Heidelberg Pharma, a subsidiary WILEX AG based in Ladenburg, Germany which primarily advances the development of innovative platform technologies for antibody drug conjugates and provides pre-clinical drug discovery and development services, has been awarded a research grant for the further development of PSMA-antibody drug conjugates for the treatment of patients with prostate cancer. The new research project with an estimated cost of EUR 1.8 million will initially run for 30 months and will receive funding of almost EUR 0.9 million from the German Federal Ministry of Education and Research (BMBF).
PSMA is a membrane antigen over-expressed in prostate cancer and an attractive target for an ADC approach, as it shows low expression by most normal tissues and sufficient internalization after antibody binding. PSMA exhibits a unique pattern of expression due to its specific overexpression in prostate cancer and its role in neovasculature of tumours which opens up the possibilities for other cancer indications as well.
In pilot studies Heidelberg Pharma evaluated the anti-tumoural potency of monoclonal antibodies targeting the prostate-specific membrane antigen (PSMA) conjugated to small molecules from the amatoxin family. The funds will be used to further develop PSMA-Antibody Targeted Amanitin Conjugates (ATACs). The preclinical project covers the humanisation and de-immunisation of the chosen anti-PSMA-antibody which will be coupled via several linker combinations to α-Amanitin based on Heidelberg Pharma’s patented technology. These human anti-PSMA-amanitin-conjugates will be tested preclinically for safety, tolerability and efficacy.
PSMA-Antibody Targeted Amanitin Conjugates
α-Amanitin is a bicyclic peptide naturally occurring in the green Death Cap mushroom. It potently inhibits the biosynthesis of RNA, a mechanism that is critical for the survival of cells. Accordingly, ATACs exhibit comparable activity against proliferating and resting tumour cells. This proliferation independent activity differentiates ATACs from other ADCs, which preferentially target proliferating tumour cells. As an additional advantage ATACs could offer a substantial capability to overcome the resistance mechanisms that might limit the efficacy of other antibody drug conjugates. The ATACs tested so far have shown strong anti-tumour activity in several preclinical tumour models.
Commenting on receiving the funding, Jan Schmidt-Brand, CEO/CFO of WILEX AG and Managing Director of Heidelberg Pharma GmbH, noted: “We are pleased that our PSMA-ATAC project was highly regarded by the BMBF experts. We have already been able to demonstrate high activity of amanitin-based anti-PSMA ATACs in prostate cancer xenograft models. The data encourage the development of these agents through IND-enabling studies to the clinical stage. The BMBF funding will support our approach.”