General Updates | Pociredir in sickle cell disease: mechanism of action and Phase Ib trial design

It has a unique, more complicated mechanism of action that inhibits ectoderm targets, specifically then impacting BCL11A and MYC. As you know, BCL11A is now a target for fetal hemoglobin induction. So it’s an oral agent that leads to the targeting of BCL11A, suppressing that to allow for the fetal hemoglobin induction. Because of the mechanism of action targeting the PRC2 complex of the EED, it’s actually highly selective, and it has a clean off-target profile. And so it’s able to really, in a selective way, impact the fetal hemoglobin induction. 

So this study was looking at specifically targeting genetic mechanisms that allow for induction of fetal hemoglobin. And so the study actually composed of several cohorts – they had a cohort 1, 2, and 3A that completed the study looking at 2 milligrams, 6 milligrams, as well as 12 milligram data. And they demonstrated it in a short period of time, an incremental increase in fetal hemoglobin. The study that is more pronounced after that was a phase cohort 3B of the 12 milligram data. That went to completion of 84 days in [unknown] 65 years of age. Those patients had to have severe genotype of sickle cell disease, HbSS, HbS beta-thal 0. Patients had to have severe characteristics of the disease – that was greater than four VOCs, pulmonary disease, nephropathy, priapism, any components of sickle cell disease that’s been really aggressive in its manifestation in those patients. And particularly patients who were no longer able to be on hydroxyurea or did not want to be on hydroxyurea. 

So basically, the primary endpoint of the study was to look at the safety and tolerability and PK parameters of the drug. And then the secondary endpoints looked at the rate of fetal hemoglobin induction, hemolysis, anemia, and then there was an exploratory endpoint of looking at the globin gene expression, the percentage of F cells with the induction of the fetal hemoglobin, as well as the incidence of vaso-occlusive crises. The patients all had access to the treatment. They enrolled for 12 weeks of treatment and then four weeks of observation. And their safety tolerability and response to the drug was collected. And that data will hopefully be presented at an upcoming American Society of Hematology meeting.

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