Regulus Therapeutics Inc (RGLS) 2015 Q3 法說會逐字稿

Good afternoon, ladies and gentlemen, and welcome to the Regulus Therapeutics third-quarter 2015 financial results conference call. My name is Taria, and I will be your coordinator for today. I would now like to turn the call over to the Company. Please proceed.

Thank you, and good afternoon, everyone. This is Amy Conrad, Senior Director Investor Relations and Corporate Communications, and I would like to welcome you to our financial results call for the quarter ended September 30, 2015.

With me today from Regulus are Paul Grint, M.D., President and Chief Executive Officer; David Szekeres, Chief Business Officer and General Counsel; and Mike Huang, M.D., who recently joined us in late August as Vice President of Clinical Development. So welcome to Mike.

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 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 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.

Now, I'll turn the call over to Paul.

Thank you, Amy. Welcome, and thank you for joining us. Since becoming CEO of Regulus two quarters ago, I've spent time reflecting upon all facets of the Company -- where we've been, where we are today and where we are headed.

Last month, we celebrated the third anniversary of Regulus being a publicly traded Company. Since that important event, we have focused our efforts on continuing to build the leading microRNA therapeutics Company, and we've accomplished many goals along the way. We nominated three candidates for clinical development, demonstrated human-proof concept, grew our clinical pipeline and biomarkers platform independently and with our partners, all while continuing our scientific leadership with publications in notable journals and presentations at key medical meetings.

These achievements have led us to a favorable position today. We have a well-balanced portfolio focused on validated microRNA targets: an exciting wholly owned lead asset in RG-101, which is our primary focus; an orphan disease opportunity with RG-012 to treat Alport syndrome; and a third candidate, RG-125, that is progressing well towards the clinic.

All told, the lifeblood of Regulus has been and will continue to be the cutting-edge discovery and research effort that enabled our lead candidate, which we hope will have meaningful impact on patients' lives.

In addition to advancing RG-101, RG-012 and RG-125, we expect to nominate at least one candidate for clinical development each year. We are currently working on multiple therapeutic targets where we believe we can engineer anti-miRs with a high therapeutic index that are matched with the right delivery approach. In the coming quarters, we look forward to sharing our progress on this important work.

Now let's turn to our recent news on RG-101, our wholly owned GalNAc-conjugated anti-miR targeting microRNA 122 for the treatment of HCV. Earlier this week, we announced the development expansion of RG-101 through a clinical collaboration with GlaxoSmithKline, or GSK, with the goal 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 2 study evaluating the combination of RG-101 and an oral tablet formulation of GSK-175, an investigation on 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 a once-a-day dosing, with the potential to prolong PK/PD activity. We believe these attributes make GSK-175 well-suited for combination with RG-101.

The primary endpoint of the Phase 2 combination study is to evaluate the potential to achieve sustained viral responses post treatment with a single subcutaneous administration of 4 milligrams per kilogram of RG-101 in combination with daily oral administration of 20 milligrams of GSK-175 for up to 12 weeks' treatment in treatment-naive patients chronically infected with HCV genotypes 1 or 3.

Regulus is responsible for conducting the study, which is planned to begin in the first quarter of 2016. For the first time, this study design offers Regulus the ability to investigate one subcutaneous administration of 4 milligrams per kilogram of RG-101 plus daily oral dosing with direct-acting antiviral for a fixed total treatment period, which we are calling our open-face-sandwich design.

While the Phase 2 open-face-sandwich 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 ability to have a very long apparent half-life, potentially weeks to months. And LAPs have been successful for indications such as HIV where sustained release is critical.

We believe that the concept is developing a long-acting HCV therapy that can be administered in a single visit is potentially disruptive to the current treatment landscape. We believe an LAP-formulated therapy will improve patient compliance through reduced dosing intervals and potentially extend opportunities for therapeutic intervention. The LAP formulation of GSK-175, once developed, may be used in additional studies together with RG-101 following completion of the planned Phase 2 open-face-sandwich study.

This GSK clinical trial collaboration is just one of the many approaches we are actively pursuing with RG-101. On our last call we announced the initiation of our four-week Phase 2 sandwich study to evaluate one subcutaneous administration of 2 milligrams per kilogram of RG-101 given on day one, 28, or four weeks, and given on days one, 28 and four weeks of either Harvoni, Alessio and Piacenza. And then one more subcutaneous administration of 2 milligrams per kilogram of RG-101 given on day 29.

Following completion of the dosing period, patients will be followed for 48 weeks to investigate sustained viral responses. The goals of the study are to investigate the potential to significantly shorten the course of therapy, improve patient compliance with our subcutaneous dosing regimen and possibly improve upon high viral cure rates.

Previously, we had discussed the expectation to report interim data from the Phase 2 sandwich study before the end of this year, which we anticipated to be sustained viral response data four weeks following conclusion of dosing, or SVR-4. Today, we need to move our timelines out a bit due to longer-than-anticipated regulatory paperwork in some of the participating countries. We now expect to report interim data early in the first quarter of 2016 and SVR-12 results in the second quarter of 2016.

We believe that the sandwich study and the potential single-visit regimen with GSK represent reasonable opportunities for RG-101 in a front-line setting in the ever-evolving HCV landscape. In addition to front line, we believe there may be an opportunity for RG-101 in a second-line setting to treat certain patient populations with unmet medical needs, such as DA failures and those with severe renal compromise.

To address these needs, we're conducting additional clinical studies for RG-101 to investigate its potential in the second-line setting. We are also conducting pre-clinical studies to round out our virology package to support work in these patient populations. For example, we're conducting in vitro combinations of RG-101 with DAAs for multiple classes and DAA-resistant HCV variance.

To wrap up on RG-101, let's touch on the catalysts coming up through the end of this year and into 2016. In two weeks, we're pleased to present additional updates from our Phase 1 study of RG-101 in the general plenary session talk at the American Association of the Study of Liver Diseases, or AASLD, meetings. In the published abstract, we reported that at 28 weeks post the single administration of RG-101, 6 out of the 22 patients have undetectable levels of HCV RNA, which we believe is an encouraging result that reinforces the sustained and prolonged effect of RG-101.

In early December, we will give another presentation on RG-101 at the [HEPTAR] meeting primarily focused on our biomarker findings from the completed Phase 1 study. And next year, we have a steady stream of data to report. Interim SVR 4 results from the Phase 2 sandwich study are expected early in the first quarter, and SVR 12 results from the same study are expected in the second quarter.

In addition to these key data updates, we will advance the program with the start of key clinical studies. In the first quarter, we expect to initiate an IND opening clinical study in the US and the Phase 2 open-sandwich study with GSK to advance our understanding of the potential for a single-visit HCV therapy.

With that, I'll turn the call over to Mike to discuss our recent progress on our second microRNA therapeutic, RG-012. Mike?

Thanks, Paul, and good afternoon, everyone. As Paul mentioned, we have made significant advances in our RG-012 program during the third quarter and recent periods. RG-012 is an anti-miR targeting microRNA 21 for the treatment of Alport syndrome, a life-threatening genetic kidney disease with no approved therapy.

The disease is driven by genetic mutations in the type 4 collagen family of proteins. The impact of the mutation on the collagen gene results in disruption to the structure of the glomerular basement membrane, increased expression of microRNA 21, increased fibrosis and then a progressive loss of renal function, which ultimately leads to end-stage renal disease requiring dialysis or kidney transplantation, often by early adulthood.

Today, we are pleased to announce an important milestone in the maturation of the RG-012 program. We have recently completed our first-in-human Phase 1 clinical study of RG-012, which positions the program favorably to advance into Phase 2. As a reminder, the Phase 1 clinical study was conducted in the United States as a randomized, double-blind, placebo-controlled, single ascending dose study to evaluate the safety, tolerability and pharmacokinetics of subcutaneous dosing of RG-012 in healthy volunteers.

A total of 40 healthy volunteer subjects were enrolled, and RG-012 was found to be well-tolerated. No serious adverse events were reported, and all 40 subjects successfully completed the study. Clinically, we're off to a great start with this program, and we look forward to advancing our plans to achieve human proof of concept with RG-012.

In addition to the Phase 1 update, I'd like to provide some commentary on our ongoing global Alport syndrome natural history study called ATHENA. Because so little is known about Alport syndrome, 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 rate, or GFR, in these patients.

Currently, we have 13 clinical sites open across the globe that are currently actively recruiting our patients. Recruitment is going very well. We have approximately 80 patients currently enrolled. Data from the ATHENA study, coupled with the results from the Phase 1 study in healthy volunteers, will provide the clinical basis for the design of a Phase 2 study to evaluate the therapeutic effect of RG-012 in patients with Alport syndrome.

This is a very exciting and important time in our Alport syndrome program. To our knowledge, this Phase 2 study, which we expect to initiate in the first half of 2016, would be the first-ever prospectively designed, randomized, double-blind, placebo-controlled study to be conducted in this indication.

To complement our clinical work on this program, we have a well-characterized, pre-clinical package on RG-012 that we are discussing at the American Society for Nephrology Kidney Week taking place this week in San Diego. At the meeting, we are pleased to present three posters. First off, we will present pre-clinical results demonstrating the favorable pharmacokinetic and toxico-kinetic results of RG-012, which supported the recently completed Phase 1 trial in healthy volunteers and which will support future evaluation of RG-012 in Alport syndrome patients.

Secondly, we will present the results describing a novel methodology developed by regular scientists that allows for direct measurement of microRNA inhibitions by determining the displacement of a microRNA from actively translating polysome complexes.

And finally, we will present data from our Regulus microMarkers division that highlights the discovery of urine micro biomarkers in a pre-clinical model of Alport nephropathy.

In addition to the updates we are providing this week at kidney week, we have a few upcoming goals for our Alport syndrome program that I'd like to mention. Looking ahead, we are working towards initiating the Phase 2 proof of concept study in the first half of 2016. In addition, we plan to submit data from our ATHENA study in a future medical meeting with the goal of sharing our increased knowledge of this little-known disease.

Overall, this program is maturing very nicely, and we're excited about our opportunity to advance the science in this field and potentially provide therapeutic benefit in an orphan disease such as Alport syndrome in indications with no currently approved therapies.

So with that, I'll turn the call over to David to provide the numbers for the quarter. Following that, Paul will wrap up the call. David?

Thank you, Mike, and good afternoon, everyone. In addition to our scientific progress, we also had an exciting quarter in a recent period on the business and financial front. We increased our investment in RG-101 to our clinical trial collaboration with GSK and realized the full economic value of our biomarker collaboration with Biogen, which we announced last week. The level of interest in our microRNA expertise remains high, and we look forward to continuing to execute on our plans.

Turning to our financial results for the most recent period, we ended the quarter with $131.7 million in cash, cash equivalents and short-term investments. We recognized revenue of approximately $1.9 million in the third quarter 2015, compared to $1.1 million in the same period 2014. This includes revenue received from Biogen in regards to achievement of the fourth and final milestone in our research collaboration to identify microRNAs as biomarkers for MS. We are pleased to have realized the full economic value of the collaboration, earning an aggregate of $3.7 million in payments.

Additional revenue in the third quarter of 2015 included $900,000 for research services provided under our collaboration and license agreement with AstraZeneca, in addition to the continued amortization of upfront payments received from our strategic alliances and collaborations, which we recognized over our estimated period of performance.

Our R&D expenses were $11 million in the third quarter of 2015, compared to $10.2 million for the same period in 2014. This increase was primarily driven by 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 for the remainder of 2015 compared to 2014 as we advance our ongoing clinical and pre-clinical forecast.

Our G&A expenses were $4.2 million in the third quarter of 2015, compared to $2.6 million for the same period in 2014. This change was primarily driven by an increase in salaries and related employee costs, including non-cash, stock-based compensation.

Our net loss for the third quarter of 2015 was $13 million, resulting in a basic and diluted net loss per share of $0.25, compared to a third-quarter 2014 net loss of $9.8 million, resulting in a basic and diluted net loss per share of $0.23 and $0.26, respectively.

Looking toward the end of the year, we have the potential to realize an important goal. If AstraZeneca initiates a Phase 1 study of RG-125 in humans, Regulus will be eligible for a $10 million milestone payment. In addition to this business goal, we expect to maintain our strong financial position and end the year with greater than $100 million in cash, cash equivalents and short-term investments.

With that, I'll turn the call back over to Paul for closing remarks.

Thank you, David. As you've heard today, we're pleased with our recent accomplishments. We've expanded development of RG-101, advanced RG-012 through Phase 1 and realized the full economic value of our biomarker collaboration with Biogen. We also continue to advance RG-125 with AstraZeneca, which is planned to enter the clinic before the end of the year, and we continue our pre-clinical work across multiple targets and disease areas of interest.

These accomplishments reflect our steady progress in building a leading microRNA therapeutic Company, and we are encouraged about where Regulus is headed.

With that, operator, we're ready to take your questions.

(Operator Instructions) Alan Carr, Needham.

Wonder if you could talk a bit more about the outcome from the RG-012 Phase 1 trial and any more details around the safety profile there. Any differences from what you saw with RG-101? And then also on the deal with GSK, are there any financial -- does each -- is each company responsible for its own costs? Thanks.

Alan, this is Paul. Let me just answer the second one quickly. The answer to your question is yes; basically, this is a clinical collaboration. Each company has obviously had their work they are going to do. Our part of it is to conduct the Phase 2 study and advance that clinically. And GSK's part is to continue to continue to advance the LAT formulation, let the formulation work and the relevant toxicology work and the Phase 1 work to evaluate that formulation. So it really is a collaboration; that's correct.

Alan, this is David. I'll take the second question. As you know, we don't typically break out spend by program. But what I can tell you is that we'll be spending a reasonable amount, and we won't break the bank on this study. I do think it's important to mention that the GSK study cost will be incurred in 2016, so it won't damage our year-end guidance.

Yes. And then, I'll ask Mike to talk a little bit more about the RG-012 Phase 1.

Sure. Hi, Alan. With regard to your question about the RG-012 study, overall the safety profile was very much as expected. We are still analyzing the data. The data's not quite final at this point. The majority of events were very mild, very much in line with what we would expect for the class of drug which is oligonucleotides. The PK profile was also very consistent with what we would expect for this class of drug.

So, the data overall are still being analyzed. However, the initial impression is that the drug was very safe, very well-tolerated. As I mentioned earlier, all 40 subjects were successfully dosed and they all completed the trial as scheduled. And we're very pleased with the safety profile thus far.

Great. And then one last one, your R&D spend dropped off quite a bit in 3Q. Should we expect that to remain at that level in the fourth quarter, or is it going to pick up again? What is your expectation there?

It is going to vary quarter by quarter, Alan. Because if you think about it -- so, we had -- if you go back to our first RG-101 study, you know obviously we spent quite a bit of money to start with that. Then the spend drops off as we are on the longer-tail follow-up now of patients. Obviously, as we've reported, it's less patients now.

We -- and, again, I think as you are all well aware, if you initiate clinical studies, you generally tend to have a lot more spend upfront as you get all the sites off the ground, all the different contracts, organizations that you're working with as you enroll the patients. And then as you follow them out, that spend tends to drop off because those specific frequencies also decrease.

The long answer, there isn't an easy answer to this question. It's going to vary. But, generally, we'll spend a bit more as through start-up activities of studies, and then it will tend to reduce over time.

All right. Thanks very much.

Bill Tanner, Guggenheim Securities.

Mike, just a follow-up on the 012 on the Phase 1. I'm wondering if you could comment on the dose that was -- I guess the -- I don't know if you were looking at [DMTV]. What kind of a dose patients were dosed up to as to whether or not that was a level that might be predicted to have some kind of a therapeutic effect, if you would have an idea of that at this point?

Yes, sure. We looked at a wide array of dosage strengths, starting from 0.5 migs per kig all the way up to 8 migs per kig. We anticipate that in the Alport syndrome population that 8 migs per kig is much higher than what we would need. We expect that the therapeutic dose will be at the lower end of that range. And this is based on what we know about the drug characteristics itself as well as a pretty extensive pre-clinical package that we have put together thus far.

But we think -- overall, we looked at a very wide array of dosage strengths. And, as we mentioned, it was safe and well-tolerated in the study. And we think that Alport syndrome patients should be dosed at the lower range of that dosage regimen.

Bill, this is Paul. It's interesting -- our philosophies on Phase 1 -- and you saw this with RG-101 -- are that we don't -- we obviously start fairly low. And starting dose is driven off of safety margins from the top studies. What we do is we very adequately sort of bracket the range that we think is going to be needed therapeutically. And we are actually pretty efficient at calculating and predicting that off many of our pre-clinical studies. For example with RG-101, we did single dose escalated up to 8 migs per kig. We could've gone to 16. We were ready to do it, but we made the decision to stop that cohort there and then move on to multiple dose and get into patients as soon as possible.

It's sort of similar here with RG-012. We've bracketed what we believe is a therapeutic dose range. We do look at the PK on an ongoing basis as we dose-escalate. So it's not just safety; we know what's happening in terms of drug exposures to the patients.

And so I think generally follow goes, it is not one of these situations where we can keep cranking up doses to get to an MPD because we could end up with weeks and weeks and months worth of work getting up to crazy-high doses, which is not going to be informative in any way, I think, for the program. And really our goal is particular for 012 and Alport patients -- Alport disease is to get to those patients as fast as we can.

Yes, so you guys are just trying to see if you can go what would be above the period of therapeutic dose and then hopefully see nothing there, and most likely need to back off, I guess, in a (multiple speakers).

Yes, that's exactly correct. Yes.

Okay. And then just on 101, Paul, just the rationale on the open-face sandwich? Just the one -- obviously twice the dose?

Again, just to remind you with RG-101, as we look to the pharmacodynamic markers, we basically saw that the -- at 2 milligrams per kilogram, we pretty much maxed out effect. And we then moved into the patients with at both 2 milligrams per kilogram and 4 milligrams per kilogram. Both of those doses were very well-tolerated. And obviously we talked about and will continue to present the results with regard to ACB responses.

The cohort side is more -- as we looked at the data, there wasn't an obvious dose response, if you like. And we discussed this at some length at the end of last year and earlier this year. But maybe some people got a sense that perhaps 4 migs per kigs was a little better than 2.

So it's -- frankly, this is the way to examine that. We're obviously generating data with 2 right now. And this study, since it's only going to be a single dose, we came to the decision that probably it would be a good idea to go with 4 migs per kig. milligrams per kilogram. That's sort of part of the rationale.

Yes, sorry, I guess my question was the rationale to go with a single dose rather than to do the initial dose and the DAA and then the subsequent dose.

Well, the goal of this is to get to a single-visit therapy, as we say.

Okay.

We are looking at -- we know -- obviously, we're reporting six-month data coming up. We know that in a proportion of patients as a single agent, we have a very long-term effect of RG-101.

The LAT formulation work that GSK has done is really incredibly elegant. You know, they can basically -- and this is what they've shown with the HIV-integrated inhibitor clinically and now show preclinically with GSK-175. In essence, is you can give -- it's an intramuscular injection of whatever concentration of drug -- that's to be determined. Basically, you emulate the equivalent of oral dosing for a period of many, many weeks just with that one injection.

So this technology and, in fact, the chemistry of the GSK-175 molecule lends itself to this formulation. So it's a pretty unique opportunity which, in discussion with GSK, we felt was a very important one to collaborate on and evaluate. You know, the concept is you come to your doctor, you have got hepatitis C. This regimen should be pan-genotypic, so everybody get into doing genotype testing. You have a subcu injection, an intramuscular injection and then it's basically come back in four months or six months and we'll test you to make sure that you're HCV negative.

Right, right. Maybe just last question. You mentioned one clinical candidate per year. Could you just give us an idea as to the characteristics of that as the Company matures? And so far, as opportunities that Regulus might be able to undertake on their own, just help us understand a little bit what's the screen on that. If there is a commercial screen or if it's really about the biology of the medicine.

That's a great question. We're taking several things into account right now, and I've talked to this before. We -- from the GalNAc delivery and liver target standpoint, we have obviously learned a lot with RG-101. And it's clear to us that GalNAc is an unbelievably effective way of delivering the hepatocytes. And so we are very actively looking for other microRNA targets in the liver because we know we can deliver. And there are -- at least, it looks as if there may be targets associated with important liver diseases. There are still unmet medical needs. So that's one potential focus.

I've also talked about as we have got the Alport study up and running, it's been a lot of work for us, but we have got -- we have built this clinical trial infrastructure now where we have really standardized very effectively measures both formally -- for example, with measured GFR through to biomarkers in patients with chronic kidney disease across multiple countries. And it's become -- and, in fact, it's right now, the American Society of Nephrology, there is a section on microRNA targets in chronic kidney disease. And there are a number of my Regulus colleagues actually attending that session. So we think that there are additional kidney diseases that also may lend themselves, and so we are actively looking at those from a research standpoint.

So I think the answer to your question is as we move forward, we're going to follow the science. Delivery is important, so we're going to focus on organs on where we know we can deliver. And then depending on the disease state and the number of other factors in the Company, we'll make decisions about whether we'll keep these molecules or potentially part with them. But we're very well-placed to move molecules into the clinic and get the clinical proof of concept.

Yes, right. Makes sense. Okay. Thanks very much.

Liana Moussatos, Wedbush Securities.

You mentioned having 80 patients enrolled in ATHENA and going to start the Phase 2 in the first half of next year. What do you need to get from Athena before you can start the Phase 2? And what medical meetings are you considering to present the ATHENA data?

Hi, Liana. This is Mike. From now until the anticipated start of the Phase 2 study, we're going to be looking very closely at the longitudinal data that's being collected in these patients. I think really the key with Alport syndrome is that it is a chronic kidney disease, and oftentimes you do need a fair bit of data on each individual patient. So what we're doing is we're following each of these patients very closely. They have visits approximately every three months. We are collecting a large number of biomarkers. We are calculating as well as measuring the glomerular filtration rates.

So what we're trying to collect here is as much longitudinal data on the natural course of the disease. And we want to be able to use this data and get a sense of how rapidly patients with Alport syndrome deteriorate over time and which biomarkers may be predictive of this type of decline. And so I think that's going to be really important at this juncture as we move ahead to design and initiate the next trial.

Now, I think your second question was regarding the medical meetings. That's still in discussion this point. We're looking at some topical meetings in the first half of next year. Once we have made a decision here internally, we'll certainly announce that and provide you all with the data.

And how many patients from Athena do you need before you can start the Phase 2?

That's a good question. I think we have a fair number of patients in the trial already, 80 patients. I think with 80 patients, we have a good amount of data and I think it really, again, comes down to the length of time for which each patient is in the trial. I think we are pretty close. We have patients at this point that have been involved in the study for over a year.

I think as we analyze the data, we're going to be doing additional data cuts later this year and next year and continuously looking at that. So we think over the next couple of months or so, we should have enough data to really make a fairly good, solid decision on the design of the next trial.

Thank you very much.

Christopher James, FBR and Company.

My first question is on RG-101. Could you maybe elaborate on the timeline for the LAP formulation and then the start of the single-injection study? And then I have a follow-up to that.

Yes, Chris, good afternoon. It's Paul. As I said in the script, it's our intention to start the Phase 2 study that we're going to run in the first quarter of next year. So that's basically the single injection of RG-101. And using the oral molecule, the GSK-175, is going to take us obviously most of next year to run that study and obviously get the results out.

At the same time, in parallel, GSK is moving forward with all the relevant work that needs to be done with the long-acting formulation to get it to a point where the next study we do is a combination of the two. I can't speak in detail today a timeline because obviously that's sort of proprietary to them as a company. But that's the plan. So there'll be a lot of activity next year, both with us conducting the clinical study and GSK moving their activities forward.

Okay, great. That's helpful. And then, why specifically did you choose 175, a non-nuc NS5B versus another mechanism for the open-sandwich approach in combination with 101?

In talking with GSK -- and they have a lot of expertise in the space of the long-acting formulation. There are certain characteristics, chemistry, structural characteristics in different molecules where they lend themselves to this long-acting formulation.

So this wasn't the case of always using this mechanism type of drug. It was a question of, okay, this molecule really lends -- based on GSK's experience really lends itself to be put into an LAP formulation.

So, for example, my understanding is that you probably can't do this for any of the commercially approved drugs that exist now. They don't have the right chemical characteristics. So it's really based on those characteristics, not on the mechanism of the drug.

Now, having said that, this is a pangenotypic molecule with good antiviral activity. GSK has reported the virology at ETHA last year, and then reported clinical data with two days of dosing at AASLD last year. And there was a good viral load drop and activity across different genotypes. So it's a good molecule for a pangenotypic approach.

Great, that's helpful, Paul. Really appreciate it. Thanks.

Jeff Chen, Cowen and Company.

Thank you for taking my questions; a couple if I may. In terms of the RG-101 Phase 2 combination data, will the SPR-4, the interim data, and SPR-12 primarily end point be announced via press release, or is this going to be at a medical conference?

Great question. Obviously, this is important data, and it is our intention to announce this via press release.

Part of the difficulty with medical conferences is the abstract deadlines -- the deadlines are so far in advance of the meetings that it's not always easy to coordinate things. So it's our intention to by press release.

Now, once we press-release, obviously, as we have done with RG-101 so far, we'll continue to put in abstracts at the major medical meetings. And absolutely it's our intention to provide appropriate updates at these meetings. It's important to do that. And that's where I think you -- we obviously get the ability to educate a lot of physicians and obviously understand their views with respect to where this therapy makes sense.

Right. Understood. Thanks. And in terms of the data itself, could you just describe what you would characterize as good data, then? Well, once we get to see the SVR-4 and SVR-12?

That's a difficult question. We'll know it when we see it. I mean, realistically, we've got to have very -- we've got to have high SVR rates. So if you're asking me if we saw a 50% SVR rate, no, I don't call that good data. We are really looking at around a 90% SVR level. That's where we need to be competitive.

Understood, understood. Okay. Maybe just one last one. In terms of maybe other partnerships for RG-101, are you contemplating other compounds, maybe one with a polymerase inhibitor or any other type of molecules that you might be looking at?

Yes, the answer is we're open to a number of things. What we've done with the current Phase 2 was to use the commercially available drugs. And the reason we designed the arms that we have is that we're using these to sort of representatives of mechanistic classes, if you like. Clearly, once we see this data, that will help us, I think, understand if potentially there are some drug classes that might be better combining with than others. So it's going to be data driven, so we will wait for the data.

Got it. Thank you very much.

Thank you. And at this time, I am showing no further participants in the queue. I would like to turn the call over to management for any closing remarks.

I'd just like to thank everyone for their time and their questions today. And look forward to talking with you early next year with the full-year results. Thank you.

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