# Development of synthetic sphingolipids for prostate cancer therapy

> **NIH NIH R44** · SIEGE PHARMACEUTICALS, INC. · 2021 · $989,405

## Abstract

PROJECT SUMMARY
The objective of this project is to develop the synthetic sphingolipid SGE-893 (893) into an FDA-approved cancer
therapy, with the ultimate goal of reducing mortality and morbidity rates in end-stage, drug-resistant prostate
cancer. 893 shows promising pharmacological characteristics and potent anti-cancer activity in pre-clinical
models while sparing normal tissues. 893 and related molecules have a novel mechanism of action,
simultaneously engaging two validated oncology targets. This dual-target approach is deadly to cancer cells and
predicted to reduce the risk of resistance. Despite its pleiotropic actions, 893 is well-tolerated by normal
proliferating cells. Thus, 893 shows potential as a single-agent therapy that could produce a durable response
even in hard-to-treat cancers like late-stage prostate, for which systemic chemotherapy remains the standard-
of-care (SOC) and high recurrence and mortality rates are driven by resistance. As 893’s mechanism of action
further suggests that it could sensitize drug-resistant tumors to FDA-approved agents, 893 may have additional
clinical applications as a component of combination therapy. With key de-risking studies completed, we are
proposing a Direct-to-Phase II approach. The objectives of Aim 1 are to extend the Target Product Profile by
evaluating efficacy in combination with FDA-approved agents and to validate pharmacodynamics markers that
can be used to measure target engagement in a phase 1 trial. Aim 2 proposes toxicology studies required for an
IND application. The expected results would become part of a strong portfolio demonstrating acceptable toxicity
to share with the FDA. Were it to be approved for patient use, this innovative molecule would become a first-in-
class compound, offering hope and reducing mortality in PC patients whose tumors fail to respond to or become
resistant to SOC.

## Key facts

- **NIH application ID:** 10269032
- **Project number:** 5R44CA257568-02
- **Recipient organization:** SIEGE PHARMACEUTICALS, INC.
- **Principal Investigator:** Alison Nicole McCracken
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $989,405
- **Award type:** 5
- **Project period:** 2020-09-24 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10269032

## Citation

> US National Institutes of Health, RePORTER application 10269032, Development of synthetic sphingolipids for prostate cancer therapy (5R44CA257568-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10269032. Licensed CC0.

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