Dicerna Pharmaceuticals, Inc.
Q1 2015 Earnings Call Transcript

Published: 12 May 2015

[Operator:]

Good day, ladies and gentlemen, and welcome to the Dicerna Pharmaceuticals first quarter 2015 earnings conference call. [Operator Instructions] I would like to introduce your host for today's conference, Mr. Peter Vozzo. Sir, you may begin.

[Peter Vozzo:]

Good afternoon, and welcome to Dicerna's conference call to discuss 2015 first quarter financial and operational results. For anyone who has not had the chance to review our results, we issued a press release after close of market today, outlining today's announcement, which is available under the Investor and Media tab on our website at www.dicerna.com. You can also listen to this conference call via webcast on our website, and it will be archived there for 30 days beginning approximately two hours after this call is completed. I'd like to remind listeners that we'll make forward-looking statements on today's call, therefore, I'd like to remind you that today's discussion will include statements about the company's future expectations, plans and prospects that constitute forward-looking statements for purposes of the Safe Harbor provision under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our Form 10-Q filed with the SEC today. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. While we maybe elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so, even if our views change. Now, I'll turn the call over to Dr. Douglas Fambrough, Dicerna's Chief Executive Officer.

[Douglas Fambrough:]

Thank you, Peter. Good afternoon, and thanks to all of you who have dialed in to the call today. Joining me to present on the call is Jim Dentzer, our Chief Financial Officer. We are pleased to be able to provide you with this first quarter update. Dicerna continues to make positive progress on key clinical objectives for our development programs for two-key product candidates, DCR-PH1, our program for primary hyperoxaluria type 1 or PH1, which is a rare inherited liver metabolic disorder, and DCR-MYC, our oncology program targeting the MYC oncogene. In addition, we continue to make positive progress on our extended Dicer substrate platform, demonstrating effective gene silencing with subcutaneously administered DsiRNA-EX Conjugate molecules, which are the basis of our earlier-stage liver targeted programs. As a reminder, Dicerna is a RNA interference or RNAi-based biopharmaceutical company, focused on treating specific indications in rare inherited diseases involving the liver and genetically defined oncology targets using Dicerna's proprietary RNAi molecules known as Dicer substrates or DsiRNAs. We're pursuing targets that have historically been difficult to inhibit, using conventional pharmaceutical approaches, but are accessible by RNAi, where connections between those targets and diseases are well understood and documented. We seek to retain substantial commercial rights to our key programs. To discuss our progress in more detail, I'd like to begin with our DsiRNA-EX Conjugate technology that enables subcutaneous delivery to the liver. These conjugates do not involve lipid nanoparticles and are built on our DsiRNA-EX technology, using an extension to one end of the double-stranded DsiRNA molecule. As you may recall from our R&D update in December 2014, we showed greater than 90% gene knockdown after a single subcutaneous administration in mice, with potency such that we can achieve 50% gene knockdown with only 2 milligrams of DsiRNA-EX Conjugate per kilogram of body weight. Recently at the 17th Annual TIDES conference, we provided additional data on our DsiRNA-EX Conjugate technology, extending our observations to non-human primates. And the work presented at TIDES, we showed that we can achieve greater than 50% gene knockdown with 5 milligrams of DsiRNA-EX Conjugate per kilogram body weight, demonstrating effective translation of the DsiRNA-EX Conjugate technology from rodents to primates. In addition, the nadir level of transcript knockdown was observed to continue beyond one month after a single dose, showing a very long duration of effect. We believe these results are supportive of clinical application of the DsiRNA-EX Conjugate technology. To that end, we are utilizing DsiRNA-EX Conjugates in our to-be-announced liver programs, including novel rare disease, and have DsiRNA-EX Conjugates in optimization against four additional liver targets, with more programs planned. I would like to turn next to our DCR-PH1 program for the treatment of primary hyperoxaluria type 1. PH1 is a rare disease, where an error in liver metabolism causes patients to have high levels of oxalate in the urine, resulting in progressive and severe damage to the kidneys. Existing disease management practices for PH1 may slow, but do not stop disease progression. And most patients eventually experience complete kidney failure, with the median age of kidney failure being in the early 30s. Aside from dual liver-kidney transplant, there are no effective treatments and no FDA approved therapies for most patients with PH1. Two aspects of PH1 make it particularly attractive as a program for Dicerna. First, PH1 is a natural application of Dicerna's technology, based on the clear genetic basis of the disease, and the fact that the disease metabolism seems to occur exclusively or nearly exclusively in the liver. Second, PH1 presents clear and easily assayed biomarkers, urinary oxalate and glycolate levels, and these markers provide a direct readout of the mechanism of pathology in PH1. As we've discussed before, we have generated highly encouraging data in the main animal model of primary hyperoxaluria type 1. In this model, mice have been genetically engineered to carry the same metabolic defect found in PH1 patients. These mice have elevated levels of urinary oxalate, roughly three times the normal background levels. That level of elevation is similar to the elevated levels commonly observed in patients with PH1. Using our DCR-PH1 product candidate to knockdown the targeted HAO1 gene transcript in these mice at doses of 0.3 milligrams per kilogram bodyweight, we saw reductions in urinary oxalate levels to background or near background levels. We believe that similar results, if observed in patients with PH1, would have a significant beneficial impact on disease progression. In normal non-human primates, we have shown that a single dose of DCR-PH1 at 0.3 milligrams per kilogram bodyweight, leads to an average of 84% gene knockdown with up to 93% knockdown observed four days after dosing. 29 days after a single 0.3 milligram per kilogram dose in non-human primates, we see an average or 68% gene target knockdown with up to 86% knockdown observed. As previously disclosed, we are initiating a natural history study of PH1. This study will enroll 50 to 75 patients with genetically confirmed diagnosis of PH1, excluding patients on dialysis. The objectives of the study are to characterize the natural history of PH1, estimate changes in oxalate and glycolate levels and renal function over time among others. We believe this information will provide a historical group for comparison to data from clinical trials, and will facilitate the clinical development of DCR-PH1. In an important regulatory milestone, we announced last month that the U.S. Food and Drug Administration has granted orphan drug designation to DCR-PH1 for the treatment of PH1. Dicerna continues to advance the DCR-PH1 program per our internal timeline, with an IND filing in the third quarter and clinical initiation in the fourth quarter. Studies in non-human primates have refined our expectations for data readout from the trial. Observations in non-human primates have demonstrated two important points that affect our timeline expectations. First, we have seen substantially longer target enzyme half-life in non-human primates compared to mice, and thus movement in key metabolite biomarkers takes longer to be observed. And second, greater levels of RNAi knockdown are required for enzyme silencing in non-human primates compared with mice, which suggests that we may need to achieve high levels of the gene knockdown in PH1 patients before observing biomarker movement. These phenomena combined suggest that we may need to go to higher dose cohorts before observing robust biomarker response during the Phase 1 trial. We therefore expect this data to emerge in the first half of 2016. I'd now like to turn to our second product candidate, DCR-MYC, which is our DsiRNA-based therapeutic, targeting the MYC oncogene, formulated in our tumor-centric on core lipid nanoparticle formulation. DCR-MYC is currently being tested in two ongoing clinical trials. Dicerna selected MYC as a high-priority target to silence with our DsiRNA technology, because it is frequently amplified or otherwise up-regulated in a wide variety of tumor types. Because MYC is a protein, which lacks the good small molecular binding site, it has been a challenging target for small molecule therapy, and has been an elusive target for drug developers for decades. We believe our Dicer substrate RNAi platform overcomes this limitation, because we don't target the protein, rather we target the RNA transcript. Our preclinical data for DCR-MYC demonstrate specific and significant MYC gene knockdown in multiple tumor-bearing mouse models. DCR-MYC entered Phase 1 clinical testing in April of 2014, in patients with solid tumors, multiple myeloma or lymphoma. The Phase 1 trial endpoints include safety and tolerability, and we'll identify the maximum tolerated dose, pharmacokinetic profile, pharmacodynamic effects and antitumor activity of DCR-MYC. We are evaluating antitumor activity by resist, using conventional imaging techniques such as CT and MRI. In addition, we have incorporated FDG-PET imaging in the study, as FDG uptake by tumors may serve as a useful biomarker of MYC activity. Reductions in MYC activity are predicted to cause a decrease in tumor metabolic rate, which can be visualized by imaging glucose uptake using the FDG-PET imaging technology. FDG-PET is also a marker of early detection of response across several tumor types. Once we have achieved the maximum tolerated dose in the study, we will be taking biopsies from patient tumors, in which we will seek to identify the direct products of RNAi cleavage of the MYC transcript. We hope to establish proof of concept for DCR-MYC by showing resist responses in patients in conjunction with reduced FDG uptake and demonstration of RNAi activity against the MYC transcript. We continue to expect a readout from this Phase 1 trial by the end of 2015. Contingent upon achieving proof of concept with DCR-MYC, we will launch our second oncology program targeting beta-catenin into IND-enabling studies. We are pleased with the progress of the DCR-MYC trial so far, including our patient enrollment rate. We have escalated through several dose levels and we're continuing with the dose escalation process. We have not identified a maximum tolerated dose. Preliminary results from early dose cohorts of the trial will be discussed in an oral presentation at the upcoming ASCO conference. As we have not identified a maximum tolerated dose, and thus are not taking biopsies, this presentation will not include the molecular data on RNAi activity. In the December 2014, we initiated a second clinical study of DCR-MYC, a Phase 1b/2 study in patients with advanced hepatocellular carcinoma or HCC, who have either failed sorafenib, or are intolerant to sorafenib, or who don't have access to other therapies for HCC. The first patient in this study was dosed in January 2015. We selected HCC as an initial focus indication for DCR-MYC, both due to the observation that the MYC gene is frequently amplified in HCC patients and due to the commercial and competitive profile of the HCC market. HCC is one of the most prevalent cancers worldwide. Patients with advanced HCC had limited treatments options and there are now approved therapies for those who do not respond or do not tolerate standard of care treatment with sorafenib. We have sites for the HCC clinical trial both in the U.S. and in Asia due to the high prevalence of this disease in the Asian population. Now, I will turn over the call to our Chief Financial Officer, James Dentzer, for an update on our financial progress. Jim?

[James Dentzer:]

Thank you, Doug. As many of you have seen, we filed our 10-Q today. There was a great deal of detail contained in that document. I would like to focus on the main financial metrics that we believe are important to use when evaluating the efficiency of our business. In the first quarter of 2015, Dicerna had a net loss of $14.1 million compared to a net loss of $11 million for the same period in 2014. Research and development expenses were $8.7 million for the first quarter of 2015 compared to $5.3 million for the same period in 2014. The increase was primarily due to the initiation of clinical trials related to DCR-MYC, an increase in research activities related to DCR-PH1, and increased employee-related expenses partially offset by a decrease in stock-based compensation of $0.9 million. General and administrative expenses for the first quarter of 2015 totaled $5.4 million compared to $2.8 million for the same period in 2014. The increase was primarily from the increased costs of operating as a public company, and an increase in payroll-related expenses, which includes an increase in stock-based compensation of $1 million. As of March 31, 2015, the company had $87.7 million in cash and cash equivalents and held to maturity investments as compared to $98.6 million in cash and cash equivalent and held to maturity investments as of December 31, 2014. Based on our current position and operating plan, the company reiterates its expectations that it has sufficient cash to fund operations through the end of 2016. This estimate assumes no additional partnership funding and no new debt or equity financings. More detailed financial information and analysis maybe found in the company's annual report and its quarterly report on form 10-Q filed today with the SEC. With that, I will turn the call back to the operator so that we can take questions.

[Operator:]

[Operator Instructions] Our first question comes from Michael Schmidt of Leerink.

[Michael Schmidt:]

So I'm trying to understand your statement around the DCR-PH1 PK/PD relationship between mouse and non-human primates. And I guess, based on that, what level knockdown do you believe you need to achieve in humans to achieve an effective biomarkers, in your view?

[Douglas Fambrough:]

Sure. So it's difficult to predict across species, but what I can do is give a little more clarity on the knockdown from a non-human primates and knockdown from the mouse model. So with 75% gene knockdown in the mouse model, we found that we could start to see movement in the biomarkers. And in order to see movement on the biomarkers in the non-human primates, you need to go to 85% or so before we'd see that moving, and get up towards 90% to see the really strong movement. So our expectations for the amount of knockdown that we need to see in humans, we track along side the non-human primates. And that would suggest that the doses that we're likely to start at in the Phase 1 trial, which might have hit the 75% threshold, may not hit the 85% to 90% threshold, and we may need to go deeper in those escalation before the biomarkers move. Is that helpful, Michael?

[Michael Schmidt:]

Yes, and so you're talking 85% to 90% transcript knockdown or protein level knockdown?

[Douglas Fambrough:]

We're talking transcript knockdown. Now, we will not be collecting biopsies from the livers of patients in the Phase 1 trial. So we will not get data on the transcript knockdown from patients.

[Michael Schmidt:]

And I guess dosing frequency, is that another variable that could affect those parameters?

[Douglas Fambrough:]

In the long-term, which is to say going to a multiple dose chronic treatment, I don't think it's going to have a very major effect because of the duration of effective RNAi in primates, if what matters is driving to therapeutic threshold levels. And then I think the kind of duration, which we have been hoping to achieve, we'll call that a minimum of 173 weeks, but a target of once monthly. I think that's very achievable to stay below even a higher threshold with the monthly dosing interval. So at this point, not thinking about any increased frequency required in the long-term.

[Michael Schmidt:]

And then I had a question on the recent TIDES presentation. So you included some data of a GalNAc conjugate formulated oligo-targeting HAO1, and I was wondering, a, if you had any plans for a subcutaneous formulated product for this indication along the term; and number two, the potency that you've observed with the subcutaneously administered product in non-human primates, I guess, how does that compare to other gene knockdown technologies?

[Douglas Fambrough:]

So we have pursued our DsiRNA-EX-Conjugate technology against the HAO1 gene, which gives us the option of continuing through a formal development program to produce a subcutaneous inhibitor. And at this point, we have not committed to such a development program, but we have the option to do so, and may do so in the future. With respect to the potency of the DsiRNA-EX-Conjugate technology, I think that compares very comparably to the data that is been presented by competitors. Somewhere if you take down myeloma as a specific competitor, the technology appears to have a potency and a duration of action that looks more like what they would describe their ESC technology, than it does what they describe is their standard chemistry, which was incorporated in the TTRsc program. So I think in a more general statement one would say, we feel the potency that we have achieved and demonstrated through the IC50 results both in mice and non-human primates demonstrates a competitive potency profile such that it would lead to a competitive product profile as well.

[Michael Schmidt:]

And then maybe back to the PH1 program. Are the metabolic pathways, how conserved are those between mice, non-humans primates, and humans?

[Douglas Fambrough:]

To the best of knowledge, the pathways are well conserved. One needs to recognize that this is not the most heavily researched part of human physiology. That said, the pathway is part of a common metabolic breakdown pathway than any vertebrate animal has as part of its metabolic repertoire. The primary role of the pathway is detoxification of hydroxyproline, which is about 10% by collagen by weight. And looking across genomic information, you see conservation of the relevant enzymes in the pathway, if you look at gene expression databases, you see that there is a general conservation of the special distribution of expression as well, which is to say that the pathway is active in the liver. Those surveys do not have cellular resolution, but as far as we have observed in the mice, its just hepatocyte activity. Given the common biochemical problem and the conservation of the enzymes both with respect to sequence identity and level of expression at the organ level, I think it's very likely that the pathway is very conserved. It is worth mentioning though that this pathway is not the only source of oxalate, and there do appear to be differences between rodents and primates with respect to other sources of oxalate, specifically regarding differences in vitamin C metabolism. These differences are predicted to result in a higher background level of oxalate in the rodents compared to primates as is observed. We do not believe this will impact the therapeutic activity of the product. It is relevant to comparing baseline oxalate levels, but not to thinking about the dynamics of oxalate production through this pathway and it is this specific pathway, which is impacted in primary hyperoxaluria type 1. Thus, in conclusion, to the best understanding of the pathway today, we would predict good conservation, and in our observations to non-human primates to date including data that we have not presented, such as elevations in urinary glycolate in non-human primates after treatment with DCR-PH1. We remain optimistic that the therapeutic mechanism will translate very nicely from the mouse model of disease to patient.

[Michael Schmidt:]

And are you planning to present more non-human primate data at some point in the near future on some of those findings?

[Douglas Fambrough:]

Not in the near future, but we would expect to have substantial presentation at the next PH1 focus meeting.

[Operator:]

And our next question comes from Stephen Willey of Stifel.

[Stephen Willey:]

Can you just remind us what's the magnitude in terms of the directional movement and enzymatic biomarkers that you need to see in order to recapitulate the phenotype in the rodent model? And I guess, when you talk about 75% knockdown as being initiating of that movement of the biomarker movement that translates into an approximate what level of reduction in terms of the markers themselves?

[Douglas Fambrough:]

So this is an interesting question to answer. In one-on-one meetings I frequently make the comment that, I don't think talking about percent reduction is really the right way to do it, even though that's the way the field has traditionally done it. So let me start by just giving some facts about oxalate in the disease and in normal individuals. Normal oxalate is standardly written as less than 0.46 of the units that are used, millimoles per body surface area per day. The median oxalate in PH1 patient is 1.8, so roughly four times the background. At the 75th percentile they're up at 2.7. Now, in the field physicians' talk about 30% reduction in oxalate as being what is really clinically interesting. So I think the way to think about that is a 30% reduction from the median. Now, let me take this in a slightly different direction. There is a well-documented correlation between oxalate level in the urine and long-term kidney outcome. And the way that data has been presented, I don't have access to all the background data that went into it, the way that date has been presented, it oxalate is below 1.3 than the risk of kidney failure over a decadal scale reduces to near zero. So I think it's more appropriate to think of 1.3 as a threshold level that we want to achieve, and if you do the math, 30% reduction from 1.8 and 1.3, that's a same place. The amount of reduction that we see in the mouse model is on the order of 55% or so. Pick the time data point that you want to measure, so substantially more than what the field is looking for. That encourages us that even if there are some differences between species that DCR-PH1 and this mechanism of action has the capability to exceed a 30% reduction, and to lower oxalate levels below the 1.3 level that one might use as a threshold for a significant therapeutic effect.

[Stephen Willey:]

So we should think about then I guess your dose escalation efforts then really being targeted towards that 1.3 number as oppose to kind of a threshold percentage reduction.

[Douglas Fambrough:]

I'm hesitating and agreeing with that, because clinical trials historically in this indication have used percent reduction. And whether we continue to use percent reduction as a clinical endpoint or whether in conjunction with the FDA we define a threshold, that's a decision that will be made in the future. I think it's useful to make sure that people understand that in the Phase 1 trial patients may have some body burden of oxalate crystals that will dissolve and contribute to oxalate in the urine, which could buffer the reduction of oxalate that we observed in a single dose trial. We do expect to see real-time elevations in glycolate, and we suggest that people look at both of those biomarkers, and we very much do expect to see oxalate reductions. But if we have a major reduction in oxalate production in the liver, you may see some additional solubilization of existing oxalate crystals. The enrollment criteria for the Phase 1, we'll attempt to select patients that do not have a lot of oxalate burden already. For later stage trials, we'll take probably all patients and we'll include enough time to washout existing oxalate levels.

[Stephen Willey:]

And then just a question on PCR mix. So I think you had indicated that there won't be any biopsy data at ASCO. So any I guess RNAi mediated on-target efficacy won't be necessarily part of the presentation. But I'm guessing and because this is an all-comers trial that you are probably getting some patients with some baseline tumor types that are probably easier to access from a biopsy perspective than others. And so should we just be thinking about this data just coming at a later time point?

[Douglas Fambrough:]

Yes. And we continue to guide to the yearend for us to have what I think will be a meaningful dataset. Patients add MTD, maybe some from prior MTD as well, if we ask them for biopsy as well as the biomarker data and the resist data, such that by yearend hopefully we'll be able to make a statement about proof-of-concept one way or the other.

[Operator:]

Our next question comes from the line of Chris Raymond of Robert W. Baird.

[Laura Chico:]

This is Laura Chico in for Chris Raymond. I think a couple my questions have already been asked. But I'd just like to circle back on PH1 a little bit, if I might, and apologies, if I missed this. Have you discussed kind of what the dose-limiting toxicity is in the mice or kind of how high you've been able to dose thus far?

[Douglas Fambrough:]

We have not discussed any of that information. However, the deliver system that is employed in DCR-PH1 is in license from Tekmira Pharmaceuticals. And this formulation was used in their Ebola-targeted program, where they have released a fair amount of data on the toxicological findings with respect to that program that I think are a direct read over onto DCR-PH1. Notably, in a healthy volunteer study, they were able to dose through 0.3 milligrams per kilograms without any pre-medication, and not have tolerability issues in the patients. This is a remarkable level of tolerability for a lipid nanoparticle program. Essentially all lipid-based drugs that are use today are used in conjunction with pre-medications to suppress infusion reaction. So based on human experience with this formulation, the infusion reaction issue appears to be minimized compared to all of their lipid products for this formulation. We do expect that a dose limiting that the tolerability issues that would limit dose would be related to infusion reaction.

[Laura Chico:]

I guess, related to PH1 and the natural history study, do you plan posting that on clinicaltrials.gov?

[Douglas Fambrough:]

Laura, I don't know the answer to that question. It's a non-interventional study, so I'm not certain it's required. We will do it, if required. I suspect if it's not required, we won't. But in fact it's got to be a non-answer Laura, I don't actually know.

[Laura Chico:]

I guess one last kind of high-level question. As you're thinking about the two platforms, oncology versus liver-targeted diseases, I wonder if you could opine a little bit or talk about how you're prioritizing your efforts in allocating resources between the two different franchises?

[Douglas Fambrough:]

There's a really clear answer to that, Laura. At this point, there is great validation in the RNAi field for delivery to hepatocytes, and that gives us the confidence to invest heavily in building out the hepatocyte or liver targeted pipeline. And so almost all of our internal resources are dedicated to creating additional pipeline programs for hepatocytes targets as well as supporting the DCR-PH1 program. The resources in oncology are best seen as being on hold. We have done I think an excellent job to creating a critical candidate with DCR-MYC that very effectively has mediated delivery to xenograft models, both orthotopically implanted and subcutaneous to genetically engineered mouse model and has more recently been shown in PDX style models. That said, those are all mouse models, and the translation of delivery in tumors and mice to tumors and patients is one where we do not understand the differences and challenges. So while we evaluate how that translation proceeds in the DCR-MYC Phase 1 trial, we have put the allocation of resources to oncology more or less on hold. We have developed a second clinical candidate, that's for beta-catenin, and it's essentially in a holding pattern prior to IND enabling studies. If and when we achieve the proof-of-concept with the DCR-MYC, and I described in the call today that proof-of-concept has three aspects to it, molecular evidence of knockdown of the MYC transcript, biomarker movement in reduce glucose uptake as seen by FDG-PET, and resist responses. If we see a set of patients, where we can link those three things together or connect the dots, as I say, then Dicerna will be satisfied that we have achieved proof-of-concept. And with that we would free-up resources to move forward beta-catenin and likely invest resources in additional oncology products as well. But until that time, and I hope that time is soon, but it's not yet. Until that time, our resource allocation is dedicated to building out the wide variety of targeted program opportunities that our liver targeted. It's also worth mentioning that all of our programs beyond PH1 for liver targets will incorporate the DsiRNA-EX Conjugate technology for subcutaneous administration.

[Laura Chico:]

And I guess just one last quick one, and I'll hop back in the queue. I think I heard you say that you will not be collecting liver biopsies in the Phase 1 PH1 trial. Did I hear that correctly? And talk a little about the rationale for not getting the transcript data?

[Douglas Fambrough:]

So you did hear that correctly. And the rationale is really two-fold. One is that it's really a big ask to poke someone in the liver and get a biopsy. There is risk associated with the procedure like that in addition to it being uncomfortable. The second is that while the transcript knockdown information is interesting, with respect to disease outcome it's really neither here nor there. What we need to see in order to have an effective therapy is reduction in urinary oxalate, an evidence that we're stopping the pathway by an increasing urinary glycolate. Absenting movement in the biomarkers, it really doesn't matter what level of gene transcript reductions that we see. So I consider it non-essential information in the trial. So for those reasons, I don't think that it's appropriate for us to ask the patients to undergo the procedure. And I think it's conceivable that IRB's wouldn't tolerate it anyway. In any event we're not making the ask.

[Operator:]

And at this time, I am showing there are no further participants in the queue. I would like to turn the call back to management for any closing remarks. End of Q&A

[Douglas Fambrough:]

I want to thank everyone for their attention today. This is a very exciting time for Dicerna, as we get towards the later half of 2015 and begin to get into the clinic for DCR-PH1 as well as seeing more data out of the DCR-MYC clinical trial. So thank you all for your attention today.

[Operator:]

Ladies and gentlemen, thank you for your participation on today's conference. This concludes the program. You may now disconnect. Everyone have a great day.