Good morning and thank you Dr Keating and ASH for the opportunity to present our data. I’m going to present the subgroup analysis of a previously presented phase III trial focussing on survival after allogeneic transplant in older patients with high risk acute myeloid leukaemia who were treated with either CPX-351 versus cytarabine plus daunorubicin. For those of you who may not be familiar with it, CPX-351 is basically a liposomal encapsulated formulation of daunorubicin cytarabine, two basic chemotherapy drugs, that are combined into a fixed molar concentration ratio within the liposome. The beauty of it is that the drugs together are delivered in a synergistic ratio that optimises leukemic cell kill and that’s the concept behind the drug. We had done previous trials in the phase I and phase II setting with some degree of success that led to the design of a phase III study which I have shown here. It was an open label randomised prospective phase III trial comparing CPX-351 versus conventional induction chemotherapy with cytarabine plus daunorubicin in patients with high risk or secondary AML in patients that had typically developed AML after having had an antecedent hematologic disorder such as myeloid dysplastic syndrome. In addition we allowed patients who had therapy related AML, a very notoriously poor prognosis type of disease.

We treated patients for up to two cycles of induction then up to two cycles of consolidation on both arms and followed them until death or five years. The primary endpoint or objective of the study was overall survival. These are the data that we presented at ASCO this year where it became evident that there was a survival advantage that was attributable to CPX-351 compared to 7 3 with a hazard ratio decrease by about 31% throughout the course of the study. So, as you can see here there was a survival advantage in favour of CPX-351 which was the primary endpoint of this particular study and a median survival of the CPX treated patients was about 3½ months longer than the induction chemotherapy patients.

Now the purposes of this particular presentation of subgroup analysis was to focus on a group of patients undergoing allogeneic transplant, recognising that allogeneic transplant is part of the treatment continuum for acute myeloid leukaemia, even in older patients. So we were interested in understanding what the contribution of allogeneic transplant was to the overall efficacy of CPX-351. Shown here are the subsets of patients who actually underwent allogeneic transplant. You can see that about one third of the entire patient population underwent transplant and a higher number that received CPX-351 underwent transplant compared to 7 3. Patients were well matched in terms of baseline characteristics; I would like to point out to you that the higher percentage of patients that entered the transplant did so in a complete remission if they had received CPX-351 compared to 7 3 but otherwise there were really no major differences between the two groups that were ultimately transplanted.

We did a landmark analysis from the time of transplant between the two arms. So we looked at the outcomes of the patients who underwent allogeneic transplant who received CPX-351 or received 7 3 and looked at their overall survival. As you can see here in this subgroup analysis, the patients who had received CPX-351 lived longer than patients who had received 7 3. Again, all these patients underwent allogeneic transplant and the hazard ratio was 0.46 for this particular study. We did a Cox proportional analysis as well as part of this trial and we discovered that as a time dependent covariant CPX-351 led to better overall survival than 7 3 in these patients that underwent bone marrow transplant.

Since the bone marrow transplant can induce significant mortality, especially in older adults, we looked at early mortality by day 100 and we discovered that the day 100 mortality rates were lower in the CPX arm compared to the 7 3 arm. As you can see, about 20% of the patients in the 7 3 arm died within day 100 and about 10% of patients on CPX-351 died within the same time frame so a current lower early death rate in patients who received CPX-351.

So, in summary, we feel that outcomes after allogeneic transplant in older patients with higher risk AML appear superior in patients who were treated with CPX-351. It included a lower early death rate and the fact that the overall survival was better. The results should be clearly interpreted with caution since this is a subgroup analysis of a large randomised trial. We feel that this may provide evidence that CPX is a potential bridge to a successful allogeneic transplant in an otherwise very poor risk disease subset of AML and that the reasons for this could include, and still need to be verified, the fact that a lower induction related morbidity mortality could reflect a healthier patient population going into transplant who received CPX-351 and possibly a better opportunity to achieve disease control before going into transplant which may explain the overall outcomes in this group  will be factors that will be looked into in more detail in the near future. Thank you.