Risk Factors Update Summary

• Addition of new product candidates: sepiapterin for PKU and Upstaza for AADC deficiency.
• The negative opinion on Translarna's marketing authorization in the EEA could lead to revenue loss.
• Expiration of Emflaza's orphan drug exclusivity in February 2024, impacting net product revenue.
• Failure to renew marketing authorization may impact regulatory approvals in other jurisdictions.
• Discontinuation of gene therapy programs for Friedreich ataxia and Angelman syndrome.
• Submission of BLA for Upstaza for AADC deficiency in the US in March 2024.
• Negative opinion issued for Translarna's conditional marketing authorization in the EEA.
• Increased accumulated deficit from $2.657 billion to $3.283 billion as of December 31, 2023.
• Potential $65.0 million payment upon regulatory milestone achievement for sepiapterin.
• Ongoing expenses and potential dilution to stockholders from raising additional capital.
• Limited personnel experience in drug manufacturing, particularly for certain product candidates.
• Completion of enrollment for regulatory milestones related to sepiapterin for PKU.
• Transition to cGMP manufacturing at the Hopewell Facility for clinical material production.
• Potential impact on income tax provision due to NOLs and tax legislation changes.