Risk Factors Update Summary

• Announced topline two-year confirmatory secondary endpoint results from the PROTECT Study in September 2023.
• Changes to UK legislation aim to streamline clinical trials, enhancing transparency and patient involvement.
• Plan to submit a supplemental New Drug Application (sNDA) in Q1 2024 for FILSPARI full approval.
• Companies in the UK can no longer use the EU centralized procedure for marketing authorizations.
• FDA approved three generic options for Thiola EC 100 mg and 300 mg, up from one.
• Initiated pivotal Phase 3 HARMONY Study in December 2023 for pegtibatinase treatment of classical HCU.
• Introduction of a Notification Scheme for clinical trials in the UK for Phase 4 and low-risk Phase 3.
• Net Operating Losses increased from $90 million to $154 million, a significant rise.
• The MHRA introduced new procedures to prioritize access to new medicines, including a 150-day assessment route.
• Workforce reduction of approximately 20% announced in December 2023 to align resources.
• The MHRA may rely on the International Recognition Procedure for certain marketing authorization applications.
• Changes in orphan designation review process tailored for the UK market with specific prevalence criteria.
• Risks related to financial institutions' failures and market-wide liquidity problems could impact business operations.