Regulus Therapeutics Inc.
Q4 2015 Earnings Call Transcript

Published: 23 Feb 2016

[Operator:]

Welcome to the Regulus Therapeutics Fourth Quarter and Year-End 2015 Financial Results Conference Call. My name is Catherine and I will be your coordinator for today. I would now like to turn the call over to the Company; please proceed.

[Amy Conrad:]

Thanks, Catherine and good afternoon, everyone. I'd like to welcome you to Regulus's financial results call for the fourth quarter and year-ended December 31, 2015. Joining me on today's call are Paul Grint MD, Chief Executive Officer; Jay Hagan, Chief Operating Officer; and Mike Huang, Vice President Clinical Development. During our call today, Paul will provide introductory remarks, Mike will provide an overview on our microRNA therapeutics pipeline, Jay will review our financials and business highlights for the year and Paul will wrap up the call. Before we begin, I would like to remind you that this call will contain forward-looking statements concerning Regulus's future expectations, plans, prospects, corporate strategy and performance which constitute forward-looking statements for the purposes of the Safe Harbor provisions 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 our filings with the SEC and also including our 10-K which we intend to file tomorrow. In addition, any forward-looking statements represent our views only as of the date of this webcast and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligations to update such statements. With that, I'll turn the call over to Paul.

[Paul Grint:]

Thank you, Amy. Welcome and thank you for joining us. 2015 was an important period of growth for Regulus, with meaningful clinical and research progress made to advance our oligonucleotide drug discovery and development expertise against validated microRNA targets. Most notably, we were pleased with the rapid progression of our clinical pipeline, finishing 2015 with three microRNA therapeutic programs in clinical development which we believe further solidifies our leadership position in the field. Specifically, we filed three investigational new drug applications in the United States, filed two clinical trial applications in Europe, presented multiple key data sets at major medical meetings, realized several partner milestones with the advancement of our science, and strengthened our team. These achievements have led us to a favorable position today. We have a well-balanced portfolio; an exciting, wholly -owned lead asset in RG-101; an orphan disease program in RG-012 in development to treat Alport syndrome; and a third clinical program, RG-125, that entered the clinic last year in collaboration with AstraZeneca. This portfolio is supported by our strong balance sheet of $115 million in cash that we ended the year with. To put the year's accomplishments into perspective, we significantly strengthened our science and our Business, which provides us with a positive outlook for 2016. To that end, we've set many aggressive goals for the coming year. We aim to accelerate development of RG-101 with the initiation of key clinical trials, both in Europe and the United States, report additional combination data for multiple clinical trials and attain clarity on the potential path for approval. In addition to the work on RG-101, we expect to initiate a Phase II proof-of-concept study with our second asset, RG-012, an anti-miR-21 in development for the treatment of Alport syndrome around mid-year, and we expect to nominate an additional clinical candidate for development. Our approach to drug development is grounded in the following principles. We're currently working on validating multiple microRNA targets where we believe we can engineer anti-miRs with a high therapeutic index that can be delivered to the target tissue at therapeutic levels, have pharmacodynamic markets to target engagements, and which have indications with unmet medical need where we can identify a treatment effect in a reasonable time frame. In the coming quarters, we look forward to sharing our progress on this important work. To close out my introductory remarks, I would like to spend a few minutes providing our perspective on the recent RG-101 data. Last week, we reported favorable interim results from the ongoing Phase II sandwich combination study of RG-101. This was the first time we have combined a microRNA therapeutic clinically with a small molecule in disease patients demonstrating positive results, and most importantly, the first clinical evidence that the duration of HCV total therapy can potentially be reduced to just four weeks by combining with RG-101, our proprietary GalNAc-conjugated anti-miR-122. As a reminder, for those HCV patients through eight weeks of follow-up, 97% or 37 out of the 38, had viral load reductions below the limit of quantification. And for those patients who reached 12 weeks of follow-up, 100% had viral load reductions below limits of quantification which is very encouraging. And we believe that RG-101 has the opportunity to become a backbone agent to any future treatment regimen. Hepatitis C represents a large unmet medical need, and we believe that the landscape is at another tipping point. Several non-interferon-containing oral regimens have been approved in the United States. Based on projections provided by another leading HCV pharmaceutical company, there are estimated to be approximately 250,000 patients treated with DAAs in the U.S. this year, while another 360,000 will be diagnosed and coming into the treatment pool. So, clearly, this is a market that has significant potential. Globally, there are approximately 185 million people chronically infected with hepatitis C. And these currently approved agents may not cure the entire population with the continued and rapid emergence of resistant mutations. We believe that RG-101 can help address this global healthcare problem in combination with other agents across all genotypes. To date, RG-101 has demonstrated potent and sustained responses in a wide range of HCV patients, genotypes 1, 3 and 4; those with varying liver fibrosis scores of baseline; treatment-naive and those patients who have failed a prior interferon-containing regimen. RG-101 has demonstrated the ability to be safely combined with all classes of direct-acting antivirals as represented by the drugs used in the current Phase II study, Harvoni, Olysio and Daklinza, nucleoside, non-nucleoside, polymerase inhibitor, and an NS5A. RG-101 is potent, pan-genotypic, has the ability to shorten the leading DAA to just four weeks, minimize the potential for virologic breakthrough, and act through a unique mechanism of action by targeting miR-122 which we believe is differentiated in the ever-evolving DAA landscape and provides us with a potential advantage. We're very excited about this program and we look forward to accelerating its development and reporting additional results throughout the year which Mike will provide more details on in a minute. With that, I will turn it over to Mike and then Jay will provide the numbers and business highlights. Mike?

[Mike Huang:]

Thank you, Paul and good afternoon, everyone. As Paul mentioned, we're extremely pleased with our progress during 2015 and so far this year, particularly with the demonstration of favorable interim combination results with RG-101 and the overall progression of our clinical portfolio. Following last week's interim readout on RG-101, we expect to submit a late-breaking abstract for potential presentation at the upcoming EASL meeting to be held in Barcelona in mid-April. And we expect to report on primary endpoint analysis of all 79 patients through 12 weeks of follow-up from that study late in Q2. We're highly encouraged by the results seen to date, and we look forward to providing additional updates from the Phase II sandwich combination study soon. As you know, we have developed a multifaceted clinical development plan for RG-101 which includes evaluating RG-101 in combination with multiple different oral agents, but also potentially in combination to enable a single visit therapy through our clinical trial collaboration with GSK announced last November and in certain underserved populations such as HCV patients with chronic kidney disease, where treatment options are limited. The goal of the clinical collaboration with GSK is to evaluate the potential for a single visit therapy to treat HCV. To achieve this goal, we and GSK will be taking multiple steps. The first step will be to conduct a Phase II study evaluating the combination of RG-101 and an oral tablet formulation of GSK 175, an investigational, non-nucleoside NS5B polymerase inhibitor for the treatment of HCV. In previous clinical studies, GSK 175 has demonstrated substantial reduction in HCV RNA across all genotypes as monotherapy and has displayed a PK profile consistent with once-a-day dosing with the potential for prolonged PK/PD activity. We believe these attributes make GSK 175 well suited for combination with RG-101. The primary endpoint of this Phase II combination study is to evaluate the potential to achieve sustained virologic responses post treatment with a single subcutaneous administration of 4 milligrams per kilogram of RG-101, in combination with daily oral administrations of 20 milligrams of GSK 175 for up to 12 weeks in treatment-naive patients chronically infected with HCV genotypes 1 or 3. For the first time, this study design offers Regulus the ability to investigate one subcutaneous administration of RG-101 in combination with daily oral dosing of a direct acting antiviral for a fixed total treatment period which we're calling our open-faced sandwich design. We're pleased to announce to you today that the open-faced sandwich study has been initiated and we expect to report interim safety and efficacy data from this study by the end of 2016. While this study is ongoing, the next step is for GSK to advance their long-acting parenteral for injection or LAP formulation, of GSK 175 into humans. By way of background, LAPs are injectable formulations of a drug whose solubility limited release results in the inability to have very long apparent half-lives, potentially weeks to months. LAPs have been successful for commercial applications in indications such as HIV, where sustained release and compliance benefits are critical. We believe that the concept of developing a long-acting HCV therapy that can be administered in a single visit could potentially transform the current treatment landscape by improving patient compliance through reduced dosing intervals and potentially extending opportunities for therapeutic intervention. The LAP formulation of GSK 175, once developed, may be used in additional studies together with RG-101, with the ultimate goal of achieving a one-visit cure for HCV following completion of the planned Phase II open-faced sandwich study. In addition to both of these Phase II combination studies, we're also enrolling patients in our first Phase I study being conducted in the United States. The goal of this study is to compare the safety, tolerability, pharmacokinetics and pharmacodynamics of RG-101 in subjects with severe renal insufficiency or end-stage renal disease, to healthy control subjects and to further explore RG-101 in HCV patients with severe renal insufficiency or end-stage renal disease which we believe is an underserved population. Enrollment is expected to be complete in the first half of 2016, with efficacy data from the HCV severe renal impairment or ESRD arm, anticipated in the second half of 2016. Now, in addition to the ongoing clinical work with the aforementioned Phase I and Phase II studies, we're actively working on additional clinical studies to evaluate the potential of RG-101 in different combinations and regimens to treat a wide range of HCV patients. Furthermore, as we mentioned last week on our call, we have manufactured the first commercial batch of RG-101 and we intend to perform additional manufacturing scale-up work to support the additional combination studies being designed, while we work to define the proper regulatory path to a potential approval. Now let's turn to our second clinical program, RG-012, our anti-miR targeting microRNA 21 for the treatment of Alport syndrome, a life-threatening genetic kidney disease with no approved therapies. By way of background, Alport syndrome is driven by genetic mutations in the type 4 collagen family of proteins. The impact of the mutation in the collagen gene results in disruption to the structure of the glomerular basement membrane, increased expression of microRNA 21, increased fibrosis and progressive loss of renal function which leads to end-stage renal disease requiring dialysis or kidney transplantation, often by early adulthood. Last year, we were pleased to complete our first-in-human Phase I clinical study of RG-012. The study was conducted in the United States to evaluate the safety, tolerability and pharmacokinetics of subcutaneous dosing of RG-012 in healthy volunteers. 40 healthy volunteer subjects were enrolled and RG-012 was well tolerated. No serious adverse events were reported and all 40 subjects successfully completed the study. Further, we've made good progress in maturing our global Alport syndrome natural history study, called ATHENA. The goal of the ATHENA study is to learn more about the actual progression of Alport syndrome by documenting the change in certain renal biomarkers and glomerular filtration rates or GFR, in these patients. Data from the ATHENA study, coupled with the results from the Phase I study in healthy volunteers, will provide the clinical basis for the design of a Phase II study to evaluate the therapeutic effect of RG-012 in Alport syndrome. Currently, we expect to initiate the Phase II study by the middle part of this year. By establishing the ATHENA observational study, we believe we can have a very strong start to enroll in the Phase II program by shifting eligible patients identified during the ATHENA observational study over into the Phase II interventional study with RG-012. And we have also submitted data from our ATHENA study to a medical meeting in the hopes of sharing our increased knowledge of this little known disease. Overall, this program is maturing very nicely and we're excited about the opportunity to provide therapeutic benefit in Alport syndrome, an orphan disease with no approved therapies. So, to summarize, we believe that 2016 will be another exciting year and we remain focused on building a meaningful clinical portfolio based on microRNAs. So, with that, I will turn the call over to Jay to provide a financial and business overview.

[Jay Hagan:]

Thanks, Mike and good afternoon, everyone. As both Paul and Mike have mentioned, 2015 and the early part of 2016 has been an extremely busy and productive period for Regulus. During that time, both our science and the overall Business has matured. We set a goal to have three clinical candidates by the end of 2015 and we achieved this feat in December last year when AstraZeneca initiated a Phase I single ascending dose study of RG-125, a GalNAc-conjugated anti-miR targeting microRNA 103/107 for type II diabetes and NASH. In connection with this achievement, Regulus received a $10 million milestone payment from AstraZeneca which is one of the larger milestone payments we have received to date. As we reported today, we exceeded our previous cash guidance for the year, ending 2015 with $115.3 million in cash, cash equivalents and short term investments. The $10 million milestone is not included in that ending year cash balance figure, further strengthening our balance sheet. Another key business highlight during the year was the realization of the full economic value of our scientific collaboration with Biogen to discover microRNA biomarkers for Multiple Sclerosis. In the third quarter last year, we achieved the third and final milestone as part of that collaboration and the payments to Regulus totaled $3.7 million. We were very pleased to have increased our revenue stream year over year and we look forward to realizing additional milestones from our partner programs as we advance in clinical development. Turning to our financial results for the year ended December 31, 2015, we recognized revenue of approximately $20.8 million in 2015 compared to $7.7 million in 2014. Revenue in 2015 included total milestones of $13.2 million, of which $12.5 million were earned from our collaboration agreement with AstraZeneca. These milestones included a $2.5 million clinical candidate selection milestone for RG-125 earned in the first quarter and the $10 million clinical milestone earned in the fourth quarter upon the initiation of a Phase I clinical study for RG-125. Additional revenues in 2015 included $4.5 million for research services provided under a collaboration license agreement with AstraZeneca, in addition to the continued amortization of up-front payments received from our strategic alliances and collaborations which we recognized over our estimated period of performance. Our research and development expenses were $56.4 million in 2015, compared to $41 million in 2014. This increase was primarily driven by Phase II clinical trial costs for RG-101, pre-clinical study costs for RG-125 and an increase in salaries and related employee costs, including non-cash stock-based compensation. We expect our research and development expenses to continue to increase as we advance our ongoing clinical and pre-clinical programs. Our general and administrative expenses were $19.1 million in 2015, compared to $11.5 million in 2014. This change was primarily driven by an increase in salaries and related employee costs, including non-cash stock-based compensation. Additionally, the majority of this increase was driven by non-recurring personnel-related charges. Our net loss for 2015 was $55.7 million, resulting in a basic and diluted net loss per share of $1.08, compared to a 2014 net loss of $56.7 million, resulting in a basic and diluted net loss per share of $1.29. Looking towards 2016, we expect to finish the year with between $50 million and $60 million in cash, cash equivalents and short term investments. With that, I will turn the call back over to Paul for closing remarks.

[Paul Grint:]

Thank you, Jay. As you've heard from the team, we're very pleased with our progress during the last year and so far in 2016. And this year will be another important one for the Company. Our priorities include advancing RG-101 and RG-012, obtaining more data from ongoing clinical programs, nominating a fourth microRNA candidate for clinical development and defining the regulatory pathways to bring our microRNA therapeutics to patients in need. With that, Catherine, we're ready to take questions. Thank you.

[Operator:]

[Operator Instructions]. Our first question comes from Bill Tanner with Guggenheim Securities. Your line is open.

[Bill Tanner:]

Mike, unfortunately, I missed your call last week when the data were out. And I was just trying to circle back up little bit on the two SAEs, wasn't quite sure exactly as to the commentary related to that. So maybe if there's anything else to add or any kind of clarification. And then just thinking about that in the context of the Phase 1 study that's ongoing to look at the safety and PK and whatnot in patients with compromised kidney function or ESRD, if there's any connection there. And then I guess the final part on that, what would be the theoretical issues related to the delivery of the compound and renal function and then as it relates to hepatitis C patients with some kind of compromised function?

[Paul Grint:]

Okay, Bill. This is Paul. So let me just summarize with regard to the SAEs and thanks for the question. We did report the two SAEs in the call last week. But from what we've seen so far, we're certainly not worried about the safety profile of RG-101 or in fact the reported SAEs. As we mentioned last week, both of these occurred in the treatment follow-up period, both these patients received treatment and neither patient discontinued from the study. It's important to note that obviously if you look at the package inserts for the DAAs that we're treating in combination with, they obviously documented a list of numerous adverse events there. And basically what we relayed last week is that we're going to report more detail on these at the first available opportunity at the major medical meeting.

[Bill Tanner:]

Okay. So then is the implication as you look at the label on the DAAs, is that the AEs that were experienced were similar to those?

[Paul Grint:]

So what we talked about is obviously for appropriate balance, we report a summary of the safety and the efficacy, and we had two serious adverse events. And I think people need to understand that's a regulatory definition term. Basically adverse events are graded and these two met the grade to be called serious under a regulatory definition. Just to remind you, these are patients that have chronic hepatitis C, they have multiple other co-morbid conditions, and we're following them for very prolonged periods of time, and we'd expect to see other things reported over a follow-up period.

[Bill Tanner:]

Okay. And then maybe sorry, go ahead, Paul.

[Paul Grint:]

No, that's all I was going to say.

[Bill Tanner:]

Okay. And then as it relates to the open label Phase 1 study that's currently being enrolled to look at safety in PK PD, what is the contemplation of what one might see with the pharmaca for and patients that have impaired renal function? And then let's say that there is a population of patients that the use of the drug might be contraindicated in, what does that look like in the context of the greater Hep C patient population?

[Paul Grint:]

So just to remind you, Bill, the reason we're interested in patients either with severe renal compromise or even those patients who are on dialysis, is that as far as we're concerned, the pharmacokinetics of an oligonucleotide should not be significantly affected by severe renal compromise, and that's obviously not the case with certain oral agents or ODAAs [ph]. So we believe that this is an important medical need patient population. And clearly, if we can demonstrate there isn't an effect in PK, and that RG-101 is potentially -- one can use that to treat these patients at the same dose that we already have experience at that would be an advantage. So that is basically what we're assessing right now in the Phase 1.

[Operator:]

And our next question comes from Eric Schmidt with Cowen and Company. Your line is open.

[Eric Schmidt:]

Just on the RG-101 open label sandwich trial, I assume -- I'm sorry, the open sandwich trial, I assume that is open label. And if so, when might we see initial results from that?

[Mike Huang:]

So you're right. So this study is an open label study with different arms, primarily related to the fact that there's different durations of therapy of the GSK 175 oral formulation that we're looking at. So we're looking at having some interim results towards the end of 2016, again, pending the rate of enrollment, but that is what we're going to be targeting for the study.

[Eric Schmidt:]

Okay. Are there any corporate development objectives for 2016 on RG-101 or for that matter, pipeline and platform?

[Jay Hagan:]

We're actively in dialogue with folks all the time on both our platform as well as our clinical programs. As I mentioned on the data call, though, we're not in a pressing need to partner 101. I think it is more important that we best understand the full profile of the product in combination with different available DAAs before we're in a position to think about how we would best commercialize the product via any potential collaboration.

[Eric Schmidt:]

Okay. What about the burn for 2016, Jay? Is there any guidance? Is Q4 run rate what we're looking at or should we expect that to gradually increase over the course of the year?

[Jay Hagan:]

Yes, I think it is going to go up a bit. If you do the math on the delta between what we ended the year with plus that $10 million milestone minus what we said we would end the year with, the total gross cash burn this year is up a bit over last year, and this figure from this year does not include any anticipated additional visit the moment activity.

[Operator:]

Our next question comes from Alan Carr with Needham. Your line is open.

[Alan Carr:]

So I had a question on ATHENA. Is what you are seeing right now similar to what is seen in medical literature in terms of disease progression?

[Mike Huang:]

Yes. This is Mike. I would say yes that overall it is pretty consistent with what is available out there in the literature. But I think that is also a good point to make that there actually isn't a whole lot out there in the medical literature, especially with regard to prospectively designing longitudinal observational studies. I think most of the literature out there that we've been able to identify has really been retrospectively analyzed and not as well standardized in terms of the types of assessments and tests. So I think what we're getting from the ATHENA study is, is really a very good look in terms of the prospectively defined longitudinal data where patients are measured and looked at regular time points. There's a lot of standardized processes that we've put into place, so that all sites, all patients are being treated in exactly the same fashion. So really I think what we're getting is data that's going to be more accurate and more useful than what is actually available in the public domain. And I think most importantly, these data will really help to inform us on the design of the phase 2 study and especially for discussions with the FDA coming up fairly soon.

[Alan Carr:]

And in terms of RG-101, I think last week you said that you were going to test various therapies for less than four weeks. Could you tell us what gives you confidence in that? Is that a certain two or three week data that you've been looking at?

[Paul Grint:]

No, this is Paul. I think what I remarked on last week, if you look at the variables now that we could assess. Obviously, one of them is one injection of RG-101 instead of two. And that in essence is being looked at in the GSK clinical collaboration. But we've got great looking data so far at four weeks. And so an obvious question we're being asked is, do you need four weeks? Many of these DAAs are very effective at dropping viral load significantly in a period shorter than four weeks, so one of the options that we have is to investigate a treatment period shorter than four weeks.

[Operator:]

And our next question comes from Liana Moussatos with Wedbush Securities. Your line is open.

[Liana Moussatos:]

I have two questions on monotherapy for RG-101. What's the current status of the single dose patients in Phase 1 that are still BLOQ and how many months? And the second question is, what are the plans for a repeat dose monotherapy clinical testing?

[Paul Grint:]

So we currently still follow -- we follow patients for a prolonged period of time for the Phase 1 study. Just to remind you, we reported six months of follow-up information at the ASLD meeting in November. Hopefully we will -- or actually we will, at EASL, provide one year follow-up data on that patient cohort. So that is our goal there. So that's good news and obviously that's only couple of months away. I'm sorry, the second question was? Well right now, we don't currently have plans for multi-dose of RG-101 monotherapy. As we went into hepatitis C, it was always our expectation that this would be a combination therapy approach. So clearly, the design of the phase 2 study that we reported data on last week was to combine with a number of different mechanisms. The idea was to see maybe could be one mechanism that might be better than another to combine. But obviously, as we have at least seen the data so far, there is nothing obvious that leads you to that conclusion at the moment. And so I think as we continue to look forward, frankly, we're just looking at combination therapy so we don't have any plans in the short term to investigate multiple doses of monotherapy.

[Liana Moussatos:]

And unless the open sandwich is the way you get approved, if you have to do two injections, won't you have to have a monotherapy arm with two injections separated by four weeks?

[Paul Grint:]

That's an interesting point. We have not obviously talked to the FDA yet as we discussed last week about a path forward. Don't forget, you're in this interesting situation where when you consider at least the DAAs, you are limited to the period of time that you can give a monotherapy for. Generally it is very short, just one or two days because of concern about resistance developments. And then drug could develop in a combination and in this field, you don't have to clearly identify the contribution of each one of those drugs that's in combination.

[Liana Moussatos:]

Even for unapproved drugs?

[Paul Grint:]

That's a good -- well given our mechanism, again, I think this is a discussion that we will have at the right time with the FDA to understand what is required.

[Operator:]

And our next question comes from Jim Birchenough with Wells Fargo. Your line is open.

[Jim Birchenough:]

The first one is just going back to RG-101. And can you elaborate a little bit more on what sort of bio-markers we might expect to see data on? And also if there's a role for miR-122 in glumcite biology and what the potential impact might be on IVM 8 or adaptive immune system for inhibition of 122? And then I have a follow up.

[Paul Grint:]

So when you talk about bio-markers, you're really talking about pharmacodynamic types of markers?

[Jim Birchenough:]

Yes.

[Paul Grint:]

We clearly and as we reported, associate it with the Phase 1 study. We continue to look at those and yes, obviously it's our intention to report data out on those. It won't just be viral load data and safety data, but wherever possible we'd like to report our PD markers. And then with regard to the effects of 122 mechanism on innate immunity, that's something that we do -- we're interested in and we plan to investigate and obviously it's something that we can definitely look at in the future.

[Jim Birchenough:]

And then on 012, so you've completed this first in man trial. Did you see the expected pharmacodynamic changes to mirror inhibition there and what where they? And then as a follow-up to that, I note that University of Minnesota has this ASTOR registry ongoing. I've not seen any data from that, but I'm wondering has there been any data? And is there overlapping patients between your registry and ASTOR? And can ASTOR also serve as a way to kick start enrollment into the phase 2 later on in the year? Thank you.

[Paul Grint:]

I will let Mike speak to the ASTOR registry in a moment. Just to remind you, we're in this interesting situation where miR21 is a very low level in normal kidneys, but significantly upregulated in Alport. So as we have done the Phase 1 in normal healthy volunteers, we wouldn't expect to see any -- there are not PD affects that we can measure, if you like, from that standpoint. So the goal of the Phase 1 was primarily safety tolerance in pharmacokinetics and that's what we've achieved. And I will get Mike to cover the comments in the ASTOR registry.

[Mike Huang:]

So with regard to the ASTOR registry, so you're correct. The University of Minnesota does manage and maintain the ASTOR registry. And what we have been able to access is using ASTOR registry, we have been able to identify a number of our patients who then qualify for the ATHENA study through ASTOR. So I wouldn't say that we actually have access to that database, however our investigators of in particular our University of Minnesota investigators, they have access to that registry and have utilized that registry as a way to help feed patients into the ATHENA trial.

[Operator:]

And our next question comes from Christopher James with FBR & Co. Your line is open.

[Christopher James:]

My first question with respect to RG-101, can you remind us of the rationale of development, specifically in patients with renal impairment? And really, is there a potential to combine that with a one two considering that's a renally directed drug? Have you looked at an regulation of miR21 in HCV, could you combine those two drugs?

[Paul Grint:]

As you know, we haven't looked at combining it with miR21, so that is an interesting point. Going back, so the rationale was for patients with severe renal compromise and dialysis as you know well, there are some DAAs you can use and many you can't. And so, suffice it to say, you've hit the nail on the head. We have a lot of experience with another oligonucleotide, 012, working in animal systems with severe renal compromise. And so we have experienced giving oligos. And our belief is that the degree of renal compromise we know, as I've said before, should not affect PK and therefore dosing. And so we're doing the Phase 1 study to prove that. So if that turns out to be true, then obviously we potentially have RG-101 as a potential therapeutic. And there are other -- and there are currently approved DAAs that can be used in patients with severe renal compromise. Generally, the issue is they can't be used as monotherapies. So you'd be looking to combine them, so we could combined with RG-101. And as you know well, this is a patient population that really is pretty delicate. And if we can, I think work out a therapeutic course that is well tolerated and relatively short, not necessarily four weeks, but definitely shorter than some of the currently used treatment courses. I think it really offers a major opportunity in this significant under-served population.

[Operator:]

Thank you and I am showing no further questions at this time. I would like to turn the call back to the Company for any closing remarks.

[Paul Grint:]

Thank you very much for your time this afternoon.

[Operator:]

Ladies and gentlemen, that concludes today's conference call. Thank you for your participation. You may all disconnect. Good bye.