美国中盘生物医药公司 Summit Therapeutics Inc. 目标价调整报告

9.80 USD(7.70OLD) SMMT SMMT: Even the bull case for HARMONi-3 fails to justify thecurrent valuation. We sharpen our SMMT price target by pressure testing the upside bull-case that Akeso’s(covered by Rebecca Liang) China-only HARMONi-6 OS results translate to SMMT’s globalHARMONi-3 Exhibit 1. In this scenario, the historical PFS to OS degradation for PD-1+VEGF(including ivonescimab) in NSCLC Exhibit 3 doesnotoccur - potentially due to differentialperformance in squamous vs non-squamous histology (Exhibit 4). However, in this scenarioutilization of the PD-1+VEGF class would be limited to the ~40% of squamous patientsyounger than 65 years old given lack of clinical benefit for ivonescimab (SMMT's ivonescimabnot effective in all HARMONi-6 subgroups; OS HR= 0.93 in age 65+ can’t be ignored.)and other PD-1+VEGF regimens in advanced age patients Exhibit 2. Furthermore, thePD-1+VEGF class faces significant competitive intensity from Sac-TMT Exhibit 5 and otherdrugs in development which will lead to increased segmentation Exhibit 6 of the 1L NSCLCtreatment landscape. Increasing the PTS (to 75%) for the bullish scenario of PD-1+VEGFclass taking significant share in1L NSCLC Exhibit 6 leads to an upward revision of ourPT to $9.80. Our PTS assessment for the other Ph3 trials (HARMONi-GI/-7/-3’s NSQcohort) remains unchanged because key questions are still unanswered (e.g., contribution ofcomponents for anti-PD-1 in MSS CRC and PFS to OS degradation in NSQ NSCLC). Accounting for HARMONi-3’s upside bull case scenario has increased our conviction in theoriginal recommendation: investors should exit SMMT long positions because of significantdownside risks at the current share price. It should be repeated that SMMT’s high-risk drugdevelopment pipeline limited to ivonescimab makes is hard to estimate the potential shareprice floor in the event HARMONi-3 misses OS or PFS FA later this year. We recommendinvestors exercise caution in advance of this read-out because this bear case scenario isplausible given HARMONi-3’s missed PFS IA and the significant PFS to OS degradationfor all eight PD-1+VEGF NSCLC trials other than China-only HARMONi-6 Exhibit 3. Takentogether, even the bull case for HARMONi-3 fails to justify the current valuation. Investment Implications We reiterate SMMT rating of Underperform with upward revision of PT to $9.80 basedon our DCF valuation. DETAILS HARMONI-6 SHOWED NO CLINICAL BENEFIT FOR IVONESCIMAB IN PATIENTS ≥65 YEARS OLD: OUR BULL CASEMODELING LIMITS PD-1 + VEGF MARKET SHARE TO THE SQUAMOUS PATIENTS (~40%) YOUNGER THAN 65YEARS OLD Akeso’s China-only HARMONi-6 excluded patients >75 years old. Also, the data presented at ASCO 2026 showed decreasedefficacy (increased HR) in ≥65 years old patient population. HARMONi-6’s OS IA: ITT HR= 0.66, vs Age 65+ HR= 0.93. (Exhibit5). As per a retrospective study conducted in 151,919 patients, the median age at diagnosis of NSCLC in US is 68 years and 62%patients >=65 years were at TNM stage 4 (distant metastasis) (Link) while as per SEER-NPCR 2010 to 2017 database (Link),there were over 1.5 million new lung cancer cases; of these, approximately 1.28 million were NSCLC (51% male; 70% aged≥65 years). We adopted a conservative approach assuming 60% aged ≥65 years and 40% of patients less than 65 years old.Our bull case modeling limits PD-1 + VEGF market share to the squamous patients (~40%) younger than 65 years old becauseof HARMONi-6’s lack of efficacy in ≥65 years population. SQUAMOUS-ONLY HARMONI-6 IS THE LONE PD-1+VEGF PH3 TRIAL IN NSCLC WITHOUT SIGNIFICANT PFS TO OSDEGRADATION As mentioned in our sector initiation note (Link) and SMMT company note (Link) there was an average (HR= 0.31) degradationfrom PFS to OS for the seven prior Ph3 clinical trials which investigated the co-administration of anti-PD-1 and anti-VEGF inNSCLC (Exhibit 3). Six of the trials that reached final analysis included exclusively non-squamous population and only LEAP-007had a squamous counterpart. Although the PFS to OS degradation of PD-1+VEGF is well documented for patients with non-squamous histology, there is limited precedent for the squamous histology patients included in HARMONi-6. Therefore, our bullcase scenario models increased PTS and share take for PD-1+VEGF in SQ vs NSQ NSCLC. 1.Results from final OS analysis study (Socinski et al, J of Thorac Oncol, 2021), ITT-WT cohort, WT for targetable mutations.2.Calculated by dividing OS HR of ABCPvs BCP by OS HR of ACP/BCP for ITT-WT and Age 75-84 year-old cohorts respectively; NR= not reported.3.Interim OS analysis, not finalSource: Company reports, Medical journals, Bernstein analysis EXHIBIT 3:China-only HARMONi-6 is lone outlier without significant PFS to OS degradation for PD-1+VEGF inNSCLC. Three of the other eight trials with degradation utilized ivonescimab. EXHIBIT 4:Hypothesis for the reduced PFS to OS degradation in HARMONi-6: Limited precedent for PD-1+VEGF Ph3trials in squamous histology THE BULL CASE SCENARI