Ann: Additional Positive Patient Cases - Special Access Scheme, page-21

Trials for life threatening conditions, including cancer, don't usually get compared to a placebo in advanced trials (for reasons you've highlighted).

The novel therapies usually get compared to standard of care treatments. Or sometimes they are used in combination with SoC treatments, with the control group being SoC alone.

In the case of 327, it may be used in combo with existing antibiotics and compared to monotherapy with existing antibiotics. But they would probably have to do work to show no dangerous drug interactions first.

They may trial it in 'prophylactic' settings such as UTI and other infections at risk of becoming blood-borne. Take pre- and post-327 blood samples for culture to determine which patients were bacteraemic at the time of treatment, and of those how many were culture negative after tx. And possibly include a control group treated with a first line antibiotic. This may be included in the pre-sepsis UTI trial?

After proof of concept, they may get to trial it in actual sepsis cases, being compared to conventional antibiotics. This could be the phase 2 sepsis trial, or maybe the phase 3?

Any SAS outcomes would help inform trial designs and ethics submissions.

I still don't believe 327 is appropriate for actual sepsis in it's current form, due to the previously discussed low plasma concentrations (or can think of it as extremely short plasma half-life).