AAIP 8/13/2020

.I have no relationships with commercial interests related to the content of this presentation.

J. Russell May, Pharm.D., FASHP Clinical Professor University of Georgia College of Pharmacy

® After attending the presentation and discussion, the .Lefamulin (Xenleta ) by Nabriva Therapeutics attendee should be able to: .Cefiderocol (Fetroja ®) by Shiongi .Bremelanotide (Vyleesi®) by Amag Compare and contrast newly approved drugs with older agents ® regarding their pharmacology, pharmacokinetics, efficacy, safety, .Lasmiditan (Reyvow ) by Lilly dosage and cost. .Ubrogepant (Ubrelvy ®) by Allergan Apply the “formulary approach” to evaluating new drugs. .Eptinezumab-jjmr (Vyepti ®) by Lundbeck Identify other recently approved medications and discuss their ® indications and potential usefulness .Crizanlizumab-tmca (Adakveo ) by Novartis Discuss any pipeline drugs that may be significant releases in the .Voxelotor (Oxbryta ®) by Global Blood therapeutics next few years. .Solriamfetol (Sunosi®) by Jazz

. A finite list of therapeutic agents For a drug to be recommended for addition to our . Established value in light of current medical Formulary, it must meet at least one of the following: opinion . New Pharmacological Class . Sufficiently broad to meet the usual clinical . More Efficacious problems . Safer . Avoids duplication of clinical effect . Pharmacokinetic Advantage (clinically relevant) . Subject to continuing revision based on new . More Cost Effective therapeutic knowledge

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Lefamulin (Xenleta®) Pharmacology • A pleuromutilin antibacterial: A NEW CLASS • Inhibits bacterial protein synthesis • Active against: • Bactericidal: S. pneumonia, H. influenza, and M. pneumonia • Bacteriostatic: S. aureus and S. pyrogenes • NOT active against: • Enterobacteriaceae and Pseudomonas aeruginosa • Indication • Treatment of adults with community-acquired bacterial pneumonia caused by susceptible microorganisms

https://www.pharmacytimes.com/publications/issue/2020/February2020/xenleta-from-nabriva-therapeutics

Lefamulin (Xenleta®) Lefamulin (Xenleta®) Pharmacokinetics Efficacy • Absorption • Two randomized, double-dummy, non-inferiority • Bioavailability of oral tablets ~ 25% trials (n = 1289) • Distribution  Trial 1: lefamulin IV/PO for 5 - 10 days versus • Protein binding: 95 – 97% moxifloxacin IV/PO for 7 – 10 days if MRSA found • Volume of distribution: 86.1 L added • Metabolism  Trial 2: 5 days oral versus moxifloxacin oral for 7 days Early response rates • Primarily via CYP3A4 • Trial 1: 87.3 % (L) 90.2% (M) • Elimination • Trial 2: 90.8% (L) 90.8% (M) • Half-life ~ 8 hours • Excreted primarily in feces

Data on file with manufacturer

Lefamulin (Xenleta®) Lefamulin (Xenleta®) Safety Dosage and Cost • Drug interactions • 150 mg every 12 hours IV over 60 minutes • Avoid this drug with moderate to strong 3A4 • Must be diluted in 250 ml of 10 mM citrate buffered inhibitors or inducers 0.9% sodium chloride (supplied) • Concomitant use with CYP3A4 substrates that • 600 mg every 12 hours PO prolong QT interval is contraindicated • May prolong QT interval • 1 hour before or 2 hours after food • Potential risk to fetus • Swallow whole • Excreted into breast milk • Adjustment to q24hr in severe hepatic impairment • Common adverse effects • ~ $275 per day (IV or PO) • Diarrhea – 12% Nausea – 5% • Vomiting - 3% IV site reactions – 7%

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Lefamulin (Xenleta®)

New Pharmacological Class More Efficacious Safer Pharmacokinetic Advantage (clinically relevant) More Cost Effective

https://www.fetroja.com/

Cefiderocol (Fetroja®) Cefiderocol (Fetroja®) Pharmacology Pharmacokinetics • An IV cephalosporin antibiotic • Metabolism – minimal <10% • Similar structure to cefepime • Elimination – Urine (90% unchanged) • Catechol group = siderophore • Half-life 2 – 3 hours • Siderophores • Iron chelating molecules • Transport iron into bacterial cells • Note: spectrum of activity: • Cefiderocol – binds ferric iron and uses bacterial • No gram + coverage iron transport system to penetrate gram negative • No anaerobic coverage cell wall • Indication: treatment of cUTIs caused by gram – • BUT: activity against many MDR organisms bacteria in adults with limited or no alternative • ESBLs treatment options • Carbampenemases

Cefiderocol (Fetroja®) Cefiderocol (Fetroja®) Efficacy Safety • Randomized, double-blind, non-inferiority trial vs imipenem (N = 448)* • • All organisms carbapenem susceptable Most common • 2 gm IV q8hr (C) vs 1 gm IV q8hr (I) • GI related: nausea, vomiting, diarrhea and • cUTIs including pyelonephritis caused by gram - bacteria constipation (2 – 4 %) • Clinical response/micro eradication 73% (C) vs 55% (I) = non-inferior • Randomized, double-blind, non-inferiority trial vs meropenem (N = 298) • Others • Most organisms were carbapenem susceptible • Rash, cough, increased liver enzymes, • Nosocomial pneumonia infection site reactions, candidiasis, • All cause mortality and clinical cure rates similar • Randomized open-label trial (N = 150) headache, and hypokalemia • All critically ill with carbapenem resistant infections • Pregnancy – no data • Versus best available therapy “BAT” (mostly colistin based- combination therapy) • Likely present in breast milk • Infection related deaths 21% (C) vs 8% (BAT)

*Portsmouth S et al. Lancet Infect Dis 2018;18:1319, others unpublished

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Cefiderocol (Fetroja®) Cefiderocol (Fetroja®) Dosage and Cost • 2 gm IV q8hr infused over 3 hours for 7 – 14 days • CrCl >120: q6hr New Pharmacological Class ? • CrCl 30 – 59: 1.5 gm q8hr More Efficacious ? • CrCl 15 – 29: 1 gm q8hr Safer? • ESRD: 0.75 gm q12h with or without HD Pharmacokinetic Advantage (clinically relevant) More Cost Effective • Cefiderocol $7699.90 • Meropenem $237.80 • Ceftolozane/tazobactam $2629.60 • Ciprofloxacin $65.10

Bremelanotide (Vyleesi®) Pharmacology • A melanocortin receptor agonist • Exact is unknown • Activation of melanocortin receptor subtypes including MCR4, thought to play a role in female arousal, sexual desire, and orgasm* • A subcutaneous injection • Indication • Treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD) • NOT for men or postmenopausal women

https://www.medscape.com/viewarticle/915229 *Uckert et al. Expert Opin Investig Drugs 2014;23:1477

Bremelanotide (Vyleesi®) Bremelanotide (Vyleesi®) Efficacy Pharmacokinetics • Two unpublished 24-week double blind, placebo- • Tmax = 1 hour controlled trials (n = 1247) • Metabolism – hydrolysis to amino acids • Patients with at least 6 months duration of HSDD • Elimination • Self administered SC injection, 45 minutes prior to • Urine: 64.8% anticipated sexual activity no more than once per 24 hours • Feces: 22.8% and 12 times per month • Half-life = around 2.7 hours • Modest increases in sexual desire score 25% vs 17% • Modest decrease in distress score 35% vs 31% • Duration of effect unknown • A 40 % dropout rate before completion of study • No trials comparing it to flibanserin

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Bremelanotide (Vyleesi®) Bremelanotide (Vyleesi®) Safety Dosage • Most common • 1.75 mg SC in abdomen or thigh at least 45 prior to anticipated • Nausea 40% Vomiting 5% Flushing 20% sexual activity • Injection site reactions 13% Headache 11% • Antiemetic therapy required in 13% • No more than one dose in 24 hours • Most common reason for dropouts was nausea • Use of > 8 doses per month not recommended • Transient increases in blood pressure and decreases in heart • If no improvement after 8 weeks trial, stop therapy rate • Resolves within 12 hours Cost • Hyperpigmentation 1% (MC1R activation): face, gingiva, Flibanserin $400 (30 day supply) breasts Bremelanotide $269.70 per auto-injector • These women took 8 doses per month • Up to 38% in those who used it daily for 8 days • No interaction with

Bremelanotide (Vyleesi®)

New Pharmacological Class More Efficacious ? Safer ? Pharmacokinetic Advantage (clinically relevant) More Cost Effective

https://www.biospace.com/article/eli-lilly-s-reyvow-wins-fda-approval-for-acute-treatment-of-migraine/

Lasmiditan (Reyvow®) Lasmiditan (Reyvow®) Pharmacology Pharmacokinetics • Oral serotonin (5HT )receptor antagonist 1F • Tmax = 1.8 hours • First “ditan”: selectively bonds to 5HT on 1F • Metabolized by non-CYP enzymes trigeminal neurons > inhibits pain pathways • Do not use in severe hepatic impairment • Unlike triptans, no vasoconstrictive effects* • Elimination • Indication: • Urine 66% as metabolites, 3% unchanged • Acute treatment of migraine in adults with or • Half-life = 5.7 hours without aura

*Raffaelli et al. Expert Opin Pharmacother. 2017;18:1409 Oswald and Schuster. J Pain Res. 2018;11:2221

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Lasmiditan (Reyvow®) Lasmiditan (Reyvow®) Efficacy Safety • Two double-blind trials vs placebo (n = 5100) • Most common (dose-related) • Patients had 3 – 8 migraine episodes per month • Dizziness • Lasmiditan 50 mg, 100 mg, 200 mg or placebo within 4 • Paresthesia hours of migraine onset • Sedation • Measured pain freedom and freedom from migraine • Others (dose-related) bothersome symptoms (photo-phono phobia, nausea) • Fatigue, nausea and vomiting, muscle weakness, Lasmiditan Pain Freedom* MBS Freedom* Pain Relief* vertigo, incoordination, lethargy, palpitations, cognitive 50 mg 28.6% 40.8% 59.0% changes and confusion 100 mg 28.4% 40.9% 61.5% • Hypersensitivity 0.2% 200 mg 35.5% 44.7% 62.0% • Angioedema, rash Placebo 18.3% 31.5% 44.5% • Serotonin syndrome was also reported Kuca et al. Neurology 2018;91:e2222 Goadsby et al. Brain 2019;142:1894

Lasmiditan (Reyvow®) Lasmiditan (Reyvow®) Dosage • 50, 100, or 200 mg po once in a 24 hour period • Safety of treating > 4 migraines in a 30 day period is New Pharmacological Class unknown More Efficacious Safer Cost (one dose at the usual lowest dose) • Lasmidtan $80 Pharmacokinetic Advantage (clinically • Ubrogepant $85 relevant) • Oral Triptans $0.9 – $117 More Cost Effective

Ubrogepant (Ubrelvy®) Pharmacology • First small molecule CGRP receptor antagonist (gepant) • CGRP is a potent vasodilator and pain-signaling neurotransmitter • Four SC anti-CGRP receptor antibodies are approved for migraine prophylaxis • Erenumab, fremanezumab, and galcanezumab • Approved in 2020: eptinezumab-jjmr (next drug to be discussed) • Rimegepant approved this year (same class as ubrogepant) • Indication: • Acute treatment of migraine in adults with or without aura

https://www.thepharmaletter.com/article/fda-approves-ubrelvy-a-new-treatment-for-adults-with-migraine

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Ubrogepant (Ubrelvy®) Ubrogepant (Ubrelvy®) Efficacy Pharmacokinetics • Two double-blind trials vs placebo (n = 2797) • Tmax = 1.5 hours • Patients had 2 – 8 migraine episodes per month • Metabolized in liver by CYP enzymes • Ubrogepant 50 mg, 100 mg, or placebo within 4 hours • Use reduced dose with severe hepatic of migraine onset impairment • Measured pain freedom and freedom from migraine • Elimination bothersome symptoms (photo-phono phobia, nausea) • Urine 6% unchanged, feces 42% unchanged Ubrogepant Pain Freedom* MBS Freedom* Pain Relief* • Half-life = 5 - 7 hours 50 mg 20.6% 38.8% 61.7% 100 mg 21.2% 37.7% 61.4% Placebo 13.3% 27.6% 48.6%

Dodick et al. N Engl J Med 2019;381:2230 Lipton et al. JAMA 2019;322:1887

Ubrogepant (Ubrelvy®) Ubrogepant (Ubrelvy®) Safety Dosage • Most common • 50 or 100 mg orally • Nausea 2 – 4% • Second dose if needed given >2 hours after first • Somnolence 2 – 3% • Serious adverse events or discontinuation 2 – 3% • Max dose 200 mg in 24 hour period • Use with a strong CYP 3A4 inhibitor or inducer: • Safety of treating > 8 migraines in a 30 day period is contraindicated unknown Cost (one dose at the usual lowest dose) • Lasmidtan $80 • Ubrogepant $85 • Oral Triptans $0.9 – $117

Ubrogepant (Ubrelvy®)

New Pharmacological Class More Efficacious Safer Pharmacokinetic Advantage (clinically relevant) More Cost Effective

https://www.biospace.com/article/lundbeck-s-vyepti-is-greenlit-for-the-preventative-treatment-of-migraine/

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Eptinezumab-jjmr (Vyepti®) Eptinezumab-jjmr (Vyepti®) Pharmacology Pharmacokinetics • Humanized immunoglobulin G1 monoclonal • Vd = 3.7 liters antibody specific for CGRP ligand. • Degraded by proteolytic enzymes • Blocks CGRP ligand from binding to its • Half-life ~ 27 days receptor • Not affected by renal or hepatic dysfunction • Indication • An injection for the preventive treatment of migraine in adults

Eptinezumab-jjmr (Vyepti®) Eptinezumab-jjmr (Vyepti®) Efficacy Safety • Two double-blind, randomized trials, one in • Most common episodic migraines and one in chronic migraines • Nasopharyngitis 6 – 8% • IV infusion every 3 months • Hypersensitivity reactions 1 – 2% • Endpoint measured at 12 weeks • Angioedema, rash, pruritis, flushing, hot flashes • Monthly migraine days (MMD) change form baseline • 1.9% patients dropped out due to ADRs • Episodic (n = 665) • Possible development of anti-eptinezumab-jjmr • 100 mg = -3.9 300 mg = -4.3 placebo = -3.2 neutralizing antibodies • Chronic (n = 1072): 15 – 26 headaches per month • 100 mg = -7.7 300 mg = -8.2 placebo = -5.6

Data on file. Lundbeck Seattle BioPharmaceuticals, Inc. 2020

Eptinezumab-jjmr (Vyepti®) Eptinezumab-jjmr (Vyepti®) Dosage • Must dilute in 100 ml 0.9% sodium chloride • 100 mg infusion over 30 minutes every 3 months New Pharmacological Class • Some patients benefit from 300 mg dose More Efficacious Cost Safer • Epitinezumab-jjmr $1794 q 3 months IV Pharmacokinetic Advantage (clinically relevant) • Erenumab $732 monthly SC More Cost Effective • Fremanezumab $482 monthly SC • Galcanezumab $724 monthly SC

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Crizanlizumab-tmca(Adakveo®) Pharmacology • Monoclonal antibody that binds to P-selectin (initiates adhesion of platelets, leukocytes, and sickle erythrocytes to the endothelium). • Inhibits adhesion • Reduces vaso-occlusion • Increases microvascular blood flow • Indication • To reduce the frequency of vaso-occlusive crises in adults and pediatric patients ≥16 years of age with sickle cell disease

https://www.hcp.novartis.com/products/adakveo/sickle-cell-disease/

Crizanlizumab-tmca(Adakveo®) Crizanlizumab-tmca(Adakveo®) Pharmacokinetics Efficacy • Vd = 4.26 L • Double-blind, placebo-controlled trial (n = 198) • Metabolism – catabolism to small peptides • Ages 16 – 65 • Half-life • Any genotype • 7.6 days in sickle cell patients • 2 – 10 sickle cell pain crises in previous year • 60% taking hydroxyurea (continued during study) • 10.6 days in healthy volunteers • Primary endpoint: annual rate of sickle cell pain crises • Crizanlizumab 1.63 • Placebo 2.98

Ataga et al. N Engl J Med 2017;376:429

Crizanlizumab-tmca(Adakveo®) Crizanlizumab-tmca(Adakveo®) Safety Dosage • Most common • 5 mg/kg IV over 30 minutes on weeks 0 and 2, then • Nausea 18% every 4 weeks • Arthralgia 18% • Back pain 15% Cost • Fever 11% • Crizanlizumab $122,571.30/year • Others (all <10%) • Voxelotor $126,739.70/year • Pruritis, abdominal pain, diarrhea, vomiting, infusion site • Hydroxurea $866.50/year pain or swelling

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Crizanlizumab-tmca(Adakveo®)

New Pharmacological Class More Efficacious ? Safer Pharmacokinetic Advantage (clinically relevant) More Cost Effective

https://www.outsourcing-pharma.com/Article/2019/12/02/US-FDA-approves-Oxbryta-by-GBT-for-sickle-cell-disease

Voxelotor (Oxbryta®) Voxelotor (Oxbryta®) Pharmacology Pharmacokinetics • Sickle hemoglobin (HbS) polymerizes when • High fat, high calorie meal increases Cmax by 45% deoxygenated > red blood cell sickling and • Distributed in to RBCs membrane damage • Protein binding 98% • Voxelotor binds to HbS inhibiting polymerization • Hepatic metabolism • Indication • CYP3A4 involved • Treatment of sickle cell disease in patients >12 years • Half-life ~ 35 hours • Excretion: • Feces 63% (33% as unchanged) • Urine 36%

Voxelotor (Oxbryta®) Voxelotor (Oxbryta®) Efficacy Safety • Double-blind, placebo-controlled trial (n = 274) • Most common • Age 12 – 65 years • Headache 26% Fatigue 14% • 1 to 10 vaso-occlusive crises in previous year • Skin rash 14% • Hemoglobin level 5.5 – 10.5 g/dL • Diarrhea 20% Abdominal pain 19% Nausea 17% • 66% patients on hydroxyurea (continued during study) • Fever 12% • Endpoint: increase from baseline hemoglobin of >1.0 at • Hypersensitivity reaction (mild) <10% week 24 • Other • Results: • Hypersensitivity reaction (severe) <1% • 900 mg dose 33% • 1500 mg dose 51% • Pulmonary embolism 1% • Placebo 7% • Decrease in sickle cell crises not determined

Vichinsky et al. N Engl J Med 2019;381:509

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Voxelotor (Oxbryta®) Voxelotor (Oxbryta®) Dosage • 1500 mg orally once daily • If dose missed, continue on the next day New Pharmacological Class • With strong 3A4 inhibitor, 1000 mg daily More Efficacious ? Cost Safer • Crizanlizumab $122,571.30/year Pharmacokinetic Advantage (clinically relevant) • Voxelotor $126,739.70/year More Cost Effective • Hydroxurea $866.50/year

Solriamfetol (Sunosi®) Pharmacology • A dopamine and norepinephrine • Other options for this indication include: • Modafinil (Provigil®) and Armodafinil (Nuvigil®): • both work by inhibiting dopamine reuptake • Amphetamine salts (Adderall® and generics) • Sympathomimetic stimulants • Methylphenidate (Ritalin® and generics) • Promote release of dopamine and norepinephrine and inhibit their reuptake • Indication: • Excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea (OSA)

® Solriamfetol (Sunosi®) Solriamfetol (Sunosi ) Efficacy Pharmacokinetics • Two 12-week double blind, placebo-controlled efficacy • Tmax = 2 hours trials (narcolepsy, n = 239 and OSA, n = 476) • Metabolism – minimal • Looked at Maintenance of wakefulness test (MWT) And Epworth Sleepiness Scale (ESS) • Elimination • For the narcolepsy trial • Urine: >95%, ~ 95% unchanged • MWT improvement for 150 mg and 300 mg dose • ESS improvement for 75, 150, and 300 mg dose • Half-life = around 7 hours • For the OSA trial • Improvement with both tests at 37.5, 75, 150, and 300 mg • In withdrawal trial, responders to drug randomly switched to drug or placebo. • Placebo: significant increase in sleepiness

Thorpy et al. Ann Neurol 2019;85:359 Schweitzer et al. Am J Respir Crit Care Med 2019;199:1421 Strollo et al. Chest 2019;155:364

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Solriamfetol (Sunosi®) Solriamfetol (Sunosi®)

Safety Dosage • Narcolepsy: start with 75 mg po once daily • Most common • OSA: start with 37.5 mg po once daily • Transient headache 16% • Can be doubled every 3 days up to 150 mg po once daily • Nausea, decreased appetite, dry mouth, anxiety, insomnia > 5% • Take upon awakening. NOT within 9 hours of planned sleep • May increase blood pressure and heart rate • Note: a Schedule IV medication Cost (30 day supply) • Do not use within 14 days of a MAO inhibitor Solriamfetol once daily $660 • Increased risk of hypertensive crisis Armodafinil once daily $66 Modadinil once daily $60 Methylphenadate twice daily $15 Amphetamine salts twice daily $20

Solriamfetol (Sunosi®)

. Tenapanor (Ibsrela ®) - IBS-C

. Lactitol (Pizensy ®) – chronic idiopathic constipation (off label: hepatic encephalopathy) New Pharmacological Class . (Barhemsys ®) – post-op nausea and vomiting . Ruxolitinib (Jakafi®) – steroid-refractory acute graft versus host disease More Efficacious . PrabotulinumtoxinA (Jeuveau®) – frown lines . Trifarotene (Aklief ®) - acne Safer . Suberabsorbent hydrogel (Plenity®) – weight loss . Risankizumab (Skyrizi®) – plaque psoriasis

Pharmacokinetic Advantage (clinically . Istradefylline (Nourianz®) – Parkinson’s Disease relevant) . Lumateperone (Caplyta ®) – . Imipenem, cilastatin, relebactam (Recarbrio®) – intra-abdominal and urinary tract infections More Cost Effective . Pitolisant (Wakix®) – excessive daytime sleepiness . Semaglutide (Rybelsus ®) – first oral GLP-1 receptor agonist

. Bempedoic (Nexletol ®) - first in class lipid lowering agent

. L-lactic acid, citric acid, potassium bitartrate (Plexxi ®) – non-hormonal contraceptive gel

. Lemborexant (DayVigo ®) by Eisai

UPDATE . Update on drugs from last year’s list… .Background . Aducanumab – Treatment of Alzheimer’s Disease. Monoclonal antibody that clears beta-amyloid . . UPDATE: Phase III trials terminated 7,000 medicines in development . NKTR-181 – An opioid with a lower risk of dependence .74 % represent a new pharmacologic class . Less euphoria produced . Low permeability across the blood/brain barrier . FDA Advisory Committee meeting postponed . Sotagliflozin – SGLT-1 and SGLT-2 inhibitor used in addition to insulin therapy in Type I diabetes . First oral treatment for Type I diabetes . March 22, 2019: FDA “could not approve application in its present form” . Viaskin Peanut – Immunotherapy for the treatment of peanut allergy . Vericiguat – 10% drop in risk for CV death or first heart failure hospitalization (high risk heart failure patients)

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. Diabetes (just the tip of the iceberg) . Asthma and Allergy (just the tip of the iceberg) . Immunotherapies: . Insulin inhalation powder Type I in pediatrics in Phase II . Grass pollen, peanut allergy, cat allergy, cow’s milk, dust mites . Bimagrumab Type II in Phase II . Allergic Rhinitis: . Type II-B activing receptor modulator . Several new combination drugs . BTI-320 Type II in Phase II . AOB201 Phase II . Alpha glucosidase inhibitor . Intranasal ammonia oxidizing bacteria-based agent . CHS-131 Type II completed Phase II . Asthma: . PPARy modulator and partial agonist . AZD1419 Phase II . CLBS03 Type I, recent onset in Phase I (fast track) . TLR9 agonist . Ex-vivo expanded polyclonal regulatory T lymphocyte cell therapy . CJM112 Phase II (severe asthma) . IL17 protein inhibitor . Islet cell replacement therapy Type I in Phase I/II . QAW039 Phase III . Golimumab Type I in Phase II . Prostaglandin D2 receptor antagonist . Also for pre-symptomatic Type I in Phase I . Tezeplumab Phase III (severe uncontrolled asthma) . TSLP inhibitor Source: wwww.phrma.org Source: wwww.phrma.org

. Mental Health (Anxiety) . Mental Health (Depression) . AVN-101 serotonin6 receptor antagonist anxiety Phase II . Apimostinel partial NMDA receptor agonist MDD Phase II . BLI-1005 NET inhibitor MDD Phase II . ELND05 amyloid beta-protein inhibitor agitation in . BTRX-246040 nociception receptor antagonist MDD Phase II Alzheimer’s disease Phase II . CERC-301 NR2B selective NMDA antagonist MDD Phase II . Eltoprazine serotonin 1A/1B partial agonist agitation in . Ganaxolone GABA-A receptor agonist PPD Phase II Alzheimer’s disease Phase II . JNJ-39393406 alpha7 nicotinic acetylcholine . FKW00GA serotonin 1A receptor agonist social phobia receptor modulator MDD Phase II serotonin 2A receptor antagonist Phase II . MIN-202 orexin2 antagonist MDD Phase II completed . NSI-189 neurogenesis stimulant MDD Phase II . JNJ-42165279 FAAH inhibitor social anxiety disorder Phase II . PH10 nasal spray chemoreceptor cell modulator MDD Phase II . NBTX-001 NMDA receptor antagonist social anxiety disorder Phase II . Rapastinal NMDA receptor agonist MDD Phase III . SRX246 vasopressin-1A antagonist PTSD Phase II . SAGE-217 GABA A receptor modulator MDD/PPD Phase II . TNX-102 SL cyclobenzaprine (low dose) PTSD/fibromyalgia Phase III (note: SAGE-47 for PPD in Phase III)

Source: wwww.phrma.org Source: wwww.phrma.org

. Mental Health (others)

. Phase III - 4 Phase II - 12 Phase I – 15 . Substance Abuse* Phase III - 4 Phase II - 18 Phase I – 9 *includes opioids, cocaine, tobacco, alcohol

[email protected]

Source: wwww.phrma.org

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