VT3989, Vivace Therapeutics' Best-in-Class, Hippo Pathway-Targeting Therapy, Demonstrates Promising Antitumor Activity in Refractory Mesothelioma

Latest Data from Phase I/II Study Reported in an Oral Presentation at the European Society for Medical Oncology (ESMO) Congress 2025 and Published Concurrently in Nature Medicine

VT3989 Achieves 32% Overall Response Rate, 86% Disease Control Rate, and 40 Weeks of Median Progression-Free Survival in Heavily Pretreated Mesothelioma Patients

Vivace to Advance VT3989 into Phase 3 Registrational Trial in Mesothelioma Patients in First Half of 2026

VT3989, a First-in-Class TEAD Autopalmitoylation Inhibitor, is the First Therapy Targeting the Hippo Pathway to Demonstrate Compelling Clinical Activity in Cancer

SAN MATEO, Calif., Oct. 19, 2025 /PRNewswire/ -- Vivace Therapeutics, Inc., a small molecule discovery and development company developing first-in-class cancer therapies targeting the Hippo pathway, today announced new data from the company's ongoing Phase 1/2 clinical trial of its first-in-class transcriptional enhanced associate domain (TEAD) autopalmitoylation inhibitor, VT3989. Findings demonstrated notable antitumor activity for VT3989 in refractory mesothelioma patients, along with a manageable safety and tolerability profile. Based on these positive study results, Vivace plans to advance VT3989 into a registrational Phase 3 trial in mesothelioma in the first half of 2026. The findings were the focus of an oral presentation at the European Society for Medical Oncology (ESMO) Congress 2025, as well as a peer-reviewed paper in Nature Medicine that was published concurrently with the ESMO presentation.

The presentation highlighted a cohort of 22 refractory mesothelioma patients treated with the optimized Phase 3 dose and schedule for VT3989. Key findings for VT3989 in this population include:

• Objective Response Rate (ORR) of 32% (7 of 22 patients achieved a partial response).
  
  
• Disease Control Rate (DCR) of 86% (19 of 22 patients achieved a partial response or stable disease).
  
  
• Median Progression-Free Survival (PFS) of 40 weeks, which is more than double the 15-week benchmark for standard-of-care salvage chemotherapy.

Study results showed VT3989 treatment to be safe and well tolerated with no dose-limiting toxicities in 172 patients across dose escalation and dose expansion cohorts. The majority of reported adverse events (AEs) were categorized as mild or moderate in severity and the discontinuation rate due to AEs was low (3.5%). The most commonly reported treatment-related AEs were low grade fatigue, proteinuria (a reversible increase of protein in the urine), and swelling in the extremities. The total number of patients experiencing Grade 3/4 treatment-related AEs was low at 15 (8.7%).

"These findings make a compelling case for the therapeutic potential of VT3989 in the treatment of mesothelioma, a cancer that presents significant treatment challenges and for which there are few therapeutic options beyond first‑line therapies" said Timothy A. Yap, M.B.B.S.., Ph.D., Head of Clinical Development in the Therapeutics Discovery Division at the University of Texas MD Anderson Cancer Center and lead clinical investigator for the study. "We are encouraged by the clinically meaningful disease control that was achieved with VT3989, especially in these heavily pretreated patients. We believe that the strength of these efficacy findings, combined with the encouraging safety profile demonstrated in the study, support the advancement of VT3989 into a registrational clinical trial for mesothelioma."

The ongoing Phase 1/2 study (https://clinicaltrials.gov/ct2/show/NCT04665206) 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 mesothelioma. The mesothelioma patients treated with the optimized Phase 3 dose represented a heavily pre-treated patient population, with all having received immunotherapy and 82% having received chemotherapy.

"It is gratifying to share these positive study data, particularly considering how much hard work our team has undertaken in not only developing a first-in-class therapy against a novel target, but doing so in a notoriously hard-to-treat cancer," said Neelesh Sharma, M.D., Ph.D., chief medical officer of Vivace. "Demonstrating such a clear and substantial benefit compared to salvage chemotherapy benchmarks gives us great confidence as we prepare to advance VT3989 into a Phase 3 program. We are committed to bringing this first-in-class therapy to patients who are in desperate need of new treatment options."

VT3989 was recently awarded Orphan Drug Designation and Fast Track Designation by the United States Food and Drug Administration for the treatment of mesothelioma. The Fast Track Designation specifically applies to the treatment of patients with unresectable malignant non-pleural or pleural mesothelioma whose disease has progressed on prior immune checkpoint inhibitor therapy and platinum-based chemotherapy.

The ESMO presentation will be available on Vivace's website at www.vivacetherapeutics.com following the conference. The Nature Medicine paper can be accessed on the publication's website at www.nature.com/nm/.

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 needs. Based in San Francisco Bay Area, the company has raised $105 million to date. For more information, please visit www.vivacetherapeutics.com.

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SOURCE Vivace Therapeutics, Inc.