# Demonstrating the feasibility of CCG-257081 as a preventive therapy to inhibit bleomycin-induced lung fibrosis in mice

> **NIH NIH R43** · FIBROSIX, LLC · 2020 · $2,500

## Abstract

ABSTRACT
Front-line therapy for patients diagnosed with Hodgkin’s lymphoma or germ cell cancers includes the drug
bleomycin, a highly effective agent with a debilitating side effect. About 10-12% of bleomycin-treated patients
develop pneumonitis with progression to pulmonary fibrosis during therapy as a direct result of bleomycin. An
estimated 10-20% of these cases are fatal. The current standard approach to this problem involves elimination
of bleomycin from the chemotherapy regimen and long-term treatment with corticosteroids, which have no effect
on fibrosis. This makes bleomycin-induced lung fibrosis a significant treatment-limiting side effect that impedes
the ability of patients to complete therapy. The team behind FibrosIX LLC has developed a novel compound,
CCG-257081, that has shown efficacy in preventing bleomycin-induced fibrosis in several mouse models. The
molecular target of this compound was recently found to be a nuclear protein regulator of NFkB, a crucial
mediator of inflammation. Our data suggest the target is also a regulator of the pro-fibrotic myocardin-related
transcription factor (MRTF)/serum response factor (SRF) gene transcription pathway. The MRTF/SRF gene
transcription pathway is a critical step in the fibroblast-to-myofibroblast transition that occurs in fibrosis
development. This unique dual mechanism means that our compound can inhibit both inflammatory (NFkB) and
pro-fibrotic (MRTF) effects of bleomycin toxicity. The goal of this Phase I SBIR is to test the hypothesis that
targeting this dual mechanism with CCG-257081 can prevent lung fibrosis in mouse models that mimic bleomycin
chemotherapy. We will test the ability of CCG-257081 at multiple doses to prevent lung fibrosis in mice given
repeated, systemic injections of bleomycin. Fibrosis in the lungs will be measured by collagen content assessed
through both histopathological and biochemical assays. Our results will be validated by an independent
contractor and compared to standard therapy with prednisolone and a potential anti-fibrotic competitor,
pirfenidone. Blood and peripheral tissues will also be examined for preliminary measures of toxicity. Upon
successful achievement of milestones in Phase I, we will submit an application for a Phase II SBIR to conduct
IND-enabling studies of CCG-257081. Our ultimate goal is to incorporate CCG-257081 as a standard component
of all bleomycin-containing chemotherapy regimens to allow oncologists to treat patients with the full course of
bleomycin treatment, resulting in reduced mortality and improved patient outcomes. With over 8,000 new cases
of Hodgkin’s lymphoma and over 9,000 new cases of germ cell cancers that are treated with bleomycin each
year, this creates a total addressable market of about 17,000 patients per year who could benefit from CCG-
257081.

## Key facts

- **NIH application ID:** 10241577
- **Project number:** 3R43CA235823-01S1
- **Recipient organization:** FIBROSIX, LLC
- **Principal Investigator:** Kendell Marleen Pawelec
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,500
- **Award type:** 3
- **Project period:** 2020-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241577

## Citation

> US National Institutes of Health, RePORTER application 10241577, Demonstrating the feasibility of CCG-257081 as a preventive therapy to inhibit bleomycin-induced lung fibrosis in mice (3R43CA235823-01S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10241577. Licensed CC0.

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