Andy Chan

Andy Chan asked about the anticipated ramp speed and eventual market opportunity for zilganersen in Alexander disease. He also requested a comparison of this opportunity to other rare diseases like DAWNZERA or FCS.

Answer

Holly Kordasiewicz, Chief Development Officer, highlighted zilganersen's statistically significant and clinically meaningful Phase 3 results, positive community response, and the initiation of an early access program. Kyle Jenne, Chief Global Product Strategy Officer, detailed the market, noting approximately 300 patients in the U.S. with about 50% identified, and a focus on a dozen major leukodystrophy centers. He guided to greater than $100 million in peak revenue, with a modest launch this year and growth into 2027. Brett Monia, CEO, emphasized the strategic value of zilganersen as the first independent launch from Ionis's neurology pipeline.

Andy Chan inquired about the anticipated launch ramp and eventual market opportunity for Zilganersen in Alexander disease, asking for a comparison to other rare disease opportunities like DAWNZERA or FCS.

Answer

Executive VP and Chief Development Officer Holly Kordasiewicz highlighted Zilganersen's statistically significant and clinically meaningful Phase 3 results, positive community response, and early access program. Chief Global Product Strategy Officer Kyle Jenne detailed the U.S. patient population (approx. 300 identified), focused launch strategy targeting leukodystrophy centers, modest team size, and peak revenue guidance of greater than $100 million, with modest sales in 2026 growing into 2027. CEO Brett Monia emphasized the strategic value of Zilganersen as the first wholly-owned neurology launch.

Andy Chan asked about the patient selection strategy for the chronic rhinosinusitis (CRS) without nasal polyps trial to ensure the correct patient population was being enrolled.

Answer

CEO Will Lewis explained that the trial focuses on the most severe patients to maximize the potential to show benefit. This includes patients who are eligible for or have already had sinus surgery, and all enrolled patients are non-responders to steroid treatment. He compared this strategy to the successful approach used for ARIKAYCE in refractory patients, targeting a population with a clear and significant unmet medical need.

Andy Chan from Wolfe Research asked if autoantibodies are the primary driver of disease in ACPA-positive RA patients and questioned whether the 70,000 U.S. prevalence for difficult-to-treat RA is a diagnosed figure or an estimate.

Answer

Dr. Peter Taylor explained that while the exact contribution is unknown, FcRn is a validated target in a subgroup of RA patients, and studies with potent drugs like IMVT-1402 will clarify the role of autoantibodies. Executive Peter Salzmann confirmed the 70,000 figure is the current estimate of the diagnosed population meeting the difficult-to-treat criteria in clinical practice, and noted the number may be growing.

Andy Chan asked Dr. Taylor if autoantibodies are the primary driver of disease in ACPA-positive RA patients compared to other pathways. He also asked the Immunovant team to clarify if the 70,000 U.S. prevalence for difficult-to-treat RA is a diagnosed figure or an estimate.

Answer

Dr. Peter Taylor explained that the exact contribution of autoantibodies is unknown, as RA is a complex disease with multiple pathways, but FcRn is a validated target in a subgroup. Executive Peter Salzmann confirmed the 70,000 figure represents the current population of diagnosed patients in clinics who meet the difficult-to-treat criteria, noting the number could grow.