1、Corporate PresentationJanuary 10,2024 2024 Enanta Pharmaceuticals,Inc.|This presentation contains forward-looking statements concerning our business,operations and financial performance andcondition,as well as our plans,objectives and expectations for our research and development programs,our busine

2、ss and theindustry in which we operate.Any statements contained herein that are not statements of historical facts may be deemed to beforward-looking statements.In some cases,you can identify forward-looking statements by terminology such as“aim,”“anticipate,”“assume,”“believe,”“contemplate,”“contin

3、ue,”“could,”“due,”“estimate,”“expect,”“goal,”“intend,”“may,”“objective,”“plan,”“predict,”“potential,”“positioned,”“seek,”“should,”“target,”“will,”“would,”and other similar expressions that are predictions of orindicate future events and future trends,as well as other comparable terminology.These for

4、ward-looking statements include,but arenot limited to,statements about overall trends,royalty revenue trends,research and clinical development plans and prospects,liquidity and capital needs and other statements of expectations,beliefs,future plans and strategies,anticipated events or trends,and sim

5、ilar expressions.These forward-looking statements are based on our managements current expectations,estimates,forecasts and projections about our business and the industry in which we operate and our managements beliefs and assumptions.These forward-looking statements are not guarantees of future pe

6、rformance or results and involve known and unknown risks,uncertainties and other factors that are in some cases beyond our control.As a result,any or all of our forward-looking statementsin this presentation may turn out to be inaccurate.Please refer to the risk factors described or referred to in“R

7、isk Factors”in Enantas most recent Annual Report on Form 10-K,andother periodic reports filed with the Securities and Exchange Commission.Enanta cautions investors not to place undue reliance onthe forward-looking statements contained in this presentation.These statements speak only as of the date o

8、f this presentation,andEnanta undertakes no obligation to update or revise these statements,except as may be required by law.Forward Looking Statements Disclaimer2 2024 Enanta Pharmaceuticals,Inc.|Using a proven,chemistry-driven approach to develop best-in-class small molecule drugs for virology and

9、 immunology indicationsA Proven Approach to Drug DiscoveryProven Track Record of SuccessRobust PipelineStrong balance sheet and royalties to support robust pipeline$370M in cash at September 30,2023Glecaprevir:HCV protease inhibitor in MAVYRET/MAVIRETStrong Balance Sheet Virology:Phase 2 in pediatri

10、c patients with RSV(RSVPEDs)Phase 2 in high-risk adults with RSV(RSVHR)Phase 2 challenge study with second RSV candidate Phase 2 in COVID-19 complete(SPRINT)Phase 1b in HBV patients completeImmunology:New program in Chronic Spontaneous Urticaria3Our Therapeutic FocusLeveraging our core strength in s

11、mall molecule drug discovery to develop treatments for high unmet needsImmunologyCSUVirologyRSVHCVCOVID-19HBV 2024 Enanta Pharmaceuticals,Inc.|PRODUCT CANDIDATEDISCOVERYPRECLINICALPHASE 1PHASE 2PHASE 3MARKETVirology:LiverHCVProtease InhibitorHBVCore InhibitorVirology:RespiratoryRSVN-Protein Inhibito

12、rL-Protein InhibitorCOVID-193CL Protease InhibitorImmunologyCSUKIT InhibitorVariousUndisclosedZelicapavir(EDP-938)RSVHREDP-323Zelicapavir(EDP-938)RSVPEDsGlecaprevir*EDP-235 SPRINT*Fixed-dose antiviral combination contains glecaprevir and AbbVies NS5A inhibitor,pibrentasvir.Marketed by AbbVie as MAVY

13、RET(U.S.)and MAVIRET(ex-U.S.).Enanta Pipeline EDP-5145Our Therapeutic FocusLeveraging our core strength in small molecule drug discovery to develop treatments for high unmet needsImmunologyCSUVirologyRSVHCVCOVID-19HBV 2023 Enanta Pharmaceuticals,Inc.|Glecaprevir(licensed to AbbVie)is key ingredient

14、in MAVYRETFiscal 2023 GAAP Royalty Revenue(in millions)Effective Q4:2023,Enanta sold 54.5%of future royalty cash payments for$200M cash paymentAfter royalty sale,Enanta will:receive 45.5%of the royalty cash paymentscontinue to record 100%of royalty revenue earned in its GAAP reporting*Glecaprevir:Ou

15、r Licensed Protease Inhibitor for Hepatitis C Virus7ProductRegimen2-DAA(AbbVie)Enanta AssetGlecaprevir(protease inhibitor)Q1Q2Q3Q4Total$22.4$17.8$18.9$18.9$78.2*Royalty sale is accounted for as debt because royalty buyer gets up to a total cap of 1.42 x the$200M sale priceOur Therapeutic FocusLevera

16、ging our core strength in small molecule drug discovery to develop treatments for high unmet needsImmunologyCSUVirologyRSVHCVCOVID-19HBV 2024 Enanta Pharmaceuticals,Inc.|Populations at higher risk for severe illness:Pediatrics(infants and children)High-risk adults(65 yrs,COPD,asthma,CHF)Immunocompro

17、mised(e.g.HIV,transplant)Respiratory Syncytial Virus(RSV)RSV at a GlanceChildren 65 years233M global cases3M global hospitalizations177K U.S.hospitalizations101K global deaths14K U.S.deathsCauses severe lung infections,including bronchiolitis(infection of small airways in the lungs)and pneumonia(an

18、infection of the lungs).No safe and effective treatments.Sources:1.https:/ 2.https:/pubmed.ncbi.nlm.nih.gov/15858184/3.https:/www.cdc.gov/nchs/products/databriefs/db370.htm:33.4%in 2016&34.5%in 2018 for Age 60+4.https:/www.cdc.gov/flu/fluvaxview/dashboard/vaccination-coverage-adults-65-over.htm:54%2

19、021-2022;58%2020-2021;56%2019-2020 for age 65+Significant unmet need for antiviral treatment despite availability of prophylaxis:Adoption of prophylactic approaches with shared clinical decision-making likely to be sub-optimalPeak adoption of universally recommended vaccines for elderly range from 3

20、5%(shingles3)to 55%(flu4)Pediatric prophylaxis approaches provide passive immunity;will shift first infection to next seasonAntibody approach has a low barrier to resistanceEven with adoption,breakthrough infections will still occur9 2024 Enanta Pharmaceuticals,Inc.|Zelicapavir is the only N-inhibit

21、or in clinical developmentDirectly targets viral replication vs entryGranted Fast Track designation by the FDAStrong preclinical profileNanomolar potency against RSV-A and RSV-BAntiviral potency across all clinical isolates testedHigh-barrier to resistance Synergy with other drug mechanisms(e.g.fusi

22、on and L-inhibitors)No cross-resistance with other mechanismsZelicapavir(EDP-938):N-Protein Inhibitor for RSVRSV10 2024 Enanta Pharmaceuticals,Inc.|Zelicapavir:Robust Antiviral Effect in Human Challenge ModelRapid and Sustained Reduction in Viral Load in Both Active Arms Compared to Placebo(71%,74%A

23、UC;P0.001)First DoseDosing Period11Source:Ahmad,Alaa et al.“EDP-938,a Respiratory Syncytial Virus Inhibitor,in a Human Virus Challenge.”The New England Journal of Medicine vol.386,7(2022):655-666.doi:10.1056/NEJMoa2108903 2024 Enanta Pharmaceuticals,Inc.|Zelicapavir:Robust Symptom Reduction in Human

24、 Challenge ModelRapid and Sustained Attenuation of RSV Symptoms in Both Active Arms Compared to Placebo(68%,74%AUC;P0.001)First DoseDosing Period12Source:Ahmad,Alaa et al.“EDP-938,a Respiratory Syncytial Virus Inhibitor,in a Human Virus Challenge.”The New England Journal of Medicine vol.386,7(2022):

25、655-666.doi:10.1056/NEJMoa2108903 2024 Enanta Pharmaceuticals,Inc.|PropertiesZelicapavir/EDP-938Ziresovir/AK0529Sisunatovir/PF-079235681MechanismN inhibitorFusion inhibitorFusion inhibitorPre-clinical Effectiveness After InfectionYesNoNoClinical Efficacy(challenge study4)Viral Load Reduction275%(p0.

26、001)n/a55%(p=0.007)Symptoms371%(p0.02)n/a71%(p=0.018)Resistance BarrierHighLowLowDosing Frequency 5 days;QD5 days;BID5 days;BIDStage of DevelopmentGlobal Phase 2(Peds,HR Adults)Regulatory Review China5(Peds)Phase 2/3(HR Adults)Zelicapavir:Potential to be the Leading Antiviral Treatment for RSVOnly i

27、ncludes compounds in development with clinical data in patientsSources:1.DeVincenzo et al,2020;AAC;64(2);2.%reduction in viral load(VL)area under the curve(AUC)as measured by qPCR;3.%reduction in total symptom score(TSS)AUC;4.Data from selected dose moving forward 5.Ark Bio Press Release December 20

28、22HR=high risk;HCT=Hematopoietic Cell Transplant Recipients.n/a=not available;challenge study not performed13 2024 Enanta Pharmaceuticals,Inc.|Zelicapavir:Summary of Data Across Completed Clinical StudiesSafety SummaryGenerally safe and well-toleratedAdverse events infrequent,generally mild,and reso

29、lved in follow-upConsistent safety profile observed in approximately 500 subjects exposed to dateEfficacy Summary in Healthy AdultsPhase 2a challenge study:highly statistically significant(p4)Other COVID protease inhibitors lung to plasma AUC ratio 3 days and 5 days)prior to randomization23 2024 Ena

30、nta Pharmaceuticals,Inc.|SafetyEDP-235 was generally safe and well-toleratedLow frequency of adverse events;most were mild in severity1.3%,6.4%,and 2.6%in the EDP-235 200mg,400mg and placebo armsNo serious adverse events or discontinuations due to adverse eventsClinical SymptomsStatistically signifi

31、cant improvement in total symptom score(TSS)achieved at multiple timepoints for EDP-235 400mgPatients enrolled within 3 days of symptom onset showed a statistically significant improvement in TSS at all time pointsEffect enhanced in prespecified population enrolled within 3 days of symptom onset in

32、a subset of 6 symptomsNo difference in time to 14 symptom improvement for EDP-235 compared with placeboStatistically significant reduction in median time to symptom improvement with EDP-235 400mg vs placebo for subset of 6 symptomso1-day improvement in full ITT-c populationo2-day improvement in pati

33、ents enrolled within 3 days of symptom onsetMedian time to improvement was 3 days with EDP-235 vs 5 days with placeboSPRINT:Safety and Symptom Summary24Full SPRINT study data presentation found here.2024 Enanta Pharmaceuticals,Inc.|No difference between treatment arms and placebo for viral RNA decli

34、ne(ITTc)High degree of nucleocapsid seropositivity and rapid decline in viral RNA from nasal swabs in placebo arm indicate a highly immune population that quickly cleared virus from the noseObserved symptom effects suggest that nasal sampling may not accurately reflect the impact of EDP-235 on virus

35、 in other tissuesAdditional analyses demonstrate a virologic effect in multiple subsets of patients,with a placebo-adjusted viral load decline at Day 5 in the 400mg group of:0.4 log:baseline viral load greater than 5 log0.8 log:nucleocapsid seronegative(suggesting no recent natural infection)1 log:n

36、ucleocapsid seronegative and symptom onset within 3 daysSPRINT:Virology Summary25Our Therapeutic FocusLeveraging our core strength in small molecule drug discovery to develop treatments for high unmet needsImmunologyCSUVirologyRSVHCVCOVID-19HBV 2024 Enanta Pharmaceuticals,Inc.|In 2019,hepatitis B re

37、sulted in an estimated 820,000 deaths,mostly from cirrhosis and hepatocellular carcinoma(primary liver cancer)1Current treatments rarely give true curesInterferon is 10%effective,but with side effects2Reverse-transcriptase inhibitors effective at reducing viral load,but low cure rates(1%or lower)and

38、 treatment for life to improve cirrhosis or HCC outcomes3Hepatitis B Virus(HBV)HBV at a Glance U.S.850K 2M people4Europe and European Economic Area4.7M people5Worldwide290M people6Sources:1.https:/www.who.int/news-room/fact-sheets/detail/hepatitis-b 2.https:/www.ncbi.nlm.nih.gov/pmc/articles/PMC5401

39、664/3.https:/pubmed.ncbi.nlm.nih.gov/30342034/4.https:/ 5.https:/www.ncbi.nlm.nih.gov/pmc/articles/PMC5356432/6.https:/pubmed.ncbi.nlm.nih.gov/29599078/Potentially life-threatening liver infection27 2024 Enanta Pharmaceuticals,Inc.|EDP-514:HBV Core InhibitorHBV28Oral direct-acting antiviral targetin

40、g the HBV core proteinGranted Fast Track designation by the FDAStrong preclinical virologic profilePotent activity in HBV expressing stable cell linesCapable of preventing the establishment of cccDNAPan-genotypic activityRobust efficacy data in chimeric liver mouse modelPhase 1 demonstrated good saf

41、ety and tolerability with PK supportive of once-daily dosing with no food effectTwo Phase 1b studies in HBV patients demonstrated significant reductions in HBV DNA and RNA after 28 daysNUC-suppressed patients:mean reduction in HBV RNA of up to 1 log compared with 0.2 log in placebo Viremic patients:

42、Mean reductions in HBV DNA of 3-3.5 logs across dose groups vs 0.2 log in placeboOur Therapeutic FocusLeveraging our core strength in small molecule drug discovery to develop treatments for high unmet needsImmunologyCSUVirologyRSVHCVCOVID-19HBV 2024 Enanta Pharmaceuticals,Inc.|Expand to Immune-media

43、ted Chronic DiseasesDISCOVERY Understanding of disease pathologyDEVELOPMENTKnown clinical path and markers for early clinical signalMARKET OPPORTUNITY Improved oral treatments addressing significant unmet needFoundational Enanta CapabilitiesSTRONG DISCOVERY EXPERTISE Underlying chemistry is broadly

44、applicable across targetsVIROLOGY&IMMUNOLOGY Scientificallyadjacent areasPROVEN DRUG DISCOVERY PLATFORMDifferentiated small molecules for established and novel targets Leveraging Enantas Core Strengths for Immune Driven Diseases30 2024 Enanta Pharmaceuticals,Inc.|Severely debilitating,chronic inflam

45、matory skin disease1,2Driven by mast cell activation,triggering release of inflammatory mediatorsQuality of life impacts beyond the skin:sleep disturbances,fatigue,irritability,anxiety and depressionAffects 0.5-1%of the global population1Substantial unmet need for efficacious oral agent50%not contro

46、lled with antihistamines1,3Minority treated with one indicated biologic(28%)4Chronic Spontaneous Urticaria(CSU)Sources:1.Maurer M,et al.Allergy.2011;66(3):317330.2.Yosipovitch et al.Dermatol Ther.2023;13(8):16471660.3.H1 antihistamines up to 4x standard dose.4.Clarivate Treatment Algorithms:Claims D

47、ata Analysis-Chronic spontaneous urticaria,February 2023.2023 DR/Decision Resources,LLC.All rights reserved.Reproduction,distribution,transmission or publication is prohibited.Reprinted with permission.Clarivate makes no representation or warranty as to the accuracy or completeness of the data(“Clar

48、ivate Materials”)set forth herein and shall have,and accept,no liability of any kind,whether in contract,tort(including negligence)or otherwise,to any third party arising from or related to use of the Clarivate Materials by Enanta Pharmaceuticals Inc(“Enanta Pharmaceuticals Inc”).Any use which Enant

49、a Pharmaceuticals Inc or a third party makes of the Clarivate Materials,or any reliance on it,or decisions to be made based on it,are the sole responsibilities of Client and such third party.In no way shall any data appearing in the Clarivate Materials amount to any form of prediction of future even

50、ts or circumstances and no such reliance may be inferred or implied.HivesItchErythemaAngioedema31 2024 Enanta Pharmaceuticals,Inc.|KIT Inhibitors:Potential for Best-in-Disease EfficacyMast cells:primary driver of inflammation in skin,and implicated in multiple allergic diseasesCSU,chronic inducible

51、urticaria(CIndU),asthma,eosinophilic esophagitis(EoE),prurigo nodularis(PN)KIT:well-characterized receptor tyrosine kinase critical for regulating mast cell activityKIT inhibitors:potential for best-in-disease efficacyDirectly reduces quantity of mast cells through apoptosis and depletion,addressing

52、 key disease driverCurrent therapy reduces mast cell activator levels(eg;signal inhibition)or downstream mediators,but not mast cells themselvesPositive proof-of-concept in Phase 2 with anti-KIT mAbTherapeutic Targets for CSUActivated Mast Cell32 2024 Enanta Pharmaceuticals,Inc.|Novel,oral,potent an

53、d selective inhibitors of KIT being optimized in preclinical developmentPrototype KIT inhibitors:Potently inhibit KIT activity in both binding and cellular function assaysHighly selective for KIT versus other kinasesGood in vitro and in vivo ADME properties Targeting selection of a development candi

54、date in 2024KIT Inhibitor Discovery Program33 2024 Enanta Pharmaceuticals,Inc.|Prototype inhibitor exhibits potent inhibition of KIT in binding and cellular functional assaysPrototype KIT Inhibitor Demonstrates Potent ActivityKINOMEscan Kd(nM)Endogenous Cellular EC50(nM)Engineered Cellular EC50(nM)P

55、rototype Inhibitor0.3173.4KINOMEscan:high throughput competitive binding assay that measures tagged kinase binding to an immobilized ligandEndogenous Cellular:Growth inhibition assay using KIT expressing M-07e cellsEngineered Cellular:Growth inhibition assay using KIT expressing Ba/F3 cells34 2024 E

56、nanta Pharmaceuticals,Inc.|Prototype KIT Inhibitor Shows Greater Selectivity Compared to Other Inhibitors in DevelopmentPrototype-001THB33511.Third Harmonic Bio Corporate Deck December 2023KITKINOMEscan at 100 nM35 2024 Enanta Pharmaceuticals,Inc.|Good PK profile across multiple preclinical species(

57、dog,mouse and rat)Low potential for off-target penetration(e.g.;brain,testes and ovaries)Long half-life and no GSH adducts in human liver microsome incubationLow drug-drug interaction potential via CYP enzymesExcellent transporter selectivityPrototype KIT Inhibitor has Favorable ADME Profile36 2024

58、Enanta Pharmaceuticals,Inc.|Respiratory Syncytial Virus Zelicapavir:Report Phase 2 data in at least one study in 3Q EDP-323:Report Phase 2a challenge study data in 3Q 2024 Key CatalystsChronic Spontaneous Urticaria Select KIT inhibitor development candidateNew Program Initiate lead optimization37VirologyImmunologyBusiness DevelopmentSARS-CoV-2 EDP-235:Pursue partnership for Phase 3 studyHepatitis B Virus EDP-514:Identify third mechanism and/or out-