Dicerna Pharmaceuticals, Inc.
Q4 2015 Earnings Call Transcript

Published: 11 Mar 2016

[Operator:]

Good day, ladies and gentlemen, and welcome to the Dicerna Pharmaceuticals Q4 2015 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 follow at that time. [Operator Instructions] As a reminder, this conference is being recorded. I would now like to introduce your host for today’s conference, Mr. Peter Vozzo from Westwicke Partners. Sir, please begin.

[Peter Vozzo:]

Thanks, Vince. Good afternoon, and welcome to Dicerna’s conference call to discuss 2015 fourth quarter and full year 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 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 the call is completed. I’d like to remind listeners that we’ll be making 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-K 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 Chief Executive Officer.

[Douglas Fambrough:]

Thank you, Peter. Good afternoon, and thanks to all of you who have dialed into the call today. I would like to start by introducing you to Jack Green, our new Interim Chief Financial Officer. Jack Joined Dicerna on January 1st of this year and he brings to the company over 30 years of financial management experience including more than 20 years within the Biotechnology industry. Also joining me to present on the call today is Bob Brown, our Chief Scientific Officer and Pankaj Bhargava, our Chief Medical Officer. We are pleased to be able to provide you with this fourth quarter and full year update. As a reminder Dicerna is using our proprietary R&A interference or RNAi, gene silencing technology to develop investigational treatments for rare inherited diseases involving the liver and for solid tumors. In the past few quarters we had made significant improvements to our RNAi platform capabilities. Especially with respect to our DsiRNA-EX-Conjugates which can administered subcutaneously and for which we have observed very long duration of action. With these enhanced capabilities we are in the process of expanding our business model beyond what we have historically articulated. Historically, in order to both capitalize on the inherent advantages of RNAi while maximizing the probability of clinical success of our development programs we have pursued gene targets that have been difficult to inhibit using conventional pharmaceutical approaches, but are accessible by RNAi and with the biological connection between those targets and the underlying disease state is well understood. The MYC and HAO1 gene targets that form the basis of our clinical stage DCR-MYC and DCR-PH1 programs respectively fit these criteria. In addition we have been pursuing indications where Dicerna can maintain full or significant development and commercialization rights. Such as the rare disease primary Hyperoxaluria Type 1 in the case of DCR-PH1 and in Hepatocellular Carcinoma and Pancreatic Neuroendocrine Tumors in the case of DCR-MYC. With the success we’ve had in developing our DsiRNA-EX Conjugates, which we will describe in more detail in a moment, of the successes leading us to expand on this business model calculus. Specifically the ease of application of the DsiRNA-EX Conjugate technology to targets in the liver allows us to pursue in parallel. The discovery of RNAi inhibitors in multiple therapeutic areas of unment medical need. Including areas with very large population sizes. Such as chronic liver disease, cardiovascular disease and viral infectious disease. In some case the targets we’re exploiting are high validated like MYC and HAO1, in other cases less so. For many of these targets our path forward will likely be in collaboration with other pharmaceutical companies. In any event the breadth of exciting target opportunities enabled by the DsiRNA-EX Conjugates technology far outstrips the ability of Dicerna to pursue development against them on our own. As our discovery efforts in these therapeutic areas mature we will reveal more about these program. In addition to our RNAi platform progress Dicerna continues to make progress on the clinical objectives for our development programs for our first two product candidates. First DCR-PH1 our program for primary Hyperoxaluria Type 1 or PH1, which is a rare and severe genetic liver medtabolic disorder. Notably we recently began clinical testing of DCR-PH1 in healthy volunteers and will begin dosing patients shortly. And second DCR-MYC our oncology program targetting the MYC oncology continues to progress in two clinical trials. To discuss our progress in more detail we will begin with our CSO, Bob Brown describing the advances with our DsiRNA-EX Conjugate technology and its application to earlier stage programs. Pankaj Bhargava will then provide an update on the DCR-PH1 and DCR-MYC programs and finally Jack Green will give an update on Dicerna’s financials. Bob?

[Bob Brown:]

Thank you, Dough. Dicerna’s DsiRNA-EX-Conjugates are our proprietary form of RNAi duplexes; the mediate gene silencing in the liver after subcutaneous administration. Our DsiRNA-EX-Conjugates are designed to target the liver using the natural sugar N-acetyl galactosamine more commonly known as GalNAc. The GalNAc sugar molecules are chemically conjugated to specific physicians on DsiRNA-EX-RNA duplexes. These proprietary RNAi molecules can be administered subcutaneously as simple sailing solutions and do not require any lipids or lipid nanoparticles. DsiRNA-EX is an enhanced version of our RNAi Dicer substrate technology that we’ve reported on previously. While one of the two RNA strands has been extended these extensions are unique to Dicerna and utilized proprietary RNA structures designed to stabilize our DsiRNA-EX-Conjugates. And to provide additional space on the RNAi duplexes for enhanced pharmaceutical functions such as liver-targeting via GalNAc. Many of our DsiRNA-EX-Conjugates also incorporate a folded Tetraloop motif in the extended strand. We first described Tetraloops for use in DsiRNA several years ago and they served both as a stabilizing motif and to provide multiple independent conjugation points for GalNAc and other targeting agents. Using this approach we’ve created a differentiated and independent platform for effective subcutaneous delivery of RNAi inducing molecules to the liver. During 2015 we announced further advancement in potency of our DsiRNA-EX-Conjugates. Specifically we have achieved potencies that we believe will enable clinical dosing regimens consisting of simple and frequent subcutaneous injection. For example, we’ve shown that we can reduce expression of liver gene, the liver gene target HAO1 the molecular target via DCR-PH1 program, by almost 90% in monkeys after a single subcutaneous does of 3 milligrams per kilogram. Extensive testing of comparable DsiRNA-EX-Conjugates against additional therapeutic gene targets in monkeys is underway. We've also shown that our DsiRNA-EX-Conjugates demonstrate a long duration of action with maximum gene knockdown persisting more than 14 weeks after a short loading regimen in monkeys. We believe this level of pre-clinical RNAi potency will translate into simple clinical treatment regimens based on in frequent single side subcutaneous injections for effective liver gene knockdown in patients. As we’ve improved the potency of our DsiRNA-EX-Conjugate molecules. We’ve also been streamlining our process for screening and optimizing therapeutic leads. This has allowed us to apply our technology to a wide variety of liver associated disease gene targets. In addition to the DsiRNA-EX-Conjugates being tested in the monkeys, we’ve identified many conjugates that yield greater than 50% target MR&A knockdown in mice after a single dose 0.5 milligrams per kilogram or less. Our most potent DsiRNA-EX-Conjugate to-date yields 50% target knockdown in mice at a single dose of 0.1 milligrams per kilograms. At these potencies we can achieve greater than 90% inhibition of gene expression mice using single doses of 3 milligrams per kilogram or less. As Dough mentioned we are advancing discovery programs targeting both novel disease genes, a well established disease genes giving us an emerging library of DsiRNA-EX-Conjugate leads. It can be advanced into development by Dicerna or potentially in collaboration with partners. At this junction our library encompasses DsiRNA-EX-Conjugates targeting more than a dozen liver disease gene targets in various states of optimization, in 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 driving towards selection of our first DsiRNA-EX-Conjugate clinical candidate for Primary Hyperoxaluria Type 1 PH1 in the first quarter of 2016 based on ongoing monkey studies and we expect to advance that program into clinical development in 2017. We also expect to initiate preclinical development in 2016 of DsiRNA-EX-Conjugates for at least two other clinical indications. Now, I’d like to turn the call over to our CMO, Pankaj Bhargava for an update on our clinical stage programs.

[Pankaj Bhargava:]

Thanks, Bob. I’d first like to turn your attention to our program for the treatment of Primary Hyperoxaluria Type 1 or PH1. This program encompasses both our clinical stage DCR PH1 development program and a follow-up DsiRNA-EX-Conjugate development program. PH1 is a severe rare genetic disease where a single gene error in liver metabolism causes patients to have high levels of oxalate in the urine resulting in progressive and severe damage to the kidneys and other organs. Existing disease management practices in PH1 may slow, but do not stop disease progression. Most patients eventually experience complete renal failure with the median age of kidney failure being in the early 20s. There are no FDA approved therapies or effective treatments for most PH1 patients aside from combined liver kidney transplant. Our drug candidate for PH1, DCR-PH1 is a lipid nanoparticle encapsulated DsiRNA-EX-Molecule targeting the HAO1 gene, which encodes for an enzyme called glycolate oxidase that plays a central role in the metabolism of oxalate in PH1 patients. DCR-PH1 has been granted orphan drug designation by the U.S. Food & Drug Administration and by the European Medicines Agency. Two aspects of PH1 make it a particularly attractive 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 metabolic defect in the disease seems to occur exclusively in the liver. Second, PH1 presents clear and easily assayed biomarkers, specifically urine and plasma oxalate and glycolate levels, which provides direct read outs of the efficacy of our targeted therapies with this disease. Dicerna’s DCR-PH1 product candidate has demonstrated impressive efficacy in a validated animal model of PH1, which is a strain of mice that have been genetically engineered to carry the same metabolic defect found in PH1 patients. These mice have elevated levels of urinary oxylate roughly 3 times the normal background levels which is similar to that commonly observed in PH1 patients. When administering our DCR PH1 product candidate in these mice to knockdown the targeted HAO1 gene transcript and the enzyme that it encodes glycolate oxidase, we saw sustained reductions in urinary oxalate levels to background or near background levels. We believe that results similar to this is observed in patients with PH1 would have a significant benefit and significant impact on disease progression. The DCR-PH1 product candidate is also effective in silencing the HAO1 gene in cynomolgus monkeys. In normal cynomolgus monkeys we have seen that a single dose of DCR-PH1 led to upto 93% knockdown observed four days after dosing. We have observed that DCR-PH1 administration in monkey’s resulted in significant increases in urinary glycolate levels as expected based on the mechanism of action of DCR-PH1. While there is no PH1 disease model in monkey, this observation of urinary glycolate elevation in normal monkeys after DCR-PH1 administration supports the notion that DCR-PH1 may inhibit the metabolic pathway responsible for oxalate formation in PH1 patients and thereby may provide clinical benefit to PH1 patients. During the fourth quarter of 2015 we initiated two trials in furtherance of our PH1 program. First, we initiated an observational study of PH1 patients. This study will enroll upto 25 patients with genetically confirmed diagnosis of PH1. The primary objectives of the study are to characterize the base line variability and factors that influence changes in urine and blood oxalate and glycolate levels and renal function over the time among others. We believe this information will provide key data to facilitate the clinical development of DCR-PH1 and of subsequent DsiRNA-EX-Conjugate. In addition patients enrolled in the observational study are eligible to enroll in our planned DCR-PH1 interventional trial which will begin shortly. Second, in the fourth quarter we initiated a dose escalation trial of DCR-PH1 in normal healthy volunteers in the U.S. We have streamlined our plans for this trial such that its current role is to provide safety data to enable dosing of PH1 patients in the U.S. as soon as possible. The streamlining also allows us to apply additional resources to our DsiRNA-EX-Conjugate program for PH1. In addition we expect to soon begin a third trial, a Phase 1 trial of DCR-PH1 in patients with PH1. This global study first in Europe and later expanding to the U.S. will test single ascending doses of DCR-PH1. We expect that patients in this trial dosed at higher dose levels will show biomarker movement indicative of efficacy and our mechanism of action. Specifically we expect to see reductions in plasma and urinary oxalate levels and elevations of plasma and urinary glycolate levels over patient base line. I will now turn to our second product candidate DCR-MYC, which is our DsiRNA based therapeutic targeting the MYC oncogene, formulated in Dicerna’s proprietary tumor-centric EnCore lipid nanoparticle formulation. DCR-MYC is currently being tested in two ongoing clinical trials. First, a Phase I all-comers dose escalation trial with two additional cohorts both of which have now been initiated. The two cohorts are for respectively patients with pancreatic neuroendocrine tumors a tumor type where we have already observed clinical responses and a cohort for patient biopsies to allow us to directly observe molecular markers of DCR-MYC RNAi activity. And second, a Phase 1b/2 trial in patients with hepatocellular carcinoma, which is still in the dose escalation phase. Dicerna selected MYC as a high-potency target to silence with our DsiRNA technology, because it is frequently amplified or otherwise up-regulated in a wide variety of tumor types, suggesting a critical role in driving and maintaining tumor growth. The key role for MYC in tumor biology is also supported by a vast body of laboratory research in a wide variety of systems going back decades. But because MYC is an intracellular protein, which lacks a good small molecule binding site, it has been a challenging target for small molecules and biological therapy and has remained an elusive target for drug developers. We believe our Dicer substrate RNAi platform has the potential to overcome this limitation by targeting the MYC messenger RNA transcript. In preclinical studies, DCR-MYC has demonstrated specific and significant MYC gene knockdown in multiple tumor-bearing mouse models. DCR-MYC entered Phase I clinical testing in April of 2014 in patients with solid tumors multiple myeloma or lymphoma. The endpoints for this Phase I so-called 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 in this trial. We are evaluating anti-tumor activity by resist criteria, 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. We have not determined a maximum tolerated dose for the protocol criteria. However we have observed indications of tolerability issues from multi-cycle dosing at 1.25 milligrams per kilogram dose. Consequently we have paused dose escalations and initiated our pancreatic neuroendocrine and biopsy cohorts at the 1 milligram per kilogram dose level. This dosing level is consistent with our tolerability expectations based on preclinical toxicology studies. It is also a level where we would anticipate seeing anti-tumor activity again based on experience with preclinical studies in tumor-bearing mouse models coupled with area under the curve dose exposure calculation. This level of tolerability compares favorably with other lipid nanoparticle formulated RNAi products tested in humans. As of February 16, 2016, 40 patients have been dosed with DCR-MYC in nine dosing cohorts in our all commerce study. Anti-tumor activity was seen in two out of three patients with low to intermediate grade treatment refractory, pancreatic neuroendocrine tumors or PNET. Specifically evidence of a complete metabolic response based on imaging with FDG-PET was seen in one patient and a confirmed partial response based on resist 1.1 criteria was seen in the other patient. Both patients had failed standard and experimental therapies for PNET prior to starting the study. We have now initiated the peanut expansion cohort, which will enroll upto 20 patients with low to intermediate grade peanut who have demonstrated disease progression after treatment with standard therapies. These preliminary Phase I safety and efficacy results are encouraging and we believe support further study of DCR-MYC for use as a new treatment option for patients with cancer. We are also initiating a cohort of patients who will undergo pre and post treatment tumor biopsy, which will allow us to asses the direct effects of DCR-MYC in cleaving the MYC transcript. While we have already demonstrated resist responses and reduced FDG uptake in patients. We hope to clearly establish proof-of-concept by demonstrating RNAi activity against the MYC transcript in fresh tumor biopsy. We expect to be able to make this determination in the second half of 2016. In December 2014 we initiated a second clinical study of DCR-MYC a Phase Ib/2 study in patients with advance hepatocellular carcinoma or HCC who have either failed or are intolerant to sorafenat 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 has limited treatment options and there are no approved therapies for those who failed standard-of-care treatment with sorafenat. We have sites for the HCC clinical trial both in the U.S. and in Asia due to the high travelance of this disease in the Asian population. As of February 16, 2016, 15 patients have been dosed with DCR-MYC in 5 cohorts from the starting dose of 0.125 milligram per kilogram to the current dosing level of 0.68 milligram per kilogram. While we have not yet observed an objective response by resist criteria at the current does level we have observed reductions in circulating alpha-fetoprotein levels and HCC tumor marker where reductions can be associated with anti-tumor activity. We are continuing with dose escalation in this trial. Contingent upon achieving proof-of-concept with DCR-MYC we will launch our second oncology program targeting beta-catenin into IND enabling studies. Our DCR-BCAT has shown effective delivery and anti-tumor activity in a large series of mouse tumor-bearing models, which we have presented at research conferences. The tumor delivery capability of the DCR-BCAT formulation in animal models exceeds the results we observed with the DCR-MYC formulation. I will now turn over the call to our Interim Chief Financial Officer Jack Green for an update on our financial progress. Jack?

[Jack Green:]

Thank you, Pankaj. As many of you have seen, we filed our 10-Q today. There is a great deal of detail contained in that document. But I’d like to focus on the main financial metrics that we believe are important to use when evaluating the efficiency of our business. In the fourth quarter of 2015, Dicerna had a net loss of $15.6 million, compared to a net loss of $14.6 million for the same period in 2014. For the full year 2015 the net loss was $62.8 million compared to a net loss of $48.1 million for the full year 2014. Revenue for the full year 2015 included $0.2 million associated with a national cancer institute grand award related to cancer treatment research. No revenue was recognized in 2014. Research and development expenses were $11.3 million for the fourth quarter of 2015, compared to $9.9 million for the same period of 2014. The increase was due primarily to increased expenses related to the discovery and early development of future programs, increased expenses related to the preclinical and clinical startup activities for DCR-PH1, the initiation of clinical trials related to DCR-MYC and increased employee related expenses, including an increase in stock-based compensation of $0.3 million, offset by a decrease of $2.5 million resulting from a license fee paid to a collaboration partner in the fourth quarter of 2014. For the full year of 2015 research and development expenses were $44 million compared to $29.5 million for the full year of 2014. This increase was due primarily to increased cost related to preclinical and clinical startup activities for DCR-PH1, the manufacturing of DCR-MYC for clinical development and for our clinical trials, including our global Phase 1b/2 trial in patients with advanced HCC, which was initiated in the fourth quarter of 2014. Increased expenses related to discovery and early development of future programs, increased employee related expenses, including an increase in stock-based compensation of $1.6 million and increased occupancy costs. General and administrative expenses for the fourth quarter of 2015 totaled $4.4 million, as compared to $4.7 million for the same period in 2014. The decrease was primarily from a decrease in professional service fees and facilities allocations, primarily offset by an increase in payroll related expenses and legal costs. For the full year 2015 general and administrative expenses were $19.2 million compared to $15.6 million for the full year 2014. The increase was primarily due to an increase in payroll related expenses, which includes an increase in stock-based compensation of $1.5 million and an increase in professional fees, primarily from legal cost from ongoing litigation. As of December 31, 2015, the company had $94.6 million in cash and cash equivalents and held to maturity investments, as compared to $98.6 million in cash and cash equivalents and held to maturity investments as of December 31, 2014. In May 2015, Dicerna completed an offering of common stock resulting in net proceeds to the company of approximately $45.4 million. We have taken additional steps to create a platform to continuously achieve greater operational and financial efficiencies. Accordingly as part of that effort in December 2014 we licensed all of our non-U.S. intellectual property rights to a non-U.S. wholly owned subsidiary and in December 2015 we licensed our U.S. intellectual property rights to the same wholly owned subsidiary. Finally, based on our current cash position and operating plan, we expect that we have sufficient cash to fund operations for at least the 12 months. This estimate assumes no additional partnership funding and no new debt or equity financings. More detail of the financial information and analysis maybe found in the company’s annual report and its quarterly report on Form 10-K filed today with the SEC. And with that I’ll turn the call back to the operator so that we can take questions.

[Operator:]

Thank you. [Operator Instructions]. Our first question is from Michael Schmidt of Leerink. Your line is open sir.

[Michael Schmidt:]

Hey, thanks for taking questions. I may have missed it earlier. So what are the timelines for the healthy volunteer and the patient studies in PH1?

[Douglas Fambrough:]

So Michael, what Pankaj discussed, this is Doug and thanks for calling in. What Pankaj discussed was that we have pared back the healthy volunteer study to solely serve one of its functions, which is to help us initiate patient dosing in the U.S. and we’re going to truncate the study there and not proceed through dose escalation. The patient study should proceed as planned and should reach its completion in early 2017. The context for this really is the rapid progress that we’ve had with the conjugate technology and you may have noted on the call, we formally now discussing that we are launching a PH1 subcutaneously administered program using the DsiRNA EX-Conjugate technology and allocating resources to that development program. These two programs will proceed in parallel for the time being and as we evaluate data and other factors like the competitive environment and the performance of the conjugate in preclinical development we’ll make a decision about how to proceed with both programs in the future, but currently they’re going to run at the same time.

[Michael Schmidt:]

Yeah so when do you think the GalNAc conjugate version can - is ready for clinical studies?

[Douglas Fambrough:]

The IND enabling program as we mentioned will be - we are launching this quarter so it’s March already right so immanent. And that will be a 2017 clinical entry, but not giving more refined guidance than that at this time.

[Michael Schmidt:]

Okay. And then so can you provide some more details on the healthy volunteer study?

[Douglas Fambrough:]

So it’s going to be a small number of cohorts and it’s designed to in essence synchronize the dosing levels that we initiate in at the U.S. site and at our European sites.

[Michael Schmidt:]

Okay. And then a question on the cancelled trials. So you mentioned you have now reached an MTD basically in the all-comers study. I guess what were the tolerability issues that were observed at the 1.25 milligram per/k dose?

[Pankaj Bhargava:]

Sure, hi this is Pankaj. So we have not reached a protocol defined MTD or maximum tolerated dose. What we did observed in our dose escalation of the highest dose level was observation of [indiscernible]. And we out of abundance of caution we had a discussion with our advisory committee and external experts and we decided to pause dose escalation given that we have already achieved dose levels where we believe we would have relevant knockdown of MYC based on extrapolation from animal models. So we decided to pause dose escalation and we have now expanded the study into the pancreatic neuroendocrine biopsy cohorts at a dose of 1 milligram per kilogram in the patient study.

[Michael Schmidt:]

Okay. And I guess are you surprised not to see activity in any of the other patients beyond the two PNET patients that you reported data on?

[Pankaj Bhargava:]

So we have treated limited number of patients at these relevant dose levels. And as you can imagine in a Phase I study we have patients who have failed multiple prior therapies and patients with significantly advanced disease. So we are really looking forward to evaluating the activity in a focused cohort of patients where we have seen indications of clinical activity during our dose escalation chase which is in pancreatic neuroendocrine tumors. In some of the other patients, we have seen indications of stable disease. But again we are really focused on showing objective tumor response and shrinkage as we go forward into the PNET population.

[Michael Schmidt:]

Okay. And so in liver cancer for HCC where are you there in dose escalation at this point?

[Pankaj Bhargava:]

Yeah so as I mentioned we are currently at 0.68 milligram per kilogram dose level, which is just one dose level below 1 milligram per kilogram in our all-comers study. And dose escalation will continue in that HCC trial. And as I mentioned we have seen some indications of alpha fetoprotein tumor marker reduction.

[Michael Schmidt:]

Okay, great. Thanks for taking my questions.

[Pankaj Bhargava:]

Sure.

[Operator:]

Thank you. Your next question is from Steven Willey of Stifel. Your line is open.

[Unidentified Analyst:]

Hi this is Prakhar Verma [ph] on for Steve today. Thank you for taking my questions. So my question was on KHK program is it safe to assume that KHK will wait until to see the proof of concept data from the MYC program before they initiate the KRAS program?

[Douglas Fambrough:]

Hi, this is Doug. I don’t think that KHK is thinking about any linkage between our MYC progress and their KRAS program that incorporates our Dicer substrate. That program uses the KHK proprietary with the nanoparticle delivery system. And so its delivery system is not related to the MYC delivery system. And the performance one would expect to see in the clinic will be based I believe primarily on delivery system. KHK recently gave us an update on their pre-clinical progress with that program. And it continues to be a development program for KHK towards their resourcing. However, there is still a preclinical program and we do not have specific guidance on when it might be taken into patients.

[Unidentified Analyst:]

Okay, thank you.

[Operator:]

Thank you. Your next question is from Edward Conte of Jefferies. Your line is open.

[Edward Conte:]

Hi, I had three questions. In regards to the PNET expansion cohorts, how many patients’ data do you expect us to see in 2016 or would we see patient data?

[Pankaj Bhargava:]

So our cohort, hi this is Pankaj. Our cohort is designed to enroll a total of 20 patients. And really we are aiming to achieve enrollment of half or more than half of these patients this year. The goal is to go to high volume PNET sites, which we have already incorporated into this trial. And we are in the process of opening those sites with the first site just recently opened.

[Edward Conte:]

Okay, thank you. And then in regards to the HCC trial that’s ongoing from the PR it doesn’t seem like there is a lot of response yet. And you guys have indicated before that there could be a go or no go decision in 2016 with this program. Do you think that could come at earlier?

[Pankaj Bhargava:]

So in the HCC study, we are still in the dose escalation phase. And as I indicated, we are currently dosing at 0.68 milligrams per kilogram. And this is really our first dose level where we think we are at the - at our target doses, which we extrapolate from preclinical studies. So we have just reached that dose level in our human studies. As I mentioned, we have seen some indications of alpha fetoprotein tumor marker reductions, but it’s too early to say and make conclusions in the HCC study. We do anticipate to continue enrolling in this trial so that we have a robust number of patients to enable the decision by the end of ‘16.

[Edward Conte:]

Okay, thank you. And then final question on the PH1 single ascending dose data. You indicated study completion in the first half of ‘17, do you expect data to come at that point or would you wait until after?

[Pankaj Bhargava:]

Yes, we do expect data from patients to be available in that time frame.

[Edward Conte:]

Okay, thank you. That’s the end of my questions.

[Operator:]

Thank you. [Operator Instructions] Our next question is from Ritu Baral of Cowen and Company. Your line is open.

[Ritu Baral:]

Hi, guys. Thanks for taking the question. Doug was there any plan or at least part of the original plan in the U.S. to enroll U.S. patients as part of the first study. Just trying to dig into that I guess the decision to have patients come from Europe or Ex-U.S. at first, was there any issue with treating patients or finding patients in the U.S. or is it just European logistics are easier?

[Douglas Fambrough:]

European logistics have been easier.

[Ritu Baral:]

Are you still undertaking efforts to basically identify U.S. patients at this point? How has those efforts been going?

[Douglas Fambrough:]

Yes, we are continuing to work with the site, which is the Mayo Clinic, which is the primary aggregator if you will of patients and I’d say the main center of expertise for primary hyperoxaluria in general in the United States. So we are working with the investigators there and look forward to having the trial initiated in the U.S. at the Mayo site.

[Ritu Baral:]

Got it. Was there any change in the safety requirement or enrolling U.S. patients?

[Douglas Fambrough:]

As per normal we had our conversations with the FDA related trial protocol and that’s how we’ve reached this process.

[Ritu Baral:]

Got it.

[Douglas Fambrough:]

I think that’s all the detail we are going to give Ritu.

[Ritu Baral:]

Okay, alright. Thanks for taking the question.

[Operator:]

Thank you. At this time I see no other questions in queue. I’ll turn it back to management for any closing remarks.

[Douglas Fambrough:]

I want to thank everyone for participating in our call today and for the questions. We look forward to keeping you all up-to-date on our progress and we will talk again next quarter. Have a great night.

[Operator:]

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