火箭制药公司（RCKT）：由于关键的丹农心脏病项目出现一些不确定性，给予持有评级

2024A2025E2026E0.00.00.0-66.5242.7-(2.18)(1.47)(2.73)(2.09)(1.08) Andrew Tsai * | Equity Analyst(415) 229-1566 | atsai@jefferies.comMatthew Barcus, Ph.D. * | Equity Associate(415) 229-8703 | mbarcus@jefferies.comJohn Cox, Ph.D. * | Equity Associate+1 (415) 229-8708 | jcox1@jefferies.comBrian Balchin, ACA * | Equity Analyst(415) 229-1522 | bbalchin@jefferies.com The Long View: Rocket PharmaceuticalsInvestment Thesis / Where We DifferRCKT specializes in the development ofin vivoandex vivogene therapiesforrare,genetically-driven diseases with a strong emphasis in thecardiovascular and hematologic space. RCKT's leadin vivoAAV9-based genetherapy programRP-A501is in a pivotal Phase II study forDanon diseasewhich often leads to heart failure ($500M+ oppty). RCKT's leadex vivolentiviralgene therapy candidates,RP-L201for leukocyte adhesion deficiency-I(LAD-I)andR-L102forFanconi anemia (FA),are seeking regulatory approvals. LAD-I ($50M+ oppty) and FA ($400M+) could receive FDA approvals in 2026.Base Case,$2.5, +7%•Our base case is based on RCKT's leading invivo AAV9-based gene therapy candidate RP-A501(Danon disease).•We build the cash flow streams out topatent expirations before probability-adjustingour DCF.•Our DCFs are also supported by a 3x peak salesmultiple of $500M for the commercial program.•We assume a 15% PoS for Danon.•No credit is given for cashSustainability MattersTop Material Issue(s): (1)Product Quality and Safety:RCKT has demonstrated meaningful efficacy andsafety from its portfolio ofin vivoandex vivogene therapy programs in rare genetically-driven diseases.Still, the company has yet to receive regulatory approval for any of its gene therapies. And, long-termsafety/efficacy of the programs remain to be elucidated.(2)Business Ethics:RCKT has and may acquireor in-licenses product candidates in the future through BD, and so they must maintain the highest ethicalstandards of business conduct throughout the diligence process.(3) Employee Engagement, Diversity and Inclusion: Smaller biotech companies must ensure that theyhave sufficient talent to develop drugs (whereas large pharma/biotech may provide more stability). Thisis especially critical as companies look to supplement their commercial portfolio with newer drugs andor BD opportunities.Company Target(s):NonePlease see important disclosure information on pages 7 - 12 of this report.This report is intended for Jefferies clients only. Unauthorized distribution is prohibited. Risk/Reward - 12 Month View35302520151050Upside Scenario,$13, +458%Our upside scenario factors in:•A higher market penetration for RP-A501(Danon), supporting $1B+ in peak sales•RP-L201 (LAD-I), supporting $120M in peaksales•RP-L102 (FA), supporting $500M in peak sales•A $1B+ market opportunity for RP-A601 (PKP2-ACM) assuming a 10% PoS•RP-L301 (PKD) assuming a 15% PoS•No credit is given for cash 20252024Downside Scenario,$0.5, -79%Our downside scenario factors in:•Assigns no value to RCKT's pipeline.•Values cash at YE:26.Catalysts•Mid-2025: File IND for BAG3-DCM gene therapyprogram•Late'25/Early'26:Complete rolling BLAsubmission of RP-L102 in FA•2025/H1:26: Pot'l FDA approval of RP-L201 inLAD-I•Mid-2026: Pot'l Phase II data in Danon diseasewith RP-A501•H2:26:Pot'l FDA approval of RP-L102 in FA•2028:Pot'l approval of RP-A501 in Danondisease 2 Timeline of Safety Events in the Pivotal Phase II Trial for Danon Disease:•RCKT observed complement activation and TMA, a known safety effect of the gene therapy.The initial episode was linked to a gene mutation known for conferring complement sensitivityin some patients. Recall, in the earlier Phase I study, one patient in the adult high dose cohort(1.1e14 vg/kg) also developed TMA.•RCKTintroduced a 14-panel test to prevent patients with gene mutations conferringcomplement sensitivity from enrolling.•Another case(s) of TMA persisted.•"Several months ago", a new C3 inhibitor was introduced to the immunomodulatory regimenfor RP-A501 to irradiate complement activation and T cell responses. It is administered inconjunction with other agents (e.g., rituximab, sirolimus, steroids) before and after infusion.•Earlier in May, a patient received the new immunomodulatory regimen with the C3 inhibitor.The regimen yielded zero cases of TMA or "other gene therapy effects" (e.g., myocarditis) inthe first week. However, RCKT then began to see evidence of capillary leak and other medical/procedural complications.•The patient stabilized, and the capillary leak was improving.•Over the past weekend, he developed an acute systemic infection that accelerated.•The clinical hold was placed on Friday, May 23.•The patient subsequently passed away.•Patients who had early complement activations have completely recovered from the sequelaeand "are doing well right now".Other tidbits:•The two recent patients who experienced capillary leak syndrome received the standard 6.7e13vg/kg dose in the study•The patients' weight was mid-range and the dose was within range of pri