Heidelberg Pharma AG, a clinical-stage biotech company specializing in Antibody Drug Conjugates (ADCs), announced today that it will present promising preclinical data for its Amanitin-based ADC HDP-103 at the American Association of Cancer Research (AACR) Annual Meeting 2026, taking place in San Diego, California from April 17 to 22. The data highlight 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 be delivered on April 21. The full abstract is available at https://www.abstractsonline.com/pp8/#!/21436/presentation/5438.
HDP-103 targets PSMA, a protein overexpressed in prostate cancer cells. The ADC utilizes Amanitin, a toxin derived from the death cap mushroom, which inhibits RNA polymerase II, leading to cell death. This unique mechanism of action distinguishes it from other ADCs and may offer advantages in tumors with heterogeneous antigen expression or genetic alterations such as del(17p).
In patient-derived xenograft (PDX) models representative of mCRPC, HDP-103 demonstrated target-specific binding and robust, durable antitumor activity, including in tumors with heterogeneous PSMA expression and those harboring del(17p). Importantly, HDP-103 was superior to an anti-PSMA Exatecan ADC in these models. The safety profile was manageable; 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 monitorable. Pharmacokinetic data showed stable ADC serum levels, no evidence of drug accumulation, no sex differences, and dose-linearity.
The combination of potent anti-tumor efficacy, favorable half-life, and manageable safety results in a therapeutic index (TI) comparable to 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, particularly for patients with del(17p) who face a high unmet medical need.
Heidelberg Pharma is a pioneer in developing cancer therapies using Amanitin, and its ATAC technology platform is being leveraged across multiple programs. Lead candidate HDP-101 (pamlectabart tismanitin) targets BCMA for multiple myeloma and has received FDA Orphan Drug and Fast Track designations. HDP-102 is in clinical development for Non-Hodgkin Lymphoma, while HDP-103 and HDP-104 (targeting gastrointestinal tumors) have completed preclinical development and are available for partnering. More information about the company is available at www.heidelberg-pharma.com.
The AACR presentation underscores Heidelberg Pharma's commitment to advancing novel ADCs for hard-to-treat cancers, and the positive preclinical data for HDP-103 marks a significant step toward addressing the needs of mCRPC patients.
