# VDX-111: A novel targeted therapeutic for triple-negative breast cancer

> **NIH NIH R44** · VONA ONCOLOGY, LLC · 2024 · $995,137

## Abstract

PROJECT SUMMARY
Triple-negative breast cancers (TNBC) represent a significant challenge to basic scientists studying the 
molecular underpinnings of the disease and to patients and clinicians who deal directly with this most deadly and 
therapy-resistant of breast cancers. Presently, targeted approaches toward the treatment of TNBC are lacking. 
This project directly addresses this critical unmet need. We have developed VDX-111, a novel drug that exerts 
potent pro-apoptotic action in TNBC cell lines but, interestingly, has little or no effect on the majority of nonTNBC and non-tumorigenic breast cells. In vivo, VDX-111 reduces tumor xenograft growth from TNBC cell lines 
and a TNBC patient-derived xenograft (PDX) model. To elucidate the mechanism of VDX-111action, we carried 
out a genome-wide shRNA functional genomics screen designed to identify genes required for VDX-111 action
in TNBC and provide insight into potential resistance mechanisms. The highest-ranking hit from this screen was 
the gene, PTP4A3, encoding the oncogenic phosphatase, PRL-3. To evaluate the clinical significance of PRL-3 
in TNBC, we probed the TCGA database. PRL-3 is amplified in approximately 50% of invasive TNBCs. We
validated PRL-3 as a target of VDX-111. Knockdown of PRL-3 significantly impaired the ability of VDX-111 to 
induce apoptosis. VDX-111 directly blocked the catalytic activity of purified PRL-3 and promotes the degradation 
of PRL-3. VDX-111 inhibited PRL-3-dependent TNBC cell migration and invasion. These findings indicate that
PRL-3 is a major target for VDX-111 in TNBC and is potentially a predictive biomarker for response to VDX-111.
In TNBC cells, VDX-111 synergizes with standard of care drugs frequently administered to TNBC patients,
highlighting its potential as a combinatorial therapeutic agent that could bolster efficacy while reducing the doses 
of the chemotherapeutics. In Phase I we will extend our in vitro proof of concept studies of VDX-111 in 
combination with doxorubicin and paclitaxel in murine TNBC PDX tumor models. To develop the 
commercialization potential of VDX-111, with the ultimate goal of moving it into clinical trials, IND-enabling 
studies are proposed. In Phase II we will (i) complete development and validation of bioanalytical methods for 
clinical testing and (ii), complete IND-enabling safety, toxicity, and PK/PD testing in two species. Phase II studies
will position us for subsequent IND approval and the initiation of human trials. Moreover, accomplishing the 
proposed Phase II goals will empower the commercialization and investment required to bring VDX-111 to the 
clinic for use in TNBC. The expected outcomes of these studies will enable optimization of VDX-111 for improved 
therapeutic options for TNBC patients and determine the safety and PK/PD parameters required for a pre-IND 
meeting with the FDA. These outcomes will establish an attractive investment opportunity to acquire the support 
needed to make VDX-111 an int...

## Key facts

- **NIH application ID:** 10885215
- **Project number:** 5R44CA250674-03
- **Recipient organization:** VONA ONCOLOGY, LLC
- **Principal Investigator:** Cherie Lambert
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $995,137
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10885215

## Citation

> US National Institutes of Health, RePORTER application 10885215, VDX-111: A novel targeted therapeutic for triple-negative breast cancer (5R44CA250674-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10885215. Licensed CC0.

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