Risk Factors Update Summary

• Changes in regulatory processes may delay approval. For example, new EU clinical trial regulations may cause delays in commencing studies.
• Net losses decreased from $220.4 million in 2022 to $153.2 million in 2023.
• Changes in EU pharmaceutical legislation may significantly impact the industry.
• Approval of competing products for SCD and TDT may impact patient recruitment for RUBY trial.
• The Medicines and Healthcare products Regulatory Agency now oversees medicines in Great Britain.
• Increased risk due to cash held by financial institutions exposed to liquidity issues or bank failures.
• The passage of the Food and Drug Omnibus Reform Act introduces diversity action plans for clinical trials.
• Accumulated deficit decreased from $1.1 billion to $1.23 billion.
• List prices for approved medicines for SCD and TDT by Vertex and bluebird bio.
• Funding secured until 2026 with existing cash, marketable securities, and license fees.
• Added provisions to discourage, delay, or prevent a merger, including limitations on director removal.
• The Windsor Framework fundamentally changes the regulation of medicines in the UK.
• The enactment of the Clinical Trials Regulation in the EU simplifies the authorization process.
• Enhanced governance measures, such as advance notice requirements for stockholder proposals and nominations.
• Future capital requirements extended into 2026, dependent on clinical development progress.
• Brexit may lead to heightened risks in obtaining marketing authorization in the UK.
• Limited experience in scaled manufacturing may lead to delays or supply shortages.