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Expanded access programs are intended to provide temporary access to an investigational medication while development is ongoing. Applied is ending the EAP because the program has reached a stage where continued access through this pathway is no longer appropriate for advancing regulatory review and future development.

Ending the EAP allows Applied to focus on next steps in development and regulatory discussions for its programs, including Classical Galactosemia and CMT‑SORD.

Options for continued access vary by diagnosis, location, and individual circumstances.

Caregivers are encouraged to speak with the treating physician about possible next steps, which may include:

• Continued clinical monitoring and supportive care
• Consideration of future clinical studies, if available
• Standard management guided by the healthcare team

Applied cannot provide medical advice directly to caregivers or guarantee govorestat access outside of approved programs.

Based on clinical experience to date across development programs, there is no evidence that stopping govorestat causes withdrawal symptoms or sudden side effects.

If treatment is paused or stopped:

• The medication gradually leaves the body over several days
• There is no known physical dependence
• No new safety concerns have been identified related to stopping treatment

Stopping therapy means the medication is no longer affecting the biological pathway it targets (for example, galactitol reduction in galactosemia or sorbitol‑related pathways in CMT‑SORD). Over time, related biomarkers may return toward pre‑treatment levels. This is expected to occur gradually and is not associated with sudden symptoms.

Caregivers should continue routine follow‑up with their healthcare provider and report any new or concerning changes.

Peer‑reviewed publications describing the clinical and scientific experience with govorestat include:

• Phase 1/2 safety, pharmacokinetics, and pharmacodynamics (adults):
  Perfetti et al., Journal of Clinical Pharmacology (2024)
  https://www.appliedtherapeutics.com/wp-content/uploads/2024/08/The-Journal-of-Clinical-Pharma-2024-Perfetti-Safety-Pharmacokinetics-and-Pharmacodynamics-of-the-New-Aldose.pdf [Safety, Ph…Aldose …]
• ACTION‑Galactosemia Kids study (pediatric clinical outcomes):
  Bailey et al., Journal of Clinical Pharmacology (2024)
  https://pmc.ncbi.nlm.nih.gov/articles/PMC12034909/ [pmc.ncbi.nlm.nih.gov]

The FDA reviewed the New Drug Application (NDA) for govorestat for Classical Galactosemia and issued a Complete Response Letter (CRL) in November 2024, meaning the application could not be approved in its current form.

The FDA’s decision was not based on new safety concerns. Instead, the FDA indicated that additional information is needed before approval can be granted. When reviewing a medication, the FDA applies strict regulatory standards and evaluates the totality of the evidence, including how clinical benefit is measured and demonstrated.

Importantly:

• A CRL does not mean the medication was found to be unsafe
• It reflects that further regulatory review or data clarification is required before approval

Applied has stated that it plans to work with the FDA to understand the agency’s feedback and determine appropriate next steps.

Public sources:

• FDA CRL transparency program (openFDA):
  https://open.fda.gov/apis/transparency/completeresponseletters/ [open.fda.gov]

Applied remains committed to advancing development programs across its rare disease portfolio, including Classical Galactosemia and CMT‑SORD.

Ongoing activities include:

• Reviewing available clinical, biomarker, and safety data
• Engaging with regulatory agencies
• Evaluating appropriate next steps for each condition

Development pathways and timelines may differ by disease. Updates will be shared through appropriate public and clinical channels when available.

Applied Therapeutics and Cycle Pharmaceuticals are separate companies owned by Cycle Group Holdings. Applied Therapeutics remains responsible for the development of govorestat, including its clinical programs, regulatory interactions, and related decision‑making. While both companies operate in rare diseases, their roles, responsibilities, and product plans are distinct.

If responsibilities or development pathways change in the future, that information will be communicated clearly to healthcare providers, patients, and caregivers.