# Development of Small Molecule Inhibitors and Biologic Agents for Treatment of Glioblastoma Using Intracerebral Microdialysis and Signatures of Vulnerability

> **NIH NIH U19** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2022 · $920,861

## Abstract

PROJECT SUMMARY - OVERALL
The overall goal of this Glioblastoma (GBM) Therapeutics Network (GTN) U19 application from City of Hope,
Translational Genomics Research Institute, and University of Alabama at Birmingham is to develop superior
treatments for patients with GBM, the most common and aggressive primary brain tumors in adults. Effective
treatments remain elusive and patients are rarely cured with standard therapies. This GTN U19 application
embodies a unique combination of approaches designed to significantly advance the treatment of patients with
GBM by addressing tumor heterogeneity, blood-brain barrier penetration, and the immunosuppressive GBM
tumor microenvironment. The three proposed research projects will translate therapeutic agents from preclinical
development, through IND-enabling studies, and into phase I clinical studies in adult patients with GBM. Each
project is based on novel molecular preclinical studies with small-molecule inhibitors and immunomodulatory
agents that use signature-guided assessment and treatments. Specific goals of the projects are:
 Project 1. Develop and clinically test an engineered oncolytic herpes virus expressing a full-
 length anti-CD47 monoclonal antibody for treatment of GBM.
 Project 2. Develop and clinically test tasquinimod as an adjunct to enhance the efficacy of
 anti-GBM immunotherapies administered peri-operatively.
 Project 3. Develop and clinically test a molecular “signatures of vulnerability” guided treatment
 of GBM with neddylation inhibitor pevonedistat.
In addition, this U19 application proposes strategies that will address major barriers in drug development by
incorporating two innovative research tools: 1) intracerebral microdialysis to rationally select appropriate
systemically administered therapies for testing in GBM patients and 2) next generation exome and transcriptome
sequencing to identify molecular “signatures of vulnerability” that can guide appropriate patient selection for
clinical trial enrollment. These analytical capabilities will enable us to quantify CNS drug penetration and dissect
genomic heterogeneity in tumor and stromal cells in the proposed clinical trials. Also, two of the proposed projects
leverage City of Hope’s GMP facilities to manufacture biological agents and small molecules that will be tested
in adult GBM patients for the first time.
In summary, the innovative projects and shared resources cores in this application combine our strengths in
basic, translational, and clinical research in a highly collaborative setting that promotes the sharing of ideas,
results, resources, and clinical populations to develop effective treatments for GBM. If successful, data generated
by these studies have the potential to transform the treatment of adult GBM patients by introducing new agents
that circumvent tumor heterogeneity and immunosuppression.

## Key facts

- **NIH application ID:** 10488199
- **Project number:** 5U19CA264512-02
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** Behnam Badie
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $920,861
- **Award type:** 5
- **Project period:** 2021-09-13 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10488199

## Citation

> US National Institutes of Health, RePORTER application 10488199, Development of Small Molecule Inhibitors and Biologic Agents for Treatment of Glioblastoma Using Intracerebral Microdialysis and Signatures of Vulnerability (5U19CA264512-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10488199. Licensed CC0.

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