Statistical analysis
For statistical analyses that do not specify the software used, they were conducted using SAS version 9.4. Sample size was based on practical considerations, as efficacy analyses were considered exploratory for this study. Data collected in this study were documented using summary tables and subject data listings. Continuous variables were summarized using descriptive statistics (number of subjects, mean, median, standard deviation, minimum and maximum). Categorical variables were summarized using frequencies and percentages. Data from different study parts (A, B and C) are presented in separate tables. For each study part, data are presented by dose cohort. Placebo patients from different cohorts in the same study part were combined in one column. For statistics of maximum values (Extended Data Fig. Formal statistical testing was not pre-specified. Post hoc testing was conducted for selected analyses, and nominal Safety summaries were based on all study participants receiving at least one dose of KT-474 or placebo and included incidence and type of AEs, plus absolute values and changes in blood pressure, heart rate, temperature, clinical laboratory data, physical examination, neurological examination data and 12-lead electrocardiogram data from pre-dose to post-dose timepoints.