Heidelberg Pharma's HDP-103 ADC Shows Promise in Difficult-to-Treat Prostate Cancer Models

Heidelberg Pharma AG will present promising preclinical data from its Amanitin-based ADC HDP-103 targeting metastatic castration-resistant prostate cancer at the American Association of Cancer Research Annual Meeting 2026. The presentation, titled "HDP-103, a PSMA targeting amanitin-based ADC, is efficacious even in difficult to treat patient derived xenograft models with heterogenous PSMA expression," will occur during the Antibody-Drug Conjugates and Linker Engineering 4 session on April 21. The abstract is available at https://www.abstractsonline.com/pp8/#!/21436/presentation/5438.

HDP-103 demonstrates target-specific binding in human tissues and robust, durable antitumor activity in patient-derived xenograft models representative of metastatic castration-resistant prostate cancer. These models include tumors with heterogeneous PSMA expression and those harboring a del(17p) genetic alteration. In these challenging models, the Amanitin-based HDP-103 proved superior to an anti-PSMA Exatecan ADC, suggesting potential advantages over existing treatment approaches. The data indicate that HDP-103's unique mode of action provides benefits over other treatment modalities in use or development for metastatic castration-resistant prostate cancer, particularly for patients with del(17p) who represent a population with high unmet medical need.

Adverse events with HDP-103 in non-human primates were restricted to known off-target effects of Amanitin-based ADCs, primarily affecting the liver and kidney. These effects can be readily monitored and are transient, contributing to a manageable safety profile. HDP-103 serum levels demonstrate stability of the ADC in circulation, with no evidence of drug accumulation, no differences between sexes, and dose-linearity. The potent anti-tumor efficacy of HDP-103 combined with a favorable half-life and manageable safety profile results in a comfortable therapeutic index that falls within the range of other ADCs approved or in development for solid tumor indications.

These comprehensive preclinical findings warrant further clinical development of HDP-103 as a novel treatment option for metastatic castration-resistant prostate cancer. The data suggest that HDP-103 could address significant challenges in treating this aggressive cancer form, particularly in patients with difficult-to-treat tumor characteristics. The presentation at AACR Annual Meeting 2026 represents an important milestone in validating Heidelberg Pharma's ATAC technology platform and advancing potential new therapies for prostate cancer patients with limited treatment options.