# Novel therapeutic for HPA hyperactivity

> **NIH NIH R44** · STRESS THERAPEUTICS, INC. · 2024 · $605,404

## Abstract

Summary.
 The hypothalamic pituitary adrenal (HPA) axis is the key neuroendocrine system that controls
peripheral responses to stress. While the stress response is essential for survival, it can become
dysregulated. Hyperactivity of the HPA characterizes a variety of illnesses including alcohol use
disorder (AUD). HPA hyperactivity is characterized by higher production of corticotropin-releasing
factor (CRF) and glucocorticoids.
 This Phase II SBIR aims to develop a novel biologic therapeutic aimed at normalizing pathologic
HPA hyperactivity. Medications to modulate the HPA axis are currently sub-optimal. Therapeutic
attempts to use glucocorticoid receptor (GR) antagonists have shown some promise in conditions like
AUD and depression. However, chronically blocking GR-mediated effects can be counterproductive
as, for instance, it interferes with glucocorticoid negative feedback, leading to increased cortisol levels
and mineralocorticoid receptor activation. CRF receptor type 1 (CRF1) antagonists have been
extensively explored, but thus far have proven disappointing, possibly because of the
pharmacokinetics and pharmacodynamics properties of the existing drugs. Therefore, the
identification of novel therapeutics to normalize hyperactivity of the HPA axis represents an area of
significant unmet medical need.
 This proposal will optimize a lead validated in the Phase I SBIR and establish a stable cell line for
the production of material for the eventual Investigational New Drug (IND)-enabling studies and
clinical trials. Altogether, the present project will lay the foundations for the clinical development of a
first-in-class therapeutic for AUD and potentially for other conditions characterized by HPA axis
hyperactivity.

## Key facts

- **NIH application ID:** 10834160
- **Project number:** 5R44AA027971-03
- **Recipient organization:** STRESS THERAPEUTICS, INC.
- **Principal Investigator:** Linda S Lloyd
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $605,404
- **Award type:** 5
- **Project period:** 2019-09-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10834160

## Citation

> US National Institutes of Health, RePORTER application 10834160, Novel therapeutic for HPA hyperactivity (5R44AA027971-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10834160. Licensed CC0.

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