Sutro Biopharma (STRO) 7th Annual Oncology Innovation Summit: Insights for ASCO & EHA summary

Program overview and differentiation

• The pipeline features a differentiated ADC (antibody-drug conjugate) program, STRO-004, with a novel exatecan payload and improved linker strategy, aiming for greater potency and safety compared to existing therapies like TIVDAK.

• Preclinical studies show a higher non-severe toxic dose (HNSTD) of 50 mg/kg, significantly above TIVDAK’s 3 mg/kg, suggesting a wider therapeutic window.

• The program targets tissue factor, broadly expressed across multiple solid tumors, expanding potential indications beyond cervical cancer.

• The company rapidly re-entered the clinic after a business transformation, with strong execution and dose escalation ahead of projections.

• Up to 100 patients are planned for the phase I trial, with initial data expected mid-year from a subset.

Clinical strategy and expectations

• Dose escalation began at 1 mg/kg, higher than comparable programs, and has cleared Dose Level 3, with ongoing escalation to maximize drug exposure while monitoring safety.

• The trial includes backfill cohorts to optimize dosing and inform expansion strategies, with a focus on balancing efficacy and safety.

• Investigators are particularly interested in pancreatic, colorectal, and head and neck cancers due to high tissue factor expression and unmet needs.

• Preclinical PDX models at clinically relevant doses showed promising responses in multiple tumor types, guiding clinical expectations.

• The program aims to achieve higher tolerated doses than competitors, potentially improving response rates in heavily pretreated populations.

Safety profile and risk management

• Preclinical data indicate reduced ocular, skin, and bleeding toxicities at high doses, attributed to the improved linker and antibody design.

• The antibody is Fc-silenced, reducing risk of ILD and pneumonitis, and the linker system minimizes free payload, lowering platform toxicity.

• The construct targets a different tissue factor epitope to avoid bleeding risks seen with other ADCs.

• Platform toxicities such as peripheral neuropathy and neutropenia are expected to be reduced due to the unique linker and payload.

• Dose escalation will continue until a dose-limiting toxicity (DLT) is reached, following standard phase I protocols.