Good day, ladies and gentlemen, and welcome to the Regeneron Pharmaceuticals Third Quarter 2015 Earnings Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session and instructions will follow at that time. As a reminder, this call may be recorded.

I would now like to turn the conference over to Dr. Michael Aberman, Senior Vice President of Strategy and Investor Relations with Regeneron. You may begin..

Thank you, operator. Good morning, everybody, and welcome to Regeneron Pharmaceuticals' third quarter 2015 conference call. An archive of this webcast will be available on our website under Events and Presentations for 30 days. Joining me on the call today are Dr. Leonard Schleifer, Founder, President and Chief Executive Officer; Dr.

George Yancopoulos, Founding Scientist, President of Regeneron Laboratories and Chief Scientific Officer; Bob Terifay, Senior Vice President, Commercial; and Bob Landry, our Chief Financial Officer. After our prepared remarks, we'll open the call for questions and answers.

I would also like to remind you that remarks made on this call include forward-looking statements about Regeneron.

Such statements may include, but are not limited to those related to Regeneron and its products and business, sales and expense forecasts, financial forecasts, development programs, collaborations, finances, regulatory matters, intellectual property and competition.

Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in such statements.

A more complete description of these and other material risks can be found in Regeneron's filing with the United States Securities and Exchange Commission, or SEC, including its Form 10-K for the year ended December 31, 2014 and Form 10-Q for the quarter ended September 30, 2015, which was filed with the SEC this morning.

Regeneron does not undertake any obligation to update publicly any forward-looking statement, whether as a result of new information, future events, or otherwise. In addition, please note that GAAP and non-GAAP measures will be discussed on today's call.

Information regarding our use of non-GAAP financial measures and a reconciliation of those measures to GAAP are available in our financial results press release, which can be accessed on our website at www.regeneron.com. Once our call concludes, the team will be available to answer further questions.

With that, let me turn the call over to our President and Chief Executive Officer, Dr. Leonard Schleifer..

sarilumab for rheumatoid arthritis; dupilumab for a variety of allergic and atopic diseases; REGN2222 for respiratory syncytial virus; and fasinumab, our NGF antibody for osteoarthritis-related pain. We also made important announcements around our early stage research programs, including a collaboration with the U.S.

Health and Human Services' Biomedical Advanced Research and Development Authority Division, also known as BARDA, in Ebola, which highlights Regeneron's rapid response capabilities for emerging infectious diseases.

And the publication of our discovery of the mechanistic basis for the rare disease known as fibrodysplasia ossificans progressiva, or FOP, in science translational medicine, as well as the identification of a therapeutic candidate for this terrible disease. You'll hear more about some of these advances from George.

As we discussed on our last quarterly call, early in the third quarter we announced a major new collaboration with Sanofi in immuno-oncology, and we continue to advance our programs in this area. I want to take a moment to reflect on our achievements this quarter, as they highlight Regeneron's unique position.

While we continue to have strong top line growth from EYLEA, we are also in the midst of an important launch with Praluent and are positioned to bring multiple important new medicines to patients in the coming years, including sarilumab for rheumatoid arthritis and three additional antibodies which are in late-stage development.

Our investments in R&D have the potential to help diverse groups of patients in need. We expect to make significant investments in the coming year to support these important programs in terms of launch and development costs.

These critical investments will fuel our efforts to continue to move our pipeline forward and thereby, hopefully, allow Regeneron to continue to execute on its mission to provide important new medicines to patients in need. Bob Landry will update you on our financial results.

In addition to our progress with our late-stage antibodies, we maintain our commitment to continue to innovate, whether that is for rare diseases like FOP, emerging diseases like Ebola, or the genetics effort at the Regeneron Genetics Center, to name a few. With that, let me turn the call over to Dr.

George Yancopoulos, Regeneron's Chief Scientific Officer. He will be followed by Bob Terifay and then by Bob Landry.

George?.

Thank you, Len, and a very good morning to everyone who has joined us today. As Len mentioned, we have remained committed to being a research-driven company, and the depth and breadth of our proprietary technology and the resulting pipeline of molecules, all of which have been invented in our own labs, is a testament to that vision.

Len and I are proud of our team and what they are accomplishing.

One of the features that distinguish us as a company is that the core group of scientists who helped build Regeneron from the very beginning continues to be actively involved as leaders and is now being joined by the next generation of new scientists who are attracted to our research-based approach.

To that end, we are proud that we are one of the top two employers by Science Magazine for the fifth year in a row, and once again the top employer in the biopharmaceutical industry. Turning to developments this quarter. I would like to begin with Praluent, where we currently have a Phase III outcome study ongoing.

We expect this study to be fully enrolled by the end of the year, with final data expected in 2017, and interim analysis by the independent data monitoring committee reported next year.

At the annual meeting of the European Society of Cardiology Congress, we presented new data from a pooled analysis of over 1,200 heterozygous familial hypercholesterolemia patients, one of the major group of patients for whom Praluent is indicated. This represented the largest group of HetFH patients ever studied in a Phase III program.

This pooled analysis was concurrently published in the European Heart Journal. We look forward to presenting additional new analyses from our Phase III program at the American Heart Association meeting this upcoming weekend.

We have submitted our BLA for sarilumab, our interleukin-6 receptor antibody for rheumatoid arthritis, and look forward to a potential FDA action in the second half of 2016.

Next week, at the American College of Rheumatology meeting, we will be presenting additional Phase III data for sarilumab, including data from the positive target study which was in patients who are inadequate responders to, or intolerant of, TNF alpha inhibitors, in combination with non-biologic disease modifying anti-rheumatic drugs, or DMARD therapy.

We'll be hosting a conference call next week from ACR. The target data, along with the previously reported published data from the Phase III mobility study of sarilumab in combination with methotrexate in patients who were inadequate responders to methotrexate alone, are included in our regulatory submission in the U.S.

In addition, the Phase III MONARCH study of sarilumab versus adalimumab in the monotherapy setting is now fully enrolled, and we expect to report data from this study in the second half of 2016. Turning to dupilumab, our antibody that blocks the interleukin-4 and interleukin-13 pathways.

We expect to see data in early 2016 from our pivotal Phase III studies in atopic dermatitis, both of which are fully enrolled, with the regulatory submission to follow in the second half of the year.

A Phase II study in the pediatric atopic dermatitis population is also fully enrolled, and we are committed to moving as quickly as possible to address this important patient population. In the asthma indication, our confirmatory Phase III study is ongoing and enrolling patients.

As we have mentioned previously, following discussion with the FDA, we'll only need to conduct one Phase III efficacy study in this indication since the FDA has said that our Phase IIB trial could be considered pivotal.

In addition, we continue to explore other potential allergic indications for dupilumab such as nasal polyps and eosinophilic esophagitis. Regeneron 2222, our antibody to respiratory syncytial virus is in Phase III clinical development.

An open-label pharmacokinetic portion of this study has been completed in healthy preterm infants and has enabled dose selection for the second part of this Phase III study which is expected to commence shortly. A separate, second Phase III study is planned for next year.

Fasinumab, our antibody that blocks nerve growth factor, is currently in Phase III clinical studies for osteoarthritis-related pain. Last month, we announced a collaboration agreement in Asia for this program with Mitsubishi Tanabe and look forward to working with our new Japanese collaborators to advance fasinumab.

We also announced and launched our new immuno-oncology collaboration with Sanofi during the quarter. With the additional resources and commitment to immuno-oncology, coupled with our capabilities in both immunomodulatory antibodies and bispecific antibodies, our goal is to become a major contributor to this exciting new field.

Our PD-1, which is expected to serve as a backbone of several future combination approaches, continues to enrolling patients in an early clinical study, as is our CD3xCD20 bispecific antibody, which is not included in the immuno-oncology collaboration, but will nevertheless serve as the proof of concept for our overall bispecific platform.

I'd now like to spend a few minutes on our earlier stage pipeline. In September, we announced that Science Translational Medicine had published a paper describing the discovery and preclinical validation of a key biological mechanism that drives the pathophysiology of a rare genetic disorder, fibrodysplasia ossificans progressiva, or FOP.

FOP is a progressive, severely disabling and ultimately fatal disease in which muscles, ligaments, tendons and other connective tissues are transformed into bone.

While FOP is a very rare disease – there's approximately 800 confirmed cases in the world – we've been inspired by the stories of the patients with this terrible disease by our interactions with the International FOP Association which represents the patients and their families, and the clinical community, particularly Dr.

Fred Kaplan and his group at the University of Pennsylvania, as well as our own scientific drive to understand this important pathway's potential implications to other diseases.

A critical factor that enabled us to elucidate this signaling pathway and identify active (13:25) as a potential therapeutic target for the treatment of FOP was our proprietary VelociGene technology.

We used this to develop a genetically humanized and novel mouse model of FOP in which the hypothesized molecular pathophysiology of disease was elucidated. Additionally, our proprietary VelocImmune platform enabled us to generate an antibody highly selective to the therapeutic targets.

We think underserved diseases like FOP highlights the need for innovative R&D, and we hope that our efforts may ultimately result in important new therapies. Similarly, I would now like to provide you with an update on our efforts in emerging infectious diseases that pose a risk to public health such as ebola.

We believe we can take advantage of Regeneron's rapid response technologies in this space as they can be immensely useful in emergency situations for diseases that cause a large and quickly expanding threat to the general population.

In September, we announced that we have received funding from BARDA to advance, test and manufacture a monoclonal antibody cocktail for the treatment of ebola virus infection.

In addition to ebola, a proprietary antibody, Regeneron Rapid Response platform has been used to generate antibodies for Middle Eastern Respiratory Syndrome or MERS, which has been the recent cause of outbreaks in both Saudi Arabia and South Korea. It has the potential to address other emerging infectious diseases.

Before I turn the call over to Bob Terifay, I would like to briefly highlight the impressive speed by which the Regeneron Genetics Center, or the RGC, has become a leader in the human genetics space.

In October, we presented several abstracts at the American Society for Human Genetics meeting, which showed the potential of our unique approach, which integrates genomic data with electronic health records from a growing database of patient volunteers.

We are currently on track to sequence over 100,000 individuals by early 2016, approximately two years after we launch this initiative. With that, I would now like to turn the call over to Bob Terifay..

Thanks, George, and good morning, everyone. The third quarter was a significant one for Regeneron. EYLEA, or aflibercept injection, continued to demonstrate strong sales growth both in the United States as well as the rest of the world.

In addition, in July, we launched Praluent, alirocumab in the United States, for the lowering of poorly-controlled low density lipoprotein cholesterol in certain high-risk patient groups. Praluent was also approved in September by European regulators. Starting with EYLEA, third quarter U.S. net sales growth was 65% year-over-year. Net U.S.

EYLEA sales to distributors in the third quarter were $734 million. Underlying physician demand has continued to remain strong and grew sequentially quarter-over-quarter by 10%. A survey of 200 U.S.

retinal specialists who evaluated the reported use of VEGF inhibitors in the third quarter of 2015, indicates that EYLEA growth in the quarter was driven largely by growth in diabetic macular edema or DME and macular edema following retinal vein occlusion.

Third quarter net sales were also impacted by a slight increase in distributor inventory levels. I should note that fourth quarter net U.S. sales could be negatively impacted by several factors such as potential changes in inventory levels, seasonal fourth quarter holidays resulting in reduced offices and potential bad weather.

According to our third quarter survey of retinal specialists, the market share of eyes treated with EYLEA in DME is roughly doubled that for ranibizumab and similar to that for off-label bevacizumab.

Our market share of eyes treated for macular edema following retinal vein occlusion actually surpassed the individual shares for both bevacizumab and ranibizumab in the third quarter.

Per the survey, EYLEA continues to be the market leading product among FDA approved anti-VEGF agents in all of our labeled indications in terms of market share of treated eyes.

Outside of the United States where we share EYLEA profits with our collaborator, Bayer HealthCare, third quarter EYLEA net sales were $371 million, representing 34% year-over-year growth on a reported basis. This is notwithstanding substantial adverse currency impact. In constant currency, ex-U.S.

EYLEA net sales in the third quarter grew 58% year-over-year. Regulatory and pricing approvals for new indications continued to contribute to ex-U.S. sales growth. For example, just this past week, Bayer HealthCare received regulatory approval in the EU for EYLEA for the treatment of visual impairment secondary to myopic choroidal neovascularization.

Let's turn now to Praluent. While it is still very early in the launch, we are pleased with our operational implementation of the launch. The Regeneron and Sanofi field teams were fully trained and in physician offices on the first business day after approval.

To date, we have jointly called on over 39,000 healthcare professionals and 4,600 healthcare professionals have participated in our educational programs. Over 4,000 prescribers have submitted prescriptions to MyPRALUENT, our reimbursement and patient services hub.

Of all prescriptions received, approximately 90% of the prescriptions have been filled for our recommended 75-milligram low dose option. As reported by Sanofi, net sales to wholesalers in the third quarter were $4 million. As a reminder, the reimbursement environment is complex and will be carefully managed by payers.

Our goal has been to ensure that payers and healthcare providers understand the value that Praluent can offer to patients. And to that end, we are actively engaged in extensive discussions with payers. We continue to emphasize to payers that physicians and patients should have choice in selecting a PCSK9 inhibitor.

We expect that it will take several months for some commercial and government payers to conduct formulary reviews, make reimbursement coverage decisions, and to begin process of patient claims. Given these reasons, we expect an initial gradual uptake at launch.

In response to potential delays in formulary decisions and reimbursement decisions, we are offering samples and free product to appropriate labeled patients who are awaiting an insurance coverage decision. This may delay uptake in commercial sales reporting.

For example, for Medicare Part D or government-paid patients, there can be up to a six-month coverage decision period. So, for the next several quarters, performance cannot be judged based upon reported sales or filled prescriptions. We would expect that this would understate both the volume of physician and patient adoption.

As a proxy for physician prescription demand, we are currently evaluating physician prescriptions submitted to the MyPRALUENT hub for reimbursement verification. In the third quarter of 2015, submissions were consistent with our expectations.

Outside of the United States, Praluent was approved in the EU in September with some launches expected before year-end. As mentioned earlier, we recently submitted a BLA to the U.S. Food and Drug Administration for sarilumab, our interleukin-6 or IL-6 inhibitor for rheumatoid arthritis. We're actively preparing for a potential U.S. launch in 2016.

As part of our prelaunch preparation, we will have a large presence at the upcoming American College of Rheumatology meeting in San Francisco this weekend. We also continue to prepare for the potential U.S. launch of dupilumab, our IL-4 and 13 inhibitor in 2017.

For example, last month, at the European Academy of Dermatology and Venereology meeting in Copenhagen, hundreds of dermatologists participated in our educational symposium on atopic dermatitis. We are actively in the process of hiring internal commercialization team members for both sarilumab and dupilumab ahead of their potential launches.

With that, let me turn the call over to our Chief Financial Officer, Bob Landry..

initiating in the first half 2016 the funding of 20% of dupilumab's Phase III clinical development cost for both the asthma and atopic dermatitis indications, assuming positive Phase III data is reported for dupilumab and atopic dermatitis; the continuation of funding 20% of Phase III studies in both Praluent and sarilumab; advancement of our Phase III REGN222 and fasinumab programs in progressing our early stage, un-partnered pipeline forward (30:46).

In addition to incurring these investment expenses, it's important to remember that the intellectual property associated with our late-stage pipeline has been migrated offshore; thus these expenses will be incurred in foreign jurisdictions with tax rates lower than the U.S.

federal statutory rate, which we expect will result in higher cash tax and effective tax rates for 2016. With that I'd like to turn the call back to Michael..

Thank you, Bob. That concludes our prepared remarks. We'd now like to open the call to Q&A. As we'd like to give as many people a chance to ask questions as possible, as always, we request you to limit yourself to one question. For other questions that you don't get to ask, our team will be available in our office after the call for follow-up questions.

Thank you, and operator, if you could please open the call for questions..

Thank you. One moment for our question. Our first question comes from the line of Ying Huang of Bank of America. Your line is now open..

Hi. Good morning. Thanks for taking my questions and congratulations on a great quarter for EYLEA. So, first I have a question on the formulary access for Praluent. You have got the branded Tier 2 preferred formulary access from Express Scripts.

Should we expect a similar tiering for the other payers? And then some investors have been wondering that given this preferred status, branded Tier 2, you probably have to provide a sizeable rebate for Praluent.

Is that the case? And the secondly, maybe for Bob Terifay here, you have been gaining share for EYLEA in both AMD and DMD (32:49)? In the fourth quarter, maybe you're saying that there are some headwinds here, but shall we assume that you'll continue to gain share from both off-label Avastin and also Lucentis? Thank you..

Ying, thank you for your three questions..

Yeah, Ying, do you have one of those that you'd like us to answer? We'll take them all..

You can pick one, Len..

Well, first of all, as formulary access, we've always stated and Bob has stated that the company believes what's best in this field for patients is that patients and doctors have a choice, and they are the ones who make the decision. And so, that's where we'd like to see things turn out.

How things actually turn out and the size of rebates, et cetera, et cetera, is not something that we can predict or speculate or comment on at this time. If Bob wants to comment on the EYLEA gaining share or, go ahead Bob..

So obviously, we've been encouraged by the growth that we've seen, especially in DME with market share. Physicians have been very pleased with the outcomes of the independent Protocol T study which compared the three available products for DME in the marketplace, and have adopted EYLEA very rapidly there.

To project where things are going to go in the future, Ying, I can't do that for you. So, we'll have to see how the market plays out..

Thanks..

Next question?.

Thank you. Our next question comes from the line of Joseph Schwartz of Leerink Partners. Your line is now open..

Thanks very much. You have two very large Phase II studies looking at PDGF and ANG2 in combination with EYLEA.

So I was wondering if you could talk about how you're thinking about positioning the – or alternatively – are you looking to select one of these programs versus the other to take it to Phase III?.

Yeah. I'm sure this is going to be a data-driven decision, and we'll see what we get.

George, you have anything further to add on that?.

Well, just as Len said, we let the data speak and help us guide our decision, so we can't predict how it will work out..

Does it make sense to target any different solutions (34:50) with ANG2 versus PDGF?.

We'll see..

In terms of PDGF, as you probably know, it's not appropriate for use in diabetic macular edema. So certainly, the ANG2 has a broader potential application..

But at the end of the day, we have to look at the data and we don't have it yet..

Next question?.

Okay. Thank you..

Thank you. Our next question comes from the line of Terence Flynn of Goldman Sachs. Your line is now open..

Hi. Thanks for taking the questions. First, just on Praluent, can you comment at all of the prescriptions that have been submitted, what percent you'd expect to get filled? Or maybe to ask another way, what percentage meet the label criteria? And then just the second one is on the antibody for FOP.

Just wondering what's gating to moving that into human and if we could see proof of concept data next year. Thanks..

So, I don't think we can get into the details – I'm not even sure we have all the details at that level of granularity. In this competitive environment, we probably can't even share them. Sorry about that, Terence.

In terms of FOP, George, any feeling when we might be able to get that into patients?.

Yeah. I mean, certainly, we're moving it along.

And I think, as with any complex setting like this in a rare disease, it's going to be – we're going to have to deal with the complexities of dealing with the patient population and also try and design the right clinical study where it's not clear that all the right endpoints and approaches have been defined to date.

So, it's a complex problem, but we do think that there's a lot of reason for hope here. And we hope to do our best to bring the – to develop this in the right way and see if we can really make a difference in these patients' lives..

Great.

And the next question?.

Thank you. Our next question comes from the line of Chris Raymond of Raymond James. Your line is now open..

Hey. Thanks. Just a question on Praluent. I wanted to clarify exactly the range of outcomes around this ODYSSEY outcomes interim look. I think this is the first time I think I've heard you guys overtly talk about this interim look in 2016.

Last time, I think I heard you guys talk about it, you were saying that the DSMB would be taking this look and you'd be blinded. Can you maybe talk about if there's a chance that there could more detail? Thanks..

George, do you want to take that?.

Well, let me ask my man, Aberman here.

Are we allowed to disclose the details on this?.

Yeah. There was a publication where these details were spelled out..

All right. Thank you..

So, if people want to look at that, they can. But I wouldn't – not everything – but yes..

Okay. All right. So as you all know, this is an event-driven trial and it all depends on when the events actually occur and that's not entirely predictable. But the interim analyses are gated to occur when 50% of the events have occurred. That initial analysis will be an interim analysis by the Data Safety Monitoring Board for futility.

And then when 75% of the events have occurred, there will be a second interim analysis for both futility and overwhelming efficacy..

So I don't think that we'll be expecting to get anything, any information that we can relay other than if something has been met and we get that information. Beyond that, these things sort of occur out of our sphere of influence and information. They just go on by the DSMB. Okay.

Next question, Mike?.

Yeah.

Next question?.

Thank you. Our next question comes from the line of Adnan Butt of RBC Capital Markets. Your line is now open..

Hey. Good morning, everyone. So, first on Praluent. One of the payers did not offer exclusivity. Could other payers take a similar approach, or could exclusivity still exist for others? And then on 2170, the combo PDGFR and EYLEA.

Either Leonard or George, what kind of a benefit do you think would be of interest to clinicians over EYLEA alone?.

So, on the first question, I don't think there's any real correlation between what one payer does versus what another payer could or might do. Obviously, we continue to feel that patient and physician choice is the best way to go and we'd like to see all or most of the market, if possible, go in that direction.

As far as what the patients – what doctors would like to see in any of these combination trials, it's always the two things; which is the potential for better efficacy or a longer duration of action with potentially less injections.

George, anything to add to that?.

Yes. I do think that it's important to point out that, I mean, obviously, safety here will be key because of the longstanding experience with EYLEA in this space. And so I think that that will be the first thing people, physicians should not want to be endangering their patients' lives for a little bit of benefit.

But if there is a benefit in the setting of good safety, I think it's important to point out that I think any benefit should be of interest to physicians, particularly because, in our approach, we will be providing both agents in a single intra-vigial (40:15) approach.

So, for example, if physicians had to think about giving a second injection to gain just a little bit of efficacy, that would take maybe, a lot more thinking.

But the fact that it's all provided in a single intra-vigial (40:29) injection, assuming that the safety is good, you would think that any benefit would then be adopted by the physicians and their patients..

Great.

Next question?.

Our next question comes from the line of Matt Roden of UBS. Your line is now open..

Great. Thanks very much for taking the picture – for taking the questions – and congrats on a nice quarter here again. George, big picture of question for you on how you think about the opportunities you have with your bispecifics, as it relates to other technologies out there like cellular therapies, CAR T, et cetera.

CAR T has shown some pretty profound efficacy in some smaller studies, selective indications, but bispecifics, of course, have potential benefits on logistics, convenience, potential safety advantages, et cetera. But I guess when I think about cancer therapy, I always think about efficacy being paramount.

So, can you talk about what you'd like to see from your bispecific programs, whether or not you think a similar level of efficacy is potentially achievable with bispecifics versus CAR T, and if not, whether or not the other advantages are sufficient to be important to patients. Thanks..

Yeah. We agree with you. I mean, our goal is to have our bispecific program essentially achieve the sort of efficacies that one can imagine by genetically engineering the T cells themselves but also producing, and as you said, a logistically much more reasonable way, for more widespread utilization by physicians and patients.

So, yeah, our target, our goal, and the science that's backing it up, is hoping that we are going to be achieving those levels of efficacy. It may not be an immediate – there may have to be combinations of bispecifics and so forth – but that is, indeed, the goal..

Yeah. Just to add one of the things that George, I think, has talked about publicly about this, is that bispecifics do add the advantage of better ability – not just convenience and logistics, but dose titration.

George, maybe you want to comment on that?.

Yeah. That's also an important point in that, as we've seen with the CAR T cells, one will be able to, for example, slowly dial up the bispecific level to get more gradual kill, which could result in much better safety and efficacy in the patients.

And also, in settings where one might want to withdraw treatment, either temporarily or permanently, you have those opportunities as well. So, as Len said, there is the possibility – and there's also the possibility of mixing and matching the right bispecifics, that one could get actually even better efficacy and improved safety and so forth.

But of course, it's going to be a long process. There's going to be a lot of work to be done, and there's a lot of unknowns here. But we have a lot of potential here, we feel..

Yeah. And of course, building the whole pipeline of immuno-oncology under one program allows us, I guess, George, to do combinations which....

Yeah. I think that that's the one thing that we are, perhaps, the most excited about is – it's not clear to me if anybody else has the toolkit – has built a toolkit over the years that we have here. And that we have here, in ways which are more easily, perhaps, matched and tested.

So, that's one of the reasons we also have a lot of excitement about this program..

Operator, next question?.

Our next question comes from the line of Matthew Harrison, Morgan Stanley. Your line is now open..

Great. Thanks very much for taking the question. I just wanted to go back to EYLEA and some of the potential headwinds that you guys had mentioned for the fourth quarter, and just make sure that we understood what you were trying to say.

If you look at your guidance, obviously, at the high end of the range, there's some sequential growth, and at the sort of midpoint, it actually goes negative quarter-over-quarter.

I'm just wondering, are you expecting a lot of inventory? Do you view your guidance as conservative? Or do you just think the seasonality that you've seen in years past, and you're sort of baking that into the number? Thanks..

So, we're trying to give the best guidance we can give based on the information we have, and while we've always said to you (44:58) that looking into the future is not necessarily the most productive thing one can do, but we do our best.

And the fact is – Bob, you want to comment that you took into account?.

Yeah. I think historically, if you look even last year, when we had rapid growth occurring in diabetic macular edema, fourth quarter over third quarter growth did slow down. And it's related to a seasonality we see. We do see some inventory adjustments many times. We also have the holidays.

And it's not just, for example, a Thanksgiving or a Christmas, it's the days preceding and the days following, where a number of the patients just don't want to go to the doctor's office around the holidays. So we see less visits and less injections. Len calls me the weatherman.

I can't project what's going to happen with the weather, but we do have to take into account that the fourth quarter often does have storms, which also does impact office visits. So, that's why our guidance is the way it is; some growth on the high end, and some loss on the low end..

Great.

And next question please?.

Our next question comes from the line of Phil Nadeau of Cowen & Company. Your line is now open..

Good morning. Thanks for taking my question and congratulations on the progress. First, one clarifying question. On your guidance for the interim analysis for Praluent in 2016, is that specifically referring to the first interim? And, when do you expect to see the second interim at 75% of events? And then second, on the scripts for Praluent.

I know you said that they're not accurate. Your competitor, Amgen, is saying that, in their opinion, their scripts are becoming increasingly more accurate. Is the difference between you based on your sampling program specifically? Thanks..

Yeah. As far as the interim analyses, this is speculation, because it's not based on enrollment or time. It's based on the number of events. We think there's a good possibility that we could see both analyses during 2016, based on the event rate that we've seen.

The first one is, George mentioned, would be for futility, and the second one would be for futility and overwhelming efficacy..

And remember, you don't know what to root for because, if the drug works really well, you'll actually accrue events at a lower rate, so it's complicated..

Anyway, as far as – I don't think we have anything further to add on the Praluent story, Bob, unless you have any...?.

I would caution you, if you look at the IMS prescription data, the numbers are very, very small right now. Both companies are offering samples and have bridge programs for patients who don't yet have insurance coverage, to allow patients to get access to the product while we're working with the payers to achieve coverage.

So, it's hard – I wouldn't project anything off samples at this – or off RXs at this time..

And just remember, for example, as Bob mentioned I think in his remarks, that Medicare can take up to six months.

And many of our – since one of our main indications is for people who have atherosclerotic cardiovascular disease and insufficient lowering, with current therapies, of their LDL, many – since they have disease, many of these people are elderly, are Medicare, and they may not get coverage for six months, which would put us into the early part of next year..

Next question?.

Our next question comes from the line of Mark Schoenebaum of Evercore ISI. Your line is now open..

Hey, guys. Thanks a lot for taking the question. And Lenny, just for the record, I thought this was fantastic, absolutely fantastic quarter. And I thought, for my question, I would just back up a little bit.

And as one of the longest serving CEOs in big-cap biotech and big-cap pharma and small-cap biotech for that matter, just wondering if you could share some wisdom about what we're all hearing right now around drug pricing? And I think coming from the platform of Regeneron to opine on this is powerful because you're developing specialty medicines, primary care medicines, biologics across all different disease types including ultra-orphan, as well as things like obviously the PCSK9 canine antibody.

So, what do you think is happening right now? Do you think the current price points of drugs are sustainable? Do you think the rate of inflation's got to decline? What's your sort of – what are your sort of thoughts on that, Len? Thank you..

Yeah. This is probably more than a 30 second comment. There's a lot of....

I've got till 4:00 PM booked. So....

Yeah. Well, we can take it offline because I do have a lot of thoughts on the subject of drug pricing. I am a big believer that we need pricing power in this industry. Pricing power comes from patents. I like to say, remember what President Lincoln said is, that patents add the fuel of interest to the fire of genius.

And I think that basically translated into modern terms, capital being the fuel that fires things up here, capital is agnostic. And it will only go where we can get a good return. So, if we want innovation, we want new drugs, we have to figure out ways to make sure that it's attractive for investors, and that means to be able to reasonably price.

On the other hand, to some respect, the pharmaceutical industry, maybe might say the biopharmaceutical industry, is reviled for lots of different reasons and is attacked from many different quarters, including some from my next door neighbor in town, Secretary Clinton, and sometimes for very good reason.

There have been some scandalous things that are done in the industry. You read them about every day, and it's no surprise if you couple that with high prices that people get very disgusted with the industry.

On the other hand, as I said, if you're an innovative company such as – that we are – innovation needs to be rewarded but you have to do it in a way where you create value for patients in the healthcare system.

So, Mark I would like to just go back to – I'd like to say that we have a lot we can say on that issue – but I prefer changing the subject back to what I thought I heard you say which is we had a fantastic quarter, which is nice of you to say that. Next question..

Thank you. Next question operator..

Thank you. Our next question comes from the line of Lyn Boyton (52:04) of Guggenheim. Your line is now open..

I think we lost that question..

Why don't we go to the next person?.

All right. Our next question comes from the line of John Newman of Canaccord..

Hi, guys. Thanks for taking the question and my congrats on the quarter even if it's not – I suppose – as enthusiastic as Mark's, but great numbers. So, my question is a general question on Praluent.

I'm just wondering, how do you think long-term about the compliance on the product? Because even with oral drugs, sometimes, unfortunately, patients don't take their medication but given the dosing interval for Praluent, I'm just curious when you think about the drug internally, what do you think about in terms of kind of the ranges of compliance that (52:57)?.

So, compliance for a drug that is preventative for a silent killer can be very difficult because people for lots of reasons don't want to think or admit that they have problems that need to be treated. They feel fine.

Why do I have to take these medicines, et cetera, et cetera? In terms of specifically compliance for Praluent, the only thing – the only data that we have because it's too early to tell from the commercial world yet – the only data we have is from our clinical trials where, I believe, and Bob or George can correct me if I'm wrong, that the compliance for the injections was extremely high, even higher perhaps than for the concomitant statin therapy that people were on..

That is the situation with the clinical program. One thing I would say is that Praluent is an injectable specialty product. The nice thing about that is we have to refill the prescription by mail on a monthly basis to the patient.

So, we have an opportunity to encourage patient adherence with the product on a monthly basis, actually with outbound calls or if the patient wants a text message or however. So, I do hope that with the constant contact with the patients, we will be able to add to the adherence.

I will also say that at least from the clinical program, the safety profile for Praluent was very good so the patients were not feeling bad on the product which should also help with adherence..

And I think it should also be pointed out that paradoxically, one should realize that there may be advantages vis-à-vis compliance with long-acting antibody drugs because if you're late by a day or even a week or longer with the dose, it's not like skipping even a day or let alone a week with one of these small molecule drugs where you completely lose your efficacy, because these are such long-acting drugs.

So, I think that in terms of the biological effects and the ability, not that we would encourage it, but being late or even missing a dose, you can still retain long-term biological effects.

And I think that that's – those sorts of effects of missing doses of short-acting drugs, obviously, that's been demonstrated in other fields such as in the hypertension field and so forth – so I think that that's something to consider as a major advantage for long-acting biologicals..

Operator, another question?.

Thank you. Our next question comes from the line of Geoff Meacham of Barclays. Your line is now open..

Good morning, guys. Thanks for taking the question. It sounds like from Bob's comments in the prepared remarks that 2016 will be a big investment year.

And I know you guys aren't a position to give guidance for next year, but I was hoping to maybe in broader brush strokes to get a sense as to what some of the bigger variables were as you look to next year? Thanks..

Yeah, Geoff. I think, if you go back over to transcript, what Bob referred to and what I was trying to direct you towards, is that we have a lot of investment related to the launch of Praluent. We have investment related to the ongoing ODYSSEY trials where we split 20%.

In dupilumab, if in the early part of the year, if the Phase III are positive, we'll start picking up 20% of the expenses in the entire Phase III program for both atopic dermatitis as well as in asthma. And also, we'll be picking up prelaunch expenses for dupilumab.

We also have some unpartnered assets in NGF and RSV and we also have the launch of sarilumab.

So, those sorts of pipeline events, we think these are great investment opportunities because we think of the potential – if you think about the potential, for example, of dupilumab, we think that's a very high-potential product – and the rest of the pipeline has high potential. So, we have to make these investments.

But clearly, we will be making them next year.

Bob, did you want to add anything?.

Yeah. So, just to punctuate what Len said, I mean, again, it's the convergence of a lot of things, as Len kind of listed verbally and again, what's in our transcript all kind of coming to ahead in 2016. And again, it's also important that we've talked about the migration of our late stage antibodies, offshore.

And again, a lot of our expenses related to these things will be taken in tax jurisdictions that are going to be lower than the federal statutory tax rates. So that will also have an impact with regards to ETR and cash tax rates. So again, it's all of these things together, all for – as a good story type message..

Operator, we have time for one last question..

Thank you. Our next question comes from the line of Cory Kasimov of JPMorgan. Your line is now open..

Hey. Good morning, guys. Thank you for squeezing me in here. I wanted to ask more broadly on Praluent.

Now that you've had three months on the market, are you able to gather and share any real-world feedback on the key aspects of Praluent's profile that's really resonating most with physicians? Or maybe said in other way, are there any early points of pushback aside from gaining broader coverage? Thanks a lot..

Yeah. I mean, I think, Bob has said in his talk and what's important to emphasize is that we have a low dose option and that's the recommended starting dose. And what we're seeing in our prescriptions is 90% of docs are opting for that recommended low 75-milligram starting dose, so we think that's resonating with physicians.

Beyond that, I think it will kind of much further to say, it's too early..

Thank you, everybody, for joining. Operator, this will be the conclusion of our call. And again, if you have any follow-up questions, please e-mail myself, Manisha, Colleen (59:00), on the IR team and we'll get back to you as soon as we can..

Ladies and gentlemen, thank you for participating in today's conference. That does conclude today's program. You may all disconnect. Have a great day, everyone..