PROTALIX BIOTHERAPEUTICS, INC. (PLX)

[Spideyboy]

I looked up another October 2018 Avrobio presentation and was interested to see a couple additional slides which look over the treatment process. Specifically slide 7.

http://investors.avrobio.com/static-files/7ab96b05-3ee8-4bee-8461-b747abc0e21b

From the previous information it looked like they were doing the treatment in-vivo, but from this slide it's cleat they are doing this ex-vivo.

This provides clarity on my confusion as to why the use of the chemotherapy agent Melphalan which destroys the neutrophil and platelet counts in the patients.

"The use of this drug is common in bone marrow/Hematopoietic Stem Cell transplants, as part of a conditioning regimen: The treatments used to prepare a patient for stem cell transplantation (a procedure in which a person receives blood stem cells, which make any type of blood cell). A conditioning regimen may include chemotherapy, monoclonal antibody therapy, and radiation to the entire body. It helps make room in the patient’s bone marrow for new blood stem cells to grow, helps prevent the patient's body from rejecting the transplanted cells, and helps kill any cancer cells that are in the body."
https://www.cancer.gov/publications/dictionaries/cancer-terms/def/conditioning-regimen

From the procedure slide in the above linked company presentation, you can see that they are looking at taking CD34+ stem cell from the bone marrow, which are effectively the Hematopoietic stem cells. Hence the use of Melphalan.

So from the conditioning regimen explanation, they are destroying the white blood cell and platelet count, and possibly red blood cell count (red blood cells are also derived from Hematopoietic stem cell, and therefore would logically be affected too), so that they can make space for the ex-vivo expanded CD34+ cells which have the new gene in them.

While this makes sense to pack in as many of the new cells as possible, it's still not a great thing to do vs a straight PLX-102 injection, which doesn't require any chemo and destruction of the immune, platelet and logically also red blood cell counts.