Incidence of Hypophosphatemia

1
Incidence of Hypophosphatemia
15a - 70
2
Patients with GI Bleeds and Proton Pump
Inhibitors (PPI) NDA SU

• All GI bleeds 79
• PPI at anytime on-study 62 (78)
• PPI at baseline 16 (20)
• Relevant medical history 4 (5)

12c - 6
3
Dasatinib Exposure Dose Proportionality

• Dasatinib Exposure vs Dose with B7D Regimen
• Study 002 MAD study 84 subjects with CML
• At dose levels of 50120 mg BID, the exposure
  increase was slightly more than dose proportional
  at steady state

25 - 1
4
Major Cytogenetic Responses in Imatinib-resistant
Patients in Phase I
Chronic Phase CML Study 002
23 - 4
5
Mechanism of Action of Pleural Effusion

• Likely related to the inhibition of PDGF-ß
• PDGF-ß regulates interstitial fluid homeostasis
  in mouse model(Heuschel et al, PNAS 1999)
• Fluid retention described with other drugs known
  to inhibit PDGF-ß
• e.g. Imatinib, CDP860 (humanized antibody)

13c - 2
6
Pretreatment Characteristics
Study 017
24 - 2
7
Patient Disposition
Study 017
24 - 3
8
Efficacy
Study 017
24 - 4
9
Major Cytogenetic Response at 3 Months
Study 017
Percent Responders
63
34
15
39
74
33
N
24 - 5
10
Time to Treatment Failure
Study 017
Dasatinib
Imatinib

Censored
Months
24 - 12
11
Non-Hematological Adverse Events
Study 017
24 - 7
12
Myelosuppression
Study 017
24 - 8