Heidelberg Pharma AG (FSE: HPHA), a clinical-stage biotech company developing innovative Antibody Drug Conjugates (ADCs), announced today 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. According to the company, HDP-103 shows 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, Amanitin-based HDP-103 was superior to an anti-PSMA Exatecan ADC.
Adverse events with HDP-103 in non-human primates were restricted to known off-target effects of Amanitin-based ADCs, primarily in the liver and kidney, which the company notes can be readily monitored and are transient. HDP-103 serum levels demonstrate stability of the ADC in circulation, 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 a manageable safety profile leads to a comfortable therapeutic index (TI) that is well in the range of other ADCs that are approved or in development for solid tumor indications,” the company stated. “Taken together, these data warrant further clinical development of HDP-103 as a novel treatment option for mCRPC.”
HDP-103’s unique mode of action, based on the Amanitin toxin derived from the death cap mushroom, gives it advantages over other treatment modalities in use or development for mCRPC, including in patients with del(17p) who have a high unmet medical need. Heidelberg Pharma is the first company to develop cancer therapies using Amanitin, and its ATAC technology represents a new therapeutic modality.
Heidelberg Pharma’s 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. A second ATAC candidate, HDP-102, is in clinical development for Non-Hodgkin Lymphoma. HDP-103 against mCRPC and HDP-104 targeting gastrointestinal tumors such as colorectal cancer have completed preclinical development and are available for partnering.
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,” will be presented on 21 April from 2:00 pm to 5:00 pm PDT in the Antibody-Drug Conjugates and Linker Engineering 4 session. The abstract is available online at https://www.abstractsonline.com/pp8/#!/21436/presentation/5438.
