{"url_path":"/sec/ions/8-k/2026-07-09/item-8-01","section_key":"item-8-01","section_title":"Item 8.01 Other Events.","topic":"sec","document":{"doc_type":"8-K","doc_date":"2026-07-09","source_url":"https://www.sec.gov/Archives/edgar/data/874015/0001140361-26-028092-index.html","accession_number":"0001140361-26-028092","cik":"0000874015","ticker":"IONS","issuer_name":"IONIS PHARMACEUTICALS INC","edgar_url":"https://www.sec.gov/Archives/edgar/data/874015/0001140361-26-028092-index.html","primary_entity_key":"0000874015","primary_entity_name":"IONIS PHARMACEUTICALS INC"},"word_count":499,"has_tables":true,"body_markdown":"Item 8.01\n\nOther Events.\n\n \n\nOn July 9, 2026, Ionis announced that the CARDIO-TTRansform Phase 3 trial for eplontersen in patients with ATTR-CM did not meet the primary efficacy endpoint of the\ncomposite outcome of CV mortality and recurrent CV clinical events up to Week 140 compared with placebo. In this contemporary patient population treated with standard of care, including a majority on a stabilizer, adding eplontersen did not provide a\nstatistically significant benefit.\n\n \n\nIn a prespecified subgroup analysis of patients treated with eplontersen monotherapy compared to placebo, a nominally significant hazard ratio of 0.71 was observed on\nthe composite outcome of CV mortality and recurrent CV events. In patients who were on stabilizer therapy at baseline, no treatment effect was observed.\n\n \n\nIn the overall population, multiple secondary, imaging and biomarker analyses favored eplontersen versus placebo. Large and\nsustained reductions in transthyretin were observed, consistent with the silencer class for ATTR. Eplontersen was well tolerated, with a favorable safety profile consistent with previous results.\n\n \n\nCARDIO-TTRansform is a Phase 3, multicenter, randomized, double-blinded, placebo-controlled study to evaluate the safety and efficacy of eplontersen compared to placebo\nin participants with ATTR-CM receiving available standard of care: 57% of patients in each arm received a stabilizer treatment at baseline, and a further 24% in each arm initiated a stabilizer during the trial.\n\n \n\nIonis and AstraZeneca will continue to analyze the full data set, and results will be shared with the scientific community at the European Society of Cardiology Congress\nin August 2026.\n\nForward-Looking Statements\n\n \n\nThis report includes forward-looking statements regarding Ionis’ business and the therapeutic and commercial potential of eplontersen, Ionis’ technologies and other\nproducts in development . Any statement describing Ionis’ goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain\nrisks and uncertainties including those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines.\nIonis’ forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis’\nforward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. Except as required by law, we undertake no obligation to update any forward-looking\nstatements for any reason. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis’ programs are described in additional detail in Ionis’ annual report on Form 10-K for the year ended\nDecember 31, 2025, and most recent Form 10-Q, which are on file with the Securities and Exchange Commission. Copies of these and other documents are available from the Company. In this report, unless the context requires otherwise, “Ionis,”\n“Company,” “we,” “our” and “us” all refer to Ionis Pharmaceuticals and its subsidiaries."}