Response of metastatic thyroid carcinoma and OSA to STA-1474 treatment.

<p>a) Patient #14 had a locally recurrent thyroid carcinoma with metastatic disease to the lungs. This patient received STA-1474 on the 8 hour infusion protocol and experienced a partial response to therapy of both the locally recurrent and metastatic disease. Shown are representative radiographs before and after 15 treatments with STA-1474. The yellow arrows point to the metastatic pulmonary nodules. b) Patient #18 had metastatic OSA to the lungs following amputation and chemotherapy for an appendicular OSA. This patient received STA-1474 on the 8 hour infusion protocol and experienced a partial response to therapy. Shown are representative radiographs before and after 4 treatments with STA-1474. The yellow arrows point to the metastatic pulmonary nodules.</p

Serial CT demonstrating regression of oral malignant melanoma following treatment with STA-1474.

<p>Patient # 5 had an aggressive oral malignant melanoma that had invaded into the nasal cavity. During the 4^th treatment cycle with STA-1474, an extravasation event occurred resulting in altered drug pharmacokinetics. A marked decrease in the oral mass was observed 7 days later and a subsequent CT scan confirmed a partial response to therapy. Shown are two representative matched CT images of tumor before and after treatment.</p

Subject demographics.

<p>Subject demographics.</p

Mean pharmacokinetic parameters of STA-9090.

<p>*NR: not reportable due to insufficient terminal phase characterization.</p

Structure of STA-1474.

<p>Shown is the chemical structure of STA-1474, a water-soluble phosphate prodrug of ganetespib.</p

Response of cutaneous mast cell tumors to STA-1474 treatment.

<p>a) Patient #19 had recurrent grade 3 cutaneous MCTs. This patient received STA-1474 on the 1 hour infusion protocol twice per week and experienced a partial response to therapy of the cutaneous lesions after 7 treatments. b) Patient #24 had a large previously untreated cutaneous MCT. This patient received STA-1474 on the 1 hour infusion protocol twice per week and experienced a partial response to therapy of the cutaneous lesions after 4 treatments.</p

Analysis of HSP90 and HSP70 expression in dogs before and after treatment with STA-1474.

<p>a) PBMCs were collected from normal control dogs (cont 1 and cont 2) and study dogs before and 24 hours after treatment with STA-1474 at 9.5 mg/kg over 8 hours. Protein lysates were generated and following SDS-PAGE, Western blotting was performed for HSP70. Blots were then stripped and reprobed for β-actin. b) Tumor biopsies and PBMCs were collected from dogs treated with 5 mg/kg STA-1474 over 1 hour before treatment and at 7 and 24 hours post treatment. Protein lysates were generated and an ELISA was performed to detect HSP70. Results are expressed as HSP70 protein (ng/ml) and percent of baseline. c) Protein lysates generated from the tumor biopsies described above were subjected to SDS-PAGE followed by Western blotting for HSP90. Blots were then stripped and re-probed for β-actin.</p

Pharmacokinetic analysis of STA-1474 following administration using three different dosing regimens.

<p>a) Mean ganetespib plasma concentration – time profile for each dosing regimen b) Representative ganetespib plasma concentration – time profiles for two patients in each dosing regimen.</p