瑞信-美股-生物科技行业-美国生物科技：管理团队的主要问题-2020.1.6-78页.pdf

U.S.Biotechnology Prep Materials for Next Weeks Biotech Circus in SF:What to Expect at the Conference and Key Questions for Management Teams Biotechnology|Comment Ahead of next weeks major healthcare conference the US Biotech Team(both Seigerman and Auster)have put together a comprehensive list of what to expect for each company that we cover that will be presenting.We have also included a comprehensive question bank for company management.Below you will find a summary of what to expect from our covered companies,including who is likely to pre-report of earnings,provide guidance,commercial launch updates,pipeline updates,and/or other program status updates.Possible UpdatesHighlights Early 2020Pre-reporting of Earnings or 2020 GuidanceCommercial LaunchUpdatesSignificant Pipeline UpdatesProgram Status Updates6 January 2020 Equity Research Americas|United States 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.Research Analysts Martin Auster,M.D.212 325 6573 martin.austercredit- Evan Seigerman 212 325 4463 evan.seigermancredit- Tiago Fauth 212 325 7569 tiago.fauthcredit- Mark Connolly 212 325 7576 mark.connollycredit- Thomas Deal 212 325 3719 thomasavery.dealcredit- Matthew Terwelp,MD 212 325 3493 matthew.terwelpcredit- 6 January 2020 U.S.Biotechnology 2 Table of Contents Expectations for Early January 2020 3 Question Bank 6 Acceleron XLRN.6 Aimmune AIMT.8 Alexion ALXN.9 Allena ALNA.12 Amgen AMGN.14 AnaptysBio ANAB.16 Apellis APLS.17 Arena ARNA.19 argenx ARGX.21 Ascendis ASND.23 Biogen BIIB.25 BioMarin BMRN.27 Cortexyme CRTX.29 Cyclerion CYCN.31 Esperion ESPR.33 Entasis ETTX.35 Forty Seven FTSV.36 Galapagos NV GLPG.38 Gilead GILD.39 Incyte INCY.41 Insmed INSM.43 Intellia NTLA.45 Intercept ICPT.47 Ironwood IRWD.49 MyoKardia MYOK.51 Neurocrine NBIX.53 ObsEva OBSV.55 Portola PTLA.57 PTC Therapeutics PTCT.58 Regeneron REGN.60 Sarepta SRPT.62 Solid Bioscience SLDB.64 Stoke STOK.66 Ultragenyx RARE.68 uniQure QURE.70 United Therapeutics UTHR.72 Vertex VRTX.74 6 January 2020 U.S.Biotechnology 3 Expectations for Early January 2020(*denotes company has scheduled an analyst event the week of January 13)Acceleron(Martin Auster)Little new info likely on luspatercept MDS regulatory review or Bthal launch.Sotatercept Ph2 PULSAR(PAH)is next major catalyst(we think February);XLRN may discuss development plans should the outcome be positive(we note that companion trial SPECTRA is open label,possibly providing insights to inform expectations for PULSAR).ACE-083 CMT Ph2 results are expected in January 2020.Aimmune*(Evan Seigerman)We expect Palforzia to be approved and launched by late January,possibly during JPM or earlier.We expect incremental detail on the launch plan as well as updates from interactions with payers and regulators.Alexion*(Martin Auster)We expect incremental conversion and pipeline updates for Alexion,a possible unexpected highlight could see some interim Ph1 data for ABY-039(FcRn antagonist).We expect 2020 guidance to come on the Q4 report in February,consistent with prior years.Amgen*(Evan Seigerman)We anticipate a quieter JPM for Amgen,and expect commentary on the recent BeiGene collaboration in China,as well as updates on the Otezla integration.In prior years,Amgen has used JPM to highlight upcoming pipeline milestones across the portfolio.JPM will likely be new CFOs Peter Griffiths first major investor event since assuming the role on January 1st;we will look for details on his strategic priorities for Amgen.Apellis(Tiago Fauth)PEGASUS Ph3 PNH data(head-to-head versus Soliris)is expected early in January,and is the key event for the stock in 2020,though we expect debate over the commercial opportunity for APL-2 in PNH to continue.Argenx*(Tiago Fauth)Focus will be on Ph3 gMG readout in H2 2020,with incremental details possible on study design and dosing regimen(we discussed disclosures made in a recent patent application in a previous note).We could also see an update on PV and potential development plan.Ascendis*(Tiago Fauth)The company will likely focus on regulatory status and commercial prep for TransCon hGH,Ph1/2 data for TransCon PTH(expected Q1)and its TransCon CNP program.Biogen*(Evan Seigerman)We expect the focus will be on aducanumab,and we will look for any incremental color on filing timelines and interactions with regulators.The company has typically used JPM to provide an update on strategy,and we may get additional color on the earlier neuroscience pipeline.BioMarin*(Martin Auster)Last year,the company provided updated guidance on the just-completed fiscal year and could repeat this,if needed.The company may also provide updated Palynziq launch stats and may provide more granularity regarding 2020 guidance(it has already guided for GAAP profitability in 2020).Confirmation of Valroxs US filing is also expected.Cyclerion(Martin Auster)Ph1 data for IW-6463,an sGC stimulator designed to be brain penetrant,was expected by YE19 and may be disclosed over the next few weeks.Galapagos*(Evan Seigerman)On filgotinib,we look for updates on the commercial buildout,feedback from KOL and payer engagement.We may get incremental timing details for the earlier pipeline,including proof-of-concept trial initiations for Toledo assets.Gilead*(Evan Seigerman)Now that filgotinib has been filed in the US,we expect the company will provide detail on the commercial plan.We may get incremental timing details on the UC topline readout and phase 3 initiation in ankylosing spondylitis.Last year,the company highlighted upcoming pipeline events,and set the stage for new CEO Dan ODay(who started in March).This year,well be looking for details on managements strategy to re-accelerate growth,particularly R&D,BD and capital allocation priorities.6 January 2020 U.S.Biotechnology 4 Incyte(Evan Seigerman)With the negative GRAVITAS-301 readout behind us,we expect a broader strategic update at JPM.We think new disclosures as unlikely,as the next meaningful catalysts are expected later in the year.Insmed*(Martin Auster)We expect INS1007 bronchiectasis Ph2 results to come at any time(trial is listed as complete on clinicaltrials.gov as of mid-December).See our preview for details.Also,the company has been non-committal,but may report Q4 revenue/launch stats,given the company pre-reported this data last year(we model$44m in Q4 2019 revenue vs Factset consensus$45m).Arikayce guidance for 2020 is also possible,but not expected.We model$220m in 2020 sales vs consensus$221m.Mirati(Evan Seigerman)We expect JPM to be relatively uneventful for Mirati.Last year,the company provided an R&D overview at the conference we will look for any incremental details on timelines for updated MRTX849 data and the sitravatinib interim analysis(expected 2H20).MyoKardia(Martin Auster)The company may provide additional details on the nHCM opportunity and regulatory path forward,although we expect many of these details may not be disclosed until full nHCM Ph2 data is presented at an academic conference later in Q1 2020.Neurocrine*(Evan Seigerman)The company is likely to pre-announce 4Q and FY19 Ingrezza sales and TRx data at JPM-consensus estimates$215M/$730M.Some investors weve spoken to have discussed the possibility that Neurocrine may start giving sales guidance,but we believe this is less likely due to occasional volatility caused by seasonality and contracting.We may get more detail from the companys interactions with regulators on NBI-74788 in CAH and the VY-AADC program in Parkinsons.ObsEva(Martin Auster)The company may disclose results for OBE022 for the treatment of pre-term labor(results were expected Q4 2019).We believe investors assign limited value to the program.PTC Therapeutics(Martin Auster)We expect the company may announce the AADC deficiency gene therapy BLA has been submitted(expected in Q4 2019).We also expect the company could provide additional details on AADC deficiency patient identification efforts.Meanwhile,FIREFISH Ph3 SMA results are expected Q1 2020,although we expect actual details will not be disclosed until an academic conference in early February.Translarna dystrophin study results are expected anytime now,and could provide a free call option;if the study is successful,it could support US approval of the drug.We expect the company will pre-report 2019 earnings and will disclose 2020 guidance(this was done in previous years).We model Q4 2019 revenue of$95m(consensus$90m).Portola*(Tiago Fauth)We expect more details on the cerdulatinib development plan(investor currently assign limited value to the asset),along with potential updates for Andexxa/Ondexxya.Regeneron*(Evan Seigerman)The company is likely to pre-announce 4Q and FY19 US Eylea sales(we are in-line with consensus forecasts of$1.2B/$4.6B)and provide some 2020 financial guidance,which in prior years has included Sanofi commercial expense reimbursement,non-GAAP unreimbursed R&D,SG&A,effective tax rate and capital expenditures.We may get R&D updates for the emerging novel oncology portfolio,which we believe is becoming an increasingly important driver for the company.Sarepta*(Martin Auster)The company may pre-report 4Q19 revenue and update the status of its gene therapy manufacturing build out and enrollment of the DMD and LGMD2E gene therapy trials.Ultragenyx(Martin Auster)Cohort 3 data for the OTC deficiency gene therapy program(DTX301)was expected by year-end 2019,and could come over the next couple of weeks.The key read-through of the update is to the overall gene therapy platform capabilities for Ultragenyx,since we dont expect the 3-patient update to meaningfully change investors assessment of DTX301.6 January 2020 U.S.Biotechnology 5 UniQure(Martin Auster)The AMT-130 IND for the treatment of Huntingtons Disease is active and the first patient could be dosed anytime.There may be comments updating the status of this trial.United Therapeutics(Martin Auster)The company may announce data from the ongoing Ph3 INCREASE study of Tyvaso in PH ILD(enrollment completed in Aug19,16 week treatment period).Data from the Ph2/3 study of dinutuximab in small cell lung cancer is also possible(est.primary endpoint completion of Dec19 per Clinicaltrials.gov)but less likely.Vertex*(Evan Seigerman)The company has typically used JPM to deliver an update on overall strategy;we believe incoming CEO/current CMO Reshma Kewalramani is likely to outline her vision and strategic priorities for the next few years,ahead of the management transition after 1Q.We may get incremental detail on how the Trikafta launch is progressing.6 January 2020 U.S.Biotechnology 6 Question Bank Acceleron XLRN Luspatercept Refractory MDS and TD B-thal Luspatercept was approved for the treatment of B-thal in November 2019.How should we think about the US launch trajectory for luspatercept in B-thal?How many clinics are you targeting in the US and how many patients are seen at these clinics?What is the latest in terms of your payer discussions and what can you say about access to the drug at this time?How should we think of relative positioning of luspatercept relative to some of the other agents in development for B-thal?What is the timing for approval in Europe and can you frame the puts and takes for the EU launch relative to the US launch?You originally expected to have an AdCom in mid-December to discuss the luspatercept BLA for the treatment of ESA refractory/ineligible MDS.However,that meeting was subsequently canceled.What is the likelihood of needing an AdCom at this point?What is your level of confidence in approval and what questions do you anticipate from FDA?Can you characterize the most recent interactions with the agency?Can you frame how we should think about the MDS launch relative to the Bthal launch?What is the unmet need here can patients just receive infusions chronically to manage low Hgb?XLRN has mentioned there are 200-400 specialists treating MDS at academic centers.How many patients do these specialists manage?Can you walk through the actual administration of the drug is this at home or in the clinic?Can you characterize your recent payer discussions?Do you expect the drug will be reimbursed under Medicare part D or part B?Can you walk us through the MDS competitive landscape,including drugs that are currently used to treat the disease and agents in development?Can you outline the XLRN/CELG agreement?What are your responsibilities relative to Celgene and what are the terms of the agreement?Can you outline your go-to-market commercial strategy in MDS?How does this compare to your go-to-market strategy in B-thal(expected sales force size,target physicians,etc.)?What is luspatercepts IP position?Luspatercept Life-Cycle Can you provide an update on the front-line MDS study(COMMANDS)and the non-transfusion dependent B-thal(BEYOND)study?What is the powering of COMMANDS?You have suggested that you might explore luspatercept in other indications.Can you walk through the broader luspatercept strategy?What are you looking for in future disease indications?You recently announced top-line myelofibrosis(MF)Ph2 data.Can you summarize the data?Why do you think you saw greater benefit in combination with ruxolitinib vs monotherapy(particularly in light of what was seen with sotatercept in MF)?MF:You have mentioned the plan is to move the program forward in a subset of patients.How many patients have MF that fall within the target subset?How should we think about duration of therapy for MF relative to MDS?Can you walk through what other agents are in development for MF and outline the potential differentiation for your drug(such as Constellation Pharmas CPI-0610)?Rest of the Pipeline/Corporate How does sotatercepts MoA differ from currently available PAH treatments?What gives you confidence that sotatercept is a potentially effective agent for PAH?How would sotatercept fit into a relatively crowded PAH landscape?Do you expect sotatercept will be administered at home or in the clinic?6 January 2020 U.S.Biotechnology 7 Sotatercept is in two Ph2 trials for PAH.Can you walk through the design of these two studies?What are you looking to see in the studies/what do you see as clinically meaningful and supportive of advancing the program to a Ph3 study?Will you proceed into a Ph3 based on the PULSAR study or will you wait for the SPECTRA study results before evaluating next steps?A number of the earlier approvals in PAH are based on 6MWD.Can you provide your perspective on the potential approvability of 6MWD today and the range of endpoints you may consider for a potential Ph3?PULSAR