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Regulus Therapeutics Inc. (NASDAQ:RGLS)

Q4 2013 Results Earnings Conference Call

February 27, 2014 5:00 PM ET

Executives

Amy Conrad - Director, Investor Relations and Corporate Communications

Kleanthis Xanthopoulos - President and CEO

Neil Gibson - Chief Scientific Officer

Dan Chevallard - Vice President, Finance and Accounting

David Szekeres - Chief Business Officer and General Counsel

Analysts

Jim Birchenough - BMO Capital Markets

Simos Simeonidis - Cowen & Company

Alan Carr - Needham & Company

Greg Wade - WedBush

Operator

Good afternoon, ladies and gentlemen. And welcome to the Regulus Therapeutics Fourth Quarter and Year End 2013 Conference Call. My name is Janie, and I will be your coordinator for today.

I would now like to turn the call over to Amy Conrad, Director, Investor Relations and Corporate Communications. Please proceed.

Amy Conrad

Good afternoon and thank you for joining us. On behalf of Regulus Therapeutics, I would like to welcome everyone to our conference call for the quarter and year ended December 31, 2013. I hope you've all had a chance to review today's press release. If you have not and you need a copy, you can visit our website at www.regulusrx.com.

Joining me on today's call are Kleanthis Xanthopoulos, Ph.D., President and Chief Executive Officer; Neil Gibson, Ph.D., Chief Scientific Officer; and Dan Chevallard, Vice President, Finance and Accounting. Also with us in the room is David Szekeres, our newly appointed Chief Business Officer and General Counsel.

During today's call, Kleanthis will provide introductory remarks, including an update on our corporate strategy and our outlook for 2014. Dan will summarize our fourth quarter and year end 2013 financial results, and Neil will provide an update on our microRNA therapeutic programs. Following your questions, Kleanthis will wrap up the call.

Before we begin, I would like to remind you that this call will contain 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.

At this time, I would like to turn the call over to Kleanthis.

Kleanthis Xanthopoulos

Thank you, Amy, and thank you for joining us this afternoon. 2013 was another good year for Regulus and our team has continued to solidify our position as the leader in the [killer] microRNA therapeutics.

Over the last and recent periods, we focused our efforts in advancing our pipeline towards the clinic to drive significant long-term value for the company and our shareholders.

Under our relative clinical strategy for 2013, we outlined several critical corporate goals that focus in identifying microRNA candidates for clinical development, advancing our pipeline in meaningful way enabling a smooth transition into clinical stage company.

Specifically, we set a goal of nominating two microRNA candidates clinical development, be in a position to file our first application with regulatory authority by the first half of 2014 and maintain a strong year end cash position to support this goals.

Today we are pleased to announce that we successfully exceed our Road to the Clinic goals. We have nominated two candidates for clinical development, RG-101 for the treatment of HCV and RG-012 for the treatment of Alport Syndrome, a life threatening orphan disease that is driven by genetic mutations.

Our RG-012 program underscores our internal focus on orphan disease and we hope continue to expand this portion of our clinical portfolio. We also maintain our strong financial position and exceeded our cash guidance thinking 2013 with $140 million in cash -- cash equivalent in certain investments.

Following completion of our [relative clinic] goals we are now ready to transition our microRNA therapeutic pipeline into the clinic. We successfully navigate entry and progressing through the clinical trial process we have developed our clinical mark initially.

This outlines a clear clinical corporate milestone side is necessary to advance our therapeutic pipeline over the next several years, leveraging our advanced technology platform, our strong strategic alliances and broad intellectual property state. We have marked the following goals with the first phase of this initially.

First, establishing a proof-of-concept with our RG-101 program which targets microRNA-122 for the treatment of HCV, which we believe maybe transformative for regulators in the field of RNA therapeutics.

Today we are one step closer to achieving this goal. We are pleased to announce that we recently received approval from the regulatory authority in the Netherlands to commence dosing in our Phase 1 trial of RG-101. Later on the call Neil will provide you with our clinical remark for RG-101 and the overall goals of our program

Second, in addition to establishing human proof-of-concept results we expect to initiate the Phase 2, I am sorry, Phase 1 clinical study of RG-012 for the treatment of treatment of Alport Syndrome in the first half of 2015. We are very excited about this program because it strengthens our internal focus on orphan disease.

A key component to advancing this program was the recent renewal of our strategic alliance with Sanofi in which we received an additional $10 million in equity investment, bringing the total ownership of Regulus to about 12%.

With this renewal we are now driving development of the RG-012 program and Sanofi also increase the interest in our oncology effort by retaining opt-in rights through the miR-21 program and gaining opt-in rights to our program targeting microRNA-221/222 for the treatment of hepatocellular carcinoma.

As you may recall, microRNA-221 has been an important microRNA target for us for sometime and it is considered one of the most validated microRNA target with an abundance for scientific leaders who are out there.

In 2010 we entered into the original strategic alliance with Sanofi around this project in fibrosis and expanded the alliances in 2012 for oncology target, they are now focus relationship on three programs with Regulus gaining a greater stake in development and great upside potential and commercialization milestone and royalty payments.

If Sanofi chooses to exercise its auction of any of this program they will pay us an auction exercise fee, reimbursement for a significant portion of our pre-clinical and clinical development cost on any of this program and in addition pay us milestones all the way to approval.

We’re also pleased regarding option to co-promote in the United States or receive royalty payments in the mid 10% to 20% range for any of these three programs. Currently, we are planning our clinical development for RG-012 and Neil will provide you with more information on this program and alport syndrome later on the call.

Third, by the end of 2014, we also expect to nominate the third microRNA candidate for clinical development. In order to achieve these goals in our clinical (inaudible) initiative, we expect to maintain our strong financial position and guide to amend 2014 with at least $7 million in cost.

And important component to achieving our goals and maintaining our leadership is recruiting the best talent. Earlier this month, we announced that David Szekeres join as Chief Business Officer and General Counsel and he will be key contributor member of our executive management team.

David brings over a decade of legal and deal-making experience within the global life sciences industry, most recently as Deputy General Counsel, Chief M&A Counsel and Assistant Secretary at Life Technologies Corporation. David’s transactional deal experience will be tremendous answer to our achievement as we continue to mature our company.

In closing, we had another good year with many achievements. We believe that with a backbone for these achievements is the potential of our emerging product class room based on microRNAs, a recently discovered class of non-coding RNAs that controlled the majority of genes in the human genome.

microRNAs have been found to be dysregulated in many if not all the stages that we have looked at and we believe that modulating them, they therefore provide a very good therapeutic utility. We believe our microRNAs therapeutics meeting in next wave of innovative RNA therapies and may have the potential to truly transform the field of drug discovery.

With those introductory remarks, I’d like to turn the call over to Dan Chevallard, our Vice President, finance and accounting for the review of our fourth quarter and year end 2013 financial results. Dan?

Dan Chevallard

Thank you, Kleanthis and good afternoon. In 2013, we managed our operating costs and working capital in line with our operating plan which allowed us to exceed our cash guidance for 2013, ending the year with $114 million in cash, cash equivalents and short-term investments compared to $98.1 million in 2012.

Turning now to our full year 2013 financial results. We recognize revenue of $19.6 million in 2013 compared to $12.7 million in 2012. Revenue in 2013 included approximately $15.4 million from the Sanofi collaboration and license agreement and $4.2 million from other strategic alliances and collaboration. Revenue during these periods consisted primarily of amortization of upfront payment received from these strategic alliances and collaborations, which we recognized over our estimated period of performance.

Total operating expenses were $37.4 million in 2013 compared to $25.3 million in 2012. Our research and development expenses increased $29.9 million in 2013 compared to $20.3 million in 2012. This increase was substantially due to costs associated with regulatory filing activities for RG-101 and other programs in 2013. We expect our research and development expenses to continue to increase as we begin -- as we began clinical studies and initiate additional IND enabling regulatory filing activities in the future.

Our general and administrative expenses increased $7.4 million in 2013 compared to $4.9 million in 2012. This was primarily due to administrative costs associated with the growth of Regulus as well as incremental costs associated with being a public company.

Our net loss for the ended December 31, 2013 was $18.7 million compared to a loss of $17.4 million in 2012. Our net loss in 2013 included total net non-cash charges of $1.1 million associated with the change in value of the amended and restated convertible promissory note originally issued to GSK in 2010.

In 2012, net loss included total non-cash charges of $4.7 million. These charges were primarily attributable to increases in the value of our common stock over the respective period.

We expect to finish 2014 with at least $75 million in cash, cash equivalents and short-term investments, which includes the recent $10 million equity investment from Sanofi received in conjunction with the renewal of our strategic alliance.

With that, let me now turn the call over to Neil to run an update on our recent scientific progress.

Neil Gibson

Thank you, Dan and good afternoon everyone. As Kleanthis mentioned early on the call, 2013 was another productive year for us. We are focused on scientific execution and believe that we achieved significant progress in advancing our microRNA portfolio towards the clinic.

We're also looking forward to advancing our newly launched Clinical Map Initiative of 2014 and beyond which focuses on RG-101 and RG-012 and a third clinical date could be potentially nominated before the end of this year. On today's call, I plan to focus my comments on RG-101, RG-012 and we’ll provide a general update on the advancement of the remainder of our microRNA portfolio.

In 2013, we made significant progress across our therapeutic pipeline. We announced today that we received regulatory approval to commence building in our Phase I clinical study for RG-101 a GalNAc-conjugated, anti-miR targeting miR 122 for the treatment of HCV.

At last year's American Association for the Study of Liver Disease or AASLD meeting, we presented data from preclinical study evaluating RG-101 for in-vitro and in-vivo, potency, pharmacokinetic/pharmacodynamics, toxicology and safety pharmacology and inhibition of HCV replication. These positive clinical data provided evidence for the favorable properties of RG-101. It’s potent, safe and the mechanism appears (inaudible) and no resistance having been observed to date.

In efficacy studies, we have shown single dose of RG-101, significantly reducing HCV viral load up to a 2 log reduction in a human chimeric mouse model infected with HCV genotypes 1a and our genotype 3a. Genotype 3a is considered a hard to treat genotype even with current direct-acting antiviral DAA therapies.

The viral load reduction up there is similar in potency to the oral DAAs in this model and the duration of action of their priority RG-101 supports the potential for once a month dosing regimen, which we believe maybe commercially attractive. This data and the favorable preclinical profile to date supports the advancement of RG-101 into the clinic.

The Phase 1 clinical study of RG-101 will have four parts. First, the single ascending dose study in healthy volunteers. Second, a multi-ascending dose study in healthy volunteer. Third, a single-dose drug-drug interactions study of RG-101 in combination with an approved DAA and healthy volunteer subject. And four, a single-dose study in HCV patients to assess the safety and viral load reduction, which is designed to demonstrate human proof-of-concept.

The primary objective of the Phase 1 clinical study of RG-101 is to evaluate safety and tolerability. The secondary objectives are to evaluate pharmacokinetics, viral load reduction and any impact on oral DAA that may have on the pharmacokinetics of RG-101.

Up to approximately 100 healthy volunteers and HCV patients are planned to be enrolled in this Phase I study. The study is being conducted in the Netherlands, and dosing is expected to commence in the near term. We continued to be encouraged by this program and believe that RG-101 has the potential to be a best-in-class host factor for the treatment of HCV.

Let me now turn to our second program poised for clinical development, RG 012, an anti-miR targeting microRNA-21 for the treatment of Alport syndrome, a life-threatening kidney disease driven by genetic mutations. Alport syndrome is caused by genetic mutations affect the type IV collagen family of proteins. The impact of mutation in the collagen gene results in disruption to the structure of the glomerular basement membrane, increased expression of miR21, increased fibrosis in the kidney, loss of renal function, which leads to end-stage renal disease and subsequent death.

This is a devastating disease with no approved therapy on the market. We are pleased with the preclinical profile of RG-012, and the results showing to date support our advancement of this compound into clinical development. At the American Society of Nephrology’s Kidney Week meeting last year, we presented preclinical data demonstrating treatment with anti-miR-21 candidate in a mouse model Alport disease that significantly decreased the rates of decline of renal fibrosis, restored the expression of the key microRNAs involved in maintaining renal function and increased the lifespan of the mice up to 50% depending on the genetic backgrounds of the collagen 4A3 deficient mice.

Today, we have a framework of the clinical map for our RG-012. In the third quarter this year, we plan to initiate a natural history of disease study, which will allow us to gather greater information about the actual progression of patients with Alport syndrome, as this is not well described in the current literature.

RG-012 maybe a transformative therapy for Alport syndrome patients, but the clinical and regulatory path is unclear. Our learnings from plan natural history of disease study and our ongoing discussions with the regulatory agencies will help us establish clinical endpoints for our upcoming trials amidst the unclear clinical path.

We do know that there is a preliminary biomarker of renal disease known as glomerular filtration rate or GFR, which may be an appropriate clinical endpoint. And we will continue to assess this as we learn more about the progression of disease through a natural history of disease study.

In addition to looking at GFR and other real biomarkers for clinical endpoint to our study, we also have the ability to look at other exploratory biomarkers. Additionally, through a Regulus microMarkers technology, we also have the ability to investigate microRNA levels in both the serum and the urine to help us refine the potential clinical endpoints.

Once we have identified appropriate clinical endpoints with our trials, we expect to conduct Phase 1 clinical study of RG-012 in healthy volunteers and transition to Alport syndrome patient’s to evaluate affects on inhibiting miR-21. Currently, we are manufacturing drug product and conducting additional toxicology studies prior to entering into clinical development with RG-101 in the first half of 2015.

This is a critical goal in our clinical map initiative. And we look forward to reporting progress on this exciting program over the coming year. We continue to make progress with our exploratory efforts to identify attractive new microRNA targets that fit with our internal expertise and align with our focus on oncology and orphan diseases.

We also communicated today our intent to nominate a third clinical candidate for development before the end of the year, which may come from these efforts or from a partner target or program. Over the last year, we have streamlined our strategic alliances, and believe that we strength in those relationships to help us advance candidates into clinical development.

We gained full control of RG-101 from GSK. We gained greater control of our RG-012 from Sanofi, and we announced today that we rebalance our efforts with AstraZeneca by terminating the miR-33 program for atherosclerosis and focusing on our miR-103/107 metabolic program and our miR-19 oncology program.

We and AstraZeneca choose to terminate a miR-33 program due to certain technical challenges with the program and increasing complexity in the competitive landscape for atherosclerosis. We continue to collaborate with AstraZeneca on additional targets, namely miR-103/107 for metabolic disease and miR-19 for oncology.

AstraZeneca also had replacement rights for the miR-33 target. We are pleased with this successful relationship we have build with AstraZeneca and believe that their continued commitment RNA therapeutic will enable us to build a meaningful clinical pipeline. We look forward to communicating additional progress from this alliance in the future.

Turning now to our proprietary portfolio, I would like to provide you with a brief update on the programs that fit within our focus on oncology and orphan disease. In our miR-10b program for the treatment of glioblastoma or GBM, critical experiments are still ongoing and we are currently assessing early microRNA candidates.

As we mentioned earlier in the call, with the recent renewal of our strategic alliance, Sanofi gained opt-in rights to our miR-221/222 program for the treatment of hepatocellular carcinoma. We have identified important lead candidates and are working to optimize our ability to deliver those lead molecules using listed formulations with the GalNAc conjugation technology that we are utilizing RG-101.

To close out the therapeutic pipeline review, we also continue to make significant progress with our biomarkers technology platform. Earlier this year we announced that we’re expanding our efforts here and established Regulus microMarkers and R&D division designing to support our growing therapeutic pipeline, our strategic alliance partners, and our collaborators, and which is aimed at identifying microRNA’s biomarkers for disease.

We have developed a highly reproducible proprietary platform for extracting, profiling and analyzing microRNAs and have successfully applied this platform to identify microRNAs that are disregulated compared to healthy in human samples. We plan to demonstrate the value of the Regulus microMarkers technology by identifying microRNA biomarkers in patient populations of specific indications, such as our miR-221/222 program for HCC.

In 2012, we formed research collaboration with Biogen Idec focused on the discovery of microRNAs biomarkers for multiple sclerosis. We are currently working out the next phase of our relationship with Biogen around biomarkers and hope to report additional progress in the near term.

To summarize, 2013 and the recent periods has been very successful for the advancement of our microRNA therapeutic pipeline. We have established a Clinical Map for RG-101 and RG-012 and look forward to reporting further progress over the coming year.

With that, I will turn the call back over to Kleanthis for closing remarks.

Kleanthis Xanthopoulos

Thank you, Neil. In closing, 2013 was an extremely productive year for us and we had a very good start for 2014. We are significantly matured as a company and ready to entertain those developments. We completed our goals in the road to the clinic and have launched our Clinical Map Initiative to clearly define our clinical plans. Under the initiative, we’ve mapped our very aggressive goals to rapidly advance our microRNA candidates in clinical development, which will drive long-term value for our shareholders.

Later this year we expect to demonstrate human proof-of-concept results from our RG-101 program, which we believe will validate our microRNA technology and maybe transformative for us in the overall RNA therapeutic space.

We also expect to further advance our second clinical candidate, RG-102 for the treatment of Alport syndrome by conducting a natural history of disease study and planning for a Phase 1 clinical study in the first half of next year.

Lastly, we expect to nominate a third microRNA candidate for clinical development by the end of 2014. With this important upcoming catalyst, we believe the 2014 will be another exciting year, as we advance our programs and continue to build a meaningful clinical portfolio.

With that, I would like to thank you again and we are now ready to take your questions.

Question-and-Answer Session

Operator

(Operator Instructions) The first question comes from Jim Birchenough from BMO Capital.

Jim Birchenough - BMO Capital Markets

Hi, guys, congratulations on all the progress. A couple of questions. Just first on the Alport syndrome program, I’m trying to get a sense of, over what period of time with this natural history of this new study, do you expect to learn what patient population the target, get there I guess a broad sense of the natural history to target in on some portion of it over a reasonable period of time. Could you just talk us through that?

Neil Gibson

Hey, Jim, this is Neil. We’re going to look at the progression of disease within Alport patients over minimum of 12 months going out for as long as 18 to 24 months.

Jim Birchenough - BMO Capital Markets

And are you looking at a certain subset patients that are pre-dialysis or earlier in the continuum or is it a broader study?

Neil Gibson

Yes. What we’re planning to do is look at patients who have Stage III chronic kidney disease, it’s thought that those patients have a reasonably consistent decline in [GFR] and would allow us to get an appropriate way of looking at the efficacy of the molecule. So we are going to try and reach this natural history study for patients in stage III chronic kidney disease and use those patients also in our proposed efficacy study.

Jim Birchenough - BMO Capital Markets

And then just a question on one-on-one, when you get to the point of testing in HCV patients, do you expect to enroll patients with failed, approved FDA’s like severity?

Neil Gibson

This has been done in the Netherlands. At the moment, it is likely that the patient population will either be sensitive or insensitive or naïve to interferon, but a number of the patients are not likely to have received the oral DAA that have been approved in the U.S.

Jim Birchenough - BMO Capital Markets

And what you think you might gain that type of experienced Neil?

Neil Gibson

Second half of this year is when we anticipate being able to get human proof-of-concept in HCV patients. In that study, we will have a mix of genotype 1 and genotype 3 patients. So we will get a real good handle on what the level of viral load reductions is in both these specific genotypes.

Jim Birchenough - BMO Capital Markets

Got it. And I guess I am just trying to understand in terms of getting a sense of activity in patients with failed existing DAAs that may require study in the U.S., when might that happen?

Neil Gibson

Yes. So that would be a potential design of a Phase 2 study. So that the single dose HCV study is likely to rebound in the second half of this year as I mentioned. So more than likely, the phase 2 study would be 2015 type of study.

Kleanthis Xanthopolis

One of the primary objectives of the study is to demonstrate pan-genotypic activity, say, if way obviously and well tolerated. So that’s the goal of these study. We expect to hit that milestone before the end of the year. And we’ll have a combination at least one DAA. The question you're asking about potential [robotic] failures, that’s going to be addressed in as Neil said after that probably in 2015.

And also to your first question to clarify the natural history disease study is going to be join in parallel with Phase 1. So they’re not going to be sequential of course. So we are going to continue that study as we are entering into Phase 1 which we’ll plan to be in the first half of next year.

Jim Birchenough - BMO Capital Markets

Kleanthis, I treat this as final question strategically, as you’re building out biomarker part of the business. How do you think about that as a separate revenue generating business and is that some thing that you think should stay part of the regulator, does it become a separate business, how are you thinking about that?

Kleanthis Xanthopolis

We’ve been very surprised with the success of the biomarker technology, Jim. So those are subject to intense discussions internally. Part of the broad experience that David Szekeres is bring to the table. He is understanding this part of our business quite well. So we’ll have a clear strategy over the next quarter or two that we’ll be able to communicate. But in the meantime collaboration with Biogen and another pharmaceutical companies are ongoing.

Our own networks in number of disease that we looking for biomarkers now in blood, serum and urine, giving us a very high level of confidence that this is a very, very valuable asset for Regulus that will find a way to ultimately monetize the bottom beyond what we’re doing now.

Jim Birchenough - BMO Capital Markets

Great. Thanks for taking the questions.

Kleanthis Xanthopolis

Thank you.

Operator

Our next question comes from the Simos Simeonidis from Cowen & Company.

Simos Simeonidis - Cowen & Company

Hi guys, thank you for taking the question. Counseling up on what Jim was asking on the clinical and commercial plan for RG-101. So I’m familiar you planning to start Phase II trials assuming the Phase I is successful in and you achieved those concept in the U.S. in 2015. Is that correct?

Kleanthis Xanthopolis

Simos, to clarify that, that’s a good question. Our stated objective is we want to demonstrate human proof-of-concept with 101. We have so many opportunities that I hope you got a glimpse from what Neil was saying on how microRNA is operating so many different diseases that we want to -- our objective is to ultimately find a home for someone who transfer pan-genotypic agent on top of our number of DAA oral agents that they are applying.

So we do not intend to (Inaudible) start a Phase II trial. We’ll counter their proof-of-concept, validate the approach and we already have started a number of discussions potentially from the appropriate home for RG-101.

Simos Simeonidis - Cowen & Company

I see, that’s very helpful. And then again going on what Jim was asking about the 012 and you might have been able to answer the question yet. But intentional where you thing that might be safe for this drug, in the question to disease or how we would help patients, would -- that it would delay them from going to dialysis, it would extend life by preserving function. And I know it’s too early because we’ve only seen the animal experiments. But how do you think this drug may work that may help these patients?

Kleanthis Xanthopolis

Based on the pre-clinical studies Simos, we’re anticipating that innovation of miR21 in patients with Alport Syndrome will likely delay the progression of disease.

Simos Simeonidis - Cowen & Company

Okay. And then Neil finally, a couple more for you. On the new targets you announced tonight on your AZ partnership. Can you tell us a little more about what 103, 107 and metabolic disease and 19 are implicated in. What type of tumors for 19 and what type of metabolic diseases in 103 and 107?

Neil Gibson

103, 107 is highly expressed microRNA in hepatocyte (Inaudible). So it’s really thought to play an important role in modulating glucose control. And we're looking at the effects of inhibition of that specific microRNA in metabolic disease. For the miR-19 program, a lot of the focus has been on lymphoma and in par miR-19 is activated or increased in its expression as a result of MYC amplification. And MYC amplification is a common genetic lesion in lymphoma, getting as a reasonably clear path with how we can advanced this type of mechanism when we have the potential clinical candidate.

Simos Simeonidis - Cowen & Company

Okay. Great. Well, thanks for taking the questions and congrats on the progress.

Operator

The next question comes from Alan Carr from Needham and company.

Alan Carr - Needham & Company

Can you talk about what you said to be outputs program. Are we going to be seeing any more preclinical data conferences over the course of the year. And then also what’s the scale of the natural history of the disease study? And can you comment what’s build, what’s the limiting factor to starting the Phase 1 trial. Thanks.

Neil Gibson

So let me start with the initiation of the Phase 1 trial. Alan, it is basically currently manufacturing the drug substance to allow the GLP toxicology studies to get completed. So in essence that time frame is what will drive the filing of the regulatory documents towards the end of this year, but the anticipation that we will be starting dosing in humans early in 2013. So that's the key therefore. The natural history disease study, we are really looking there to get a stance of maybe between 30 and 50 patients on a number of different clinical endpoints over the course, as I mentioned of at least 12 months and more likely to be 18 to 24 months.

Kleanthis Xanthopoulos

And, Alan, to add to the third part of your question between Sanofi class enzyme and Regulus, we have a lot, a plethora of pre-clinical experiments done on multiples sites, multiple times. We've got an elite compound indicating a very significant improvement, oncology improvement in kidney function and more importantly extension of survival of these polycystic genetic mutations due to the humans and we will have full information both in publishing in scientific journals as well as participating in many of the upcoming scientific conferences presenting additional data.

Alan Carr - Needham & Company

Okay. Great. Thanks very much.

Operator

(Operator Instructions) The next question comes from Greg Wade from WedBush.

Greg Wade - WedBush

Good afternoon. Let me have my congratulations as well on a great year and thanks for taking my questions. Neil, can you help us understand what will define proof-of-concept in the Alport setting. Is it going to be the same endpoint that you would need to demonstrate you think for approval or something different?

And then secondly with respect to 10b program in GBM. Could you just maybe highlight for us the nature of the experiments that are ongoing, if there has been any particular challenges if you are trying to overcome and whether do you think this will be last set of pre-clinical work before you are able to figure out which drug might go into clinic? Thanks.

Neil Gibson

So for the endpoint question on patients with Alport syndrome, Greg, we've really been looking at a number of different endpoints. So there is obviously the GFR, Glomerular filtration rates I talked out and that discussion that we would need to have with the agency is to whether that would be an acceptable endpoint for subsequent approval.

But clearly, it's an endpoint that we could use in terms of helping us make a subsequent investment decision into a potential registration study. But also we are going to back that up by looking at a number of the different approved or FDA approved renal biomarkers and study those in the natural history of disease study and to see which one potentially give a nice signal to mice.

Example, Beta-2-microglobulin, KIM-1, NGAL, these are three of the seven approved renal biomarkers tests that are available for us to look at, to see whether they provide a good signal to mice. And thirdly, we will be looking at exploratory biomarkers including understanding the microRNA expression as I talked about earlier either in serum or in urine as well as looking at for instance, urinary peroxide which we know in the pre-clinical studies were highly elevated in the progression of disease in mutant mouse.

And are intervention of miR-21, actually dramatically reduce the level of urinary peroxides. So there are multiple levels to what we could do from the endpoint question and obviously looking at it from, one, the decision to add additional investment into the program and two, a discussion with the regulatory authority as to what maybe an approvable endpoint or key areas we are going to focus upon.

For the 10b program in essence, we've been -- we see interesting phenotypic changes with some of our lead molecules. But the challenge in the program has been really to define what's the right target messenger RNA, that we instead of messenger RNA that we can use to help us with our pharmacodynamic endpoint. And to really understand by what mechanism modulation of 10b maybe driving progression of GBM and in which specific segment of GBM that is occurring, whether that’s the Mesenchymal patients or the Proneural patients. So we've got a number of challenges just around that target messenger RNA read out that we're trying to solve at the moment.

Greg Wade - WedBush

Great, thanks. And if I just may have a quick follow-up with respect to GFR in Alport, another inner disease that affected kidney. GFR can be a little misleading, whether it’s a high filtration period followed by decline in GFR. Are you aware in the natural history of Alport, whether it's a steady decline in GFR or are these patients might go through hyper filtration period as well and thanks for taking my questions?

Kleanthis Xanthopoulos

Greg, let me make a few comments about this, as you are very well aware, Alport -- the Alport syndrome is now gaining a lot more publicity. We saw at friends and media coverage just yesterday with the report originally on television with ABC-Good Morning America. And an expectation that there is a lot of patients out there estimates now up to 60,000 in the U.S. and a lot more than we originally anticipated. And more importantly, the reason I’m making those comments is that at the Alport Syndrome Foundation of United States is working very closely with us. You're going to hear more about that in the future. We’ve already been network to cables regarding their wisdom in terms of comments like, whether GFR would be the appropriate biomarker on that. So, we basically are going to cover all bases, as we think that this is a great exit point for a microRNA treatment. And this is of course that has a huge upside potential if we identify treatment. So we're not going to be focusing on one or two biomarkers. We are going to do everything at the [KOL] was suggesting and we can do that very effectively in a short period of time during that positive disease. Neil, do you want add some things?

Neil Gibson

Yes. I would just add, Greg that we do know that there are multiple different mutations that drive the progression of Alport syndrome and the type for mutation can strongly influence the rate of progression. So that’s something we're very aware off and are actually incorporating that thinking into how we think about the design of our subsequent study.

Greg Wade - WedBush

Great. Thanks. Sound like you have a lot of end points to look at, so there will be no shortage of measurements to make. Thanks.

Neil Gibson

Yeah.

Operator

At this time, I’m showing no further question. I would now like to turn the call back over to Kleanthis Xanthopoulos for closing remarks.

Kleanthis Xanthopoulos

Thank you again for joining us in the call this afternoon. And as we stated, we're very pleased with our recent accomplishments and look forward to communicating further progress with you. Thanks again for your time this afternoon.

Operator

Ladies and gentlemen, that those conclude the conference for today. Again, thank you for your participation. You may all disconnect. Have a good day.

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Source: Regulus' CEO Discusses Q4 2013 Results - Earnings Call Transcript

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