Applied Therapeutics Announces Presentation of Pre-Clinical Data on AT-001 for the Treatment of Diabetic Cardiomyopathy at the American Heart Association (AHA) Scientific Sessions 2020

Rhea-AI Summary

Applied Therapeutics (Nasdaq: APLT) announced pre-clinical data showing that AT-001, an Aldose Reductase inhibitor, normalizes cardiac energetics and improves cardiac function in a mouse model of Diabetic Cardiomyopathy (DbCM). AT-001 treatment led to decreased cardiac fatty acid oxidation rates and improved cardiac efficiency. This promising data supports the ongoing Phase 3 ARISE-HF study targeting patients at high risk for heart failure. The findings indicate AT-001's potential to shift cardiac cells towards a non-diabetic state, offering meaningful implications for DbCM patients.

Positive

• Pre-clinical data indicates AT-001 normalizes cardiac energetics in diabetic models.
• Improved cardiac efficiency observed with decreased fatty acid oxidation and oxygen consumption.
• Supports ongoing Phase 3 clinical trial ARISE-HF in diabetic cardiomyopathy patients.

Negative

• None.

Treatment with AT-001 normalizes cardiac energetics and improves cardiac function in a mouse model of Diabetic Cardiomyopathy (DbCM)

NEW YORK, Nov. 09, 2020 (GLOBE NEWSWIRE) -- Applied Therapeutics, Inc. (Nasdaq: APLT), a clinical-stage biopharmaceutical company developing a pipeline of novel drug candidates against validated molecular targets in indications of high unmet medical need, announced today  presentation of pre-clinical data demonstrating that Aldose Reductase (AR) inhibition, using the novel AR inhibitor AT-001, normalizes cardiac energy metabolism and prevents cardiac structural and functional abnormalities in a mouse model of Diabetic Cardiomyopathy. AT-001-treated mice exhibited decreased cardiac fatty acid oxidation rates and decreased cardiac oxygen consumption resulting in an improved cardiac efficiency. AT-001 is presently being studied in ARISE-HF, a global Phase 3 randomized, placebo-controlled, pivotal study in DbCM patients at high risk of progression to overt heart failure.

“Aldose Reductase activity causes damage to cardiac tissue in two distinct ways – by actively converting glucose into toxic metabolites which damage cardiomyocytes, and by detracting glucose from otherwise energy efficient pathways,” said Riccardo Perfetti, MD, PhD, Chief Medical Officer of Applied Therapeutics. “We have previously demonstrated that Aldose Reductase inhibition with AT-001 prevents insult to cardiomyocytes caused by oxidative stress and mitochondrial dysfunction. Data presented here at AHA confirms that not only does AT-001 treatment prevent damage to cardiomyocytes, but it shunts glucose back through energy efficient pathways, shifting the cells towards a non-diabetic state. This results in improved cardiac function, which has meaningful implications for patients with Diabetic Cardiomyopathy.”

Presentation Details

P645 (Abstract #15649): Pharmacological Inhibition of Aldose Reductase by AT-001 Prevents Abnormal Cardiac Energy Metabolism and Improves Heart Function in an Animal Model of Diabetic Cardiomyopathy
Time: Friday, November 13, 9:00 a.m. – 10:00 a.m. EST

The presentation and poster will be available on the Presentations and Publications section of the Applied Therapeutics website following the conference.

About Applied Therapeutics
Applied Therapeutics is a clinical-stage biopharmaceutical company developing a pipeline of novel drug candidates against validated molecular targets in indications of high unmet medical need. The Company’s lead drug candidate, AT-007, is a novel central nervous system penetrant aldose reductase inhibitor (ARI) for the treatment of Galactosemia, a rare pediatric metabolic disease. The Company initiated a pivotal Phase 1/2 clinical trial in June 2019, read out positive top-line biomarker data in adult Galactosemia patients in January 2020 and announced full data from the trial in April 2020. A pediatric Galactosemia study commenced in June 2020. The Company is also developing AT-001, a novel potent ARI that is being developed for the treatment of Diabetic Cardiomyopathy, or DbCM, a fatal fibrosis of the heart. The Company initiated a Phase 3 registrational study in DbCM in September 2019. The preclinical pipeline also includes AT-003, an ARI designed to cross through the back of the eye when dosed orally, for the treatment of diabetic retinopathy, as well as novel dual PI3k inhibitors in preclinical development for orphan oncology indications.

About AT-001
AT-001 is an investigational oral, novel, potent Aldose Reductase inhibitor in Phase 3 clinical development for the treatment of Diabetic Cardiomyopathy. AT-001 has been previously studied in a Phase 1/2 study in approximately 120 patients with type 2 diabetes, a subset of which had DbCM.

Investors:
Maeve Conneighton
(212) 600-1902 or
appliedtherapeutics@argotpartners.com

Media:
Gleb Sagitov
media@appliedtherapeutics.com

FAQ

What is the significance of AT-001 in treating Diabetic Cardiomyopathy?

AT-001 has demonstrated the ability to normalize cardiac energy metabolism and improve heart function, which is crucial for patients with Diabetic Cardiomyopathy.

When was the pre-clinical data for AT-001 presented?

The pre-clinical data was presented on November 13 during the AHA conference.

What are the next steps for Applied Therapeutics regarding AT-001?

Applied Therapeutics is currently conducting the Phase 3 ARISE-HF study to evaluate AT-001's effectiveness in patients with Diabetic Cardiomyopathy.

What role does Aldose Reductase play in cardiac function?

Aldose Reductase activity can damage cardiac tissue by converting glucose into toxic metabolites, adversely affecting heart function.

How does AT-001 affect cardiac cells in diabetic models?

AT-001 treatment shifts cardiac cells towards a non-diabetic state, thereby improving their function and efficiency.