ACADIA Pharmaceuticals' CEO Presents at 25th Annual Piper Jaffray Healthcare Conference (Transcript)

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 |  About: ACADIA Pharmaceuticals Inc. (ACAD)
by: SA Transcripts

Charles Duncan - Piper Jaffray

Thank you for joining us. It's a pleasure to introduce ACADIA Pharmaceuticals. Thank you for coming to the 25th Annual Piper Jaffray Healthcare Conference. I am Charles Duncan, I'm a Senior Biotech Analyst and Managing Director for the firm.

I've been covering ACADIA for a long time, joined the firm just last year, but have known the name or company since it was very much a private company. And I got to tell you, this last year has been really an interesting one to watch for those investors who are long in ACADIA.

So it's a pleasure to introduced Mr. Uli Hacksell. Dr. Uli Hacksell is the company's CEO; Mr. Tom Aasen is company's CFO. So we'll make this interactive, hopefully. Ask questions, if I miss you, just yell at me, and we'll get underway.

Really what a year, what a difference a year makes? How you feel?

Uli Hacksell

It's like an exciting time at ACADIA. We are happy about starting to feel that we are getting closer to the commercial stage for the company, which is something new for ACADIA. We have been working on pimavanserin for a number of years, as some of you may know. And now to be in a position, where we are approaching the final NDA before commercialization, it's very exciting.

Currently, our focus is clearly on conducting the remaining activities that are required for the NDA, and you may know that we have guided that the time limiting activities that we currently have is the CMC program, the stability testing of the regulatory batches. So having that in mind, we have guided submission of the NDA near the end of 2014. We have to wait for the stability testing on the drug, that's what takes time and the sort of requirement is that you should have 12 month stability on regulatory bathes.

Despite the fact that we already have three years stability on the clinical batches of drug product, which is the same formulation, you still have to redo it, since you have to do regulatory batches in the law just came. We also have to conduct some additional work in the drug-drug interaction program, before we have completed all remaining activities required for NDA submission.

At the same time, we are starting up pre-marketing activities. We did hire a Chief Commercial Officer in the third quarter, in August in fact. And we are adding to him a core infrastructure of additional expertise and competence and that small group will ensure that they conduct all pre-marketing activities that are required for a successful launch. So it is indeed very exciting for us and we expect that the coming years will be equally exciting.

Charles Duncan - Piper Jaffray

Long time coming, but congratulations on your success and progress, it's been fun to see. Before we start to drive into some of the kind of the details and things that are going on, if you look at the next 12 to 18 months, what would be the greatest source of value creation that you could look forward to, why you want to be measured?

Uli Hacksell

I think clearly one important step for us is to submit the NDA, that's an important milestone. We also believe that we will be able to present more information about the market itself, as part of us doing more market more in-depth market research over time. Clearly, those are the key value drivers for us.

In addition to that, we do expect to have clarified the path to regulatory submission also in Europe by mid next year. So I think that's another piece of very important information for us, and meanwhile we will continue to work hard and moving the program forward.

One additional activity that I should mention that we will spend time on next year is to sort out exactly how we want to continue with schizophrenia, which is a separate opportunity for pimavanserin. We did several years ago complete a very interesting large Phase II study in schizophrenia, where we treated acutely psychotic schizophrenic patients with a combination of the low doze of risperidone and pimavanserin.

And the outcome of that study really showed that that kind of combination therapy provided many advantages as compared to a standard therapy with risperidone. We had much more attractive side effect profile and a faster onset of action of the combination therapy. So this is something that we want to continue to plan for and think about and go up and running with the ongoing Alzheimer's disease psychosis study that we started two weeks ago.

Charles Duncan - Piper Jaffray

One of the big surprises in the last 12 months, in addition to very positive clinical data that has been published in or presented in a couple of venues, so very solid. Is that the FDA gave you guidance that you could file based on that one Phase III? I got to tell you, a lot of biotech companies miss interpret what the agency says to them. So help us understand, what was the magic pixie dust in our view with regard to your interaction with the FDA, in terms of them allowing you to file on that Phase III? Was it the previous work that had been done, was it the long-term safety study, was it the compelling efficacy or was it the current standard of care, which is definitely not favored by the FDA?

Uli Hacksell

I think it was a combination of all these things, that's my belief. The FDA didn't tell us the exact reason, why it was so favorable to us. But clearly the data were stellar. That must have been one important reason. Second, we have multiple endpoints and multiple possessors of the endpoints that still provided the same highly significant separation from placebo with the 40 milligram dose of pimavanserin. The FDA is obviously aware of the high unmet medical need for the indication as well. So I think that probably contributed as well to their decision.

And I think finally, we all the time have had good interactions with the FDA around the pimavanserin program. We went to them before we started the pivotal study and asked them if they were onboard with the design of the -020 Study. So they really thought of that decision to move ahead with that design and I think that may also have had to contribute to their decision.

Charles Duncan - Piper Jaffray

Are there any questions at this point, before we start to talk about some of the details of the future?

Question-and-Answer Session

Unidentified Analyst

To your question, Charles, just to follow on that. How did they treat the first [indiscernible], it wasn't just one study that worked, right, it's just one study that worked and one that missed its primary endpoint, so maybe could you talk about that?

Uli Hacksell

So then we have that study in our hands and then we had analyzed it. When we understood, while it did not turn out to be a pivotal study, we went to the FDA and we explained to the FDA why it did not work. And at the same time we showed them very clearly that although that study did not provide significant separation from placebo, it provided a very clear signal from a psychological activity and we also very clearly could demonstrate for the FDA. But the high placebo response that we saw in that study was really driven by patients who were rated or were not rated I should say by independent raters and came from Eastern Europe and India.

So for this is relatively straight forward, I think in our stepwise analysis of that study to show the FDA that they had a real signal, and if we enhanced the design of the study in the way we did, we would be able to demonstrate that that signaling type of significance. So I think it's a combination of many factors, but the fact that we really learned a lot from the first launch study and then could apply those lessons in the design of the successful study.

Unidentified Analyst

So at this point the tiebreaker study is kind of like [indiscernible] or wherever it's called, that's off the table completely?

Uli Hacksell

The kind of response -- so what we did when we had the data in hand was that we provided a very substantial briefing package that contained not only the data from the -020 Study, but also everything that we had done previously. And then we went to the FDA, and if they would be willing to file based on one pivotal. And they came back to us with an unambiguous answer, both in writing and at the face-to-face meeting. So there is no way that one can interpret that as any kind of uncertain answer, it's completely clear.

Charles Duncan - Piper Jaffray

So that study is necessary and sufficient for the filing?

Uli Hacksell

Yes.

Charles Duncan - Piper Jaffray

And then the CMC work and the drug interaction study, any chance that the timeline could accelerate? I've come to know you as a pretty conservative guy with regard to guidance, but it seems to me that maybe shorter stability and you already have a fair amount of information in terms of drug-drug interaction implied by the ongoing safety study. What's your sense of that timeline?

Uli Hacksell

Well, we are still planning for a standard 12 month stability testing. You may realize that we think that this is some time that is a little bit odd, since we have three years of stability on the same formulation. But this is the kind of regulations that you have to deal with in drug development.

Unidentified Analyst

[indiscernible].

Uli Hacksell

Yes, we have done on stability already. We did in fact report that we put them on stability in October.

Charles Duncan - Piper Jaffray

So six months stability testing, if you got stable drug would you discuss that with the agency or would you just wait for 12 months?

Uli Hacksell

Well, that's a very hypothetical question. So again, what I can say is that we are planning for 12 months stability.

Charles Duncan - Piper Jaffray

Is there some reason to be concerned about stability or is that a check-the-box thing that the agency asked you for?

Uli Hacksell

I don't see any reason why one would be concerned about stability. Pimavanserin, it's a very stable molecule. As I've said, we have already shown that the same formulation has stability for three years. We have the same producer of the drug product as we have had throughout the development. We will continue with same producer in the commercial phase, same thing with the API. So the CMC program is very straightforward and we expect the product to be very, very stable.

Charles Duncan - Piper Jaffray

And then what do you think about the drug-drug interaction study. How long do you have patients on that?

Uli Hacksell

The longest exposure now exceeds eight years.

Charles Duncan - Piper Jaffray

Eight years?

Uli Hacksell

Yes. And we have had more than 200 patients on drug for more than one year. That's a rapidly increasing number. Of course, we have had more than 100 patients on drug from more than two years.

Charles Duncan - Piper Jaffray

That's amazing given the average age is not young.

Uli Hacksell

That's correct. So when we conduct our efficacy studies, the average age of our PET patients is around 72 years. We have had patients from drug that have been in the 90s, and those patients are frequently quite sick. They may have 10 to 12 different drugs that they are taking for various kind of problems that they have. And we see despite that a very nice safety and tolerability profile of pimavanserin. And of course, the interesting thing is that in the long-term safety study, we have tested all kinds of drug-drug interactions in real life, which is very important. We don't see any safety problems with pimavanserin.

Charles Duncan - Piper Jaffray

That's what I am thinking? Are there any questions on this on the potential for the NDA?

Unidentified Analyst

[indiscernible].

Charles Duncan - Piper Jaffray

So go ahead though.

Unidentified Analyst

Are there any opportunities to redomicile the IP in pimavanserin?

Thomas Aasen

The question is on redomiciling the IP, now that is something we will be taking a look at, but currently all IP is located in the U.S.

Unidentified Analyst

With the precedence, where FDA has allowed accelerated stability testing at elevated temperatures?

Uli Hacksell

So the question is if one can do accelerated testing at higher temperature, I don't think that would be appropriate for the regulatory approval of the regulation batches because those have to be done at room temperature with slightly increased humidity. So there is no way you can sort of speed up the stability testing by increasing the temperature here.

Unidentified Analyst

[indiscernible].

Charles Duncan - Piper Jaffray

That's a great question. I was wondering about that. What keeps you up at night in terms of drug-drug interactions, given some thought to how the drug disappears?

Uli Hacksell

So first of all, I am sleeping really well.

Charles Duncan - Piper Jaffray

Are you?

Uli Hacksell

Yes.

Charles Duncan - Piper Jaffray

You take pimavanserin?

Uli Hacksell

I don't have to. So pimavanserin is metabolized and delivered and that has about 20 metabolized or so in total. It has a long half-life of about 57 hours. None of the metabolized is large metabolized by the way we have not seen any metabolized, which have a meaningful pharmacological activity. And so it's a very simple kind of scenario in that sense.

As I mentioned based on the real life experience we have done a lot of drug-drug interactions already in real life and not seen any problems. We have not provided a lot of information about what is required here, but what we have said is that obviously we need to do some formal drug-drug interaction studies, clinical studies, one of them is an L-dopa interaction study.

By the way more than 90% of our patients are in L-dopa. So that it's a no brainer that we'll be able to survive that without any problems. And then we are also doing preclinical studies. We're doing modeling. All of that is part of the program that we have to comeback with pimavanserin.

Charles Duncan - Piper Jaffray

Have you ever seen any adverse motoric effects, I know statistically, but what about numerically in these patients?

Uli Hacksell

So this drug does not negatively impact the motoric effect of the dopaminergic therapy at all. And in fact we believe that when patients are on pimavanserin, the neurologist will be able to optimize the dopaminergic therapy for the motor symptoms without having to worry about psychotic kind of problems. So I think that's one additional benefit -- potential benefit with pimavanserin therapy.

Charles Duncan - Piper Jaffray

So you could actually have better therapy for the parkinsonian symptoms as well.

Uli Hacksell

As an indirect kind of consequence of pimavanserin being available and being able to deal with all kinds of therapy-induced psychotic problems.

Charles Duncan - Piper Jaffray

Maybe before we hop into other indications, let's use that as a segue to the value proposition of pimavanserin and potential pricing. Now, I'm not going to press you on pricing. I know you're well ahead of that, but let's talk about how you might logic the thinking of the value proposition that you would make to payer?

Uli Hacksell

So let me start, and then Tom can add to what I'll say, but first of all, we know that that we have a serious unmet medical need and that's the key thing here. There is nothing approved to deal with this serious unmet medical need. And the need is, I think very well defined by the fact that PDP, Parkinson psychosis is the main driver of nursing home placement of Parkinson's disease patients.

And the reason for that is that the caregiver who is frequently, the spouse that lives with the patient cannot deal with the patient anymore. It's too problematic. It gets extreme distressful for the caregiver and for the patient eventually because the dilutions sort of lead to distress. You may know that a frequent kind of a problem is that the patient accuses the spouse of infidelity, and these are old patients, and it's of course, stressful for both spouse and patient.

And again, what is given today is off label antipsychotic drugs, frequently its Seroquel, which is one of the atypical antipsychotics. The problem is that Seroquel has been shown in the controlled clinical trials that has been tested and I think it's now filed to be ineffective. It's well tolerated, but it's ineffective. And it's in fact used as a sedating agent, and I think that the sedation that it produces in the patients is used in a way to mask the remaining psychosis, which is still there.

Charles Duncan - Piper Jaffray

So they knocked them out.

Uli Hacksell

They knocked them out, but it's a bad thing for patients with Parkinson's disease, because it also affects their posture negatively. And the kind of problems with the pneumonia and other kind of infections in the respiratory tract is worsened by the poor posture.

Charles Duncan - Piper Jaffray

So high unmet medical need, lots of value in the drug, maybe we ought to talk about other indications, but are there any other questions with regard to the NDA and timing and risk there? Yes, sir.

Unidentified Analyst

[indiscernible].

Uli Hacksell

And we haven't seen any indication whatsoever on any carcinogenicity problems with pimavanserin. So it was a very nice kind of thing to see and we decided to do the two year carcinogenicity studies early on, just to make sure that we didn't have the problem there.

Unidentified Analyst

[indiscernible].

Uli Hacksell

Yes. Several years to go I think, if I'm correct.

Charles Duncan - Piper Jaffray

Acceptable standard protocols to the [ph] AMC.

Uli Hacksell

Yes.

Charles Duncan - Piper Jaffray

So we only have few minutes left unfortunately, but let's talk about an indication that would significantly expand even this interest in market opportunity. For pimavanserin, that's Alzheimer's disease psychosis, you recently initiated a Phase II for that indication. Tell you me about ADP versus PDP? Why do you have confident that the PDP results have predictive value for ADP?

Uli Hacksell

What we saw in PDP was that it really had a antipsychotic activity, we really saw in that pimavanserin was effective in reducing the psychosis in the patients. And that's what we are looking at in ADP as well, psychosis, and it's a similar type of psychosis that you see in ADP as you see in PDP, similar symptoms. We're dealing with the symptoms, the visual hallucinations for example in both Parkinson's and Alzheimer's psychosis of visual character and visual hallucinations come from the 5-HT2A receptor, which is the target for the pimavanserin therapy.

Charles Duncan - Piper Jaffray

Sure, so they see things.

Uli Hacksell

They see things that don't exist. And the delusions are also coupled to the 5-HT2A receptor over activity, which is common in the two indications. So we think that we have a very strong reason why pimavanserin will be effective in both indications. And clearly the safety data that we have assembled with PDP patients also predict that we will be safe and well-tolerated by ADP patients. Like I mentioned that the FDA for example has already informed us, that we can use the same safety database that we used in the PDP application for an ADP application. So they look at the patients being essentially the same.

Charles Duncan - Piper Jaffray

So the Phase III that worked, we were pleased. The first Phase III did not work, we were surprised. Why do you believe that you're not going to be surprised by a placebo effect, if you will, or the conduct of the trial going array in the Phase II for ADP?

Uli Hacksell

I think they have designed the Phase II ADP study in a clever way, based on what we have learnt previously. We are conducting the study at King's College. It's formerly a one-center study, but it's a center that has 100 nursing homes, which are research sites associated with it, which are located in a closed geographical proximity, which means that we can use a very small group of raters to assess the endpoints in these sites.

And if you really want to ensure a good consistent rating, which is key, that you want to have as few raters as possible and as well trained raters as possible, and that is what we can do at this site at King's College in London. In addition to that we have designed a study, so that we start off with a three-week of brief psychosocial therapy, which is in other way you're removing as much as possible of the placebo response off from the patients, before you randomized that. So I think we have included the key elements of the -020 design, the successful design into the Phase II design as well for ADP.

Charles Duncan - Piper Jaffray

Very well or very good, really always a pleasure to see you. Thank you for sharing the ACADIA story with us. Thank you for everyone's interest in the ACADIA story. Look forward to following-up with you some time soon. Thank you.

Uli Hacksell

Thank you very much.

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