Good afternoon. My name is Vanessa and I'll be your conference call operator today. Welcome to the Anavex Life Sciences Fiscal 2020 Year-end and Fourth Quarter Conference Call. As a reminder, this conference call is being recorded. I would now like to introduce your host of today’s conference Clint Tomlinson. Please go ahead..

Thank you, and good morning, everyone. We appreciate you joining us today for Anavex Life Sciences conference call and webcast. Our agenda is to review the company's financial results for its fiscal 2020 year and provide a clinical study update.

A taped replay of this call will be available approximately 2 hours after the call's conclusion and will remain available for one month. The call will also be available for replay on Anavex's website at www.anavex.com..

Thank you Clint. We appreciate everyone joining us for today's conference call to review our financial results and clinical updates. First, I would like to provide new key clinical updates given the very encouraging data of the U.S. Rett syndrome study. We plan to advance the AVATAR adult Rett syndrome study into a pivotal Phase 2/3 clinical trial.

In December 2020, Anavex announced top-line results from a U.S. Phase 2 controlled trial of ANAVEX 2-73 in adult female patients with Rett syndrome.

Primary safety, pharmacokinetics, and secondary efficacy endpoints were met with statistically significant and clinically meaningful consistent improvement in Rett syndrome behavior questionnaire RSBQ, and clinical global impression improvement, CGI-I scores.

Improvements in RSBQ total scores were correlated with decreased improvement in plasma glutamate. Based on these results, we are planning to meet with the FDA to discuss an accelerated approval pathway.

Further, we are planning a pipeline expansion for 2-73 using gene biomarkers of response and applying precision medicine for neurological disorders with unmet medical need.

This includes a planned initiation of a pivotal Phase 2/3 study in Fragile X Syndrome, the most frequent genetic cause of autism spectrum disorder for which we have convincing preclinical data.

We also are planning to initiate a Phase 2/3 clinical trial for the treatment of a new, rare-disease indication, ANAVEX 3-71, an orally administered small molecule targeting sigma-1 and muscarinic receptors that is designed to be beneficial for neurodegenerative diseases is currently in a Phase 1 clinical trial and on track with top line data anticipated in the first half of 2021..

Thank you, Christopher, and good afternoon, everyone. We reported continued fiscally responsible activities with a net loss of 26.3 million or $0.45 per share for the 2020 fiscal year as compared to 26.3 million or $0.54 per share in the comparable 2019 fiscal year.

General and administrative expenses fell by approximately $1 million as a result of a reduction in non-cash compensation charges..

Thank you, Sandra. In summary, despite all of the new challenges 2020 was an extraordinary year for Anavex with significant progress across our portfolio.

We look forward to building on this momentum with key milestones expected from multiple programs, including data on the ongoing late stage Rett syndrome trials, AVATAR and EXCELLENCE; expanding the clinical biomarker-driven 2-73 rare disease program into additional late-stage studies with high unmet medical need; completing the late stage 2-73 Phase 2b/3 Alzheimer’s disease trial; and advancing 2-73 into clinical disease modifying testing in Parkinson’s disease.

At this point, I would like to thank the patient, the doctors, and the entire Anavex team who made all of this progress possible. We look forward to providing further updates as advancements continue. I would now like to open the call for questions. Operator, please go ahead..

Our first question comes from Charles Duncan from Canton Fitzgerald..

Hi. Yeah. Thanks for taking my questions. Happy Holidays. And Christopher all the great progress recently, congratulations.

I have couple of quick questions regarding the Rett program and AVATAR versus the recent adult study, you mentioned that you are going to move forward with AVATAR as a pivotal, I'm kind of wondering what has changed, what will change in moving that forward? And then when you consider the, I guess, characteristics of the cohort that was included in the sample and the recently read-out adult study, how is that different in any way with the AVATAR study? And then, I have a follow up question..

Right. So, the AVATAR study is designed as a Phase 2 right now with the safety as a primary endpoint. So what are we doing, we are switching to secondary endpoint, which is the efficacy measure of RSBQ and CGI-I to a primary endpoint. So that's a change which you can do in ongoing studies without being blinded. And the difference to the U.S.

study, the AVATAR study is on average higher drug exposure profile where the doses are higher than the U.S. study. So, this way, we also think we can capture a very important element, which the FDA is looking for which is dose response..

Okay, and then when you think about the efficacy measures that were made and efficacy seen in the U.S.

adult study, how do you feel about the sample size or the planned effect size or the hope for effect size out of AVATAR? Is there going to be a change in the sample size that you plan to enroll in that study?.

Yeah, excellent question. Right now, we don't have any need to change the number of patients in the AVATAR study, but it could well be that we will make an adjustment not to increase the size, but maybe just to increase additional regions in that regard, but still it’s not completed enrollment that might not require any change of numbers.

But we want to basically let this discussion then – the part of the discussion, come out of discussion with FDA before, you know, before making a change on that level at this point..

Okay.

So, you do plan to meet with the FDA, you're going to perhaps request a meeting here soon or have you done so, and then the outcome of that meeting will possibly impact design and conduct and sizing of AVATAR?.

Right. I mean, we have very good strong effect size of the U.S. study, knowing that it was even a low dose, we expect the high dose to even stronger effect size.

So right now, we don't have an immediate need to change the design of the study other than switching the primary and secondary endpoints, but what I want to point out is that ultimately, we want to discuss with the FDA because we also want to make this as the final pivotal study.

And if there are additional changes the FDA the agency recommends, and we certainly will be open to that..

Yeah, that makes sense. It seems prudent.

Last question on this is regarding the Rett study that read out recently, but also the Parkinson's disease, cognition or dementia study that you alluded to, when would you anticipate being able to present the data from those two studies in a peer reviewed form?.

Yeah. So, we want to be very transparent, and we will. You have to appreciate that the co-primary endpoint of both studies and secondary, the efficacy endpoints will also be looking at a genetic outcome of the patient’s genetic background of the patient, and that requires a bit more time than the usual analysis of studies.

That's why we have to go through this before we can basically submit this to a publication, but we mentioned that we will submit to a publication to the studies, and we will present probably over the course of early 2021 more details about the PDD study as well as the Rett study..

Okay, last question, and then I'll hop back in the queue, regarding the pipeline, and sorry for taking up all this time.

But regarding the pipeline, you mentioned another rare disorder and I'm wondering if you had mentioned it actually in the IP discussion that you alluded to, for example, Angelman or could that be inclusive of Huntington-type indication or an indication beyond say, a neuropsych rare disorder?.

Yeah. Excellent question.

We didn't want to not mention it because we don't want to, you know, prevent the knowledge, but it is just because the drug is shown now in addition to infantile spasm and Angelman syndrome in addition to Rett syndrome, which we have in the clinical trial, but we have infantile spasm clinical, pre-clinical data as well as Angelman presented already in the past.

In the meantime, we were able to get additional preclinical data, of confirmation of efficacy in models of diseases, which are rare and developmental in nature, which are basically on top of those I just mentioned.

And since this is our – also now strategic discussion with repertory as well as with clinical design, so which study would be quicker to perform versus others? How's the competitive landscape look like for these rare diseases? We just want to do that homework first before we engage into mentioning what it is, but it will be one new indication which I not have yet – we don't have yet mentioned in the slides and presented so far..

More color in 2021, you suspect?.

Exactly, definitely more colors come in 2021. And again, it's a rare disease, maybe it is even a ultra rare disease.

So this is really intriguing thing about it that we never stopped finding or engaging in communities, which has an unmet need based on the approach of the drug to be upstream and regulate the downstream features of homeostasis imbalance in the biological system, and that benefits quite a lot of additional indications, and among them quite rare diseases and that's why we want to basically not pass-on this opportunity for patients to have..

Got it. Thanks for taking all my questions. Happy Holidays..

Likewise. Happy New Year to you and your team..

Our next question comes from Robert LeBoyer from Ladenburg Thalmann..

Good afternoon and congratulations on all the recent progress.

My question has to do with the Alzheimer's study, and you had mentioned that you expect to complete enrollment early in 2021, and I was wondering when we might see the first cut of the data?.

So the study is a 48-week study. So it's very simple to add. Once last patient had been enrolled, then add 48 weeks. Because last patient enrolled in the study will also determine the last patient finishing the study. And that's the – basically the simple arithmetic to do. So that will be early 2022..

Okay, great.

And there was also in addition to the cash balance as of September 30, and the 29.2 at September 30 as of today and I was wondering where that extra money came from?.

Yeah. So, we have two programs in place, in order to basically be always able to, I would say, strategically, and also least dilutive as possible when stock price moves up to a higher level, to basically utilize the ATM and the purchase agreement.

And one of those two features we were able to utilize to basically make sure we always have two years of cash. Now that we have to use cash as of today, we obviously will not need to use it anymore going forward in a high frequency.

And that's basically the message we want to also send to our shareholders that we always want to make sure we have enough cash and resources. So, we don't have any problems executing our activities..

Okay, good to hear. Okay, thank you very much..

You're welcome..

Our next question comes from Tom Bishop from BI Research..

Hi, Christopher..

Hello..

Yeah. Hi.

Can you hear me?.

Yes..

Okay. I noticed this comment about the planned initiation of ANAVEX 2-73 imaging focused Parkinson's disease clinical study, it didn't say dementia and I didn't understand the imaging focused either.

Could you put a little bit more on that?.

Right. So, we have been fortunate that we have been received funding previously for Michael Fox for a preclinical study in disease modification for Parkinson disease, which is not Parkinson's dementia, just movement disorder. And that was very successful.

And now as a next step, we want to make sure that in Parkinson patients not dementia, we also understand better how the drug works. And this is something we'd like to explore this year..

Okay, getting to the Australia trial, why the company had to go to U.S.

sites, I would have thought that there would be enough patients in Australia to reach your goal of what is it 300? Can you just explain a little bit more? I mean, and what does that say about the market size in Australia?.

In the Australian Alzheimer study, you mean?.

Yes..

So the Australian Alzheimer study is now an international study. So, we started it in Australia and the Phase 2b/3 is actually now enrolling in Germany, Netherlands, the UK, and Canada, in addition to Australia. And so what we studied in Australia has been now expanded, you know, in three continents overall.

And so, we just want to make sure that an international study has advantages, and there was not that we were limited in Australia, but it's always an advantage to have sides running up this proportion in many different places..

Okay, and also, is there any thought being given to some interim analysis? So, the Alzheimer’s study, that's not unusual? Or we got to wait till 2022?.

The option is there because the protocol allows for an interim analysis, it is explicitly mentioned that it can be useful in different analysis. And we have seen that interim analysis could be misleading as shown in another company. So, we don't know if we want to use that at this point in time, but the chances are there.

So there's possibility that there is data before 2022 for the Alzheimer’s study..

Okay, and with regards to Avatar and the adult Rett syndrome study, moving on to Phase 2/3, you know, I kind of thought that that was initially just a study so that you could advance into the adolescent market, which I thought was your primary market, but are you going to prong – you're going to test all the way through the adult?.

Right, sorry for interrupting. So the adult population is a little bit a population, which has not received much attention.

Mostly trials go for younger patient, patriotic patient, because the expectation is that the brain is more and has a higher potential response than if the patient's already advanced in age, and therefore, the brain doesn't respond anymore, as much to a intervention.

We've seen a very strong response in an older population Rett syndrome, which is very favorable to be interpreted, because that makes us even more excited to see the data when we go to younger patients.

But ultimately, you want to capture the entire market, right? So it's not limited to one age group, but it's just often – the signal is often stronger in younger patients.

So what we capture we are aiming with the AVATAR and the excellent study exactly to capture both age groups, and the adults above 18 years old, and the age group below 18 year of age..

Is the excellent study now enrolling?.

Yes, it's enrolling very nicely. That’s the case..

Okay, thank you..

You're welcome. Thank you..

Thank you. There are no further questions at this time. This concludes today's call. Thank you ladies and gentlemen, you may now disconnect..