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spk16: Good morning, and thank you for standing by. Welcome to the Horizon Therapeutics PLC second quarter 2022 earnings conference call. As a reminder, today's conference call is being recorded. I would now like to introduce Ms. Tina Ventura, Senior Vice President and Chief Investor Relations Officer. Ms. Ventura, please go ahead.
spk15: Thank you, Chris. Good morning, everyone, and thank you for joining us. On the call with me today are Tim Walbert, Chairman, President, and Chief Executive Officer, Liz Thompson, Executive Vice President, Research and Development, Erin Cox, Executive Vice President, Chief Financial Officer, and Andy Pasternak, Executive Vice President, Chief Strategy Officer. Tim will provide a review of the business, including our second quarter performance and our revised full year guidance. Liz will then review our R&D program, followed by Erin, who will discuss our financial performance and guidance in more detail. After closing remarks from Tim, we'll take your questions. We posted our investor slide deck this morning as well. During today's call, we'll be making certain forward-looking statements, including statements about financial projections, development activities, our business strategy, and the expected timing and impact of future events. Our actual results could differ materially from these forward-looking statements due to a number of factors, including the risk factors and other information outlined in our latest Forms 10-K, 10-Q, and any 8-Ks filed with the Securities and Exchange Commission, and our earnings press release, which we issued this morning. Your caution not to place undue reliance on these forward-looking statements and Horizon disclaims any obligation to update such statements. In addition, on today's conference call, non-GAAP financial measures will be used. These non-GAAP financial measures are reconciled to comparable GAAP financial measures in our earnings press release, our slide presentation, and other filings from today that are available on our investor websites at www.horizontherapeutics.com. With that, I will turn the call over to Tim.
spk07: Thank you, Tina, and good morning, everyone. Before we move into the details of the quarter, I wanted to summarize a few key points today. Our orphan segment generated net sales growth of 13% driven by our strong commercial execution. We delivered another quarter of outstanding Christexa performance of nearly 30%, driven by increased uptake of our immunomodulation strategy and strong momentum in nephrology. A relaunch of Aplizna is also tracking well, and our rare disease medicines business delivered another solid quarter. And as expected, Tepeza net sales were impacted by Omicron-related effects in the second quarter. Of course, we're disappointed that Tepeza didn't rebound from Omicron as fast as we anticipated. We expected Tepeza trends to continue to show the positive progress we saw in the post-Omicron recovery, and that didn't happen. We have spent a considerable amount of time to understand the reasons for this and identified what we need to do to accelerate growth. We are now executing on these plans to drive near-term results and realize the full potential of Tepeza, which is significant given our estimates of more than 100,000 addressable U.S. patients with thyroid eye disease. A revised full year to peasant net sales guidance this morning is for growth in the high teens. Still significant growth of our 2021 net sales of $1.66 billion. While our pace of growth to reach peak sales is different given the slower start to this year, we remain highly confident in our global peak annual net sales expectation of more than $3.5 billion. We expect to drive at least mid-teens growth next year. We also see upside opportunity to our peak annual net sales expectations from a potential launch in Europe, which I'll touch on later. With that, let me provide additional perspective on Tepeza and then move on to the rest of the business. We launched Tepeza into an undeveloped and complex market in what turned out to be an unprecedented external environment with both COVID and the ensuing government-mandated Tepeza supply disruption. The journey since launch has been anything but typical, driven by the fact that Tepeza, with its impressive profile, has dramatically changed the TED treatment paradigm for both physicians and patients. And we've learned a great deal. In fact, the first year of our launch, we initially expected net sales of approximately $35 million, and we ended the year at $820 million. We achieved this rapid success because we executed extremely well to prepare the market and drive adoption of Tepeza among our core prescriber base. Ocular specialists, such as oculoplastic surgeons, who are TED specialists and know the disease well. We generate particularly fast uptake with early adopters and their highly motivated patients who had symptoms aligned to our clinical child data. We have a clear commercial strategy, which, as we shared on our last earnings call, has not changed. With ocular specialists, we are focused on increasing the breadth as well as the depth of our prescriber base. so that they identify more patients appropriate for TPEZA. With ophthalmologists, we are working to increase the breadth of prescribers while encouraging those who are not yet comfortable prescribing to diagnose and refer to a TED specialist. And with endocrinologists, our focus is on driving an urgency for them to diagnose and refer their patients to a TED specialist as well. So what's changed since we provided our previous full-year guidance? First, Based on prior trends, we expected a faster pace of growth from ocular specialists as we moved from the early adopters and the most motivated patients to a broader set of physicians and patients. We realized that we underappreciated some of the challenges in further penetrating this segment and that it will take more time and effort to accomplish this. Second, we also expected a faster pace of referrals from ophthalmologists and endocrinologists to our core TAPESA prescribers. We now realize that our sales force does not have adequate bandwidth to properly dedicate the time required not only to engage with ocular specialists, but also educate physicians about TED to drive key referrals. This underscores the need to expand our sales force, which I'll touch on shortly. The timing and broad impact of Wilmacron complicated our ability to understand these dynamics more quickly to make these necessary adjustments. As we discussed in our first quarter call, Compesa growth trends dipped with Omicron earlier this year. We expected that to persist into the second quarter, with growth accelerating in the second half of the year as the Omicron impact waned. However, the recovery didn't progress as fast as we expected, indicating to us that Omicron wasn't the only dynamic impacting the business. After digging deeper, we better understood those dynamics. We made several adjustments and are deploying more resources in a targeted manner to drive short and long-term growth of Tepeza. First, we are adapting our commercial focus to these new learnings. This includes focusing our targeting, simplifying our messaging, and increasing the accountability of our field organization. Accordingly, we have recently made several changes to the leadership of Tepeza commercial and Salesforce organizations. Second, we're spending more time and focus on the reimbursement process, which as we've mentioned previously, is burdensome on physicians, especially with surgeons who are not accustomed to it. We have changed how the patient services team operates, combining our patient and reimbursement access teams to streamline the process to more effectively support physicians and patients in the patient access journey. These changes free up time for our sales force to focus on driving to PESA prescriptions. Third, we are spending more time educating physicians as part of the medical management process for their patients. Unlike most diseases which are managed by one physician, defensive patients are typically co-managed by their surgeon and either their ophthalmologist or their endocrinologist. We are educating physicians on monitoring requirements and best practice protocols through peer-to-peer education. And finally, based on recent learnings and findings from our market segmentation work, we realized the importance of expanding our sales force more significantly than we had initially planned. We're in the process of doing just that. We are adding about 60 field-based employees. This gives our sales representatives more time for engagement with ocular specialists and now ophthalmologists and endocrinologists. We'll now cover a universe of approximately 12,000 total physicians. This broader effort will enable them to further educate ophthalmologists and endocrinologists about thyroid eye disease, driving urgency to diagnose and refer their patients to a TPEZA prescriber. These physician specialties see tens of thousands of potential TPEZA patients, but are much less familiar with TED, the pathology of the disease, and the relevance of the TPEZA mechanism of action as a key treatment approach. So currently, we believe many patients never make it out of their ophthalmologist or endocrinologist office to find the care they need. And this is why our Salesforce expansion and our TPEC investments are so critical. Over time, we expect more and more ophthalmologists to prescribe TPEZA. We recently completed a survey of ophthalmologists whose awareness of TED and TPEZA is very high. The survey showed over 60% intend to increase their TPEZA prescribing. underscoring the benefits of a larger Salesforce expansion. We'll conclude my comments on Tepeza with a brief review of the market. It is one of the key reasons we are so confident in the continued growth of Tepeza. We recently completed an exhaustive market analysis to better identify the types of TED patients and where they're being treated. It confirmed that patient symptoms, regardless of the time since diagnosis, are what motivates them to seek treatment and drive physicians to prescribe Tepeza. This research also confirmed our estimates that there are more than 100,000 patients in the U.S. appropriate for treatment with Tepeza. We have segmented these patients based on disease severity and clinical activity score, or CAS. We estimate that more than 20,000 have high CAS with key severity symptoms, such as high proptosis, diplopia, or both. It is also where we have currently the highest penetration at less than 20%. These patients are more likely to be seen by an ocular specialist. We believe we have the highest penetration in this segment because it's where we conducted our pre-launch work, where we primarily focused our sales force, and where we have shown impressive efficacy in our randomized placebo-controlled trials. We estimate that more than 80,000 patients in the next segment are also appropriate for TPEZA. They have low clinical activity scores with high proptosis, diplopia, or both. And we have low single-digit penetration of this segment today. These patients are primarily treated by ophthalmologists or endocrinologists where, as I mentioned before, there is relatively low awareness of the disease. It's also where we're focusing our Salesforce expansion. In addition to our sales and marketing efforts, we are generating additional clinical evidence intended to drive adoption in low-CAS patients. Today, most TPEZA uses in high-CAS patients, so our chronic trial, the trial in low-CAS patients, will be important because it will round out the picture of the efficacy of TPEZA in all CAS types. We have already seen good efficacy from TPEZA in this patient population through various physician-driven case reports. We expect to release top line data from this randomized placebo-controlled trial in the first half of next year. We also anticipate presenting the data at key medical conferences and publishing it in peer-reviewed medical journals beginning in the second half of next year. As a result, we have the potential for more meaningful uptake in the market from this data beginning in 2024. Our continued significant investment in DTC will amplify all of our actions discussed today. and our campaigns continue to generate above average returns. Beyond the significant opportunity in the U.S., we expect our global expansion to contribute meaningfully outside of the U.S. beginning in 2025. While our current competitive peak annual net sales estimate does not assume a launch in Europe, we are finalizing our assessment of that opportunity and expect to be in a position to provide an update later this year. We expect this will provide upside to our peak annual net sales expectations for Tepeza. We have learned a great deal over the last two and a half years, first in creating the market for Tepeza, then as the market has evolved. Our track record of commercial execution gives us confidence in building towards a long-term growth expectation to help thousands more TD patients with this life-changing medicine. Moving on to Cristexa, second quarter net sales were $168 million, representing strong year-over-year growth of nearly 30%. This continued strong performance was driven by a growing adoption of both rheumatology and nephrology market segments, as well as uptake of Cristexa with immunomodulation, which is now running at more than 50% of new patients. Following the recent FDA approval of our SBLA for the co-administration of Cristexa with methotrexate, the team was well prepared to execute the launch. In less than 24 hours, we launched our new promotional campaign, trained the field force, and launched new websites for both physicians and patients. We also hosted a live national launch broadcast, which included physician and patient speakers to educate more than 700 physicians across the country. Since acquiring Cristexa, we have dramatically transformed the growth trajectory of this life-changing treatment for patients with uncontrolled gout. Through our efforts to educate the physician community on the benefits of Cristexa, as well as investing in clinical data to show its efficacy and safety, this SBLA approval is the culmination of our efforts. With the expanded label, our commercial team is now promoting the benefits of Cristexa with methotrexate for the first time. We expect this to drive higher clinical conviction, rounding our reach to more physicians and increasing patient penetration among current treating physicians. In fact, we are already seeing this happen. Physicians who have never prescribed Cristexa before, who have not prescribed in a long time, are changing their opinion. One physician who had not prescribed Cristexa in over a decade said the new data shifted the way he viewed Cristexa and he already had a patient in mind who would be a good candidate for treatment. Building on the momentum we are seeing in this launch and to leverage the current nephrology progress, we're expanding the Chris Texas sales force by approximately 20% over the coming months. We're driving a significant momentum with this medicine, giving us continued confidence in our peak annual net sales expectation of more than $1 billion. With Aplizna, we delivered another strong quarter, generating net sales of $39 million, where we doubled our US sales compared to last year. We continue to make progress on our relaunch in the United States and are encouraged by the steady and consistent growth of new prescribers and new patient starts. As part of our global expansion strategy, our commercial launch is now underway in Germany. We're increasingly confident in the prospects for replacement in NMOSD, and we're progressing towards our global peak annual net sales expectation of more than $1 billion across all potential indications. I will now turn the call over to Liz.
spk01: Thank you, Tim, and good morning, everyone. We continued to make progress on our R&D strategy in the second quarter and advanced our pipeline programs. Starting with Cristexa, as Tim just mentioned, the FDA label expansion was a result of a successful priority review by FDA and was based on the data from our MIRA trial. As you know, the six-month primary endpoint showed a 30 percentage point improvement in the response rate using Cristexa with methotrexate compared with Cristexa alone. New 12-month data from the trial are also now included in the expanded label and also show a nearly 30 percentage point improvement in the Cristexa with methotrexate arm. From a safety perspective, infusion reactions were meaningfully reduced in the Cristexa with methotrexate arm. Only 4% of patients randomized to receive Cristexa with methotrexate, experienced an infusion reaction, compared to 31% in the Cristexa monotherapy group. Taken together, the data around co-administration with methotrexate are a significant change to the original label that was used to launch this medicine, the only one for uncontrolled gout 12 years ago. Moving to dextilamabs, which is the first and only plasmacytoid dendritic cell depleter in clinical development. We're studying dexedilumab in several indications and made notable progress this quarter. First, we completed enrollment in our phase two trial, evaluating dexedilumab in patients with systemic lupus erythematosus, or SLE, in the second quarter. We expect to announce top line results in the second half of 2023. We also initiated a Phase II clinical trial in the second quarter in alopecia areata, an autoimmune disorder characterized by non-scarring hair loss. This open-label trial is expected to enroll approximately 30 patients with moderate to severe disease, and we expect to announce top-line data in 2023. Looking forward, we expect to initiate three additional clinical trials with dexfilumab. our Phase II randomized controlled trial in patients with discoid lupus erythematosus, or DLE. DLE is a chronic inflammatory skin condition characterized by lesions. Second, our Phase II randomized controlled trial in lupus nephritis, or LN. LN is an autoimmune inflammatory condition of the kidney and is the most common major organ manifestation of SLE. Current treatment regimens include intensive immunosuppressive therapy that can be associated with adverse events, supporting the need for a more specific medicine to address the unmet need in those with proliferative LN. And third, our Phase II trial in dermatomyositis, an autoimmune inflammatory disorder characterized by rashes that often burn, as well as by debilitating muscle weakness. Moving on to Dazidelibep. our CD40 ligand antagonist designed to block a central pathway involved in many autoimmune and inflammatory diseases. We completed enrollment in the Phase II trial evaluating Dazidalibep for Sjogren's syndrome in the second quarter, and we expect results in 2023. We also announced top-line results from our Phase II double-blind placebo-controlled trial of Dazidalibep in rheumatoid arthritis patients. demonstrating that the primary endpoint was met in all four dazodelibep dosing arms and showing that it was well tolerated. We expect to present the full results at an upcoming medical meeting. We're also working with regulatory agencies to finalize the details of our trial design for FSGS, a rare kidney disorder. As for TPEZA, We're continuing to enroll patients in our Phase IV randomized controlled trial in TED patients with a low clinical activity score, otherwise referred to as our chronic TED trial, with top-line data expected in the first half of 2023. We continue to advance our TPEZA subcutaneous administration program, recently initiating enrollment in a Phase Ib trial in TED patients. and we continue to progress our work on our high concentration formulation as well. We also continue to enroll patients in the OPTIC-J trial in Japan. Aplysna is our anti-CD19 humanized monoclonal antibody, currently indicated for NMOSD, a rare and devastating neuroinflammatory autoimmune disease that attacks the optic nerve, spinal cord, and brainstem. We continue to enroll patients in our Myasthenia gravis trial. However, the complex geopolitical situation in the Russian and Ukrainian regions, along with the COVID lockdowns in China, have impacted enrollment and site availability. As a result, we now expect the top-line data readout for this trial in 2024. We continue to work diligently with patients and sites across the impacted regions and are putting the appropriate measures in place to meet enrollment targets. Enrollment is also advancing in our IgG4-related disease phase three clinical trial. And with that, I will now turn the call over to Aaron.
spk14: Thanks, Liz. My comments this morning will primarily focus on our non-GAAP results, unless otherwise noted. I will review our second quarter results, followed by our revised 2022 financial guidance. Our orphan segment generated second quarter net sales of $841 million, representing year-over-year growth of 13%. Our orphan segment operating income was $315 million. Net sales for the inflammation segment were $35 million, and segment operating loss was $7 million, primarily due to the impact of the at-risk launch of a generic PennCED 2% entrant on May 6th. As a result of the subsequent market erosion, we are in the process of winding down the inflammation segment, which we expect to conclude by the end of the year. Our second quarter gross profit ratio was 86% of net sales, somewhat below our expectations driven by the inflammation segment. Second quarter operating expenses were $448 million. This included R&D expense of $95 million, or 11% of net sales, and SG&A expense of $352 million. Second quarter adjusted EBITDA was $307 million. The tax rate for the second quarter was 11.7%. As we have seen in prior years, there can be variability in our tax rate across quarters. Net income in the quarter was $254 million, and diluted earnings per share were $1.07. The weighted average shares outstanding used to calculate second quarter 2022 diluted EPS were 236 million shares. Second quarter operating cash flow was $251 million. As of June 30th, cash and cash equivalents were $1.89 billion. Backed by this strong cash position and expected future cash flows, we expect business development to continue to play a critical role in expanding our pipeline and diversifying our business. The total principal amount of our outstanding debt is $2.6 billion, with the earliest maturity in 2026. Our gross debt to last 12 months adjusted EBITDA leverage ratio was 1.6 times as of June 30th, and our net leverage ratio was well under one times. I will now turn to our revised outlook for 2022 and how we see the rest of the year playing out. We are revising our full-year 2022 net sales guidance to $3.53 to $3.6 billion, representing year-over-year growth of 10% at the midpoint. We now expect to PESA full-year 2022 net sales growth in the high teens, with quarter-over-quarter sequential growth expected over the third and fourth quarters. For Cristexa, we continue to expect full-year 2022 net sales growth of more than 20%. For the inflammation segment, we expect net sales of less than $30 million in the second half of the year due to the market erosion caused by the generic PennCED 2% entrant. As we wind down the business, we expect our net sales for this segment to be immaterial beginning next year. We continue to expect full-year 2022 gross margin of approximately 87%. We expect full-year adjusted EBITDA to be between $1.3 and $1.35 billion. As it relates to operating expenses, we expect third and fourth quarter expenses to be in a similar range as the second quarter. We expect a modest benefit in the fourth quarter from the wind down of the inflammation business unit, which will be mostly offset by the expansions of the Tepeza and Christexa field forces. We continue to expect our full year net interest expense to be approximately $85 to $90 million. We continue to expect our full year 2022 tax rate to approach 12%. As with every year, we anticipate variability in our tax rate on a quarterly basis. We continue to estimate that our 2022 cash tax rate will be in the mid to high single digits. As always, our tax rates could change significantly as a result of acquisitions or divestitures we may make or any changes in tax laws. We continue to expect our full year 2022 weighted average diluted share count to be approximately 238 million shares. With that, I will turn it over to Tim for his concluding remarks. Thank you, Aaron.
spk07: A few thoughts this morning. We delivered strong growth this quarter with Gristexa, Apliza, and our rare disease medicines, as well as the continued advances we're making with our pipeline. With Tepeza, we're expanding our presence and putting in place the actions we believe are needed to accelerate growth. We're revising our growth this year to high teens and expect at least mid-teens growth next year. While the expected pace of growth is different than our original expectations, we remain highly confident in our Topesa Global Peak annual net sales expectations of more than $3.5 billion, which does not include our potential entry into Europe. We've also updated our full-year guidance of the recent and unexpected at-risk launch of a generic PennCED 2%. We'll be winding down the inflammation business by the end of the year. It is our legacy business that launched Horizon 12 years ago and which provided the investment to allow our rapid and successful diversification into rare diseases. Five years ago, the inflammation segment represented roughly 60% of our net sales, and it's a reminder of how quickly we have executed to transform Horizon to the rare disease-focused biotech company we are today. Part of executing our business is recognizing the changes that need to be made in the short term to drive long-term growth. We have demonstrated this strategic agility throughout our history. We have leveraged our commercial and R&D expertise to breathe new life into underutilized medicines. We've built new markets, and we've made some of the highest-returning acquisitions in the healthcare sector, and we've completely transformed our company in an incredibly short period of time. As we look ahead, the medicines that are driving our future growth are truly remarkable medicines with impressive efficacy, significant opportunity for increased penetration, and they address important patient needs. We continue to expand our pipeline to support our future growth and look forward to several key readouts beginning the first half of next year. With nearly $2 billion in cash at the end of the quarter, we are in a strong position to continue to build and diversify our company through our business development activity and pipeline programs. We remain committed as ever to continue to make a difference in the lives of patients and build long-term value for shareholders. I'll pass it on to Tina, and we'll now open the call up for questions.
spk15: Thanks, Tim. Chris, if you'd like to do that.
spk16: Thank you. To ask a question, you'll need to press star 11 on your phone. Please stand by as we compile the Q&A roster. Our first question will come from Chris Schott of J.P. Morgan. Your line is open.
spk11: Great. Thanks so much. Just two on Tepeza. I guess the first one is just how different, I guess, is the profile of the patient sitting today at the ophthalmologist or endocrinologist versus those who are at the ocular specialist? I guess are these all these low-caste patients you referred to in the opening remarks? And I guess I'm just trying to get my hands around, what is the risk that, I guess, these patients symptoms just aren't severe enough to motivate the patient to get therapy, even if the physicians are better educated and better aware with some of the promotion efforts that you're planning. And then just maybe my second question is, again, both up front, is if I look at the guidance on Tepeza, it seems like pretty limited sales growth in the second half of the year versus the first half, if I take the midpoint of the guide. And I'm just trying to understand why we aren't expecting a bit more growth in the second half. I guess, given the COVID impact you talked about in the first half and then some of these promotion efforts that you're investing behind, is it just not enough time to see traction with those or just a little bit more color there would be appreciated? Thank you.
spk07: Sure, Chris, and thanks for the question. So first, when we look at the approximately two-third percent of patients of that 100,000 plus that are in ophthalmologists and endocrinologists, right now we're doing a very effective job through our PTC of activating patients and getting them into those offices. When you look at those patients relative to the two segments we're talking about, high versus low-cast, they're not all low-cast patients. Many of them are also high-cast patients. It's just that they have been sitting in ophthalmologists and endocrinologists' offices without us being able to effectively pull through because we haven't had sales reps focus on that broader audience. The real focus of our Salesforce expansion is to get into that broader 12,000 target where 65% of patients fit. It's a mix of high and low-cost patients. And based on our research and market research and talking to ophthalmologists who we expect to continue to increase their prescribing, 60% of them said they indicate they'll significantly increase their prescribing. So we feel confident that these efforts will work. begin to generate the growth we need. To your second question, Chris, it's a good one. We expect to complete the expansion here in the third quarter. We have moved a number of our original IBU or inflammation business representatives who have had great long-term success into the TEPEZA team and they will begin training shortly. So we expect to have training done and them out in the territories. beginning to make an impact as we end the year and expect that growth to really accelerate as we move into 2023, which is really what guides us to talking about at least mid-teen growth in 2023. And that is we get to the end of the year in 23, we expect to get the data from the chronic low-caste study, which will allow that to really start accelerating in 24 and lead into 25 when we expect to start also seeing the global launches come into market. So that's how we view things moving forward.
spk15: Thanks, Chris. Chris, next question, please.
spk16: Thank you. One moment for the next question. Our next question will come from Ken Cacciatore of Cowan & Company. Your line is open.
spk03: Thanks so much. Tim, it seems we've moved from Tepeza of a question of are the patients out there, which is always key when you're launching it to a new market, to now just more logistical on three levels. And I don't want to be repetitive. I just want to make sure I have this right and then make sure I understand the focus. So the first level here is helping to support the current practices. I mean, in our conversations, it does sound as it's very labor intensive on reimbursement and scheduling. So just wanted to understand as we think about investments, how much are we upping to kind of support the current high volume practices? Sounds like the second is bringing on new ocular surgeons. Wonder if you could just flush that out a little bit more of maybe those high volume practices that haven't adopted and to what degree this Salesforce expansion supports them. And then you've talked in great detail about digging out from the community ophthalmologists and endocrinologists. And that sounds like the biggest point of investment. But could you hit on all three and do we have it right? Is this more now just logistical kind of investment focus as opposed to patient focus? Thanks so much.
spk07: Thanks, Ken. I think you hit on a number of the key points. When we look at our Salesforce expansion, there are a couple key aspects to it in addition to the changes we made in our patient and reimbursement access team. So with With the reps, they're going to have smaller territories. As you heard in my prepared remarks, we talked a lot about that combination of trying to sell and also manage the reimbursement process and not having enough time to focus on selling. So with our expanded sales force, we'll have more time to focus on selling, not only in that initial core oculoplastic specialist group, but also being able to get into those broader ophthalmologists and endocrinologists offices and allow our combined patient access and reimbursement access group to have a single point of contact with key offices to really help pulling those patients through to get their infusions. So that's the real focus of our broader effort there.
spk15: Great. Thanks, Ken. Next question, please.
spk16: Thank you. One moment for our next question. Our next question will come from David Amselem of Piper Sandler. Your line is open.
spk04: Okay, thank you. So just taking a step back here, this is a question for Tim. As you look at what has become a fairly heavy lift in terms of marketing and promotion of Tepeza and how that is and how the trajectory is playing out, does that mean that you are more likely to get more aggressive on M&A, not just to sort of add to the pipeline, but to bring in another commercial stage asset or assets? So how do you think about that given where Tepeza is? And then secondly, just sort of a backward-looking question, In hindsight, do you think there may have been just a bolus of patients or low-hanging fruit, if you will, in the thyroid eye disease setting that you worked through, and now you're in what I guess I would call an air pocket in terms of demand? How should we think about that? Thank you.
spk07: So relative to the bolus, I think that there
spk04: that you work through and now you're in what I guess I would call an air pocket in terms of demand. How should we think about that? Thank you.
spk07: So relative to the bolus, I think that there were, when you look at any launch, there are early adopters and based on our pre-marketing work, we have prepared a number of those key oculars, especially get patients onto treatment and to COVID Our DTC efforts were able to activate those patients to take action, and we outperformed extremely well there when we look at it, David. So when you look at the next phase, our DTC continues to outperform. The bottom line is these patients are being sent to broader ophthalmologists and endocrinologists' offices. We're not actively there, so we need to expand, get into those offices with the existing ocular specialists We're now moving into the moderate to late adopters, and we need to continue to increase our efforts there, continue to drive them into looking at broader sets of symptomology and taking action. When we talk about ophthalmologists and endocrinologists, it's twofold. Endocrinologists, it's all about driving awareness and getting them to refer to it as a writer. With ophthalmologists, it's really bifurcated from ophthalmologists willing to prescribe and also ophthalmologists that we need to focus on referring to as writers. So we really look at it as the next phase of launch. I think a lot of it, as I discussed, was masked by what was going on with COVID, then supply shortage, and then Omicron. But I think we feel really good about the plans we have in place, the focus of our new sales force, the focus of our patient services organization, and it's now the blocking and tackling and really driving day-to-day conversion of those patients. To read through to your second comment, first of all, we have three key growth drivers in Tepeza, Christex, and Aplizna, and we see over $5.5 billion in potential peak sales with further upside from Tepeza in Europe as we'll get into further detail throughout the rest of this year. So we feel great about those growth drivers. As I mentioned, Cristex and Plisner are tracking extremely well. But whenever you have a launch that has the blockbuster uptake, as we talked about, getting into billions of dollars, that changes the slope of your curve and the focus of your business development efforts. And maybe, Andy, you want to speak to that?
spk09: Sure.
spk07: Thanks, Tim, and thanks, David.
spk10: I think it goes without saying that Horizon has had a very successful track record of business development. And as Aaron said, BD is going to continue to play a pretty critical role in expanding our pipeline and further diversifying our business. So we remain focused on individual asset licensing and collaboration deals, but we are certainly also looking at larger transactions. And we have the financial flexibility and capacity for such transactions. I think in a larger transaction, you know, we'd be seeking a combination of approved medicines and development stage assets to manage risks. So we wouldn't want to take binary bets at that kind of scale. And I think VL is a good example of that. There are some larger opportunities we see right now that make sense strategically for us. However, you know, we remain financially disciplined and aligning, frankly, aligning on deal terms that work for both us and the seller. That remains the biggest barrier to getting deals done right now, and there are some management teams and boards who haven't adjusted their expectations relative to where the equity market is currently setting their valuations, so we're just going to have to see how that plays out.
spk07: But I think the bottom line is we see a lot of opportunities, and we expect to be aggressive.
spk15: Thanks, Tim. Chris, next question, please.
spk16: Thank you. One moment for the next question. Our next question shall come from Annabelle Samimi of Stiefel. Your line is open.
spk06: Hi. Thanks for taking my question. So just for Tepeza, I want to clarify that the bottleneck is not necessarily reimbursement per se, but the support needed to usher the patient through the system. Obviously, this is a product that's grown very rapidly. So have there been any new roadblocks that The payers have put up given the high demand. And then my second question is more of a long-term margin impact. Obviously, you're putting a lot of support behind TPEZA and just want to verify that the mid-40s margin and possibly 50s operating margin is still a goal that you can attain. And I guess along those lines, obviously your DTC, was very effective, maybe too effective, because it brought more patients in that you could support. So is there any thoughts of pulling some of that back for a bit so you can absorb some of the demand and get these patients through? Thanks.
spk07: I'll start with the last question. We do not plan on pulling our DTC back at all. It's been highly effective. It's driving both uptake in the core oculoplastic specialists, but also in continuing to put patients into those ophthalmologists and endocrinologists offices where our sales force will be focusing. From a margin standpoint, the mid-40s to 50, you mentioned that it certainly continues to be an achievable goal for us. And as Darren mentioned in his remarks, we are offsetting that reduced spend in the information business with moving those resources over to PESA and to a smaller extent, to Cristexa. When we look at the roadblocks, reimbursement or really access, so policies and efforts by payers have not changed materially over the last, I would say, really through the last year plus. The roadblocks are not greater. This is a function of ocular specialists have been the key early adopters that have driven the great uptake we've had not being generally comfortable or even experienced in managing reimbursement. So it's really moving patients as fast as possible through that process. And that is part of why we restructured our patient access and reimbursement groups into one, so we can put one point of contact and continue to find efforts to reduce the effort there. And as we move into ophthalmologists and endocrinologists, they do have more experience in both managing reimbursement, managing medical monitoring of patients, as well as just the broader process of treating patients. So we feel confident in our ability to continue to drive the business there.
spk15: Thanks, Tim. Chris, next question, please.
spk16: Thank you. One moment for our next question. Our next question will come from Michael Ults of Morgan Stanley. Your line is open.
spk17: Yep. Hey guys, thanks for taking the question. Maybe I could just ask one on Christexa here. Seems like you're still seeing nice growth in QQ, so maybe you can give a little bit more color on what the key drivers there have been through the past quarter here. And then also, now that you have an expanded label and you touched on this in your prepared remarks, but Maybe you can give a little bit more color on the impact you've seen so far over the past month and then maybe how that could evolve moving forward in the second half. Thanks.
spk07: Thanks a lot for the question. We've seen great progress. I think we've been really impressed by the fact that our growth, our sequential growth and growth metrics in nephrology have caught up to our growth metrics in rheumatology. That team is really performing and that's part of where we're going to be expanding to leverage that uptake. Additionally, we're seeing our Cristexa with methotrexate and other immunomodulators penetration now exceed 50% so we continue to see entrenchment there and also the vials per patient continue to increase. as we move forward. So that has all contributed to the success and the 30% year-over-year growth that we saw in the quarter. With the expanded label, and some of this I mentioned in my remarks, we've had physicians who've been out of the market for a decade who were either fearful of 40% efficacy and that meant 60% that weren't going to respond, and then that brought them to questioning whether there were infusion reactions or other things That they needed to worry about or they had a bad first experience and and those are the kind of dialogues That are really changed we can go in a lot of folks that I need to see it in the label I need to see the data to get the confidence to get back in given my early experience And those are the dialogues that are occurring and they've been really promising so far So I think we're seeing new prescribers come into the market that haven't been there so as we look at existing and new prescribers Those are really, both groups are growing extremely well, along with the real progress we've made in nephrology.
spk15: Thanks, Jim. Chris, next question, please.
spk16: Thank you. One moment, please. Our next question shall come from Madhu Kumar of Goldman Sachs. Your line is open.
spk13: Hey, thanks for taking our question. This is Rob. Two quick questions here. One, just how are you thinking about business development versus deleveraging? I know you made some comments about, you know, the M&A outlook so far. And then on to PESA, what do you think the potential for the chronic PED readout is to drive further uptake in 2023?
spk07: Sure. So we are deleveraged, and I think on a net basis under one. and feel we're in a great position with approximately $2 billion on the balance sheet to be aggressive in M&A, both for on-market assets and to fill in the pipeline. So we feel we're in a great place to be aggressive there and really leverage, as Andy discussed, continuing to see movement and willingness for management teams and boards to recognize the environment that we're in. With the chronic market, that is something that I talked about in a few of the prior questions, but as we look at the key growth drivers, when we look at 23 and the mid-teens, that's really going to be driven by expansion into those broader ophthalmologists and endocrinologists office, expanding our call-on targets to 12,000, getting that data in the first half of 23 on our chronic low-caste study, will expect to be published in the second half. And as we head into 2024, we do expect that to be the next leg of growth that will then drive us into our global launches coming from the broader international markets.
spk15: Thanks, Tim. Chris, next question, please.
spk16: Thank you. One moment. Our next question will come from Jason Gerberry of bank of America. Your line is open.
spk05: Hey guys. Uh, thanks for taking my questions. So Kim just wanted to confirm for the 2023 to PESA growth outlook that does not assume like a positive phase four chronic TED trial outcome. And then my, my second question is just appetite for repurchasing your own stock. You know, the stock right now, I think it's trading in the low $60 and the pre-market on the quarter update. So just curious, I mean, if your confidence remains strong in your peak sales outlook, why not buy back some of your own stock?
spk07: Well, thanks for the question. What was the first one? I think around chronic pain. We do not expect that to be the key driver in 23. The at least mid-teens growth that we expect is going to be driven by our expansion, our focus on the broader targets where 65% or two-thirds of those patients now sit. continued execution of our DTC to really funnel patients in there and begin to in earnest pull them through. And then the chronic low-cost study would then feed into 24 and beyond. Relative to buying back shares and those actions, with our balance sheet, our history of successfully buying assets like Tepeza, like Cristexa, where we can drive them differentially We think our cash is best used to significantly bring on assets that are going to drive our long-term value.
spk15: Thanks, Tim. Chris, next question. Next question, please.
spk16: Yes, thank you. One moment for the next question. Our next question shall come from Akash Tiwari of Jefferies. Your line is open.
spk00: Hi, everyone. This is Amy on for Akash. Would the insurance reauthorization benefit you historically have seen between Q1 to Q2 suggest that TPEZA new starts this quarter are even lower than expected? Additionally, recently, you talked about seeing inflection in PES post-Q1. What's happened since then? And then finally, what gives you confidence to reiterate the $3.5 billion plus long-term TPEZA guidance? And does that now account for the chronic study reading out positively and a potentially higher penetration in chronic patients? Thanks so much.
spk07: So from the 3.5 billion or greater than 3.5 billion in peak sales, we are extremely confident. Again, that does not include our expected entry into Europe, so certainly upside there. As we look at, it's a three-phase approach that we think are going to drive our approach to those peak sales. It's really driving our expansion, putting additional 60 field force folks out there, getting to that broader targets where 65% of the patients are now sitting the chronic trial and penetrating into that audience. We don't look at the market as acute and chronic anymore based on our understanding of how physicians treat these patients. It's really based on high and low-cost patients who have high proptosis or high or double vision. So we see our ability to drive there sufficient to meet or exceed our peak sales expectations, and that would carry us into our global launches in 2025. When we look at the first quarter and insurance reauthorizations, we don't feel that that had any impact on the second quarter.
spk15: Thanks, Amy. Chris, next question, please.
spk16: Yes, thank you. One moment for the next question. Our next question will come from Derek Arcilla of Wells Fargo. Your line is open.
spk02: Great. Good morning. Thanks for taking the question. Maybe just first, can you talk to the level of the PESA awareness among the endos and the ophthalmologists that are not referring patients right now to ocular specialists? Is it that they just don't know about it, or is it that they don't want to refer patients for treatment? And then one pipeline question. I guess, when can we see the Phase II data from the sub-Q TPEZA presentation? Thanks.
spk07: As far as TPEZA awareness among endocrinologists and ophthalmologists, it is extremely high. I think the biggest challenge has been that we're not in those offices. We're not helping them understand the seriousness of thyroid eye disease and the seriousness in getting them treated in the short term with medicine like Tepeza and then where to refer them to get treated. This is not an issue of lack of willingness to refer, it's lack of us being in there to drive that action. Liz, do you want to speak to the second question?
spk01: Yeah, so we're making good progress on our sub-Q program with Tepeza. We've gotten through our first, very first phase, which was a single dosing we've just initiated as we announced on today's call. Our dosing in patients with thyroid eye disease We will continue to update as we proceed along with these trials and anticipate more information on upcoming calls. Thanks, Liz.
spk15: And Chris, we have time for one more question, please.
spk16: Yes, thank you. Then our last question shall come from Mr. Gary Nachman of BMO Capital Markets. Mr. Nachman, your line is open.
spk12: Okay, great. So, Tim, with all your market research, just talk about your confidence in the number of these TED patients that are out there, the 20,000 acute and 100,000 total. And with the increased sales force, how many of those patients will you be covering if you hit the broader 12,000 positions that you're talking about? Then on the chronic TED study, just, you know, talk about your confidence with enrollment in that study. and how it's designed for success. And then lastly, just how should we think about operating margins trending over the next few years with revenue run rates coming down and now increased spending that you're talking about? Thanks.
spk07: Sure. So from a spend standpoint, we think a lot of that increased spend will be offset by reduced spend. In our inflammation segment, I'll let Aaron in a second here take the question on operating margins over time. From an enrollment standpoint, we feel that we're well on track to achieve our goal to release data in the first half. Liz, do you want to speak to how you feel about the trial?
spk01: Absolutely. We've taken into account a number of learnings that we've had about chronic thyroid eye disease or specifically patients with low clinical activity scores who nevertheless have high rates of proptosis when we were designing our trial. We feel confident that we've designed this appropriately to show a clinically meaningful outcome, and we do have a lot of data that supports in that direction with all the case reports and case series out there. And to reiterate, as Tim said, we had a little bit of a slowdown in enrollment during Omicron. That's picked back up. We're very confident in completing enrollment this year and having data in the first half of next year.
spk07: So relative to the market size question that you asked, We see 100,000 patients being covered by those 12,000 targets, with a third of them being in the osteoplastic specialist and two-thirds being in the ophthalmology endocrinology group. Aaron?
spk14: From a margin standpoint, as Tim mentioned, over the long term, targeting 50% remains our longer-term goal. From a near-term perspective, we expect third quarter and fourth quarter to be similar to the second quarter from an OPEC standpoint with modestly higher R&D offset by modestly lower SG&A. Then as we look forward to 2023, which will provide guidance on our fourth quarter call, we'd anticipate 2023 SG&A to increase modestly versus 2022 with a more meaningful step up in R&D spend given the trial initiations that we've discussed.
spk15: Thanks, Eric. And Chris, that concludes our call this morning. That concludes our call this morning. Webcasts will be available in about two hours. Thank you, everyone, for joining us.
spk16: This concludes today's conference call. Thank you all for participating. You may now disconnect and have a pleasant day.
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