Pyxis Oncology (PYXS) Leerink Global Healthcare Conference 2025 summary

Strategic focus and program overview

• All resources are dedicated to advancing the lead ADC program, PYX-201, after discontinuing other clinical assets.

• PYX-201 targets EDB, a novel extracellular domain B splice variant of fibronectin, marking the first clinical development of an ADC against this target.

• The approach aims to disrupt the tumor microenvironment structurally, differentiating from other ADCs that target cell surface proteins.

• Innovation and novel targeting are prioritized over incremental improvements on existing ADC targets.

Clinical trial design and findings

• Phase I trial enrolled 80 patients across 9 tumor types and 10–11 dose levels, focusing on dose escalation and mechanism validation.

• High EDB expression was observed across multiple tumor types, supporting broad applicability.

• The ADC cleaves in the extracellular matrix, not requiring internalization, which is distinct from approved ADCs.

• The trial aimed to identify signals for further development and optimal dosing.

Safety and tolerability

• Safety profile was favorable, with negligible target expression in normal tissue and a well-designed, stable ADC construct.

• No grade 3/4 neuropathy or ocular toxicity observed; neutropenia and skin lesions were manageable.

• Only one patient discontinued due to treatment-related reasons; no grade 5 treatment-related events.

• Safety at 5.4 mg/kg dose was comparable or better than approved ADCs, with potential for further dose optimization.