Anavex Life Sciences Corp. (AVXL) | Key Takeaways from the Alzheimer's Disease KOL Call; Biomarker Data Likely in Early 3Q23

We recently hosted a KOL call with Dr. Charbel Moussa on Alzheimer's disease, and focused our discussion on the real world AD addressable population for drug's like Aduhelm, Leqembi, Anavex's blarcamesine, a critical look at Anavex's latest clinical data, key physician's focus, unmet needs following approval of IV infusion drugs, role of biomarker data and it's importance in making prescribing decisions, and a realistic sense of market uptake following potential approval of blarcamesine. Overall, Dr. Moussa views Anavex's data as highly competitive with the approved drugs in AD. Given a slightly harder to treat patients and shorter duration on drug, Anavex's data showing on par clinical benefits with Leqembi and Aduhelm without the safety concerns. Additionally, the KOL believes that there will be a building patient population to get on drugs following Leqembi, etc. where plaques have been removed but discontinued often due to safety concerns. We can easily see Anavex's blarcamesine taking share of that market. Key upcoming catalyst for Anavex is biomarker data, likely in early 3Q22. Dr. Moussa does not expect to see plaque reduction of the magnitude seen with Leqembi, as Anavex's blarcamesine is not targeting amyloid plaques, but any reduction would be highly supportive of Anavex's data and should be seen as a positive.

1. Dr. Moussa mentioned that approx. 60-65% of patients are diagnosed with Alzheimer's disease in the mild-moderate stage and approx. 35-40% are diagnosed in the prodromal/MCI stage of disease. Patients at early stage of disease usually get diagnosed due to high risk to develop AD, factors include family medical history and genetic factors( e.g. APOE gene).

2. Mild cognitive impairment (MCI) is an early stage of memory loss or other cognitive ability loss. Approx. 50% of MCI patients will develop AD, the rest might develop other types of neurodegenerative diseases, such as Parkinson's disease. In earlier stage of disease there is a higher possibility for treatments to reverse or at least resist disease progression.

3. According to MMSE scale, prodromal/MCI stage can be scored as 28-27, mild stage can be scored as 27 to 20 or 18, moderate stage 15-20 and severe stage is <15. Mean baseline MMSE in Anavex's trial was around 23, while Leqembi trial at approx. 25 and Aduhelm's trial had mean baseline MMSE of approx. 26. Hence, Anavex's patients were more in the mild stage while the other two approved drugs were tested in patients at early stage/MCI.

4. To be noted that the rate of CDR-SB decline in the placebo arm in Anavex's trial was faster compared to the placebo arm in Leqembi's CLARITY trial—drop of approx. 1.6 in 11 months versus approx. 1.2 in the similar time span, indicating patients were progressing faster in Anavex's trial and were slightly harder to treat patients.

5. Dr. Moussa mentioned that the accuracy and ability of different cognitive tests to detect disease progression depends on stage of disease—CDR-SB is more sensitive in MCI patients while ADAS-Cog is more sensitive in mild stage patients.

6. We note that Anavex's blarcamesine showed inline slowing of CDR-SB decline— 27% at 11 months, versus 27% with Leqembi at 18 months, 22% with Aduhelm at 18 months, and 29% with donanemab at 18 months (in intermediate + high tau patients); Exhibit 2.

7. Anavex's blarcamesine outperformed the approved drugs in slowing the rate of by ADAS-Cog—45% at 11 months, versus 27% with Leqembi or Aduhelm and 19% with donanemab at 18 months (in intermediate + high tau patients), To be noted, Leqembi trial used ADAS-Cog14, while all the others used ADAS-Cog13. To be noted that Anavex's trial was smaller and for a shorter duration compared to the approved drugs' trials.

8. Dr. Moussa sees the percent slowing of decline in mid-20 range as meaningful and makes real life impacts. In terms of benefit to patients, slowing decline by 27% in CDR-SB score at 18 months indicates delay in AD progression of approx. 7-8 months and slowing decline by 36% indicates delay of almost 9 months. While there are safety concerns with anti-Aβ antibodies, delay in disease progression of 1-2 years has significant clinical and social benefits in AD patients.