In their natural state, these cells do this by secreting certain cytokines that promote growth and development of specific biological systems. Placental cells in their natural state are automatically programmed to secrete the right cytokines at the right times. If you’re growing them in a 3D model like Pluristem though, you need to be able to tweak more exactly what the cells should secrete in order to aid in the development of any given system on demand, in this case the hematopoietic system. Pluristem’s method of manufacture of these cells, which originate from donated placentas, is proprietary, but generally speaking they are cultured inside 3D models that mimic the human body and “prodded” in such a way as to secrete the desired cytokines for a given indication.
In the case of PLX-R18, the theory according to Dr. Lazarus is that incomplete HCT happens because the cytokines that originally aided in the development of the system in the womb are absent in a subsequent transplant as an adult. Meaning, if Pluristem tweaked the cells right, they should in theory aid in the full redevelopment of the hematopoietic system post transplant. Preclinical evidence has suggested this may be the case, and now we will see if this can translate to humans.
So how exactly can this early Phase I trial be seen as an implicit shortcut to approval? Typically, Phase I trials are designed to assess safety. Safety is not by itself a sufficient condition for approval obviously though it is a necessary one, so successful Phase I trials do not usually inspire much speculative buying. This Phase I trial is similar in its structure in that the primary endpoint is safety, though that is not expected to be a hurdle because these are simply human cells with no immunogenicity, so the chances of them causing a reaction are very low. It is the secondary endpoints that are much more interesting, and here is where the inherent shortcut may apply.
These secondary endpoints include changes in platelet and hemoglobin levels, frequency of blood transfusions, how fast a patient shifts from transfusion dependence to independence, and general quality of life. Since the trial will be open label, both the company and its investors will be able to see results as they happen (or at least as they are reported) and we will get a pretty good idea not only if these PLX-R18 cells work as intended, but also whether by implication whether Pluristem’s entire cell manufacture and tweaking strategy is on target or not.
If it is, then this early Phase I trial will show more than just safety of something expected to be safe in the first place. It could vindicate Pluristem’s approach to both stem cell therapy in its choice of placental cells as well as their method of manufacture, opening up the company to opportunities currently closed to it due to its small size and limited capital. Is this an explicit shortcut to approval? Not exactly, and keep in mind that the company is still risky and that the higher importance of this Phase I trial is a bit of a double-edged sword. Regardless, this Phase I trial could have Phase II-like effects on Pluristem Therapeutics Inc. (NASDAQ:PSTI) and its stock, and is not your average typical safety trial.
Note: This article is written by David Rich and originally published at Market Exclusive.
