# Clinical Development of Elafin as a PAH Therapy

> **NIH NIH P01** · STANFORD UNIVERSITY · 2020 · $723,280

## Abstract

The central goal of this translational P01 grant is to advance and apply the knowledge gained from Cycle I
pre-clinical and clinical findings to the treatment of pulmonary arterial hypertension (PAH). Current
therapies for PAH largely address the potential for dilatation of unobliterated pre-capillary pulmonary arteries
and augmentation of right ventricular function but do not effectively target the extensively remodeled
vasculature or the altered inflammatory or immune processes that contribute to this pathobiology. Project
3, Clinical Development of Elafin as a PAH Therapy addresses this unmet need by moving a very
promising agent into the clinic while, at the same time, carrying out ancillary studies that will uncover an
extensive biology of PAH related to altered innate and adaptive immunity. Elafin is a promising therapy
for PAH because of its multiple functions as an inhibitor of neutrophil elastase, proteinase 3 and NFκB
and as an activator of bone morphogenetic protein receptor (BMPR)2 signaling. Under the guidance of
the NIH-SMARTT program and in collaboration with our industry partner, Proteo Biotech, we have
developed a solid clinical development plan for Elafin focused on establishing its safety, tolerability, and
efficacy in a step-wise fashion. This plan will be extensively discussed and reviewed with the United
States Food and Drug Administration (US-FDA) at an anticipated pre-IND meeting in late Fall. Aim 1 of
Project 3 is to carry out a Phase I clinical trial utilizing the facilities of the new Stanford Clinical
Research and Translation Unit (CRTU), the resources of the Stanford Center for Clinical Research
(SCCR) in monitoring safety and tolerability, and the expertise of SRI International in carrying out
pharmacokinetic, and immunogenicity studies. The Phase I clinical trial will be followed by an extended
180-day good laboratory practices (GLP) toxicity, pharmacokinetic, and immunogenicity study in the rat. In
Aim 2, we propose a small multi-center, randomized, placebo-controlled, double-blind Phase II clinical
trial in PAH patients that will evaluate safety, tolerability pharmacokinetic and immunogenicity endpoints
as well as indices of efficacy as judged primarily by reduction in pulmonary vascular resistance on right
heart catheterization study. Other efficacy endpoints will include the six minute walk distance, NT-pro BNP
and New York Heart Association Class. In conjunction with the Advanced Proteomic Phenotyping core,
and Projects 1 and 2, we will determine the impact of Elafin on the immune/inflammatory signature of PAH
in circulating blood cells using a novel hybrid cytometry-mass spectrometry time of flight technique
(CyTOF). We will also elucidate the nature of the Elafin responder vs. non-responder by utilizing bioassays
and gene expression studies in personalized induced pluripotent stem cells differentiated into endothelial
cells.

## Key facts

- **NIH application ID:** 9970522
- **Project number:** 5P01HL108797-09
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Roham Zamanian
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $723,280
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970522

## Citation

> US National Institutes of Health, RePORTER application 9970522, Clinical Development of Elafin as a PAH Therapy (5P01HL108797-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9970522. Licensed CC0.

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