This write-up serves as an overview for Anavex's PDD results from 6 Nov 2020. Included I mention aspects of the slide presentation that I believe may be currently overlooked by investors and hope to provide some context while you read along.
Slide 11: Even in the subtitle Anavex couldn't help but mention use of their 'oral capsules'. As we know, this is the least invasive method of providing a drug and does not require any specialized equipment or hospital visits. Notice under 'key primary and secondary endpoints' the motor endpoints to include the most titillating actigraphy monitoring. I will briefly mention significance on this later.
Slide 15: Some have already gone online to tout the presentation as absurd due to 'cherry-picking', at first glance it would be easy to confuse retail investors with this statement. On slide 15 we see an overarching view of ALL patients (SIGMA 1 carriers, non-carriers, placebo, 30-mg, 50-mg) and the results of the Episodic Memory count. You will notice that as a whole, the placebo group declined from baseline over the time period. Its now important to carefully distinguish between the 30-mg and 50-mg effects.
- the 30-mg DECREASES NEGATIVE score in episodic events. Basically, 30-mg in the entire patient population virtually halted decline.
- the 50-mg INCREASES POSITIVE score in episodic events. The entire 50-mg patient population IMPROVED as a whole over baseline. From placebo to 50-mg means, the improvement is a whopping 202%.
Slide 16 suggests that the PDD trial and MCI-AD diagnostic facets are all directly comparable. That is to say, you can expect the phase 2/3 AD trial to have similar results to the PDD cognitive data. I will talk about this a bit more in a moment.
Slide 17 is really interesting. In slide 17, they begin cherry picking the patient subgroups (total population [132] on the left and SIGMAR1 WT carriers on the right [87]). Notice blue bars specifically on this slide. Most significantly, notice how the week 14 blue bar on the left (66%) is increased in the WT populations week 14 blue bar on the right (74%). This implies that by week 14, the SIGMAR1 WT carriers had an 8% greater benefit over non-carriers. Notice the same blue bars for week 8, there is only a 2% difference there. This is proving two things: the benefit of being a carrier INCREASES AS TIME GOES ON and that there is a noticeable difference between SIGMAR1 carriers and non-carriers to begin with. This validates previous trial data and I am VERY interested to see if this effect (2 to 8%) increases even more in the continuation study.
Slide 18 shows as a whole, SIGMAR1 WT carriers on the drug had a statistically significant (0.05%)improvement over placebo for episodic memory counts. In fact, the improvement noted virtually ceased decline as is evidenced by a 600% reduction... notice that this increase is for mean population, and that some SIGMAR1 carriers actually improved... as was similar in the 32-patient AD study.
Slide 19 and 20 should be looked at as a combination. On slide 19 you can see how minimally complex tasks and complex tasks are accomplished (by time in seconds) for four subgroups. These groups are the young, the old, Parkinson's patients, and Alzheimer patients. Once again, Anavex couldn't help themselves to a big circle and a gigantic box noting an unmet need in Parkinson and Alzheimer's. See how much longer it takes for these diseased minds to accomplish tasks. Slide 20 is where things really heat up (note that slide 20 is in milliseconds and I convert them to seconds to compare to slide 19). This shows two charts comparing SIGMAR1 WT carrier reaction time to placebo groups in two separate reaction time tests. On the left you have the 'choice reaction time' and on the right you have the 'digital vigilance reaction time'. It is important to recognize that slide 19's data is based on 'choice reaction time', so the left chart is 100% comparable.
- Left chart: decline of 5 seconds from baseline for SIGMAR-1 dosed groups, and a nearly 29 second decline from baseline for placebo group. This constitutes a huge 474% reduction in decline. You also see that some patients with SIGMAR1 WT reversed effects and improved, not just reduced decline.
- Right chart: decline of 0.00551 seconds from baseline for SIGMAR-1 dosed groups, and a 0.05054 decline from baseline for placebo group. This constitutes an ASTOUNDING 818% reduction in decline. Likewise, you see that some SIGMAR1 WT reversed effects and improved, not just reduced decline. And they accomplished this with an EXTREMELY significant effect of 0.008%
Slide 21 is significant of course because it details effects on sleep. Despite a marginally significant improvement of 0.054%, it is important to look at other Anavex 2-73 studies (AD study, Rett studies, preclinical), and you see that sleep is very clearly aided by Anavex 2-73. What strikes me as interesting is the mention of REM sleep. This is the portion of sleep where you dream, and is also known to be the sleep needed in healing.
Slide 22 alludes to penetration of the blood brain barrier (BBB) with bullet 3. It is interesting that bullet 2's dropout stats are virtually the same for both the active cohort and the placebo cohort. This, combined with bullet 1, indicates that patients from both cohorts likely dropped out for reasons completely separate to the actual dosing. Parkinson disease dementia is rough on these individuals and COVID-19 likely exacerbated a lot of issues endured by these patients. One that comes to mind is depression. I am very interested to see quality of life data on these patients.
Slide 24's 3rd bullet is of interest. Again, Anavex mentions that PDD outcomes will likely be similar or at least comparable from PDD - AD studies. We actually see this throughout the presentation, I will make a closing remark encompassing that thought.
Slide 25 in the first bullet mentions 'PDD/PD'. Isn't it interesting that they included PD. PD of course focuses more on the motor functionality of the disease. It seems to me that the endpoints located in bullet 3 (MDS-UPDRS and actigraphy) have ALREADY shown to researchers a clear improvement to motor impairment, which prompted funders (MJFF and SIUF) as well as regulators/trial initiators to branch out to a PDD/PD trial. "DATA WILL BE SUBMITTED TO THE U.S. FOOD AND DRUG ADMINISTRATION TO SEEK REGULATORY GUIDANCE'. Isn't it interesting that the PDD PR in October made use of buzzwords and sensory language found in the TGA PA guidance and the FDA AA guidance? I will let you make your own assumption here, but it is my opinion that Anavex is at least SEEKING accelerated approval. The SIUF PR not mentioned an actual PD trial phase number (3 vs. 4) seems to lead credence to that. Note that accelerated approval does not need to be granted and the next trial could very well be a phase 3. Make your own assumption, do your own DD.
As a final note, take a look at slide 30 (old 32-patient AD data). Look at how the green lined super responders barely decline and in fact, some improve. Now go back up and look at slides 15, 18, and 20. Do you notice a striking similarity? Anavex is absolutely paving a remarkable case in this proof-of-concept which merges multiple trials, and ground breaking precision medicine/genomic sequencing data (some ongoing). Someone with an agenda could say that the trial data, and while this is partially true, it doesn't share the whole story. Slide 15 shows the entire patient population. The other slides show SIGMAR-1 WT to placebo. SIGMAR-1 carriers are 80-90% of the population. These 'cherry picked' charts do in fact show more of the holistic story than some of these posters would try to have you believe.. they have an agenda and are trying to confuse retail investors.
The data in this presentation is overwhelmingly positive and warrants an investment in Anavex Life Sciences Corporation (AVXL). As always, please do your own research and make your own conclusions.
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