Summary

• Hsp90 is required for proper ALK function
• Onalespib (AT13387) is a second generation Hsp90 inhibitor
• Onalespib in ALK-driven pre-clinical models:
  • Displays potent antitumor activity
  • Delays the onset of resistance
• In the clinic, onalespib
  •  Has a safety profile consistent with the class
  • (diarrhea, mild transient visual changes)
  • PK & PD results support weekly dosing
  • – Has antitumor activity (PR) at a dose of 220 mg/m2 (D1,8,15 of 28 Day cycle)
• Crizotinib (CZT) has demonstrated clinical activity in ALK-pos NSCLC
• AT13387-05 is a 3-part, Phase 1-2 study in ALK-pos NSCLC
  • Part A (Phase 1 of the study demonstrated the safety of Onalespib/CZT in combination with some activity in progressing patients
  • Results are presented for Part B of the study, randomization to combination of Onalespib added to CZT vs CZT alone prior to development of resistance (Fig 2)

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Addition of onalespib to crizotinib prior to progression in pts with ALK-pos NSCLC: P2 Results