In September 2016, Heidelberg Pharma had signed an exclusive option agreement with the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) in Berlin covering various B-cell maturation antigen (BCMA) antibodies. In January 2017, the option was exercised and a license agreement was signed.
BCMA is a surface protein that is highly expressed in multiple myeloma cells and in approximately 50% of Chronic Lymphocytic Lymphoma and Diffuse Large B-Cell Lymphoma cells to which the selected antibodies specifically bind. Scientists at the MDC developed these BCMA-specific antibodies. Heidelberg Pharma has synthesized several proprietary ATAC molecules with these antibodies and generated comprehensive preclinical data. Based on these data, Heidelberg Pharma has selected a lead candidate for later clinical development, HDP-101, which consists of a BCMA antibody, a specific linker and the Amanitin toxin.
Preclinical data showed that HDP-101 had strong in vitro anti-tumor activity and led to complete tumor remission in mouse models for multiple myeloma even at very low doses.
In addition, tolerability studies conducted in different in vivo models identified a very favorable therapeutic window. Multiple myeloma is a cancer affecting bone marrow and the third most common hematologic cancer; it represents a major unmet medical need where new, more effective therapies are urgently needed. HDP-101 also has potential in other hematologic indications.
Preparations for formal preclinical as well as the clinical development of HDP-101 are now ongoing. This includes cell line development for the production of non-GMP (Good Manufacturing Practice) and GMP batches of antibody material to be used for the manufacturing of HDP-101 clinical material. These tasks are being performed externally by Celonic AG, Basel, Switzerland, a contract development and manufacturing organization (CDMO) for biopharmaceutical proteins. Other preclinical trials are planned to be conducted at the same time, including tolerability studies in monkeys, in line with high quality standards (GLP/GMP) to guarantee safety for subsequent human trials.
Further ATAC Partnerships
Heidelberg Pharma has in-licensed several antibodies to create and evaluate follow-up ATAC pipeline development candidates.
The German Cancer Research Center in Heidelberg provided, among others, access to a couple of CD-19 specific antibodies that were genetically improved and transformed via conjugation to ATAC molecules. CD-19 is a B-lymphocyte antigen, a protein found on the surface of follicular dendritic cells and B-cells, a type of white blood cell in humans. Antibodies addressing this antigen are used to treat different forms of leukemias.
Furthermore, Freiburg University licensed several PSMA (prostate-specific membrane antigens) specific antibodies to Heidelberg Pharma. PSMA is overexpressed in prostate cancer and is a promising target for ATAC technology, as it shows very low expression in normal tissues. In pilot studies, Heidelberg Pharma investigated the anti-tumor efficacy of several monoclonal antibodies targeting PSMA conjugated to amatoxin. After humanization and de-immunization of the chosen anti-PSMA antibody, this was used to produce various ATACs, which will be tested in preclinical studies for safety, tolerability and efficacy.
Heidelberg Pharma has entered into alliances with several biotech companies (including MabVax Inc. and Nordic Nanovector ASA for the development of new antibody drug conjugates. These companies are using Heidelberg Pharma’s proprietary ATAC technology with different antibodies of their own to develop new ATACs for cancer therapy.