# A novel long-acting conjugate of the vasodilative hormone, human brain natriuretic peptide (hBNP), to treat resistant hypertension

> **NIH NIH R44** · ANTLIA BIOSCIENCE INC · 2024 · $999,998

## Abstract

SUMMARY
 Hypertension affects one-third of US adults (68-88 million cases), contributing to >500,000 deaths per year
and healthcare expenses of $51-131 billion annually. Despite the availability of myriad FDA-approved drugs to
lower blood pressure, 15-20% of patients are resistant to treatment, and many more patients are unresponsive
because of non-adherence to their medication schedule. With an aging population and the increasing prevalence
of hypertension, effective treatment for hypertension is likely to become progressively more critical.
 Human brain natriuretic peptide (hBNP) potently lowers blood pressure. hBNP is produced by the heart in
response to high blood pressure, leading to vasodilation, excretion of salt and water in the urine, and inhibition
of certain enzymes that raise blood pressure. The safety and effectiveness of hBNP as a therapeutic (aka
nesiritide, Natrecor®) were proven for short-term use, but it must be given by constant intravenous infusion or
multiple suboptimal daily injections, because it is rapidly removed from the blood. Sale of Natrecor® was
discontinued by the manufacturer in 2018 due to decreasing sales after it was shown that a short-term infusion
of the acute-acting endogenous peptide had no beneficial effect on reducing long-term rehospitalization or death.
Antlia Bioscience has resolved the issue that previously impeded the long-term effectiveness of Natrecor®
 Antlia Bioscience has discovered an innovative method to extend the lifespan of hBNP in the blood, while
keeping its ability to lower blood pressure without increasing heart rate. Antlia has added a block of 200 units of
the three amino acids—Proline-Alanine-Serine, PAS(200)—to the hBNP peptide, creating a large molecule that
resists degradation and elimination from the blood. Importantly, dogs treated with PAS(200)-hBNP demonstrated
significant and sustained blood pressure lowering after a single injection, with minimal adverse side effects.
Subsequently three additional hBNP compounds have been made with 400, 600, and 800 PAS units, which were
shown to produce progressively longer and higher plasma exposure in a rat pharmacokinetic study. The
PAS(400)-hBNP analog is anticipated to be suitable for up to 2x monthly dosing in humans, while the PAS(600)
and PAS(800) analogs could provide once monthly or longer dosing intervals. For first proof-of-concept studies
designed to establish safety and efficacy in patients, we will use the PAS(400)-hBNP product with an anticipated
>72-hour half-life in humans. In preparation for human studies, this Direct-to-Phase-II proposal will pursue bulk
manufacture of clinical-grade PAS(400)-hBNP with formulation and stability studies (Aim 1). The first non-clinical
batch of the compound made during manufacturing process development will be used for dose-range-finding
PK/PD studies in rats and dogs with the goal of defining the therapeutic range of doses with associated plasma
concentrations over time (Aim 2). From the r...

## Key facts

- **NIH application ID:** 10815642
- **Project number:** 1R44HL169016-01A1
- **Recipient organization:** ANTLIA BIOSCIENCE INC
- **Principal Investigator:** Brian Laurence Johnson
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $999,998
- **Award type:** 1
- **Project period:** 2024-09-19 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10815642

## Citation

> US National Institutes of Health, RePORTER application 10815642, A novel long-acting conjugate of the vasodilative hormone, human brain natriuretic peptide (hBNP), to treat resistant hypertension (1R44HL169016-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10815642. Licensed CC0.

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