# Dihydroceramide Desaturase-1 Inhibitors for Treatment of Diabetes and Other Metabolic Diseases

> **NIH NIH R44** · POTRERO HILL THERAPEUTICS, INC. · 2020 · $1,069,999

## Abstract

NIH SBIR Phase 2B
Title: Dihydroceramide Desaturase-1 Inhibitors for Treatment of Diabetes and Other Metabolic Diseases
 Potrero Hill Therapeutics
Project Summary/Abstract:
 Despite the current FDA-approved glucose-lowering agents, the prevalence of type 2 diabetes (T2D)
and its complications continues to reach epidemic proportions. Globally, 387 million people have overt
diabetes, and the prevalence of impaired fasting glucose (precursor to T2D referred to as “pre-diabetes”) is
26% of the US population. Consequently, T2D and its frequent complications (high triglycerides, non-alcoholic
fatty liver disease / non-alcoholic steatohepatitis [NAFLD/NASH], diabetic kidney disease (DKD), and
cardiovascular disease) increasingly account for a large proportion of global end-stage renal and liver failure,
limb amputations, blindness, myocardial infarctions, and strokes. To address this highly unmet need, Potrero
Hill Therapeutics (“PHT”) is developing highly-potent, drug-like, and orally-active small molecule inhibitors of
dihydroceramide desaturase-1 (DES1), a key enzyme which catalyzes the final step in the de novo formation
of ceramides, molecules which drive insulin resistance, high triglycerides, NAFLD/NASH, and DKD when
produced in excess. This work has been partially funded through SBIR Phase 1 and Phase 2 grants, and in
this Phase 2B grant, PHT will take the next critical steps of advancing its lead preclinical development
candidate into IND-enabling activities, including GMP process development and GLP toxicology/safety studies.
In addition, efficacy in a validated rodent model of DKD will also be explored. Ultimately, completion of these
aims will get us to the point of being ready to open an initial IND to execute a first-in-human Phase 1a clinical
trial.

## Key facts

- **NIH application ID:** 10145104
- **Project number:** 2R44DK116450-04
- **Recipient organization:** POTRERO HILL THERAPEUTICS, INC.
- **Principal Investigator:** Jeremy Blitzer
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,069,999
- **Award type:** 2
- **Project period:** 2017-09-11 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10145104

## Citation

> US National Institutes of Health, RePORTER application 10145104, Dihydroceramide Desaturase-1 Inhibitors for Treatment of Diabetes and Other Metabolic Diseases (2R44DK116450-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10145104. Licensed CC0.

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