Takeda Pharmaceutical Company (4502) investor relations material

Study background and objectives

• Oveporexton is an oral orexin 2 receptor agonist developed to address the root cause of narcolepsy type 1 (NT1) by restoring orexin signaling and normalizing symptoms to improve patient quality of life.

• Two global, randomized, double-blind, placebo-controlled phase III trials enrolled 273 adults with NT1 for 12 weeks, with over 95% entering long-term extension studies.

• The trials assessed 14 primary and secondary endpoints, including excessive daytime sleepiness, cataplexy, cognition, nighttime symptoms, and quality of life.

• Oveporexton is positioned as a first-in-class therapy for NT1, with anticipated regulatory filings in fiscal year 2025 and projected global peak revenue of $2–3+ billion.

• The commercial strategy includes investments in education, access, and diagnostic innovation, with additional orexin agonists in development for related disorders.

Key efficacy results

• Statistically significant and clinically meaningful improvements were observed in wakefulness (MWT), sleepiness (ESS), and cataplexy rates, with most patients reaching normative levels at 12 weeks.

• Cataplexy rates were reduced by 80–90%, with a substantial increase in cataplexy-free days and sustained benefits over 12 months.

• Disease severity, as measured by NSS-CT, was significantly reduced, with over 70% reporting only mild symptoms after 12 weeks.

• Patient-reported outcomes showed 69–79% had no or mild symptom severity, and 74–97% reported much or very much improved symptoms.

• Nighttime symptoms, cognition, and quality of life measures improved significantly, with many patients reaching normative ranges.

Safety and tolerability

• Oveporexton was generally well tolerated, with most adverse events being mild or moderate and transient.

• The most common adverse events were insomnia and urinary frequency/urgency, typically resolving within the first week.

• No serious treatment-related adverse events or cases of hepatotoxicity were reported.

• Visual disturbances were rare, balanced between placebo and active groups, and not clinically significant.

• No significant safety concerns were identified in laboratory or vital sign assessments.