- TEAD inhibition holds great promise as a therapeutic approach as the Hippo pathway is genetically altered in up to 10% of cancers. In mesothelioma, an aggressive and untreatable cancer often caused by asbestos exposure, 60 to 70% of patients have mutations in the Hippo pathway leading to striking sensitivity to TEAD-inhibitors.
SpringWorks Expects to Nominate a Development Candidate and Commence IND-Enabling Studies in 2022
LEUVEN, Belgium, May 6, 2021 – KU Leuven, CD3 and VIB today announced that they have entered into an exclusive worldwide license agreement with SpringWorks Therapeutics, Inc. (Nasdaq: SWTX) for a portfolio of novel small molecule inhibitors of the Transcriptional Enhanced Associate Domain (TEAD) family of transcription factors, designed for the potential treatment of biomarker-defined solid tumors driven by aberrant Hippo pathway signaling. The licensed portfolio includes advanced lead compounds and multiple backup compounds from diverse chemical series, which were discovered at KU Leuven’s Centre for Drug Design and Discovery (CD3) in collaboration with Professor Georg Halder of the VIB-KU Leuven Centre for Cancer Biology. SpringWorks, a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer, expects to nominate a development candidate and move into IND-enabling studies in 2022.
“Since first identified by our group and others in the fruit fly Drosophila almost 20 years ago, the Hippo pathway has come to be recognized as a central regulator of cell proliferation and organ growth. Given that the Hippo pathway is genetically altered in up to 10% of cancers, TEAD inhibition holds great promise as a therapeutic approach,” said Professor Georg Halder.
Patrick Chaltin, Managing Director of CD3 at KU Leuven added: "This agreement demonstrates CD3’s strong drive to translate promising scientific insights into attractive novel therapies that improve patients’ lives. We have generated potent TEAD inhibitors which show impressive regression of mesothelioma cancer in preclinical animal models. We are very excited to be at the basis of this potential treatment option for patients with mesothelioma and other devastating cancers driven by aberrant Hippo pathway signaling such as certain forms of lung, liver and kidney cancer. It is very gratifying to see this technology be advanced towards the clinic by SpringWorks.”
Jérôme Van Biervliet, Managing Director of VIB added: “The collaboration between SpringWorks, CD3, and VIB, exemplifies VIB’s mission to combine excellence in research with proactive technology transfer to advance early innovative science towards the clinic, maximizing societal impact.”
Under the terms of the agreement, SpringWorks will pay KU Leuven and VIB an upfront payment of $11 million. KU Leuven and VIB are also eligible to receive up to $285 million in development, regulatory and commercial milestones from SpringWorks and tiered single-digit percentage royalties based on any future net sales.
About the Hippo Pathway and TEAD
The Hippo pathway is an evolutionarily conserved signaling cascade that regulates organ development and tissue growth and regeneration. The Transcriptional Enhanced Associate Domain (TEAD) family is a group of four homologous transcription factors whose activity is regulated by the Hippo pathway. The TEAD family is the terminal component of the Hippo pathway and transcriptional activity of this family has been implicated in a variety of tumors characterized by aberrant Hippo signaling. Transcription of TEAD target genes requires TEAD to form a transcriptional complex with the co-activators YAP or TAZ. Activation of the Hippo pathway prevents YAP and TAZ from translocating to the nucleus, preventing TEAD-dependent transcription. Aberrations and genetic mutations that limit Hippo pathway activation can result in significant increases in TEAD dependent transcription and have been identified as key drivers in several tumor types, including subsets of mesothelioma, non-small cell lung cancer, head and neck cancer, and kidney cancer.