Ann: Appendix 4C & Quarterly Update, page-60

Hi Adreamer,

Thankyou for that study material. I will attempt to answer it in 3 posts.

This first post is a simple mathematical one.

I am either a science based retail investor or a retail investor with a science base.

What I want is a simple trial with all the participants on a same level. Remember we have limited patient cohorts, so I don't want any scientific surprises that I and others have not been made aware of.

In other words I wished all our patients to be " limb onset" MND so as to gain a mathematical advantage if I can say that.

The median survival time for limb onset is 29.8 months. The median time for Bulbar longevity is 15.3 months.

So as a retail investor I can see if one patient dies it skews the longevity mathematical results of the trial in a negative way.

My question is why have a patient in a trial that potentially underpowers the trial.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3787117/

As to including bulbar patients on a forth coming trial , that doesn't concern me as you can have a seperate arms length cohort so as not to compromise limb onset results which is where MPL will excel.

Katyal et al states this and it makes sense .

Patients with variable clinical subtypes are often pooled in the same study group, which later leads to significant statistical differences in the observations.

The majority of studies enroll patients regardless of their clinical subtype in the same study group, which confers statistical challenges.

Recent trends suggest that studies should be formulated taking genotypic features into consideration to avoid discrepancies in recognizing the ALS subtypes .
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5626834/

Kpax