The Science

May be a good time to have a quick look at what will ultimately determine the 'value' of this company, and hence SP, profit/loss etc etc.  It really does come down to whether or not the molecules are efficacious (in this case, discussing Trofinetide for Retts).  After the SP drop, thought I would look back at the PII - to me, nearly all hinges on whether I think PIII will be positive - that is what I base my risk-taking behavior on (i.e. buying and holding shares!).

I was reassured reading the paper again: safety (the primary outcome) was excellent and consistent signals were found to suggest efficacy despite the small sample numbers and short duration of therapy (remember, efficacy measures were made after only 26 days of treatment!).  Importantly for me, efficacy measures were continuing to improve in the 70mg/kg group up to completion of trial, after which these measures started to return to baseline (off therapy).  See graphs below.  This would suggest a longer study may enable greater separation between those on tronfinetide and those on placebo.



Also important, efficacy was demonstrated at the Group-Level (i.e. across the group taking 70mg/kg) and at the Individual Level (i.e. looking at each patient taking the drug).  Group-Level: efficacy in three core efficacy domains (all P values less than the pre-defined 0.2).  Individual Level: higher mean efficacy score in the 70mg/kg group compared to placebo (2.7 vs. 1.5, P=0.091 respectively).  A permutation test was applied to work out whether these efficacy measures may have been by chance alone (performed on the assumption that there was no difference between treatment and placebo) with a P of 0.023: that is, 2.3% chance the efficacy measures were a false positive (i.e. 97.7% chance they were not by chance, and were due to trofenitide).

Some selected quotes from the Discussion section:

"The magnitude of the clinical effect of trofinetide on several of the outcome measures was consistent and was accompanied by a lack of worsening in the remaining measures of efficacy."

" ..treatment with trofinetide resulted in improvement in the core features of this disorder (including communication and speech, behavior, breathing abnormalities, hand movements or function, motor or muscular dysfunction, and seizures), which has never before been addressed in a substantive way by any therapeutic agent."

"Demonstration of improvements across multiple domains of the Rett syndrome phenotype was of fundamental importance in conferring syndrome-specific benefit. These results represented clinically meaningful changes (i.e., improvement) from the perspective of the clinicians as well as the caregivers"

It is important to remember that no effective therapy exists for this group and therefore, treatment effect will only need to be modest (but safe) in order for it to be accepted in practice.

A PIII trial with larger patient numbers and longer duration of therapy, IMO, has a good chance of success based on the PII results.  Right now, we are sitting in an enviable position of having someone else pay for it to be done while remaining involved with the trial design and conduct and NOT relinquishing all the potential financial rewards.  I have therefore added to my holdings as I don't trade and bought this years ago based on the science.  We are in a better position now than at any point.