瑞信-美股-生物科技行业-美国生物科技行业模型更新-2019.2.10-47页.pdf

DISCLOSURE APPENDIX AT THE BACK OF THIS REPORT CONTAINS IMPORTANT DISCLOSURES,ANALYST CERTIFICATIONS,LEGAL ENTITY DISCLOSURE AND THE STATUS OF NON-US ANALYSTS.US Disclosure:Credit Suisse does and seeks to do business with companies covered in its research reports.As a result,investors should be aware that the Firm may have a conflict of interest that could affect the objectivity of this report.Investors should consider this report as only a single factor in making their investment decision.10 February 2019Americas/United StatesEquity ResearchBiotechnology U.S.Biotechnology COMMENTResearch AnalystsMartin Auster,M.D.212 325 6573martin.austercredit-Tiago Fauth212 325 7569tiago.fauthcredit-Mark Connolly212 325 7576mark.connollycredit-Model UpdatesModel Changes.We updated our models to incorporate quarterly 2019 projections.We decreased our TP for XLRN(from$60/sh to$58/sh)and RARX(From$34/sh to$32/sh).We also revised our estimates for BMRN,SRPT,UTHR,RARE,ONCE,ANAB,OBSV,FTSV and ETTX.CategoryEarnings Focus AreasQ1 CatalystsCommercial UpdatesProgram Status Updates10 February 2019U.S.Biotechnology2Figure 1:Catalysts Across Our Coverage UniverseTickerCatalystTimingALXNALXN1210-gMG Phase 3 Trial to initiateearly 2019ALXNOral Proceedings-New Soliris CoM Patent in EUPostponed,TBDALXNSYNT001 Phase 1b/2a in WAIHA1H 2019ALXNSoliris-NMO US Launchanticipated H2 2019ALXNSYNT001 Phase 3 WAIHA Trial to initiate2H 2019ALXNALXN1210-ALS PoC Trial2019ALXNALXN1210-PPMS PoC Trial2019ALXNALXN1210-NMO Phase 3 Trial to initiate2H 2019ALXNWTX-101 Ph3 Complete enrollmentby YE 2019ALXNALXN1210 IV 100mg/ml Formulation Launch2020ALXN1210 Weekly SC FilingQ1 2021ALXNWTX-101 Ph3 Data2021ALXNALXN1810 SC(1210+PH20)Potential Launch2023BMRNBMN290 IND Submission2H 2018BMRNPegvaliase CHMP OpinionQ1 2019BMRNValrox Ph3 Enrollment Completion-6E13Q3 2019BMRNValrox Ph2-2yr Update 4E13;3yr Update 6E13Mid-2019BMRNValrox Decisionon Potential Accelerated Filing2H 2019BMRNBMN 307(PKU Gene Therapy)IND Filing2H 2019BMRNBMN250 Ph1/2 Update2019BMRNValrox Ph3 Enrollment Completion-4E132019BMRNVosoritide Ph3 ResultsYE 2019BMRNValrox Ph3 ResultsMid-2020SRPTExon 51 Amenable(Exon Skipping)SRPTSRP-5051(Exon 51)Ph1 Safety ResultsEarly 2019SRPTExondys 51 PROMOVI Ph3 Results(May Support EU Approval)2019SRPTWaves WVE-210201 Initial Efficacy Data2H 2019SRPTSRP-5051(Exon 51)Ph2 Initial Efficacy DataEarly 2020SRPTExon 53 Amenable(Exon Skipping)SRPTSRP-5053(Exon 53)IND FilingEnd 2018SRPTGolodirsen(exon 53)Potential US ApprovalMid-2019SRPTExon 45 Amenable(Exon Skipping)SRPTCasimersen(Exon 45)ESSENCE-48 Wk Biopsy to Support Possible Accelerated ApprovalEarly 2019SRPTCasimersen(Exon 45)Possible NDA Submission Based on Dystrophin ImprovementMid-2019SRPTOther-Exon SkippingSRPTIND Submissions for Several Other PPMOs2019SRPTCasimersen and Golodirsen ESSENCE Ph3 Full Trial Results2020SRPTDMD Gene TherapySRPTNovartis-AVXS-101(SMA Gene Therapy)Pricing 1H 2019SRPTUpdated Results for SRPTs DMD Gene Therapy Ph1/2Possibly 1H 2019SRPTPFEs PF-06939926 DMD Gene Therapy Initial Ph1/2 Results2H 2019SRPTSLDBs SGT-001 DMD Gene Therapy Ph1/2 Results-Update2H 2019SRPTManufacturing Update/Commencement of Confirmatory Trial2H 2019SRPTLGMD Gene TherapySRPTMYO-101 60-Day Biopsy Data-LGMD 2EEarly 2019SRPTMPS 3A Gene TherapySRPTCommencement of the LYS-SAF302 Pivotal TrialYE 2018SRPTCMT Gene TherapySRPTCommencement of the Ph1/2 clinical trial in CMT Type 1A2019Source:Company data,Credit Suisse estimates10 February 2019U.S.Biotechnology3Figure 2:Catalysts Across our Coverage Universe(cont.)TickerCatalystTimingUTHRRemodulin Generic Launch?UTHRRemoPro IND FilingH2 2018UTHRRemUnity Regulatory Process Updatesubmission in Jan,approval expected H1 2019UTHRBEAT Study ReadoutQ2 2019UTHROrenitram Label Expansion(FREEDOM-EV)2019UTHRISR Commercial Launchearly-2019UTHRRalinepag-Phase 3 Program Initiation2H 2018/1H 2019UTHRTRITON(early oral triple therapy in PAH)2020UTHRRalinepag-Differentiation Study Readoutmid-2020UTHRRalinepag-Exercise Capacity Ph3 Readoutsmid-2021UTHRRalinepag-Events Ph3 Readout1H 2022RARECrysvita-Finalize registration plan in TIOH1 2019RAREDTX301-OTC Ph 1/2 Cohort 3 DataMid-2019RAREDTX401-GSDIa Ph 1/2 Cohort 2 DataMid-2019RAREUX007-FAOD NDA Filing Mid-2019ARNARalinepag-Phase 3 Program Initiation2H 2018/1H 2019ARNAEtrasimod-UC Phase 3 InitiationMid-2019ARNAEtrasimod-Phase 2/3 in Crohns Disease Intiation 2H 2019ARNAEtrasimod-Phase 2 in Atopic Derm Initiation2H 2019ARNAEtrasimod-PBC Phase 2a Datalate 2019/early 2020ARNAOlorinab-Phase 2b IBD/IBS Pain Initiation2019ARNAAPD418-IND2019XLRNLuspatercept NDA/MAA-Refractory MDS and TD Bthal1H 2019XLRNACE-2494 Preliminary Ph1 Results in Healthy Volunteers1H 2019XLRNLuspatercept-Potential Expansion into Other Indications2019XLRNACE-083 Ph2 Part 2 FSHD Results2H 2019XLRNACE-083 Ph2 Part 2 CMT ResultsYE 2019XLRNLuspatercept Myelofibrosis Ph2 Results2H 2019XLRNLuspatercept BEYOND NTD Ph2 Results2020XLRNSotatercept PULSAR PAH Ph2 Results1H 2020INSMQuarterly Earnings2019INSMComplete the Design/Protocol of the Arikayce Confirmatory Trial1H 2019INSMArikayce EU MAA filingMid-2019INSMINS1007 Ph2 NCFBE Enrollment CompletionMid-2019INSMArikayce Japan Regulatory Filing1H 2020ANABEtokimab Asthma-Phase 2a Detailed Data2019ANABANB019 GPP-Phase 2 Datamid-2019ANABANB019 PPP-Phase 2 DataH2 2019ANABEtokimab Atopic Dermatitis-Phase 2b DataH2 2019ANABEtokimab CRSwNP-Phase 2 DataH2 2019MYOKMavacamten PIONEER-OLE 6-Month DataMarch 2019MYOKInitiate MYK-224 Ph1 Clinical Trial2H 2019MYOKMYK-491 Ph2a Data2H 2019MYOKMavacamten MAVERICK-HCM Ph2 Results(noHCM)2H 2019MYOKMavacamten PIONEER-OLE 12-Month Data2H 2019MYOKMavacamten EXPLORER Ph3 oHCM Enrollment CompletionMid/Late 2019MYOKAmgen/Cytokinetics Complete Enrollment of Omecamtiv Mercarbil Ph32019MYOKInitiate Mavacamten Ph2/3 Trial in noHCM1H 2020MYOKInitiate MYK-491 Ph2/3 Clinical Trial2H 2020MYOKMavacamten EXPLORER-HCM Ph3 Results2H 2020MYOKMavacamten PIONEER-OLE 18-24-Month Data2020Source:Company data,Credit Suisse estimates10 February 2019U.S.Biotechnology4Figure 3:Catalysts Across our Coverage Universe(cont.)TickerCatalystTimingONCESPK3006(Pompe)INDQ2 2019ONCESPK-1001(CLN2 disease)IND-enabling studiesH1 2019ONCESPK-8011 Additional Ph 1/2 Datamid-2019ONCESPK-8016(hem A inhibitor)Initial Data2019PTCTRisdiplam FIREFISH Top-Line ResultsPotentially 1H 2019PTCTAVXS-101 Initial STRONG Type 2 Clinical Data1H 2019PTCTAVXS-101 SPRINT(Pre-Symptomatic)Trial ResultsAAN 2019PTCTAVXS-101 Possible Approval(IV)May 2019 PDUFAPTCTRisdiplam SUNFISH Top-Line ResultsLate 2019PTCTTranslarna Dystrophin Trial ResultsEnd 2019PTCTPotential Tegsedi Approval-BrazilYE2019PTCTPTC-258 for Familial Dysautonomia-IND Filing2019PTCTFriedreich Ataxia Gene Therapy IND2019PTCTBLA/MAA Submissions for AADC Deficiency Gene Therapy2019PTCTTranslarna Confirmatory Trial(Study 41)-Results2H 2021ESPRPh2 Results of Sustained Release Formulation of BA in NASH1Q 2019ESPRBA NDA Submission1Q 2019ESPRBA MAA Submission2Q 2019ESPRCLEAR Outcomes Enrollment Completion3Q 2019ESPRPh2 BA FDC Results in Patients with High LDL-C and T2D2H 2019ESPRPotential BA US and EU Approval1H 2020ESPRCLEAR Outcomes Results2022SLDBNovartis-AVXS-101(SMA Gene Therapy)Pricing 1H 2019SLDBUpdated Results for SRPTs DMD Gene Therapy Ph1/21H 2019SLDBPFEs PF-06939926 DMD Gene Therapy Initial Ph1/2 ResultsQ2 2019SLDBSLDBs SGT-001 DMD Gene Therapy Ph1/2 Results-Update2H 2019RARXRA101495 gMG Phase 2 Detailed Data H1 2019RARXRA101495 gMG end-of-Phase 2 meetingH1 2019RARXRA101495 PNH Phase 3 Trial InitiationH1 2019RARXRA101495 2nd Neurology IndicationH1 2019RARXRA101495 gMG Phase 3 Trial Initiation2019RARXRA101495 Extended Release(XR)IND2H 2019RARXOral Small Molecule C5 Inhibitor IND2H 2019NTLAATTR:Initiate IND-Enabling GLP Toxicology Studies2019NTLAAML:Nominate Development CandidateYE 2019NTLASubmit IND for TTR program2020OBSVLinzagolix Endometriosis Ph3 Trial Commencement1Q 2019OBSVOBE022 Ph2a PROLONG Interim Data(Pre-Term Labor)1Q 2019OBSVNolasiban-Finalize US Ph3 Trial DesignMid-2019OBSVLinzagolix Uterine Fibroids(PRIMROSE 1 and 2)Ph3 6-Month Top-Line Results2H 2019OBSVOBE022 Complete PROLONG Ph2a Follow-Up;Ph2b Commencement2H 2019OBSVNolasiban EU IMPLANT4 in IVF-Results4Q 2019OBSVNolasiban Target EU MAA Submission for IVF4Q 2019OBSVLinzagolix Endometriosis Ph3 Results1H 2021Source:Company data,Credit Suisse estimates10 February 2019U.S.Biotechnology5Figure 4:Catalysts Across our Coverage Universe(cont.)TickerCatalystTimingFTSVNHL-5F9+rituximab Phase 2 Efficacymid-2019FTSVAML-5F9+azacitidine Phase 1/1b Datamid-2019FTSVCRC-5F9+cetuximab Ph1b Safety+Ph 2 EfficacyQ4 2019FTSVOvarian-5F9+avelumab Phase 1b DataQ4 2019FTSVBladder-5F9+atezolizumab Phase 1b Data2020FTSVAML-5F9+atezolizumab Phase 1b Data2020PGNXPSMA-TTC(Bayer)Ph1 initiationYE18PGNX1095 Ph2 initiation Q1 2019PGNXAzedra commercial uptake1H 2019PGNX1095 interim dataend 2019PGNXPyL interim data1Q20PGNXVISION(Ph3 pivotal)Top-line data3Q20ETTXETX2514SUL Initiate Phase 3 trial1Q 2019ETTXETX0282CPDP Phase 1 data readout1H 2019ETTXZoliflodacin Initiate Phase 3 trial2019ETTXNBP Program Select initial clinical candidate2019ETTXETX2514SUL Phase 3 data readout2020ASNDTransCon hGH Ph3 heiGHt top-line dataQ1 2019ASNDTransCon PTH Ph2 InitiationQ1 2019ASNDTransCon hGH Ph3 fliGHt(switch)top-line dataQ2 2019ASNDTransCon hGH Ph3 US subjects switched to auto-injectorQ2 2019ASNDAscendis Research Day-(details on oncology pipeline)Q2 2019ASNDTransCon hGH Database lock for filing packageQ3 2019ASNDTransCon CNP Ph2 InitiationQ3 2019ASNDPotential somatrogon Ph3 data(OPKO/PFE)Q3 2019ASNDTransCon PTH Phase 2 DataQ4 2019ASNDTransCon hGH Regulatory FilingQ1 2020ASNDTransCon hGH Commercial Launch2021IFRXIFX-1 HS Phase 2b DataQ2 2019IFRXIFX-1 New Indication2019IFRXIFX-1 HS Phase 3 Program Startlate 19/early 20Source:Company data,Credit Suisse estimates10 February 2019U.S.Biotechnology6Earnings Focus Areas L90D%Change-1.5%YTD%Change10.7%RatingOUTPERFORMTarget Price$131$96$94Mkt Cap($m)$16,78811/10/20182/8/2019Cash($m)$1,648BioMarin(BMRN,Outperform,Target Price:$131).Focus areas include:Revenue growth and 2019 guidance.See below for current consensusValrox 6E13 vg/kg mid-year update management stated that it is blind to the ongoing Ph1/2 extension,but it has communicated it that would be notified by the DSMB of any emerging safety issues or major bleed events in the extension,suggesting that no news is good news Valrox Ph3 interim analysis 2H 2019 and potential BLA filingVosoritide Ph3(results expected late 2019)BMRN Earnings Call February 21,2019(4:30 pm ET).Dial-in information:(866)502-9859(US/Canada)or(574)990-1362(international).Conference ID:8265006.Figure 1:BMRN CS vs.Consensus($in millions except EPS)CSCons.(%)CSCons.(%)CSCons.(%)Vimizim$125$120$44%$493$488$51%$548$557($10)-2%Naglazyme$80$79$00%$349$349$00%$363$360$31%Kuvan$124$125($0)0%$446$446($0)0%$463$480($17)-4%Aldurazyme$16$17($1)-4%$134$135($1)0%$109$114($5)-5%Firdapse$5$5($0)-1%$20$20($0)-2%$20$20($1)-3%Brineura(Batten)-WW$13$14($0)-1%$41$41($0)0%$89$89($1)-1%Pegvaliase(PKU)$10$9$110%$14$13$17%$94$90$45%Other revenue$5$8($2)-31%$20$23($2)-10%$20$25($5)-21%Total Revenue$379$377$21%$1,517$1,515$20%$1,707$1,736($29)-2%COGS -Non-GAAP$75$74$22%$305$303$21%$324$329($5)-2%R&D-Non-GAAP$159$152$75%$612$604$71%$654$640$142%SG&A-Non-GAAP$137$128$97%$495$486$92%$520$521($1)0%Operating Income-Non-GAAP$8$27($20)-72%$105$124($20)-16%$209$240($31)-13%Income before tax-Non-GAAP$6$26($21)-79%$107$126($19)-15%$209$252($43)-17%Tax expense(benefit)$0$0$0N/A$0$0$0N/A$0$0$0N/ANet income-Non-GAAP$6$26($21)-79%$107$126($19)-15%$209$252($43)-17%Non-GAAP Dil.EPS$0.03$0.15($0.12)-79%$0.61$0.71($0.11)-15%$1.17$1.38($0.21)-15%Shares outstanding(m)178178(1)0%177177(0)0%178182(4)-2%Q4 2018FY 2018FY 2019Source:Company data,Credit Suisse estimates,FOA10 February 2019U.S.Biotechnology7L90D%Change1.9%YTD%Change17.2%RatingOUTPERFORMTarget Price$189$125$128Mkt Cap($m)$8,54511/10/20182/8/2019Cash($m)$1,270Sarepta(SRPT,Outperform,Target Price:$189).Focus areas include:Potential 2019 guidance(the company has provided sales guidance historically).Street estimates$420m 2018 expenses(the company already reported 2018 revenue)DMD competitive landscape(see our DMD monthly for more details)Casimersen(for exon 45 amenable patients).The company expects 48-week biopsy data by Q1 2019,which if positive(at least 1%dystrophin expression),could support an accelerated filingAn update on its PPMO platform.The company has guided for safety data for SRP-5051(its lead PPMO program)in Q1 2019LGMD2E initial data.Our experts believe a win would be(1)dramatic reduction in CK 70-80%+,(2)restoration of the dystrophin/glycan complex,and(3)an increase in-sarcoglycan protein;on this later point,our experts believe 20-30%expression should be sufficient,but caution that functional improvement is likely needed to validate this as a suitable thresholdFigure 2:SRPT CS and Consensus(GAAP)Q4 2018FY 2018FY 2019($in millions except EPS)CSCons.(%)CSCons.(%)CSCons.(%)Total Revenue$84$84($0)0%$301$301$00%$398$416($18)-4%COGS-GAAP$12$10$223%$33$31$27%$48$50($2)-5%R&D-GAAP$79$82($2)-3%$335$337($2)-1%$350$339$113%SG&A-GAAP$56$58($1)-2%$200$201($1)-1%$230$236($6)-3%Other-GAAP$0$0$00%$1$0$1N/A$0$0$0N/AOperating income(loss)($64)($65)$1-1%($268)($269)$10%($229)($211)($18)9%Profit(Loss)before tax($69)($72)$3-4%($290)($293)$3-1%($251)($232)($19)8%Income tax expense(benefit)($0)($0)$0-57%$0($0)$0-100%$0($1)$1-100%Net profit(loss)-GAAP($69)($72)$3-3%($290)($293)$2-1%($251)($231)($20)9%GAAP EPS-Diluted($1.01)($1.08)$0.07-6%($4.38)($4.46)$0.08-2%($3.54)($3.44)($0.10)3%Source:Company data,Credit Suisse estimates,FOA10 February 2019U.S.Biotechnology8L90D%Change1.8%YTD%Change7.0%RatingUNDERPERFORMTarget Price$105$114$116Mkt Cap($m)$5,07711/10/20182/8/2019Cash($m)$979United Therapeutics(UTHR,Underperform,Target Price:$105).Focus areas include:Expected generic Remodulin launch and impact to UTHRs franchise;though we have seen updates to FDA applications(Sandoz ANDA 203649 and Par Sterile ANDA 209382),recent channel checks still indicate no signs of generics on the market placeFREEDOM-EV results supporting label expansion in the US and potential ex-US approvalAdditional clarity/details on the supply limitation for the ISRs launchStatus update on RemUnity/TrevyentExpectations for the BEAT study readout in Q2Figure 8:UTHR CS and ConsensusQ4 2018FY 2018($in millions except EPS)CSCons.(%)CSCons.(%)Remodulin$156$147$96%$596$589$71%Tyvaso$91$98($6)-7%$400$405($5)-1%Adcirca$19$31($12)-40%$301$313($12)-4%Orenitram$58$57$23%$214$212$21%Unituxin$19$21($2)-9%$80$82($2)-2%Total Revenue$344$354($10)-3%$1,590$1,600($10)-1%COGS$20$39($18)-48%$187$202($15)-7%R&D$65$95($30)-32%$284$318($34)-11%SG&A$41$83($42)-51%$228$280($53)-19%GAAP Opex$126$217($91)-42%$699$801($102)-13%Operating Income$217$137$8159%$891$800$9211%Income Before Tax$215$141$7453%$882$799$8310%Provision for Income Taxes$52$31$2168%$195$173$2212%Net Income$163$110$5348%$687$626$621