# Novel targeted therapy for treating Ovarian Cancer

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2022 · $689,000

## Abstract

PROJECT SUMMARY:
Ovarian cancer (OCa) is the deadliest of all gynecologic cancers in the United States. Patients with OCa initially
respond to standard combinations of surgical and cytotoxic therapy; however, nearly 90% will develop recurrence
and inevitably succumb to chemotherapy-resistant disease. OCa stem cells are implicated in the tumor re-
initiation and therapy resistance. Lack of targeted therapies that promote apoptosis of tumor cells and eliminate
cancer stem cells in OCa represents a critical barrier. The goal of this Academic-Industry Partnership (AIP)
grant application is to develop a novel targeted therapy for treating OCa. Through this AIP grant, we will establish
a collaborative framework between the University of Texas Health at San Antonio and Evestra Inc., a San
Antonio based biotech to create a novel targeted therapy for treating OCa. With Evestra Inc.'s expertise in
developing novel small molecule inhibitors that disrupt protein-protein interactions, we have rationally designed
and synthesized a first-in-class leukemia inhibitory factor receptor (LIFR) inhibitor, EC359. Our preliminary
studies have shown that EC359 reduces the growth of OCa cells with high potency, promote apoptosis, reduce
stemness, sensitize therapy resistant OCa cells and has in vivo activity with favorable PK parameters. The
objective of this AIP proposal is to synthesize EC359 in grams using GLP protocol, establish its mechanisms,
identify biomarkers, conduct efficacy studies using PDX models, and perform off target screening studies that
are needed to file the Investigational New Drug (IND) Application to FDA. Our overarching hypothesis is that
LIFR signaling plays a critical role in OCa progression, and disruption of LIF/LIFR signaling with small molecule
inhibitor EC359 will have a therapeutic effect by promoting apoptosis of OCa cells, reducing stemness, and
promoting anti-tumor immunity by altering the tumor microenvironment. Our AIP team is unique due to
synergistic expertise in drug development, availability of GMP facility, experience with OCa biology, preclinical
models and geographic proximity. In Aim1, we will evaluate translatability of EC359 by determining maximum
tolerated dose, toxicity, biodistribution, in vivo efficacy using xenografts and PDX models and test the utility of
EC359 in combination with standard of care chemotherapy. In Aim 2, we will define EC359 mechanisms,
establish molecular correlates of EC359 activity using unbiased genomic and proteomic approaches, define the
role and mechanism by which EC359 reduces stemness and determine the role of EC359 in reprogramming
the anti-OCa immunity, including macrophages, in syngeneic and humanized mouse models. In Aim 3, we will
synthesize EC359 using multi-gram scale, conduct metabolite studies, perform cardiovascular safety screens,
and establish formulation and chemistry manufacturing controls. The studies proposed in this AIP proposal will
establish a novel targeted therapy that wi...

## Key facts

- **NIH application ID:** 10522920
- **Project number:** 1R01CA266970-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Hareesh B Nair
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $689,000
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10522920

## Citation

> US National Institutes of Health, RePORTER application 10522920, Novel targeted therapy for treating Ovarian Cancer (1R01CA266970-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10522920. Licensed CC0.

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