Background

Over the past decade, the pharmaceutical industry has experienced major business challenges, including an estimated cost of US$ 1–2 billion and development timelines of 15–20 years for a new drug, and a failure rate that approximates 95 percent. As a consequence, many pharmaceutical companies downsized their operations, especially in early drug discovery. To fuel their R&D pipelines, major companies began to establish a more open innovation model, which was based on partnerships with small biotechnology companies and academic institutions to develop programs focused on novel drug targets or novel drug scaffolds.
A few universities in the US recognized the pharma industries’ new business model early on, founded internal research alliances and offered early drug discovery services to external collaborators. By the end of 2011, leaders from Vanderbilt University (VU), the University of North Carolina (UNC), Harvard University and others formed the Academic Drug Discovery Consortium (ADDC) and invited other centers within and outside the US to join the consortium. As of early 2018, 149 drug discovery centers, mainly from the US, have joined the consortium with the objectives

to establish an interactive network of the growing number of academic drug discovery centers,
to exchange know how and expertise related to drug discovery programs and industry partnerships,
to create a central repository of drug discovery centers, partnerships, job opportunities and events,
and
to provide a platform for partnering and collaboration between consortium members and the life science industry including pharma, biotech, CRO´s and other service providers.

The University of Tübingen, as a worldwide recognized source of first-class basic research in life science, adopted this concept of joining scientific competences, founded the Tübingen Center for Academic Drug Discovery and Development (TüCAD2) and joined the ADDC in 2015.

Goals and Activities

Within TüCAD2, without any restrictions regarding the specific medical area or indication, each scientific innovation with the potential of translation from basic research to clinical application is being supported. High quality projects will be highlighted and made visible to potential external collaborators.

Currently, TüCAD2 supports projects in oncology, infectious diseases, regenerative medicine and cardiovascular diseases.

Oncology

Chemotherapy has been and remains to be the most powerful tool to treat cancer, and, despite all progress of recent years, research continues to find new chemotherapy drugs as well as new uses for existing ones. The concept of targeted therapy aims at identifying mechanisms which are highly critical for the survival and growth of cancer cells while being less relevant for normal cells.

RNA interference (RNAi) technology is a powerful tool and nonbiased approach for identifying genes whose suppression affects cell proliferation and viability. Although genome-wide RNAi screens have been widely used for the identification of new therapeutic targets in cancer, these screens are technically challenging, tedious, and error-prone because of the high complexity of the short-hairpin RNA (shRNA) libraries.[1] Using this conceptual approach, a series of relevant tumor suppressors have been identified which led to new therapeutic concepts for the treatment of various cancers, e.g. acute myeloid leukemia (AML), hepatocellular carcinomas (HCC), lung and pancreatic cancer.

The Medical Hospital in Tübingen harbors one of the very few facilities (Prof. Lars Zender’s laboratory) in the world with an established in vivo RNAi screening platform. Employing this technique, the molecular mechanism, which leads to the development of resistance against Nexavar® (sorafenib), the only available targeted therapy of HCC, was elucidated and the activity of a protein kinase has been identified as molecular target and being responsible for the developed resistance.[2] Subsequently, in collaboration with the Dept. of Pharmaceutical Chemistry (chair: Prof. Stefan Laufer), a drug substance, which blocks the activity of this kinase was discovered and after testing in non-clinical safety studies, successfully applied in patients with HCC and a developed resistance against sorafenib treatment. This example demonstrates Tübingen’s capacity for bench-to-bedside development of a new therapeutic concept, as illustrated in the scheme below.

Privacy settings