Company Summary - Applied Therapeutics, Inc.

Overview:
Applied Therapeutics, Inc. is a biopharmaceutical company focused on developing therapies for rare, debilitating, or life-threatening diseases, particularly through the inhibition of Aldose Reductase (AR), an enzyme implicated in various metabolic and neurological disorders.

Core Focus and Programs:

• Development of Novel AR Inhibitors (ARIs) targeting multiple rare diseases and conditions, including:

  • Galactosemia: A genetic disorder affecting galactose metabolism leading to toxic metabolite accumulation and long-term complications.
  • SORD Deficiency: A genetic neuropathy caused by deficiency in Sorbitol Dehydrogenase, leading to high sorbitol levels and neuronal degeneration.
  • PMM2-CDG: A glycosylation disorder where AR inhibitors may increase enzyme activity.
  • Diabetic Cardiomyopathy (DbCM): A fatal fibrosis of the heart with high unmet medical need, where AR activity contributes to disease progression.
  • Diabetic Retinopathy (DR): An eye disease linked to AR activity involving sorbitol and fructose pathways.

• Lead product candidate: AT-007 (govorestat)

  • Investigated for multiple rare diseases and disorders.
  • Received orphan and rare pediatric disease designations from the FDA.
  • Progressed through Phase 2/3 clinical trials for SORD Deficiency and Galactosemia.
  • A New Drug Application (NDA) for Galactosemia was accepted but later received a Complete Response Letter from the FDA in November 2024.

• Other product candidates include AT-001 (caficrestat) for DbCM and AT-003 for Diabetic Retinopathy, but the company is currently focusing resources on rare diseases.

Partnerships and Licensing:

• Europe: Licensing agreement with Advanz Pharma for commercialization of AT-007 in Europe, including milestone payments over €130 million and 20% royalties.
• US and other regions: Licensing agreements with Columbia University and University of Miami for patents and Know-How related to AR inhibition and treatment of related disorders.
• Additional licensing: License from University of Miami for SORD-related therapies and an agreement with Mercury Pharma (Advanz) for European rights.

Employees and Bedrock Operations:

• As of December 31, 2024:
  • Number of employees: 35 (18 in R&D).
  • No product has been approved for sale.
  • No revenue generated from product sales.
  • Significant operating losses:
    • Net loss (2024): $105.6 million
    • Accumulated deficit: $574.2 million

Financials (2024):

• Cash and cash equivalents: $79.4 million
• The company has a "going concern" explanatory paragraph from auditors, indicating doubts about continuing operations without additional funding.
• Multiple equity financings, including IPO, secondary offerings, private placements, and ATM sales, have raised significant capital, but no ongoing revenue stream exists.

Intellectual Property:

• Patents licensed from Columbia University and University of Miami, covering composition of matter, methods of treatment, and uses related to ARIs.
• The patent portfolio includes ten families with patents and pending applications globally, with terms generally through 2031–2041, depending on jurisdiction and extensions.

Research and Development Focus:

• Developing compounds with improved potency and selectivity.
• Using biomarkers to demonstrate biological activity.
• Employing accelerated regulatory pathways for rare diseases.
• Addressing unmet needs with therapies for rare metabolic and neurodegenerative diseases.

Summary:
Applied Therapeutics, Inc. is a clinical-stage biotech company with a focus on rare disease therapeutics targeting AR, with multiple product candidates in development, no current revenue, significant operating losses, and a strategic emphasis on specialized patient populations through licensing and partnering agreements.