# Evaluating the efficacy of a novel NASH therapeutic

> **NIH NIH R43** · SIEGE PHARMACEUTICALS, INC. · 2023 · $298,159

## Abstract

PROJECT SUMMARY
Obesity and other characteristics of metabolic syndrome are key underlying factors in the development of non-
alcoholic fatty liver disease (NAFLD). If left unchecked, NAFLD can progress to non-alcoholic steatohepatitis
(NASH), cirrhosis, and hepatocellular carcinoma. Up to 60% of the 80-100 million Americans with NAFLD will
progress to NASH, yet there are no FDA-approved therapeutics; the only treatment option currently available is
weight loss. The overall objective of this project is to determine whether the Siege compound merits development
as a NASH therapy. Recently published work demonstrates improvement of liver phenotypes in a diet-induced
obesity model without toxicity in normal tissues and thus the potential to address an as-yet unmet need for NASH
patients. Siege Pharmaceuticals is taking a new approach to treating this disease: correcting ROS, ER stress,
and hyperleptinemia upstream of liver dysfunction, inflammation, and fibrosis instead of just targeting the pheno-
types without addressing the root cause. Aim 1 will evaluate the efficacy of Siege’s compound in a mouse model
that reproduces the pathological features seen in patients with NASH while Aim 2 will test SGE-893 in a liver
microtissue model derived from primary human cells, allowing for dissection of liver-specific and weight loss-
driven effects and validation in a human model system. These studies will establish whether development as a
NASH therapeutic is merited and could support a future Phase II program. If the Siege compound performs as
expected, both improving NASH phenotypes and correcting metabolic dysfunction, it could dramatically im-
prove the overall health of patients who currently have no therapeutic options.

## Key facts

- **NIH application ID:** 10698971
- **Project number:** 1R43DK136429-01
- **Recipient organization:** SIEGE PHARMACEUTICALS, INC.
- **Principal Investigator:** Alison Nicole McCracken
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $298,159
- **Award type:** 1
- **Project period:** 2023-08-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10698971

## Citation

> US National Institutes of Health, RePORTER application 10698971, Evaluating the efficacy of a novel NASH therapeutic (1R43DK136429-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10698971. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*