Dicerna Pharmaceuticals, Inc.
Q1 2016 Earnings Call Transcript

Published: 10 May 2016

[Operator:]

Good day, ladies and gentlemen, and welcome to the Dicerna Pharmaceuticals First Quarter 2016 Earnings 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 be given at that time. [Operator Instructions] As a reminder, this call is being recorded. I would now like to introduce your host for today's conference, Mr. Steve Silver please go ahead.

[Steve Silver:]

Thank you operator. Good afternoon and welcome to Dicerna's conference call to discuss the Company's 2016 first quarter results. For anyone who has not had the chance to review our results, we issued a press release after close of market today, which is available under the Investor tab on our website at www.dicerna.com. You may also listen to this conference call via webcast on our website which will be archived there for 30 days beginning approximately two hours after the call is completed. I'd like to remind listeners that management will be making forward-looking statements on today's call related to 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 may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so if our views change. Now, I'll turn over the call over to Dr. Douglas Fambrough, Dicerna's President and Chief Executive Officer.

[Doug Fambrough:]

Thank you, Steve. Good afternoon, and thanks to all of you who have joined today's call. Joining me are Jack Green, our now permanent Chief Financial Officer and Pankaj Bhargava, our Chief Medical Officer. The first quarter of 2016 was marked by steady progress towards our goal of utilizing our proprietary RNAi technologies to develop innovative therapies for areas of unmet medical need. This is true for our emerging pipeline of subcutaneously administered therapeutics against liver disease genes and in our two clinical stage programs utilizing intravenous delivery technology. Progress is been especially rapid with our DsiRNA-EX-Conjugates technology where we are building a pipeline of [indiscernible] targeted subcutaneously administered inhibitors of disease driving genes in our core area of rare diseases as well as three additional therapeutic areas chronic liver diseases such as NASH, cardiovascular diseases and liver viral infectious diseases. We believe the common threats amongst these distinct therapeutic areas are the expression of faulty genes in the liver and the substantial need for new treatment options for patients with these chronic diseases which represent attracted market opportunities for RNAi based therapeutics. In total, we have qualified more than two dozen disease associated genes across these therapeutic areas where we believe an RNAi based inhibitor could provide substantial patient benefit and have parallel tracks the discovery and optimization of DsiRNA-EX-Conjugates inhibitors against half of these identified targets. Importantly, we view this list of qualified gene targets as far from exhaustive, without question the breadth of this liver opportunity space extends far beyond those targets currently identified and in development across the RNAi space or for that matter, the broader pharmaceutical pipeline. There's plenty to do here. We remain confident in the extensive growth opportunities that exist for novel therapies that can address currently underserved markets. We are confident that, we can capture value with this emerging pipeline given the simple dosing regimens enabled by the potency and duration of action of our Conjugate technology. Per our stated business model, we plan to retain a full or substantial ownership stake for certain rare genetic diseases, while selectively pursuing profitable partnerships for other candidates who's development would be maximized by larger companies with enhanced resources and commercial infrastructure. We are excited by the data being generated by our DsiRNA-EX-Conjugate technology and by their prospects to attract partnering interest on favorable economic terms to Dicerna. As one example of our progress, we recently selected and began IND-enabling studies for our subcutaneously dosed DsiRNA-EX-Conjugate clinical candidate for the treatment of primary Hyperoxaluria Type 1 or PHI. While I will provide some additional information on our Conjugate technology during this call, we will discuss our data and pipeline in more detail during our inaugural Investor Day in New York City on June, 29. Regarding our clinical stage programs of note since our last call at March in our DCR-MYC oncology program we have dosed our first patient in the expansion cohort of patients with Pancreatic Neuroendocrine Tumors or PNET. For our DCR-PHI program for the treatment of primary Hyperoxaluria Type 1 or PHI rare and severe genetic liver metabolic disorder first patient dosing is imminent. On the corporate front, I'd like to take this opportunity to welcome Jack Green as our new permanent CFO. We look forward to Jack's contributions as Dicerna expands its R&D initiatives around the DsiRNA-EX-Conjugate platform and advances these programs towards commercialization. I will now turn the call over to our Chief Medical Officer, Pankaj Bhargava who will provide an update on the clinical stage DCR-PH1 and DCR-MYC programs. After that, I will discuss the DsiRNA-EX-Conjugates work in more detail and finally Jack will give an update on Dicerna's financials. Pankaj?

[Pankaj Bhargava:]

Thank you, Doug. I'd like to begin with our program for the treatment of primary Hyperoxaluria Type 1 or PH1. As a brief reminder PH1 is a severe rare genetic disease where a single gene error in liver metabolism causes patients to have high levels of oxylate in the urine resulting in progressive and severe damage to the kidneys and other organs. As existing disease management practices do not stop disease progression most PH1 patients experience complete renal failure with the median age of kidney failure in the early 20s. Aside from combined liver kidney transplant there is no FDA approved therapy or effective treatments for most PH1 patients. Two aspects of PH1 make it a particularly appealing program for Dicerna. First, PH1 is a natural application of Dicerna's technology based on a clear genetic basis of the disease and the fact that the metabolic defect in the disease seems to occur exclusively in the liver. Second PH1 presents clear and easily assayed biomarkers, specifically urinary and plasma oxylate and glycolate levels which provide direct read-out of the efficacy of our targeted therapies for this disease. Our experimental treatment for PH1 is DCR-PH1, a lipid nanoparticle encapsulated DsiRNA-EX-Molecule targeting the HAO1 gene. DRC-PH1 has shown a profound ability to reduce urinary oxylate levels in the mouse genetic model of PH1. DCR-PH1 is the subject of two clinical trials. First an abbreviated dose escalation trial in healthy volunteers that is a prelude to dosing patients in the US and second a dose escalation trial in patients. In the healthy volunteer trial dosing is ongoing. In the patient trial, we anticipate imminently dosing the first patient at a site in Europe. In addition to DCR-PH1, we remain on track to advance our first clinical candidate using our subcutaneously administered DsiRNA-EX-Conjugate technology in PH1 into clinical development in late 2017. In addition to the healthy volunteer and the patient focus clinical trials of DCR-PH1, we are also enrolling an observational study of PH1 patients called PHYOS, P-H-Y-O-S for which we intent to enroll up to 25 patients, who are genetically confirmed diagnosis of PH1. This study will provide key data such as the baseline variability off and factors that influence changes of urine and plasma levels of biomarkers oxylate and glycolate. These two biomarkers are key measures of efficacy by which we will validate the mechanism of action of DCR-PH1 and which will help and guide late stage development plans. As we mentioned on our last earnings call, we plan to advance development of current DCR-PH1 clinical program as well as development of our subcutaneously administered DsiRNA-EX-Conjugate clinical candidate in parallel for the time being. We will evaluate clinical and market data to determine the optimal path forward for a long-term development plan in PH1. Turning to our second clinical stage product candidate DCR-MYC is our DsiRNA based therapeutic targeting the MYC oncogene, formulated in Dicerna's proprietary tumor-centric EnCore lipid nanoparticle formulation. Dicerna selected MYC as a high priority target, since there is a large body of literature showing its frequent amplification of up-regulation in a wide variety of tumor types suggesting a critical role in driving and maintaining tumor growth. In pre-clinical studies DCR-MYC has demonstrated specific and significant MYC gene knockdown in multiple tumor bearing mass models showing the tumor delivery activity of our EnCore lipid nanoparticle technology. With EnCore, we expect to achieve the long socked [ph] goal of effective inhibition of MYC gene in human tumors, an achievement that has to-date been beyond the reach of pharmaceutical technologies. DCR-MYC is currently being tested in two ongoing clinical trials. First, a Phase I all-comers dose escalation trial for which we have initiated two additional cohorts. One cohort focusing on pancreatic neuroendocrine tumors or PNET, a tumor type where we have already observed clinical responses and another expansion cohort for enrolling patients who will undergo pre and or post treatment biopsies that will allow us to directly observe molecule markers of DCR-MYC activity in tumors. The second clinical trial of DCR-MYC is a Phase 1b/2 trial in patients with Hepatocellular Carcinoma, which is in the dose escalation phase. DCR-MYC entered Phase I clinical testing in April, 2014 in patients with solid tumors multiple myeloma or lymphoma. The endpoints for this Phase I all-comers trial include safety and tolerability and we will also evaluate the maximum tolerated dose, pharmacokinetic profile, pharmacodynamic effect and antitumor activity of DCR-MYC. As we disclosed in our last call, we have completed the dose escalation phase of our all-comers study by establishing safety at the 1 milligram per kilogram dose level. This dose level should provide relevant knockdown of MYC and human tumors based on extrapolation from animal liver cancer models. DCR-MYC has been well tolerated at this dose and its' safety profile compares favorably with other lipid nanoparticle formulated RNAi products tested in humans. During dose escalation, anti-tumor activity was seen in two out of three patients with low to intermediate grade treatment refractory PNET. Specifically evidence of a complete metabolic response based on FDG-PET imaging was seen in one patient and a partial tumor response based on resist 1.1 criteria was seen in a second patient. Both patients had failed standard and experimental therapies for PNET prior to starting with the study. Since our last earnings call, we have dosed the first patient in the PNET expansion cohort, which we expect will grow up to 20 patients with low to intermediate grade PNET. Our goal is to enroll a majority of these patients this year. Since we're working high volume PNET sites such as Dana-Farber Cancer Institute, Massachusetts General Hospital, Stanford University Medical Center and the MD Anderson Cancer Center. In addition to the two existing sites START, San Antonio and University of Chicago Cancer Center, we plan to release preliminary data from this cohort in 2016. The second expansion cohort will enroll patients who will undergo pre and or post treatment tumor biopsies which will allow us to assess the direct effect of DCR-MYC [indiscernible] the MYC transcript in tumors. We believe that a direct molecular demonstration of RNAi activity against MYC in tumor biopsies will establish proof-of-concept for DCR-MYC when coupled with the already demonstrated resist and FDG-PET responses in patients. We expect to make this determination in the second half of 2016. Turning to the second clinical trial of DCR-MYC. In December 2014, we initiated a Phase 1b/2 study in patients with advanced Hepatocellular Carcinoma or HCC, who have either failed 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 for three reasons. First; the activity observed in preclinical HCC disease models, second; observation that the MYC gene is frequently amplified in HCC patients and third; the commercial and competitive profile of the HCC market. HCC is one of the most prevalent cancers worldwide. Patients with advanced HCC have limited treatment options and there are no approved therapies for those who have failed standard of care treatment with Sorafenib. We have active sites for the HCC clinical trial both in the US and in Asia due to the high prevalence of this disease in the Asian population. As of April 26, 2016 19 patients have been dosed with DCR-MYC in five cohorts from the starting dose of 0.125 milligram per kilogram to the current dosing level of 0.85 milligram per kilogram. While we have not yet observed an objective response by resist criteria, we have already observed reductions in circulating alpha-fetoprotein levels in a patient treated in the dose escalation cohort. Alpha-fetoprotein is an HCC tumor marker, where reductions have been associated with anti-tumor activity. We are continuing with dose escalation in this trial. We expect to have preliminary data from this trial by the end of 2016. Contingent upon achieving proof-of-concept with DCR-MYC we will launch into IND enabling studies of our second oncology program targeting the Wnt beta-catenin pathway. Our DCR-BCAT candidate has shown effective delivery and anti-tumor activity in a large series of mouse tumor bearing models. Particularly, colorectal carcinoma and hepatocelluar carcinoma zero graft and PDX tumor models, which we have presented at research conferences. These two tumor types are associated with Wnt pathway activation. The tumor delivery capability of the DCR-BCAT lipid nanoparticle formulation is an enhanced and improved version of Dicerna's EnCore delivery technology that is used in the DCR-MYC program. The performance of the DCR-BCAT formulation in animal models exceeds the results we observed in the DCR-MYC formulation. I will now turn the call back over to Doug to discuss developments with our DsiRNA-EX Conjugate technology. Doug?

[Doug Fambrough:]

Normally, our Chief Scientific Officer, Bob Brown described developments with our conjugate technology but he's attending a scientific conference at the moment. As we've highlighted previously, Dicerna's DsiRNA-EX-Conjugates are our proprietary form of RNAi duplexes that mediate gene silencing in the liver after subcutaneous administration. Our DsiRNA-EX-Conjugates are designed to target the liver using the natural sugar N-Acetylglucosamine more commonly known as GlcNAC. GlcNAC has been used as a liver targeting moiety for multiple therapeutic modalities including [indiscernible] since at least the early 1990s. In our proprietary implementation of the technology, the GlcNAC sugar molecules are chemically conjugated to specific basis on the DsiRNA-EX RNA duplexes in a configuration that is unique to Dicerna. These proprietary RNAi molecules can be administered subcutaneously as simple saline solutions and do not require any lipids or lipid nanoparticles for affective delivery to the liver. Our conjugates utilize our DsiRNA-EX technology which is an enhanced version of our RNAi Dicer Substrate technology. One of the two RNA strands has been extended, a unique property of our Dicer Substrate RNA structures that provides additional space on the RNAi duplexes for elements that provide enhanced pharmaceutical functions. Many of our DsiRNA-EX-Conjugates incorporate in this extended region a folded motif known as a tetra loop. We first described tetra loop's for the use in DsiRNA several years ago. They serve as both a stabilizing motif and our ideally student to provide multiple independent conjugation points for the GlcNAC moieties and potentially targeting agents for other cell types in the future. Using these proprietary elements of our RNAi technology we've created a differentiated and independent platform for effective subcutaneous delivery of RNAi inducing molecules to the liver. We are encouraged by our progress using this DsiRNA-EX-Conjugate technology as we have achieved advances in both potency and targeted gene knockdown and the process by which we have been able to generate conjugates directed at new targets. In 2015, we reported a nearly 90% reduction in expression of the liver gene HAO1 after a single administered dose of 3 milligrams per kilograms in monkeys and that we have observed a long duration of action of our conjugates with maximum gene knockdown persisting more than 14 weeks after a short loading regimen. Results such as these support confidence to develop innovative therapies with simple treatment regimens based on infrequent single side subcutaneous injections for effective liver gene liver knockdown in patients with significant unmet medical needs. As we've mentioned during our last quarterly call, streamlining our process per screening and optimizing therapeutic leads has allowed us to apply our technology to a wide variety of liver associated disease gene targets. In addition to the testing we've done in monkeys, we've also identified many conjugates that yield more than 50% target knockdown in mice after a single dose of 0.5 milligrams per kilogram or less with a most potent showing, a 50% knockdown at a single dose of 0.1 milligrams per kilogram and 90% gene knockdown at a dose of 1 milligram per kilogram. We believe this level of potency is likely to support such a simple and frequency subcutaneous dosing regimen in patients. As I mentioned, our library now encompasses DsiRNA-EX-Conjugates targeting more than a dozen liver disease gene targets in various states of optimization and rare diseases as well as chronic liver disease, cardiovascular disease and viral infection all of which demonstrate, the broad applicability of the DsiRNA-EX-Conjugate technology. We are excited about the prospects of building a robust pipeline of novel product candidates some of which we will advance internally and other we will look to develop in collaboration with the pharmaceutical partners. We look forward to unveiling some of this promising early data including additional non-human primate data that is emerging from DsiRNA-EX-Conjugate platform at our upcoming Investor Day in June. I will now turn the call over to our Chief Financial Officer, Jack Green for an update on our financial progress. Jack?

[Jack Green:]

Thank you, Doug. I'd like to briefly summarize the key financial results for the quarter end March 31, 2016 and direct you to Form 10-Q filing for additional details. In the first quarter of 2016, the company had a net loss of $15.7 million or $0.76 per share compared to a net loss of $14.1 million or $0.79 per share for the same period in 2015. Research and development expenses were $11.3 million for the first quarter of 2016 compared to $8.7 million for the same period in 2015. The year-to-year increase was due primarily to increased expenses related to discovery and early development of future programs including development of the DsiRNA-EX-Conjugate delivery platform. Increases in clinical activities from initiating additional studies in PH1, increased employee related expenses primarily due to additional hiring during the period, increased stock-based compensation expense and increased occupancy cost. General and administrative expenses for the first quarter of 2016 totaled $4.5 million as compared to $5.4 million for the same period in 2015. The decrease was primarily due to lower stock-based compensation and payroll related cost and to cost related to the facility move that were incurred in the first quarter of 2015. As of March 31, 2016 we had $80.6 million in cash, cash equivalents and held-to-maturity investments. As compared to $94.6 million as of December 31, 2015. In addition, we also had $1.1 million of restricted cash on the balance sheet, which reflects collateral securing our facility lease obligation. Finally, based on current cash position and operating plan. We expect that we have sufficient cash to fund operations through at least the next 12 months excluding any additional partnership funding, debt or equity financing. More detail of the financial information and analysis maybe found in the company's quarterly report on Form 10-Q filed today with the SEC. And I'd like to turn the call back over to Doug.

[Doug Fambrough:]

Thanks Jack and thanks to everyone at Dicerna for their hard work that has enabled the advancement of our clinical pipeline as we discuss today as well as the significant progress made with our proprietary DsiRNA-EX-Conjugates platform which has us so excited about our future. We look forward to unveiling new data from the conjugate platform at our first Investor Day in New York City on Wednesday June, 29 and thank you for attending today's call and we look forward to continuing to update you on our progress. We can now take some questions.

[Operator:]

[Operator Instructions] our first question comes from the line of Eun Yang with Jefferies. Your line is open, please go ahead.

[Eun Yang:]

Well, thank you. This is Eun.

[Doug Fambrough:]

Hi, Eun.

[Eun Yang:]

Hi, how are you doing? For PH1 national [ph] history study, can you give us an update how many patients have been involved to-date?

[Pankaj Bhargava:]

Yes, hi, Eun this is Pankaj Bhargava. We have currently enrolled approximately 10 patients in the study and we are continuing to screen and work with our sites for additional patients.

[Eun Yang:]

Okay and I just want to make sure that I heard you correctly, so is it volunteer trial because single ascending dose where as multiple ascending dose, is the data expected in 2017?

[Pankaj Bhargava:]

So the healthy volunteer study as we previously mentioned it's now an abbreviated where we are going to have data available to us this year to enable dosing in our Phase 1 study in the US.

[Eun Yang:]

Okay, thanks and then my last question is, where are you in potential partnership discussions and do you expect to announce a partner [indiscernible] partnership this year? Thank you.

[Doug Fambrough:]

So, Eun I think it's probably not a good idea for us to give very precise guidance around the partnering process just due to the nature of that kind of discussion, but I will give you this amount of color. The ability to have the kind of performance that we've achieved with our DsiRNA-EX-Conjugate technology that's a rare capability and it's presents a very desirable pharmaceutical profile. We have numerous companies that are interested in having that sort of clinical profile associated with the targets that they're interested in. It's important to us that, it be appropriately compensated in the partnership and that we have a good working relationship. I'm very encouraged by the state of our discussions with multiple parties and we'll see where that goes.

[Eun Yang:]

Thank you.

[Operator:]

Thank you. Our next question comes from the line of Steven Willey with Stifel. Your line is open, please go ahead.

[Steven Willey:]

Hi, good afternoon. Thanks for taking the questions. Doug, just a question on the one AFP response you've seen in the DCR-MYC study in HCC, have you disclosed that which dose that reduction has been observed at?

[Doug Fambrough:]

That patient was dosed at 0.45 [indiscernible].

[Steven Willey:]

Okay and then I with respect to kind of next of our experience HCC, I think it was recently announced that I think it was Regorafenib showed a stat sig benefit, in I guess second line HCC. So just wondering if you think that might impact enrollment a little bit or is your protocol designed in such a way that you can take patients who have perhaps seen multiple lines of prior TKI therapy.

[Pankaj Bhargava:]

Hi, Steven this is Pankaj Bhargava. So in our Phase 1 dose escalation phase of the study, we allow patients who have received multiple prior therapy. So we don't expect our enrollment to be impact and quite frankly, we have been in close touch with our sites all of them have other studies ongoing in this space. So we have not noticed any impact on enrollment on our study, so far.

[Steven Willey:]

Okay, I think that's it from me. Thanks guys.

[Operator:]

Thank you. Our next question comes from the line of Ritu Baral with Cowen and Company. Your line is open, please go ahead.

[Unidentified Analyst:]

Hi, this is Alex on for Ritu, just another question on the PHYOS natural history study, can you give us any more insight on what you think maybe the most important parameters for us to keep in mind whether it's functional or biomarkers and now you mentioned [indiscernible] which is obvious, any further insight would be great.

[Pankaj Bhargava:]

Sure, this is Pankaj Bhargava. So the key biomarkers to test the efficacy of any product in this disease are oxylate and glycolate levels mostly in the urine but also in blood in some patients. And there really have been a gap in the literature looking at variability in levels in these patients. Very little has been published and we have not found a systemic or systematic study of baseline variability overtime and all the samples tested in a common central laboratory. So our study is essentially aimed at doing exactly that collecting samples overtime in these patients having them all analyzed in a central lab, so that there is no variability in the asset and really understanding the baseline oxylate levels in these patients, so that we're able to make educated decisions regarding endpoints and measuring efficacy of the drug in the space.

[Doug Fambrough:]

I may add a second element to supplement to Pankaj's answer. We initiated the PHYOS trial several months before our patient dosing is initiating and we are intending to enroll our Phase 1 patient study largely from patients who are already participating in the PHYOS study, so this gives us a run in period of baseline oxylate and glycolate data from these patients without us needing to build that sort of run in period delay into the Phase 1 trial. So that is a real benefit as the patients that enter the Phase 1 we're going to have to lot of information including a series of baseline measurements overtime that should allow us to best interpret the biomarker data, we get from the patient trial.

[Unidentified Analyst:]

Great, thanks so just a follow-up. Would it be [indiscernible] to say that, you would catch the Phase 1 enrollment to people who have only been in this observational study?

[Pankaj Bhargava:]

So it will be mostly patients who have been in observational study. We don't restrict it entirely to patients who are in this observational study, but we expect most of the patients enrolled in the Phase 1 to come from this observational study.

[Unidentified Analyst:]

Great, thanks for taking the question.

[Operator:]

Thank you. Our next question comes from the line of Madhu Kumar with Chardan Capital. Your line is open. Please go ahead.

[Madhu Kumar:]

Thanks for taking my questions. So first question is about DCR-MYC in liver cancer. So do you guys have a sense of kind of what would be the cut off points for kind of go/no go on continuing with DCR-MYC in liver cancer?

[Pankaj Bhargava:]

Hi, Madhu thanks for the question. So we have built this as a Phase 1b/2 study and as you can imagine the Phase 1 study is mostly focused around defining safety maximum tolerated dose and biomarker data AFP etc. Once we get the safety and the dose defined in the Phase 1 portion then we move on to a Phase 2 portion where we enroll up to 30 patients with HCC and in the Phase 2 portion we are more restrictive in terms of eligibility. We have patients who have failed prior Sorafenib, so one prior therapy. We have defined our thresholds for efficacy in our Phase 2 based on the sample size, it's a small sample size as you can imagine as well as the competitive environment we are going to look at response rate as well as the progression free survival in that cohort of patients, we make our go/no go decision.

[Madhu Kumar:]

Okay, great and so then along with that. So you have the pre and post [indiscernible] biopsy study you have the peanuts study and you have the liver cancer study. So you mentioned the idea that, beta-catenin program would be contingent upon the MYC program. So how do you kind of sort these three ongoing trials in terms of their relative to value for their decisions to whether to progress in beta-catenin.

[Doug Fambrough:]

Hi, Madhu that is, it's obviously it's an interesting data set to be considering. Now I think the first way to think about this is to separate out the biopsy work from the response rate. I think it's really critical that we understand that the drug is having the molecular impact we seek it to have, right that is actually causing destruction of MYC transcript and we can observe that in studies, that's an important check that we are doing what we think we are doing, but that is not, that sort of requirement for having confidence in the product but is really separate from a go/no go decision. A go/no go decision is really about do we think drug has the potential to have a competitive commercial profile as a therapeutic and that boils down to how's it performing therapeutically in patient. Now as I think your first question alluded to the use of response rate can be more challenging in a Hepatocellular carcinoma than in other tumor types due to the fact that there's often less shrinkage even if there's a tumor death in the HCC context due to liver fibrosis. We're utilizing M resist in the HCC study in that pancreatic neuroendocrine trial objective response rate is much more straight forward and that will be the primary basis on which we think about making the go/no go decision. But it's not a case of hard and fast rules that I could articulate to you. We will take the totality of the data as a whole and make that decision based on the data, is that helpful?

[Madhu Kumar:]

Yes that's really helpful. Thank you very much. I think I'll get off. Thanks very much.

[Doug Fambrough:]

Thanks Madhu.

[Operator:]

[Operator Instructions] and I'm showing no further questions at this time. I'd like to turn the call back over to President and CEO, Dr. Doug Fambrough for any closing remarks.

[Doug Fambrough:]

Well thanks for your attention and your questions. I hope you share the kind of excitement that we have here. It's an exciting time with the DCR-MYC trial reaching a point where we're enrolling, our inspection cohort and peanut and obviously our pipeline is in a state where, this is lot of stuff we can do with the conjugate technology, so we're very optimistic about our future, until next quarter. See you then.

[Operator:]

Ladies and gentlemen, thank you for participating in today's conference. This does conclude today's program. You may all disconnect. Everyone have a great day.