This conference call transcript was computer generated and almost certianly contains errors. This transcript is provided for information purposes only.EarningsCall, LLC makes no representation about the accuracy of the aforementioned transcript, and you are cautioned not to place undue reliance on the information provided by the transcript.
spk09: Good morning and thank you for standing by. Welcome to the AbbVie Second Quarter 2020 Earnings Conference Call. All participants will be able to listen only until the question and answer portion, and you may ask a question by pressing star 1. I would now like to introduce Ms. Liz Shea, Vice President of Investor Relations.
spk08: Good morning and thanks for joining us. Also on the call with me today are Rick Gonzalez, Chairman of the Board and Chief Executive Officer, Michael Severino, Vice Chairman and President, and Rob Michael, Executive Vice President and Chief Financial Officer. Joining us for the Q&A portion of the call is Laura Schumacher, Vice Chairman, External Affairs, Chief Legal Officer, and Corporate Secretary. Before we get started, I remind you that some statements we make today may be considered forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. ABBYY cautions that these forward-looking statements are subject to risks and uncertainties, including the impact of the COVID-19 pandemic on ABBYY's operations. results and financial results that may cause actual results to differ materially from those indicated in the forward-looking statements. Additional information about these risks and uncertainties is included in our 2019 Annual Report on Form 10-K and in our other FCC filings. Abgander takes no obligation to update these forward-looking statements except as required by law.
spk01: I'm rubbing the arms of my chair, admiring the craft and detail I've put into it. That way I try to convince myself that I'm in control of the business side of my business.
spk12: Intuit QuickBooks makes it easy for you to get a complete view of your business so you can sit back and relax. At a time when most universities look like this. The founders of Walden University saw a chance to rethink the classroom. Their vision would spark a revolution in distance learning and inspire us to pioneer online education. That's because we've been there at every turn to help students of all backgrounds find their moments to shine. We've provided a launch pad for social change. preparing our students to lead from the heart and the head. The reality is, not every university will change. Not every university can change. Their past is not your future. Their way forward doesn't have to be yours. Wherever today takes you, whatever tomorrow demands of you, you'll be prepared. Because for more than half a century, we've been preparing for you.
spk08: On today's conference call, as in the past, non-GAAP financial measures will be used to help investors understand Abbey's ongoing business performance. These non-GAAP financial measures are reconciled with comparable GAAP financial measures in our earnings release and regulatory filings from today, which can be found on our website. Please note that the second quarter financial results and guidance provided on today's call for sales, EPS, and line items of the P&L reflect a full period of legacy Abbey operations and a partial year contribution from the Allergan portfolio since the transaction closed in early May of this year. In addition, we have provided a quarterly comparable historical trend analysis for key product revenues of the newly combined company as a supplemental table in our earnings release this quarter. This table supports the comparison of sales growth on a comparable operational basis, including full quarter, current year, and historical results for Allergan on a pro forma basis. Comparable operational percent changes are presented at constant currency rates. For this comparison of underlying performance, all historically reported Allergan revenues have been recast, conformed to policies, and exclude the recent divestitures of ZenPAP and BioCase. Following our prepared remarks, we'll take your questions. So with that, I'll now turn the call over to Rick.
spk19: Thank you, Liz. Good morning, everyone, and thank you for joining us. Today, I'll discuss our second quarter performance and highlights, and for the first time, I'll provide our 2020 outlook for the newly combined company. Mike will then discuss recent advancements across R&D programs, and Rob will review the quarter and our updated guidance in more detail. Following our remarks, we'll take your questions. I'd like to start off by recognizing all of our employees, including those joining AbbVie from Allergan, for all of their hard work and dedication during this pandemic. The AbbVie team has been working diligently and carefully within our facilities and remotely. to ensure that our business continues to operate properly and our patients continue to receive their medicines. Before I speak to the strong financial performance this quarter, I'd like to characterize the state of the recovery of the business from the COVID crisis. Let me start with the legacy AbbVie side of the business, which has demonstrated robust performance leading into the pandemic and has remained resilient. The impact on continuing patients for Humira, and new patients for RENVOTE, Skyrizzy, and VanClexta were not as pronounced as we had previously anticipated. While patient flow has not recovered in most therapeutic segments, we're encouraged by the level of stabilization and the recent positive demand trends. Overall, the legacy AbbVie business continues to perform very well with standalone revenue growth in the second quarter of approximately 8.5% on an operational basis, excluding the negative impact from COVID. On the Legacy Allergan side of the business, we saw significant COVID-related impacts on Botox Therapeutic and our Aesthetics business in the second quarter. Both businesses are seeing a rapid recovery and are now performing near pre-COVID levels. Other key brands, such as Valar and Ubrelvi, were impacted in a manner similar to the AbbVie-based business and were pleased with the recent trends and progress. Overall, COVID had a substantial impact on second quarter reported revenues, with an estimated net unfavorable impact of more than $900 million. However, by the end of June, the total business had recovered to more than 90% of pre-COVID levels. So I'm pleased with the resilience and the rapid recovery across our portfolio, and I'm confident in the continued strong underlying demand and performance of the combined new company. Despite the impact from COVID, we delivered a strong second quarter performance. Adjusted earnings per share of $2.34 were well above our expectations. The 21-cent beat included 11 cents of net accretion from Allergan, as well as 10 cents of favorable performance versus the midpoint of our standalone guidance. Total revenues were $10.4 billion, including approximately $8.4 billion of legacy AbbVie sales, significantly above our expectations for the standalone portfolio. With continued robust performance in both HEMON and immunology despite the impact from COVID. PMOC revenues of approximately $1.6 billion were up strong double digits again this quarter. And Theravica sales grew approximately 17% on an operational basis reflecting continued strong performance in CLL where we remain the clear market leader. And Klexta sales were up more than 80% on an operational basis with strong growth in CLL and AML. During the quarter, we also announced a strategic collaboration with GenMap.
spk00: They say all good things must come to an end. And there it was, the inevitable client handover.
spk01: So, I guess that's it. Yes, Diane, I think we're done.
spk00: Well, it's been a hell of a ride. It was. It really was. So you just switch it between them. Can I give it a try? Yeah, sure. Oh, I'm sorry. You go first.
spk01: No, you go first. Honestly, I just really feel like it would look better this way.
spk00: Fine. I love this.
spk01: Hold on. I'm writing this down. What is this for the homework? So she'd be in the first grade. Amazing. Thank you.
spk15: Hey. Can we go through the breakpoints one last time?
spk00: I thought you'd never ask. To further build our oncology portfolio, with a CD3 by CD20 bispecific antibody,
spk19: It has the potential to be a best-in-class therapy across B-cell malignancies. Our leading immunology business delivered revenues of more than $5.3 billion, reflecting growth of more than 8.5% on an operational basis. U.S. Humira revenue growth remained strong, up 5%, with continued demand from the large installed patient base partially offset by the impact of COVID-19. the international humoral biosimilar dynamics in the quarter were better than our expectations. Sky RISD continues to perform well and has maintained its leading in-place psoriasis patient share, which includes both new and switching patients, at more than 30%. As expected, we saw modest delays to new patient starts during the quarter as a result of the COVID-19 dynamics. However, Recent prescription trends and increasing enrollment in our ambassador program, two leading indicators, demonstrate a strong growth trajectory and support our four-year guidance of $1.4 billion. We're also seeing very encouraging trends for RINVOC, where rheumatology office visits are approaching pre-COVID levels. RINVOC revenues were up more than 70% on a sequential basis and currently reflect 15% in-play RA patient share which is now nearly at parity to Humira, the market leader in in-play share and above all other agents in the segment. We're also making excellent progress with our immunology pipeline which Mike will discuss further momentarily. As I noted during the quarter, we successfully completed the acquisition of Allergan. creating a stronger and more diverse AbbVie. The transaction significantly expands and diversifies AbbVie's revenue base and complements our existing leadership positions in immunology and hematological oncology with additional growth franchises in aesthetics and neuroscience. We have growth opportunities in neuroscience with Botox Therapeutics, Baylor, and UBrelvi. And we have the leading global aesthetics business with flagship brands including Botox Cosmetics and Juvederm. I'll start with neuroscience, which had sales of roughly $735 million to AbbVie in the second quarter. Baylor continues to demonstrate rapid growth and is well on its way to surpassing $1 billion in annual revenues. Underlying demand has remained resilient despite the COVID-19 pandemic. with strong double-digit growth again this quarter. We see significant room for continued expansion within Baylor's existing indications, bipolar disorder and schizophrenia. Major depressive disorder or MDD represents another potential large indication with two phase three trials well underway. Also within neuroscience, we now have a portfolio of migraine therapies that have the potential to support long-term growth in a highly attractive and underserved market. Our migraine portfolio is anchored with Botox Therapeutic, which had revenues of roughly $300 million to AbbVie in the second quarter. Despite multiple new competitive entrants, Botox Therapeutic has largely retained its total treated patient base, a testament to its efficacy, safety, and brand recognition. Like many physician administered products, Botox Therapeutics saw a significant impact from COVID-19 in the second quarter, with global sales down approximately 20% on a comparable operational basis. However, we're pleased by the recent data trends, which demonstrate a fast recovery and performance is now close to pre-COVID levels.
spk15: An iconic shot. Like Capital Group's new ETFs, there's so much behind it. Like navigating ups and downs. Can I find an ETF with a whole lot behind it? With Capital Group, I can.
spk19: The launch of UBrelvy, the first to market in leading oral CGRP for acute migraine, is off to an excellent start. Feedback from physicians has been very positive, giving UBrelvy's efficacy, safety, and and convenient dosing profile relative to current standards of care. Commercial access for ULB is now at 70% which along with increased consumer promotion will further support the product's launch trajectory. We're also developing a Toe Japan for the prevention of episodic and chronic migraine. We recently disclosed positive top line results from a phase three study in episodic migraine which will support regulatory submission early next year. As a fourth pillar of growth, we now have the world's leading global aesthetics franchise, which generated sales of roughly $480 million to AbbVie in the second quarter. As anticipated, we saw a decline in year-over-year comparable operational growth with aesthetics healthcare providers closed during the initial phase of COVID. It's now been roughly two months since most major geographies have begun to reopen, and we're pleased with the strong recovery trends we're seeing. As of the end of June, the vast majority of our aesthetics accounts have reopened in the U.S., and we're seeing considerable pent-up demand. Current U.S. aesthetic revenues have recovered and are approaching 95% of pre-COVID levels. Outside the US, we're also seeing steady recovery trends in China and Western Europe. Current international aesthetics revenues have recovered to approximately 90% of pre-COVID levels. Overall, we're very pleased with the momentum we're seeing on our aesthetics franchise. More broadly, we see aesthetics as a durable cash pay business with an opportunity for significant market growth, as well as continued new innovation driving long-term performance. While strategically important, the acquisition of Allergan will also drive strong financial benefits. Integration has been relatively seamless, and we're impressed by the caliber of talent that we've welcomed into AbbVie. We remain on track with our synergy target of more than $2 billion in expense rationalization by the third year from transaction closing, which Rob will discuss further in his prepared remarks here momentarily. When you take these synergies into consideration, along with the continued P&L leverage from our expected sales growth, we expect further operating margin expansion over the next couple of years. While the COVID crisis remains a fluid situation, our business continues to remain resilient and demonstrate strong underlying growth. Although we continue to carefully watch COVID-related events in the U.S., we're pleased with our recent business trends and the progress we're making towards recovery, and we expect performance will continue to ramp to normalized levels over the course of the second half of 2020. With these current assumptions and based on our recent outperformance of our base business, today we're issuing full-year 2020 adjusted earnings per share guidance for our new combined company of $10.35 to $10.45, reflecting growth of 16.3% at the midpoint. This guidance assumes 70 cents of net accretion from the Allergan transaction in 2020, which represents 11% accretion on an annualized basis ahead of our initial projections for the transaction despite the COVID impact that I outlined earlier. Overall, we continue to see good momentum across our total portfolio and across our pipeline. We reported a very strong second quarter performance and remain encouraged by the recent recovery trends, which are faster than we expected. We continue to expect the COVID pandemic will have a transient impact on our business, with further recovery continuing through the second half of 2020. With the closing of the Allergan transaction, AbbVie is well positioned for enhanced long-term growth potential, a growing dividend, rapid debt repayment, and strong investment and innovation across our therapeutic categories. With that, I'll turn the call over to Mike. Mike? Thank you, Rick.
spk05: We had a very productive quarter with continued progress across all stages of our pipeline. Additionally, With the recent closing of the Allergan acquisition, we added promising pipeline assets in the areas of aesthetics and neuroscience. We look forward to sharing updates as those programs progress through development. In immunology, we continue to advance our programs for RINVOC and SCIRISI in several new disease areas. This year, we intend to submit regulatory applications for three additional indications for RINVOC. In June, we submitted applications for RINVOC and psoriatic arthritis, and we expect to file applications for atopic dermatitis and ankylosing spondylitis later this year. We also recently reported top-line results from our three registrational trials for RINVOC and atopic dermatitis. Two of these Phase III studies, MeasureUp1 and MeasureUp2, evaluated RINVOC as a monotherapy for the treatment of adolescent and adult subjects with moderate to severe atopic dermatitis who are candidates for systemic therapy. In the measure-up one and measure-up two studies, both doses of RINVOC met all primary and secondary endpoints, demonstrating significant improvement in skin clearance and itch compared to placebo. In measure-up one, roughly 70% of patients receiving the 15 milligram dose and 80% of patients on the 30 milligram dose achieved a 75% or greater improvement in skin lesions by week 16. We saw similar rates of skin clearance in the measure of two study with roughly 60% of patients receiving the low dose and 73% of patients on the high dose achieving a 75% or greater improvement by week 16. We also saw very rapid responses in these studies. with clinically meaningful reductions in itch observed as early as one day after the first dose in patients receiving 30 milligrams and two days after the first dose in patients receiving 15 milligrams in both studies. We also saw very strong results in our third registrational trial, the ADD-UP study, which evaluated RINVOC in combination with topical corticosteroids. Similar to the results from the two measure-up trials, RINVOC met all primary and secondary endpoints in the add-up study, with patients who received RINVOC showing significant improvements in skin clearance and reduction in itch compared to patients receiving placebo plus topical steroids following 16 weeks of treatment. Treatment with RINVOC also led to a significant increase in the number of steroid-free days, and more patients receiving RINVOC were able to stop topical corticosteroids altogether. We're very encouraged by both the level of efficacy and the safety profile we've seen across all three Phase III atopic dermatitis studies, and we remain very confident that RINVOC has the potential to provide a strong benefit-risk profile in moderate to severe atopic dermatitis. In addition to these three registrational studies, we are also evaluating RINVOC in a head-to-head Phase III trial against dupilumab, and expect to see data from this study later this year. In the area of inflammatory bowel disease, our Phase III program for invoking ulcerative colitis is progressing ahead of schedule, and we now expect to see top-line data from the first Phase III induction study later this year. We also recently reported top-line results from a proof-of-concept study evaluating our novel TNF steroid conjugate, ABBV3373, in RA. In this study, our goal was to drive a greater reduction in disease activity beyond the levels that can be achieved with Humira or other high-efficacy agents, such as RINVOC. To achieve adequate statistical power, we used pre-planned historical Humira data in combination with in-trial data when comparing ABBV3373 to Humira. The study used two analyses for the primary endpoint, which evaluated improvement from baseline in DAS28 score. The first analysis used a propensity matching strategy to compare 3373 with historical Humira data. This analysis showed a greater change in DAS28 from baseline to Week 12 for 3373 compared to the pre-specified Humira data. The second analysis used a Bayesian approach to compare 3373 to a combined in-trial and historical Humira dataset. And this analysis predicted with a 90% probability that 3373 was associated with a greater improvement in DAS28. Based on these encouraging results, we plan to advance the TNF-storied conjugate program in RA. with a Phase IIb dose-ranging study expected to begin in the first half of 2021. We also plan to begin clinical studies next year in other immune-mediated diseases. Also in the area of immunology, we're making good progress advancing the programs for SCI-RISI in new disease areas. We expect to see data from Phase III studies in psoriatic arthritis later this year and in Crohn's disease at the end of this year or early next year. with regulatory submissions for both indications expected in 2021. In oncology, we continue to advance our HEMONC strategy with several important data readouts and study starts occurring this year. We've established a leading HEMONC portfolio with Imbruvica and Benclexta in areas such as CLL and AML. and we will continue to generate data to demonstrate the utility of both drugs across a wide range of patient populations and cancer types. At the recent EHA Congress, detailed results from the Phase III Viali-A study were reported, which showed that treatment with a combination of Vanclexta plus azacitidine resulted in a 34% reduction in the risk of death compared to azacitidine plus placebo. in AML patients who are ineligible for intensive chemotherapy. The median overall survival for patients in the Benclexta arm was 14.7 months versus 9.6 months in the placebo arm. Patients in the Benclexta arm also showed more than double the rate of composite complete remission compared to those treated with azacitidine alone. This filing is currently being reviewed by the FDA under the Real-Time Oncology Review Program and Project Orbis. To date, the AML program has focused on Venclexta's use as a frontline treatment in transplant ineligible patients. This year, we are expanding the program into other patient segments with the goal of establishing Venclexta as a gold standard across the AML patient spectrum. Earlier this year, we initiated two Phase III studies evaluating Venclexta as a maintenance therapy in AML, one trial in FIT patients with AML who have received stem cell transplant but remain at high risk for relapse, and a second trial in patients with AML who are in first remission after receiving conventional induction and consolidation chemotherapies. In addition, Building upon the survival advantage observed in the transplant ineligible population, we are planning to initiate a new randomized study later this year testing Van Clexta in combination with intensive chemotherapy in patients who are eligible for more intensive induction regimens. Our comprehensive development program will position Van Clexta as a foundation for combination therapies in AML across all patient segments. We also recently announced a broad oncology collaboration with GenMab to jointly develop and commercialize three next-generation bispecific antibody products and establish a discovery collaboration to create additional differentiated antibody-based therapeutics for cancer. The lead asset in this partnership, Epcoridamab, a CD3 by CD20 bispecific antibody, has demonstrated a strong efficacy profile, favorable safety, and a more convenient dosing regimen in early-phase trials. We believe that Puridimab has the potential to become a best-in-class therapy across a number of B-cell malignancies, including diffuse large B-cell lymphoma and follicular lymphoma, and we are rapidly advancing it to Phase III trials. And lastly, a few updates from other areas of our pipeline. We previously presented positive progression-free survival data from two Phase III studies for boliparib in frontline ovarian cancer and BRCA breast cancer. Based on developments in the field and additional discussions with the FDA, we will not be submitting regulatory applications without mature overall survival data. We will continue to follow patients in the ongoing trials as overall survival data mature. In eye care, We recently announced receipt of a complete response letter from the FDA for the Abiquipar BLA. The CRL indicated that the rate of intraocular inflammation observed in the Phase III program resulted in an unfavorable benefit-risk ratio. We are currently reviewing the Abiquipar program to determine next steps and will provide updates as they become available.
spk15: An all-time classic. Like Capital Group's new ETFs, there's so much behind it. Like thinking long-term. Can I find an ETF with a whole lot behind it? With Capital Group, I can.
spk05: as the first non-surgical oral treatment for the management of heavy menstrual bleeding associated with uterine fibroids in premenopausal women. This new non-surgical treatment represents an important therapeutic option for women suffering from uterine fibroids. And in neuroscience, we recently reported top-line results from a Phase III study evaluating etogepat for the prevention of episodic migraine. In this study, All three doses of etogepat met the primary endpoint, evaluating the change from baseline in mean monthly migraine days across the 12-week treatment period. The two higher doses, 30 milligrams and 60 milligrams, also met all secondary endpoints, while the 10 milligram dose met four out of six of the secondaries. Allergan had previously reported positive results from one registration-enabling study, and following this second positive study, we plan to submit our regulatory applications in episodic migraine prevention in the first quarter of 2021. In summary, we've seen tremendous progress across all stages of our pipeline in the first half of the year, and we remain on track for further advancements in the remainder of 2020. With that, I'll turn the call over to Rob for additional comments on our second quarter performance and financial outlook. Rob?
spk06: Thank you, Mike. Starting with second quarter results, we delivered top and bottom line performance ahead of expectations. We reported adjusted earnings per share of $2.34, above our guidance midpoint by 21 cents. This includes 10 cents of stronger performance from Legacy AbbVie and 11 cents of accretion from Allergan. Total net revenues were $10.4 billion, including $2 billion in sales contribution from the Allergan portfolio. Legacy Abbey was approximately $300 million ahead of our standalone sales guidance, driven by RENVOQ, SkyRizzy, and Humira. COVID-related inventory stocking for the first quarter largely reversed as expected. U.S. Humira sales were approximately $4 billion, ahead of expectations due to the lower impact from COVID on continuing patient prescriptions. Wholesaler inventory levels remained below half a month in the quarter. International Humira sales were $863 million, down 17.4% operationally, reflecting biosimilar competition across Europe and other international markets, and ahead of our expectations. Guy Rizzi global sales were $330 million, with continued strong U.S. in-play market share. We also continue to see robust demand for RENVOC, with sales of $149 million in the quarter and a rapid increase in U.S. in-play market share. hematologic oncology global sales were nearly $1.6 billion, up 25.8% on an operational basis, with continued strong performance of both Imbruvica and VanClexta. Imbruvica global net revenues were approximately $1.3 billion, up 17.2%, driven by continued strong performance in CLL. VanClexta revenues were $303 million, with strong demand across all approved indications. Global Maverick sales were $376 million, down 51.4% on an operational basis as treated patient volumes have declined during the COVID pandemic. Allergan Aesthetics contributed sales of $481 million in the quarter. Botox Cosmetic with sales of $226 million and Juvederm with sales of $113 million are both seeing a faster than expected recovery from the COVID pandemic. Neuroscience global revenues were $734 million. These results were led by Botox Therapeutic, Raylar, and Ubrelvi, with combined sales of more than $500 million. We also saw a significant contribution from our eye care business, which had global sales of $417 million. Turning now to the P&L profile for the second quarter, adjusted gross margin was 82.8% of sales, Adjusted R&D investment was 12.8% of sales, and adjusted SG&A expense was 22.9% of sales. The adjusted operating margin ratio was 47% of sales, including a negative impact of 70 basis points due to the reversal of COVID-related inventory stocking from the first quarter. Adjusted net interest expense was $484 million, and the adjusted tax rate was 11.4%. Today, we are issuing combined company guidance for the first time. As Rick previously discussed, we are closely monitoring the impact of the COVID pandemic and have factored the latest trends into our updated forecast. We now expect full year adjusted earnings per share between $10.35 and $10.45, including 70 cents of accretion from the Allergan transaction, which represents an annualized contribution of 11%. Excluded from this guidance is $6.23 of known intangible amortization and specified items. This guidance now contemplates full-year revenue of approximately $45.5 billion. At current rates, we now expect foreign exchange to have a 30 basis point unfavorable impact on full-year reported sales growth. Included in this revenue guidance are the following updated full-year assumptions. We now expect U.S. Humira sales growth of approximately 8%. we now expect international Humira sales of approximately $3.5 billion. For RENVOC, we now expect global revenues of approximately $600 million. For global HCV, we now expect sales of approximately $2.1 billion as treatments remain below pre-COVID levels. For aesthetics, we expect global sales of approximately $2.4 billion, including approximately $1 billion from Botox Cosmetic and approximately $650 million from Juvederm. For neuroscience, we expect global sales of approximately $3.5 billion, including approximately $1.4 billion from Botox Therapeutic and approximately $950 million from Raylar. For eye care, we expect global revenues of approximately $2.1 billion, including approximately $700 million from Restasis, which assumes no generic competition in 2020. For women's health, we expect global revenues of approximately $700 million. All other foliar product guidance assumptions remain unchanged. Moving into P&L, we now forecast adjusted gross margin just above 82% of sales, adjusted R&D investment to be approximately $5.8 billion, adjusted SG&A expense to be approximately $9.9 billion, and adjusted operating margin of approximately 48% of sales. This P&L guidance includes approximately $600 million in expense synergies for the partial year in 2020. We remain on track to deliver greater than $2 billion in expense synergies by 2022. We now expect adjusted net interest expense of approximately $2 billion, which includes the cost of financing the Allergan transaction. We now model a non-GAAP tax rate of just above 11% for the newly combined company. Finally, We now expect our full year average share count to approach 1.7 billion shares, including the equity issued to finance the Allergan acquisition. As we look ahead to the third quarter, we anticipate adjusted revenue of approximately $12.8 billion. At current rates, we expect foreign exchange to have a modest unfavorable impact on reported sales growth. We are forecasting an adjusted operating margin ratio of just above 48% of sales. We model a non-GAAP tax rate of 11.6%, and we expect the average share count to approach 1.8 billion shares. We expect adjusted earnings per share between $2.73 and $2.77, excluding approximately $1.59 of known intangible amortization and specified items. AVI remains well-positioned to execute on our capital allocation priorities, including rapidly paying down debt supporting a strong and growing dividend, and pursuing additional innovative mid- to late-stage pipeline assets. We generated $6.9 billion of operating cash flow in the first half of the year, and our cash balance at the end of June was $6 billion. We are on track to pay down $15 to $18 billion of combined company debt by the end of 2021, of which nearly $7 billion has already been repaid. We expect to achieve a net debt to EBITDA ratio of 2.5 times by the end of 2021, with further deleveraging through 2023. In closing, Avi's performance and financial condition remain strong. We are very pleased with the momentum of the business heading into the second half of 2020. With that, I'll turn the call back over to Liz.
spk08: Thanks, Rob. We will now open the call for questions. Operator, first question, please.
spk09: Thank you. And as a reminder, to ask a question, please press star 1. Our first question today is from Randall Stanicki from RBC Capital Markets.
spk04: Great. Thanks, guys. I just have two, one for Rick and one for Rob. Rick, a bigger picture question, a huge part of the AbbVie story is – Randall, Randall, sorry to interrupt.
spk08: We can't hear you very well. Is there any way you can turn up your mic or speak up?
spk04: Great. Is that better?
spk08: Slightly. Much better. Yes.
spk04: Great. Rick, I wanted to ask, a big part of the AbbVie story is growth on the other side of Humira in 2023. There's still some trepidation from investors in getting comfortable with the step down. What would you say to those investors to get people comfortable that there's a growth story on the other side of Humira? And what do you need to do specifically between now and then strategically to position the business for that?
spk19: Okay. Randall, did you have a second question?
spk04: Yeah, the second question, I'll ask it up front for Rob. If you could help us understand the steady state, the run rate for R&D, I think you said $5.8 billion for this year. That will go higher on an annualized basis, but you're also pulling $1 billion of R&D synergies out of that as well.
spk19: Okay. I'll cover your first question, Randall, and then Rob can jump in and talk through the R&D funding question that you had. So, look, I think it's a great question. It is one that obviously the vast majority of investors are interested in. We have described, I think, to investors the rationale of why we were excited about doing the Allergan transaction. It obviously gives us a tremendous amount of ability to be able to manage our way through the loss of exclusivity in the U.S. of Humira. It provides us with two more major growth franchises for the company to help drive growth and it allows us to continue to invest aggressively both in internal R&D as well as external. And so I think it provides the framework to allow us to continue to perform as we have performed over the last number of years. I mean, clearly we have a, we certainly have a track record of showing that we can grow this business and we can build on this business. We've demonstrated that since 2013 when we spun out. So what makes me excited and what makes me comfortable that I can ultimately grow the business through the LOE? I think it starts with, look, we have six, yeah, six major growth assets in our business today. if you step back and you look at them. Six medicines that have tremendous opportunity to be able to grow. Skyrizzy, Rynvoke, Imbruvica, Benflexta, Valar, Ubrelvi. We'll probably have a Tojapan here in the not too distant future. Then we'll have a seventh asset. All in markets that have a significant opportunity to be able to grow. When I look at our R&D productivity, both in the indication expansion area, as well as new assets, and I'll talk about that here in a second, I'm very comfortable with our ability to be able to continue to drive the pipeline. When you look at the projections that we made for Renvoke and Skyrizi as an example, when we made those projections a year or two ago, those peak projections for 2025, we based those projections on the fact that those assets had to achieve roughly high single-digit market share positions. As we mentioned, right now, if you look at Sky Rizzy, it's achieving in-play share of 30%. Wing Oak has really stood up and rapidly started to capture share. It's at 15% and growing at a very aggressive clip. I would predict it will quickly become the in-play market leader above Humira here in the not-too-distant future. But they're already significantly above what those estimates were. The longer you stay, At in-place shares that look like that, obviously the greater you're going to exceed that. If you get to 20% instead of high single digits, obviously the revenue will be approximately two times what we originally projected. So that gives me a high level of comfort. When I look at Venclexta as an example, there's still a significant opportunity to grow there. If we get an indication expansion, both broadening AML as well as the T11-14 and multiple myeloma, Those are two significant opportunities that will continue to be able to drive growth. Imbruvica still has significant opportunity to be able to drive growth. When I look at Velar as an example, that's a very interesting asset. It has a great profile in that market, the drug does. It's obviously growing significantly. I mean, it's been growing now at the rate of about 80 or 90% year over year. There's still plenty of room to grow in bipolar and schizophrenia. And if one of those two phase three studies plays out effectively, MDD will be a very large additional indication which will allow us to be able to drive significant growth there. And then there's the migraine franchise. I think migraine is something that's underappreciated. If you look at the penetration right now of oral agents in the acute area, it's running about 12 to 14% of total scripts. So obviously there's a significant opportunity to be able to continue to expand that market. We think we have the asset to be able to do that. And obviously we think we have the promotional ability to do it. So I think we have the tools right now to be able to drive significant growth through the LOE. On the other side of the LOE, obviously, our pipeline will continue to play out with the additional indications. You're starting to see assets like our TNF steroid evolve. I think the GenMAP collaboration is an important collaboration to continue to build out. Our HEMOC and potentially solid tumor platform. And so, there's a lot of exciting opportunities. So, you know, I feel very confident in one, how the business is running now. despite all of the disruption associated with COVID. But if I look at the part of the business that we control directly, I feel very good about how the business is running. And so I believe we will navigate our way through it. And I think as we get a little closer, investors will gain an even greater appreciation of that.
spk06: Randall, this is Robin. Your question on R&D. So if you think through the partial year synergies of $600 million, about $400 million of that comes from R&D. And by 2022, about 50% of the greater than $2 billion in synergies will come from R&D. So while I would expect the expenses to annualize, obviously, or the partial year close, we'll also see those synergies ramp up. So the best way to think about it is a steady state R&D level in the $6 billion range.
spk15: A Hall of Fame swing. Like Capital Group's new ETFs, there's so much behind it. Like years of honing your skills. Can I find an ETF with a whole lot behind it? With Capital Group, I can.
spk04: Great. Thanks.
spk08: Thanks, Randall. Operator, next question, please.
spk09: Thank you. Our next question is from Navin Jacob from UBS.
spk17: Hi. Thanks for taking the question. Just wanted to expand on some of the opportunities that Rick had just mentioned.
spk08: Again, Naveen, can you speak up a little bit?
spk17: Well, let's see if we can turn our end up. Sure, sir. Is this okay? Can you hear me okay? That's better.
spk09: Thank you.
spk17: Okay. I will yell. So with regard to... Yeah, we turned our end up. So you probably don't need to yell. All right. All right. Fair enough. With regard to... the Van Cleck's opportunity in multiple myeloma, the Canova's trial. Wondering if you could give us an update there and how large could that potential opportunity be? Obviously, relapsed refractory multiple myeloma is pretty competitive. So just wondering what sort of, how we should be thinking about that, where that excitement's coming from. And then if you could remind us also about your subcutaneous version, pump version of of duopa that's supposed to read out in the first half of 2021. How should we be thinking about that opportunity? Could that be a blockbuster opportunity?
spk05: This is Mike. I'll take those. With respect to Benclexa, we see very real potential in the T11-14 multiple myeloma population. If we look across our trials, early phase trials and then some set analyses of later phase trials where we have data from T11-14, we see very consistent responses. We see high response rates and we see long progression-free survival in the T11-14 population. And that makes sense because that T11-14 population has a transformed cell that has a B cell-like phenotype and it's BCL2 high, so it would be expected to be uniquely sensitive to Van Clexta and to BCL2 inhibition. So we have the phase three study well underway now. It's an event-driven trial, but we would hope to have data in the near future, in 21. And that study is designed to confirm those earlier observations. In terms of how large an opportunity it can be, The T11-14 population is about 20% of multiple myeloma, and multiple myeloma is a big indication, so 20% of that is a lot. Now, as you mentioned, it's becoming a competitive space, but one of the advantages of having a biomarker-driven therapy is that we can identify and physicians can identify in practice what patients are likely to respond to Benclecta, so they'll know what a Benclecta patient looks like. and we think that'll be a real opportunity and a real advantage. So we're very optimistic about that aspect of the program, and we think it represents an important additional role for Van Clexta. With respect to 951, that is a program that's designed to deliver duopa-like efficacy through a subcutaneous insulin pump-like device. And so to do that, we had to develop two novel prodrugs. These are NMEs. that are rapidly converted to the active agents in circulation. And they allow delivery of levodopa and carbidopa ultimately through this insulin pump-like device that you just can't do with the parent compounds because of their physical properties and chemical limitations and local tolerability limitations. So it really does represent a real breakthrough. What we know about the efficacy of Duopa is that it is very, very strong. It really is transformational. But it takes a lot to get that efficacy. Patients have to have a gastric tube placed and threaded down into the small bowel. They have to maintain that. So this is a much more patient accessible, patient friendly, if you will, way to deliver the same sort of efficacy. And so we think that has the potential to really expand the number of patients who would be willing to consider a therapy such as 951. And it's a big market. If you look at Duopa, despite all the limitations, it's doing about half a million dollars in sales. If you look at deep brain stimulation, there's also considerable use. In aggregate, this market today is well over a billion dollars, probably a billion and a half dollars. not all patients who would qualify by their patient profile are willing to undergo these therapies. So we think that 9-501 can be a very raw opportunity and can be quite substantial.
spk08: Thanks, Savine. Operator, next question, please.
spk09: Thank you. And our next question is from Chris Schott from J.P. Morgan.
spk03: Great. Thanks so much for the questions. Just two for me. The first, can you just elaborate a little bit more about how you're thinking about the size of the opportunity for RINVOC in atopic derm now that we have the phase three. I guess just a little bit more just how you see this fitting into the treatment paradigm. And then my second question was on the 2020 guidance. If I back out the 70 cents of Allergan accretion, it seems like the base AbbVie numbers are unchanged despite what looked like very, very strong results the first half of the year. So, just help me understand a little bit of the dynamics that are happening with that kind of underlying AbbVie set of assumptions. Thanks so much.
spk05: This is Mike. I'll take the first one, and then I'll hand it over to Rick for the second one. With respect to atopic dermatitis, we're very pleased with the results that we demonstrated across the Phase III trials. They actually exceeded our expectations based on the Phase IIb results, and those IIb results were very strong and had earned us a breakthrough therapy designation. And we're pleased not only with the efficacy but also with the safety profile. We've said for quite some time that one needs to look at the safety of the drug in the intended population, because things like background therapies, risk factors in the population can have a substantial influence on what that profile looks like, not only for the active agent, but for the comparator or for placebo. And if you look at the profile in the AD studies, it looks very favorable to RI. And these were substantial studies and a substantial program overall. This wasn't a quick study to get an indication expansion. We ran a phase three program for atopic dermatitis that could stand alone for an additional submission. So we think that very strong data package will be a real advantage when we bring this indication to market. If you look at the size of the market overall, I think it's been underappreciated for years. Now, that's changing now. There are a large number of patients who would be eligible for systemic therapy. Obviously, dupilumab is off to a good start over the past several years in that indication. But if you look at their efficacy, only about half of patients achieve an adequate response, if you consider that adequate response in EZ-75. And so, you know, in our study, we drove, you know, very good numbers there, higher than that, you know, roughly 50%, albeit there through, you know, cross-trial comparisons. So we think that there is a real opportunity for, you know, a high-efficacy agent in this space. And so, you know, it really can play on both ends of the spectrum. Patients who don't achieve an adequate response with earlier therapies, this is an obvious choice. But with the efficacy and the safety profile that we've observed, we see no reason why it wouldn't be used up front as well. And, of course, we'll have head-to-head data against dupilumab later on this year, as we said in our prepared remarks.
spk06: So, Chris, this is Rob. I'll take your question on guidance. So, if you take that 70 cents of accretion and you back off the midpoint of 1040, it gives you a standalone of 970 EPS, which is 4 cents higher than our previous guidance. And it's really driven by the sales changes that we've made today. So for U.S. Humira, we took that up 1%, which equals about $150 million, because we're seeing less impact of COVID on continuing patients. Humira OUS, we've taken up $100 million. We're seeing less erosion than we initially had planned. On RINVOC, that's up $100 million as well, really driven by the rapid in-place share that we're seeing. And that's partially offset by Maveritt, as we've seen the market really decline during COVID. But net-net, Revenue is up about 150 million. EPS is up 4 cents versus our previous guidance for standalone AbbVie.
spk19: And the only thing I'd add on that is, you know, obviously we were more favorable on base AbbVie in the quarter than the 4 cents, but there's still uncertainty as it relates to COVID, and so we're keeping some coverage there to see how things play out in the third quarter.
spk08: Thanks, Chris. Operator, next question, please.
spk09: Thank you. And our next question is from Steve Scala from Cohen.
spk16: Thank you. First, congratulations on delivering ahead of expectations in the midst of a major integration, new launches and a global pandemic. It's really impressive. Rick, you stated that the impact of the pandemic was less than expected. That certainly hasn't been the case at other companies. You also said that you're seeing recovery in the aesthetics portfolio, which sounds as though it's snapped back faster than the legacy of the. So I'm just curious to what you attribute these dynamics And do you expect the second half of the year to look more like the first half or more like May and June relative to patient volumes, clinic traffic, and so forth? And then secondly, you stated that you expect margin improvement over the next few years. Could you provide some parameters around that expectation? Thank you.
spk19: Okay. So this is Rick. I'll take the first one. Your observation is correct. So I think the way to think about it is that both in the second quarter, many of the assets didn't drop as far as we expected. That was part of the favorability. I'd say that was particularly the case in a number of areas in the legacy AbbVie portfolio associated with the business. On the aesthetics, it is pretty much the way you're describing it. What we saw happen in the aesthetics business and to a very similar extent to Botox Therapeutic is that we saw a rapid drop in the case of aesthetics as those practices virtually closed. You know, I say almost all, if not all of the practices had closed. So, aesthetic revenues dropped significantly for a period of time in that mid-April timeframe. As we started to see geographies remove the shelter-in-place orders around the U.S., we saw the aesthetics practices quickly put in place safety measures to be able to allow patients to come back into their offices. And I'd say the vast majority of those practices ramped back up and went back into doing procedures fairly quickly as we approached that mid-May timeframe. We actually saw, let's take Botox as an example. And Botox would be the leading indicator because it's the procedure, Botox cosmetic. It is the procedure that people would go to first. It ramped back up, went well over 100% of pre-COVID levels to around 120, 125%. And then it, and that was obviously pent up demand that was coming back in to the channel. So patients returned quickly. And then as that pent-up demand started to burn off as we got through June, you started to see it drop back down. And now it's settled in sort of in the mid-90s right now. We think it'll reach, you know, it'll stabilize back up over the course of third quarter, back close to pre-COVID levels, and then start growing again. And so I can tell you I'm extremely pleased with how both Aesthetics and Botox Therapeutics have returned. I think it is a testament of those brands and those patients. As far as the assumptions we made in the second half, obviously we're assuming the second half performs a lot better than the first half. We're not assuming any kind of a broad-based shelter-in-place activity. And we'll continue to see more and more patients come back into physicians' offices. On the AbbVie side of the business, we are monitoring those patients by individual practice. It's appropriate for our particular businesses. And I'd say, for the most part, they are returning close to pre-COVID levels. They do vary a little bit by specialty. As an example, room and GI have come back faster than medical derm has. But medical derm has returned as well. To some extent, we're continuing to see it return. Oncology practices in certain conditions, we've seen, we saw some tailing off. CLL treatment in the second quarter, that's now returning back to normalized levels. So I think the second half will obviously be much better than the first half, and I think we should return to normalized levels as we proceed through the second half of the year. Rob, anything you want to add on that?
spk06: I can answer the question on op margin. Steve, this is Rob. Operating margin, I think when you think about we have a partial year of synergies and a top line that's been pressured by COVID, we have a 48% operating margin profile. If you think about 21 and 22, you know, we're going to obviously run, you know, we're going to ramp those synergies as well as we'll see top line growth and where you'd see the P&L leverage that we've demonstrated in past years. So I would expect to see our operating margin expand in 21 and 22. We get to 2023 with the U.S. eMira event, obviously we would see operating margin pull back, but I would expect it to be in the 45% range, which still puts us top tier in the industry.
spk08: Thank you. Thanks, Steve. Operator, next question, please.
spk09: Thank you. Our next question is from Jeffrey Porges from Lear, Inc.
spk20: Thank you very much, and congratulations. Very helpful to get the guidance. Could you talk a little bit about Toe Japan? Particularly, what's the size of the addressable opportunity for the full portfolio of oral migraine medicines? And perhaps, how much of an issue is the constipation data that you've seen? And then, Rick, look, there's a massive economic disruption going on, and I'd be interested in your commentary about how consumers and payers are reacting. to that disruption and how that's factored into your guidance. You know, are we seeing switches from IV to oral, from generic to brand? How is that playing out in your experience and observation? Thanks.
spk19: All right, great. So, maybe we'll have Mike talk a little bit about the profile of the drug. And what I'd say is, I think we probably want to come back at a later date once we've had a little better opportunity to analyze the chronic and the chronic migraine market. And it's going to depend to a great extent on the profile of the drug, obviously. But it's a very large market, a very significant market. And but Mike, maybe if you want to talk a little bit about constipation, I'll come back and talk about the pair dynamics.
spk05: I'll talk about atogepant. We're very pleased with the data we've seen, and of course this fits into an important part of our migraine portfolio with Hugh Brelby for acute migraine, now with atogepant with two data readouts in episodic migraine and an ongoing program in chronic migraine, and of course there's Botox therapeutic in chronic migraine. So it really rounds out our portfolio. The efficacy that we saw was very strong. As we said in our prepared remarks, we hit the primary and all secondaries across the two upper doses, and the primary and four out of the six secondaries for the lowest dose studied. So that is an efficacy profile that I think exceeded our expectations going into the study. With respect to the safety, our view of the safety profile looks very favorable. The constipation that was observed in the overwhelming majority of cases was mild or moderate. It didn't limit treatment, so patients stayed on treatment. It could be managed easily with interventions like stool softeners or fiber supplementation. So we don't see it as something that is limiting, particularly in light of the very strong efficacy that we have demonstrated. You know, the only other point I'd add is that we have a good understanding of it and it's on target, so it comes with the efficacy. You get the very strong efficacy and you have this manageable tolerability profile that I described.
spk19: Jeff, on your second question, you probably recall back on our first quarter guidance when we outlined that we had built in to our forecast for the remainder of the year some impact or some channel shifting that we thought could occur due to the high unemployment. And, you know, essentially we haven't seen much of that at all. In fact, I would tell you, we haven't seen any of it, any material effect right now. And one of the things that we do to watch that carefully is our PAP program. We've been advertising extensively to consumers to make sure that they know if they lost their insurance, or they lost their jobs and they don't have insurance coverage and they can't afford their absentee medicines to come to us. We have a very extensive patient assistance program. And we're not seeing any significant increase in those requests. Could be because of the furloughs. We're not 100% sure yet. And potentially we could see some increase as we go further here depending upon what happens with stimulus programs going forward. We have still maintained some level of coverage in our forecast that we're providing now. So, we believe we have sufficient coverage to deal with it and we'll just have to see how it sorts itself out.
spk08: Thanks Jeffrey. Operator, next question please.
spk09: Thank you. Our next question is from .
spk07: Hi, great. Thank you so much for taking my questions. Maybe just to continue on the migraine question. You mentioned UBELV and the potential there. Can you maybe just talk a little bit about the net pricing that you're thinking about in that space? I guess, you know, maybe relative to the injectable antibodies that are out for prevention already, there's only the two players, it sounds like, here between you and Biohaven, especially the four on the injectable side. So just trying to get a sense how you see this sort of pricing dynamic play out. We're getting a lot of questions on that front. And then maybe for Rick, I'm just curious, around some of the executive orders we've seen on the drug pricing side for the administration. I don't know if I may have missed some of your comments earlier, but just curious if you have any sort of additional thoughts about what we heard from some of your peers on this issue this week on their calls. But every company obviously has a different product mix and maybe some different perspectives. So curious what your views are, especially as it relates to the rebate rule order. Thanks so much.
spk19: Right. Okay. I'll cover both of those questions. So on migraine, I mean, obviously, we don't publicly talk about our net price. We have fairly significant managed care coverage on the asset already. I think it's about 70%. And obviously, it had to be priced in a way that was appropriate to be able to get that level of coverage. This is a market where market expansion is important. As I said, I think if you look at the penetration right now of acute migraine products against the, or at least the oral CGRPs against the total migraine acute market, it's about 12% penetrated right now. So there's a significant opportunity to be able to grow that market. And it gives you some idea of the magnitude of this market. So you certainly want it to be in a position where it can have access to be able to allow patients to be able to use the products. These products certainly have demonstrated that they have strong demand from patients to be able to provide them appropriate levels of relief. And so, I would just tell you that's an important aspect of the overall strategy here is to be able to grow this market over the long term. On the executive orders, you know, as you have probably seen, they're pretty high level. at this point and they provide some high level direction so I think until we see them sort of start to sort out I think it's a little difficult to give you a lot of specificity around what they look like now I will say if I look at them in the backdrop of AbbVie's business I would say I don't think they will have a significant impact on our business if you look at part B is an example. We have a very small Part B business. I think it's around 2% or 3%. 3%, I guess, is the right number now. So it's a very insignificant part. If you look at the importation bill or executive order, it's very similar to what's already been given out to the states. And it excludes biologics, which obviously is an important part of our business. If you look at the third one, it's insulin and EpiPen. We're not in that business. And then the rebate rule. You know, certainly as we look at rebates, we're absolutely supportive of patients being able to get the benefit of the discount associated with the rebate or discount. As we've said many times before, for us, whether it's a rebate or a discount is not very material to us. What I would say is when I look at that executive order, It does say that you have to be able to implement it without increasing premiums. And everything I know about how rebates are redistributed, I would say that I think that that will be difficult to do. So I don't know how that will ultimately play out. So that's a high-level look at what we think about them right now. But I think right now, I wouldn't anticipate that they have a significant risk associated with AbbVie.
spk08: Thanks, Amal. Operator, next question, please.
spk09: Thank you. And our next question is from David Reisinger from Morgan Stanley.
spk11: Great. Thanks so much. And congrats on all of the encouraging updates. So first, Rick, could you please discuss maybe in a little bit more detail the most significant revenue synergy opportunities you see as a result of the combination with Allergan? I know that The combined company can do more with certain franchises, but if you could put some finer points on that, that would be very helpful. Then second, with respect to next year's readouts, AbbVie has a very large pipeline of phase two candidates with proof of concept readouts in 2021. But could you point us to the ones that have the biggest commercial potential? So if there is validation in 2021, what are the biggest product opportunities that we should be paying attention to? And then one little tidbit, the Ubrelvi number was $22 million in the quarter. That was strong. How much stocking was in there? Thank you.
spk19: Okay. So I'll cover the first one, then we'll have Mike cover the second, and Rob can cover the third. So if I look at the business overall, I said that the integration has gone very seamlessly and I think, you know, that's a tribute to all the planning that we did. We had some extra time to be able to do it and I think that benefited us. And so I think the two organizations have come together in a way that's been quite good. Now, I would say I think the places where we have an opportunity to be able to provide some synergy and benefits. Certainly when you look at our therapeutic businesses, when you look at our many of the tactical kinds of execution techniques that we use in the marketplace, I think many of those are applicable to the Allergan therapeutic portfolio. Certainly when you look at managed care, that's an area that we have demonstrated that we're quite skilled. at being able to effectively manage our way through that. And then the third area I'd say is, if I look at aesthetics, aesthetics is a very attractive market. It has a significant opportunity to be able to grow that market, which I mean by bringing in more people into the market more quickly. You can do that several different ways. Obviously, some of it's driven by promotional activity. I'd say Allergan is very skilled from a social media standpoint, and I think that's an area that's probably been underfunded historically. It's an area that we have a high level of interest in funding to a greater extent, and we obviously have the financial wherewithal to be able to do that. The second thing is being able to bring more new innovation more rapidly into that market, and I think that's an area that we'll also be able to provide a benefit both in the way we operate R&D and the ability to be able to rapidly innovate. I think that will be a benefit to the overall business. And I think we have an opportunity to be able to accelerate the growth of that business in a meaningful way over time. And it's a market I like a lot. I think both based on demographics, the cash pay aspects of it, and how it responds to appropriate innovation in that market. So that's an area that over time you can expect us to continue to make sure that we're doing what we know how to do to be able to ultimately grow that market over the long term. Those would be some of the things I'd tell you at eye level. Mike?
spk05: I'll take the second question. So we do, as you point out, have a number of data readouts from Phase II studies or other proof of concept studies in 2021 and also in the following years, in 2022 and beyond. And a number of these are very large opportunities. You know, I'd point to our oncology programs. We have a number of immuno-oncology programs that would be large opportunities if they hit. Our GARP program, I think, is a very good example of that. Our bispecifics, I think, are a very good example of that. You know, we just brought in through the GenMab collaboration F-carritamab, which is a large opportunity. Obviously, that's post proof of concept, but there are two additional molecules there that are just a little bit earlier in development that could be large opportunities. We have, by specifics in BCMA, more than one program that could be very large opportunities if they were, in fact, best in class, and we think they have the potential to be best in class. The last thing I would point to in oncology is our novel, so targeted, ADC technology with ABBV155 being in the lead in non-small cell lung cancer. That is a BCL XL warhead. targeted by a B7H3 antibody, if that were to hit and we'd see those data next year, that would be a large opportunity. Obviously, in immunology, we're advancing our TNF steroid program, but those are data that we've already reported out. And then the last thing that I would mention is in our neuroscience portfolio, obviously, Alzheimer's disease, if those programs were to hit, they would be a very large opportunity given the enormous unmet medical need. Now, obviously, in Alzheimer's disease, it's higher risk, higher reward, but if we got favorable data, it would be a very, very meaningful opportunity.
spk06: And, David, this is Rob on Urelvi. If you look at just the full quarter revenue of $27 million, it really follows the prescription growth on a sequential basis, so there's really a negligible stocking impact, and we'd expect to see continued sequential growth for that product.
spk08: Thanks, David. Operator, next question, please.
spk09: Thank you. Our next question is from Chris Raymond from Piper Sandler.
spk02: Thanks. Just back to Tojapan and sort of the competitive setup. So, Rick, I heard your comments on how this is underappreciated. We've done some checks that seem to indicate that that's the case. And I know this is not approved yet, so pardon if you don't mind the commercial question here. But there's been some chatter out there, especially from some BioHaven bulls, that the placebo-adjusted migraine days maybe don't matter as much as absolute days. And so just maybe, you know, you're in the field with Ubrelvi. You know, from a rep to doc dialogue perspective, what do you guys see as the most important attribute, especially, you know, as you'll be positioning this in the prevention setting versus, you know, sub-Qs and the other oral therapies or the other oral therapy that happens to be a dissolving tablet?
spk05: Well, this is Mike. I'll take the first part of that, and then Rick may want to add. With respect to efficacy, the most important attribute is the placebo-adjusted migraine days. If one were solely to look at the total days, one could conclude that placebo is, in fact, a good therapy for these patients because we see reductions. And so you have to account for that. And there are differences from study to study based on design, population, and role, and what that placebo difference is. So it absolutely has to be taken into account. And when you look at our placebo-adjusted results, they're very strong. They range between 1.2 and 1.7 days, which in this disease area is a very meaningful response rate. And it's higher than what has been reported with other oral agents, obviously with the caveat of cross-trial comparison. on the most important efficacy parameter, we performed very, very well. And, of course, we've hit all the secondaries across two of those three doses, as I described. And as we get the data out into the public domain, you'll get more color on that.
spk19: I would just reiterate what Mike said. I mean, physicians are well skilled in understanding what placebo rates are. I just don't even think it's appropriate not to represent a product's efficacy without looking at the placebo rate. So, I mean, I think that will be the way doctors look at it. And I think that is the way the products will be marketed. And certainly, if I had a lower rate, I may have an interest in that. But at the end of the day, I think that is the appropriate way to look at it.
spk08: Thanks, Chris. Operator, next question please.
spk09: Thank you. Our next question is from Tim Anderson from Wolf Research.
spk18: Hi. Thank you. A few pipeline questions please. On the TNF steroid conjugate, some KOLs have a mixed view of that approach. For those that are skeptical, what's the most common reason that you hear? Second question on BRAILAR, what are your odds of regulatory success in depression, even just qualitatively? Is this a high risk, medium risk, or low risk endeavor? And then can you clarify why your GENMAB CD3, CD20 would be best in class?
spk05: Okay, I'll take those questions. With respect to the TNF steroid conjugate, what I would say is it's important to keep in mind that this is an early phase trial and this was intended to be a proof of concept trial. One can't do a fully powered head-to-head against an active competitor like Humira in phase one or phase two. because that typically requires or always requires essentially a large Phase III study. Head-to-head studies are often amongst the largest studies in a Phase III program. So what we were looking for was evidence to support the profile that I described, which is that we had a high probability of success in those trials downstream. folks have mixed view then you know what we hear is they'd like to see those later data and what I would say is we're well on the path to generating them we're pleased with the results that we've seen and we think it's a very promising platform and we're going to be advancing into larger scale trials and and people will get the data that they're looking for you know with respect to Raylar in the adjunctive treatment of major depressive disorder. I think the question was how would I characterize the risk there? You know, there already is one positive study in hand, and so of the two studies that are underway, we would need one additional study to read out positive to support the indication. You know, I think that, you know, historically, this has been a challenging indication. But I think both the rationale and the data from earlier studies in the Vrelar program are strong. So I would probably put it in the moderate probability range. We didn't build it into our model. Our success with Vrelar was not dependent on it, but we think it represents a very attractive upside opportunity if, in fact, it hits. And with respect to why GENMAB CD3 by CD20 has the potential to be best in class, I would point to two things. One is the efficacy data reported from the early phase trials, particularly in DLBCL, which is a very difficult to treat tumor type, puts it at the higher end of efficacy. And the safety profile has been very favorable in terms of what's been observed to date, both with respect to cytokine release syndrome and the lack of occurrence in the early phase trials of higher grade CRS, and also with respect to the neurological symptoms that can accompany this class of therapy. So it seems to have threaded that sweet spot between achieving very strong efficacy with a good safety profile. It also has sub-Q administration with its existing formulation. Others are working towards that, but GENMAB already has the data in hand. And the dosing schedule fits very well into the regimens that will be used in the diseases that we'd study, particularly DLBCL on follicular lymphoma. So it's the aggregate of that that we think gives it a very, very strong profile. Thank you.
spk08: Thanks, Tim. Operator, we have time for one final question, please.
spk09: Thank you. Our final question today is from Terrence Flynn from Goldman Sachs.
spk10: Great. Thanks for taking the question. Congrats on the elegant integration. You mentioned in your comments that Renvoke uptakes accelerating here. I was just wondering if you could provide a little bit more color on that. Is that being driven by COVID and maybe teleprescribing having an advantage over some of the injectables? And if so, do you see that as being a durable change here as we come out of the pandemic? And then the second one I had was just on Van Clexta. I noticed you're running some trials for solid tumors. Maybe just remind us of the rationale here behind that approach and how optimistic are you there as you move into later stages? Thank you.
spk19: Okay, thanks. I'll take the first question, Mike, and cover the second one. So Wimbo clearly has started the ramp in a fairly significant way. I think it's associated with two things. One is anytime you see a product, it's about eight months into its launch, you typically start to see that inflection point on successful products as you go out and you present the data to physicians and start to educate physicians and they start to get some use. You tend to see that inflection point start to happen around six months. So I think it's the natural inflection point that we would have expected. if the product is being successfully accepted into the marketplace the way we hoped as a high-efficacy agent. I think there is some benefit that we're seeing during the COVID crisis that it is an oral, so it's a little easier to prescribe than an injectable might be, so we're probably getting some collateral benefit associated with that, but I don't think that's the fundamental benefit that we're seeing.
spk05: So I'll take the question with respect to Van Clexta in solid tumors. I think there's two different lines of evidence. In breast cancer, there is an investigator-sponsored study that showed promise in breast cancer, and so there's a follow-up study there to confirm that, and if that were confirmed, it would be obviously a substantial opportunity given the unmet need there. And then there are other solid tumors such as both small cell lung cancer, non-small cell lung cancer, where there's preclinical rationale that warrants exploration. And so I would characterize the solid tumor program as, you know, higher risk but high reward, worthy of exploration. The solid tumor program in MedClex has not been baked into our thinking and isn't necessary for any of the success that we have talked about with the molecule. But if something were to hit there, it represents a very nice upside, and I think there's enough rationale to warrant the exploration.
spk08: Okay, thank you. So that concludes today's conference call. If you'd like to listen to a replay of the call, please visit our website at investors.abbey.com. Thanks again for joining us.
spk09: Thank you. This does conclude today's conference. You may disconnect at this time.
Disclaimer