Sangamo Therapeutics Inc (SGMO) 2005 Q1 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Sangamo BioSciences first-quarter teleconference. My name is Mia, and I will be your coordinator for today. (OPERATOR INSTRUCTIONS). I will now turn the presentation over to your host for today's call, Dr. Elizabeth Wolffe. Please proceed.

Thank you. Good afternoon, and thank you for joining Sangamo's management team on our conference call to discuss the Company's first-quarter financial results. Also present during this call are several members of Sangamo's senior management team including Edward Lanphier, President and Chief Executive Officer; Dr. Dale Ando, Vice President of Therapeutics and Chief Medical Officer; and Greg Zante, Senior Director of Finances and Administration.

Following this introduction, Edward will review first-quarter activities, highlighting Sangamo's recent events. Greg will then briefly review first-quarter financial results, and finally Edward and Dale will update you on our specific ZFP Therapeutic programs. Following that, we open the call up for questions.

As we begin, I would like to remind everyone that the projections and forward-looking statements that we discuss during this conference call are based on the information that we currently have available. This information will likely change over time. By discussing our current perception of the market and the future performance of Sangamo with you today, we're not undertaking an obligation to provide updates in the future. Actual results may differ substantially from what we discuss today, and no one should assume at a later date that our comments from today are still valid. We alert you to be aware of risks that are detailed in documents that the Company files with the Securities and Exchange Commission, specifically our quarterly reports on Form 10-Q and our Annual Report on Form 10-K. These documents include important factors that could cause the action results of the Company's operations to differ materially from those contained in our projections or forward-looking statements.

Now, I would like to turn the call over to Edward.

Thank you, Liz. And thanks to all of you for joining us on our 2005 first-quarter conference call. As promised, we are off to a great start in 2005. In the first 100 days, we presented the first data on our HIV CCR5 gene disruption program; we announced two new protein production deals with Pfizer and Amgen; we published a major ZFP gene correction paper in the journal, Nature; we brought on board a Senior Vice President of Business Development and added a new member to our Board of Directors; and last, but certainly not least, we filed our first proprietary IND, receiving FDA clearance and beginning the study and are now actively recruiting patients -- a good start for the year with much more to come.

On the call today, I will briefly highlight some of these recent accomplishments, and then Greg will update you on the first-quarter financial results. In the second part of the call, I have asked Dale to review the status of two of our most visible ZFP Therapeutic programs, our clinical trial of SB-509 for diabetic neuropathy and our program for ZFN-targeted disruption of the CCR5 gene as a treatment for HIV/AIDS.

In January, we announced the filing of our first IND for a Phase 1 trial of SB-509, a ZFP transcription activator of the VEGF-A gene for the treatment of diabetic neuropathy. I am pleased to inform you today that we have now completed all of the required steps to open the trial, including institutional review board approval. We have opened the study at one of the four -- expected four clinical sites and have begun patient screening. Later on this call, Dale will provide you with more information about the specifics of this clinical study.

This quarter also saw important business development success at Sangamo. We announced two new protein production agreements -- the first with Pfizer and a second with Amgen. We were providing our zinc finger gene activation and zinc finger nucleus technology to Pfizer and our high producing CHOZn cell line to Amgen, both of which are accessing the technology for use in enhancing mammalian cell-based protein pharmaceutical production. This is an area of active discussion with other companies. And as these agreements are all nonexclusive, we anticipate that we will be making more announcements of this type throughout 2005.

Perhaps the most visible events for us this quarter centered around the publication and presentation of data from our gene modification programs. In April, we published an important paper in the journal, Nature, describing data from our ZFN-mediated gene correction program. The paper, which appears in the advanced online edition of the journal, describes our research on the correction in the mutation in the IL2 gamma receptor gene that causes X-linked SCIK, or the Bubble-boy disease. The paper describes the first precise and efficient method to edit the human genome. As you can imagine, these data were very well-received by the scientific community and were covered extensively by both delay and trade press.

We were also invited to present these data to a stakeholders' meeting organized by the American Society of Gene Therapy, the FDA, and the NIH. The purpose of this meeting was for stakeholders in gene therapy to come together to assess the progress in clinical gene therapy research and to discuss collaborative ways in which the field could be effectively advanced. Dr. Philip Gregory, Sangamo's Senior Director of Research, was asked to present the data that we just published in Nature in order to highlight a possible solution to many of the problems that have frustrated and limited traditional gene therapy in the past.

Specifically, some gene therapy approaches require random insertion of the therapeutic gene into the patient's genome. In contrast, our technology needs only transient expression of the ZFNs, does not require gene or vector integration, yet provides permanent correction of mutated genes. Again, the response to these data was very positive and encouraging.

In late February, Dr. Carl June presented the initial results of our collaboration at the Conference for Retroviral and Opportunistic Infections held in Boston. The data from our ZFP Therapeutic program aimed at developing a permanent modification of the CCR5 gene as a potential therapeutic for HIV/AIDS, demonstrated that we successfully disrupted the CCR5 gene in cells. This was a very important first step, and Dale will update you on our progress and plans.

I would also like to take this opportunity to thank Bill Rutter, a great friend and long time supporter of Sangamo, who retired from our Board of Directors in March. We have benefited tremendously from Bill's wealth of experience, acquired over years in the biotech industry. He is leaving to devote more time to several early stage technology companies of which he is a founder and principal supporter. And we all wish him the very best in his many ventures.

We're pleased to welcome a new board member, Dr. Margaret Liu, an accomplished leader in the research and development of vaccine and immunization programs for infectious diseases, particularly HIV. We will benefit enormously from her insights, as we advance the therapeutic applications of our ZFP technology.

And with that quick summary of the first 100 days, I would like to turn the call over to Greg to summarize the first-quarter financial results. Greg?

Thank you Edward. For the first quarter of 2005, our consolidated net loss was $3.6 million or $0.14 per share. In the comparable quarter of 2004, our consolidated net loss was $2.9 million or $0.12 per share. Our research and development expenses were $2.7 million for the 3 months ended March 31, 2005, as compared to $3 million for the first quarter of 2004. General and administrative expenses were $1.1 million for the first quarter of 2005, compared with $997,000 for the same period last year.

Revenues for the first quarter of 2005 were $256,000, as compared to first quarter 2004 revenues of $811,000. Revenues in the first quarter of 2004 were higher than in 2005 due primarily to the receipt of a milestone payment from Edwards Lifesciences for the filing of the investigational new drug application and their program to develop a ZFP therapeutic for peripheral artery disease.

Finally, I am pleased to report that we ended the quarter with cash, cash equivalents, investments, and interest receivable of $30 million. On that note, I will now turn the call back over to Edward.

Thanks, Greg. As you can see from the first-quarter financial results, we continue to invest aggressively in our products, while retaining the strength of our balance sheet. I would like to now turn the call over to Dale, who's going to give you more information about the progress of our two therapeutic programs under development. Dale?

Thanks, Edward. As you heard, our first human clinical trial is active, and patients are being screened at one of the sites -- the Diabetes and Glandular Disease Medical Association's clinic in San Antonio, Texas. The trial is designed to test the safety of SB-509, a ZFP Therapeutic, that up-regulates, or turns on, the expression of the VEGF-A gene for the treatment of diabetic neuropathy. This therapeutic approach takes advantage of the potent direct neurotrophic and neuroprotective effects of VEGF. And we believe they provide a therapeutic solution for a significant unmet medical need.

As most of you know, diabetes is a growing problem in the U.S. And diabetic neuropathy is a significant problem for as many as 50% of the current 14 million diagnosed diabetics in the U.S., who have been living with the disease for 10 years or more. We are focused initially on sensory motor diabetic peripheral neuropathy. The initial symptoms of which are pain and tingling in the hands and feet and then an eventual loss of strength and numbness in the extremities. This frequently results in injuries and infections, particularly in the feet that may not heal -- eventually ulcerates and can lead to amputation. Unfortunately for these patients, there are only approved therapies for the pain symptoms associated with diabetic neuropathy, and only very strict glucose control can help the progression of this condition.

Sangamo has developed a ZFP activator of VEGF-A to treat diabetic neuropathy. Free clinical animal efficacy studies in the diabetic rat model demonstrate that a single treatment with the VEGF-activating ZFP transcription factor shows a statistically significant increase in limb nerve conduction velocities. Our collaborator, Dr. David Tomlinson of the University of Manchester will present these data in June at the American Diabetic Association meeting in San Diego, and they will also be submitted for publication later this year.

The Phase I trial is a single-blind, dose-escalation trial and is primarily designed to evaluate the safety and determine the maximal tolerated dosage of SB-509 when given as a single treatment by intramuscular injection. The secondary objective is to evaluate the clinical effects of SB-509 treatment on lower limb diabetic neuropathy. Clinical effects will be measured by evaluation of patients' symptoms in the physical extent of peripheral neuropathy by neurological examinations and electoral physiologic testing.

Patients with mild-to-moderate diabetic neuropathy will be screened before acceptance into this study. And all patients will be treated with SB-509 in one leg and placebo in the other. The physician treating the subjects will be blinded to which leg has been administered, SB-509 or the placebo. Patients' safety will be monitored throughout the study and visits at 1, 2, 3, and 6 months will include neurological examinations and electoral physiologic testing.

Although the clinical trials is tended to be a dose escalation study, we will be observing the critical effects of the treatment and placebo against the baseline symptoms and compare the SB-509 treated leg and the placebo treated leg in each patient and look for examples of improvements in symptoms or neurologic evaluations. Patients will receive injections in the distribution that targets specific major peripheral nerves in the legs and feet. The first dose level will be injected in the distribution in the muscle to treat nerves to the foot. The second will be distributed in the muscle to include nerves in the outside of the lower leg and food -- the third, the whole lower leg and foot -- and the fourth for major nerves in the whole leg from the thigh down. We anticipate that the trial will take 12 to 18 months to complete, and we expect to treat approximately 12 patients. We do not anticipate presenting into interim data or discussing the progress of this trial until we have completed accruing subjects.

I would now like to briefly turn to our zinc finger nucleus gene modification program, in particular our program for the therapeutic disruption of the CCR5 gene. Our programs in both gene correction and gene disruption make use of our proprietary ZFP technology and the cells' natural mechanism for DNA repair. As Edward mentioned, we recently published a high-profile paper in the journal, Nature, that describes data and the scientific foundation of these programs. Using two engineered zinc finger proteins linked to DNA cutting enzymes called endonucleases, Sangamo scientists have been able to target a double strand break in DNA to a specific site in the genome. As we published in the Nature paper, this break can be targeted to the site of a mutation that causes a monogenetic disease, such as the mutation responsible for X-linked SCID or sickle cell anemia.

Alternatively, the double stranded break can be used to disrupt a target gene sequence, encoding a functionally normal protein. This is the basis for our ZFP Therapeutic that we are developing for the treatment of HIV and AIDS.

The ability to use zinc finger nucleuses to interrupt the gene allows us to take advantage of rare, naturally occurring mutation of the CCR5 gene that has been shown to make people resistant to HIV. This mutation alters the critical co-receptor, CCR5, that is used by the HIV virus to enter a cell. This example in nature shows us that if we could interrupt CCR5 in the CD4 T-cells of a patient with HIV, that we could protect these cells and ultimately the patient from progressive HIV-infection and depletion of the CD4 T-cell population.

Inhibitors of HIV binding to the CCR5 have shown some effectiveness in early studies. But these inhibitors are not able to eliminate CCR5 completely. It takes only 1 CCR5 receptor, amongst the thousands on the surface of a T-cell for HIV to infect the cell. We believe that there are similar advantages to our zinc finger nucleus approach. With only a transient expression of our ZFNs, we believe we can permanently remove the CCR5 HIV code receptor from the surface of key immune cells and thus protect them from infection. The treatment would be specific and permanent and could be used in combination with other therapies.

Furthermore, we do not believe that this modification of the cell would force the virus to mutate and become able to circumvent the treatment. In contrast, patients undergoing current antiretroviral therapies develop virus that eventually become resistant to the drugs.

As you may have heard, a new strain of HIV, a so-called super HIV, has reportedly been identified in a patient in New York. Initial report suggests that this virus is multiple-drug resistant. Specifically, the patient in question has a virus that did not respond to three or four types of antiretroviral drugs commonly prescribed. So clearly, there is a need for a new approach.

We have been working closely with Dr. Carl June at the University of Pennsylvania to test our ZFNs in T-cells. To-date, as we presented at the Conference for Retrovirology and Opportunistic Infections, we have identified ZFNs that allow us to disrupt the CCR5 gene in primary human T-cells. We are currently testing these cells in in vitro challenged models designed to directly test the inhibition of virus replication. This in vitro work will be followed by experiments in animal models to fairly characterize the ZFN modified T-cells.

We aim to present those data later in the year at the International Conference on Antimicrobial Agents and Chemotherapy, or ICAAC, in late September. If all goes well, our goal is to begin the first clinical trial in this area in the first half of next year.

We had a collaborative belief that ZFN mediated gene modification has enormous potential, and we are allocating significant internal/external resources to realize this opportunity and to rapidly translate our initial reason research successes at the clinical trial. We look forward to keeping you informed of our progress. And as you have heard, we plan to update the scientific community on our achievements in this program throughout this year. Edward?

Thank you, Dale. As you can see, the CCR5 gene disruption program is a very exciting, a very important and will likely be a very visible aspect of our ZFP Therapeutic platform.

So to conclude and summarize this first-quarter update, we are now actively recruiting and screening patients for our first human clinical trial. Our science has been showcased in a high-profile publication and two important scientific forums this past quarter. This has given us the opportunity to increase the visibility of our technology, its potential applications in gene correction and gene disruption, and the significant technical advantages over previously available methods for the broader audience. We anticipate further opportunities to do this over the coming months at ASGT, ISSCR, and ICAAC. We are commercializing and monetizing our technology to new agreements with Pfizer and Amgen and expect to announce more in the future. And we continue to carefully manage our cash.

I'll look forward to keeping you updated on our progress. We are scheduled to present at several investor conferences in the next few months, including the Rodman & Renshaw Techvest Global Healthcare Conference, the Needham Biotech Conference, and the William Blair Growth Stock Conference. This completes our prepared comments. I would now like to open the call up for your questions.

(OPERATOR INSTRUCTIONS). Charles Duncan, JMP Securities.

Edward, congratulations on a good quarter. A couple of questions related to the diabetic neuropathy program. I am wondering if you or Dale could run through the kind of expectations that you have with regard to the degradation and function that you would expect to see over the course of the period in which you would be evaluating the patients. Pick an efficacy measure, say walking time or whatever.

In the diabetic neuropathy trial?

Yes.

Go ahead, Dale.

At this point, we are treating the moderately large spectrum of diabetic neuropathy as respect to endpoint, and this includes mild-to-moderate diabetic neuropathy. And to give you an example -- there's a scaling system that we are using to evaluate the neurologic exams called the NIS Scale. And this a range of patients on the NIS Scale from 2 to 66 from a total of approximately nearly 100. So the sensitivity of our analyses is quite good, though the numbers aren't very big. But we should be able to see pretty -- differences between the baseline and the control that are actually quite small. And that is using the -- this is a composite of neurological symptoms, the physical exam.

Then, the third instrument we are using is the nerve conduction velocities. I do now know if you're familiar with those, but that is measured in millimeters per second. Normal is around 60 to 70. In a year's time, generally patients will drop 5 to 10 millimeters in time. The other thing they can move is actual conduction across the nerve. The most common is say for instance, the nerve to the lower foot called the seral nerve can be lost. And usually that -- it gradually goes away; then, it is just a loss. So the patients that we have now have to have detectable seral nerves, but their nerve conduction velocities could be quite reduced there. So we should be able to measure those levels quite accurately, given the studies that we're doing now and what we know from historical studies.

And these are all measures that you folks did not necessarily come up with. They're all pretty well standard, validated --?

Yes, there's just been over -- if you include all the pain medications and seizure medications, there's been over 50 diabetic neuropathy trials in New York. And a lot of these measurements are actually validated in Phase III trials, which have large control groups. So you can see what the degradation is per year in these control groups.

Well, in addition, each patient in your trial, each patient serves as its own control, right?

Yes, right. Well, we have two controls. One is the other leg. But every given time point, we can compare one leg to the other. And then at every given time point, we can compare the same leg probably to the time point it was measured and then from baseline. So this allows us to I think pretty effectively try to analyze the changes.

And then second set of questions are on the CCR5 program. Let's see, what are some of the hurdles that you see in getting that program to the clinic?

Well, let's back up and tell you where we are in things, and then we will see if either Philip or Dale will want to expand upon it. The data that were presented by Carl June in February shows that we are able to generate zinc finger nucleuses that disrupt the CCR5 gene in primary human T-cells. And so that really was the critical first step in this.

Where we are now and or have been in continuing to move forward is selecting the optimal group of zinc finger nucleases, determining an optimal formulation or delivery strategy for those in a clinical setting in T-cells, optimizing that sell processing component, developing the release criteria for those and then moving it into clinic.

Along the way and as Dale mentioned, we expect to do validating efficacy studies in both in vitro as well as in vivo models, looking at HIV challenge of these T-cells that have been disrupted with the CCR5 gene by the zinc finger nucleases. So that's in general, Charles, the process. Does that cover your question?

It in part does, but the other aspect of the question that I was trying to get a handle on is -- have you started to discuss with investigators, prospective clinical investigators, the approach? And what has been their response to the Nature article and what is kind of qualitatively the level of enthusiasm in the community for the program?

I think there's been quite a bit of interest. Over the last 10 years, use of adoptive therapy of T-cells in HIV has advanced considerably. At this time, there are a number of trials where people are trying strategies to put on -- to put using therapy to put in some protective product or gene into a T-cell and basically try to see whether or not that will protect the T-cells.

Say for example, the Virexus (ph) antiplants (ph) envelope, retroviral vector in T-cells, using a lentiviral vector. So the field is quite well developed. And I think the fact that we are really pursuing a known mutation that protects against HIV in patients really has our collaborators quite enthusiastic about this approach.

On the broader question in terms of a scientific community response to the Nature paper, Philip, why don't you take that?

Sure. Well, obviously since the paper came out in the advanced online publication in early April, we have been quite literally inundated with requests for both the reagents that were in the paper and also for new collaborations around this technology. Obviously, from one of the first requests was from Kathy High (ph), the President of VCAC, to go and present at the stakeholders' meeting. And I think that really shows you how the field is thinking about technology as perhaps a new approach that can get around some of the historical challenges -- sort of historical gene therapy approaches have had to phase. So we have been really -- internally, we are very proud of the response that we have got from the community. But it has been very successful so far in just attracting a lot of attention scientifically.

And finally, Charles on this, I would say that you will see more data, broader sets of data presented at ASGT, at the ISSCR meeting, the stem cell meeting that is out here in San Francisco at the end of June. And then as Dale and we have discussed -- the more of the CCR5 challenge data at ICAAC.

And then last question is -- I know it's not your responsibility, but can you give us any color on how Edwards is doing with their programs?

Really can't, Charles, sorry.

Matt Arens, Kopp Investment Advisors.

Yes, did you say you are looking for the IND on the HIV/AIDS program first half of next year?

Yes. The goal is -- the stretch goal is to have the IND late this year. But what Dale said is, our plan is to start the trial in the first half of 2006.

That was the clarification I was hoping for. So did you kind of view it you, as you said, as a stretch goal for this year, spill over possibly into next year if things don't line up exactly?

Right. To actually begin accruing and treating patients in '06.

Great. So there has been no change in that?

No.

Thanks, congratulations on the continued progress.

John Sullivan, Leerink Swann.

A couple of quick questions. First, regarding the detail on the diabetic neuropathy study -- congratulations on the first sight up in screen patients. 12 to 18 months to complete the trial in your own guidance -- 12 patients, the goal. Over what period of time do you think you will be screening and treating patients versus time left to accumulate data and prepare it for release? The point being -- can you talk a little bit about the screening process? It seems like it must be a pretty rigorous progress over a year for just a yield of 12 patients.

It will probably take 9 to 12 months. A lot of this is related to again both the screening process, which requires blood tests, specific procedures, such as -- electrophysiological testing, neurologic exams, eye exams, etc. And these people are working. So as we go through these tests, they come in, get test. We evaluate whether the tests are okay; then, they have to come in and get the next level in terms of passing through the inclusion/exclusion criteria. So that's generally taking for us right now probably a month per patient. And we are obviously screening a lot more patients than one patient at a time.

I think as we get more centers up; this is going to accelerate. Some are saying probably between 6 to 9 months to accrue the first, accrue the 12 patients. And then they obviously have to be followed for 6 months to get all the evaluations.

Does that address your question, John?

Yes, it does. Thank you very much. Can we reasonably assume that the other centers will be prepared to screen patients in the relatively near future?

Yes, I think within the next 2 to 3 months, we should get them all open.

Shifting gears, thanks for the ZFN-based information. Regarding ZFP beyond the VEGF ZFP, are there other ZFP-based gene up-regulation, therapeutic approaches that you are considering even on a preclinical basis or even in vitro? And can you say anything about the genes or the conditions in which you're focused?

I will be happy to give you a quick summary of that John. And it also allows me to give -- we do not usually do this but -- one of our plans for the second-quarter conference call in July is really going to be to focus on some of these preclinical programs in the gene regulation space. But just to give you a quick sense of that -- in the activation area, we continue to look at the neurotrophic and neurodegenerative effects of VEGF activation. And you will hear more about data and nerve models, both in nerve injury as well as nerve diseases.

We are also looking at a disease, an ophthalmic disease in the area of macular degeneration, where we're looking at both VEGF repression and then activation, simultaneous activation, of an anti-antiangiogenic factor called PEDF. And those studies are also in preclinical development now.

In the repression area, we are focused in two major areas -- one in the area of congestive heart failure and specifically repression of phospholamban. And those preclinical studies are also underway. And the other area is in the area of neuropathic pain. There are two targets we're going after there. And again, those programs are in active, preclinical animal efficacy studies.

So that's just a quick thumbnail. But our plan is to give you a bit more detail on those programs on the next conference call.

David Wood, America's Growth Capital.

I cut myself off earlier, so I apologize if this has been asked. But in terms of where Edwards stands on its programs -- Edward, can you just update us quickly?

Sure. The question was asked. And unfortunately, the answer is, I really don't have any incremental guidance on that. And so, I again would refer you to the folks at Edwards. I'm sure they would be happy to tell you what they know.

The other question that I had is kind of a bigger picture question for Dale. You had talked about 50 different trials for diabetic neuropathy over the years and nothing really for these patients other than pain. Can you give us a sense of why these trials have failed? Is it because of design? Is it because of heterogeneity in the population? Can you give us some sense of why you think these trials failed?

First of all, I just want to clarify that a lot of those trials were successful. And there were successful medications for treatment of pain -- Delapatin (ph), etc. So it turns out that you can apply antidepressants' medications, and that can actually attenuate symptoms of pain. In a lot of these other trials use products that were already in the treatment for depression. And they were added on for the treatment of diabetic neuropathy pain.

The second major step -- and this has all been big pharma -- is use of muscle relaxants. They also can affect or dull the type of pain. And those trials have also been done. Many of them and those having -- often were approved studies.

The two major classes of drugs that were used to actually treat the diabetic neuropathy -- the first set is aldose reductase inhibitors. And basically, aldose reductase is an enzyme that is turned on when the cell can't bring in sugar. It tries to synthesize a sugar and produces sort of a toxic alcohol sugar-like compound. Those studies -- the aldose reductase does work on decreasing the deaths related to hypoglycemia and aldose reductase. However, they also affected the liver, and most of those drugs caused a moderate-to-medium level of elevated liver enzymes that were not clinically significant but were felt to be unacceptable for long-term use in this disease.

So unfortunately, that group of drugs showed some activity. But because of the type of patient -- it is pretty much a normal patient -- a long-term elevation of liver function tests could eventually over 10 or 15 years lead to liver damage. So those drugs were not developed.

There are some newer third or fourth-generation studies being done right now. Currently, I think there are 3 or 4 Phase III trials with aldose reductase inhibitors that have a little bit better profile of toxicity.

And then finally, the big trial that Genentech did with NGF was about a 1,000 patient trial. And the problem with NGF is that it is also a mediator of pain in the nervous system. An injection of NGF, even though it could improve the nerve growth, actually was quite painful. And that trial was limited in terms of dosage, and they were never able to use the dose of NGF that they wanted because of the pain side effects of NGF. So I would say the major reason for a lot of these products not being approved was related to side effects and not due to limitation of efficacy.

Okay. And to extend that perhaps, it was not due to the trial design or anything like that? What I am trying to get at, as Charles had alluded to earlier, you're not really blazing a new trail with these types of trials going forward, are you?

No, so a lot of these trials that were done undergo a process called a special protocol assessment with the FDA. That means the FDA meets with the sponsor for both the clinical trial they are manufacturing and basically agrees that if this trial comes out, as written and it has designs statistically, they will approve the drug. So this area is actually, from a precedent point of view, it's quite nice because there are a lot of designs and endpoints and evaluation scales that have been validated by these previous efforts.

(OPERATOR INSTRUCTIONS). You have no further questions at this time.

Thank you. We would like to thank you for joining us. And we look forward to speaking with you again when we release our second-quarter financial information. Thank you.

This concludes your conference. You may now disconnect.