Alnylam Pharmaceuticals, Inc. (ALNY) Q1 2012 Earnings Report, Transcript and Summary

Ladies and gentlemen, thank you for standing by. Welcome to the Alnylam Pharmaceuticals Conference Call to discuss the First Quarter 2012 Financial Results. There will be a question-and-answer session to follow. Please be advised that this call is being taped at the company’s request. I would now like to turn the call over to the company.

Good afternoon, I am Cynthia Clayton, Vice President of Investor Relations and Corporate Communications at Alnylam. With me today are John Maraganore, our Chief Executive Officer; Akshay Vaishnaw, Chief Medical Officer, Mike Mason, Vice President of Finance and Treasurer, Laurence Reid, Chief Business Officer and Barry Greene, President and Chief Operating Officer. For those of you participating in the conference call the slides we have made available via webcast and also be accessed by going to the Investors page of our website at www.alnylam.com. During today’s call and as outlined in slide 2, John will provide some introductory remarks and provide general context. Akshay will summarize our clinical progress; Mike will review our financials and guidance. And Barry will provide a brief summary of our business highlights and goals before opening the call to your questions. Before we begin, and as you can see on slide 3, I would like to remind you that this call will contain remarks concerning Alnylam’s future expectations, plans and prospects, 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 most recent annual report on file with the SEC. In addition, any forward-looking statements represent our views only as of the date of this recording and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligations to update any such statements. And we will now turn the call over to John.

Thank you, Cynthia. Welcome and thanks to everyone for joining us this afternoon. As Alnylam celebrate its 10th anniversary next month, we have never been positioned better to execute on our mission of building a top-tier biopharmaceutical company founded on RNAi. Indeed as you can see in slide 4, the past period has been one of remarkable accomplishments in our scientific and clinical development efforts, with positive results in three clinical programs including human proof of RNAi mechanism in our ALN-VSP liver cancer program, human proof of concept in our transthyretin-mediated amyloidosis program and clinical efficacy in our ALN-PCS severe hypercholesterolemia program. These results confirm what we have always believed; namely that RNAi can be harnessed and manned to create a whole new class of high impact, innovative medicines. Turning specifically to activities in the first quarter of 2012 and the recent period, we made significant clinical and business progress focused on our Alnylam 5x15 product strategy for the development and commercialization of RNAi therapeutics. Just a couple of weeks ago, we’ve reported extremely encouraging clinical data from our Phase I ALN-PCS trial for the treatment of severe hypercholesterolemia. We also recently initiated dosing in our Phase I clinical study with ALN-TTR02 and RNAi therapeutic targeting the transthyretin gene for the treatment of transthyretin-mediated amyloidosis. And we are on track to report clinical data from this study in the third quarter of this year. We also made excellent progress in our hemophilia program, and we look forward to updating you on in this effort in the months to come. These important accomplishments combined with the recent strengthening of our balance sheet, gives us great confidence in the continued execution of our Alnylam 5x15 product strategy, which is focused on advancement of RNAi therapeutics directed to our genetically defined targets for diseases, where there are limited treatment options for patients and their caregivers. I will now turn the call over to Akshay for a more detailed review of our clinical activities, our pipeline progress and also our scientific accomplishments. Akshay?

Thanks, John, and hello everyone. As John mentioned, we continue to make important progress in advancing our Alnylam 5x15 programs into the clinic. I will start with the review of clinical data presented just a couple of weeks ago from our ALN-PCS, as noted on slide 7, which targets PCSK9 for the treatment of severe hypercholesterolemia. This exciting results showed very robust statistically significant and dose-dependent knockdown of PCSK9 and lowering of LDL cholesterol levels in a single dose study performing in the absence of statin. The Phase I study was conducted as a randomized, placebo-controlled, single-ascending dose study, in healthy volunteers with elevated baseline LDL cholesterol. The primary objective of the study was to evaluate the safety and tolerability of ALN-PCS. Secondary objectives included assessment of pharmacodynamic effects on plasma PCSK9 protein levels and evaluation of clinical efficacy as measured by LDL cholesterol levels. A total of 32 subjects were enrolled into six dose cohorts ranging from 0.015 to 0.4 milligram, per kilogram. In this study, as you can see on slide 8, a single dose of ALN-PCS resulted in rapid, dose-dependent, and durable reductions in LDL cholesterol of up to 50% relative to baseline in placebo, with a statistically significant mean reduction of 41% of the highest dose. In addition ALN-PCS administration resulted in rapid, dose-dependent and durable knockdown of PCSK9 protein levels and plasma of up to 84% rather to baseline placebo, with a statistically significant mean reduction of 68% in the highest dose group. ALN-PCS was certainly generally safe and well tolerated in the study, and there were no serious adverse events related to study there. There was no significant change compared to baseline in level of HDL cholesterol consistent with the phenotype observed in human PCSK9 loss of function in mutations. We are very excited by this new ALN-PCS data that once again demonstrate robust clinical efficacy for RNAi therapeutic. As you can see on slide 9, ALN-PCS are the unique mechanism of actions since it inhibits the synthesis of PCSK9 liver cells, thereby reducing both the intracellular and extracellular functions, and that’s provide the differentiate of strategy for PCSK9 antagonism in comparison to monoclonal antibodies under development for this drug. Specifically, this mechanism of action results in potent and durable LDL cholesterol reductions, enabling once monthly dosing, and potential synergistic effects with (inaudible). In addition ALN-PCS is a novel mechanism enables consistent clinical activity, across a wide range of patient PCSK9 plasma levels, including individuals with very high PCSK9 plasma levels. We believe these differentiating factors could be very important in the development of PCSK9 agents and will be important to the partnership we able to form prior to initiating a Phase II study. In a meantime these data mark yet another important milestone in our Alnylam 5x15 efforts, as they demonstrate continued safety, tolerability and robust clinical efficacy of an RNAi therapeutic tolerating a liver expert disease gene utilizing our second generation lipid nanoparticle delivery technology. The same delivery formulation we are currently using in ALN-TTR02. Now turning to our ATTR program, we continue to make rapid clinical development progress with this very exciting effort. We’re developing ALN-TTR for the treatment of transthyretin-mediated amyloidosis or ATTR, a devastating inherited orphan disease affecting the nerves and heart. Our RNAi therapeutics aims to reverse disease by silencing the disease causing gene TTR. As you recall, made last year, we reported positive preliminary clinical results from our first generation ALN-TTR01 Phase I study changed statistically significant reductions in serum TTR protein level in ATTR patients. ALN-TTR01 was out to be well tolerated in this study. These results as highlighted on slide 10, were very important since TTR is the pathogenic protein in this disease, and we have demonstrated that we can knock it down in ATTR patients. We are presenting the final data from this trial next week at the ISA meeting. These encouraging data combined with major improvements we have made in our delivery technology, as evidenced in our ALN-PCS trials give us great confidence in our second generation product ALN-TTR02, which we believe will be our go-to-market product for this program. ALN-TTR02 is comprised with same as on as ALN-TTR01 it is formulated in the more potent second generation LNP which is proprietary on Alnylam lipid MC3. In March, we initiated the Phase I clinical trial with ALN-TTR02; this trial is being conducted in the UK, as a randomized single-blind, single-ascending to study enrolling up to 32 healthy volunteer subjects. The objectives of the study are to elevate safety and tolerability, as well as clinical activity, as mentioned by serum TTR levels following a single-dose of ALN-TTR02, with subjects being enrolled into five sequential dose cohorts ranging from 0.01 to 0.5 milligram per kilogram. This trial is well underway, and we are on track to report data in the third quarter of this year. We also expect to initiate a Phase II multi-dose study of ALN-TTR02 in ATTR patients in the second half of 2012. And assuming positive results, start a pivotal trial for ALN-TTR02 in 2013. In addition, in January, we also announced the plan to advance subcutaneous delivery asset in our ATTR program utilizing a GalNAc-conjugate delivery approach. This approach provides an opportunity for product differentiation in the ATTR indication. Turning to slide 12, another area of focus for us with Alnylam 5x15 strategy is our hemophilia program. Alnylam is developing ALN-APC for the treatment of hemophilia and inherited orphan bleeding disorder. Our RNAi therapeutics is a completely new approach, which resets the clotting cascade to stop bleeding by targeting Protein C a genetically defined target. This strategy has been validated in human genetics based on co-inheritance of Prothrombin mutations in hemophilia patients, where these patients exhibit significantly reduce bleeding complications. We have plans to present updated preclinical data from this program at the World Federation of Hemophilia in July 2012 and we’ll continue to advance this program toward the clinic with a goal of initiating a Phase I trial in the first half of 2013. And as you can see on slide 13, we also continue to advance other Alnylam 5x15 programs including our ALN-TMP program for the treatment of hemoglobinopathies, and ALN-HPN for the treatment of refractory anemia. ALN-TMP comprises systemically delivered RNAi therapeutics targeting transmembrane protease, serine 6 or Tmprss6 for the treatment of hemoglobinopathies, including beta-thalassemia and sickle cell anemia. Alnylam plans to partner this program prior to conducting a Phase I study. Alnylam also plans to partner its ALN-HPN program which targets the hepcidin pathway for the treatment of refractory anemia prior to conducting a Phase I study. With that, I would like to turn the call over to Mike for review of our financials. Mike?

Thanks, Akshay, and good afternoon, everyone. Please refer to slide 15 in our deck. We continue to maintain a strong financial profile ending the first quarter of 2012 with $316.9 million in cash, cash equivalents and marketable securities. Our cash position increased this quarter as a result of a public offering of common stock that we completed in February issuing 8.6 million of common stock and generating net proceeds of approximately $87 million. Our GAAP revenues for the first quarter of 2012 were $20.6 million, as compared to $20.9 million first quarter of 2011. We continue to report the amortization of upfront payments from the strategic alliances that we have formed, which account for a significant and recurring portion of our quarterly GAAP revenue. Looking ahead, the amortization of Roche, Arrowhead revenues which represented approximately $14 million in the first quarter of 2012 we’ll come to its planned during the third quarter of 2012. Moving to expenses, R&D expenses were $21.1 million in the first quart of 2012, as compared to $26.3 million in the prior year period. This decrease was due primarily to lower clinical trial and manufacturing costs related to our ALN-RSV and ALN-VSP programs and was partially offset by a one-time charge of $3 million related to the corporate restructuring we implemented in January. G&A expenses were $10.4 million in the first quarter of 2012, including a restructuring charge of $900,000, as compared to $10.2 million in prior year period. With respect to guidance for 2012, we believe we will finish the year with greater than $250 million in cash, and in summary, with the financing we completed in the first quarter combined with our corporate restructuring resulted in a balance sheet and operating plan that we believe will enable us to continue to advance our “Alnylam 5x15” product strategy. This concludes the financial highlights and I’ll turn the call over now to Barry.

Thanks Mike. As you’ve heard this afternoon, we are demonstrating with human clinical data that the RNAi pathway can be harnessed to create high impact, innovative medicines. We continue to focus on our “Alnylam 5x15” efforts to what we believe to be our highest value opportunities driving key programs for pivotal trials. This includes accelerated clinical development plans for ALN-TTR02 for the treatment of ATTR, a devastating and debilitating genetic orphan disease affecting the nerves and heart. It also includes our RNAi therapeutic for the treatment of hemophilia, which we believe represents an exciting opportunity that could fundamentally change the management of this inherited orphan bleeding disorder. Now, in addition to our Alnylam 5x15 programs, we’ve a number of programs focused on other disease indications as noted on slide 17 that we are advancing with existing partnerships or with partnerships that we expect to form in the future. These programs include ALN-VSP for the treatment of liver cancers, where we expect to report updated data at ASCO, and also our ALN-RSV program which remains blended, and where we expect to report results in mid-2012. Regarding our Huntington’s Disease Program, today we announced that consistent with our value creation strategy, and as part of the alignment of resource on our Alnylam 5x15 programs, we have elected to exercise our option to opt-out of the 50/50 expense arrangement with Medtronic and CHDI. This decision gives us the opportunity to receive future milestones and royalties on this program without the need to co-invest on a 50/50 basis. Medtronic has indicated their continued interest in the development of ALN-HTT and we look forward to assisting them and are committed to assisting them in these efforts. Also as a result, our increased focus in 2012 and beyond, in January we implemented an organizational restructuring, which included an approximate 33% reduction in our workforce. This is a very difficult decision to make, but we are confident that it was an important step in continuing to build our company for the long-term. I will note that we are extremely grateful to all of our employees, past and present, for their dedication, passion and commitment in advancing RNAi therapeutics to patients. As Mike mentioned, we strengthened our balance sheet this quarter and remain poised to execute on our goals as detailed on slide 18. Specifically, key goals we are focused on include, reporting on the complete Phase I data for ALN-TTR01 this month at the ISA Meeting, reporting on our Phase I data for ALN-TTR02 in the third quarter, initiating our Phase II study for ALN-TTR02 in the second half of the year, putting us on track to start pivotal trials in 2013, reporting an update on our pre-clinical results in our hemophilia program, as Akshay mentioned, at the WFH Meeting in July, while advancing these efforts toward start up clinical in the first half of next year. Partnering our ALN-PCS program prior to start Phase II and advancing other “Alnylam 5x15” programs with Phase I with partnerships we aim to form. We’ll also, as we mentioned, be reporting on our ALN-VSP Phase IIb study in mid-year and advancing our ALN-VSP liver cancer program into Phase II with a partner. As I previously mentioned, we are going to be supporting Medtronic and CHDI and our efforts to ALN-HTT and form additional partnerships on programs and technologies. Importantly, we remain consistent in our guidance of ending the year with over $250 million in cash. Clearly it’s been an eventual and highly productive quarter and we are looking forward to continue progress including clinical data over the coming months. With that, I would like to turn the call back over to the operator for your questions. Karas, we’ll now take questions. Thank you.

[Operator Instructions] And your first question comes from the line of Charles Duncan with JMP Securities.

This is Gena Wang on behalf of Charles Duncan. I basically have two questions around the TTR program. First question is, I wonder what would be the primary endpoint for the Phase II and the pivotal trials. And the second one is kind of following the same line. I’m wondering what would be your thoughts on the competitive landscape since a vendor crew will have PDUFA date coming and Isis is also developing similar drug for FAP, and maybe a little bit faster than - at the TTR02 program. So wondering about your thoughts on the competitive landscape?

Sure. Those are two great questions. So I’m going to have Akshay answer the first question on the endpoints, and then Barry answer the second question on the competitive landscape. So, Akshay you start.

Sure. So with respect to the endpoints, we are very excited to announce that we will indeed be initiating the Phase II study in the second half of the year, and the goal of that study, essential apart from full safety and tolerability, is to consolidate a view of the pharmacodynamic activity of our drug ALN-TTR02. And we’re confident that we’ll show very impressive knockdown with the TTR02 product, which shows the same third and second-generation LNP as with LNP-PCS, and of course we’ve also seen the very exciting PCS data. So, I think all bodes well there in terms of safety and PD and then that will take us to the Phase III study, which we mentioned, which we hope to start in 2013. And we believe the clinical endpoint there in FAP patients will be a composite measure of the neuropathy that is being termed NIS-LL and that was used by the [indiscernible] folks in their Phase III study and is obviously now validates and has a lot of infrastructure around it, including clinical interoperability and level of clinical benefit of change the - so we are very excited about that and I think we’re in good shape.

And Barry, you want to comment on the competitive landscape.

Yeah. So, as we’ve mentioned on the call, TTR-mediated amyloidosis is incredibly painful, devastating and debilitating disease. People are dead within five to 15 years. So when you think about TTR-mediated amyloidosis both the polyneuropathy and cardiomyopathy, you want to do everything you can for these patients and as typical with these kind of devastating diseases we see with cancer, multiple drugs will be used over the course of time to help these patients out. What you want do with these patients is, as Akshay mentioned, remove the insulting protein, in this case it’s transthyretin, which will have the amyloidosis reserved causing reversal of disease. When we think about ALN-TTR02 and “once-a-month” dosing that removes the insulting protein, we believe that we have absolutely the best drug profile out there and ultimately with reversal disease we’ll have - the have been a best drug for treating TTR-Mediated Amyloidosis. Don’t see Tafamidis as a deterrent that patients may - combine with Tafamidis, what you’re doing there is binding to protein and you have to remove the protein and in terms of Isis programs as it have been mentioned this is a kind of patient population where multiple drugs will be used overtime and we really like our profile the best.

So the bottom-line of that is that we believe we will have the best in class drug in this indication. Bottom-line.

Thank you and congratulation on the progress.

And your next question comes from the line of Mike King with Rodman & Renshaw.

I wanted to ask a strategic question about the decision on PCSK9 with regard to partnering at this juncture. While I would view the data as extremely encouraging, I also think there is a lot of questions that need to be answered and if there is a partner sitting across the table from you, these are kind of the items that multi-dose, a combination of statin and et cetera that they will try to ding you for - on the value of your program. So can you talk a little bit about how you feel that the program has advanced enough now to add the kind of value to your shareholders that they really should receive from the program?

Yes. But let me make some comments and then maybe Laurence Reid who is here, can also comment. I mean, Mike, the PCSK9 data that we generated, I think, are incredibly exciting. Obviously the next steps in the program, it would be clearly to do combination studies with ALN-PS with statin and I think that’s very, very clear-cut as well as to do multi-dose type studies. And so, these are things that are clearly in front of the program in terms of the next steps. It’s really our belief that the current data set provides an amazing level of de-risking of the program and really take the program to a position of its performance that is at a stage today wonderfully strong to form a partnership, I mean obviously one can continue to invest and always make things better and stronger over time, but you have to balance that as a company with the other organizational aspects of what you’re doing, which of course has been a major focus within the company on advancing ALN-TTR02 in hemophilia, where we think the competitive landscape and our overall ability to play ultimately in those commercial marketplaces is stronger proportional to where it would be in the hypercholesterolemia space. So I think we’re making an overall integrated business decision around the effort, which at the end of day factors into our decision to partner it at this current juncture point. I mean Laurence you should comment as well from a market standpoint as you’ve been out there talking to potential partners.

Yeah I mean I think the interest has been generated in this field is PCSK9 field over the last - in the last year or so as some of the big antibody pharmacologists come along is very significant estimates kind of market that can be associated with PCSK9 pharmacology it is to come and we believe that all therapeutic having a different modality, different mechanism of action initiate [indiscernible] in a molecular pharmacology and the antibodies by acting inside and outside the sellers we discussed. But all of that makes our drug very attractive opportunity in this marketplace and obviously we will see how that plays out precisely in negotiations and deals discussions but there are many pharmaceutical companies and biotech companies out there who don’t have a prominent play in this area. Who have a strategic commitment to cardiovascular area, who I think are interested in an alternative modality versus the antibodies and realize this is a massive market and any form of therapeutic has a long way to go from here to get - or actually get into the commercial marketplace and I think with those factors that are generating interest that we’re seeing in the program.

Mike there are clearly going to be a significant number of players that ultimately make it to the marketplace with this target and having the only approach out there that is based on PCSK9 synthesis inhibition, which we think is very important differentiated mechanism. We think makes it a compelling value opportunity. So we will play this out. We’re excited about where to go with the partner and in an integrated way, we are ultimately making decisions about how we allocate resources across, a lot of really exciting programs so we just can’t do everything.

Yeah no, I’m not asking you to do everything, it just seems like the incremental investment here with respect to your proprietary programs wouldn’t be all that great compared to the incremental increase you could realize in terms of your economic retention of the program, I mean just one or two additional doses, may be a little correlation between PCSK9 gene knock down and protein, some other things that helps you inform that don’t cost a lot but could be worth, you know whatever, some multiple in terms of front end payments or downstream royalties?

Yeah I mean all very valid points, Mike, you know obviously we’re thinking about all these things as well. You know and these are just judgment calls as to where we think we can get the most value and the best value and we will see how all that plays out.

And your next question comes from the line of Ted Tenthoff with Piper Jaffray.

Question around the HTT program and the decision to not continue to invest here, this is one that has been you guys have been working on for a long time with Medtronic. Can you give us a little bit more color on that decision? Is it based on delivery? I know it’s been a long time to get this thing moving towards the clinic. So can you give us a little bit more on that decision?

Yes, I can and I think others, Akshay and Barry may want to comment as well. The fundamentals of this - it’s a very exciting program and it’s really a program that for a lot of reasons has generated some very compelling data in a number of animal models, both rodent models and also non-human primate models. But it’s a program that of course requires the use of an implantable infusion pump technology and therefore for reasons that I think anybody who understands drug development will understand, is a much more complicated program than other programs that we have in our pipeline. It’s also a program that in the context of clinical development doesn’t have the types of things we like in our Alnylam 5x15 programs namely a very early biomarker that we can measure on Phase I it’s got a longer type of timeframe. So we’ve always have the option in the agreement with Medtronic to either continue to co-invest on 50-50 basis and share this at the end of the day or the option to essentially opt out and become a milestone of royalty player and we’re just making a fundamental business decision consistent with our overall focusing of efforts on TTR and hemophilia for the most part at least in the near term and then other Alnylam 5x15 programs longer term that puts that program into the bucket where being a milestone of royalty play for Alnylam is a pretty damn good place for us to have it, I mean I know Barry you have all the thoughts...

John I think you covered it and said consistent with really the strategy that we set out at the beginning of last year. We solved delivery to deliver, we know exactly how it works and it works elegantly with that two platforms to deliver LNPs and conjugates and we got programs that will be in pivotal trials in short order where we’re seeing significant commercial opportunities in that kind of value creation timeframe between now and 2015. So this is consistent with that the good news is the program got to a stage where we had understood – way ahead of time via the contract that we could in fact opt out and move to a different arrangement seamlessly where we will continue to provide a support for the program.

So you know it’s following the strategy, exactly we’re excited about the program but it really makes sense for us to drive TTR hemophilia to pivotal trials into the market for the greatest value creation.

That’s great, that’s really helpful additional color. And since Laurence is sitting with you guys, can you give us sort of an update on the general partnering interest of RNAi medicine here. I really think that we hit a lull two years ago and where some of the important data that you guys have reported in terms of validating RNAi’s mechanism also some of the other technologies that are targeting RNAi , I’ve seen a shift in interest and I just want to see if you guys had something that from potential partnering precautions.

Yes, Larry is going to handle it.

So we definitely see the shift I mean from a sort of parochial view, I have been here for nearly two years now and even those two years I think I’m seeing the same trend that you are referring to debt relative to where that has gone to over the previous bit of time. And I think [indiscernible] was six months since the two sets of clinical data came into TTR data in Thanksgiving and the PCSK9 data over the last quarter that I think the belief in the demonstration of Molecular Pharmacology in human beings is very compelling and brings people to a discussion who probably a year ago were really sitting on the sidelines watching. I think how that plays out exactly in terms of the deals and the kinds of deals we’ll do in the coming months remains to be seen to be frank, and I think it’s also fair to say that there are still some pharmaceutical companies who prefer and are looking for more advanced clinical data then that we’ve yet produced, but I think overall the move, change and the willingness to entertain the discussions and to talk about products like PCSK9, we got a lot of incoming interest in our TTR amyloidosis program and the rest of the pipeline. I would say it’s changed significantly on the back of clinical data in the last several months.

Of course, the case of our TTR programs, we’re not partnering that program at least for vast the majority of the world.

[Operator Instructions] And your next question comes from the line of Alan Carr with Needham & Company.

This is Mark in for Alan. I was wondering if you guys might be able to give us a little bit of an update on various ongoing litigation?

Yes, I mean it’s – Mark, it’s hard for us to say very much about ongoing litigation other than we don’t comment about ongoing litigation. But I think what we can say is, we are as convinced as ever that the suit that was brought against us by Tekmira is completely without merit, is baseless and we will defend ourselves fully in that suit and we will be meritorious and that’s all we can say.

Okay, that’s good. Also want to ask a little bit about the RSV program. I know it’s difficult to say in general what kind of data do you expect to be getting from that, but what kind of data are you expecting to be getting from that? What’s going to happen with positive data, how does that affect your relationship with Cubist going forward?

Yes. Good. I’ll let Akshay comment on that in a minute, but let me just remind you Alan is - no, you’re not Alan, Mark and others that the RSV Phase IIb study that is currently blinded is an effort to reproduce a very interesting finding in a small, underscore small, Phase IIa study that was done a couple of years back. And we have been very clear with people that obviously we are looking to reproduce a finding in a small study, and very often when you do an effort to reproduce a finding in a small study, that is repetitive, and so we have been clear with people that it’s not all clear if this is going to report out of positive results or negative results for that matter. We did it because we believe that there might be an opportunity for positive results, but it’s certainly not a program, because it is partnering with Cubist that is in our core sweet spot of Alnylam 5x15 that said, we did the experiment of Phase IIb with the goal of seeing a positive result and we will see how that plays out, middle of this year, but I will leave it to Akshay, who will comment further on the types of data that we will be seeing Akshay?

Yes, so in terms of the types of data, Mark, the small Phase IIa study that John mentioned, which showed an impact on the instance of bronchiolitis obliterans, which is a syndrome that leads the narrowing of the airways in the transplanted lung after an RSV infection in fact devastating and very serious complications in the five year, 50% mortality and so it clearly worthwhile and those perceive to understand that benefits further and so the study, which is fully enrolled, the primary endpoint was going to read out of six months comparing ALN-RSV01 to placebo in lung transplant patients treated, RSV infected lung transplant patients treated with one or the other. And the primary end point is going to be just that was power to show superiority of RSV01 against placebo for the bronchiolitis obliterans, and around mid-year we should get the data and we will be happy to report. Obviously that would be safety that the lung functions tested a along the way, that the symptoms goes and that those are really the highlight that we will be looking for.

And in terms of Cubist, I mean obviously, when we get the data we we’ll sit that with our partners Cubist and also Kyowa Kirin who are partners in Japan and Asia and we will certainly discuss the results with them but you know that’s in excess, it’s really do the unblinding, get the results, get the data and analyze the results, communicate them to the outside world and communicate them with our partners.

The next question comes from the line of Stephen Willey with Stifel, Nicolaus.

Just a quick question on TTRsc. Just wondering, I guess when you plan on having the GalNAc-conjugate delivery version into the clinic, and I guess if that would influence your plans on the version of protein C that you intended before to hemophilia.

That’s a great question. So, first of all the conjugate platform is an exciting development at Alnylam that builds up a work that we have been doing, I mean, since 2004 actually was when we published our first paper using conjugate. But more recently over the last two years in particular using a GalNAc targeting to the Glycoprotein receptor in a parasites we have been incredibly successful with developing simple conjugates of sRNAs for delivery. TTR subcu will be the - to file our IND in the second half of this year, so all those well this time next year, we will have clinical data from that study and then obviously, we’re looking at any of our 5x15 programs where there might be a competitive advantage of using a subcu delivery for the opportunity of using our conjugate platform as compared to our LNP platform and it does weigh into our developing candidate decision for the hemophilia program which we’ll be making by the end of the second quarter of this year and we’re looking forward to updating people at the World Federation of Hemophilia Meeting that will be taking place in July. And so I would say stay tune till then to know a little bit more about the call forward on that program, but I think it’s fair to say that having the luxury of multiple delivery technologies both the LNP platform as well as the subcu conjugate platform has really both of which are very efficient toward the liver and liver’s best target genes has really strengthened our fundamental strategies for product development in the company.

Okay, that’s helpful and then with respect to the patent that was received, today I guess regarding the TTR gene, can you maybe just talk a little bit about what that covers?

Yes. Let me -- it’s really simple to cover our -- the sequence of our sRNAi that’s used in our drug, so it is the TTR02, sRNAi structure, composition of matter that’s covered in that patent, so it’s a pretty important pattern from a product development standpoint and product commercialization standpoint.

And we have another next question from the line of Mike King with Rodman & Renshaw.

I just wanted to find out, I got on the call a little bit late. So I want to be sure is the pivotal for TTR2 was in early ‘13, was that correct?

The guidance has been in ‘13.

In ‘13 okay and just question for Akshay what are you envisioning in terms of duration of therapy, number of patients et cetera?

Yes, Mike, we are still in the planning stages. It will be premature before we complete our diligence and how all the appropriate confirmations and regulations. And just the matter of guidance to tell you what was done from the study. 120 patient study and they study patients about 18 months. And one of the things you want to remember in terms of duration of treatment with a drug that’s attempting to look at neuropathy is that in neuropathy is a slowly onset and slow to get better when they get better. We are not going to be fortunate with a drug that will take away the pathogenic protein that we are optimistic about stabilization probably improvement in the neuropathy. But it’s not going to be days or weeks. It certainly a significant period of time during the month, so more to come.

And do you think you’re going to have to go on top of Tafamidis or you still be in a population of what mark so we get to Tafamidis?

Yes, I think as I was discussing earlier we see scope for this growth in many of the prospects, but let’s reiterate one thing that’s important is we think we’ll be the best in class and that we’re going to have a therapeutic that’s once a month or maybe less frequent with very significant [indiscernible] protein and we’ll do because of that type of potency and convenience will do more for these patients than anything for parameters or any other drug we believe could do. Certainly there is a possibility to combine with the Tagamidis. That’s not an impossibility, but given the confidence we have and the likelihood of profile, we think we are going to have the best-in-class.

And then, just quickly when do you think you will do cardiomyopathy?

We’re very excited about that opportunity as well. Thanks for bringing that up, and that is another major problem of these patients. We want to get through the Phase II study that we will start in the second half of this year and emerging confidence we’ll have from the program in combination of the lot of safety data final and lots of PD data both in Amyloidosis patients, I think will be define the final plan, not just of the pivotal in 2013, but also graphic, while they are cutting off.

And at this time, there are no further questions in queue.

Good. Well, thanks, everyone. Alnylam continue to lead the advancement of RNAi therapeutics to patients and we are extremely proud of our recent clinical and business accomplishments and we are excited to share lots of interesting news and exciting news in the months to come. So stay tuned. Bye-bye now.

Ladies and gentlemen, that concludes today’s conference. Thank you for your participation. You may now disconnect. Have a wonderful day.