Zai Lab Limited - ADR

zoci (DLL3 ADC) shows standout efficacy + tolerability; Phase III expansion is the centerpiece - At ESMO, Zoci + atezolizumab in first-line small cell lung cancer (33 patients, 1.6 mg/kg) achieved a confirmed ORR of 81.8% with responses rapid (most in first assessment) and durability: 6-month PFS 81.9%; in the first 15 patients with ~10 months median follow-up, median PFS and median DoR not reached and 10/15 had not progressed. - Safety/tolerability differentiator: grade ≥3 zoci-related AEs: 9.1% (plus only a single grade 1 ILD case noted). Management contrasts this with ~60%+ grade ≥3 treatment-related AEs typically seen with chemo-IO. - Plans: advancing zoci 1.6 mg/kg + immunotherapy into a global randomized Phase III; also building combinations via T-cell engager collaborations (Amgen and BI) and continuing a registrational Phase III (DLLEVATE) in second-line and later including patients previously treated with tarlatamab.

Potential accelerated approvals in 2027 are being lined up—clear regulatory framework, but still execution/risk heavy - DLLEVATE (second-line SCLC): accelerated approval possibility based on response rate in a formal interim analysis. - Interim analysis includes ~200 patients (a mix of patients after platinum progression and after platinum + tarlatamab), with ~6 months follow-up after the first scan assessment to judge durability. - They emphasized no disclosure of assumptions, but stated the design is overpowered given historical context (~20% range); management highlighted their disclosed 60%+ overall response in second-line plus. - epNEC (extrapulmonary neuroendocrine carcinomas): FDA-aligned discussion suggests a potential accelerated approval supported by a single-arm Phase I/II. - Management set a “bar” they say is achievable: historical response 10–20%, PFS ~2 months; they characterized their data as potentially supporting ~40% response with durability 5–6 months (tomorrow’s NANETS presentation is expected to update the dataset, cited as ~60 patients). - Challenge/negative: accelerated approval and “pivotal acceptance” still depend on durability timing, follow-up adequacy, and confirmatory study execution (confirmatory design discussed with FDA is planned, but details weren’t fully provided).

Next 12–24 months: management targets multiple registrational milestones and a potential first US BLA—ambitious timeline - By year-end 2026: expectation of three registrational studies underway across small cell lung cancer and neuroendocrine carcinomas. - In 2027: expect two registrational results plus the first potential US BLA submission, positioning a US launch as early as 2028 (management calls this a defining company milestone). - Surprising/positive: the call strongly contrasts high efficacy with notably improved tolerability versus chemo-IO, which if sustained could materially change the standard-of-care trajectory.