Phase II Results: Highest Response Rates

in Chronic Phase

Study 0110

Chronic Phase

IFN-α Failure*

(N=454)

Hematologic response 93% 69% 31%

Complete response 93% 37% 7%

No evidence of leukemia – 12% 5%

Return to chronic phase – 20% 19%

Study 0109

Accelerated

Phase*

(N=181)

Study 0102

Blast Crisis*

(N=229)

Major cytogenetic response 53% 19% 7%

Complete response 32% 13% 1.5%

Gleevec® (imatinib mesylate) Prescribing Information. For important safety information, please see slide 3 or full Prescribing Information.

*Chronic phase: 400mg/day; advanced phases: 400mg/day or 600mg/day. Dose escalation permitted in all trials.

[slide 10]

Phase II Results: Highest Response Rates in Chronic Phase1

• These results demonstrate that there is a continuum in the response rate throughout all stages of the disease, with the highest response rates when therapy with Gleevec® is started in chronic phase.

• Chronic phase patients received a dosage of 400mg/day; advanced phase patients received 400mg/day or 600mg/day (the currently recommended dosage). Dose escalation was permitted in all trials (see slide 22 or full Prescribing Information).

• The overall rate of confirmed hematologic response ranged from 31% in blast crisis to 69% in patients in accelerated phase, and 93% in patients in chronic phase.

• Importantly, the rate of confirmed MCR was 53% (unconfirmed 61%) in patients in chronic phase failing prior IFN-α therapy.

• An unexpected finding has been a relatively high rate of confirmed MCR in advanced CML, both in patients with blast crisis (7%; unconfirmed 15%) and in patients with accelerated phase disease (19%; unconfirmed 25%).

– These response rates contrast sharply with the negligible responses reported with traditional therapies in these patient populations.

• Hematologic response criteria (all responses confirmed after ≥4 weeks).

– Chronic phase: complete response: WBC <10 x 109/L, platelets <450 x 109/L, myelocytes + metamyelocytes <5% in PB, no blasts and promyelocytes in PB, <20% basophils in PB, no extramedullary disease

– Accelerated phase and blast crisis: complete response: absolute neutrophil count ≥1.5 x109/L, platelets ≥100 x109/L, no blasts in PB, BM blasts <5%, no extramedullary disease. No evidence of leukemia: Same criteria as for CHR, but ANC ≥1 x 109/L and platelets ≥20 x 109/L. Return to chronic phase: <15% blasts in BM and PB, <30% blasts + promyelocytes in BM and PB, <20% basophils in PB, no extramedullary disease other than spleen and liver. WBC = white blood cell; PB = peripheral blood; BM = bone marrow; N/A = not applicable

– Cytogenetic response criteria (all responses confirmed after ≥4 weeks except as noted)

– All studies: complete response (0% Ph+ cells); major response (≤35% Ph+ cells)

• Initiating treatment in chronic phase yields better responses than starting in advanced stages of CML.

Reference

1. Gleevec® (imatinib mesylate) Prescribing Information. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2003.