Ann: Commencement of BNC210 Phase 2 Agitation Trial, page-33

You can hear about the PTSD Trial design in the Webcast I linked above, starting at the 1:17:00 mark.
PTSD can be broken down into 4 symptom clusters:
- Intrusive thoughts and Nightmares
- Avoidance
- Negative alterations in cognition and mood
- Arousal and reactivity
There is reason to hope that BNC210 works in all these areas.

The Primary objective is to assess the effects of BNC210 as measured by the CAPS-5 Scale.

Secondary objectives are to assess the effects of BNC210 on:
- each of the 4 symptom clusters.
- other psychiatric outcomes including anxiety and depression.
- global functioning and Quality of Life.
- patient-reported outcomes.
- safety and tolerably.

193 PTSD patients were enrolled.
Some of these patients may:
- have different levels of the 4 symptom clusters
- have anxiety and/or depression as well as PTSD
- be on anti-depressant medication
- be smokers

Patients are placed on either Placebo, 150mg, 300mg or 600mg BNC210.

Trial is powered such that you should be able to see Statistically Significant p<=0.05 effects on:
- CAPS-5 Total Score
- Intrusive thoughts and Nightmares
- Arousal and reactivity

There should also be Meaningful Effect Size vs Placebo on:
- Avoidance (harder to move the needle in a 12 week trial as behaviour is habitual and may take months to get over their Avoidance)
- Negative alterations in cognition and mood (distinct symptoms that may really belong in the depression camp rather than PTSD)

Remember that some of the 193 patients will also have anxiety and/or depression symptoms. There should be Statistically Significant p<=0.05 effect:
- on the Depression patient subset for Negative alterations in cognition and mood
- on the Anxiety atient subset for Arousal and reactivity
And Meaningful Effect Size vs Placebo for the Anxiety and Depression patient subsets for the other symptom clusters.

Smokers will also keep a smoking diary.

Then when the results come in we should be able to see the effect on PTSD overall for the Primary Objective with the CAPS-5 score, but also the effect of BNC210 on each of the patient sub-groups:
- Placebo vs 150mg vs 300mg vs 600mg BNC210
- with high level symptoms in each of the 4 symptom clusters
- with anxiety and/or depression
- Tolerability for those also on anti-depressant medication
- Did smokers reduce smoking?

As you can start to see there are a lot of sub-groups and with only 193 patients in a 12 week trial we may not have enough power to see the needle moved vs placebo for all the Secondary Objectives in all the sub-groups. We could have a bigger, longer trial to get more power, but that's expensive, takes longer, and may be futile for some sub-groups. Even a small impact on some symptoms could be very encouraging and informative. Remember there hasn't been a PTSD drug approved by the FDA in the last 20 years.

Data read out for the Primary Objective will definitely be reported. Data read out is not expected to be reported if there isn't a decent effect size for Secondary Objective sub-groups. This is shown in Slide 77 of the Webcast, "Example of a Successful Phase II Trial in PTSD".

The results from this trial will be very useful for designing future Phase II trials for anxiety and depression and of course for designing a Phase III trial for PTSD.