Good afternoon. My name is Aaron, and I will be your conference call operator today. Welcome to the Anavex Life Sciences Fiscal 2021 First Quarter Conference Call. As a reminder, this conference call is being recorded. I would now like to introduce your host for today's conference, Clint Tomlinson. Sir, go ahead..

Thank you, and good afternoon, 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 the first quarter of its fiscal 2021 financial year and provide clinical study and business update.

A taped replay of this call will be available approximately two 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 on today's conference call to review our financial results and business updates. I would like to first share with you our recent clinical and pipeline updates. Let me start with Rett syndrome. Based on recent Phase II U.S.

Rett syndrome clinical trial data, which showed positive clinical activity and safety data, potential accelerated approval strategy planning is underway, as the progress with ongoing Phase II/III AVATAR adult Rett Syndrome and Phase II/III EXCELLENCE pediatric Rett syndrome studies.

At the same time, the FDA has approved an extension of ANAVEX 2-73 U.S. Rett syndrome Phase II open-label extension study from 12 weeks to 36 weeks.

In Australia, Anavex received compassionate use Special Access Scheme approval for Rett syndrome patients to continue treatment with ANAVEX 2-73, after completing the AVATAR adult Rett Syndrome clinical extension study. This is very good news for the patients.

And as a reminder, we had previously received compassionate use Special Access Scheme approval for Alzheimer's disease in Australia. Anavex has sufficient ANAVEX 2-73 drug substance available to support all ongoing and planned clinical trials and first year commercial launch needs for the Rett syndrome program.

And ANAVEX 2-73 drug substance and oral solution exhibit excellent chemical stability based upon 3 years of stability data in both cases. That is very important. Let me now briefly switch to Parkinson's disease. We announced recently that Anavex has been awarded a research grant of nearly $1 million from the Michael J.

Fox Foundation for Parkinson's Research to develop ANAVEX 2-73 for the treatment of Parkinson's disease to explore utilization of PET imaging biomarkers which demonstrates the continued focus on a potential disease-modifying treatment for Parkinson's disease.

As a reminder, our clinical strategy is clearly differentiated from other biopharma companies and clinical studies in central nervous system..

Thank you, Christopher, and good afternoon, everyone. We reported a net loss of $7.9 million for the quarter or $0.12 per share as compared to $6.6 million, also $0.12 per share, in the comparable quarter of last year.

Research and development expenses were $7.9 million for the quarter compared to $6.3 million in the comparable period, while general and administrative expenses remained unchanged over the comparable period. Our clinical trial expenditures continue to increase gradually as enrollment progresses and the trials expand internationally..

Thank you, Sandra. In summary, we are thrilled to begin the new year with this strong business outlook, which will allow for multiple near-term data announcements, combined with continued fiscal responsible management of resources.

This adds to the breadth of strong clinical data we've reported across our precision medicine pipeline using orally once-daily available ANAVEX 2-73 for Rett syndrome, Parkinson's disease dementia and Alzheimer's disease. We look forward to providing, on a timely basis in 2021, multiple clinical data readouts from these clinical programs.

The converging biomarker-driven clinical data and further molecular understanding of our biological target, the sigma-1 receptor, is giving us added confidence in our efforts to meet our goal of potentially bringing new therapeutic interventions to patients.

Further, clinical milestones are provided in our latest corporate presentation, available on www.anavex.com. We are very excited about this year before us, and we look forward to continue with new data updates throughout 2021. I would now like to open the call for questions. Operator, please go ahead..

Your first question comes from Charles Duncan with Cantor..

I had a couple of questions. First, on the Rett program with 2-73, I'm wondering with regard to the US Rett study, when would you anticipate being able to provide additional details from that study? And congratulations on being able to extend the open-label extension of that study from 12 weeks to 36 weeks.

But can you help us understand a little bit kind of the rationale for that extension of the study? And what is the percentage of patients that have enrolled or continued on into the study in that extension phase?.

Let me start with the last first. So from the patients who finished the placebo controlled part of the US study, 100%, all patients continued in the extension study.

And the reason for the extension of the extension by another six months was the interest from the participating patients and families as well as the ability to continue to learn and add long term safety data for Rett syndrome patients with our compound.

Regarding the first question, we actually have not yet fully released the precise data on the Rett syndrome outcome, the baseline situation of the RSBQ and the other measures as well as the precise changes, and this can be done relatively near term, it will be near-term, together with what we have prespecified in the protocol and in the SAP, the genetic feature of the biomarker effect of the sigma-1 variance, which we identified previously in the clinical Phase IIa study in Alzheimer's patients.

So the answer is that this can be relatively near-term to provide more details on exactly the outcomes of the study measures measured..

We'll look forward to that.

And Christopher, would you anticipate it with -- in conjunction with an upcoming psychiatric or neurological meeting? Or one that's specifically driven, I guess, from the Rett advocacy community?.

So the community only is interested in learning more about it, and we are happy to provide it as soon as we can in order to get the data because this variant data requires genetic analysis, which is not ready to be available until now, but we will have it soon.

We can either do this in a conference, which we find timely and suitable or we will provide it in a press release with webinar together, and that will allow for everybody to be informed about this data..

One last question on Rett.

Can you provide any color on how the pediatric trial, EXCELLENCE, is going? And then the adult trial, AVATAR? And when would you anticipate being able to read out those two studies?.

So we think these trials are proceeding well. We stated that the AVATAR study will be a readout within the first half of this year, and the EXCELLENCE study in the second half of this year. That is right now our latest update and time expectation on these studies..

And then my last question is on the Parkinson's disease side for 2-73, not a lot of companies have had success in Parkinson's disease dementia.

And I guess I'm wondering with your provocative data that you spoke about recently, I believe it was at CTAD last year, what are the next steps for that program? Could we see that move into a later stage study this year? And would you be seeking agency guidance on that?.

So we have noticed that there were at least 3 Parkinson's disease dementia studies which had failed with other companies recently, and it shows that Parkinson's dementia is an extremely difficult study to execute. And we are fortunate that our study was positive.

And what we are now doing and we pointed it out when the data came out at CTAD, that we are now gathering the entire understanding of the participating patients with their background information, the correlation with the outcome, and then present that data to the FDA, to the agency, in order to seek guidance and to agree on a pivotal study design, which we would then undertake based on that detailed data for patients with Parkinson's disease dementia..

Final question regarding the platform, then I'll hop back in the queue. 3-71, new candidate, congrats on moving that one forward.

But can you tell us anything about that candidate relative to 2-73, how does it differ? Is it from a different chemical series? Does it have different brain penetration, different pharmacology? What -- any color on that would be helpful..

So what we know about ANAVEX 3-71 is that it is a completely different molecule. It was licensed in from Weizmann Institute in Israel, and we developed all the necessary preclinical data, toxicology, manufacturing, CMC to bring it to where it's now. And what we do know, the differences in 2-73 are twofold.

ANAVEX 3-71 has a strong affinity to the sigma-1 receptor and has also a more pronounced muscarinic M1 affinity and ANAVEX 2-73, which has more stronger affinity to other muscarinic receptors, but in a much weaker point. So we will really need to see the direct one comparison, how they are playing out.

What we have noticed that we received for ANAVEX 3-71 orphan drug designation by the FDA for frontotemporal dementia, and we might bring 3-71 towards indications first, which are not competing with ANAVEX 2-73 directly.

But we are very excited that we have another compound with the same valuable target of sigma-1 activation, and turns out to be so important biologically that we can use this also for indications, which we have not yet covered 2-73..

And our next question in queue comes from Ram Selvaraju with H.C. Wainwright..

Congratulations, Chris, on all of the recent progress. I wanted to just, first of all, start off with a few questions regarding the Rett syndrome program. Firstly, I was wondering if you could elaborate upon any additional gating items, assuming that the data from the upcoming studies is positive.

You had mentioned previously that this could potentially serve as the basis for regulatory submission in the United States, but I wanted to gain a better understanding of what additional gating items there may need to be or that there still are as you go through the steps in potential preparation of an NDA? Secondly, just wanted to clarify whether this program, if it were to be the subject of an ultimate regulatory approval, would qualify you for the receipt of a priority review voucher? And then thirdly, if you could maybe comment a little bit on the nature of the Rett syndrome competitive landscape as it currently stands.

Where you expect that to be at the time when blarcamesine might potentially be introduced into the market as a treatment for Rett syndrome? And also if you could give us a sense of what might be required to launch a drug like blarcamesine into the Rett syndrome population?.

So the first question was about gating items. So we are doing the same, what I mentioned for Parkinson's dementia, which is the entire genome/exome analysis, which is part of the clinical study, and we want to prepare that package and meet the FDA and share the data with the FDA.

The additional data from AVATAR and EXCELLENCE will be supportive, and I expect it to be supportive. The ability to get voucher is given that we have a faster designation and orphan designation, and we also have the voucher eligibility so that also is a positive answer if the pedriatric study is positive.

Regarding the landscape, we have heard and learned that one of the competitors in Rett syndrome has dropped out entirely, which is GW Pharma. They initiated and stopped, because of the COVID situation, their trial and retired entirely the program in Rett syndrome, which is a positive for us, we believe. And the fourth question is regarding marketing..

Also, I was wondering if you could comment on the current status of the special access team in Australia and whether you think that, that element of the overall Rett syndrome program, is likely to yield usable or significant clinical data that you could use in support of future regulatory applications? And if you could maybe give us a sense of what the size of that program is right now? How many patients are receiving drug as part of the FAF?.

So the compassionate use program in Australia has the benefit that it allows for patients who are on the clinical study, and after finishing the study on the extension study, and after finishing the clinical extension study would basically be left up without any further treatment.

And that allows them to continue the drug with the supervision of a physician and right now, we limit this pretty much to the existing patients which entered our study.

And the advantage is that once the drug will get approved, they will be overly automatically becoming eligible then to be prescribed the drug once it's approved for market authorization..

Just a couple more from me. I was wondering if you could comment on the recent activity in the Alzheimer's space and the fact that there seems to be a great deal, more enthusiasm at this juncture for proof-of-concept clinical results in Alzheimer's disease.

And I think part of that can be attributed to anticipation that perhaps with favorable regulatory decision on aducanumab, the goalpost may have been moved actually a little further apart, and in point of fact, the process by which Alzheimer's drugs get approved, could conceivably be construed as getting easier, a potential reflection, in fact, of the severe unmet need out there.

But what are your thoughts regarding what the regulatory environment might look like in a post-aducanumab approval situation? And what implications that has for your Alzheimer's program?.

Obviously, I cannot predict what will happen on June 7 when the meeting from the FDA will take place to decide about adu. But I would say that if it turns out positive, and that is a scenario you referred to, it would actually mean that the FDA would agree that one robust clinical study would be sufficient to approve a drug in Alzheimer's disease.

And since we are running now a robust Phase IIb/III study as well, this could be a positive for us in that regard.

If the decision on the 7th of June is more negative in outcome, then it would still I believe will not in way or shape impaired because we are basically, by that time, advanced with our study, and there's also ability for supportive data from the Phase IIa with our Phase IIb/III study. So we just put our heads down and move ahead.

But I would think that it's possible that there will be positive resonance if the study would be approved -- the other study would be approved mid of the year..

And then just three other very quick ones.

Firstly, assuming you have positive data in Rett syndrome, what implications might that have for future development of blarcamesine in other orphan neurological diseases? And can you elaborate at this juncture, what would potentially be your highest priority choices with regard to future orphan CNS indication development? Secondly, what is the significance from a commercial standpoint of the oral solution, in particular, as this pertains to Rett syndrome? I think we may have touched upon this in the past, but it probably is worthwhile reiterating that.

And then lastly, I was wondering if you could comment at this point about the possibility of co-formulation, co-administration, synergistic combination of blarcamesine with other compounds in the Anavex pipeline? And if that's likely to be the case, if that is something that you think might be something you wind up exploring in the future, which other compounds or which other types of compounds from the Anavex earlier stage portfolio might be likely to be most synergistic with blarcamesine?.

So the first question regarding -- or the second question regarding the solution, I think it's a very strong advantage because many of these kids or girls, they have a hard time swallowing. Some even cannot even eat.

They have an artificial pouch, a feeding tube, and liquid formulation is the only way actually to provide a drug substance to the patients other than by injection, which is very overly inconvenient and cumbersome. So that is a very strategic advantage of the therapeutic administration.

The first question regarding what could trigger the approval of Rett syndrome, we have seen that ANAVEX 2-73 has been extremely strong in treatment studies, but to also affect the pathology of Fragile X, which is autism spectrum disorder as well as infantile spasm and Angelman syndrome, another rare disease, these all three diseases.

But Fragile X is the largest rare disease of this autism spectrum disorders and with a multiple of the patient than Rett syndrome patients.

So since we have very strong preclinical data, and Rett syndrome happens to be a part of the autism spectrum disorder, given now we have basically supportive data, very strong data preclinically in clinical in Rett syndrome. We have now very strong and supportive data in preclinical in Fragile X.

We believe that the chances have increased to also be successful in a clinical study in the Fragile X. And that's why we're planning, and we already have developed the study design to move into Fragile X as a next study for ANAVEX 2-73.

Regarding the last questions about synergies, we don't know if the synergy with another sigma-1 agonist might be the best choice. I would rather think that a synergy could be with other compounds targeting other pathways, like if adu will get approved, we believe it will be synergistic to ANAVEX 2-73 because it is a different pathway.

But also, we have seen that ANAVEX 2-73 has been shown preclinically to prevent the disease.

So it's not only the treatment, which is the goal, and that's what we're now finding out with our ongoing Phase III study in Alzheimer's disease, but also thinking ahead strategically that one day of ANAVEX 2-73 could be used as a daily mini-aspirin potentially to avoid being -- coming in near to be in a situation where you get affected by such a horrible disease like Alzheimer's disease..

And your next question in queue comes from Robert LeBoyer with Ladenburg Thalmann..

I had a quick question on 3-71 and you mentioned that the DSMB had recommended continuing the trial. So I was wondering how long it's going to continue for? When we might see results? And if positive, when that might move forward? And also, in the Parkinson's program, I saw that the data from November included some secondary endpoints.

Is there any plan or anything where you might be presenting the full study data on the Parkinson's trial?.

First question, 3-71, we have several panels in the Phase I, and the first 2 panels was a single ascending dose. And that was very impressive that we got this green light to move forward now in the panels of going into female/male effect, their differences as well as recurring treatment as well as food effect of the drug.

So basically, the most important hurdle of a Phase I is like dose ascending, that was well tolerated to the highest dose, a planned dose was positive. That is the most, I would say, crucial information about the Phase I study. And now comes just nunances of the Phase I. We said that we would have the data within the first half of 2021.

I think it looks like it will be earlier than -- not waiting until the June time but much earlier than that, given where we are with the study.

Regarding the second question, remind me again the question, please?.

Just -- that had to do with the presentation of the full….

So the CTAD was really focused on the Dementia portion of the study, the Dementia portion of the PDD study.

What is now -- will come up, and we will present that in a proper fashion, either at a conference or in a peer-reviewed form or in a webinar or that fashion, we will provide the entire data of all the other measures of the CDR system, which are many more than the ones presented at CTAD, which also was a very short time frame of presentation of only 10 minutes, so we have to factor that in.

And it will also include the actigraphy data and other data related to Parkinson's disease. So this will be something which we are also planning to present on a relatively short notice.

And so in order to have that full picture of PDD, and the same applies here, this data, this aggregated data will be put in front of the FDA and to seek guidance in order to design a pivotal study in PDD..

And did you mention any plans to move Fragile X or into clinical trials this year?.

So one of the anticipated milestones which we have provided at the last call was to initiate a Fragile X clinical study, and we will do that with the guidance from the FDA.

Also, I'd like to mention that we have submitted a paper of the entire preclinical package, preclinical data for Fragile X with ANAVEX 2-73, and we expect that paper to be published eventually and hopefully, soon.

So this will be the entire preclinical data package of Fragile X of ANAVEX 2-73, which should and will make the case, a strong case, that the moving Fragile X with ANAVEX 2-73 into the clinic is warranted..

And next question in queue comes from Tom Bishop with BI Research..

Christopher, a little puzzled at the -- back in November, you said you were over 80% enrolled, and now you're saying 86% enrolled.

If you had a little quick math, 6% of 450, it's only about 27 patients in the last 3 months, which is -- what am I missing here about the complexity of signing this up?.

So you have to appreciate that before the last time we spoke and now it was in December, was the holidays. And during the holidays, it's literally a full stop in enrollment and activities of such things. We also want to point out that we added more sites, and I think there will be an acceleration from now on.

So I don't think that is too much to worry about. On the other hand, I want to pin -- point out that we want to make sure we're getting the right patients into the clinical study, and we have a very solid screening process to make sure that they are fulfilling the requirements of inclusion of the study.

And so we rather want to have the right patients then enrolling too quickly and have the wrong patients. That's basically the. But really, I would not read too much into this, it literally really is the holidays, which led to this, relatively. But I think we are very comfortable that there's actually a very good enrollment compared to other companies..

So how many sites are enrolling right now?.

I think if I'm adding all up, it's between around 40 to 40 -- almost 50. I have to count again all the sites. But we added sites in Germany, in U.K., in Canada and Netherlands..

So we're still hoping for early 2021 end of the enrollment?.

Yes. We have not changed it, and we set the data announcement of the data, which actually what matters, will be in the first half of 2022. It will be a year after the last patient gets enrolled. And then you have to add also time for data lock and data clean, but the time line is still unchanged for that..

And regarding the $75 million in the bank as of today, does that indicate that you've been able to take advantage of the recent increase in the stock price, maybe with your ATM? Or that was a big jump, given that you've also had a quarter of spending in the last , I think it was $48 million.

So I myself have been hoping that you've been able to somehow use that ATM at these higher prices and not have to dilute the shares as well….

That's an excellent point, and good that you asked this question, Tom.

Really fortunate that we have this tool in place, and it was exactly meant to, for that reason, to when there is really an unexpected and positive share price move that we're able to, with least dilution to basically use this tool in order to make shareholders the least dilutive way possible of continue to progress in work because without capital, we cannot advance our assets, as you know.

And that was possible in the last weeks to do that. That's right..

So how many shares are outstanding now?.

We were obviously very fortunate to take advantage of this stock move, but I think the details will be provided in the next Q, which will show up early next week because our -- the latest filing will be on Monday because Monday is a holiday, so it will be next week, Tuesday, most likely..

So you'll have the share count on the cover of the 10-Q?.

But as you can figure out, least dilutive possible. So it will be not by much..

So SFVA or Cassava has proven that interim data may allow a company to start on a Phase III trial, as well Phase IIb or IIIa trial is still continuing, if my perception of the news is correct. So is there any more thoughts of an interim readout? Or maybe I'm wrong on this? So go ahead..

I think the trial you're referring to is an open-label study. So that is a different situation you have here. But I just want to point out that we, obviously, are almost completing the randomization of our Phase III study, if you so like, the other company you mentioned still has to start.

And the other point I tried to make is that we have the program in Rett syndrome, which could generate revenue pretty soon by itself in addition to Parkinson's disease dementia data, which also is unique for Anavex. So I think we're in a good position, and we just are making progress as we go..

But as regard to an interim analysis of the Phase IIb/III trial for Alzheimer's?.

Yes. So in theory, it's possible, and there is a chance to do that. It's a possibility. In the protocol, it's allowed to do that. If we do that, I don't know yet. And I think we will let the discussion with the FDA guidance on that. So the possibility is certainly there..

But is my understanding correct that is it possible that the interim data from this study could enable you to just get going already on the Phase III study, even while the full enrollment and readout of the Phase IIb/III study is ongoing?.

Well, the Phase IIb/III is our Phase III study, so we think that is a pivotal study..

And I think if I understood somebody else's question, he was fading in and out of my line was that Parkinson's physical data, we're still awaiting that, right?.

The genome data and the Parkinson's, the actigraphy data and so forth, is that what you're referring? That will be presented….

Well, the dementia data, and then there's the effect on Parkinson's itself which I think is….

Right on the movement, that's correct. This is what I mentioned. We will release the data in short order once we have it all together, and that will be something we will present either at a conference or in a webinar for everybody to see exactly the effect of the drug in these patients..

Thank you. Ladies and gentlemen, this concludes today's questions and today's conference. Thank you for participating. You may now disconnect..