Vivace snares $30M to push Hippo-targeting drugs into the clinic

The Hippo pathway, despite playing a role in a variety of different mechanisms in a variety of different tumor types, was considered impossible to drug. (Gene Taylor/Pixabay)

Three years after coming of out stealth, Vivace Therapeutics has raised another $30 million to pursue drugs targeting the Hippo-YAP pathway. The funding, drawn from Boxer Capital, RA Capital Management and Canaan Partners, will push its lead program into the clinic in the first half of 2021.

The company emerged in 2017 with $40 million in series A and B funding to pursue a two-pronged strategy in oncology: developing drugs that inhibit the Hippo signaling pathway and developing bispecific antibodies dubbed BINspecific antibodies, discovered in the lab of Vivace’s scientific co-foudner, Bin Liu, Ph.D.

Vivace spun out its bispecifics work in 2018 so it could throw its resources behind its efforts to drug the Hippo pathway, which—despite playing a role in a variety of different mechanisms in a variety of different tumor types—was considered impossible to drug, said Vivace CEO Sofie Qiao, Ph.D., and Chief Scientific Officer Len Post, Ph.D.

Len Post, Ph.D., (left) and Sofie Qiao, Ph.D.
(Vivace Therapeutics)

RELATED: Vivace uncloaks with $40M, U.S.-China backing for cancer trials

“The Hippo pathway is all about the mechanism for controlling a particular program of gene expression in a group of genes driven by a transcription factor called YAP,” Post said. “While YAP is turned on, it makes this set of genes tend to be involved in growth and survival and various stress responses.”

In healthy cells, the Hippo pathway controls organ size and apoptosis, or programmed cell death. But mutations in the Hippo pathway drive several cancers, including mesothelioma, a cancer of the mesothelium, the thin tissue that lines the lung, chest wall and abdomen, and meningioma, a tumor that forms on membranes that cover the brain and spinal cord just inside the skull. Such tumors depend on activated YAP to survive and grow, but, even though researchers have long known about the role of YAP in some cancers, there wasn’t a way to turn the protein off, Post said.

“There were no obvious drug targets like the usual kinases or receptors we usually target in oncology drug discovery,” he added.

Instead of aiming at YAP directly, Vivace is targeting proteins in the transcriptional enhanced associate domain (TEAD) family.

RELATED: Boosting cancer immunotherapy by switching off a protein

“For YAP to work, it needs to form a complex with another protein called TEAD. And for TEAD to work, it needs to have a fatty acid called palmitic acid covalently attached to it,” Post said.

Vivace’s compounds block the attachment of the fatty acid onto TEAD, making it unable to combine with YAP and throwing a wrench into the survival mechanism of certain cancers.

Most of the series C will go toward clinical trials, but it will also fund expansion into other indications.

“The Hippo pathway is really important to a number of tumors due to mutations and activated YAP. The whole field is still working heavily on understanding further the implication of the pathways in various cancer indications,” Qiao said. “We will be continuing our work in collaboration and also by ourselves on indication expansion for our development candidates."