• ARISE-HF is a global registrational study in 675 patients with Diabetic Cardiomyopathy (DbCM), evaluating the potential of AT-001 to improve or prevent worsening of cardiac function vs. placebo
• Primary study endpoint is cardiac functional capacity (measured by Peak VO₂) at 15 months
• DbCM is a form of heart failure affecting approximately 20% of Type 2 Diabetes patients (~6M patients in the US and ~5M in EU), which represents a significant commercial market opportunity
• There are currently no treatments approved for DbCM, and AT-001 has the potential to be the first therapy approved

NEW YORK, Oct. 25, 2022 (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, today announced full enrollment in the Phase 3 registrational ARISE-HF trial, studying AT-001, a selective Aldose Reductase inhibitor, in patients with Diabetic Cardiomyopathy (DbCM).

The ARISE-HF study is a randomized double-blind placebo-controlled Phase 3 registrational trial. The study enrolled 675 patients with DbCM at high risk of progression to overt heart failure in the US, EU, UK, Canada, Australia and Hong Kong. The primary endpoint is cardiac functional capacity (as measured by Peak VO₂) at 15 months of treatment. Topline data is expected around year-end 2023 or early 2024, and if positive, the company plans to submit for potential regulatory approval. Patients will continue in blinded format for an additional 12 months of treatment (up to 27 months total) to produce secondary endpoint data on progression to overt heart failure, hospitalization, morbidity and mortality, which is not anticipated for regulatory approval, but will support long-term market access. The ARISE-HF trial also includes an embedded sub-study in patients with both DbCM and Diabetic Peripheral Neuropathy evaluating the impact of AT-001 on neuropathy progression.

AT-001 is a novel, potent, highly selective Aldose Reductase inhibitor. Aldose Reductase is a well validated molecular target, and over-activation of this enzyme is known to result in many diabetic complications, including Diabetic Cardiomyopathy and Diabetic Peripheral Neuropathy. In the ARISE-HF study, AT-001 is dosed twice daily in oral capsules as an add-on to other Type 2 Diabetes standard of care medications. AT-001 is safe and well tolerated to date, with approximately 80 patients having already completed the primary endpoint at 15 months of treatment in the study.

Diabetic Cardiomyopathy is a specific form of heart failure affecting approximately 20% of patients with Type 2 Diabetes (or 1 in 5 people living with diabetes). There are no treatments approved for DbCM to date, and AT-001 has the potential to be the first therapy approved to treat this devastating disease. DbCM is diagnosed via cardiac echo abnormalities or elevated cardiac biomarkers (via a simple blood test) in the absence of coronary artery disease or uncontrolled hypertension. Patients with DbCM have decreased cardiac functional capacity at the time of diagnosis, leading to early symptoms of disease, which continues to progressively worsen over time, resulting in overt heart failure and death.

“Diabetic Cardiomyopathy is a devastating disease that we see every day in clinical practice, but until now have had no treatments to offer patients,” said James Januzzi, MD, Hutter Family Professor of Medicine at Harvard Medical School, cardiologist at Massachusetts General Hospital and Lead Investigator on the ARISE-HF trial. “The ARISE-HF study is a huge step forward in advancing AT-001 as a potential treatment for patients with DbCM. This could be life-saving for millions of people. The global study team is an impressive group of leaders in cardiology and diabetology, and I’m excited to be a part of such a ground-breaking trial.”

“Diabetic Cardiomyopathy is a major health issue, which continues to expand with increasing prevalence of Type 2 Diabetes,” said Riccardo Perfetti, MD, PhD, Chief Medical Officer of Applied Therapeutics. “We look forward to the study readout next year, and the potential to offer the first approved treatment for DbCM to patients.”

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. The global ARISE-HF study is currently ongoing, and is designed to evaluate the ability of AT-001 to improve or prevent worsening of disease, as measured by changes in cardiac functional capacity, in 675 patients with DbCM at high risk of progression to overt heart failure. 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.

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 CNS rare metabolic diseases, including Galactosemia, SORD Deficiency and PMM2-CDG. The Company is also developing AT-001, a novel potent ARI, for the treatment of Diabetic Cardiomyopathy, or DbCM, a fatal fibrosis of the heart. 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.

To learn more, please visit www.appliedtherapeutics.com and follow the company on Twitter @Applied_Tx.

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Contacts:

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

Media:
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Applied Therapeutics, Inc.