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Message: Epigenetic Therapeutic Targets Virtual Summit Presentation July 28, 2020

"COVID-19

• ACE2 is a cell surface receptor used by 2019-nCoV to gain entry into host cells. Apabetalone reduces circulating ACE2 protein levels in patients, and downregulates ACE2 gene transcription by 40-90% in vitro

• Phase 2 trial planned"

I would love to see the data that they are referring to above. As I posted before, I could only find one study in which they treated whole human blood "ex vivo," meaning in a tube, with apabetalone for 24 hours and found a 1.3-fold (30%) decrease in ACE2. From the above quoted text from yesterday's presentation, it sounds like they have additional data in vitro data that showed a more robust effect. Additionally, they imply that they have patient data. Hopefully this is not just the human whole blood ex vivo data but instead data from blood collected from apabetalone treated patients in clinical trials.

Does anyone recall seeing any other data other than the human whole blood ex vivo study that I cited above?

I commented on this ACE2 stuff before here, but will paste again. Some of it may not be true based upon what Resverlogix stated in their presentation (sounds like they have more data than I am aware of), but again I haven't seen the data so cannot verify.

"There is zero publicly available data that I know of on how apabetalone affects ACE2 in apabetalone treated patients. All I could find was data in which blood was taken from untreated donors, treated in a test tube or dish with apabetalone, and then assayed for changes in gene expression 24 hours later. This has very limited extrapolation.

1) The apabetalone dose used in that isolated blood study may not be the same as dosing patients.

2) The kinetics of metabolism of Apabetalone when given orally may prevent a blood concentration of apabetalone from ever reaching the dose used in the isolated blood study.

3) A 30% change in ACE2 mRNA in isolated blood study is a pretty modest change in expression. mRNA is translated to protein, and mRNA levels don't always correlate with protein levels. Further, the amount of ACE2 on the cell surface is what is most relevant. Even if they did measure total ACE2 protein, this would not necessarily be cell surface ACE2.

4) An intact whole animal or human has numerous cell types and organs, each of which may be exposed to different amount of apabetalone and may respond differently. One can't generalize expression changes in whole blood to other tissue/cell types.

5) With respect to ACE2 and virus infection, one would want to know what tissue(s) and cell types are relevant for viral infection and replication, and then assess whether apabetalone modulates ACE2 in those relevant tissues. ACE2 changes in a cell that never sees the virus would not be relevant."

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