• AT13387 exhibits dose dependent systemic exposure and linear
pharmacokinetics. Half-life of AT13387 in GIST patients across Phase 1 and
Phase 2, range between 6.8 – 11.2 hours.
• HSP70 induction of 2-7 fold magnitude was observed representing
pharmacodynamic evidence of target engagement.
• AT13387 demonstrated clinical activity after failure of multiple TKI treatment
with 2 PR of 14 treated patients in Phase1 and Phase 2 thus far.
• Phase 1 DLTs consisted mainly of multiple Gr 2 Adverse Events of GI toxicities
(diarrhea, vomiting), systemic infusion reactions, and fatigue. Few patients had
Gr 3 toxicities and no Gr 4 AEs were reported. Visual disturbances were all Gr 1
with only 1 patient reported as Gr 3 due to ERG changes. All were transient
and reversible. Visual disturbances are considered on target pharmacological
class effects of potent HSP90 inhibition. GIST patients safety profile similar to
overall enrolled population.
• AT13387 is a promising agent in GIST, including TKI-resistant c-KIT positive and
c-Kit negative GIST.
• Phase 2 study in combination with imatinib is ongoing for imatinib-resistant
Data looked good. All of these patients had exhausted previous treatments and we see a benefits of 300 days with at13387. That looks impressive. If we see similar benefits in prostate trial, this will be partnered at a very large deal, IMHO.