Daiichi Sankyo Company (4568) Status Update summary

Disease landscape and unmet need

• SCLC accounts for 13.8% of lung cancers, with a 5-year survival rate of 9% and high incidence of brain metastases, leading to poor prognosis and high unmet medical need.

• Most patients present with extensive-stage disease, and standard second-line therapies offer limited efficacy, with median OS of 6.0-9.3 months.

• Recent drug approvals, including immunotherapies and tarlatamab, have modestly improved options, but significant unmet needs remain and long-term outcomes are limited.

I-DXd program and clinical data

• I-DXd is a B7H3-directed ADC using DXd technology, showing high selectivity for tumor cells and broad activity across multiple tumor types.

• In Phase I trials, I-DXd showed a 52% response rate and median duration of response of 5.9 months in heavily pretreated populations.

• In the IDeate-Lung01 Phase 2 study (n=137, 12 mg/kg), confirmed ORR was 48.2%, median DOR 5.3 months, median PFS 4.9 months, and median OS 10.3 months; efficacy was consistent across subgroups, including those with brain metastases and prior therapies.

• Responses were rapid (median TTR 1.4 months) and durable, with meaningful intracranial activity and a 46% response rate in patients with brain metastases.

• I-DXd demonstrated activity regardless of platinum resistance and in patients previously treated with T-cell engagers and topotecan.

Safety profile

• I-DXd 12 mg/kg was generally well tolerated; most common TRAEs were hematologic or GI, with 12.4% incidence of adjudicated ILD/pneumonitis, mostly low grade.

• Grade ≥3 TRAEs occurred in 36.5% of patients, with 4.4% associated with death.

• I-DXd offers a differentiated safety profile compared to tarlatamab, notably lacking cytokine release syndrome.