Alnylam Pharmaceuticals (ALNY) TTR Investor Day summary

Strategic vision and future growth

• Positioned Amvuttra for first-line use in ATTR cardiomyopathy, leveraging robust HELIOS-B data and quarterly dosing for strong adherence and broad access.

• Built a global commercial presence in over 60 countries, with direct sales in all major markets and a strong track record in ATTR polyneuropathy.

• Anticipates multi-billion dollar franchise growth, with a focus on early diagnosis, patient-centric commercialization, and expanding the diagnosed patient pool.

• Plans to double the clinical pipeline by end of 2025, with 15 current clinical programs and new INDs in liver, CNS, adipose, and muscle targets.

• Committed to sustainable innovation, progressing next-generation assets like TTRsc04 for deeper knockdown and more convenient dosing.

Market opportunity and commercial readiness

• ATTR cardiomyopathy market estimated at 300,000 patients globally, with majority undiagnosed and untreated; U.S. prevalence around 150,000.

• Three key patient segments targeted: new to treatment, stabilizer progressors, and undiagnosed patients, with initial focus on new to treatment for rapid uptake.

• U.S. infrastructure already covers 65% of treating physicians and 45% of key health systems, with plans to expand to 100% at launch.

• Over 99% of patients have coverage for Amvuttra in hATTR-PN, with 70% paying zero out-of-pocket; similar access expected in ATTR-CM.

• Patient support services and site-of-care flexibility drive 95% adherence, with 90% of patients within 20 miles of a treatment site.

Competitive landscape and differentiation

• HELIOS-B data show significant reductions in mortality and CV events, with benefits consistent across all subgroups, including those on background tafamidis.

• Early treatment yields greater benefit; Amvuttra’s quarterly dosing and strong adherence differentiate it from daily oral stabilizers.

• Anticipates increased diagnosis rates and market expansion as awareness grows and more therapies enter the space.

• Confident in maintaining first-line positioning even as tafamidis goes generic, due to clinical profile and patient/physician preference.

• Next-generation TTRsc04 aims for biannual/annual dosing and no third-party royalties, supporting long-term franchise durability.