Regulus Therapeutics Inc.
Q3 2014 Earnings Call Transcript

Published: 6 Nov 2014

[Operator:]

Welcome to the Regulus Therapeutic's Third Quarter 2014 Financial Results Conference Call. My name is Sam and I will be your coordinator for today. I would now like to turn the conference over to the company. Please proceed.

[Amy Conrad:]

Good afternoon everyone. This is Amy Conrad, Senior Director, Investor Relations and Corporate Communications at Regulus Therapeutic and I would like to welcome you to our financial results call for the quarter ended September 30th, 2014. Joining me on today's call are Kleanthis Xanthopoulos, Ph.D., President and Chief Executive Officer; Paul Grint M.D. , Chief Medical Officer; Neil Gibson, Ph.D., Chief Scientific Officer; and Dan Chevallard, Vice President, Finance and Accounting. Before we begin, I would like to remind you that this call will contain forward-looking statements concerning Regulus' 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. 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. I would like to turn the call over to Kleanthis.

[Kleanthis Xanthopoulos:]

Welcome everyone and thank you for joining this afternoon. This past quarter and recent period have been very exciting for us. We made major advancements on both the scientific and business fronts which have significantly strengthened our leadership position in the field of microRNA therapeutics. Two weeks ago we reported our first human proof of concept results with microRNA therapeutic, RG 101 our wholly owned GalNAc conjugated anti-miR targeting miR 122 for the treatment of Hepatitis C. We reported that at the lowest dose tested in HCV patients so far RG 101 as monotherapy demonstrated an impressive durable effect on the HCV virus. In the first cohort of 16 patients with various genotypes and treatment history, (indiscernible) and 14 actives were included. All 14 patients in active had logical response and in these patients there was a mean viral reduction of 4.1 logs at day 29. At day 29, six out if the 14 patients had HCV RNA levels below the limit of quantification. More over from this six patients the three patients that agreed to 57 days remain undetectable. On the use of this interim RG 101 result we were able to strengthen our balance sheet with a public offering of common stock with a net proceeds to the company being about 76.1 million to rapidly advance RG 101 and further support the growth of our pipeline. And we have also increased our year-end guidance to end 2014 with now greater than 150 million in cash. To rapidly advance RG 101 we have updated our Clinical Map Initiative goals to reflect our current thinking. We believe that RG 101 maybe be a potentially disruptive agent to the current treatment landscape and are currently having discussions with key opinion leaders in this space as we’re planning for dialogue with regulatory authorities in order to refine our potential plans. To that end we’re investigating the possibility to pursue a potential dual track for RG 101 focused on a first line combination strategy with existing DAAs to optimize clinical outcomes and potentially shorten the duration of overall therapy. And the second first to market combination strategy in patients failing direct antiviral agents. In the second quarter of next year we expect to initiate a Phase 2 combination study of RG 101 with a potential to begin even earlier depending on the speed of our dialogues with regulatory authorities and input from key opinion leaders. Later on the call Paul will provide more insight into our anticipated development plans. In addition to the ongoing work for RG 101 we’re also advancing RG 102 in anti-miR targeting microRNA 21 to treat renal dysfunction in Alport syndrome basis in the rest of the portfolio. Under the Clinical Map Initiative we expect to initiative a Phase 1 study of RG 012 in healthy volunteers. We’re also advancing multiple other programs towards the clinic and expect to nominate a third candidate for clinical development in the first half of 2015. With all of this exciting recent progress our confidence in our approach to treating this disease with microRNA therapeutics remains at all-time high. The rich biologics of microRNA's and their critical role in pathophysiology continue to provide us with tremendous opportunities to apply or establish technology platform to develop a new and major class of therapeutics based on microRNAs. Let me now turn the call over to Neil, to provide additional remarks on the topic.

[Neil Gibson:]

Thank you Kleanthis and good afternoon everyone. As Kleanthis mentioned we are extremely pleased with our recent scientific progress particularly to the demonstration of our human proof of concept results with our RG 101. Falling our call two weeks ago I want to spend a few minutes to discuss the biology behind targeting microRNA 122 and the benefits of a host factor of therapy in ACV. miR-122 is the most prevalent microRNA in hepatocytes and is a critical host factor for Hepatitis C. miR-122 interacts with the HCV virus by binding to the two closely spaced seed sequences in the (indiscernible) of the HCV virus, that facilitate HCVs replication and function. (Indiscernible). Published data has shown mutations in those two miR-122 binding sites prevents viral replication and function potentially making the development of escaped mutants unlikely. In addition to the function of miR-122 in a disease state the normal biological function of miR-122 has been studied in mice and non-human primates through both genetic and pharmacological approaches. The published data show that miR-122 is key regulator of metabolic function in the liver although it is not essentially for (indiscernible) development. In the miR-122 knock out mode hepatocytes doses develops early in life promoting inflammation which progresses to fibrosis and eventually leads to hepatocellular carcinoma or ACC after approximately 12 to 15 months. However contrary to the phenotype in the knock out mouse, pharmacological inhibition of miR-122 in mice with anti-miRs for upto 50 weeks led to sustained reduction in cholesterol with no adverse findings observed after histopathological evaluation in liver. In addition, inhibition of miR-122 treatment in a high fat mouse model resulted in significant improvement in liver steatosis, a result that indicates a beneficial rather than detrimental effect. Furthermore, (Indiscernible) have recently shown short term inhibition of miR-122 for upto six months in a mouse liver did not increase the risk of ACC relative to control animals. This finding highlights a potential difference between short term pharmacological suppression of miR-122 compared to germline knockout or elimination of miR-122. These findings support our approach of short term pharmacological inhibition of miR-122 with RG 101 as opposed to chronic long term suppression of miR-122. We believe that the current HCV treatment landscape highlights the need for combination therapies that not only target the virus but also target indigenous host factors such as miR-122. Let me now turn the call over to Paul, who can take us through the attractive opportunities we have with RG 101 and the important upcoming clinical timelines in our portfolio. Paul?

[Paul Grint:]

Neil, thanks and good afternoon everyone. So on today's call I will provide a summary of the recently reported interim data on RG 101 and the different options we’re considering for Phase 2 development, I will also touch on RG 012 and the upcoming catalyst over the next several quarters. RG 101 is our wholly owned GalNAc-conjugated anti-miR targeting microRNA-122 for the treatment of Hepatitis C. RG 101 is an extremely unique molecule that combines the most advance chemistry 2.5 from Isis Pharmaceuticals. The GalNAc-conjugated from Alnylam Pharmaceuticals and Regulus' unique and proprietary chemistry including novel linker to facilitate the release of the parent oligonucleotide after hepatocyte uptake. RG 101 is currently being evaluated in an ongoing four part clinical study being conducted in the Netherlands. Upto a 100 healthy volunteer subjects in HCV patients with multiple HCV genotypes and treatment history are planned to be enrolled. In Part 1, healthy volunteer subjects received a single subcutaneous dose of RG 101 at five doses upto 8 milligrams per kilogram or placebo. The RG 101 was well tolerated and no significant adverse events were observed. We continue to dose healthy volunteers in Part 2 of this ongoing study in which healthy volunteers subjects receive a monthly single subcutaneous dose of RG 101 or placebo for four months. Results for this portion of the study our plan to be submitted for publication in the first half of 2015. In Part 3 of the ongoing study, we combined RG 101 with simeprevir or OLYSIO an approved oral DAA in healthy volunteers. No drug-drug interaction effect was observed. These data provide pharmacokinetic evidence that RG 101 may be combined with oral agents and we plan to investigate further combinations in an upcoming Phase 2 study. Lastly HCV patients received single subcutaneous dose of RG 101 at 2 milligrams per kilogram the first cohort or four milligrams per kilogram, the second dose cohort or placebo in part four of the ongoing study to assess the safety and viral load reductions. As Kleanthis mentioned earlier on the call we recently reported favorable interim results from the 2 milligram per kilogram dose cohort which demonstrated human proof of concept. We enrolled 16 patients in that cohort, 10 GT-1 patients, five GT-3 patients and one GT-4 patient. 14 patients received a single subcutaneous dose of 2 milligrams per kilogram of RG 101 and 2 received placebo. After the 14 patients who received RG 101 eight patients were treatment naïve and six patients had experienced viral relapse after a prior interfere on containing regimen. We reported that the single subcutaneous dose of RG 101 demonstrated a virologic response in all RG 101 treated patients and we saw a mean viral load reduction of 4.1 log at day 29 with a range of minus 5.8 to minus 2.3. Also importantly six out of the 14 patients had HCV RNA levels below the limit of quantification and three patients who have reached a 57 and continue to have these HCV RNA levels below limit of quantification. We continue to follow these patients enrolled in part four of our study for upto six months after dosing to investigate the possibility of these patients achieving a viral cure after single administration of RG 101. Today we’re also pleased to announce the 4 milligram per milligram dose cohort is now fully enrolled and we expect to report results from this portion of the study in the first quarter of 2015. Currently we’re considering different designs for the Phase 2, our goals will be to evaluate the potential to shorten the duration of therapy and enhance compliance with our subcutaneous dosing. To satisfy this criteria we’re investigating the possibility to pursue a potential dual track for RG 101 focused on both the faster market, first line combination strategy with existing DAAs to optimize clinical outcomes and potentially shorten the duration of overall therapy and the second line combination strategy in patients failing DAAs. We’re considering options in both Europe and the United States and we’re aggressively planning for our next study which we expect to commence in the second quarter of 2015. There is a potential to begin earlier in 2015 but this depends on the speed of our dialogues with regulatory authorities and input from key opinion leaders. Let's switch gears now to RG 012 and the upcoming Clinical Map Initiative timelines. RG 012 is an anti-miR targeting microRNA 21 for the treatment of Alport Syndrome, a life threatening genetic kidney disease with no currently approved therapy. The disease is driven by genetic mutations and 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 therapeutic 21, increased fibrosis and progressive loss of renal function which leads to head stage renal disease requiring dialysis or kidney transplantation. Since our last quarterly call we have made steady progress in this program. We’re pleased to initiate our ATHENA Natural History study of disease to learn more about the actual progress of Alport Syndrome by documenting the change in certain renal biomarkers and glomerular filtration rate or GFR in Alport Syndrome patients. Data from the ATHENA study will provide the clinical basis of the design of a Phase 2 study to monitor the therapeutic effect of RG 012 on the decline in renal function and time to end stage renal disease in Alport Syndrome patients. We’re currently enrolling patients in ATHENA and working towards filing an investigation on new drug application. RG 012 has received orphan drug designation from the U.S. FDA and we filed a similar application with the European authorities. Under our clinical math initiative we expect to evaluate RG 012 in healthy volunteers in a Phase 1 study expected to commence in the first half of 2015 and the Phase 2 proof of concept study in Alport Syndrome patients thereafter. Next week we plan to report additional preclinical data on RG 012 at the American Society of Nephrology Meeting being held November 11 through the 16th in Philadelphia specifically we will present preclinical combination data of RG 012 with an angiotensin converting enzyme or ACE inhibitor. ACE inhibitors are emerging as a standard of care in patients with Alport Syndrome used to treat proteinuria or abnormal amounts of protein in the urine, an indicator of chronic kidney disease. Together with the key opinion leaders we believe that ACE inhibitors are not sufficient to treat the actual progression of Alport Syndrome, the preclinical combination data will be important to demonstrate the utility of adding a microRNA therapeutic to this emerging standard of care. To summarize, we’re entering a very busy period focused on advancing our clinical portfolio with both RG 101 and RG 012 and the rest of our growth portfolio. Let me now turn the call over to Dan to review of our financials. Dan?

[Dan Chevallard:]

Thanks Paul. During the third quarter of 2014, we maintained our strong financial position and entered the quarter with $94.1 million in cash and cash equivalents and short term investments. We recognize revenue of approximately $1.1 million in the third quarter of 2014 compared to revenue of $6.1 million for the same period in 2013. Consistent with prior periods revenues primarily reflect the amortization of upfront payments received from our strategic alliances and collaborations which we recognized over our estimated period of performance. Our research and development expenses were $10.2 million in the third quarter of 2014 compared to $7.1 million for the same period in 2013. This increase was primarily driven by costs associated with our Phase 1 clinical study of RG 101, initiation of our ATHENA Natural History of Disease study in Alport Syndrome patients, IND enabling costs for RG 012 and a continued advancement of other therapeutic programs. We expect our research and development expenses to continue to increase as we initiate additional clinical studies and IND enabling or other regulatory filing activities in the future. Our general and administrative expenses were $2.6 million in the third quarter of 2014 compared to $1.9 million for the same period in 2013. This change was primarily driven by an increase in salaries and related employee costs and other operating expenses associated with general business activities. Our net loss for the third quarter of 2014 was $9.8 million compared to a net loss of $2.2 million for the same period in 2013. Our resulting basic and diluted net loss per share was $0.23 and $0.26 respectively for the third quarter of 2014 compared to a basic and diluted net loss per share of $0.05 and $0.07 respectively for the same period in 2013. As Kleanthis mentioned earlier on the call we’re pleased to have closure public offering of common stock earlier in the week and have increased our cash guidance in 2014 with greater than $150 million in cash, cash equivalents and short term investments. With that I will turn it back over to Kleanthis to wrap up the call.

[Kleanthis Xanthopoulos:]

Thank you, Dan. We’re very pleased with our progress over the last quarter in recent period and I'm excited about the opportunity we have to create a new and major class of drugs with our proven technology platform. We look forward to reporting additional progress at the Asian Medical Meeting and at the Credit Suisse Healthcare Investor Conference later in the year. Operator we’re ready to take questions. Thank you.

[Operator:]

(Operator Instructions). And our first question comes from Eric Schmidt with Cowen. Your line is open.

[Eric Schmidt:]

Just first on RG 101, I know you have committed to the Phase 2 combo studies starting in the second quarter, I guess I'm just kind of curious as to how you choose or how you think about choosing the right combination for RG 101 at this stage and how that sort of filters into your decision and whether take this into a first line setting or refractory setting or both?

[Kleanthis Xanthopoulos:]

Obviously first of all scientifically given how the oligonucleotides are so different and metabolize so completely different and small molecules, we don’t anticipate any problems combining with any of the heterocycle based direct acting anti-virals and as such basically we can pick and choose from all of the existing opportunities. It will depend on two things, one the availability of the particular DAA in the site or the country that we’re going to be doing this study and two on discussions that we’re having or potentially combining with certain pharmaceutical companies and these discussions are ongoing. There is a potential that we’re going to try to test with as many as possible and those are the things that are we’re now fine tuning.

[Eric Schmidt:]

And then maybe switching over to Alport Syndrome and the ATHENA trial. Is there anything you can learn from the Natural History Study that kind of informs you on the role of miR-122 in this disease or any connection between that microRNA and what's happening in patients, so is it purely just to see how patients perform overtime with kidney function.

[Paul Grint:]

So hopefully it's both of those, so one of the key goals of study in a prospective fashion is to follow these patients and use and look at end points of both measured and estimated GFR and obviously that’s going to be important for us in a rate of decline and look at these methodologies and contemplate the use of those in Phase 2. Now together with that we’re taking multiple both blood and urine samples from these patients to look at some of the known and recognized biomarkers but also to look at microRNA signatures as well and so we hope that maybe there is something there that we can see that will educate us as well.

[Eric Schmidt:]

Last question just on the upward side, I think it was you or Neil who mentioned ACE inhibitors are becoming more of standard care there. Do you know in your add-on models whether you’ve additive or synergistic activity with an ACE background?

[Neil Gibson:]

That will be presented at the ASN, Paul alluded to the next what is it 7 or 8 days?

[Paul Grint:]

Yes, in the next week.

[Operator:]

Thank you. Our next question comes from Jim Birchenough with BMO Capital. Your line is now open.

[Jim Birchenough:]

Just following-up on the earlier question, just in terms [Technical Difficulty].

[Kleanthis Xanthopoulos:]

Operator maybe we should take the next question and when Jim gets back online we will reconnect him.

[Operator:]

Okay. Our next question comes from Alan Carr with Needham & Company. Your line is now open.

[Alan Carr:]

Quick one, can you clarify, you were talking about a dual track earlier, one on was combination with the DAA, presumably (indiscernible) and second one also combo with DAA but in patients who failed it, just DAA alone up?

[Kleanthis Xanthopoulos:]

That is correct Alan.

[Alan Carr:]

And then the other question, can you I missed the beginning of the call, but can you comment on I guess big picture about relationship with pharma here and your overall strategy maybe a transition towards doing, trying on more programs on your own. I'm wondering what -- you know the GSK collaboration ended, wondering what you get back from that? Can you give me an update on that? Thanks.

[Kleanthis Xanthopoulos:]

Let me start with the GSK, basically all of the 122 related programs and activities are now fully owned by Regulus, as is all the activities around microRNA 155 that was nominated as a collaboration target a couple of years ago. So, we have the total control over both of these programs right now.

[Alan Carr:]

They pictured you, you see yourself transitioning from away from these collaborations to independent development?

[Kleanthis Xanthopoulos:]

That’s our goal for RG 101 at least for the Phase 2s that we’re outlining right now so we like to combine and we think RG 101 has a very strong basis and a legacy as a program to be combined with just about every direct anti-viral. So we’re going to be doing this experiments in the Phase 2 that we just outlined independently of the collaboration at least at this stage at least.

[Alan Carr:]

How many of these programs do you think you can operate in the chronic and parallel?

[Kleanthis Xanthopoulos:]

Let me not comment, we’re in the middle of all these discussions with KOLs and internally that’s part of the reason why we are updating our Clinical Map Initiative because RG 101 has with that data behind us demands a lot of attention as it should, so we’re working through all of these details. Any more comments?

[Paul Grint:]

I think if we from the Hepatitis C standpoint, this data is new. It was just over two weeks ago and clearly as Kleanthis has outlined we based on what we know about the molecule we have the opportunity to combine this with a lot of different molecule. It's an interesting time of year within the last month there has being a new combination approved in Hep C, AASLD starts later this week, I'm sure there is going to be lots of new information there and so clearly our goal is to improve aggressively into Phase 2 but we’re at a point in time where the landscape is changing quickly and where we’re obviously working with some key opinion leaders to take that into account as we design our programs.

[Alan Carr:]

Are you thinking actually beyond RG 101 and 012, how many programs do you think -- you’re not committing I guess to how many beyond those two that you will be able to carry on in particular going forward?

[Neil Gibson:]

We have obviously multiple programs in the portfolio and we have always being looking at managing a steady state of upto 4 to 6 programs as we mature a portfolio.

[Operator:]

Thank you. Our next question is from Jim Birchenough with BMO Capital. Your line is open.

[Jim Birchenough:]

Maybe I will just focus on what's meant to be learned from the RG 101 Phase 1 and what the timelines will be for key milestones like sustaining viral responses that sort of thing, could you maybe layout the timelines for data from the Phase 1 we will see going forward?

[Paul Grint:]

So I think the news we announced today was that we have obviously completed the enrollment of the 4 milligram per kilogram dose cohort. So the original protocol was designed in essence for eight week to follow-up for these patients and so as you can do the simple math from now on and we stated we obviously intend to report at least that component of the study both for the 2 milligram per kilogram and the 4 milligram per kilogram HCV treated patients in the early part of next year. We have amended the protocol so we can continue to follow those patients upto six months, I mean clearly those folks that have gone below the limits of quantification in the treatment course we’re very interested to see the durability of that response. And as we have stated before, you know our goal is to at least from the Hepatitis C standpoint to be able to present a more complete picture of that at the appropriately medical meeting in the first half of next year.

[Jim Birchenough:]

And maybe just a follow-up just in terms of what we have learned so far with 4.1 log reduction in such a quick period of time. Is there anything for modeling, the kinetics of the decline in viral load that would suggest that you might have success at shortening course of therapy when added to other DAAs? Is there any way to model out what you think the additive effect might be and how might you be able to shorten the course of therapy by adding RG 101?

[Kleanthis Xanthopoulos:]

Yes, Jim, if you look at the individual patient response to RG 101, you will see that we have significant responses by DAA that continue to be sustainable reach the maximum on average a day 29 and then for the ones that we just said before, the ones that have reached the limit of quantification they continued to stay there almost a month after that at least the three most advance patients. So if you take day 8 as an example and you see a response of 3 log and above and you’re then the direct anti-viral at some point between day 1 and day 8 with a rapid decline of the viral kinetics following a good direct anti-viral, you would expect to see most of these patients reaching below the level of quantification in that timeframe. So you extrapolate that to the course of therapy and there is reasonable expectations of why you may reach 8, 6 or potentially even 4 weeks that will be sufficient.

[Operator:]

Thank you. Our next question comes from Liana Moussatos with WedBush. Your line is open.

[Liana Moussatos:]

When do you expect to have human proof of concept results disclosed for Alport and then are there any mutations or probably morphisms and miR-122 that could affect RG 101 binding?

[Paul Grint:]

I mean there is no reported changes in the miR-122 sequence in humans that we have being able to find. So we don’t anticipate there is any potential impact of mutation or a polymorphism on miR-122 that would impact RG 101 binding to that microRNA.

[Kleanthis Xanthopoulos:]

And virtually Liana, all genotypes and all clinical isolates that we have looked at have identical binding sequences for 122. So not only we don’t see any variations on the microRNA but we don’t find any variations on the target on the virus [ph].

[Paul Grint:]

So to answer your question, our goal is to commence the Phase 2 proof of concept study in the fourth quarter and next year and so obviously based on what we see from the Natural History Study now with respect to the timing that we got to follow our patients out, I think we’re looking probably in about the 2017 timeframe to establish the clinical proof of concept.

[Operator:]

Thank you. Our next question comes from Bill Tanner with FBR Capital Markets. Your line is open.

[Bill Tanner:]

Paul, I had a couple for you, as it relates to the RVR at four weeks I guess on the day it came out there were some folks that were wondering about the competitiveness versus the DAA and obviously at 57 weeks you had a better RVR, I think you talked about the derivative administration and the mechanism of action for 101. But I'm just curious if you think maybe the drug is caught up over the ensuing four weeks, the observation at 57 weeks and if not then what would you view as competitive RVR?

[Paul Grint:]

I mean obviously not sure at this point, we’re following the people out and we will have the answer to that in the early part of next year. I'm ID [ph] trained and there is what simplistic thinking the way we like to think is if you, you know in chronic disease it's like this, for infectious disease is if you can combine therapeutics with different modes of action generally you get a much better response in terms of why the (indiscernible) replication or killing bacteria that you want to get rid of. So I think the good news for us is that we have got a novel mechanism, it's targeting a host factor that you’ve heard, it's potentially (indiscernible) and the good news from at least the limited information we have is that prior response to therapy doesn’t seem to affect the outcome. So we’re in a very unique position here I think to combine RG 101 with a number of different potential agents and time will tell with respect to you know the outcome of that and our ability to shorten treatment courses.

[Kleanthis Xanthopoulos:]

Bill, Let me also clarify so that we’re comparing apples-to-apples here. All the studies that I’ve done with direct anti-virals including the most successful ones, OLYSIO and Sovaldi. They did not -- as monotherapy they had between 3 and 7 days and that’s for very specific reason, the FDA demanded that because in monotherapy again you don’t want to expose the virus with single agent because of potential resistance onset. So it's impossible to compare RG 101 single dose to a monotherapy because they are RVRs where were not remarkable, the ones that you’re referring they were always done in combination with rivo and interferon originally.

[Bill Tanner:]

Yes didn’t want to blame unnecessarily the RVR observations for 101 yet because I guess the proof is in the pudding, it's more like when you’ve data for the combination or whatever and then maybe in larger number of patients. Second question I had maybe Paul is, I guess Kleanthis mentioned earlier about maybe a probably no expectation that there would be any kind of drug, drug interaction with other DAAs, what's the contemplation then as it relates to maybe differential efficacy of 101 with the DAAs and the point being is that it's fine if there is not a drug-drug interaction but as one begins to look at combining it with other DAAs and studies need to be done. How are you guys thinking about whether you’re going to see some kind of differential combination effect?

[Paul Grint:]

Well that’s exactly the discussions we’re having now with some of the key opinion leaders to help us guide us with regard to, you know we have a lot of options and drugs out there what would be a priority list of those options, what are the other variables that we might want to look at in a Phase 2 study such as we talked about such as shortening the duration of the therapy. So those are all ongoing discussions right now.

[Operator:]

(Operator Instructions). Our next question comes from Christopher James with Brinson Patrick Securities. Your line is open.

[Christopher James:]

Just a quick question, regarding to the two paths, do you plan a position RG 101 across continued position across all genotypes or is there a path to specifically target GTE-3 patients and do you anticipate 101 in being investigated in cirrhotics and/or HIV co-infected patients in Phase 2?

[Kleanthis Xanthopoulos:]

The success with RG 101 on non-genotypes and treatment history is actually creating some interesting challenges for us in choosing all of the above possibilities that you outlined. We’re going to a little more after all of the conversations that we’re having and of course going into AASLD we have a lot of meetings planned with KOLs but I can tell you that most likely from at least my point of view and take that as preliminary outline, the objective to combine it as a first line and with an endpoint to certain therapy. We will probably focus on naïves but secondly line would be very interesting into looking relapse -- potentially to difficulty to treat patients such as coinfected or cirrhotics.

[Christopher James:]

And do you think there is a potential to, and I know you’re using the 8 milligram dose in the first part of the Phase 1 study, is there a potentially use that to dose up to 8 milligrams per kg in the future studies?

[Paul Grint:]

So in the single dose part of the Phase 1 study, we did dose up to 8 milligrams per kilogram as a single dose. We had the ability to dose higher but frankly we choose not to because as we looked at some of the pharmacodynamic markets both cholesterol and alkaline phosphatase and no healthy volunteers, we saw changes that were pretty much maximal between 2 milligrams and 4 milligrams per kilogram and that information that helped us select 2 milligrams per kilogram as the initial dose -- dose initial cohort in Hepatitis C patients. So we stopped because we felt that we covered the doses that were needed to have a biological effect. I think we have the ability to go higher but at this point clearly we believe based on the information we have seen the 2 milligram and 4 milligram per kilogram dose in Hepatitis C patients is in the right range based on pharmacokinetic data but also based on the interim data that we showed as well. So at this point in time we don’t have intentions to go higher but we do have the ability if we needed to.

[Kleanthis Xanthopoulos:]

That’s exactly, right. Just to clarify because of an excellent and safety and tolerability profile we have the ability to go to 8 and 16 mix per kg if we wanted to do. Obviously we’re waiting for 4 mg per kg data to see how -- what response we are seeing there, if indeed that matches the pharmacokinetic profile that Paul just alluded to and the flexibility that we have will of course, it will be exercised depending on the patient population, if we have to go for higher doses in cirrhotics for example, the beauty is that we do have the safety and tolerability to go there. So we will take one step at a time and we will decide on the dose depending on the specific (indiscernible) we’re going to be treating.

[Operator:]

Thank you. And at this time I'm showing no further questions. I would like to turn the call back over to Kleanthis for further remarks.

[Kleanthis Xanthopoulos:]

Thank you all again for joining us on the call. We’re very excited as you can tell about the future of our company and microRNA therapeutics in general and look forward to reporting more progress soon.

[Operator:]

Thank you. Ladies and gentlemen that concludes today's conference. Thank you for your participation. You may now disconnect.