Researchers Report Clinical Proof-of-Concept Data for Vivace Therapeutics' VT3989, a First for a Cancer Drug Targeting the Hippo Pathway, in Oral Presentation at AACR 2023

First-in-Class TEAD Autopalmitoylation Inhibitor is Well Tolerated and Demonstrates Antitumor Activity in Advanced Mesothelioma and NF2-Mutant Cancers

VT3989 is the First Therapeutic Targeting the Hippo Pathway to Demonstrate Clinical Activity in Patients with Cancer

SAN MATEO, CA, USA I April 16, 2023 I Vivace Therapeutics, Inc., a small molecule discovery and development company developing first-in-class therapies targeting the Hippo pathway, today announced that the first clinical data for a cancer treatment targeting the Hippo pathway was presented at the American Association for Cancer Research (AACR) Annual Meeting 2023. Results from the company's Phase 1 clinical study of its first-in-class transcriptional enhanced associate domain (TEAD) autopalmitoylation inhibitor, VT3989, showed the compound to be well tolerated with durable antitumor responses in patients with advanced malignant mesothelioma and other tumors with neurofibromatosis 2 (NF2) mutations. These findings were presented by Timothy A. Yap, M.D., Ph.D., of The University of Texas MD Anderson Cancer Center, during an oral plenary session at the conference. The AACR conference is being held April 14-19, 2023, in Orlando, Florida.

Seven (7) of 69 patients had reductions in tumor size meeting the rigorous criteria for being partial responses that persisted up to 21 months, and 34 had stable disease. Tumor response was observed in patients with mesothelioma with and without NF2 mutations and other solid tumors with NF2 mutations. Because mesothelioma patients often have NF2 mutations or loss of Merlin it was an a priori indication of interest. Six (6) of the seven (7) partial responses were in patients with mesothelioma. The other response was in a sarcoma patient with an NF2 mutation. Of the 69 patients presented, 43 had advanced malignant mesothelioma and 26 had other solid tumors. Patients were heavily pre-treated with a median of three prior lines of therapy. A total of 37 patients had NF2 mutations. Ongoing dose optimization cohorts of the study are investigating different doses and schedules in two-stage designs.

"These are encouraging results that provide the first clinical proof-of-concept for drugging the Hippo-YAP-TEAD pathway," said Dr. Yap. "Preclinical data suggested that blocking the YAP-TEAD interaction could shrink tumors, and these clinical data validate that approach. These are early clinical trial data, but we look forward to future results from this trial and continuing to investigate the benefits to patients."

VT3989 was well tolerated with no dose-limiting toxicities observed. The most common adverse events were albuminuria (a reversible increase in the protein albumin in the urine), swelling in the extremities, fatigue, and nausea. There were only seven grade 3 adverse events that were possibly treatment-related, which included albuminuria, swelling, fatigue, and increased liver enzymes alanine transaminase and aspartate aminotransferase, and one possibly related grade 4 cardiomyopathy. 

Based on robust efficacy seen in dose escalation and plasma levels of VT3989 at and exceeding the concentrations projected for activity, the study has now expanded in patients with mesothelioma to define the dose and schedule that will become the basis of registrational development in patient with mesothelioma.

"It is gratifying to see the extensive preclinical data that we have generated for VT3989 translate so well into humans in both the anti-tumor activity and tolerability profile demonstrated in this clinical study. We view this as a significant milestone as these data position VT3989 as the very first cancer treatment targeting the Hippo pathway to show clinical relevance," said Sofie Qiao, Ph.D., chief executive officer of Vivace Therapeutics. "Based on this initial successful translation of preclinical data into humans, we now have high levels of confidence in a registrational path for VT3989 as a single agent in mesothelioma as well as in combination with targeted therapies to expand utility into major solid tumors. We look forward to continuing our development efforts in mesothelioma and proving the combination treatment hypothesis in a clinical setting."

The AACR presentation will be available at after the conference.

In additional news from the AACR conference, Vivace Therapeutics announced that Tracy Tang, Ph.D., the company's vice president of biology was named winner of the inaugural Molecular Cancer Therapeutics Award for Outstanding Journal Article by AACR. The award is given to the authors of a Molecular Cancer Therapeutics article published in 2021-2022 that has had significant impact on the fields represent by the journal. It was presented to Dr. Tang and her co-authors for the paper entitled, "Small Molecule Inhibitors of TEAD Auto-palmitoylation Selectively Inhibit Proliferation and Tumor Growth of NF2-deficient Mesothelioma," at the AACR Journals Reception during the conference.

About Phase 1 study of VT3989
The Phase 1 study of VT3989 ( is a multi-center, open label trial designed to evaluate the safety, tolerability, pharmacokinetics (PK) and biological activity of VT3989 in patients with refractory metastatic solid tumors, including refractory pleural malignant mesothelioma. The study includes both a dose escalation and a dose expansion phase, the latter of which is enrolling mesothelioma patients who have tumors with or without NF2 mutations.

About Vivace Therapeutics, Inc.
Vivace Therapeutics is a small molecule drug discovery and development company focused on targeting the Hippo pathway. The company is pursuing a first-in-class approach to treat human carcinomas of high unmet medical need. Based in San Francisco Bay Area, the company has raised $70 million to date, and is funded by leading biotechnology investors, including Canaan Partners, WuXi Healthcare Ventures, Cenova Capital, Sequoia Capital China, Boxer Capital and RA Capital Mangement. For more information, please visit

SOURC: Vivace Therapeutics

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