Heidelberg Pharma AG will present preclinical data for its investigational antibody-drug conjugate HDP-103 targeting metastatic castration-resistant prostate cancer at the American Association of Cancer Research Annual Meeting 2026. The data, detailed in a 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," shows the compound's potential as a novel treatment option for this aggressive cancer.
According to the company, HDP-103 demonstrates target-specific binding in human tissues and robust, durable antitumor activity in patient-derived xenograft models representative of mCRPC. This includes tumors with heterogeneous PSMA expression and those harboring a del(17p) genetic alteration. In these models, the amanitin-based HDP-103 was superior to an anti-PSMA Exatecan ADC. The abstract for this presentation is available at https://www.abstractsonline.com/pp8/#!/21436/presentation/5438.
The significance of these findings lies in the treatment of mCRPC, an advanced form of prostate cancer that has stopped responding to hormone therapy and often has limited treatment options. Patients with del(17p) mutations represent a particularly challenging subgroup with high unmet medical need. HDP-103's unique mode of action, utilizing amanitin derived from the green death cap mushroom, gives it advantages over other treatment modalities in development for this condition.
Safety data from non-human primate studies showed adverse events were restricted to known off-target effects of amanitin-based ADCs, primarily affecting the liver and kidney. These effects were described as transient and readily monitorable. Pharmacokinetic analysis revealed HDP-103 serum levels demonstrate stability in circulation, no evidence of drug accumulation, no differences between sexes, and dose-linearity.
The combination of potent anti-tumor efficacy with a favorable half-life and manageable safety profile results in a therapeutic index for HDP-103 that falls within the range of other ADCs approved or in development for solid tumor indications. This favorable profile supports further clinical development of HDP-103 as a potential new treatment for mCRPC. The company notes that these preclinical findings warrant advancing the compound toward human trials.
Heidelberg Pharma's ATAC technology platform represents a novel approach in oncology, utilizing amanitin's biological mechanism of action as a new therapeutic modality. The company's lead candidate, HDP-101, is already in clinical development for multiple myeloma with Orphan Drug and Fast Track designations from the FDA. More information about the company is available at http://www.heidelberg-pharma.com.
The presentation of this data at AACR 2026 highlights ongoing innovation in ADC development for difficult-to-treat cancers. As prostate cancer remains a leading cause of cancer death in men worldwide, new treatment approaches like HDP-103 could potentially expand therapeutic options for patients who have exhausted standard treatments. The advancement of this compound through preclinical development represents progress toward addressing significant gaps in prostate cancer care.
