# Phase I Therapeutic Award - Developing Split, Conditionally Active Peptidomimetics of IL-12 For the Treatment of Rare Pediatric DIPG

> **NIH NIH N43** · UTTER THERAPEUTICS INC. · 2024 · $299,500

## Abstract

Diffuse intrinsic pontine glioma (DIPG) is a rare, universally fatal childhood brainstem tumor, striking about 150-300
children in the US with a median survival of only 9-11 months. For 50 years, clinical trials in DIPG have been an
abject failure; however, recently GD2-CAR-T therapy has shown promise in small DIPG clinical studies.
A new paradigm for the treatment of DIPG is proposed using tumor-targeted mimics of a powerful immune stimulating
cytokine IL-12, naturally found in the body. As a therapeutic, IL-12 bridges innate and adaptive immunity in human
clinical trials but severe systemic toxicities limit the ability to achieve maximum benefit.  This proposal radically engineers IL-12 so its biological activity is conditional to binding GD2 uniquely expressed on DIPG tumors. Instead of IL-12 protein, we use high content screening of macrocyclic peptidomimetic libraries containing 10^14 compounds to create completely new compounds that mimic IL-12, bioactivity, allowing precise chemistry-based
tools to 1) conditionally activate IL-12R signaling upon GD2-binding (creating an AND gate), 2) minimize systemic
exposure via tunable pharmacokinetics and 3) increase tumor penetration by minimizing molecular weight. Finally, a
synthetic targeted IL-12 mimic sets the stage for future scalable manufacture that increases accessibility of
immunotherapy to more DIPG patients.

## Key facts

- **NIH application ID:** 11036428
- **Project number:** 75N91024C00004-0-9999-1
- **Recipient organization:** UTTER THERAPEUTICS INC.
- **Principal Investigator:** DEBORAH CHARYCH
- **Activity code:** N43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $299,500
- **Award type:** —
- **Project period:** 2024-02-15 → 2025-02-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11036428

## Citation

> US National Institutes of Health, RePORTER application 11036428, Phase I Therapeutic Award - Developing Split, Conditionally Active Peptidomimetics of IL-12 For the Treatment of Rare Pediatric DIPG (75N91024C00004-0-9999-1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11036428. Licensed CC0.

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