Chi

Chi, on behalf of Jason Gerberry, questioned the increased confidence in olezarsen's peak revenue exceeding $2 billion, asking if this implies a potentially higher peak number and what recent research or assumptions on price/volume drove this confidence. She also inquired about the market opportunity, target profile, competition, and expected Phase 2 data timing for ION532, licensed to AstraZeneca for APOL1-mediated kidney disease.

Answer

Kyle Jenne, Chief Global Product Strategy Officer, confirmed the >$2 billion peak revenue estimate is based on olezarsen's strong product profile, positive Phase 3 data, and extensive prescriber demand research, with increased confidence stemming from strong underlying demand trends. Brett Monia, CEO, described ION532 as a significant market opportunity for renal disease with strong preclinical data and unmet need. He noted AstraZeneca's decision to advance to Phase 2 was based on Phase 1 data showing strong target engagement and good safety, but stated that the timing of Phase 2 data is a question for AstraZeneca.

Chi inquired about quantifying the impact of higher-than-planned residual volume from state Medicaid in Q4, asking if it was segment-across or product-specific. She also asked about the scope of business development the company is willing to consider given its current capital structure.

Answer

CFO JJ Charhon stated that most of the residual Medicaid volume was associated with Xifaxan in Q4, primarily in October and November, and amounted to less than $50 million in revenue. CEO Thomas Appio explained that the company is looking at all types and sizes of business development deals, constrained by the capital structure but focused on maximizing portfolio value and leveraging commercial capabilities, considering both on-market and development assets.

Asked two questions about the immunology pipeline: one on the R&D strategy for CAR-T in autoimmune diseases beyond lupus, and another on the potential for expanding the TYK2 inhibitor (3667) into new indications like uveitis.

Answer

For the TYK2 inhibitor, the company is focused on delivering proof-of-concept results in lupus and dermatomyositis before considering expansion into other indications. For autoimmune CAR-T, they are actively exploring new non-viral vector technologies through internal R&D and external collaborations.