Zai Lab (ZLAB) Status Update summary

Clinical data highlights

• ZL-1310, a DLL3-targeted ADC, demonstrated a 74% objective response rate in recurrent small cell lung cancer, including patients with brain metastases and those previously treated with tarlatamab, across all tested dose levels.

• Responses were rapid, often seen by the first tumor assessment (6–9 weeks), and included significant reductions in intracranial lesions; all six evaluable patients with baseline brain metastases achieved partial responses.

• Activity was observed even in tumors with low DLL3 expression, though no response was seen in DLL3-negative tumors, suggesting a bystander effect from the TMALIN platform.

• 80% of patients remained on study at data cutoff, with 13 of 14 responders still on treatment and some responses ongoing beyond six months, the longest at 6.5+ months.

• One patient previously treated with DLL3 bi-specific therapy achieved a partial response.

Safety and tolerability

• ZL-1310 was well tolerated, with most adverse events being Grade 1 or 2, and no discontinuations due to adverse events.

• Grade ≥3 treatment-related adverse events occurred in 20–40% of patients, mainly hematologic or gastrointestinal, with one dose-limiting toxicity (Grade 4 neutropenia/thrombocytopenia) at the highest dose.

• Serious treatment-related adverse events occurred in 8% of patients; 12% required dose reductions.

• Safety profile compares favorably to other ADCs, with less neutropenia and no prophylactic Pegfilgrastim use.

• No patients discontinued treatment due to adverse events.

Study design and patient population

• Data are from an ongoing global Phase 1a/1b study with 25 patients across four dose cohorts, all of whom had progressed after standard platinum-based chemotherapy; 92% after immune checkpoint inhibitors.

• 56% had failed at least two prior lines of therapy; 28% had brain metastases at baseline.

• Median follow-up was 2.4 months at data cutoff (October 10, 2024).

• DLL3 expression was assessed in 16 of 19 patients with post-baseline tumor assessments.

• No significant differences in response rates between US and China patient populations.