Alnylam Pharmaceuticals Inc (ALNY) 2013 Q1 法說會逐字稿

Welcome to the Alnylam conference call. There will be a question and answer session to follow. Please be advised this call is being taped at the Company's request. I would now like to turn the call over to the Company.

Good afternoon, everyone. I'm Cynthia Clayton, Vice President of Investor Relations and Corporate Communications at Alnylam. With me today are John Maraganore, Chief Executive Officer; Barry Greene, President and Chief Operating Officer; Akshay Vaishnaw, Executive Vice President and Chief Medical Officer; and Mike Mason, Vice President of Finance and Treasurer. Laurence Reid, our Chief Business Officer, is also here and available for Q&A.

For those of you participating via conference call, the slides we have made available via webcast can also be accessed by going to the investor's page of our website at www.Alnylam.com. During today's call, as outlined in slide 2, John will provide some introductory remarks and provide general context. Akshay will summarize the clinical progress with our Alnylam 5x15 and printed program. Mike will review our financials and guidance. And Barry will provide a brief summary of our business highlights, goals, and upcoming milestones before we open the call for 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 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 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 such statements.

I will now turn the call over to John.

Thank you, Cynthia. Welcome, and thanks, everyone, for joining us this afternoon. By all accounts, these are incredibly exciting times at Alnylam. With our Alnylam 5x15 product strategy, we are focused on development and commercialization of RNAi therapeutics, directed toward genetically-defined targets for diseases where there are limited treatment options for patients and their caregivers. Our efforts here drive what we believe is a compelling opportunity for the development of high impact medicines that can drive significant value creation.

Activities in the past quarter and recent months represent a notable period of pipeline and business accomplishment for Alnylam. On the pipeline side, we continued enrollment in our ALN-TTR02 Phase II trial, started enrollment in our TTR subQ Phase I trial, completed a number of key pre-IND activities for our AT3 hemophilia program IND filing for mid-2013, and ramped up efforts in our PCSK9 hypercholesterolemia program following completion of our alliance with The Medicines Company. With these and other efforts, we are positioned for a very data-rich period with key data that we'll report in May, June, and July. We also plan to host an R&D day in New York on July 11 to put all of these data into context for you as we continue to execute on our Alnylam 5x15 product strategy. So we are very excited about the months and year ahead, as we advance our programs into late stage development and toward the market.

And with that, I'll now turn the call over to Akshay to provide a more detailed review of our clinical activities, our pipeline, and our scientific progress. Akshay?

Thanks, John, and good afternoon, everyone. As John mentioned, we've had an extremely rewarding and productive period on the clinical front, with our Alnylam 5x15 product strategy.

I'll start with an update on our ALN-TTR02 program. As most of you are aware, ALN-TTR02 is our lead program and is aimed at the treatment of TTR-mediated amyloidosis or ATTR. ATTR is a devastating hereditary and often fatal disease caused by mutations in the TTR gene. As an orphan disease, ATTR afflicts approximately 50,000 people worldwide and is associated with significant morbidity and a mean life expectancy of just 5 to 15 years from symptom onset. It is clear that new therapies are needed for the treatment of ATTR and we believe that our mechanism of action that is silencing of the disease-causing TTR gene leading to knockdown of the circulating pathogenic TTR protein have the potential to generate a profound therapeutic impact. We are conducting a Phase II study with ALN-TTR02, this is an open-label, multisymptom, multidose, dose escalation trial. Primary objectives of the study are to evaluate the safety and tolerability of multiple doses of ALN-TTR02 and to measure clinical activity based on serial measurements of circulating serum TTR levels. We're announcing today that we expect to report initial results from this trial at the biannual meeting of the Peripheral Nerve Society, being held June 29 to July 3 in St. Malo in France, pending acceptance of our submitted abstract.

We also plan to expand the study to a total of about 30 patients with additional study sites to explore additional cohorts treated with once every three-week dosing regimen and the reduced steroid premedication regimen. We expect data from these additional cohorts to be available later in the year and to add to our overall body of data to finalize dose and dose regimen for start of our Phase III. Furthermore, the additional sites that we add in our Phase II will assist in our site accrual efforts for Phase III. We also remain on track to initiate an open label extension study of ALN-TTR02 for patients treated in this Phase II study. Importantly, this extension study will include a number of clinical end point measurements with initial data to be presented in 2014. Assuming positive results from the Phase II study, we remain on track to start our Phase III pivotal trial for ALN-TTR02 in familial amyloidotic polyneuropathy, or FAP, by the end of 2013. To support the start of this trial, we have successfully completed the necessary long-term nonclinical studies, including six-month rat and nine-month nonhuman primate studies. Importantly, we believe these results support chronic dosing in humans.

We're also advancing ALN-TTRSc, a subcutaneously delivered RNAi therapeutic for the treatment of ATTR. We began enrolling in our Phase I trial in the first quarter. This is a very exciting milestone for Alnylam and the entire field of RNAi therapeutics, as this is the first subcutaneously administered systemic RNAi therapeutic to start clinical development. It's also the first program from our proprietary GalNAc-conjugate platform to enter the clinic. The trial is designed as a randomized double-blind, placebo-controlled, single and multiple dose, dose escalation study enrolling up to 40 healthy volunteers. The primary objective of the study is to evaluate the safety and tolerability of single and multiple doses of subcutaneously administered ALN-TTRSc. Secondary objectives include assessment of clinical activity of the drug, as measured by serum TTR levels. We expect to report data midyear, and upon completion of this trial, start a Phase II clinical study of ALN-TTRSc in ATTR patients with cardiomyopathy by the end of 2013. Looking ahead and assuming positive results, we expect to start a pivotal trial for ALN-TTRSc in ATTR cardiomyopathy patients in 2014.

Our other Alnylam 5x15 programs also continue to advance. ALN-AT3 is our RNAi therapeutic targeting antithrombin for the treatment of hemophilia and rare bleeding disorders. This is a very exciting program, since antithrombin knockdown can reset the coagulation cascade in patients with hemophilia and other rare bleeding disorders, enhancing thrombin generation and improving hemostasis. Furthermore, as a subcutaneously administered medicine, ALN-AT3 could provide patients with a new and far easier approach for prophylaxis in a clinical setting where all other current drugs are administered by frequent intravenous infusions. Our preclinical findings to date for this program show that subcutaneous administration of ALN-AT3 results in potent dose-dependent and durable silencing of antithrombin in preclinical models, and the antithrombin reduction can normalize thrombin generation in animal models of hemophilia, thereby establishing proof of concept for this program. We plan to present new preclinical data for this program at the International Society of Thrombosis and Hemostasis, otherwise referred to as ISTH at the meeting in early July, and are on track to file an IND in mid-2013, leading to the start of a Phase I trial in late 2013. The ISTH meeting is the world's leading meeting in hemostasis and thrombosis research, and we're very pleased to be presenting our data there as an oral presentation.

Beyond our TTR and AT3 programs we were pleased in the first quarter to designate ALN-AS1 as a new program in our Alnylam 5x15 product strategy. ANL-AS1 is a RNAi therapeutic targeting aminolevulinate synthase, or ALAS-1, for the treatment of acute intermittent porphyria, or AIP. AIP is an ultra rare orphan disease caused by loss of function mutations in porphobilinogen deaminase, or PBGD, an enzyme in the heme biosynthesis pathway. Loss of function mutations in PBGD can result in accumulation of toxic heme precursors. Patients with AIP suffer from acute and/or recurrent life-threatening attacks with severe abdominal pain, peripheral autonomic neuropathy, and neuro psychiatric manifestations. Approximately 5,000 patients in US and Europe suffer AIP attacks annually, and approximately 500 are afflicted with recurrent debilitating attacks. ALN-AS1 is a GalNAc-conjugated siRNA targeting ALAS-1, a liver-expressed rate-limiting enzyme upstream of PBGD in the heme biosynthesis pathway. Inhibition of ALAS-1 is known to reduce the accumulation of heme precursors that cause the clinical manifestations of AIP.

We plan to present preclinical data from this program at the International Congress of Porphyrins and Porphyrias in a couple of weeks in Lucerne. We're making terrific progress in this program and we expect to identify a final development candidate by late 2013 to advance the clinic in 2014. Clearly, we continue to make tremendous progress with our Alnylam 5x15 programs and we look forward to continuing to share data and updates from these programs with you in the coming weeks and months. Indeed, as John mentioned earlier, and as you can see on slide 11, the strong progress we made in the first quarter will now bear some important data readouts that occur in May, June, and July. With that, I would like to now turn the call over to Mike for a review of our financials. Mike?

Thanks, Akshay, and good afternoon, everyone. I will be referring to slide 13 to review our financial results for the quarter. Alnylam continues to maintain a very solid balance sheet, ending the first quarter with $400.8 million in cash, cash equivalents, and marketable securities. In the quarter, we further strengthened our balance sheet with a public offering of 9.2 million shares that resulted in net proceeds of $174 million.

Our GAAP revenues were $18.6 million in the first quarter of 2013 as compared to $20.6 million in the first quarter of 2012. In the quarter, we recognized the remaining deferred revenue of $9.7 million under our agreement with Cubist, which was terminated in the period. As a result, we expect net GAAP revenues from research collaborators to decrease for the remainder of 2013. Regarding the $25 million upfront payment from our Q1 Medicines Company alliance, we will be recognizing GAAP revenues related to this payment on a straightline basis over five years.

Moving to expenses. R&D expenses were $22.2 million in the first quarter of 2013 as compared to $21.1 million in the prior-year period. This increase was due primarily to additional expenses related to the advancement of our ALN-TTR02, ALN-TTRSc, and ALN-AT3 programs. G&A expenses were $6.3 million in the first quarter of 2013 as compared to $10.4 million in the first quarter of 2012. The decrease in G&A expenses in the first quarter of 2013 as compared to the first quarter of the prior year was due primarily to a decrease in consulting and professional services-related expenses, related to business activities, primarily legal activities. For the remainder of 2013, the Company expects that general and administrative expenses will remain consistent with the first quarter.

With respect to guidance for 2013, we continue to believe we will finish the year with greater than $320 million in cash. In sum, we believe we have a very strong balance sheet that will enable us to advance our Alnylam 5x15 product development and commercialization strategy. This concludes the financial highlights. I'll now turn the call over to Barry.

Thanks, Mike. As you've heard this afternoon, we're demonstrating with human clinical data that the RNAi pathway can be harnessed to create what we believe will be high impact, innovative medicines. In addition to the exciting clinical advancements we made in the recent period, we also made excellent progress on the business and operational fronts. Specifically, as you heard from Mike, we completed a very successful offering that strengthens our balance sheet for continued execution on our Alnylam 5x15 product strategy. We also formed a strategic global alliance with The Medicines Company to advance ALN-PCS, an RNAi therapeutic targeting PCSK9 for the treatment of hypercholesterolemia. This alliance includes ALN-PCS02 and ALN-PCSsc, which are RNAi therapeutic product candidates administered by intravenous infusion and subcutaneous injection respectively. We're particularly excited about the opportunity for subcutaneous administration and have made some very strong progress on that aspect of this program.

Per the terms of the agreement, Alnylam will lead completion of certain preclincal and Phase 1 clinical studies while The Medicines Company will lead and fund development from Phase II forward and will own commercializing ALN-PCS program, if successful. The Medicines Company has made an upfront cash payment of $25 million to Alnylam. In addition, Alnylam is eligible to receive development and commercial milestone payments totalling up to $180 million, as well as double-digit royalties on ALN-PCS product sales. In aggregate, these recent business achievements strengthen our efforts in bridging innovative medicines to patients who currently have limited treatment options.

In closing, I want to take a moment to summarize our goals and our plans to share data. With regard to our TTR program, we expect to present data from our Phase II trial with ALN-TTR02 at the PNS meeting being held June 29 through July 3. We aim to begin our open label extension study in mid-2013, and plan to initiate the Phase III pivotal trial in polyneuropathy patients by the end of this year. With our ALN-TTRSc Phase I trial under way, we're on track to present data from that trial midyear. And we expect to start a Phase II study in cardiomyopathy patients with ALN-TTRSc later this year, leading to the start of a Phase III trial in cardiomyopathy patients in 2014. In our ALN-AT3 program for hemophilia, we'll be presenting a new preclinical data at the upcoming ISTH meeting being held June 29 through July 4. We intend to file an IND for this program in mid-2013 with a Phase I start later this year. And with our ALN-AS1 program for the treatment of acute intermittent porphyria, we plan to present preclinical data at the Porphyria meeting being held May 16 through 18, the meeting that Akshay already touched on. We expect to identify final development candidate for the program by late 2013 and enable advancement into the clinic in 2014.

Now turning to the business side. We intend to seek additional partnerships on other Alnylam 5x15 programs while retaining significant rights in major parts of the world for our core programs. And following our successful financing earlier this year, we plan to end the year with greater than $320 million in cash. As John mentioned earlier, we welcome you to our R&D day in New York City on July 11. We hope to see you all there. Cynthia will be providing more information in the coming weeks, but please save the date.

In summary, I think it's clear we are executing on our goal of driving innovative RNAi therapeutics to patients in need. Our efforts in the first quarter have positioned the Company for important data readouts in May, June, and July, and we look forward to sharing all of this with you. With that, I would like to turn the call back over to the operator for your questions. Kate, we'll take questions now.

(Operator Instructions)

Our first question comes from the line of Marko Kozul with Leerink Swann. Your line is open.

Hi. Thanks for taking the question. This is Irene in for Marko.

Hi, Irene.

Hi. On ALN-TTR02, you've mentioned that data will be coming in late June, and you are extending the study to 30 patients. Just want to ask if you can clarify for us if the data for all 30 patients will be presented in late June?

Let me let Akshay answer that.

Yes, so we will be presenting initial data at the meeting in France at the end of June, early July, as you mentioned. And we are expecting those data to be in line with the original study, whereby we had said we are dosing across the dose range going up to 0.3 milligram per kilogram dosing every four weeks. And I think we'll be in good shape to present those data, both from a safety perspective, as well as, importantly, the clinical type data with the pharmacodynamic activity of the drug, now looking to see how does it look like over multiple doses after the very exciting data from last year, with single doses of 0.3.

Thanks very much. That's very helpful. Just one more on TTR -- it seems that there could be a lot of data presented at the November [ISFAP] meeting. Could you give us a preview of what you believe might be presented there?

Well, Akshay, you should make some comments, but obviously, we will be presenting additional data at that meeting as well. We certainly plan on being at that meeting. Our program is a very important program in the community, and we're going to be obviously presenting our Phase II data mid this year, and we'll also present our TTR subQ data middle of the year as well. We haven't given more precise dates on that. But we'll also be presenting data at that November meeting.

Akshay, anything else?

No, I think it's a wonderful opportunity in front of a key audience. Both those areas will be highlighted with more data, I'm sure.

Yes.

Thanks very much. Regarding ALN-AT3, can you talk about your control of the test gate therapeutic window, and any predictions you have on what the ideal therapeutic titration level might be?

And last week, Bayer ran into a snag with a 6150 program. Can you talk about maybe the competitive landscape of the candidates being developed specifically for patients with inhibitors?

Yes, absolutely.

Akshay, do you want to handle that?

Yes, let's just start with the competitive landscape. I think, sadly, these patients are in a very disadvantageous position compared to other bleeding disorder patients. They can't have any prophylaxis treatment currently, because the one drug that's available to them, NovoSeven, and they can, of course, use the related fiber product as well. They have to be given intravenously, and they have short half lives, and they just can't be given frequently enough to make them practical prophylactic treatment. So really, they need something that will prevent bleeding when they are in this terrible situation where they have antibodies as their replacement factor.

The product you're speaking about, the Bayer long-acting VIIa -- the idea there was that it's long-acting, so then it could be given several times a week, as opposed to NovoSeven would have to be given every day, several times a day almost, for it to be effective. So the Bayer product would have been given less frequently, but sadly, as is often the case (inaudible) [developed to fat], and so that's really a bad situation, and understandably, the study was stopped.

Now, with respect to our product, and as you said, we're initially very interested in developing in inhibitor patients where there's high unmet need, and if you look at hemophilia patients that have inherited deficiency of AT3, rather than any issues in terms of thrombosis or anything like that, they are in a much better position than the average hemophilia patient. They stop bleeding later in age. They consume less replacement factor. And most of them have much fewer in the way of joint and muscle complications, which are sadly common in hemophilia.

So there's a very wide therapeutic index perceived from that experiment of nature, where hemophilia patients have inherited so-called thrombophilic mutations like AT3 deficiency. We also get information from the mouse. And so if you take a hemophilic mouse and you cross onto that AT3 deficiency, it's the same as in the human context. Those mice in fact do very well, and they benefit, and they have fewer reductions. Again, there's no evidence of thrombosis or blood clots.

So all of this goes to say, and we're increasingly finding with our laboratory work, that knocking down AT3 in the hemophilic context really to our data and our minds, speak to very expanded therapeutic index, and the idea that there would be significant benefit. The details beyond that we're going to present at the ISTH meeting, but we're really pretty excited about this.

John, I don't know whether you want to add --

Yes, I would just add, Irene, obviously we are going to be presenting some data relatively soon in June -- late June, early July, and that's a very important data set by our accounts, and just stay tuned. But we are very excited about the program. We think it could be a transformative therapy for many segments of the hemophilia patient population, and certainly including the inhibitor patients. And the Bayer -- unfortunate news from the Bayer program obviously just speaks to the need for new, important medicines in that segment.

Thank you so much for taking questions. And congratulations on very exciting progress.

Thank you.

(Operator Instructions)

Our next question comes from the line of Ted Tenthoff with Piper Jaffray. Your line is open.

Great. Thank you very much. Thanks for the update. It's going to be an exciting summer and remainder of the year.

We agree, Ted.

My question is for Barry, and kind of the comments along the lines of some additional partnering opportunities. My understanding is that these core programs -- TTR, hemophilia, and the new one that you announced -- are programs that Alnylam really intends to retain and develop internally. But what are some of the partnering opportunities beyond that? Are we talking specific target type deals, almost like with respect to what Isis has been doing with some of their rare disease? Is there -- what is sort of the higher-level thinking in terms of additional partnering opportunities?

Well, so Ted, let me have Barry and Laurence, who is here -- (multiple speakers)

Great, hi, Laurence.

-- also answer part of that question. Barry, why don't you start with some context, and then, Laurence, you can give some general dimensions.

Ted, thanks for the question. As you're well aware, first of all, from the beginning, our business model was to develop and commercialize important therapeutics in major markets on our own. And at the beginning of this year, we clarified that to say that our TTR program, the hemophilia program, and the new porphyria program were programs we were going to commercialize in North and South America, Europe, and selectively partner, as we do with TTR, in the Asia region. So for those core programs, we're going to take the drugs forward on our own. We've given guidance that other programs, in order to move forward, would require partnerships.

Let me ask Laurence to touch on some of those.

Yes, hi, Ted. Two categories I would say as we think about it actively these days, and they are product-driven types of partnerships, as you are referencing. And then to actually broader things as the technology platform continues to expand its obvious capabilities. So on the product side, you have understood and recapitulated very nicely that the strategy to focus our key investments and bandwidth currently in the three leading projects as a 5 by 15 strategy has really expanded in the last couple of years. We're getting a number of other very exciting projects that are behind that, where we're looking to partner them so we can bring extra resources in through a partnership to really expand the pipeline and our participation and the value of the overall 5 by 15 program.

And the two leading examples of that, that we've talked about publicly -- also we have others coming behind that we're getting increasingly excited about. But the leaders are really the AAT liver disease program. So that's for the liver disease that follows from AAT genetic deficiency, and that program is in a preclinical research program. And then secondly, but equal priority really, the ALN-TMP program which targets Tmprss6 for our iron overload diseases, particularly beta-thalassemia, potentially other disorders in which iron overload is a chronic problem. So both those projects we talked about publicly -- very exciting data sets. Both cases, we have world-class collaborators, and we think those are both exciting projects that may be in a lot of our business development conversations in a very active, ongoing way.

And then broadening out from that, as we have come to understand the potential of the conjugate subcutaneous platform, we think there's really going to be an increasing set of diseases where chronic administration of a subcutaneous drug product is really going to open up for us in a number of new disease areas that historically we've not been focused on. And we haven't really talked a lot about those publicly, but they're, I think, going to increasingly become part of our strategy. And I think there, we will probably look to bring in partners early in some of those programs, maybe taking from a partnering perspective into disease areas where Alnylam probably may not be best suited to go all the way towards the commercial product ourselves, at least in the earlier years of that strategy. And I think about it in two broad categories.

Ted, just to add to that, clearly there are going to be some programs beyond porphyria, and hemophilia, and TTR amyloidosis that we will continue to keep ourselves, and advance into the major markets of the world as a commercial -- direct commercial effort. So we are trying to find the right balance. There's certainly more here than we can possibly do on our own. So there will be partnerships in the future. But most importantly, the things that we think really drive value are the programs that we are retaining ourselves, and driving all the way to the market.

I agree. Quick question, if I may, on TTR02 and TTR subQ. I like how you're using FAC to explore the potential of the subQ administration, and I know that you had really good knockdown with the IV formulation. What if subQ just looked significantly better? I know that it's potentially a little bit less potent, but there's more administration. In a longer term, is this something where potentially you could seek approval for both drugs if they both work, and we're so fortunate in both indications, and then let patients kind of determine how they want to be treated or sort of see how the clinical data really leads out? What's your sort of longer-term view of this balancing of TTR02 and TTR subQ between the different manifestations of TTR?

I'm going to let Barry answer that question, but I'm just going to start by saying that we are very, very committed to best-in-class medicines for patients with ATTR, and so it has been important for us to really launch what we think is the industry-leading effort in this disease.

And then, Barry, you should comment a little bit on our thinking with [Oved] and our commercial thinking around how this all plays out.

Let me just emphasize what John said. In a significant disease setting such as this, we want to do everything we can to treat these patients, and that includes the two product efforts we have right now. ALN-TTR02 is very focused on the polyneuropathy opportunity where we'll start a Phase III later this year. And we have a clear set of end points in terms of the neuropathy end points. We think that, given the patient population, how they are disseminated, that subcutaneous approach with ALN-TTRsc is very attractive for those patients, so we are very focused on that for cardiomyopathy.

Now, if you play this out longer term, Ted, and we're fortunate enough to have both products approved and on the market, the pharmoeconomic support for both programs are similar, in that we've got life threatening diseases with significant co-morbidities. So there wouldn't be a financial incentive for a physician or patient to switch on product. So we won't sort of have that issue, if you will. More importantly, we have the opportunity of, as you said, looking at each product in the other patient setting, and then making sure that there's a dose convenience schedule that's right for the patient and their provider, their physician, so that someone gets on our drug early and stays on our drug for the rest of their life, preventing death from their disease.

All right. Excellent. Thanks, guys.

Thanks, Ted.

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

Hi. Thanks for taking my questions.

Hi, Alan.

Good evening. Can you comment on the regimen change that every three weeks versus every four weeks, and some of the changes you're talking about with respect to steroids in the Phase II trial that you're expanding? Can you comment on that?

Yes. I mean, Akshay, you want to --

Hi, Alan. So we are going to present the initial data from the study [in the Journal], and we're pretty excited about that. We've met all of the objectives there -- those patients are enrolled, they're studied. And I think we have opportunity now to really look at a couple of other things. We've talked about the steroid pre-regimen. It's nice to look further into that with additional patients to see how we can optimize it. So we have an opportunity to do that now.

And also to study variance on the Q4 weekly. We've shared the data that we expect around once every four weekly knockdown, and it looks pretty exciting. But I think we want to pick the best dose and dose regimen to go into Phase III by the end of the year. We look on track to do that; these additional data is just going to be helpful in that decision-making.

What prompted the shift to Q3?

We shared -- as you probably recall, Alan, we shared earlier in the year some nonhuman primate data looking at the Q4 weekly regimen longer term, and one of the possibilities as we've always looked at those data was that Q3 weekly might be a more interesting approach as well. We want to just see how that plays out in humans as well. We've got clearly time to explore that before we launch the Phase III, along with obviously the potential of looking at a significantly reduced steroid pre-med regimen. And getting those additional data points we think will give us the best information for dose selection and dose regimen selection for the Phase III.

Okay, and then -- thanks. Then, with respect to your work with Medicines Company, can you give us any sense of what sort of work is still needed, and when that might be ready to hand over to Medicines for Phase II?

Yes. I mean, in general terms -- why don't I go ahead and answer that. The program, as you know, completed a Phase I study -- single-dose Phase I study. There was work that was needed to facilitate a multidose study, mostly preclinical type tox work. In addition to that, we've made this progress with our subQ platform, and there really is some quite promising work that we've generated on the subQ approach for PCSK9. Before we get back into the clinic with the program, there are certain preclinical, nonclinical IND-enabling type work that's going on to facilitate a multidose approach and a Phase II study. And how that plays out between the subQ approach going forward I think is to be informed by the data that emerges over the next short period. And so stay tuned on that. But we certainly like where the subQ drug positions the product vis-a-vis the competitive landscape out there with the anti-PCSK9 antibodies.

I take it no specific guidance on a timing then at this point?

Not yet, Alan. We'll hopefully provide that sometime later in the year, but it's -- efforts have been restarted, and things are going along real well.

All right, great, thanks very much.

Thanks, Alan.

I'm not showing any further questions at this time. I would like to turn the call back over to Alnylam for closing remarks.

All right. Thanks, everyone. We continue to lead the development of RNAi therapeutics to patients, and we're very proud of the clinical and business accomplishments. As I think you've heard today, May, June and July will be important months for data readouts. We look forward to sharing these with you, along with our overall progress on RNAi therapeutics and our 5 by 15 efforts. Thank you very much.

Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program, and you may all disconnect. Everyone have a great day.