The current phase 1 IV dose rate of 6,000mg, or roughly 70mg/kg, resulted in peak plasma concentrations of 175ppm. In rats and dogs administered 70mg/kg IV, peak plasma concentrations were ~600ppm (dogs) and ~1100ppm (rats). Based on the time-kill data for ESKAPE pathogens, MICs range from 250ppm to 1000ppm, with better kill rates at even higher concentrations (2000ppm looks to be a highly effective concentration for controlling all ESKAPE pathogens).
Peak plasma concentrations in the human trial are orders of magnitude lower than that achieved in other species and, more importantly, orders of magnitude lower than MICs for the bacteria of interest. Differences relating to PK/PD and ADME would surely only offer subtle differences in bacterial kill rates compared to those seen in-vitro. And given how quickly 327 appears to move from plasma to urine, follow up doses would likely be building on negligible plasma concentrations.
Based on all this information, does the board see any issue with Recce 327 in its current IV formulation as a treatment for sepsis/bacteraemia?
If not, is there a pre-clinical data set that shows bacteraemia control at plasma concentrations around 175ppm? Because that is what would be required to give the board confidence in the current 327 formulation in the face of the above points.
If anyone attends, I would love for this line to be thoroughly discussed. I've largely been brushed off and ignored when contacting James.
RCE Price at posting:
64.5¢ Sentiment: Buy Disclosure: Held
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