Regeneron Pharmaceuticals Inc (REGN) — Q3 2018 Transcript

Thank you, John. Good morning, and welcome to Regeneron Pharmaceuticals' third quarter 2018 conference call. An archive of this webcast will be available on our website under Events 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 and Chief Scientific Officer; Marion McCourt, Senior Vice President and Head of Commercial; and Bob Landry, Senior Vice President and Chief Financial Officer. After our prepared remarks, we will open the call for Q&A. I would also like to remind you that remarks made on this call today include forward-looking statements about Regeneron. Such statements may include, but are not limited to, those related to Regeneron and its products and business, financial forecast and guidance, development programs and related anticipated milestones, collaborations, finances, regulatory matters, intellectual property, pending litigation, 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 that statement. A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, or SEC, including its Form 10-Q for the quarter ended September 30, 2018, which was filed with the SEC earlier today. Regeneron does not undertake any obligation to update publicly, any forward-looking statements, whether as a result of new information, future events, or otherwise. In addition, please note that GAAP and non-GAAP measures will be discussed in today's call. Information regarding our use of non-GAAP financial measures and a reconciliation of those measures to GAAP is available in our financial results press release, which can be accessed on our website. Once our call concludes, Bob Landry and the IR team will be available to answer further questions. With that, let me turn the call over to our President and Chief Executive Officer, Dr. Len Schleifer.

Thank you. Manisha does such a fabulous job at Investor Relations, we should at least get her name right. It's Manisha Narasimhan. Good morning to everyone who has joined the call. In the third quarter, Regeneron delivered record financial results and important pipeline progress. EYLEA sales continue to grow. For the first time, U.S. EYLEA net quarterly sales surpassed $1 billion. Also, for the first time, third quarter worldwide Dupixent sales exceeded $0.25 billion. And Dupixent was recently approved for asthma, its second major indication. Additionally, we launched Libtayo, our first approved immuno-oncology therapy. For EYLEA, we significantly strengthened the franchise through a recently expanded label for less frequent dosing and the potential for a new indication in diabetic retinopathy. And we expect to advance a high-dose formulation of aflibercept into the clinic in the first half of next year. Libtayo, our first commercial entry into the exciting and fast-evolving area of immuno-oncology, is the foundation upon which we intend to build with multiple additional agents and approaches in many different cancer settings. We have described Dupixent as a pipeline and a product, and it is living up to that potential. Compared to other approved biologics for asthma, Dupixent has a differentiated profile and label. The recent asthma approval, together with the ongoing robust launch in atopic dermatitis, positive Phase 3 results in chronic rhinosinusitis with nasal polyps, and positive Phase 2 results in eosinophilic esophagitis validate the scientific hypothesis that the IL-4/IL-13 pathway is responsible for a spectrum of allergic or Type 2 diseases. You'll hear more from Marion about the launch of Dupixent in asthma and atopic dermatitis, and George will update you on our clinical programs. We have continued to make steady progress with our other commercialized products. From Praluent, our LDL cholesterol-lowering PCSK9 antibody, we anticipate that the U.S. treatment guidelines for lipid lowering will be updated shortly. We hope the updated guidelines will facilitate greater access and support increased use of the PCSK9 class. Although it gets drowned out in the debate about drug prices, the fact remains that cardiovascular disease is the number one cause of death in the United States, and high LDL cholesterol is a major cause of cardiovascular disease. Our early pipeline continues to progress. At the beginning of the year, we set a goal of advancing four to six new molecules into clinical development. I'm happy to report that to-date, we have already advanced four new molecules into clinical development. These include a bispecific antibody for ovarian cancer, a new antibody for pain, a leptin receptor agonist, and an antibody to CTLA4. We also expect to advance into the clinic by year-end a BCMA CD3 bispecific antibody for multiple myeloma. We now have seven approved drugs and our clinical pipeline has 20 product candidates spanning a range of therapeutic areas. All of these molecules were discovered by our scientists. With that, I will now turn the call over to George.

Thanks, Len, and good morning, everyone. I'd like to begin with EYLEA. In August, our supplemental Biological Application was approved for EYLEA dosed every 12 weeks after one year of effective therapy in wet age-related macular degeneration or wet AMD. EYLEA is now the only anti-VEGF drug for the treatment of wet AMD that offers the flexibility to optimally treat patients, regardless of whether they require fixed-interval dosing of 4, 8, or 12 weeks. In September, the FDA accepted our sBLA for EYLEA in diabetic retinopathy with an action date in May 2019. This sBLA was based on the data from the Phase 3 PANORAMA study, which investigated the use of EYLEA in patients with moderately severe to severe non-proliferative diabetic retinopathy without diabetic macular edema. Positive six-month top line results from PANORAMA were announced in March 2018. Just a couple of weeks ago, we announced positive data from the one-year time point from this same study. On the primary endpoint at one year after initial monthly dosing period, followed by every 8- or every 16-week treatment, 80% and 65% of patients, respectively, experienced a two-step or greater improvement from baseline on the diabetic retinopathy severity scale compared to only 15% of patients receiving sham injections. The results were highly statistically significant, with the p-value less than 0.0001. Regarding the two key secondary endpoints which achieved statistical significance based on the pre-specified hierarchical analysis, compared to sham injection, treatment with EYLEA reduced vision-threatening complications by 82% to 85%, and the development of center-involved diabetic macular edema by 68% to 74%. Diabetic retinopathy is the leading cause of blindness in working-age adults in the United States. What is perhaps underappreciated is the rate at which non-symptomatic patients can develop serious complications that threaten their vision. Strikingly, within the first year of PANORAMA, more than one-third of previously asymptomatic diabetic retinopathy patients who were treated with EYLEA went on to develop vision-threatening complications or diabetic macular edema. EYLEA markedly reduced these complications and reversed the anatomic severity of the disease. These results underscore the potential value of earlier intervention in diabetic retinopathy. In addition to data from our PANORAMA study, the government-funded Diabetic Retinopathy Clinical Research Network is conducting its own Phase 3 study of EYLEA in diabetic retinopathy. This study known as Protocol W is ongoing. Turning to the competitive landscape. In our view, there isn't any product in the near-term that can have a substantially different safety and efficacy profile compared to EYLEA. EYLEA is approved in a number of retinal diseases and has demonstrated safety and efficacy with over 20 million doses administered worldwide. It doesn't appear that any potential near-term entrants can provide substantially different dosing flexibility, duration, or visual gains than are already achievable with EYLEA. Nevertheless, we believe that higher dose formulations of aflibercept might provide additional or longer-lasting benefit, and thus, we are advancing this program into clinical development in 2019.

Thank you, George, and good morning, everyone. I would like to start with EYLEA, where global net sales in the third quarter were $1.68 billion, an increase of 11% year-over-year. U.S. net sales of EYLEA were $1.02 billion, a 7% year-over-year increase. This increase was driven by overall market growth in both wet AMD and DME, physician preference and the aging population, as well as the increase in the prevalence of diabetes. Based on net sales, EYLEA currently holds about 70% of the overall branded U.S. and anti-VEGF markets. In an effort to educate consumers and raise brand awareness and interest, we recently launched the pilot EYLEA DDC campaign for approved indications in select markets. Beyond the approved indications of wet AMD, DME, retinal vein occlusion, and diabetic retinopathy with DME, we see potential opportunity for EYLEA in diabetic retinopathy. As you just heard from George, we recently reported positive data in this indication and expect a regulatory decision in the U.S. in May of next year. Following this potential approval, we plan to initiate a focused campaign to drive adoption in this large untapped indication. Additionally, in August, we announced that the FDA approved an sBLA for EYLEA for a modified every 12-week dosing schedule for wet AMD after one year of effective treatment. This makes EYLEA the only approved anti-VEGF drug for wet AMD with 4-, 8-, and 12-week dosing specifically referenced in its label. I'd like to spend a moment discussing our prefilled syringe for EYLEA. As previously announced, we received a Complete Response Letter from the FDA. We remain confident that we will be able to satisfy the agency's request, which included the completion of a usability study evaluating a single injection in approximately 30 patients. We plan to make a regulatory submission in the first half of 2019. Our launch timelines for the prefilled syringe have not changed, and we continue to be on track for an expected 2019 launch.

Thanks, Marion, and good morning, everyone. I'm pleased to report both solid top line results and strong operational performance for the third quarter of 2018. We are encouraged by EYLEA and Dupixent sales growth, progress across our portfolio, and improvements on our operating leverage as reflected in the reduction of our full year 2018 expense and tax guidance line items. For the third quarter of 2018, we earned $5.87 per diluted share on non-GAAP net income of $675 million. These results represent a 47% and 44% year-over-year increase in our non-GAAP diluted EPS and net income, respectively. Total revenue grew 11% year-over-year to $1.66 billion driven by performance of U.S. EYLEA, revenue increases for both the Sanofi and Bayer collaborations, and growth within other revenue. EYLEA net product sales in the United States grew 7% to $1.02 billion compared to $953 million in the third quarter of 2017. U.S. EYLEA distributor inventory decreased in the quarter compared to the second quarter of 2018, yet remained within our normal one- to two-week targeted range. As disclosed in our last earnings call, commencing in the second week of June, we increased the existing EYLEA discount that we offered to physician practices regardless of volume. As a result, there was a slight degradation in EYLEA's gross-to-net percentage in the third quarter of 2018 compared to both the third quarter of 2017 and first half of 2018.

Hey, guys. Good morning. Thanks for taking the question. I guess, Len, given all the commentary coming out of the White House around Part B proposals and HHS, just wanted to get to your latest thoughts on that messaging and anything that you guys can do to either mitigate that front on either on the – yeah, I'll leave it there.

Yeah. Hi. Thanks for your question, Carter. Obviously, it's tough to know what's going to actually become policy given a lot of these announcements were pre-election. I do think the administration is serious about trying to do something with drug pricing. But whether or not they will be able to get in a demonstration pricing which covers a large fraction of the country starting in the year 2020 with international reference pricing, I think that's a wide, big, open question mark at this time.

So certainly, it's early days, Greg, in the launch for asthma. But I can certainly report that with Dupixent for the new asthma indication, we are making steady progress and are very pleased with initial dialogue with payors. But I'll just remind everyone that this is only our third week in the market with the asthma launch. Then, as a comment, you alluded to atopic dermatitis and payor coverage. Certainly, we see the majority of the market with adequate coverage. And, of course, that reflects in the uptake we're seeing with Dupixent performance.

Hey, good morning, guys. Thank you for taking my question. I'm curious how you're looking at the market opportunity for Dupixent in the moderate eosinophilic asthma population when considering the low biologic penetration you referred to for severe asthmatics to-date. So, I guess, given those historic dynamics, do you think you'll be able to penetrate much of the moderate patients in the first year or so of the product's launch, or should we really be focused on severe? Thanks.

I'm going to let Marion answer that question after I just make one brief comment. The market has yet to see a self-administered product. And it is – penetration is expected to be exceedingly low for the moderate population when you have to get to the doctor's office in an infusion or hang around for half a day, et cetera.

Yes. So, I'd add to that, that it's not unusual that physicians, and in this case, it's pulmonologists and allergists, will often use a product, Dupixent, in this case, for asthma on some of their tougher patients first. I'll share that anecdotally, the reports we're getting have been very, very positive. So, over time, most definitely, I think we'll have success not only with severe but also the moderate patients. And I think that continuum will evolve over market experience. But there are really compelling reasons why, and that relates to the clinical profile of Dupixent in asthma, its overall efficacy, not only in exacerbations, lung function, OCS reduction and quality of life, but then also the broad category of patients that we achieved in our label; moderate-to-severe patients, of course, EOs greater than 150, OCS-dependent regardless of phenotype or EOs. As Len mentioned, another element that we're hearing is that we are the only asthma biologic to offer both at-home self-administration and when physicians want to, they can always start a patient in the office to help educate and train them. But this is a really important factor in the ability to have broader use. And then the other item I'd add is that, of course, with Dupixent, we're not launching a new product, we're launching a new indication. So, allergists who already had experience with Dupixent, and we already have shown an established safety profile. So, we're really excited about the launch. It is very, very early days. I look forward to giving you reports in the future.

Thank you very much for taking the question. Just to follow-up on Dupixent a little bit. Could you just address the question of the adolescent indication and what your expectations are there? And you mentioned the population, but would you expect adoption to be faster or slower there? And then just back to the asthma launch. Could you comment on whether you think this is going to be actively managed by payors, whether there'll be step edits and rebates involved, or do you think that you're largely going to sort of be able to price more or less at the same price as you have in AD and have unrestricted access? Thanks.

Geoff, before Marion answers, we invite you to come by. We might have an antiviral antibody we can give you there.

So, Geoff, addressing your comments first on Dupixent uptake in adolescence, well, as mentioned, we very much look forward to the indication and helping this group of patients with moderate-to-severe disease, and the agony that goes with that for both them and their families. We would anticipate that the uptake should be similar to potentially a bit faster than what we saw in adult atopic dermatitis, and I think it's for two reasons. I want to be a little conservative in saying similar, but the reason why I think realistically it might be a little bit faster for these patients is that physicians now have experience with Dupixent. And the product is becoming well known, depth of prescribing is increasing. And for that reason, coupled with the fact that this is an alarming disease for adolescents, we believe it's very important that we get the word out quickly, and there's great excitement and enthusiasm in the market for this indication, for this group of patients who are truly suffering. Your second question related to asthma and payor uptake, it's very early days. This is our third week of launch, so things are going well. There's been great receptivity to the clinical profile of the product. But I think I'd rather come back and give more detail on payor specificity as we have more time in the market.

Hi, great. Thanks for taking the question. Just on Dupixent, we've had the DTC campaign ongoing now for a little while. I was wondering if you could give us an update or your latest view on the patient mix that's currently receiving the drug for atopic dermatitis, as well as perhaps your view on current persistence or refill rates. That's something that I don't think was mentioned in the earlier remarks. Thank you.

Sure. So, let me take persistence and refill rates first. So the persistency that we've commented on in the past at the 12-month point being approximately 80% continues. So, we see strong persistency with Dupixent. Similarly, on the first script refill, that's an important factor and we still see that at over 90%. So, these are indicators that when patients go on Dupixent therapy for atopic dermatitis, they want to stay on therapy because their lives are better. The second piece you mentioned is a little bit on the DTC, I believe, was part of the question, and also, the types of patients. So, similar to the comment I made before, it's not unusual for physicians to start with their most severe patients. But clearly now, we're getting penetration not only with severe, but also moderate patients. And we really thought it was part of our responsibility to educate patients who potentially previously had given up because therapies were not really helping them at all, we thought that this product was absolutely ideal for an on-air branded campaign. We're still only in months of that branded Dupixent TV campaign. It was perceived, as some would recall, by a disease awareness campaign, and we thought that was the right order to do things. We've been in national broadcast mode with the Dupixent TV campaign now since about August timeframe. So, we're several months in. The signs we see so far are encouraging.

Hi. Thanks for taking the question. I know you are unlikely to give EYLEA guidance for 2019, but maybe you could just talk about the puts and takes heading into next year. It looks like we're on track for another double-digit year of branded growth here. So, just wondering if we think that, that should continue heading into 2019. And then you mentioned this higher dose formulation of EYLEA. Maybe what have you learned here that drove this decision? And what would actually be required to bring that to market? Thanks.

So maybe George can take the higher dose, and then we can comment about the market.

Well, in terms of a higher dose, I guess the point is that we remain impressed with the fact that EYLEA has stood up with so much competition, and that no one has really been able to come up, seemingly, with a fundamentally different profile in terms of the benefit, effects on vision or duration of treatment. And so, we thought that it was time, especially because we've been working on this in the labs for a while, to see whether just giving a higher dose of EYLEA can actually take EYLEA past what is now, we think, the gold standard in the field and see if we could either improve the benefit and/or extend the duration of the interval. And so we're poised, we've been working on this for a while, and we're going to be putting it in the clinic this year, 2019.

In terms of the market growth, we see nothing that will change the underlying demographics for the increase in diabetes and the increase in AMD continuing to grow the market somewhere in the mid to high or low-double-digit growth over time. Those demographics do not seem to be letting up at all. Obviously, where we fit in there, based on competition, what have you, we'll have to see how all that plays out. But I echo what George says, we haven't seen anything that's disruptive.

Hi. Thanks for taking the questions. I have one for NGF. In the recently released Phase 3 top line, you saw the placebo adjusted rate of – adjudicated arthropathy at about 2%. And then we saw the Pfizer fasinumab at ACR showed less than 1.5% incidence of RPOA. Just wondering whether you think that this kind of safety is acceptable for the FDA and for the treating physicians, and what's the gating factor for the long-term safety in your Phase 3 trial? And then next, if you could give us a little bit more color on the collaboration with bluebird, exactly what kind of target and what kind of style of therapy you're focusing on. Thank you.

Thanks, Ying. Let me just comment on the fasinumab and then maybe George can comment on the bluebird or add to fasinumab. But I have to say that I think we know that in any drug dosing – any drug development program, getting the dose right is really, really important. And that becomes super important when you have a very steep dose response curve for side effects. And we think that our approach has been to really try and get that dose right. And we're hopeful that the very long dose that we got that is still able to produce what's basically so far at least best-in-class efficacy results – and notwithstanding, of course, study comparisons and all that – but really good efficacy results thus far, but perhaps, as George said in his prepared remarks, mitigating the safety.

Yeah, just to add to that. As you know, we're continuing our long-term safety study with NGF. And as Len said, I mean, the most important data is to see what the benefit will be compared to adverse events with, we believe at this point, since we seem to have mitigated against at least the arthropathies, the total joint replacements numbers are going to be very important certainly with the competitor's program that is a concern, and we'll have to see whether our dose gets around that.

Thank you, George. Operator, that concludes our prepared remarks. We'd now like to open the call for Q&A.

Thank you. This is Greg Harrison on for Geoff. Thanks for taking the question. Can you talk us through the trends you're seeing recently with payor access for Dupixent? Have asthma patients been able to get access? And how is this compared with the launch in atopic dermatitis?