Arcturus Therapeutics Holdings Inc. (ARCT) Q2 2015 Earnings Report, Transcript and Summary

Good day, ladies and gentlemen. Welcome to the Alcobra Second Quarter 2015 Earnings Results Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session and instructions will follow at that time. [Operator Instructions] As a reminder, this conference call is being recorded. I would now like to turn the conference over to Debbie Kaye. Please begin.

Good morning and thank you. Before the market opened this morning, Alcobra announced financial results for the second quarter ended June 30, 2015. If you have not yet received this news release or if you would like to be added to the company's distribution list, please call LifeSci Advisors in New York at 646-597-6979. Before we begin, let me remind you that this conference call will contain forward-looking statements within the meaning of the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. Because such statements deal with future events and are based on Alcobra's current expectations, they are subject to various risks and uncertainties. Actual results, performance or achievements of Alcobra could differ materially from those described and/or implied by the statements on this conference call. For example, forward-looking statements include statements concerning among other things the expected milestones and the development of Alcobra's lead product candidate and its various indications, including the timing and design of clinical trials, timing of reporting results of such trials, Alcobra's ability to better design future clinical trials and reduce high placebo response, the benefits of the utilizing certain monitoring tools in our clinical trials, the cost of clinical trials reaching the milestones required for FDA approval, timing of timing of the FDA's feedback regarding our pediatric study plan, the potential of MDX to treat adult and pediatric ADHD and Fragile X Syndrome, statements regarding Alcobra's future uses of cash and the sufficiency of the company's financial resources to meet further milestones and whether such milestones may be achieved at all. In addition, historical results or conclusions from scientific research do not guarantee that future results would not suggest different conclusions or the historic results referred to on this call would not be interpreted differently in light of additional research or otherwise. Also, while the FDA has indicated to Alcobra that positive efficacy results from certain clinical studies may be sufficient to demonstrate efficacy for approval of MDX, the FDA is not bound by these communications and, accordingly, may change its position in the future due to reasons within or outside the control of Alcobra. The forward-looking statements contained or implied on this call are subject to other risks and uncertainties, including those described in the Risk Factors section of Alcobra Limited's Annual Report on Form 20-F for the fiscal year ended December 31, 2014 filed with the Securities and Exchange Commission and in subsequent filings with the SEC. Except as otherwise required by law, Alcobra disclaims any intention or obligation to update or revise any forward-looking statements, which speak only as of the date of this call, whether as of the result of new information, future events or circumstances or otherwise. Hosting today's call from Alcobra senior management team are Dr. Yaron Daniely, President and Chief Executive Officer, and Dr. Tomer Berkovitz, Chief Financial Officer. It is now my pleasure to turn the call over to Yaron. Yaron, please go ahead.

Thank you, Debbie. Good morning, everyone. Today, I will provide a short update on the progress we have been making, our development programs for our lead drug candidates, Metadoxine extended-release or MDX. I will then hand over the call to Tomer to review Alcobra's Q2 financials, which were disclosed earlier this morning. Alcobra continue to execute on its operational milestones in the second quarter. After a productive meaning with the U.S. FDA in the first quarter, we have moved efficiently to start enrollment in our second pivotal Phase III study and adult ADHD. As a reminder, the study protocol has been reviewed by FDA and the agency concurred that building on the findings from our first Phase III study and other data to-date positive efficacy results from the second study will be sufficient to demonstrate efficacy in the adults' population. The study which we named MEASURE short for MDX Evaluation in Adults Study of Response and Efficacy will enroll approximately 750 patients in the 15 clinical sites. In addition to enhancing the powering assumptions, the MEASURE study includes multiple design and operational elements that are expected to provide rigorous controls over the magnitude of placebo responses and response variability. We have previously disclosed several such design elements, including extending treatment duration, clinical center selection and patients screening method. In addition to the study design changes, we have upgraded our monitoring tools by utilizing an electronic sources or e-source system, which allows real time remote, expert review of subject enrollment and assessment. The state-of-the-art technology provided by our new CRO partners and utilized by many leading pharmaceutical companies in our space, provides the clinical sites and our internal clinic team with a beneficial platform to maximize protocol adherence and data quality. The validated e-source system and radars stations document patients' selection and interviews and can be reviewed by remote experts ensuring standardization and compliances with study procedures and training. We believe that various design and logistics elements in MEASURES greatly enhance our potential for a successful outcome in this study. Enrollment into MEASURE study as ongoing and we expect to report data by the middle of 2016. We are also awaiting FDA's comments on the pediatric study plan or PSP, which we submitted following the meeting with the agency. The FDA's feedback is due this quarter. The PSP includes the proposed designs for the two studies in pediatric ADHD, a single Phase II and a single Phase III, which the FDA advised us, would be sufficient to demonstrate efficacy for approval of MDX in this subpopulation. Following the successful completion of our pharmacokinetic safety and tolerability study adolescents with ADHD, we look forward to finalizing the design of these two registration studies with the agency's feedback as soon as possible. Late in the second quarter, we also reported the outcomes from our Phase II exploratory study in adolescents and adults with Fragile X Syndrome. As a reminder, Fragile X Syndrome is a rare neurogenetic disorder characterized by severe intellectual behavioral and learning challenges. It is a leading known genetic cause of autism. There are no approved medications to treat Fragile X Syndrome. Metadoxine was granted orphan drug status by the FDA in 2013 for the treatment of this disorder. Our study was a multi-center, double-blind, placebo-controlled study of 62 adolescents and adults with Fragile X Syndrome. Although the trial did not show a statistically significant difference on the primary endpoint of change on the inattentive subscale of the attention deficit hyperactivity disorder rating scale, in Fragile X patients, MDX did achieved statistical significance and the intent to treat population on two secondary endpoints, including most notably the Vineland Adaptive Behavior Scale or VABS Daily Living Skills Domain. The Daily Living Skills Domain of the VABS is a validated and clinically relevant and meaningful measure used previously in Fragile X trial. It is assessed through a clinical interview with a caregiver and covers a range of functional skills, including basic ones such as eating, dressing or undressing and maintaining personal hygiene to more complex skills such as assessing the subjects' understanding and proper management of time, money, phone and computer use. As individuals with Fragile X Syndrome typically have significant intellectual disability, including impairment in Daily Living Skills, a statistically and clinically significant effect on the VAB Daily Living Skills Domain, represents a meaningful change that is highly relevant to this population. In the context of several recent placebo-controlled trials in adolescents and adults with Fragile X Syndrome, all of which have failed to show statistically significant outcomes in the ITT population on any major primary or secondary endpoint. Our trial yielded statistically significant findings on a very outcomes the clinicians, patients and their caregivers by meaningful. We are encouraged by the findings, which further support the procognitive activity of MDX and plan to discuss these results with the FDA in the near future. Finally, I would like to take a moment to personally welcome Dr. Joao Siffert to Alcobra's Board of Directors. Joao was elected to our board last month at our Annual Shareholders Meeting. He brings over 20 years of executive-level pharmaceutical industry and clinical experience to our company. He currently serves as Executive Vice President of Research and Development and Chief Medical Officer of Avanir Pharmaceuticals, a subsidiary of Otsuka Pharmaceutical Joao joined Avanir four years ago and has led therapeutic development programs in dementia, depression, neuropathic pain, and migraine and Parkinson disease. Joao previously held academic positions at Beth Israel Medical Center and Albert Einstein College of Medicine, and completed residencies in pediatrics at New York University School of Medicine and in Neurology at Harvard Medical School. All of us here believe that Joao strategic thinking and extensive CNS focus experience will be very valuable to Alcobra. This concludes my operational update. Let me now turn the call over to Tomer.

Thank you, Yaron. Let me start by discussing our second quarter 2015 results, which were reported in our press release issued earlier today. We reported total operating expenses of $5.2 million for the second quarter of 2015, in line with the previous quarter and compared to $7.8 million in the second quarter of 2014. Total operating expenses include non-cash charges for stock-based compensation $0.4 million this quarter and $0.9 million in the same quarter last year. Most of our operating expenses are tied to our research and development activity. In the second quarter of 2015 R&D expenses were $3.7 million compared to $5.9 million in the second quarter of 2014. R&D expenses this quarter consisted primarily of costs associated with the completion of our Phase II Fragile X study and the initiation of the MEASURE study. We expect the total cost of the MEASURE study to be in the $16 million to $18 million range. G&A expenses for the second quarter of 2016 were one $1.2 million compared to $1.3 million in the same quarter last year. Pre-commercialization expenses were $0.3 this quarter compared to $0.6 million in the same quarter last year. Finally, we closed the second quarter with $41.1 million in cash and bank deposits compared to $45 million at the end of the previous quarter. Our recurring balance reflects net cash used in operating activities of $3.9 million this quarter. In the future periods, we expect our cash used in operating activities to increase as we continue to advance the MEASURE study. We believe that our existing cash resources will be sufficient to fund our operations through 2016, including the completion of the Measure study. I will now turn over the call back to Yaron.

Thank you, Tomer. I want to thank all of you for participating in this morning's call. The entire Alcobra team is enthusiastically advancing our development program and I look forward to communicating our progress over the coming months. Our solid financial position will support our continued efforts to establish MDX as an effective procognitive compound, demonstrating significant clinical benefits together with a favorable safety and tolerability profile. I will now turn the call back to the operator for Q&A.

Thank you. [Operator Instructions] The first question is from Charles Duncan of Piper Jaffray. Your line is open.

Good morning guys. First of all, thanks for taking the question and congratulations on getting the MEASURE study up and running.

Thanks, Charles.

Regarding the Measure study, I wanted to ask you, you mentioned that enrollment is ongoing. Can you tell me what that planned, call it, geographic spread for the different centers will be and would you anticipate that percentage of patients to come from different geographies?

Sure. The record for the MEASURE study is available on ClinicalTrials.gov, including all the sites that have been already activated and are enrolling patient. There are a few sites that are in the final stages of being activated. We expect to have 15 sites participating in the study, 13 in the U.S. and two in Israel, most of which are selected from pool of sites that that participated in the previous Phase III study. In the previous Phase III study we had a little under a third, I think it was around 90 patients out of the 300s recruited in the two central academic sites in Israel versus the U.S. sites. I expect the ratio to be similar. We did not stratify or predefined this, but I think that we are using high enrolling sites in both countries and I expect you know the geographic distribution to be similar to the previous time.

Okay. Then with regard to the future plans talking about the enrollment do you expect to be able to provide any additional granularity on not only the enrollment numbers, but say a blinded read on the quality of patients. I know that you be monitoring that, but will you be able to talk about that?

I think what we will do is, we will try and guide more on projections for data availability rather than talk specifically about enrollment rates or numbers. We do not want to get our sites or our clinicians worried or focused too much on getting patients in or being in some sort of a race against the other site. What we will do is, we will try and frequently communicate whether we are on target with data availability by the middle of next year. With regards to blinded look at data, as I mentioned we are using state-of-the-art electronic storage system, which allows several of our subject matter experts, CROs as well as the panel of clinical experts to review the data in real-time to run consistency and quality check. The visits are actually being taped and listen to by the CROs in case issues regarding scale administration or consistency of responses are allowed, so we are very excited about some of these new operational and monitoring elements that we have included in the trial. We will continue to talk about this and explain the benefits of this tool. I do not know that we will be specifically talking about the blinded distribution or appearance of the data that I do not think is extremely useful for us, so I imagine not very useful for you as well.

Okay. Then just one quick question on pediatric ADHD, regarding the adolescent PK data you mentioned, will you be able to talk about that what do you anticipate that. Also, when would you anticipate the start of that first Phase II, and is the pediatric program rate limiting for the filing of the NDA or could you start with and adult NDA. Then follow on with the pediatric label expansion.

Yes. The adolescent PK study that we reported on that at the end of the first quarter, we reported the top-line or critical data from that. It has also been recently approved or accepted for presentation at a psychiatric conference, which we will disclose once that conference actually takes place in the next couple of months. With regards to the timelines on initiating studies, the way it goes is we submit the pediatric study plan 60 days after the FDA meeting and the FDA has approximately 90 days to provide comments. When we see these comments on the design of the Phase II registration studies, we will know more whether we could quickly initiate these studies or whether another round of discussions needs to take place with the FDA. At this point, I can't really say with a significant clarity whether the studies will likely launch this year or maybe early next year, but that is the general timeframe. With regards to what is rate limiting, with the FDA's acceptance of only a single Phase II and a single Phase III in kids for registration as well the combined safety database in terms of long-term exposure of both, adults and children, our plan still appear to have combined NDA filing for adults and children. At this point the pediatric studies are not rate limiting at all. Again, if that changes in anyway based on feedback from FDA, we will be sure to communicate that, but at this point that is the best we can.

Just to be clear, it sounds like you will have both, adult and pediatric within one NDA and that will occur together. Correct?

Correct. That's what the plan looks right now.

Okay. Thanks for the additional color.

Thank you. The next question is from Annabel Samimy of Stifel. Your line is open.

Hi, guys. This is Andrew in for Annabel. I just had a couple of questions. First, on the MEASURE study, I think you mentioned - will it be sufficient to file an NDA and in what event would the FDA require another Phase III study to be conducted? Second on Fragile X, you have mentioned endpoint VABS end point, so going forward for FXS, do you see a Phase III or Phase II study initiating next year? What is your timeline on that? Will have enough cash to fund that study through? Thank you

Sure, Andrew. With regards to MEASURE, the FDA was very clear and I hope that we been equally as clear in our communications that the FDA was in agreement that the MEASURE study as described and as disclosed would be sufficient for proving efficacy in the adult population. With a statistically significant finding in that study, we do not expect any efficacy studies in adults with ADHD beyond MEASURE. With regards to Fragile X, I mentioned that we will be meeting with FDA in the near future and we will know more about what FDA thinks about the outcomes of our AL014 study and the findings on the Vineland Daily Living scale assessment we think these are meaningful findings and that a rapid route to approval given the orphan drug designation that Metadoxine had for Fragile X would be in order, but I will be able to say more about this after I hear what the agency has to say. Therefore, I guess, the last part of your question is a little bit too far in into future for me to address with regards to starting a pivotal study or the other resources required to complete such pivotal studies. We would really want to sit with FDA and understand their view of the development path forward in Fragile X studies and then we will be able to communicate about this more.

Great. Thank you.

Thank you. The next question is from Debjit Chattopadhyay of Roth Capital Partners. Your line is open.

Hey, good morning guys. Can you hear me?

Yes. We can, Debjit.

Just a clarification on the pediatric/adolescent study, would that kind of reflect the ongoing MEASURE study in terms of what duration and screening and everything else or do you think you have a little bit more flexibility given the potential larger effect size that you might see in this population?

Yes. That is a good question and, I think part of the answer is embedded in your question, so you are correct that it would be reasonable to expect a greater effect size given the same drug in a younger population it. That is how other drugs have behaved previously, so again a reasonable expectation. Now, we do not know that yet, because we have not done chronic administration studies in children for efficacy and we have to take a look. Our view is that we suggested to FDA relatively conservative expected pediatric efficacy studies that are not extremely aggressive in terms of their Powering or sample size or duration of treatments similar to what other drugs have done before with a single Phase II and a single Phase III for approval. These studies still are likely to be smaller and they are still likely to recruit faster simply because of just the abundance of subjects with the ADHD that are children that may not like to or cannot tolerate stimulant therapy, which is kind of the mainstay for pediatric ADHD. Sorry for the long-winded answer. The basic assumption for your question is correct, which is it would not be surprising to find a greater effect size in children for the same drug, mostly because of a much lower placebo response in pediatric studies given that it is not a self-reported study. It is a teacher or parent reporting on improvement, which are usually more objective in terms of pediatric ADHD, but we will wait to see FDA's comments before we say the final word on that.

Great. Then on Fragile X, I realize you still have not heard back from the FDA, but logically what would you like to see as a primary outcome measure for that study given the history of the prior failed efforts from pretty much everybody else?

Yes. I think on the primary endpoint, I would be surprised if our proposal for using the Vineland Adaptive Behavior Scale Daily Living Skills Domain would not look favorably upon by FDA. I mean the Vineland is one of the most if not the most widely used the validated scale in psychiatry. It is validated for virtually every age. It is a very simple to administer, relatively objective or binary assessment looking at fundamental daily functions, eating, drinking, putting your keys in place, opening the computer, answering the phone. I think that it is not only a simple validated powerful tool, but something that goes straight to the heart of the dysfunction and the impairment in Fragile X, which is the impairment in functional independent productive life. I would strongly suggest that this would be an adequate and an appropriate selection of primary endpoint. I think the discussion with the agency would revolve mostly around the remaining development path, which is what additional trials or single trial would be required and other things that we may want to capture in this trial beyond the primary endpoint, but I believe we have selected the primary endpoint both, in terms of what are most likely to succeed based on the AL014 study as well as what is most appropriate for this population.

Great. Just another follow-up on the Fragile X. Now logic would seem to suggest that the younger patients would benefit more. If you enroll patients who are say adolescent or older, the effect side is probably is smaller and because the impairment is progressive you may not get the treatment benefit. Are you thinking of two different studies, one primarily focused on the pediatrics and adolescent and a separate study for adults or are you going to enroll both, subgroups and then stratify results accordingly?

Again, your assumptions are correct and that at least the common thinking in the field is that Fragile X as a kind of progressive chronic dysfunction is best treated as early as possible, where the brain is more plastic, where learning is more easily achieved. We have actually seen a signal for that in looking at the adolescents in our AL014 study which fared a lot better than the more adult and an older patient. However, in terms specifically, Debjit, of what we have proposed to FDA and again what FDA would ask us to do for approval in this population children and adults, I would really like to kind of put you on hold for, not a very long time I promise, and then communicate a clear answer after we have our meeting with them.

Sorry to harp on the same thing, but what do you think is the appropriate value creation point for the Fragile X program? Given that it is an ultra orphan indication with potential of pricing differentiator. The question is, do you want to take this further yourself or do you want to partner this? I would assume that you would probably get more interest partnering this program at this point if you get a team feedback from the FDA?

It is a little early to talk about partnering or taking it forward ourselves, but I will speak generally about Alcobra as the company, Alcobra as the company has been contacted and we have been for a while in discussions regarding partnering of MDX for ADHD, for Fragile X and for additional cognitive indications both, in the U.S. and abroad. Our belief is that we need to continue to create value in a very aggressive and our own way. We have on board some of the best quality pre-commercialization and commercialization experts that you could have in commercializing assets, again, both in the U.S. and outside of the U.S. I think the best way forward is for us to aggressively move our development programs forward and keep engaging in discussions on this molecule for various indications in various geographies.

One last question on the cash burn guidance going forward, with the MEASURE study starting up, what are you factoring in right now? I mean, are you fully funded for the MEASURE study and the two pediatric studies or at some point you will have to make that choice whether you want to primarily focus on the MEASURE study and get that and be up and running before you even start thinking about the pediatric or adolescent programs?

I will say maybe a short comment and I will refer it to Tomer, if he wants to add any more technical color on this, but the MEASURE study, what we are communicating right now is we have a little over $40 million in cash. The MEASURE study is fully funded within this amount. Tomer can give you some color on our expected costs for that study as well as our running costs. With regards to the two pediatric studies, it would be easier for me to address that once I hear back from FDA on our proposed study design, therefore I will be able to project cost on those. Clearly a Phase II study would not be a major financial burden. Depending on whether FDA accepts the Phase III as we propose or not, we will know more, how much of that fits in the $40 million bucket that we have, but Tomer do you want to give a little bit more granularity on that?

Yes, sure. Debjit, the estimated cost of our Phase III MEASURE study $16 million to $18 million. When you think about the cost structure of the Alcobra, the estimated quarterly cost of just running our business, running a public company is about $1.5 million, so $6 million a year. As you can see we do have flexibility within that budget through 2016, whether that flexibility allows us to take into account one or two pediatric studies, really depends on the design of the study. As we learn more about the path to approval after our discussions with the FDA, we can update you about what can also be accommodated in the current budget.

Thank you. Good luck going forward.

Thank you. That is all the time we have for today's call. I will now turn the call back over to Yaron Daniely for closing remarks.

Thanks. Thank you all, again, for joining us this morning. Have a great day.