Tumor-Agnostic TSC1 and TSC2 Inactivating Mutations

Inactivating mutations in TSC1 and TSC2 drive mTOR pathway activation and tumor growth?

  • TSC1 and TSC2 form a tumor suppressor complex that down regulate mTOR activity
  • TSC1 and TSC2 mutations occur at a rate of approximately 1.4% and 1.8% across cancers respectively (Aadi internal estimate based on TCGA database analysis)
  • No approved therapies for TSC1 and TSC2 mutant patients but numerous case reports with durable responses to mTOR inhibition
  • Standard CLIA-certified NGS panels already capture TSC1 and TSC2 mutations

Increased probability of success for FYARROTM

  • Striking clinical data in TSC1/TSC2 mutant patients in PEComa
  • Encouraging signals in TSC1/TSC2 mutant non-PEComa patients in ongoing Expanded Access Program (details presented at ASCO 2021)
  • Projected FDA approval for malignant PEComa by early 2022 significantly derisks large market opportunity in TSC1/TSC2 mutations

Tumor-Agnostic TSC1 & TSC2 Mutant Registrational Trial

  • Registrational Phase 2 Study design and strategy discussed with FDA
  • Planned 2H 2021 kickoff
  • Similar approach to other precedent tumor agnostic registration studies
  • Patient accrual at sites based on local NGS results and via diagnostic partnerships