# Elafin Therapy for Pulmonary Arterial Hypertension

> **NIH NIH P01** · STANFORD UNIVERSITY · 2020 · $1,729,729

## Abstract

We propose a TPPG Cycle II that builds on the success of Cycle I in showing pre-clinical efficacy of Elafin as a
treatment to reverse pulmonary arterial hypertension (PAH), ventilator induced lung injury of the newborn, and
lung transplant rejection. Each of these conditions could be the subject of Cycle II. However, we chose to focus
on PAH since the FDA granted orphan drug status to Elafin as a treatment for PAH, as an urgent unmet
medical need. Current therapies do not reverse or arrest the progressive obliteration of the lung blood vessels
in PAH that results in clinical deterioration and the need for lung transplantation. During Cycle I, we obtained
help through the NIH-SMARTT program, to fund non-GLP pharmacokinetic and toxicology studies that showed
a favorable profile for daily subcutaneous administration of Elafin in rats. Under the guidance of NIH-SMARTT
consultants, we worked with our industrial partner, Proteo, to prepare a preIND briefing document for our
upcoming joint meeting with the FDA. A contractual agreement between Proteo and Stanford is underway to
pursue an IND for investigator-initiated clinical trials with Elafin at Stanford in Cycle II. The goal of Project 1 is,
therefore, to better understand why and in whom Elafin is most likely to show clinical efficacy. We will
investigate the role of Elafin in neutrophil function and interaction with pulmonary arterial endothelial cells (PA
EC). EC derived from induced pluripotent stem cells will be investigated as surrogates for native PA EC to
understand the basis for responsivity to Elafin, and we will define the interactome of Elafin to identify novel
functions and potential pitfalls of this therapy. In collaboration with Projects 2 and 3 and the Advanced
Proteomic Phenotyping Core, we will use CyTOF to extend the `PAH signature' we have found in circulating
cells (PBMCs) and to investigate the extent to which this abnormal signature is modified by Elafin both in vitro
and in subjects being treated with Elafin. We will use MIBI and apply ABseq to determine the biology of
immune cells and neutrophils that are recruited to the lung perivascular niche. Project 2 aims to address the
potential synergy of Elafin and Treg immunotherapy by attacking both the abnormal innate and adaptive
immune responses in PAH. The subverted function of Tregs in the context of known risk factors for PAH
(female gender, BMPR2 mutation) is investigated in novel experimental rat models of pulmonary hypertension.
Strategic approaches are tested to amplify and improve Treg function as a combinatorial treatment with Elafin
or as a stand-alone PAH therapy. The objectives of Project 3 are to carry out a Phase I clinical trial utilizing
pharmacokinetic and toxicity endpoints in the facilities of the new Stanford Clinical Research and Translation
Unit (CRTU). An extended 180 day GLP toxicity and pharmacokinetic study in the rat will precede a small
multi-center Phase II clinical trial in patients, that will incor...

## Key facts

- **NIH application ID:** 9970516
- **Project number:** 5P01HL108797-09
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Marlene Rabinovitch
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,729,729
- **Award type:** 5
- **Project period:** 2011-08-17 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970516

## Citation

> US National Institutes of Health, RePORTER application 9970516, Elafin Therapy for Pulmonary Arterial Hypertension (5P01HL108797-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9970516. Licensed CC0.

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