Gilead Sciences Inc (GILD) — Q1 2022 Earnings Call Transcript

Thank you, Jonathan, and good afternoon, everyone. Just after the market closed today, we issued a press release with earnings results for the first quarter of 2022. The press release, slides, and supplementary data are available on the Investors section of our website at gilead.com. The speakers on today's call will be our Chairman and Chief Executive Officer, Daniel O'Day; our Chief Commercial Officer, Johanna Mercier; our Chief Medical Officer, Merdad Parsey; and our Chief Financial Officer, Andrew Dickinson. After that, we'll open up the call to Q&A where the team will be joined by Christi Shaw, the Chief Executive Officer of Kite. Before we get started, let me remind you that we will be making forward-looking statements, including those related to the impact of the COVID-19 pandemic on Gilead's business, financial condition and results of operations, plans and expectations with respect to products, product candidates, corporate strategy, business and operations, financial projections and the use of capital, and 2022 financial guidance, all of which involve certain assumptions, risks, and uncertainties that are beyond our control and could cause actual results to differ materially from these statements. A description of these risks can be found in the earnings press release and our latest SEC disclosure documents. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements. Non-GAAP financial measures will be used to help you understand the company's underlying business performance. The GAAP to non-GAAP reconciliations are provided in the earnings press release, in our supplementary data sheet as well as on the Gilead website. Now I'll turn the call over to Dan.

Thank you, Jacquie, and good afternoon, everybody. We appreciate you taking the time with Gilead today, and I also want to thank those of you who joined our virology and oncology deep dives over the last few months. These two events provided a more in-depth view of our portfolio, our strategy, and the teams behind them. We shared a much broader view of our growing clinical pipeline than we had in the past, highlighting its potential to deliver a number of new therapies to address unmet needs for patients across a diverse range of conditions. For those of you who joined, I hope you got a deeper sense of why we're confident of sustaining our leadership in virology and growing our oncology revenue so that it becomes more than one-third of our total revenue in 2030. I'll turn now to our performance this quarter, and I'm pleased to share that the year is off to a strong start in line with guidance, as shown on Slide 4. Total product revenue was up 3% from last year to USD 6.5 billion, with cell therapy, Veklury, Trodelvy, and HIV driving growth. HIV grew 2% year-over-year, primarily driven by Biktarvy, which grew 18%, and reported more than 4% market share growth compared to the first quarter of 2021. This is notable given the impact of our Truvada LOE. Sequentially, HIV was down 18%, primarily as a result of first quarter seasonality. Our growing oncology portfolio performed well, with Trodelvy revenue doubling compared to the first quarter of 2021, and cell therapy delivering another strong quarter of growth. We recently expanded our portfolio of marketed cancer therapies following the FDA approval of Yescarta for second-line relapsed and refractory LBCL. I'm also pleased to highlight the FDA approval of our new cell therapy facility in Maryland, which is part of the expected 50% increase in our manufacturing capacity by the end of 2022. The new facility will support our cell therapy growth expectations over the next several years. Moving to the pipeline. We shared the Phase III top-line readout from TROPiCS-02 in March showing that the study met its primary endpoint with a statistically significant improvement in progression-free survival versus physician's choice in chemotherapy. Additionally, the first interim analysis of the key secondary endpoint of overall survival demonstrated a trend in improvement. As you know, we are exploring potential pathways for approval with regulatory authorities to bring Trodelvy to these later-stage patients. The details of the study results will be shared at ASCO in June. At the oncology deep dive earlier this month, we highlighted the broad potential for Trodelvy across multiple tumor types and lines of therapy, with plans to initiate 13 more Trodelvy trials through 2023, including four more in 2022. Turning to Slide 5. As you know, the timing for TROPiCS-02 and the NDA decision for CAPELLA are subject to change. In the case of CAPELLA, this is due to the biocompatibility issue that we're working to resolve, and we're fully confident in lenacapavir itself. Other than that, we are on track with the remaining targeted milestones we shared with you in January. We've added some of the newly disclosed trials from our oncology deep dive as well on this slide. Additionally, we're pleased to note that the partial clinical hold for the pivotal magrolimab trials, including ENHANCE free for first-line unfit AML shown on the slide, have been lifted. I'm also pleased to share that despite the hold, there's no change to the timing of the first interim readout for ENHANCE for first-line high-risk MDS, which we expect in the first half of 2023. Merdad will share more pipeline details later in the call. Before I pass it over to Johanna, I just want to take a moment to thank the Gilead and Kite teams who are putting the full weight of their expertise, passion, and commitment behind all of this work that you're seeing. It's thanks to our 14,000 employees across the world that we're delivering for patients with diverse conditions and diseases today and advancing a pipeline of innovative new therapies for the future. We have some golden ambitions for the coming years, and we're confident in achieving them given the level of innovation and capabilities that we have in place today. Now I'll invite Johanna to share an update on our first quarter commercial performance. Over to you, Johanna.

Thanks, Dan, and good afternoon, everyone. So turning to Slide 7. We had a solid start to the year with total product sales, excluding Veklury, of USD 5 billion for the quarter, up 2% year-over-year driven by cell therapy, Trodelvy, and HIV, and offset in part by HCV pricing dynamics. Quarter-over-quarter, total product sales, excluding Veklury, were down 14% as a result of the seasonality we typically see in the first quarter of the year, primarily in our HIV business. On Slide 8, you can see that HIV sales were down 18% quarter-over-quarter to $3.7 billion, consistent with our guidance, given the seasonality we customarily experienced in the first quarter of every year. First, the channels build their inventories over the fourth quarter and then draw them down during Q1. On a dollar basis, the majority of the sequential decline was associated with inventory drawdown. Second, we realized lower net prices in part due to increased copay support, Part D discounts, and other efforts to maintain access and affordability of our HIV medicines as patients' insurance plans reset. This is a customary Q1 dynamic that we expect to normalize throughout the rest of this year. Year-over-year, HIV sales were up 2% driven by market growth for both treatment and PrEP, often in part by the impact of the lost exclusivity for Truvada in 2020. The year-over-year impact of this LOE is expected to be minimal starting in this quarter, the second quarter of this year. And excluding the LOE impact, HIV sales increased 5%. Overall, we're encouraged by the signs of recovery seen in the HIV treatment market despite screening and diagnosis rates still below prepandemic levels and the continued impact on market growth due to the Omicron surge in Q1. As a result, both the U.S. and European HIV treatment markets were down slightly on a sequential basis. On a year-over-year basis, the European market was roughly flat, and the U.S. market grew a little over 3%. The PrEP market grew 33% year-over-year and 3% sequentially. Notably, Descovy continues to hold approximately 45% market share, and we'll continue to engage with payers to ensure those who benefit from PrEP have access to their preferred regimen. We believe Gilead remains well positioned in PrEP. And as highlighted during our virology deep dive in February, we expect the market to double by 2030, catalyzed by the launch of long-acting regimens such as lenacapavir. Descovy sales in the first quarter were $374 million, up 4% year-over-year, driven by continued PrEP market growth and partially offset by generic competition in switches to newer treatment medicines such as Biktarvy. Turning to Slide 9. Biktarvy sales of $2.2 billion in the first quarter were up 18% year-over-year driven by U.S. market growth, and notably, continued share gains in both the U.S. and in Europe. Biktarvy remains the leading regimen for new starts and switches in the U.S. and new starts in Europe. In fact, Biktarvy share is up 4.5% year-over-year to 43% share in the U.S., almost 8 times larger than the next leading promoted medicine and representing the highest share of any complete regimen for the treatment of HIV. Moving to Slide 10 in HCV. We maintained steady market share, and the 22% decline year-over-year was primarily driven by unfavorable pricing dynamics. Sequentially, HCV was up 2%, while the overall market and new patient starts continue to be impacted by the pandemic. HBV and HDV on Slide 11 were up 7% year-over-year due to higher demand for Vemlidy, namely in Asia. Sequentially, HBV and HDV declined 11%, driven by the same HBV seasonal inventory and pricing dynamics impacting HIV. Hepcludex sales were $11 million for the quarter, primarily reflecting sales in Germany and France where full reimbursement has been established. Our discussions with regulatory authorities and other countries across Europe are ongoing. And of course, we look forward to potential approval in the U.S. in the second half of this year. Veklury revenues in the first quarter were $1.5 billion, as shown on Slide 12. The clear utilization tracks hospitalization rates, and therefore, due to the timing of the Omicron surges, it was lower in the U.S. after January but higher in Europe and Asia later in the quarter. We're optimistic that there will not be another surge this year in the U.S. And overall, we will maintain our readiness to support hospitalized and nonhospitalized patients. There's no change to our commitment to COVID-19 patients globally. And in that regard, we were very pleased to receive the World Health Organization's revised COVID-19 guidelines. These guidelines now conditionally recommend Veklury for the treatment of patients with nonsevere COVID-19 at highest risk of hospitalization. And earlier this week, Veklury received FDA approval for the treatment of certain pediatric patients who are at least 28 days old, highlighting our ongoing commitment to extend the reach of Veklury where we can. Now turning to oncology. Trodelvy sales were up 103% year-over-year and 24% sequentially, as shown on Slide 13. We're encouraged by adoption not just in the U.S., but notably, in Germany and France, and continue to work with health authorities and reimbursement bodies to extend Trodelvy's reach to patients globally. We've completed the expansion of our field force to support the U.S. and Europe and believe we are now at the right scale to support physicians and make Trodelvy available across all approved indications to patients who could benefit from it. We're extremely excited by the feedback from physicians about Trodelvy's impact on patients, both those who are prescribing Trodelvy today and those who expect to have access to it soon. With strong physician uptake and our expanded field footprint starting in April, we believe Trodelvy will benefit more than the 1 in 4 second-line metastatic TNBC patients we're reaching in the U.S. today. We look forward to sharing more updates as we progress throughout the year. Turning to Slide 14. And on behalf of Christi and the Kite team, cell therapy sales for the first quarter of 2022 were $274 million, up 43% year-over-year and 15% sequentially. For the quarter, Yescarta sales of $211 million were up 32% year-over-year and 16% sequentially driven by continued global demand in relapsed or refractory large B-cell lymphoma as well as in follicular lymphoma. This highlights the growing recognition of the durable long-term survival benefit showcased at last December's American Society of Hematology Meeting. For Tecartus, sales of $63 million were up 103% year-over-year due to strong demand in relapsed or refractory mantle cell lymphoma. We're pleased with the strong early uptake for adult acute lymphoblastic leukemia in the U.S. following approval last October, which contributed to the 11% sequential growth in Tecartus. The strong momentum we've seen across our cell therapy portfolio continued with the approval of Yescarta in second-line relapsed or refractory LBCL earlier this month as well as FDA's approval for our new Maryland manufacturing facility announced just last week. Through capacity improvements across our existing in-house CAR-T manufacturing site in addition to the new Maryland site, we expect our manufacturing capacity to increase by up to 50% and support our aspiration to serve a cumulative 25,000-plus patients by the end of 2025. Second-line orders started coming in the day after the FDA approval and have been steady ever since. It is truly heartening to see the immediate help we can provide for patients. Given the Yescarta second-line inclusion in the NCCN guidelines and robust clinical data, we expect Yescarta to shift the paradigm in the standard of care for LBCL patients. Christi is here with the team and is available to take any questions on cell therapy during our Q&A. And so with that, I will hand over the call to Merdad for an update on our clinical pipeline.

Thank you, Johanna, and hi, everyone. 2022 is full of clinical activity here at Gilead, and I hope the virology and oncology deep dives were helpful in highlighting the breadth and depth of our portfolio. By the end of 2022, we expect to have more than 90 clinical trials underway across oncology, virology, and inflammation. With such a broad portfolio, our focus is firmly on innovation and execution to ensure that we fully leverage its potential. Moving to HIV on Slide 16. We shared exciting 1-year data from the CAPELLA trials at CROI in February, reporting 83% virologic suppression and heavily treatment-experienced people living with multidrug-resistant HIV. Given the significant unmet need of this patient population, the lenacapavir NDA was designated prior review by the FDA, and we're planning to resubmit the NDA as soon as we resolve the clinical hold and complete response letter. As you know, the basis of these FDA actions was the compatibility of lenacapavir with vials in use at that time, not lenacapavir itself. We're in ongoing dialogue with the agency to consider an alternative vial and look forward to updating you on our progress in due course. Separately, we're on track for the HTE MAA approval in Europe in the second half of the year. At a virology deep dive in February, we shared details of the eight internal candidates that could partner with lenacapavir for treatment and highlighted the additional early development or discovery assets shown on Slide 17. In addition to our PrEP programs, these assets give us a high degree of confidence that Gilead will sustain its leadership in HIV through the 2020s and beyond. In the immediate term, we continue to generate very strong data for Biktarvy. At CROI, we showed biologic suppression at or above 98% in the MA analysis and 0 cases of treatment failure due to resistance to any components of the single-tablet regimen in two 5-year Phase III trials. Of note, this 5-year duration is unprecedented for an HIV regimen. Moving to Slide 18. Veklury is playing an important role in the fight against COVID-19 and is the only antiviral approved for use in both hospitalized and nonhospitalized patients. Just in the past few days, the FDA approved an sNDA for Veklury for the treatment of pediatric patients who are at least 28 days old and either hospitalized with COVID-19 or with mild to moderate COVID-19 and considered high risk for progression to severe COVID-19. In addition to Veklury, we have an ongoing Phase I trial GS-5245, our investigational oral COVID-19 nucleoside that once metabolized works in the same way as remdesivir. Results from this study could lead to a registrational trial. So even while we hope the worst of this pandemic is behind us, we will continue to work to ensure that COVID-19 therapies are available to as many patients as possible. Moving to oncology, and specifically Trodelvy, on Slide 19, we'll share more detailed data from the TROPiCS-02 study at ASCO in June. As a reminder, we announced that the study met its primary endpoint with statistically significant PFS versus physician's choice of chemotherapy in late-line patients. And that the results are consistent with the Trodelvy arm in the Immunomedics-132-01 Phase I/II trial. OS showed a trended improvement at the first interim analysis, and we're now targeting a final OS analysis in 2024, depending on the timing of events. In the meantime, we're engaging with regulatory authorities to explore potential pathways given the high unmet need. As a reminder, TROPiCS-02 targeted a more advanced patient population than best knee breast 04. The encouraging clinical data we've seen in this more challenging patient group has strengthened our excitement in exploring earlier-stage patients. As we shared two weeks ago, we're planning a pivotal study for frontline HR-positive/HER2-negative patients, and we'll share more information in due course. In addition to TROPiCS-02, we're targeting first patient in, or FPI, for a number of new Trodelvy trials this year. In the first half of 2022, this includes frontline studies for non-small cell lung cancer and PD-L1-positive and PD-L1-negative metastatic TNBC. In the second half of the year, we're targeting FPI for the EVOQUE 3 Phase III trial for first-line non-small cell lung cancer. TROPiCS-04 for metastatic urothelial carcinoma is ongoing, and we anticipate a readout in the 2023, 2024 time frame. As you can see on this slide, shared for the first time in our oncology deep dive earlier this month, we are in the earliest stages of evaluating how Trodelvy, either alone or in combination, could bring new options to people with cancer. In total, we're studying more than 25 combinations, including 7 Phase III combination studies. On behalf of my Kite colleagues and on Slide 20, I'm pleased to highlight the FDA approval of Yescarta for the second-line treatment of relapsed or refractory large B-cell lymphoma earlier this month. The approval is based on the ZUMA-7 trial data that showed that 2.5 times more patients receiving Yescarta were alive at 2 years without disease progression or need for additional cancer treatment versus the standard of care. This was the first cell therapy approved by FDA for initial treatment of refractory or relapsed LBCL and within 12 months of initial treatment. Yescarta was also added to the NCCN's B-cell lymphoma treatment guidelines for these patients. Moving to magrolimab on Slide 21. We're very pleased that the FDA lifted the partial clinical hold for our MDS and AML trials, and we resumed enrollment in our three pivotal studies. I'll note that the remaining partial clinical holds on DLBCL and multiple myeloma are being reviewed by a different division of the FDA, and we're actively working to resolve them as quickly as possible. In the meantime, the impact of these remaining partial holds is limited since the DLBCL trial was already fully enrolled at the time of the partial clinical hold, and the multiple myeloma trial had just initiated. Overall, we're excited by magrolimab's potential to be the first new treatment for first-line high-risk MDS patients in 15 years and have completed patient enrollment for the first interim analysis that we expect to share in early 2023. In the meantime, we look forward to sharing data from our Phase Ib trial for high-risk MDS and first-line TP53 AML with more patients and longer follow-up at ASCO in June. Finally, on Slide 22 and noting that the timing for the potential submission of TROPiCS-02 NDA decision for CAPELLA are subject to change, there are no updates to the targeted milestones shared with you in January. With our partner, Arcus, we're targeting a number of data readouts in the second half of the year and have added some new trials, including STAR-121, evaluating zimberelimab and dominilumab in combination with chemotherapy for front-line non-small cell lung cancer and R-21 to evaluate the same combination of upper GI malignancies. With that, I'll hand the call over to Andy.

Thank you, Merdad, and good afternoon, everyone. Before I get into the Q1 P&L review and the guidance update, I wanted to touch on the $2.7 billion partial in-process R&D impairment related to assets acquired from Immunomedics in 2020. This had a $1.63 per share impact on our Q1 GAAP results and on our full-year GAAP EPS guidance. There is no impact on our non-GAAP EPS in Q1 or to our non-GAAP EPS guidance for the full year. With the TROPiCS-02 data readout in March, we have reassessed the value of the assets acquired. While no final decisions have been made pending discussions with regulatory authorities, as a result of the data, we have taken a $2.7 billion impairment to reflect the likelihood of a delayed launch of Trodelvy for third-line-plus HR-positive/HER2-negative breast cancer in the United States as well as Europe and the possibility of a reduced market share in late-line patients given the emerging competitive landscape. Prior to today's update, Gilead was carrying $14.7 billion for the IP R&D indefinite-lived intangible assets acquired with Immunomedics. This now values these assets at $12 billion. Recall that the carrying value of Trodelvy reflected four potential indications in progress at the time of the acquisition, triple-negative breast cancer and hormone receptor-positive/HER2-negative breast cancer, bladder cancer, and non-small cell lung cancer. At that time, we knew that Trodelvy's potential extended beyond these indications but for accounting purposes did not assign value for the incremental opportunities that we are exploring in prostate, endometrial, and other solid tumors, as well as potential combinations such as with magrolimab, venetoclax, and PD-1s like pembrolizumab. As you saw at our oncology deep dive earlier this month, there are 13 Trodelvy programs targeted for initiation through 2023, including a number of incremental opportunities. As a result, we remain confident Trodelvy will deliver an attractive return to our shareholders over time. Moving to Slide 24. The first quarter was a strong start to the year despite the expected seasonality observed in our HIV business and was stronger-than-expected Veklury sales. Total product sales were $6.5 billion, up 3% year-over-year, with growth in cell therapy, Veklury, Trodelvy, and HIV, offset in part by lower HCV revenue. Of note, FX negatively impacted first quarter revenue by almost $100 million, net of hedges, representing approximately 160 basis points of growth. Total product sales, excluding Veklury, were up 2% from the first quarter of 2021 to $5 billion. In HIV, on a sequential basis, we were impacted, as expected, by the normal seasonality associated with Q1 inventory burn following a build in Q4 in addition to the typical first-quarter pricing headwinds that improved throughout the rest of the year. With Q1 now behind us, we expect sequential growth in HIV throughout the rest of the year. Non-GAAP product gross margin was 87.4% for Q1, up 90 basis points year-over-year, primarily due to lower inventory reserve adjustment. First-quarter non-GAAP operating expenses were largely consistent with our expectations as we support the expansion of our oncology business. Non-GAAP R&D was $1.2 billion, up 10% year-over-year. And non-GAAP SG&A was $1.1 billion, up 5% year-over-year, both primarily due to higher costs associated with Trodelvy. Moving to tax. Our non-GAAP effective tax rate in the first quarter was 18.4%. Overall, our non-GAAP diluted earnings per share were $2.12 in the first quarter of 2022 compared to $2.04 for the same period last year, reflecting the higher revenue and higher gross margin, offset in part by higher operating expenses. On a GAAP basis, our effective tax rate and earnings per share were impacted by the $2.7 billion impairment. We are excited about the strong start to the year. And as you can see on Slide 25, the only revision to our outlook is to our GAAP EPS, primarily to reflect the $1.63 share impact of the impairment discussed earlier. We now expect GAAP EPS in the range of $3 to $3.50 per share, down from $4.70 to $5.20. On Veklury, we note the strong revenue start to the year, but also, fortunately, the significant drop-off in U.S. hospitalizations during the first quarter and into the second quarter so far. With that in mind, we will monitor demand through the second quarter and evaluate our full-year guidance in the middle of the year. One housekeeping item before we wrap up. Following recent guidance from the SEC, beginning in the first quarter and similar to many of our peers, Gilead will no longer exclude acquired in-process R&D expenses from non-GAAP financial measures. Prior period results have been updated to reflect this new methodology and are shared in our supplementary data posted on the Investor Relations website. As a reminder, our full-year guidance does not include the impact of any future upfront payments related to the normal course of business partnerships or licensing deals. Going forward, we plan to update our guidance on a quarterly basis to reflect the impact of any new corporate development transactions closed in the prior quarter. Moving to Slide 26. You can see there is no change to our capital allocation priorities. In the first quarter, we repaid $500 million in debt. Additionally, we returned $1.3 billion to shareholders through our dividend and repurchase of shares. Finally, on M&A, there is no change to our philosophy here either. We are very comfortable with the breadth and quality of the pipeline that we have built, acquired, or partnered, and the growth that it will enable in the coming years. With that in mind, you can expect us to continue to opportunistically access high-quality assets through partnerships or make smaller acquisitions in the normal course of business.

Maybe I could ask about the planned or potential Trodelvy filing. You note that it's subject to change. Maybe you could just describe what you think the conversation is with FDA. Is it a combination of a modest PFS and OS trend? And is there a magnitude of OS trend that you think will be attractive and allow a green light to a filing? Maybe just talk a little bit about that and what would drive a filing.

Thanks, Michael. I'll turn it over to Merdad in just a second, but I'll just remind folks that we will be discussing the data more at ASCO coming up there in early June. We look forward to engaging with regulatory authorities in the coming months to further discuss the data and the path forward. I'll see if Merdad has anything to add on that at this stage, but...

Yes, Michael, I think as a normal course of business, we'll always discuss the totality of the data with the agency prior to a filing and have that conversation with them. As we've said, the primary endpoint was statistically significant. And so we will have that conversation with them looking at all the data and come to a conclusion based on the feedback we get.

Right. And we continue to look at earlier lines of therapy and plan those trials to move up in lines of therapy given the results we saw in TROPiCS-02 as well and hormone receptor-positive. So thanks a lot, Michael, for that.

This is Charlie Yang, on for Matthew. So I guess my question is, is Veklury currently being used in China and then actually benefit from the COVID outbreak there? And maybe if that's the case, can you talk about what the economics look like over there?

Thanks for the question. We'll go right to Johanna.

Thanks for your question. So Veklury has been used now with over 11 million patients worldwide, which I think is really impressive. And it's still one out of two hospitalized patients in the U.S. What we are seeing, though, is trends of less severe disease, and therefore, less hospitalizations, but also less treatments. Specific to your question to China, we don't have approval in China at this point in time. And we're continuing those discussions with health authorities in light of the fact that what's going on in China with the pandemic, obviously. I do think the WHO guidelines being updated just most recently is also going to help those discussions as well. So more to come on that, but not currently in play at this point in time in China. Thank you.

Sticking with the COVID theme. Anything that new that you're seeing that increases your level of confidence in 5245’s potential for success? And are there any ways to potentially expedite future development of that asset?

Thanks, Brian. I'll hand over to you, Merdad.

Yes. Nothing new to report, Brian. It's a great question. We continue to move along really well in our Phase I study that's moving forward expeditiously. And we are working with the agency to design a Phase II/III program and really moving as fast as possible. We've got a great partnership with the agency and others and are really ready to count. So right now, so far, so good.

On HIV, Johanna, you alluded to the market dynamics. I just wondered if you could give us a little bit more color and update us on how diagnosis rates are now compared to the beginning of the year. And also if you are seeing any initial impact from Glaxo’s launch of CABENUVA.

Sure. Regarding the market and CABENUVA, thanks for your question, Simon. Let me start with the market. Screening and diagnosis levels are still somewhat below prepandemic levels but are definitely improving. In the first half of 2021, the market was quite depressed but began to recover in the third and fourth quarters of last year. In the first quarter of this year, despite the impact of the Omicron surge, we saw little change quarter-over-quarter in both the U.S. and Europe. However, there was a year-on-year growth of 3.6%. This is an important signal to monitor as we continue our efforts. Since Gilead holds nearly 75% of the total HIV market, it is our responsibility to enhance screening and diagnosis to help end the pandemic. We have many initiatives underway to encourage people to get screened and prevent severe cases of AIDS, which we have unfortunately observed in the recent past. The prevention market is recovering more rapidly after the pandemic, which we’ve seen repeatedly after each surge. Quarter-over-quarter, there was about a 3% growth in the U.S. for prevention, showing modest growth that did decline slightly due to the January Omicron surge. Year-over-year, the growth was 33%, indicating a quick recovery following these surges, which has been consistent across different variants. Regarding CABENUVA, its treatment share is currently 0.6%, so we haven't observed a significant impact. We do see new entrants in the market, along with some normal switching behavior among patients. It is exciting as CABENUVA is the first long-acting treatment. However, we are also noticing a higher-than-usual drop-off rate with CABENUVA, with much of that share returning to Biktarvy. It's interesting to monitor this space, but for now, CABENUVA is having a very limited impact on Gilead's HIV market share. Thank you for your questions.

I had an HIV question for Merdad or maybe even Dan. So you built an increasingly broad pipeline around Lenacapavir. And I know getting long-acting right is strategically very important to Gilead. So the question is, what's been the main bottleneck so far? Is it a matter of matching up the PK/PD for lena? And would you wait to go into a larger scale trial if there is a candidate that may make an optimal doublet with lenacapavir?

Thank you, Geoff. I appreciate it. I'm going to hand it over to Merdad shortly. For those who missed the virology deep dive day, we covered our entire portfolio and the various opportunities we have, including lenacapavir. Lenacapavir is a unique molecule that presents opportunities and challenges in identifying the right partner. We have several candidates that will be moving into the clinic. Merdad, could you provide a bit more detail?

Sure. I'll begin by discussing the PrEP side. We don't need to rely on a partner molecule and our focus now is to address the clinical hold issues. Once those are resolved, we can resume trials and work quickly to complete the PrEP studies and file them. Regarding treatment, you're exactly right. We've developed a portfolio that provides several options to combine with lenacapavir for long-acting treatment. This includes both oral and parenteral approaches. For parenteral, we're aiming for durations longer than two months, while for oral, we hope to achieve a weekly dosing schedule. We have several candidates progressing to determine if they possess the right pharmacokinetic and pharmacodynamic properties for oral administration, as well as the necessary characteristics for parenteral use, including injection site reactions and tolerability. The focus is less on inhibiting HIV replication and more on the molecule and formulation attributes that lead to effective long-acting therapy. Lenacapavir is a particularly unique molecule that enables this, and finding another molecule with similar characteristics is the challenge we're currently tackling.

I wanted to ask about Yescarta and the launch in second-line LBCL. Was hoping you could provide some first impressions of the launch and whether your sense of the demand out there is matching with your expectations.

Yes. Thanks, Do. We're delighted to have Christi here with us. So we'll hear it from the source here. Over to you, Christi.

Thank you, Do. We're very encouraged. First, prior to the approval, the NCCN guidelines changed to classify Yescarta for LBCL second-line treatment as category 1, which is significant because physicians and providers refer to this to determine standard care. This change occurred a month before the approval, which is unusual. Following the approval, our manufacturing site in Maryland was also approved. We feel confident that we are effectively delivering this important therapy to patients. The second-line launch got approved on a Friday around 3 p.m., and by Saturday, we started receiving orders. We are already manufacturing the commercial product at our Maryland facility. It’s still early, but demand has been building since the data were presented at ASH in December, and we are beginning to see orders come in immediately after receiving approval.

It's Gavin, on for Cory. Just on Trodelvy label expansion opportunities and lung cancer, in particular, with the EVOQUE-02 study. It looks like there's multiple cohorts in the study. And we're just curious if, one, is there evidence of synergy with PD-1 inhibitors and you plan on sharing any of that this year? And then two, are you going to utilize a Trop-2 biomarker in any of these cohorts?

Thanks for the question. Merdad, why don't you cover that?

On the biomarker front, we are still assessing the impact of Trop-2 expression on responses. In our experience with the breast cancer study, we have not observed a significant effect of Trop-2 expression on responsiveness. However, we will continue our investigations, as lung cancer might exhibit different behavior than what we are currently observing, and we anticipate that expression patterns may vary. There could potentially be different cutoffs for different tumor types, so that remains to be determined. Regarding synergy, we believe that is the direction of our studies. To achieve additive benefit, larger clinical trials are necessary. We feel that using two distinct approaches to target tumors will be beneficial. I am cautious about the term synergy since it suggests a different mechanistic approach. Therefore, I expect an additive effect from the two components. We believe that Trodelvy will provide additional benefits to patients beyond what immuno-oncology agents and PD-1 and PD-L1 inhibitors offer in treating these patients.

Congratulations on the Yescarta data. I would like to revisit your comments regarding mergers and acquisitions. Some investors may think that you have strong programs, but they are concerned that we won't see results from them. You effectively addressed this during the oncology day. For short-term growth, are you considering acquiring something that could provide immediate benefits until the results from your Trodelvy and magrolimab trials become available? How does the company view this?

Thank you, Robyn. I'll begin and then Andy can chime in. I appreciate you raising that point. Over the last three years, we have purposefully strategized to expand our oncology portfolio beyond cell therapy, which has been part of our history for nearly five years. I want to remind everyone that beyond acquisitions, when a large organization buys, particularly these pan-tumor potential molecules, it initiates the process of enhancing the potential of that medicine in different treatment lines and combinations. Kite is a good example of this, especially after five years post-acquisition, and I appreciate your congratulations on Yescarta. The potential of cell therapy and the leadership Kite has shown by incorporating it into earlier treatment lines demonstrates the impact we can have with potentially curative therapies. This is similar to the strategy we are pursuing now with Trodelvy, magrolimab, and the combination with Arcus assets, which are still in the earlier stages. It's important to keep in mind the timeframe when evaluating M&A success. Additionally, we are consistently looking to augment our efforts. The expectations for Gilead have certainly increased due to the myriad of opportunities we have and the capacity any company can handle. However, we are also engaged in several collaborations, including one with Merck to operationalize a study involving Trodelvy. We will continue to seek opportunities that enhance our virology, oncology, and early inflammation programs to contribute to the growth narrative at Gilead. I know Andy has spent a lot of time reflecting on this, and I would welcome his insights as well.

Thanks, Dan. And thank you, Robyn, for the question. Look, I would just go back to start with fundamentally, we have a lot of confidence in where we are in our growth profile today. And I think it's fair to say that the market maybe underappreciates the growth. Even, Robyn, if you look at our first quarter results, especially when you adjust for the impact of LOE and FX, there's really reasonably strong growth in our business. And this is just the beginning from our perspective. So there are always things that we can do to work on our growth profile. But when you look at the strength of the HIV business, what we're seeing in our oncology business, hopefully, that gives you a sense of why we as a management team have so much confidence about not only where we are today but where we're going. And we recognize, to your question, that the growth profile should get meaningfully better in the next couple of years as the portfolio matures in the way that Dan was describing. So while we will look at things, including commercial assets, as you know, those are few and far between. Many of them are expensive, and that's not really where our focus is. We really genuinely believe we have everything that we need today to be a leading growth company in the sector, and it's just going to take a little more time. But we're definitely seeing all the right signs that we are looking for as a management team. So you should not expect that we're going to go out chasing commercial assets or large deals. The guidance is very clear. It's ordinary course partnerships, maybe smaller commercial acquisitions. Again, we'll be opportunistic. But that's not where our focus is today. Thank you.

Thanks, Andy. In addition to our molecules and medicines, the expertise we are bringing to Gilead is unparalleled. Hopefully, you noticed some of that during our virology and oncology deep dive days, as it is crucial for any company. Our leadership team has worked hard to assemble the right teams at the right time to ensure we are making the best choices and decisions regarding our portfolios as we move forward. This is a major focus for us, and we are very pleased with the progress we are making in this area.

I wanted to follow up on a previous question about remdesivir. Dan, Merdad, it seems that the progress of this program and the timeline for starting the pivotal trial feels significantly slower compared to how quickly Paxlovid advanced. My question is, what expedited pathways are you considering when discussing options with the FDA? A 505(b)(2) pathway seems reasonable given the public health emergency, or perhaps pursuing an active comparator trial against Paxlovid could establish non-inferiority relatively quickly, especially with the current rate of infections. Is it too optimistic to think this could all conclude by summer?

Yes. Umer, I'll start, and then I'll hand it over to Merdad. First of all, I want to emphasize that we are moving with great focus and speed. We have valuable lessons learned within our organization. Remdesivir represents one of the fastest developments of an antiviral, going from concept to approval in the United States. We have gained extensive experience in working with various groups to accelerate trials and navigate unique regulatory pathways with the FDA. These insights are being actively applied to GS-5245. However, we are now in a very different stage of the pandemic, which impacts both regulatory considerations and our ability to recruit participants for clinical trials, especially as the pandemic persists in the developed world. With that, I will now turn it over to Merdad for any additional details he would like to share.

Yes, not much to add other than our Phase I study is progressing rapidly and smoothly without any issues. I know, Umer, you have previously inquired about the 505(b)(2) approach. As you can imagine, we have considered and explored all the pathways you've mentioned. We will proceed with the fastest option available to us, which reflects the discussions we're having with the agency.

It might be a combo one for Andy and Merdad. So can you walk me through some of the math behind the $2.7 billion write-down? Maybe how some of the data you've seen inform the magnitude of the impairment? I'm just trying to square how your assumptions may have changed from August 2020 to now based on data updates that we've had.

Thank you for the question, Evan. It's an important one. To clarify, even before we engage with regulatory authorities, we are required to reassess the value due to accounting standards. When we reviewed the data, we found the study results to be positive and robust. While the outcomes we encountered fell within our expectations, they did not exactly align with our initial modeling for the intangible indefinite-lived asset schedule created post-acquisition. The upcoming discussions with the FDA may influence our valuation again, and we will continue to evaluate the assets connected to hormone receptor-positive/HER2-negative breast cancer and non-small cell lung cancer over the next few years, in line with standard practices for business combinations. Our valuation is based on a probability-weighted discounted cash flow analysis, taking into account the chances of approval. We approached this conservatively, operating under the assumption that there might not be a clear path forward based on progression-free survival data and that we might need to await overall survival data. However, we will gain more clarity in the coming months. Our accounting decisions led us to the $2.7 billion figure. Additionally, Trodelvy-related intellectual property R&D totaled $14.7 billion at the end of 2021, with over half, or $8.8 billion, linked to hormone receptor-positive/HER2-negative breast cancer, while the remainder pertains to non-small cell lung cancer. We have begun to amortize the assets related to other approved indications, which are now classified as finite-lived assets. Currently, we have $6.1 billion in expected cash flows from late-line and earlier hormone receptor-positive breast cancer indications. It's important to note that during the acquisition, we committed to exploring other tumor types and treatment combinations not included in our initial deal model. Ultimately, we are confident there are numerous ways to create significant value for both patients and shareholders moving forward. I'm happy to discuss this further if you need more details.

Yes. Thanks a lot, Andy. I mean, Evan, I think the bottom line is that, again, we took a somewhat conservative approach in the absence of having regulatory discussions so far. We thought it was a prudent thing to do. And to Andy's point, I mean, this is an evaluation of value at the time of the transaction, which, of course, several years later in terms of the indications, the combinations, the potential for Trodelvy is never, as you know, reflective in the initial accounting treatment of it. So hopefully, there's plenty of information in there in our press release and more than happy to take it up with you as well. So thanks, Evan, for that.

Can you share your latest insights on the potential success of the trial when we receive the Phase II PFS data later this year? Additionally, regarding the upcoming Roche results, what secondary aspects are you particularly interested in beyond the main endpoint?

Thanks a lot, Tyler. So over to Merdad, please.

Sure. I believe our perspective is that dominolumab, as a TIGIT agent, will enhance the overall response rate. However, in addition to that, we are also focused on the depth and durability of the responses. These are the key factors we will be monitoring. We are also looking forward to reviewing the Roche data when it is released at ASCO to see what they report as a benchmark. In addition to these factors, tolerability will certainly be a consideration, along with the overall profile.

Maybe a question for Andy regarding foreign exchange. Andy, you mentioned that in the first quarter there was a $100 million impact. Since you provided the guidance, the U.S. dollar has strengthened, resulting in about a 7% decline against the euro. I'm trying to understand how much of the foreign exchange impact you are factoring into the guidance you are currently maintaining. Based on my calculations, it could be over $300 million. If that's the case, it suggests that the core business is performing better than you expected. Could you help us understand the source of this strength?

Sure, that's a great question, Mohit. I'm happy to take it. It's relatively simple, and you are absolutely right. Even in April, we've seen a continued deterioration of exchange rates or strengthening of the dollar, which impacts the revenues from our European business. To clarify, the $100 million impact was based on a year-over-year comparison from Q1 to Q1. Johanna and I are closely monitoring the budget implications of the exchange rates. Part of our confidence in maintaining the guidance is that, while there are forex headwinds, there are also changes in the accounting treatment of in-process R&D that will result in additional expenses from upfront payments, which were not previously included in our non-GAAP earnings report. On the other hand, certain segments of our business are performing well, particularly the strength of Veklury that we've observed so far. Johanna, the management team, and I will reevaluate this midway through the year and provide a more detailed update. The important takeaway is to recognize the changes that could negatively affect our GAAP and non-GAAP EPS, as well as the areas where we expect additional strengths throughout the year to help offset some of that impact. We'll share more details later in the year, but we feel confident in maintaining our current guidance. Hopefully, that helps.

I just wanted to follow up on the TIGIT and adenosine asset. Can you share what you're most enthusiastic about and your strategic thoughts on this? Do you see more potential in the TIGIT and PD-1 combination despite concerns about market timing, or are you more excited about the triplet data? Please clarify your perspective on this.

Thanks, Colin. Merdad, go ahead.

Sure. We are definitely going to analyze all the data and assets available. I would say that the TIGIT/PD-1 combination appears to be the standard for treatment, particularly in lung cancer and possibly in other areas as well. Our goal is to create a strong combination so that we can introduce additional agents that may enhance responsiveness. Options like adenosine or Trodelvy, among others in our pipeline, are all worth considering. We believe that the baseline is being elevated and that the TIGIT/PD-1 combination should serve as our target moving forward.

This is Salveen. Just to revisit TIGIT briefly, you and Arcus have mentioned wanting to see an objective response rate greater than 50%. What are your expectations for progression-free survival and overall survival? It seems like more than 30 months might be adequate for overall survival, considering the KEYTRUDA mono data, and perhaps over a year for progression-free survival. I’d like to hear your thoughts on this.

I would agree with the milestones that you mentioned. It's important to remember that these milestones will take time to materialize. We will need to make decisions without having access to overall survival data for 30 months, which means we will be working with a less mature data set. You're correct that we will be considering all those factors. The key will be to evaluate tolerability and the overall response rate, as well as looking for benefits in the depth and duration of response that we can extract from the data at the level of maturity we will have at that time. I would just suggest to keep an eye on our actions, as you will see the studies starting, which should give you an indication of our confidence in those assets.

With that, I just want to thank everybody. I really appreciate the attention today for the couple of deep dives we've had. We look forward to chatting with you at ASCO and beyond to keep you updated on our progress for the year. And with that, I'll turn it over to Jacquie for some final comments.

Thank you all for joining us today. We do appreciate your continued interest in Gilead and look forward to updating you throughout the year, as Dan said. Have a great rest of your day.