Regulus Therapeutics Inc.
Q4 2017 Earnings Call Transcript

Published: 8 Mar 2018

[Operator:]

Good afternoon ladies and gentlemen, and thank you for standing by. Welcome to Regulus Therapeutics Fourth Quarter 2017 Conference Call. [Operator Instructions] And as a reminder, this conference is being recorded. Now I’d like to welcome and turn the call to Ms. Allison Wey, Vice President of Investor Relations and Corporate Communications. You may begin.

[Allison Wey:]

Thank you, Carman. Good afternoon everyone and thank you for joining us to discuss Regulus' fourth quarter and year-end 2017 financial results and corporate highlights. We are joined today by Jay Hagan, President and CEO, Dr. Tim Wright, Chief R&D Officer and Dan Chevallard, our CFO. Jay will provide opening remarks, Tim will share progress on our pipeline programs and Dan will review the financial results before we open the line for questions. Before we begin, I would like to remind you that this call will contain certain 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 call 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 will now turn the call over to Jay.

[Jay Hagan:]

Thanks Allison. 2017 was year of transition for Regulus. We had some setbacks made significant organizational changes, focus the pipeline and added key talents. We’ve learned a tremendous amount over the last year from these experiences and are applying the learnings to all of our active programs both the two clinical programs as well as pre-clinical pipeline. Importantly, our strategy as a company has not changed. We focus on leveraging our expertise in microRNA biology to develop therapeutics for areas of significant unmet medical need. We believe that our growing portfolio programs represent attractive opportunities to further develop and expand our pipeline. Key accomplishments in the quarter recent period included getting the RG-012 study right with the changes to protocol that we and our partner Sanofi believe will give the program the best chance for success. Filing the IND for RGLS4326 for the treatment of autosomal dominant polycystic kidney disease and beginning first in human testing ahead of schedule. Establishing the relationship with WuXi for manufacture of all the nucleotides to complement our existing relationships which further strengthens our ability to develop and eventually commercialize these investigational products, and importantly as you heard from Dan ending the year in line with our financial plan. I'm proud of our team's efforts in accomplishing these milestones amidst the changes we implemented. Our goals for 2018 are clear, advance our two clinical programs through key data events and milestones, prepare with Sanofi for potential option decision in 2019, and advance our preclinical portfolio toward the clinic. Regarding the RG-012 program, today's update includes an acknowledgement that we underestimated the time it would take to enroll the program. We previously had plans together with our CRO to have the approximately 40 sites across the two studies up by now. However, site initiation is taking longer than anticipated given a number of operational complexities. We're about halfway through that initiations and the pace has accelerated from added resources we have applied. While we anticipate a completion and enrollment of HERA and data from the biopsy study around the end of Q1, this is no longer looks achievable due to several factors including the longer than anticipated study start of activities and difficult to recruit target patient population. Importantly, we have dozens of patients in the queue and more being added each day. Conservatively though we are guiding for completion of enrollment in the second half of 2018 for these two studies. We plan to update investors as we reach key enrollment milestones. Now turning to RGLS4326, that program has progressed nicely through its early Phase I development. We have a period of follow up but anticipate data analysis being complete in the second half of 2018. Meanwhile we are making plans for initiation of the multi ascending dose or MAD portion of the study. Tim will share more about both programs shortly. In summary than, 2018 looks to be a year of clinical execution and pipeline advancement. I’m particularly excited about the potential microRNA as a target class beyond what we and others have already demonstrated. microRNA remain a promising and novel therapeutic frontier which we are at the forefront of partnering interest in our microRNA platform remains strong. We have the opportunity to demonstrate proof of mechanism and proof of concept in two unique kidney programs within the next 12 to 18 months further demonstrating the potential microRNA therapeutics as an important target class. We've added key talent that together with a highly focused management team is making great progress in advancing our pipeline. We will plan to share more about them as they move towards the clinic. And with that, I will turn the call over to Tim to provide more detailed R&D update. Tim?

[Tim Wright:]

Thanks Jay. Over the past year, we've enhanced key internal capabilities in R&D and built relationships with CROs to support our preclinical and clinical programs but we continue to advance our knowledge about the optimal design of Regulus to target microRNA’s and deliver to specific cell types and tissues while minimizing potential off-target effects that have led to challenges with the development of other therapeutic Regulus nuclear types. I’ll start my update with the Alport syndrome program. As Jay said, realizing that recruitment of Alport syndrome patients was more challenging than initially anticipated, we've expanded our efforts to speed up the recruitment of our RG-012 studies both the renal biopsy and HERA proof of concept study. We have also engaged additional external resources to help drive awareness within this target to orphan patient community. Once fully enrolled, we'll be able to provide estimates for delivery of our topline results. And while the biopsy data won't be available this quarter, its value in determining whether any changes to dose and frequency prior to Phase 3 initiation remains the same. We just completed a partnership meeting with Sanofi a few weeks back and it was very productive in engaging. We then provided input and advised and how to drive the program forward given their leadership in rare disease. Let's move now to our RGLS4326 program for the treatment of autosomal dominant polycystic kidney disease or ADPKD. While still early, I'm very excited about this program. This is our wholly owned anti-miR-17 program utilizing our proprietary chemistry designed to selectively deliver the anti-miR to the kidney. As Jay indicated we initiated first in single ascending dose or SAD in December 2017 and this study is progressing nicely through dose escalation. We are making plans for the initiation of the multiple ascending dose study that will incorporate ADPKD patients as a way to gain early information on the effects of RGLS4326 on disease related biomarkers. It’s still too early to give timelines on this readout since the study has not yet been initiated but our current estimate is we will have data in hand prior to initiating our Phase 2 program now slated for the middle of 2019. We continue to make significant progress on our early discovery efforts and have over half a dozen programs targeting diseases in the liver and kidney, as well as new work on infectious diseases and immunology. In addition, over the past several months, we’ve been evaluating multiple delivery technologies that hold promise to deliver all of those efficiently to tissues outside of the liver and kidney. This highly focused effort is being performed in collaboration with companies who have advanced these technologies to late pre-clinical or clinical testing for delivery of other payloads and we are now working on optimizing these platforms for Algo anti-miR delivery. These new technologies are aligned with our research strategy and well defined target product profiles. Stay tuned for future updates on these very exciting novel delivery approaches, as well as our early pipeline programs. I’ll now turn the call over to Dan for the financial review.

[Dan Chevallard:]

Thanks Tim. As Jay mentioned, 2017 was a transitional year for Regulus and one that resulted in significant operational improvements and changes. Coming out of our financing last July and in light of organizational changes, impairing of spend in areas of research that were more exploratory in nature, we guided that our perspective operating cash burn would be reduced to approximately $12 million per quarter or $48 million per year. Our second half 2017 cash burn and operating results were in line with these projections with the net cast burn of approximately $23 million over that period, finishing the year with $60.1 million in cash, cash equivalents and short-term investments. We expect this cash to extend nearly through the first quarter of 2019. As you expect, our Q4 activities both from an organizational focus and financial allocation perspective were concentrated around the ramp up of key clinical activities for RG-012 and RGLS4326. Importantly, incremental resources were applied towards the successful IND filing for 4326 and subsequent initiation of the first in human Phase 1 study which we announced in December. Cost to support these important initiatives were partially offset by reductions in spend associated with the wind down of Athena, our natural history of disease study for Alport syndrome patients. Turning now specifically to our financial results for the period, research and development expenses were $10.5 million and $53.2 million for the quarter and year ended December 31, 2017 respectively compared to $15 million and $64.3 million for the same period in 2016. This reflects a decrease of 30% and 17% versus the comparative period. The fourth quarter decrease was primarily the result of a reduction in personnel related and associated fixed costs subsequent to our May 2017 corporate restructuring. The year-over-year decrease was further driven by the completion of wind down activities and spend related to the RG-101 and [closed spaces] programs. G&A expenses were $3.3 million and $17 million for the quarter and year ended December 31, 2017 compared to $4.8 million and $18.4 million for the same period in 2016. The decreases in G&A expenses were primarily attributable to a reduction in non-cash stock based compensation. Net loss was $14.4 million and $71.9 million for the quarter and year ended December 31, 2017 compared to a net loss of $20 million and $81.8 million for the same periods in 2016. The resulting basic and diluted net loss per share was $0.14 and $0.96 for the quarter and year ended December 31, 2017 compared to a net loss per share of $0.38 and $1.55 for the same period in 2016. As we look ahead in 2018 and consistent with our past guidance, we anticipate a cash burn in line with our 2017 exit rate of approximately $12 million per quarter. Our 2018 cash burn will be focused with approximately 80% of our operating plan committed to our R&D efforts comprised of our two clinical programs and the advancement of our pre-clinical research pipeline as Tim outlined. We look forward to an exciting year ahead. And with that, I would like to turn it back over to Jay.

[Jay Hagan:]

Thanks Tim and thank you very much for your interest today. Summing it all up, 2018 is a very important year for execution. And as it is aside, we will be presenting two upcoming investor conferences Cowen next week and Needham last week in March. With that, we would be happy to take your questions. Operator, will you please open the lines?

[Operator:]

[Operator Instructions] And our first question is from the line of Liana Moussatos from Wedbush Securities. Your line is open.

[Liana Moussatos:]

The delay for starting up the sites, the clinical sites for the HERA and liver, I mean kidney biopsy trials, what kind of issues are they having and you mentioned that it's difficult to enroll target patients, how - can you talk about how it can help you with that or little more color?

[Jay Hagan:]

Sure, I'll take the first part of that Liana and then I’ll ask Tim to add, chime in as well. With respect to the operational issues, we don't want to make excuses for the issues we've confronted but one could imagine that a trial that encompasses two biopsies, as well as audiology testing, site selection amidst end of the year and so forth. And competing clinical trials affects our plans and importantly as I mentioned approximately 40 sites that the increased number of sites than we originally planned really to try to again accelerate development of the program to meet timelines. Tim I don’t know you want to add any more about that or the patient population?

[Tim Wright:]

Sure, let me just add to the question about the how to recruit patient population, obviously this is an orphan indication and in particular our intended population for the HERA study is one of actually males which tends to be a younger demographic and what's interesting is we’ve got tremendous support from the Alport syndrome community and a lot of interest and what we're trying to work through now is it’s sort of balancing the need to recruit this younger male population and the commitment to the trial. So we're trying to improve the ability to have subjects participate while making that participation not too onerous for them, so that's part of this last process of adjustments in the operational side of things but obviously this is a very different demographic than is usual for clinical trial settings except for these rare diseases in this particular case, a younger male population.

[Jay Hagan:]

Liana just to add to that two, I mean recall there is nothing approved or available for these patients, so the frequency at which they see their nephrologists is such that driving awareness about this new investigational agents in clinical trials and reaching that target patient population is one that requires specialized outreach and that's part of what we alluded to with the additional external resources that we're engaged with now to drive that awareness.

[Liana Moussatos:]

And you mentioned partnering interest do you have any comments on what areas or any kind of color on that?

[Jay Hagan:]

Yes, no I mean obviously RG-012 is already partnered with Sanofi. The anti-miR 17 which has been well published over the last several years represents a very novel approach to treating another disease where there are significant unmet need, nothing approved in the U.S. and is one that represents an attractive potential commercial opportunities. So there's that and there's other things in our pipeline, we've done a really good job of creating awareness amongst potential partners over the last year and I think that's starting to manifest in growing interest in the opportunity to target microRNAs and complex diseases.

[Liana Moussatos:]

Are you thinking, it was mentioned anti-infectious diseases in immunology for pre-clinical would those be partnerable? Or you thinking of developing something yourself?

[Jay Hagan:]

We ultimately want to develop a program for ourselves but we look at business development as an avenue to fund our aspiration, relative to other ways to for capital formation and so we driving awareness in our pipeline in our capabilities is a must do and it's yielding fruit in terms of interest there and I would also say that Tim has done a really good job of focusing our pipeline efforts in areas of significant unmet need in balancing the portfolio. So both of those things that were mentioned obviously represent opportunities for faster readouts in terms of endpoints and so I don't Tim if you want to add anything.

[Tim Wright:]

Yes, just to say that again building on the portfolio that existed here which was strong especially in renal disease branching out into areas where we can show faster proof of concepts whether it's based on biomarkers or clinical efficacy and therefore driving value early either for ourselves or in a partnership mode has been the focus of the last several months to a year.

[Jay Hagan:]

Yes and further to that early on leveraging on the validation of targeting miR-122 is a host factor and Hepatitis C there's a growing body of literature on the role of microRNA’s enabling infectious disease well beyond Hep C and it’s that lead us to some additional areas and as those programs mature we are excited to share data on those.

[Liana Moussatos:]

And for the MAD study for ADPKD you mentioned biomarkers and what are the steps to start up the trial?

[Jay Hagan:]

Yes, so actually we’re in the later stages of finalization. So once we're ready to get that going we'll be submitting it through the typical regulatory and ethics committee to review, IRB review and then starting once we have all of the operational components in place. As far as biomarkers, will be exploring those in both our healthy volunteer population but more importantly we've now prepared a plan that will integrate ADPKDs patients into our MAD and we haven't disclosed the final design on that but I will tell you it's an innovative design one that we've been encouraged to pursue by regulators to integrate patients early in the program.

[Operator:]

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

[Eric Smith:]

It's just a little unclear to me when we expect that data from the biomarker study given the revised timelines and I think that study was supposed to enroll the total of 10 patients; can you talk about exactly where you might be in the enrollment today?

[Jay Hagan:]

I guess so we will provide an update of when data can be anticipated when we complete enrollment in that and enrollment is underway and you're right, the protocol provides for up to 10 patients in two cohorts to look at an opportunity to compare dose frequency to see if any adjustments would be appropriate prior to Phase 3 initiation. Tim you want to add anything to that?

[Tim Wright:]

Yes, just so we're not going to give updates on specific numbers of subjects recruited but as Jay mentioned it is underway and we're making progress with that study the target is to deliver this in the second half of the year.

[Eric Smith:]

Deliver the data in the second half of the year.

[Tim Wright:]

Yes.

[Eric Smith:]

And there's a natural history study I think you were planning on publishing that at some point time do you have a more specific timeline.

[Jay Hagan:]

Yes, we got together with the office at ASN late last year and there's tons of work analysis underway and I think the plan is a medical conference in the second half of the year as where they're gearing towards.

[Operator:]

And our next question comes from the line of Joseph Schwartz with Leerink Partners. Your line is open.

[Unidentified Analyst:]

This is actually [Dagon] dialing in for Joe. So just wanted to get a little more clarification on the enrollment progress, did I hear you right that you currently have 30 sites that you're currently enrolling in and what exactly are you doing on the raising awareness aspect and have you seen I guess timing wise when have you commence that effort and have you seen the fruits of that effort.

[Jay Hagan:]

So what we said was that we're targeting approximately 40 sites across the two studies. And some sites actually are involved in both studies, so we not really breaking out what number for each, you can stay online ClinicalTrials.gov a number that are up thus far and we're about halfway through that targeted number of sites. And it’s also when we're conducting mid stage clinical research here some sites you put up don't really patients, you decide to add sites and make other tackle moves to help drive the pace of enrollment. And so that's where we are with respect to that. With respect to the point about additional tactics and resources, those are activities that are underway and engage, they include how to reach this targeted patient population, Tim alluded to actually males tend to be younger. And given the frequency at which they see their physician, you need other avenues to in order to drive awareness that this trial is being conducted. That includes different types of social media platforms and understanding influence theirs and ways to reach the target patient population. In addition to other techniques and as we roll them out and see the fruits of those would be happy to share in more detail but as you can imagine it's one of an iterative nature trying to for tactics and seeing how that works and we've got a lot of promising activities underway in that front.

[Tim Wright:]

What I would add is that since our site initiations have been a lot slower than anticipated, it has given us some opportunity to me to see where some of the issues maybe. And then start to put some of these additional resources in place along the way instead of waiting till after all the sites were initiated. So as Jay said it's an iterative process and it's still or too early to see the fruits of it but we expect to see it in the very near future.

[Jay Hagan:]

One of the thing I'll add as it's a genetic disease and so oftentimes you might have one person who's interested and you find out that they've got six family members with the disease as well and in other ways to leverage the information to reach the target patient population here.

[Unidentified Analyst:]

Just to I guess branch off that point, do you anticipated you guided for about $12 million OpEx per quarter do you anticipate any material change to that if you were to see any trends that would require you to invest even more heavily in patient identification for the remainder of the year.

[Jay Hagan:]

I think we can manage to that budget; these are not significant investments per se. In terms of additional tactics and we're always finding opportunities for trade off some resource allocation to meet our protective burn rate. I don't know Dan if you want to add anything to that?

[Dan Chevallard:]

No, I don't think I'd add is just to clarify $12 million in cash burn that being a bit different than operating expense as you mentioned [Dagon] but, yes I think our objective would be to them as within the confines of this guidance that we're putting out today or reiterating and will be looking to provide for those additional activities takes into they require additional resources by identifying savings elsewhere.

[Operator:]

And our next question is from the line of Alan Carr with Needham and Company. Your line is open.

[Alan Carr:]

A couple of them when to go over the output trials a little bit here and then enrollment. It sounds like its mostly finding patient but actually do find them or there any challenges with screen and all that you mentioned that there was a little bit of trouble getting sites up in running there but these all in the U.S. and then last question when [indiscernible] Sanofi and if the deal in terms of the option contemplate, these kind of delays is there just the Sanofi a little bit longer to meet the patient and continue to way for proof of concept or some other clause about - the ties to related to timing to when we'll get this data?

[Jay Hagan:]

Yes, I’ll touch on a few of those and ask Tim to amplify in areas that I missed those are all very good questions. So maybe I’ll take the last one first, then will give the operational piece. So our contract with Sanofi provides for them to have, the opportunity to opt into the program up through an outside date which is defined as a short period of time after completion of a one year proof of concept study and the one year is 48 weeks of treatment for 30 patients. And so once we provide in that sort of information, they have a fixed period of time to make an option decision. So there's no there's nothing per se that changes with the passage of time with the passage of increased money spent on that just gets included in the reimbursement component. So we invest, we get more reimbursed. And as I said we’d a very productive meeting a couple of weeks ago and really appreciate their input on ways to improve our region and drive awareness given their long experience in rare diseases. On the operational complexity side, it really is a constellation of things, you don't have sites up, you can't get patients screened and so you need to get sites up in key geographic regions where there's patients and where you've heard from investigators that they have patients to be treated. And it's one of the typical sort of hockey puck type analogies here where you get momentum in the study as the sites are up as you drive awareness and patients come through. As far as screen there, we don’t want to get all the detail around how the process is going but as you've seen in our protocol we're targeting actually males and we often get a lot of input from females interested in pursuing this trial. And obviously that they're not the target population for the HERA study based on what we learned from ATHENA. So that sort of initial interest and I think investigators are reaching out to their perspective patients and letting them know that females interested in participating in any trials with respect to RG-012 can be directed to the biopsy study where there are certain number of females allowed for that study. I know Tim as you want to add anything more.

[Tim Wright:]

And just a couple of other points, one is that our ATHENA study was based almost exclusively at academic sites and the just the contracting of logistics of getting academic sites up and running is a longer process than the central IRB community based sites and so we saw some delays in that process and we are now working through as Jay mentioned we’re in a nice clip in terms of getting a number of the academic sites up and running. Those were the sites that we've been working with for the last few years and have patients identified for potential participation. So that's part of the process that we've been working through in terms of operational logistics and then the other regarding patient screening yes, one of the challenges is not only is the young population but these patients progress. So some patients that have been identified to participate were actually a little too far beyond the progression in terms of their renal disease. So these are just some of the challenges we face in this kind of disease not that I don't think we can overcome that where in the process of trying to do that right now.

[Operator:]

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

[Unidentified Analyst:]

It’s [Nick] for Jim this afternoon. Thanks for all of the information on the Alport program, may be on 4326 is there any learning from Alport that you need to apply now, do you expect that could be challenges enrolling patients for the multiple sending dose in later trials.

[Jay Hagan:]

Yes, I'll just take the first part of that. Thanks for the question Nick. The team is doing a lot of work already on feasibility as we're incorporating ADPKD patients into the Phase 1 trial design for the goal of demonstrating proof of mechanism here before mid next year. And just a couple of points, one the ADPKD diagnosed patient population is significantly larger than the Alport population. And there are therapies that are approved outside the U.S. and there have been trials done in the U.S. number of investigational agency which demonstrates an ability to recruit fairly large numbers of patients, part of their disease as well. And the progressive nature of it I think there's a greater awareness and it's willing to mobilize what we've seen thus far when you look at precedent study, so I don't think per se that we anticipate any issues knock on wood but we're certainly incorporating all the learnings we can into our feasibility planning here for the Phase 1 and ultimately the trials after that. Tim?

[Unidentified Analyst:]

In terms of single ascending dose, you give me for about nine months or so to report data from this, is this because you’re planning a lot of dose levels, it takes a lot of data about dose selection, how do you intend to select dose, single ascending dose portion?

[Jay Hagan:]

Right, so the timeline to complete that study and have the final data from it is only driven by the duration of follow-ups that we would have with the molecule like an Algo and it doesn’t relate to the real expanded number of dose groups, in fact that is relatively small. It’s purely that we want to ensure adequate follow-up of all the healthy subjects before we lock the database. And what we have indicated is that we’re actually planning to start the MAD in the not too distant future, we're actually hoping to do that in an inter-leap fashion before the final data are in hand from the SAD. So we don't see that as rate limiting right now in terms of progressing the program. Obviously it is part of the program, we will complete that but it's not right now in any way rate limiting.

[Dan Chevallard:]

Yes, so we have several months of follow-up after the last SAD cohort is dosed and then lock the data, analyze the data and that's what we have in hand. That’s why we’re guiding to where we are but your question about dose selection with the MAD that’s guided as much about what we’ve seen in terms of our repeat dose studies in mice, as well as in monkey and the tissue exposures achieved, so we know what level is required to show efficacy in the mouse model and what's required to achieve a certain level of exposure in the non-human primate which translates to our estimation for where to start dosing in the MAD portion and where we might see efficacy.

[Unidentified Analyst:]

Just loss on running back on HERA, you are going to have some interim data, I think on 24-week interim data reported by the middle of the year, that’s obviously going to be pushed back, what is the plan now for reporting a 28-week and 48-week data from HERA?

[Jay Hagan:]

Yes, the 24-week interim analysis is a blinded analysis, so the most likely situation I would guide investors to is that the data monitoring committee met and reviewed data from all patients through 24 weeks and instructed the sponsor to continue. We obviously don’t want to break the blind in the study at the interim analysis. There is a chance that the trial could be wrapped up early by hitting the primary endpoint but that's not what we're powered to show. So, and then the 48-week data upon completion of that and data analysis we’ll be reporting that. Once we are fully enrolled we can then provide some timeline to those milestones.

[Unidentified Analyst:]

So the interim would be based on 24 weeks sort of from the last patient in?

[Jay Hagan:]

That’s right, correct.

[Operator:]

[Operator Instructions] And our next question is from the line of Matthew Luchini from BMO Capital. Your line is open.

[Matthew Luchini:]

So couple from me please. So I guess first on the Alport program, you've mentioned a couple of times now 40 sites and you’re about half way -- through about 40 sites and about halfway through site activation. Is it general plan just to stick with those 40 sites or you looking at adding or identifying additional sites to bring the total number of active sites closer to that 40. And then secondly you guys have mentioned a couple of times the guidance that Sanofi has provided in terms of helping to move the trial along and accelerate recruitment. Maybe could you just give us a little sense as to what maybe the specific guidance was that they suggested if it hasn't already been sort of discussed so far. And then finally for 4326, how should we expect you to communicate results from the single ascending dose portion of the trial and did I hear you correct that the data from the multi-ascending dose portion should be expected before or no later than mid-year next year? Thanks.

[Tim Wright:]

Yes, so adding additional sites I alluded to earlier when you are going through the process especially for mid-phase clinical trial, you put sites up, they don't appear to be getting any traction you might shut them down, move on change based on constantly evaluating opportunity to add patients. So and we are evaluating adding additional sites where we feel like we might get traction with patients recruitment. So that's all in the mix, it is all influx. With respect to, I'll just take the last one with respect to 4326, how should we expect communication, the single ascending dose portion of the study once we wrap that up and how the results will report those topline results, the MAD portion you’re correct as Tim guided to, our current plan is to initiate the Phase 2 portion of that trial mid next year and so we’d obviously have those results from MAD in the proof of mechanism complete and communicated by that time.

[Jay Hagan:]

And with respect to the guidance Sanofi has provided Tim can share more of this but they obviously have a long history in rare diseases and to sharing anecdotes amongst the joint steering committee about things that they've seen and ways to drive awareness either through foundations, through regional outreach and engagement with the physicians, different ways of driving a cooperative sense among the investigators and so all those types of tactics we’re evaluating and employing into our efforts.

[Tim Wright:]

Yes this has been an ongoing dialogue over the last well couple of years at least and I think it's been very helpful over the last several months especially as we've gotten the trial up and running. We continue the dialogue in between our formal get togethers but certainly having face to face and reviewing the program and as Jay said sharing anecdotes and new ways to identify hard to recruit population has been very helpful for us.

[Operator:]

Thank you. And that ends our Q&A session for today. I will like to turn the call back to Mr. Jay Hagan for his final remarks.

[Jay Hagan:]

Thanks very much for your time and attention today and we look forward to providing updates as these programs move forward. Thank you.

[Operator:]

And with that ladies and gentlemen we thank you for participating in today's conference. This concludes the program and you may all disconnect. Have a wonderful day.