Re: The Cantor Fitzgerald Presentation and miscellaneous
Well done that he, Missling, confirmed/clarified two points which were outstanding re PDD results leading up to the presentation:
1 - Investor’s stance that additional studies WILL be necessary! Yes, good to know, and good call, Inv. - kudos, and now we know.
2 - Also, roughly 24 min in, he stated that the subgroup with Sigmar WT gene performs “slightly better” but occurs in 80% of population which is good because overall the results would not be impacted by a mere 20% doing better. (I wrote a post using low level math assumptions to demonstrate that this would appear logical.)
So, imo - which has been confirmed, the additional phase(s) necessary are not in order to stack the population with only specific gene carriers (which should help with enrollment to allow entire population without exclusions - but, of course! Simple math made that conclusion an a priori on its face conjecture which Dr M confirmed - thank you/him.) but perhaps a larger population will now be necessary or perhaps whittle the dose down to one vs placebo rather than two - most likely possibility. (Doc, our poster, made a very insightful post that the regulatory body will often or sometimes make you commit to a dose and do a 2 prong ph3 drug v placebo only. Sounds reasonable. Thanks, Doc.)
Maybe just a standard requirement for ph 3 do over to confirm and maybe need larger n, however, sounds like it should be a short confirmatory study and he seemed sure of one, so I hope we are moving on to ph3 - full population for confirmation.
Missling stated Revenue:
Rett first
I conclude:
Then,
PDD if short, blinded, full population larger n might be needed or single dose could be same size n divided into fewer groups.
Which begs the question, where is the precision correlation? If it’s down to dose (my personal opinion), why did we need the big computing of Ariana KEM?? All pharmaceuticals whittle down to dose efficacy at some point without requiring machine computation. Just a straightforward correlation of dose to response.
And this is the good takeaway (the bicycle with all the bells and whistles)...
If the prespecified genetic market subgroups meant anything, it is that we are attempting to prove that it is present in all of the mitochondria dysfunction CNS diseases. Therefore, our drug could be useful in all, once established. So, likely, in order to avoid having to prove that again and could be a reliable biomarker for our drug in future. Laying groundwork here.
He mentioned the original signal for Rett came from preclinical Angelman or Fragile X and a sponsored research group. Very similar factors at play. That’s the only thing which remains for precision medicine to play a role in - though a very important one, imo. I’m not understating - just stating what has to be going on now in these trials. He tossed the use of SIGMAR match as a stat sig need for approval right out the window - much to my satisfaction and this implies the actual use - not indication by indication (nothing significant will change), not series of trials for each indication (again, nothing will change) ph2 will pass or fail without any help from the extra 20% WT genetic ringers, so it has to be across the board, which is great news. I’m relieved he confirmed and if results are significant this does telegraph to the attentive - a significant unseen opportunity representing risk/reward exists for the taking.
Therefore, I’m not sure why the share price wouldn’t then reflect these good things built into a third phase drug trial for this indication with good results: we don’t have to stack enrollment so it’s down to a single dose likely and same sample size or they want to see the mono therapy play out against placebo. Will be short trial. Can get by with lowest possible dose necessary gives room to titrate if patients decline or doctors see fit. If both doses were expected to work and passed then we have to determine. But should be quick do over and we know ahead what to expect - likely he nailed a flap down which will follow Rett in revenue stream. Also, gives a hint at AD and further enhances our MoA upstream components (he said many), as well as we want our reputation for success in this space to precede us - each indication like a building block helps get us there. (In future indications, when Anavex PR’s trial approval for an indication, based on a winning record, that alone should propel share price after the initial correlation has been established. Nice market Pavlovian response - which we worked hard and smart to obtain). And this had better be what the precision medicine concept was all about or it’s got me stumped. They must all connect somehow and that somehow is now more important than ever. I think it’s more obvious than ever - we made a birthday cake but aren’t serving it - must be waiting on a birthday celebration or that doesn’t make sense. [not that we aren’t extravagant and wonderful special extra thoughtful kind of folks who dabble in science] but either we are doing PM or we are just borrowing the jargon. Seems we have enough material to make a full suit so we should check out the jacket (PD/D) and wait on the trousers (Rett). The vest will tie it all together(AD). Suit yourself! (pun for the effort)
Final week of Sept “suits” me fine and Rett not far behind. I will now pivot to Rett US. The company released PR on Sept 10 (7am) that the US Rett study was complete. “The study is complete.” I can assume that does not mean that the last patient visit was 5 min prior to that PR release, so, if it is announced complete as of 9/10 7am, when was the last patient last visit? Does complete mean the data is locked? And being analyzed? Only 31 n and 8 sights...roughly 4 patients to record data checks over 7 weeks and double check that all the information is entered and accurate. How many end points?
4 primary endpoints all at baseline and at 7 weeks. 2 data points to measure, record, input, double check.
2 secondary endpoints at 7 weeks compared to baseline.
Each site has to aggregate data for 4 subjects across primary endpoints and secondary endpoints and unblind then quantify the metrics to determine drug performance versus placebo. And only a single arm dose. Assuming things wrapped up for patients a week prior to the PR, we are at 4 weeks post trial “completion” in the first full week of October, which, by the by, is 4thQ.
I would be at the “ready, set,...” position as this one may come out sooner than we know. Missling wants to put this on the front burner, I think we will see some “mach schnell” (make it quick!) movement around this indication - at least until we get the flaps nailed down (second degree of freedom in the triangle) and go for the big cherry on top - AD. With Rett and possible PD/D rev coming in by then.
Additional thought: falconer, I support your efforts to get A2-73 ASAP upon approval for personal use (and applaud you. No doubt you can persuade/educate your provider to write the script).
My question is: once a drug is approved for an indication such as Rett - Pediatric and or adult, the doses we are seeing are smaller as others have noted than for the older population which has been shown to need higher doses to achieve higher concentrations to be therapeutic, due to aging and loss of some S1r’s or slower response greater degeneration. Regardless, what does a prescribing doctor do in that case, when a lower therapeutic dose has been approved, to determine your appropriate dose and also, the rare peds price tag might be higher than the larger markets and therefore if you need (randomly chosen) three times the dose, you will be footing the bill for thrice the cost, I assume, off label. I know that Anavex will be trading higher at that point but still, ouch! And, would you foresee having to be on a maintenance dose for life? If so, any chance the drug price goes down once other indications are approved? We discussed this but can they do tiers of pricing? For PD and AD seems like they will be using higher doses than for Rett, Angelman, Fragile X, so, does pricing reflect the size of the market, or which indication came first for approval and is it priced like street drugs strictly by quantity or can a 50mg tablet be slightly more than a 30mg tab and that slightly more than a 14 ml liquid?
Best of luck with that I’m sure you will get it all figured out and needn’t report the fee schedule here - though I am curious. I wish you the best!
As soon as possible. And I think the US Rett team will be out before long. And Australia Avatar not long after that (I think we see something by end of January).
This is conjecture. Since the participants wore actigraphs throughout the trial, but no mention of actigraph endpoints for EMA/TGA, could that information have been shared with SIUF on a strictly voluntary basis (like, say, temperature or vitals, for instance) in the case where a patient/guardian signs a release? It is not trial related - for information gathering only, it appears. So, that should be proprietary and belong to the company and anyone the patients authorize to share with (HIPAA-like release).
If so, that was more geared toward movement and sleep state, not cognition. Could be that we (company) were/was able to access this the entire time - not an endpoint, although blinding still remained. Then, based on results of actigraph, regarding the conclusions reached by MJFF/SIUF - caveat emptor...”let the buyer beware”, they are big boys, with physicians/specialists/statisticians...they are free to make any assumptions regarding these results they want (and take the gamble on probability). Also, this data release violates nothing because it is not an endpoint so not even mandatory to disclose. No legal breach of material info. Like releasing each patient’s temperature doesn’t change anything.
Is that what the actigraph was for? Not sure I saw them being used in other trials.
Let’s call that just a big fat clumsy dot - in search of its meaning in life.
Purpose. Think purpose. There’s a purpose for everything (which is engineered/designed efficiently)
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