Replies to post #252135 on Anavex Life Sciences Corp (AVXL)

[XenaLives]

Running a biotech isn't quite the same as running a train line...

"Schedules" aren't usually expected to be precise.

[Jonjones325]

Missling doesn’t like to spin or embellish which I think does a disservice to our sp.

I’m not talking pump. If our results are not great, but better than the soc, that’s all that matters. And if it is, it needs to be in the pr.

If we see improvements in motor, then he needs to say we are going after PD.

This is the time to give positive forward looking statements regardless of the results.

This is the show me moment and whatever the data shows needs to be put in the best light. Which he pretty much sucks at.

The homeostasis thesis and the precision medicine thesis must stay intact. That is who we branded ourselves to be.

If the OLE data puts us in a better light, it should be shown.

Let’s hope there’s no need for spin and let’s hope we get the answer to the nagging low dose question. I don’t believe Missling would have chosen that dose when the data showed something else to be better. If he did it because he was scared of possible adverse effects. That’s bull.

He has been fearless all this time and when it’s showtime you chicken out. Don’t think so. You follow the data. That’s what he has always done and I believe that’s what he did.

When you see what we did and why, you will understand. Oh man. I hope so.

[sokol]

Gernee:

Thank you.

If we do not meet the endpoints (even if motor function is improved), the initial reaction is likely to be that the stock price moves down considerably. We should not necessarily sell if that happens.

Some large funds employ AI/Algos to trade stocks. In other words, machines trade large volumes of stock. These machines or programs are developed based on the past or what is known from the past - not what may known in the future. For example, these programs did not know that a C-virus pandemic would occur, but they were programmed to sell once the selling commenced. They contribute to big swings in the market. We are now witnessing a big swing up, but they could just as easily facilitate another big move down again. I certainly can envision that their systems may be programmed to automatically sell if endpoints in a clinical trial are not met or for any influence that a failure may have. These funds do not necessarily get hurt because they can, upon reflection, buy back at lower prices. Or, they get out early with smaller losses. Many individual investors though may get crushed. We do not react as quickly.

I have been involved with at least one biotech that missed end points in a trial, but otherwise had encouraging results because of other factors. The stock dropped precipitously. However, if one took the time to examine the results instead of automatically selling they would have realized that a segment of those in the study otherwise benefited and that segment represented a large percentage of patients with the disease in question.

If we get any type of mixed results, we could see a drop in share price because that will not meet with expectations of most investors in this clinical stage biotech. However, mixed results in this one trial (PDD) too does not mean it is all over and done.

Of course, if it is a complete failure, we know what will happen, but, to be clear, that is certainly not my expectation. I have researched this company for a number of years. Based on my research, I believe it is highly likely that AVXL 2-72 and 3-71 show promise to treat multiple CNS diseases. I believe that conclusion is reasonable based on the science and studies thus far. I am willing to wait and see. If I am wrong, there will be no meaningful impact on my life style. If I am right, .... I will just leave it at that.

[Doc328]

Question: if PDD does not meet primary endpoints but shows significant improvement in motor function, does our stock price get beaten down? Or do we rise being we will then run a ph3 for general PD with motor function as our primary endpoint?

IMO, A273 will not help the motor symptoms of PD much if at all. Hopefully, it will help cognition and attention. A273 is an M1-M4 agonist and S1R agonist. In PD, there is a selective loss of dopaminergic neurons, especially in the substatia nigra (pars compacta). These neurons project to the basal ganglia. DA and M4 receptors co-localize in many neurons in the BG. DA is inhibitory and ACh )acting through M4) is excitatory. Tremor is caused by the imbalance of these input signals. Hence, M4 activation is unlikely to help tremor and actually may worsen the imbalance of the inhibitory / excitatory inputs to the BG. Indeed, in the large 500+ rivastigmine PDD study, a drug that increases synaptic ACh (hence activating M1-M5), helped cognition but worsened tremor.

We occasionally use anticholinergic (i.e antagonists at M1-M4) to treat refractory tremors in PD patients and the risk is that it worsens confusion while helping tremors.

Of course A273 is also a S1R agonist and that may have a positive effect for the motor function. Will this positive effect outweigh the negative muscarinic effect?

If A273 does not help PDD cognitive endpoints, I expect SP drop and will be concerned that AD will miss as well. Rett is in a different category and PDD failkure will not imply a miss (though does not imply positive outcomes either).