# Therapeutic Inhibition of MYC:TRRAP Interaction in Cancer (I-Crops Supplement)

> **NIH NIH R42** · COSMYC INC · 2024 · $55,000

## Abstract

RESEARCH STRATEGY
Executive Summary of Predicate SBIR or STTR Phase I Grant and Team
cosMYC, Inc. intends to develop and commercialize small molecule cancer therapeutics that selectively target
the MYC oncoprotein, which is a transcriptional factor that regulates key transcriptional programs required for
cellular growth and proliferation. Due to its overexpression in more than 70% of human cancers and the functional
validation that MYC downregulation arrests cancer growth, MYC has been the most sought-after therapeutic
target in cancer. Despite decades of effort, therapeutic targeting of MYC has been unattainable due to a
combination of factors, including a lack of enzymatic activity or obvious ligand binding sites that can aid in
inhibitor identification. Recent research by the PI, Dr. Feris (cosMYC CEO), in the Cole laboratory at Dartmouth,
has uncovered an Achilles’ heel in MYC that has enabled therapeutic targeting of this previously undruggable
target. While unraveling the molecular mechanism underlying MYC’s interaction with the
TRansactivation/tRansformation-domain Associated Protein (TRRAP), which is essential for many of the MYC-
driven aberrant transcriptional programs that promote cancer, Dr. Feris’ research revealed a vulnerability in MYC.
This insight led to the development of a revolutionary screening platform which was later deployed to assay more
than 0.5 million compounds. Partial assessment of the high-throughput screening (HTS) efforts identified several
hits that not only blocked intracellular MYC:TRRAP protein-protein interaction (PPI) at low µM potency but also
potently (2 µM) attenuated 2D and 3D growth of multiple cancer cell lines in a highly MYC-dependent manner,
highlighting the specificity and selectivity of the hits. The specific aims of the one-year Phase I STTR project are
to: (1) conclude hit discovery efforts by completing HTS hit assessment and (2) test the hypothesis, using our
recently identified heterocyclic amide compound (A1), that MYC:TRRAP PPI inhibition attenuates tumor growth
in a human lymphoma xenograft mouse model. The goal of the future Phase II project is hit-to-lead development
of Phase I hits for future clinical development as novel MYC-targeted therapeutics for cancer.
A. Cancer B. No Cancer
Inhibitor
TRRAP
TRRAP MAX protein
X
MYCMYC
Target genes
Target genes
Figure 1. Project Premise. Small-molecule inhibitors of MYC-TRRAP interaction can block
MYC-driven aberrant transcriptional programs to prevent cancer.
Ed Feris, PhD (C-level Corporate Officer, CLO): Dr. Feris is the program PI/PD and CEO of cosMYC. He has
significant training and research experience in the fields of molecular, cellular, and cancer biology, specifically
pertaining to MYC. Dr. Feris’ expertise and experience in MYC biology and drug discovery make him ideally
suited to lead these efforts.
John F. Kaufmann, MBA (Technical Lead/Expert, TL): Mr. Kaufmann is a consultant at cosMYC, Inc. and has
served S1Biopharma Chief Financial O...

## Key facts

- **NIH application ID:** 11121194
- **Project number:** 3R42CA290915-01S1
- **Recipient organization:** COSMYC INC
- **Principal Investigator:** Ed Feris
- **Activity code:** R42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $55,000
- **Award type:** 3
- **Project period:** 2024-06-18 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11121194

## Citation

> US National Institutes of Health, RePORTER application 11121194, Therapeutic Inhibition of MYC:TRRAP Interaction in Cancer (I-Crops Supplement) (3R42CA290915-01S1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/11121194. Licensed CC0.

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