# DEVELOPMENT AND TESTING OF SUBCUTANEOUS CSD PEPTIDE FORMULATIONS FOR CHRONIC KIDNEY DISEASE

> **NIH NIH R43** · LUNG THERAPEUTICS, INC. · 2020 · $300,228

## Abstract

Project Summary
The global prevalence of chronic kidney disease (CKD) is estimated to be greater than 10%, affecting
approximately 500 million people around the world, and due to the global type II diabetes epidemic, incidence is
expected to rise. CKD-specific treatments do not currently exist. Clinical management focuses primarily on
controlling blood pressure using renin–angiotensin system (RAS) inhibitors, which results in attenuated CKD
progression, but it is not curative. Kidney fibrosis (KF) is a pathological hallmark of CKD and a major contributing
factor to progression to end-stage renal disease. Therefore, developing a therapy that targets fibrotic processes in
the kidney may slow or halt CKD progression, reducing the cost and the quality of life burdens that accompany
dialysis and transplantation. Lung Therapeutics’ patented LTI-03 is a 7-mer peptide (FTTFTVT) derived from the
20-mer caveolin-1 scaffolding domain (CSD) of CAV-1 (known as CSP7 in the literature). It attenuates
established fibrosis in multiple in vivo pre-clinical models of dermal, cardiac and pulmonary fibrosis (PF) and
attenuates multiple pro-fibrotic signaling pathways in vitro. We have developed an inhaled formulation of LTI-03
for the treatment of Idiopathic Pulmonary Fibrosis (IPF), and regulatory approval was received to start a first in
human safety trial in 2020. Cav1-/- mice demonstrate increased cell proliferation and collagen synthesis, leading
to myocardial hypertrophy and pulmonary hypertension; both are normalized by endothelial cell specific re-
expression of Cav-1. Furthermore, Cav1-/- mice exhibited more extensive interstitial fibrosis than WTs following
release of a unilateral ureteral obstruction (RUUO). Recently, CSD peptide was found to be efficacious in
reducing both heart and kidney fibrosis in an angiotensin model of systemic hypertension. Lung Therapeutics’
patented, soluble and proteolysis resistant peptide, LTI-2355, was even more efficacious than CSD (data
unpublished). Furthermore, while both of the FDA-approved (non-curative) IPF drugs Nintedanib and Pirfenidone
were efficacious for reducing KF in the UUO model, a new therapeutic, PRM-151, was efficacious in the Alport
Syndrome (AS) model of CKD and in a 2019 Ph2 clinical trial for IPF. Based on these findings, we propose to
develop both a simple and extended release form of LTI-2355 for subcutaneous (SC) delivery and to generate
stability and pharmacokinetic data. Next, after obtaining stability and PK data, leads will be rigorously evaluated
in a rapid onset AS model to identify the best lead candidate. The final lead will be assessed in a moderate onset
AS model (evaluated both against and with standard of care). Pending efficacious results, a lead candidate will
be selected, and a Phase II will be filed to support further clinical development (PK/PD, toxicology specificity of
SC formulation, IND-supporting work). This proposal caters to the aggregate strengths of the team including
pepti...

## Key facts

- **NIH application ID:** 10082145
- **Project number:** 1R43DK124010-01A1
- **Recipient organization:** LUNG THERAPEUTICS, INC.
- **Principal Investigator:** BreAnne MacKenzie
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $300,228
- **Award type:** 1
- **Project period:** 2020-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10082145

## Citation

> US National Institutes of Health, RePORTER application 10082145, DEVELOPMENT AND TESTING OF SUBCUTANEOUS CSD PEPTIDE FORMULATIONS FOR CHRONIC KIDNEY DISEASE (1R43DK124010-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10082145. Licensed CC0.

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