excitation/Inhibition (E/I) ratio in susceptible regions of the brain Acetylcholine augmentati

72. Slide 72: SPN-817: More Selective than Other Cholinesterase Inhibitors

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-817: More Selective than Other Cholinesterase Inhibitors More selective towards AChE than BuChE 1,2 Requires lower doses to block central AChE ‒ Displays higher AChE inhibitory activity in various brain regions at lower doses (improved t

73. Slide 73: SPN-817: Phase 2a FIAS Study

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. 73 SPN-817: Phase 2a Focal Onset Impaired Awareness Seizure (FIAS) Study Key Inclusion Criteria: Diagnosis of FIAS type epilepsy Current minimum average of 5 countable seizures / week to enroll in study At least 5 focal impaired awareness se

74. Slide 74: SPN-817: Significant Seizure Reduction in Small POC Study

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-817: Showed Significant Seizure Reduction in Small POC Study Patients had focal impaired-awareness seizures (FIAS) type epilepsy, treated with a maximum dose of 4 mg BID Mean reduction in 28-day seizure rate from baseline was: – 71.2% un

75. Slide 75: SPN-817: Phase 2a Synopsis

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-817: Phase 2a Synopsis Open-label study Number of study sites: up to 8 sites in Australia Number of participants: approximately 35 subjects with treatment resistant seizures Indication: focal seizures in adults (18-65 years of age) 75

76. Slide 76: SPN-817: Phase 2a Study Design

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-817: Phase 2a Study Design Screening Period: Collection of baseline seizure diary for 42 days Dose Titration and Optimization: 8 weeks Maintenance Phase: 12 weeks Open-label Extension Period: up to 52 weeks 76 Titration: • All patients i

77. Slide 77: SPN-817: Phase 2a Endpoints

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-817: Phase 2a Endpoints Primary: ‒ Safety and tolerability as an adjunctive therapy in adult patients with treatment resistant seizures Secondary: ‒ Percent change from baseline in motor seizure frequency per 28 days ‒ Improvement in sei

78. Slide 78: SPN-817 Phase 2a Study: Interim Data

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-817 Phase 2a Study: Interim Data 7 patients completed titration at doses ranging from 1.0 mg bid to 4.0 mg bid ‒ Most common TEAEs were diarrhea, nausea, headache, insomnia, and affect lability ‒ All TEAEs were mild/moderate in severity

79. Slide 79: SPN-817: Planned Phase 2b Treatment Resistant Focal Seizures

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-817: Planned Phase 2b Treatment Resistant Focal Seizures 7979 Screening Phase 8 weeks Dose Titration & Optimization Phase 9-11 weeks Maintenance Phase 12 weeks Tapering Phase Up to 4 weeks Follow-Up Phone Call 3 days after last dose of S

80. Slide 80: SPN-817: Phase 2b Endpoints

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-817: Phase 2b Endpoints Primary: ‒ Change from baseline in focal seizure frequency per 28 days Secondary: ‒ Safety and tolerability ‒ Pharmacokinetics (PK) of huperzine A Exploratory: Change from baseline: ‒ In inflammatory biomarkers in

81. Slide 81: SPN-817 Summary: Novel First in Class Selective AChE Inhibitor

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-817 Summary: Novel First in Class Selective AChE Inhibitor for Focal Seizures Phase 2 long-term maintenance: ‒ mean reduction in 28-day seizure rate from baseline (excluding titration) was 70% (n = 3) Well-tolerated according to reported

82. Slide 82: SPN-817 Q & A

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-817 Q & A 8282

83. Slide 83: Break

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Break 8383

84. Slide 84: SPN-443 Novel MOA with Reduced Abuse Liability

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-443 Novel MOA with Potential Stimulant-like Efficacy and Reduced Abuse Liability 8484

85. Slide 85: ADHD Annual Prescriptions of 92.1M

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. ADHD Annual Prescriptions of 92.1M - 89% are for Stimulants 85 64% 25% 11% The market rewards fast onset, predictable response, and good treatment Amphetamines effect. Methylphenidates Nonstimulants Source: IQVIA MAT Aug 2023

86. Slide 86: Stimulants are Effective, But have Significant Drawbacks

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Stimulants are Effective, But have Significant Drawbacks Advantages Significant treatment effect Rapid onset Allows for as needed dosing with some patients Many generics available Drawbacks DEA CII controlled substance requirements – HCPs ne

87. Slide 87: SPN-443: Leverages Qelbree's Commercial Investment

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-443: Leverages Qelbree’s Commercial Investment Sales force of 245 representatives ‒ Established relationships with HCPs and staff ‒ Leverage a well-trained and educated sales team Well-established relationships with KOLs Leadership posit

88. Slide 88: SPN-443: NCE with Triple Reuptake Activity

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-443: NCE with Triple Reuptake Activity & Low Risk for DDI or Abuse Active parent and major metabolites based on preclinical models ‒ All are triple monoamine transporter (NET, DAT, SERT) inhibitors High blood brain barrier permeability L

89. Slide 89: Parent and Major Metabolites have NET, DAT & SERT Activity

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Parent and Major Metabolites have NET, DAT & SERT Activity SPN-443 and its metabolites all bind to and inhibit NET, DAT, and SERT but with varying potencies Metabolites could provide longer duration of effect Functional Assay Transporters (I

90. Slide 90: In-vivo Pharmacology: Increase in Monoamines in a Rat Model

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. In-vivo Pharmacology: Increase in Monoamines in a Rat Model Microdialysis study: SPN-443 (0.3 mg/kg intraperitoneal dosing) significantly increased monoamines in the PFC, but not the nucleus accumbens: ‒ Dopamine (300%) ‒ Norepinephrine (391

91. Slide 91: SPN-443: Nonclinical Safety Studies Support Advancing into the Clinic

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-443: Results from Nonclinical Safety Studies Support Advancing into the Clinic No evidence of genotoxicity​ No adverse CV or CNS functional effects in safety pharmacology studies ‒ Large safety margins in hERG assay No dose-limiting toxi

92. Slide 92: SPN-443: Planned FIH Study in 2024

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-443: Planned FIH Study in 2024 Study design – Phase 1 single dose to evaluate PK in healthy adults Number of subjects: Approximately 24 enrolled and 18 completers Objectives: ‒ Estimate PK of SPN-443 and its metabolites ‒ Calculate relat

93. Slide 93: SPN-443: Summary of Potential Attributes

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-443: Summary of Potential Attributes Effect size within range of leading stimulants (1.0+) DEA scheduling of IV or better Well tolerated Long duration of activity 93

94. Slide 94: SPN-446 Narcolepsy

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-446 Narcolepsy 9494

95. Slide 95: Sleep Cycles

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Sleep Cycles A single sleep cycle normally includes non-REM (i.e., stages 1-3) and REM (rapid eye movement, stage 4) sleep. Alterations in neurocircuitry and neurochemistry can alter this cycle, resulting in different types of sleep disorder

96. Slide 96: Narcolepsy Type 1 (NT1)

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Narcolepsy Type 1 (NT1) 96 1. Szabo ST, et al. Sleep Medicine Reviews 20 19; 43: 23- 36 All trademarks are owned by their respective owners. Xyrem® 22% Xywav® 50% Wakix® 24% Lumryz™ 1% Sunosi® 3% 2. Global Data 20 23 forecast- net revenue 20

97. Slide 97: Need for New Therapies in NT1

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Need for New Therapies in NT1 More than 74% of patients still report issues with daily activities1 84% percent described impaired work or school performance and judged their condition as moderate or severe1 70% reporting excessive daytime sl

98. Slide 98: Neurocircuitry of NT1: Role of Norepinephrine

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Neurocircuitry of NT1: Role of Norepinephrine (NE) 98 a) Orexin pathways that promote and maintain wakefulness b) Orexin pathways that suppress REM sleep and maintain muscle tone during wakeful periods Krahn et al (2022) Adv Ther 39:221–243

99. Slide 99: SPN-446: Norepinephrine Transporter Inhibition & Serotonin Receptor Activity

    © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-446: Shows Norepinephrine Transporter Inhibition & Activity on Several Serotonin Receptors SPN-446 is a NET inhibitor with activity towards different serotonin receptors1 99 1 Data on file 2 Mitchel and Weinshenker (2010). Biochem Pharma

100. Slide 100: SPN-446: Decreases Cataplexy and REM Sleep in Preclinical Models

     © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-446: Decreases Cataplexy and REM Sleep in Preclinical Models Microdialysis ‒ Dose dependent increase in dopamine, norepinephrine, and serotonin in rat prefrontal cortex. Novel Object Recognition (NOR) test ‒ Improved episodic memory Orex

101. Slide 101: SPN-446: Dose Dependent Decrease in REM Sleep and Cataplexy

     © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. SPN-446: Shows Dose Dependent Decrease in REM Sleep and Cataplexy Reduces cataplexy and REM sleep up to 12 hours after dosing at the beginning of active time (ZT12 to ZT24). 101 NT1 Animal Model (Conditioned orexin neuron ablation or DTA mic

102. Slide 102: Full Q & A

     © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Full Q & A 102 102

103. Slide 103: Closing Remarks

     © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Closing Remarks 103 Jack Khattar President and Chief Executive Officer

104. Slide 104: Strong Foundation for Future Growth

     © 2023 Supernus Pharmaceuticals, Inc. All Rights Reserved. Strong Foundation for Future Growth Successfully transitioned from a drug delivery company to a profitable biopharma with strong R&D capabilities Diversified commercial portfolio that continues to deliver good cashflows while losing exclusiv

Supernus Pharmaceuticals — Investor Day (October 2023) on 6ix