Metastatic Bladder & Prostate Cancer Guggenheim Grand Rounds Highlights: GENB’s -4362 a Compelling Strategy for Bladder Cancer (MIBC/mUC); Degraders, TCEs, & EZH2 Inhibitors Advancing in Prostate Cancer

Research evidence excerpt

Metastatic Bladder & Prostate Cancer Guggenheim Grand Rounds Highlights: GENB’s -4362 a Compelling Strategy for Bladder Cancer (MIBC/mUC); Degraders, TCEs, & EZH2 Inhibitors Advancing in Prostate Cancer

GLOBAL BIOPHARMACEUTICALS

May 18, 2026

discontinuation. The experts strongly believe a ~30% relative reduction in PN is

clinically meaningful.

Both experts emphasized that PN is cumulative, likely caused by free MMAE, and the •

driver of the high dose modification and discontinuation rates seen with Padcev. Mild

PN usually appears after a few months and more severe neuropathy typically starts

at ~4-6 months. Drs. Gartrell and Koshkin estimated ~50-60% of patients develop PN

and the doctors agree that reducing PN may allow them to keep patients on EV longer

and maintain dose intensity. The experts try to find a balance between maintaining

dose intensity for efficacy purposes while protecting patients from potentially irreversible

neurologic toxicity and quality of life deterioration. For example, Dr. Gartrell specifically

stated that he will drop Padcev if necessary to avoid quality of life decline due to peripheral

neuropathy while keeping patients on Keytruda for the full two-year course. Both experts

strongly believe a ~30% relative reduction in PN is clinically meaningful ("very clinically

meaningful" and "pretty remarkable"), and Dr. Gartrell also noted a 50% reduction would

be "extremely impressive."

Skin rash is another AE in focus with EV and EVP. The experts noted rash usually •

happens sooner than peripheral neuropathy, typically in the first one or two cycles, and is

usually managed with dose reductions or delays while permanent discontinuation due to

rash is relatively uncommon. The cause of rash is less clear to our experts; rash caused