Heidelberg Pharma AG, a clinical-stage biotechnology company specializing in Antibody Drug Conjugates (ADCs), announced it will present preclinical data for its investigational ADC HDP-103 at the American Association for Cancer Research (AACR) Annual Meeting 2026, scheduled for April 17-22 in San Diego, California. The data highlights the potential of HDP-103 as a novel treatment for metastatic castration-resistant prostate cancer (mCRPC), a disease with significant unmet medical need.
The poster 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 take place on April 21 from 2:00 pm to 5:00 pm PDT. The abstract is available online at the AACR website.
HDP-103 targets prostate-specific membrane antigen (PSMA), which is highly expressed in mCRPC. According to the company, the ADC demonstrated robust and durable antitumor activity in patient-derived xenograft (PDX) models that represent the heterogeneity of mCRPC, including tumors with heterogeneous PSMA expression and those harboring a deletion of chromosome 17p (del(17p)), a genetic alteration associated with poor prognosis. Notably, HDP-103 was superior to an anti-PSMA Exatecan ADC in these models.
Heidelberg Pharma's proprietary ATAC technology utilizes amanitin, a toxin derived from the death cap mushroom, which inhibits RNA polymerase II, a novel mechanism of action for ADCs. This approach offers advantages over other treatment modalities, particularly in patients with del(17p) who have limited options. The company reported that adverse events in non-human primates were restricted to known off-target effects of amanitin-based ADCs, primarily affecting the liver and kidney, which were transient and manageable. Pharmacokinetic data showed stable ADC levels in circulation, no drug accumulation, no sex differences, and dose-linear exposure.
"The potent anti-tumor efficacy of HDP-103 combined with a favorable half-life and manageable safety profile leads to a comfortable therapeutic index well within the range of approved ADCs for solid tumors," the company stated. "These data warrant further clinical development of HDP-103 as a novel treatment option for mCRPC."
Heidelberg Pharma is the first company to develop cancer therapies using amanitin. Its lead candidate, HDP-101 (pamlectabart tismanitin), targets BCMA for multiple myeloma and has received Orphan Drug and Fast Track designations from the U.S. FDA. HDP-102 is in clinical development for Non-Hodgkin Lymphoma, while HDP-103 and HDP-104 (for gastrointestinal tumors) have completed preclinical development and are available for partnering. The company is based in Ladenburg, Germany, and listed on the Frankfurt Stock Exchange under the symbol HPHA. More information is available at www.heidelberg-pharma.com.
The AACR presentation underscores the potential of amanitin-based ADCs to address resistance mechanisms in hard-to-treat cancers, and the data support HDP-103's advancement toward clinical trials.
