2025年欧洲心脏病学会心力衰竭大会（ESC-HF）和周围神经学会（PNS）要点

Restricted - External U.S. Small & Mid Cap BiotechnologyPOSITIVEU.S. Small & Mid Cap BiotechnologyGena Wang, PhD, CFA+1 212 526 4252gena.wang@barclays.comBCI, USHang Hu, PhD+1 212 526 6364hang.hu@barclays.comBCI, USTony Deng, MD+1 212 526 0350tony.deng@barclays.comBCI, USJustin Kong, MD+1 212 526 1961justin.kong@barclays.comBCI, US vs. placebo showed stat sig reductions in CV mortality with HR 0.67 (15% vs. 23%; p = 0.038) inoverall population and trend of benefit with HR 0.64 (16% vs. 28%; p =0.052) in monotherapypopulation.CV events at 36 mon.Data hadcutoffof May 8, 2024 (same as primary analysis data cut). CVevents: At 36 mon, Amvuttra vs. placebo showed stat sig reductions in frequency of CVevents/yr with HR 0.73 (0.21 vs. 0.29 p = 0.001) in overall population and HR 0.68 (0.21 vs. 0.31;p =0.001) in monotherapy population (vs. 0.73 in overall and 0.67 in monotherapy populationat ~33-36 mon previously). Components of CV events: Amvuttra showed benefit on all typesof CV events, and was stat sig for CV hospitalizations and HF hospitalizations in bothpopulations, as well as urgent HF visits in overall population. Subgroup analyses: Amvuttrashowed benefit on CV events across all subgroups (Figure 1), including NYHA Class III pts(trend in overall and stat sig in monotherapy population). We note NYHA Class III subgroupbenefit across outcomes was largely consistent with Amvuttra vs. inconsistent with stabilizers(worsening CV events with tafamidis and worsening composite of ACM and CV events withAttruby).FIGURE 1. HELIOS-B CV Events Subgroup AnalysesSource: Company presentation; Barclays researchNTLANex-z ATTRv-PN Ph1 interim update showed clinically meaningful outcomeimprovement in ATTRv-PN pts at yr 2, including pts who progressed on patisiran.At 2025PNS, NTLA presented nex-z Ph1 interim update in ATTRv-PN, including clinical measure datafrom longercutoffof April 11, 2025 (vs. TTR-knockdown and safety data from Aug 21, 2024,see 2024 AHA note). Clinical measures: Favorable trends were observed from Ph1 part 2(Figure 2), including NIS improvement of -2.1±10.2 at yr 1 and -5.2±10.7 at yr 2, as well asmNIS+7 improvement of -0.6±11.1 at yr 1 and -8.5±9.6 at yr 2. In addition, 78% (14/18) ptsexperienced ≥4 decrease in mNIS+7 during 2-yr follow-up, including 5 (out of 6) pts whopreviously progressed on patisiran. Biomarkers: Improvements were observed in NfLreduction of -8.6%±41.7% at yr 1, Norfolk QoL-DN reduction of -8.5±19.3 at yr 2, and mBMIimprovement of 39.0±87.1 kg/m2x g/L at yr 2. TTR-knockdown and safety: no new datareportedafterAug 21, 2024.2 •• FIGURE 2. Clinical measure and biomarker data in nex-z ATTRv-PN Ph1 interim reportNegative changes reflect improvement in NIS, mNIS+7, Norfolk QoL-DN and NfL. Positive change reflects improvement in mBMI. NIS and mNIS+7 datacutoff:April 11,2025. Norfolk QoL-DNx and mBMI datacutoff:Aug 21, 2024. NfL datacutoff:April 12, 2024.•ATTR-CM Ph1 wildtype vs. variant subgroup analysis showed durable and consistentTTR-knockdowns in ATTRwt-CM and ATTRv-CM pts, while more favorable clinicaloutcomes in pts with ATTRv-CM.At 2025 ESC-HF, NTLA presented wildtype (ATTRwt-CM) vs.variant (ATTRv-CM) subgroup analysis in Ph1 study with datacutoffof Aug 21, 2024. TTR-knockdown: Deep and durable reductions in serum TTR were observed in both ATTRwt-CM(-92.5%) and ATTRv-CM (-85.4%) pts at mon 12. Clinical measures: At mon 12, ATTRv-CM ptsshowed favorable 6MWT improvement of 40 meters (vs. 5 meters in ATTRwt pts), favorableKCCQ-OS improvement of 13.4 (vs. 4.8 in ATTRwt pts) and no disease progression shown in %pt with NYHA score improved/no change/worsened of 36%/64%/0% (vs. 52%/36%/12% inATTRwt pts) (Figure 3). Biomarkers: No meaningful changes in NT-proBNP and hs-Troponin Twere observed for both ATTRwt and ATTRv-PN pts at mon 12. Safety: AEs were similarbetween 2 subgroups. The most common AE for both was cardiac failure (32% in ATTRwt-CMand 45% in ATTRv-CM), which was noted expected in the patient population.3 Source: Company presentation19 May 2025 FIGURE 3. ATTRwt-CM vs. ATTRv-CM subgroup analysis in nex-z ATTR-CM Ph1 studyDatacutoff:Aug 21, 2024Source: Company presentationCYTK•SEQUOIA-HCM subgroup analysis showed the clinical benefit of aficamten wasindependent of oHCM symptom burden.CYTK presented aficamten Ph3 SEQUOIA-HCMsubgroup analysis in pts with mild vs. moderate-to-severe symptoms and simultaneouslypublished in European Heart Journal. Mild and moderate-to-severe symptoms were definedas NYHA II + KCCQ-CSS ≥80 (n=118 total) and NYHA II/III/IV + KCCQ-CSS <80 (n=150 total),respectively. Primary endpoint of pVO2mL/kg/min) and moderate-to-severe (1.8 mL/kg/min) symptom groups (p=0.8) (Figure 4).Likewise, the change in secondary endpoints (NYHA class, Valsalva/resting LVOT-G, and NT-proBNP) did notdiffersignificantly between two groups. The only stat sigdifferencewas inKCCQ-CSS change, where moderate-to-severe symptom group showed greater improvement(+10 vs. +4 in mild symptom gr