Heidelberg Pharma AG (FSE: HPHA), a clinical-stage biotech company developing innovative Antibody Drug Conjugates (ADCs), announced that it will present promising preclinical data from its Amanitin-based ADC HDP-103 targeting metastatic castration‑resistant prostate cancer (mCRPC) at the American Association of Cancer Research (AACR) Annual Meeting 2026 in San Diego, California, from 17 to 22 April.
The data, to be presented in a poster session on 21 April, demonstrate that HDP-103, a PSMA-targeting amanitin-based ADC, is efficacious even in difficult-to-treat patient-derived xenograft (PDX) models with heterogeneous PSMA expression. The poster, titled "HDP-103, a PSMA targeting amanitin-based ADC, is efficacious even in difficult to treat patient derived xenograft models with heterogenous PSMA expression" (poster number 5639), will be available at the conference's abstract page.
HDP-103 showed target-specific binding in human tissues and robust, durable antitumor activity in PDX models representative of mCRPC, including tumors with heterogeneous PSMA expression and those harboring a del(17p) mutation. In these models, HDP-103 was superior to an anti-PSMA Exatecan ADC. Adverse events in non-human primates were restricted to known off-target effects of Amanitin-based ADCs, primarily in the liver and kidney, which were transient and readily monitored. HDP-103 serum levels demonstrated stability of the ADC in circulation, no evidence of drug accumulation, no differences between sexes, and dose-linearity.
The potent anti-tumor efficacy combined with a favorable half-life and manageable safety profile results in a comfortable therapeutic index (TI) for HDP-103, well within the range of other ADCs approved or in development for solid tumors. These data support further clinical development of HDP-103 as a novel treatment option for mCRPC. HDP-103's unique mode of action offers advantages over other treatments for mCRPC, particularly in patients with del(17p) who have high unmet medical need.
Heidelberg Pharma is the first company to develop cancer therapies using Amanitin, a compound derived from the green death cap mushroom. The biological mechanism of action represents a new therapeutic modality used in the company's ATAC technology. Lead candidate HDP-101 (INN: pamlectabart tismanitin) is a BCMA ATAC in clinical development for multiple myeloma and has received Orphan Drug Designation and Fast Track Designation from the FDA. Additional ATAC candidates include HDP-102 for Non-Hodgkin Lymphoma, while HDP-103 and HDP-104 (targeting gastrointestinal tumors) have completed preclinical development and are available for partnering. More information is available at Heidelberg Pharma's website.
