Anavex Life Sciences Corp.

Good afternoon. My name is Adrienne, and I'll be your conference call operator today. Welcome to the Anne of Ex Life Sciences Fiscal 2021 Third Quarter Conference Call. As a reminder, this conference call is being recorded. I'd like to call over your host for today's conference, Clint Tomlinson. Please go ahead.

Thank you, and good afternoon, everyone. We appreciate you joining us today for Anne of Ex Life Sciences Third Quarter Conference Call. to review financial results and discuss the company's business updates. A taped replay of this call will be available after the call. The call will also be available for replay on Anavex's website at www.anavex.com. With us today is Dr. Christopher Misling, President and Chief Executive Officer, and Sandra Boenisch, Principal Financial Officer. Following management's remarks, there will be a question and answer session. Before we begin, Please note that during this conference call, the company will make some projections and forward-looking statements. These statements are only predictions based on current information and expectations and involve a number of risks and uncertainties. We encourage you to review the company's filings with the SEC. This includes, without limitation, the company's forms 10-K and 10-Q, which identify the specific factors that may cause actual results or events to differ materially from those described in these forward-looking statements. These factors may include, without limitation, risks inherent in the development and or commercialization of potential products, uncertainty in the results of clinical trials or regulatory approvals, need and ability to obtain future capital, and maintenance of intellectual property rights. And with that, I'd like to turn the call over to Dr. Misling.

Thank you, Clint, and we appreciate everyone joining us on today's conference call to review our financial results and describe the company's growth strategy. Let me start by stating that we can proceed into the remainder of 2021 with a background of a strong balance sheet of over 157 million in cash and no debt. Starting with our lead drug candidate, Anavex 273, We expect to announce top-line results from the confirmatory, double-blind, placebo-controlled, late-stage Phase IIb-III study in Alzheimer's disease in second half 2022. The double-blind, placebo-controlled, 509-patient, late-stage Phase IIb-III Anavex 273 trial in patients with Alzheimer's disease exceeded enrollment beyond 450 patients at 52 sites across North America, Europe, and Australia using ADAS-COG cognition and ADCS-ADL activities of daily living and function as primary endpoints. This multicenter, double-blind clinical trial is measuring efficacy, tolerability, and safety of two different once-daily oral anorexia Anabix273 is an orally available small molecule activator of the Sigma-1 receptor. Data suggests that activation of Sigma-1 results in the restoration of complete housekeeping function within the body and is pivotal to restoring neural cell homeostasis and promote neuroplasticity. The study includes a pre-specified Precision Medicine Biomarker, SIGMA-1 gene expression, which demonstrated correlation with direct measures of clinical benefit, cognition, and activities of daily living, and found correlation in a previous case to Alzheimer's disease. Patent data previously confirmed dose-dependent target engagement of SIGMA-1 with Anavex 273. As a reminder, of our clinical strategy is clearly differentiated from other biopharma companies. In clinical studies in CNS, Anavex is continuing to pioneer the approach of big data in clinical trials to leverage the relevance of phenotypic and genotypic precision medicine analysis of whole exome sequencing and gene expression data in drug development and, in particular, the potential to identify patient genetic variants and gene expression changes that may predict increased chances of success of Alzheimer's disease, Parkinson's disease and Rett syndrome treatments. Additionally, we can announce that we exceeded the enrollment target for the precision medicine under VEX 273 Phase 2-3 Avatar clinical trials in patients with Rett syndrome. and currently top-line results from this study are expected in the second half of 2021. Further clinical milestones are provided in Adavex Life Sciences' latest corporate presentation, available at www.adavex.com. And now, I would like to direct the call to Sandra Boenisch, Principal Financial Officer of Adavex, for a brief financial summary of the recently reported quarter.

Thank you, Christopher, and good afternoon to everyone. We can report a significant increase in cash runway. Our cash position on June 30th, 2021 was $157.6 million, which we believe is sufficient cash runway to fund operations and clinical programs beyond 2025.

These animals usually, they basically get sick, they lose cognition, and you see that in the measures of water maze behavior and so forth. And we noticed in the arm which had been given this seven-day treatment, prevention, that these animals never developed after the injection with Abeta any symptoms of cognitive impairment. They behaved and cognitively stood as their wild-type parts. But those who were given the A-beta and without the pretreatment, they developed a cognitive impairment as you expected from the animal model. So this is the observation which led to the potential that which as we know by now is extremely upstream and possibly able to prevent the cellular stress which is caused by the ABETA interjection and so in the entire challenges of the pathology which is not limited to ABETA that this could be used as a prevention also The intelligence we have from the Alzheimer's study seems to be also giving credibility in that direction since we noticed a gradual ability to improve cognition with earlier stage status of cognitive capacities. So when I mentioned before that cognitive impairment lower than 20 MMSE and the lower score means more cognition or more cognitive impairment, that those patients were better off the earlier you treat them. So we might be able to continue the trajectory of into the ability to prevent the cognitive impairment to even take place. Thank you very much. And we compare in a way to mini aspirin, which some people take for avoiding cardiovascular problems. And they do that every morning for breakfast. So I'm not saying that this is confirmed in humans, but eventually we will be able one day to tackle that. And that is the plan in a study.

Great, thanks. And also, I wanted to ask about your thoughts regarding lessons, takeaways from the Rett syndrome experience with Blarkamathine and their applicability to your potential clinical development initiative with the compound in Fragile X syndrome. And if you could also give us a sense of when you anticipate the Fragile X syndrome program to initiate patient enrollment. Thank you.

We have included in our Rett Syndrome clinical trial a measure which is called ADAMS, and that score is, interestingly enough, a secondary score in the Rett Syndrome study, but it is often used as a primary endpoint in Fragile X studies, and that ADAMS score was extremely positive with behavior improvement of General Mood of Anxiety and Compulsive Behavior Improvement, which were very significant and very broad and global. So we believe that in a data readout of the preclinical data of RADL-X with Anavexo 73, which we submitted to a peer-reviewed paper of a Nature paper, which we expect to come out as forthcoming, that this could be a very good basis for the rationalizing, progressing Fragile X into an indication of choice also for ANAVEX 273. And the idea is obviously to move this forward as soon as possible given the unmet need of Fragile X, which is the largest population of autism spectrum disorder. And Rett syndrome is also part of the family of the autism spectrum disorder. So these are correlated diseases, although they are originated in different places in the causation, in the causality, but they have similar symptoms and overlapping symptoms with each other. So we expect the trial to be initiated once we are able to showcase the data in a peer-reviewed paper. Thank you very much.

And our next question comes from Tom Bishop from BI Research.

Hi, Christopher. You said that you expected to include a Phase III prevention study or to initiate one for the prevention indication. And I was wondering what the status of that was and how soon we could expect that.

So this is something which we would like to discuss with the agency because this is obviously a very important study and we want to get that right. So we will let that happen first before providing more details on that. But I'd like to just point out the potential for that to be the case and that gives us also a great hope that given the broad upstream effect of the Sigma-1 activation, which is, I want to remind everybody, it's not something we came up with, but it's really the endogenous, the body-owned defense mechanism to avoid and to prevent cellular stress, which causes diseases like Alzheimer's, but also Parkinson's and other cognitive impairment indications, and probably also the degenerative and as well as the neurodevelopmental indications, which is the reason why we see this strong effect, beneficial effect with the drug in this raw therapeutic different indications. So this is something we'd like to discuss with the agency first before providing more details. But this is the long shot and this is probably the big prize that one day this could be used as a prevention treatment for all degenerative diseases and not only for treatment.

That's a very exciting possibility. What is the status of the meeting to proceed on to Phase III and Parkinson's? Sometimes it seems like we lose a lot of time between I know you've presented the final data, and I'm just wondering what the timeline is here. Have you scheduled a meeting with the FDA or had one?

That's a very good question. The key background is to know that the trial itself has finished, but the analysis is not limited to the endpoints which we reported. There are more work up ongoing right now, and this is also unique for Anavex and differentiates other companies that we have included in our trials, including the PDD trial, the Parkinson's Disease Dementia Trial, the whole genomics exome analysis, both DNA, but also RNA, and you know that we reported the RNA changes of the Sigma-1 gene. What we have not yet done is to have the intelligence on the RNA of all the other genes, which is the whole genome. So there will be so much more intelligence from this PDD study, which we are right now putting together. And once we have that, then we will have the ability to put this all forward, because this will determine a much more robust face redesign of a pivotal study in Parkinson's dementia as well as in Parkinson's. But that requires also the dialogue with the agency first. But before that, we have to have the entire data at hand.

Well, okay. And the status of the Michael J. Fox Million Dollar Imaging Study, is Michael J. Fox doing that independently of you? I mean, you're supplying the drug, but they're doing the imaging. I mean, how is that going?

It's basically a grant that allows us to do the study and we are in the process of starting this year. It's a study which will capture the imaging and the profile of the Anavex SM3 of the drug in the brain in the humans. with the same PET ligand which we have done already in animals. So this will be a confirmatory of that effect in human brains and that is the study which was fully funded by Michael Fox Foundation which we are executing and they basically funded that study with a grant.

Oh, I see. Okay. And you indicated a mystery indication earlier this year. And also, there's a 371 trial. Is there not a phase one ongoing? Could you comment on those two? They were one and the same. I don't know.

Right. It's not a mystery indication. We have only said we have not disclosed yet the indication. We have several animal models where Anavex 273 has been positive very well, achieving a confirmatory effect on a disease which is and others. And we want to make sure before we move forward with the clinical trial that we pick the right one to do because we have the choice of several indications and we are doing this right now. So once we have completed that assessment, we will disclose that indication and start the trial also right away. and regarding Onivex 371. It's basically another molecule had its own IP and that is now in a phase one and we expect data readout in the second half of this year is progressing well and we are excited because it confirms the, validates the mechanism of action of our platform portfolio to focus on Sigma-1 and also it has received often drug designation for frontotemporal dementia which is also an unmet need. So we are now preparing after the phase one the next stage of that which will be a study in a indication of cognitive impairment and it could very well be a frontotemporal dementia or another indication with an unmet need with cognitive impairment.

But the phase one study, are you saying it's done?

It is about to wrap up and we will be able to report the data in the second half of this year. That's correct.

Will that include any efficacy data or just the safety trial literally?

It's predominantly a safety trial, but I will allow us to basically share the data once we have it, and that gives us better visibility on what it included in that outcome measures beyond phase one data on safety data.

Okay, well, you know, I've been very encouraged by the breadth of the positive readouts you're getting on a variety of indications, and I think that helps support the idea that A273 really does something in the brain, which I think you have little doubt of, and I do too, but it's just good to see so many different positive readouts coming. Thank you.

If I might add, it is really important to notice and to highlight the fact that in all clinical trials we have performed so far, not only was Anavex 273 efficacious at the right doses, but it also demonstrated a dose response curve, which is always a very clear indication of our effect. And thirdly, we have noticed that all the data, all the trials so far performed, had a very strong biomarker of response or predictive biomarker response, which was born by the level of mRNA expression of the target of our drug itself. So there's really no better way of showing efficacy and confirming efficacy of a drug with these strong biomarker outcomes, which correlated with all the primary and secondary endpoints of the trials we have performed.

Well, like I said, it's very encouraging. Alright, thank you.

Thank you.

Thank you, ladies and gentlemen. This concludes today's conference call. You may now disconnect.