# Development of the New Synthetic Triterpenoid CDDO-2P-IM (TTX01) for Glioblastoma

> **NIH NIH R43** · TRITERPENOID THERAPEUTICS, INC. · 2020 · $399,908

## Abstract

PROJECT SUMMARY/ABSTRACT
Glioblastoma multiforme (GBM; grade IV glioma) is the most common primary brain tumor. An estimated 700,000
people in the United States (US) are living with a primary brain tumor, and over 86,000 more will be diagnosed in
2019. GBM is the most aggressive primary brain tumor and remains a frequently incurable cancer, resulting in
more than 17,000 annual deaths in the US alone. The outlook for patients with GBM is invariably dismal, with only
5% surviving beyond 5 years. Those who do survive suffer significant therapy-related complications that greatly
diminish their quality of life and they also endure a significant financial burden. Indeed, brain tumors have the
highest per-patient initial cost of care for any cancer group, with annualized mean net costs of care in US dollars
at well over $150,000. However, despite this prevalence and the devastating prognosis, there have only been four
FDA approved drugs to treat brain tumors in the past 30 years, without significant improvement in outcomes over
this same time period. These facts regarding GBM highlight a desperate need for new and innovative approaches
to treat this lethal disease. Notably, it has been over 14 years since the U.S. Food and Drug Administration
(FDA)
approved temozolomide (
Temodar / TMZ) for the treatment of adult patients with newly diagnosed GBM,
which is now given concomitantly with radiotherapy and then as maintenance treatment as the standard of care.
Despite the addition of TMZ to the standard of care, the average length of survival for a patient with GBM remains
at 14 months. Moreover, prolonged exposure to TMZ is associated with significant toxicity, including profound
lymphopenia, and with the development of drug resistance. Because GBM is currently often incurable, there is a
dire need for novel drugs that target mechanisms that underlie therapy resistance in GBM and that can enhance
the response TMZ and radiation. This project will provide essential new information, required by the FDA, to
allow approval of an IND for use of a new drug for treatment of GBM. The drug is CDDO-2-Pyridyl Imidazolide
(“2P-Im” or TTX01), a new triterpenoid synthesized and tested for anti-cancer activities at Dartmouth, and
now licensed by Dartmouth to Triterpenoid Therapeutics, Inc. The goal of this Phase 1 grant application will
be to determine the in vivo efficacy and pharmacodynamics of TTX01 in relevant mouse models of human
GBM. To advance TTX01 toward clinical application, we will define both optimal dose and dosing schedule
to provide the most durable clinical response in well-established, human PDX and xenograft models and in an
immune competent syngeneic murine model of GBM (Aim 1). Moreover, we will also provide proof-of-concept
data that TTX01 administration can enhance the response to either Temodar or radiation (Aim 2). Variations
in combined dosing regimens will be studied, as will the possibility that TTX01 could suppress the development
of important ...

## Key facts

- **NIH application ID:** 10081123
- **Project number:** 1R43CA254786-01
- **Recipient organization:** TRITERPENOID THERAPEUTICS, INC.
- **Principal Investigator:** Michael B Sporn
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $399,908
- **Award type:** 1
- **Project period:** 2020-09-08 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10081123

## Citation

> US National Institutes of Health, RePORTER application 10081123, Development of the New Synthetic Triterpenoid CDDO-2P-IM (TTX01) for Glioblastoma (1R43CA254786-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10081123. Licensed CC0.

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