Good day, and thank you for standing by. Welcome to the Gilead Fourth Quarter and Full Year 2021 Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speakers’ presentation, there will be a question-and-answer session. [Operator Instructions] Please be advised that today’s conference is being recorded.

[Operator Instructions] I would now like to hand the conference over to your speaker today, Jacquie Ross, VP of Investor Relations. Please go ahead..

Thank you, Gigi, and good afternoon, everyone. Just after market close today, we issued a press release with earnings results for the fourth quarter and full year 2021. 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 these 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 available on the Gilead website. With that, I’ll turn the call over to Dan..

the ASCENT-03 trial, which is evaluating Trodelvy in the front-line triple-negative breast cancer in the PDL1 negative population; the ASCENT-04, in collaboration with Merck, to evaluate Trodelvy and Keytruda in front-line triple-negative breast cancer population in the PDL1 positive population; and the EVOKE-03, which will be led by Merck, to evaluate Trodelvy and Keytruda in non-small cell lung cancer.

You will also see ongoing momentum in our virology portfolio as we continue to expand our leadership in antiviral therapies. We are advancing our longer-acting HIV options with lenacapavir as the foundation and look forward to potential regulatory decisions in 2022.

If approved, lenacapavir would be the only HIV treatment option administered twice yearly. In addition, we’ll continue to drive progress across our broader virology portfolio, including hepatitis, COVID-19, and other emerging viruses. This is a really important time in Gilead’s transformation journey.

After the consistent work to execute on our strategy and expand our portfolio over the last two years, you will increasingly start to see this play out in tangible results. We’re confident that Gilead has all the elements in place for a strong year and a strong decade.

Johanna, and Merdad and Andy will now take you through the details of our progress and our plans. And let me hand first to Johanna to talk about our commercial performance in the fourth quarter and the full year. And I’ll be back to you in the Q&A.

Johanna?.

Thanks, Dan. Good afternoon, everyone. As you can see on slide 7, we had a strong end to the year with Q4 total product sales, excluding Veklury, of $5.8 billion, up 7% quarter-over-quarter, driven by favorable pricing and inventory dynamics.

This also represented 8% growth year-over-year, driven by continued recovery in the HIV treatment market and favorable pricing dynamics. Veklury sales were higher than expected in Q4 reflecting the start of the Omicron surge, but lower than both the prior quarter and prior year, and contributing to total product sales of $7.2 billion for the quarter.

Moving to slide 8, total fourth quarter Veklury sales were $1.4 billion, bringing total sales for 2021 to $5.6 billion. Gilead is proud of the role that Veklury continues to play in this pandemic. Veklury has demonstrated activity against the Omicron variant and has helped many patients with COVID-19 in the most recent surge.

Although symptoms have generally been less severe, the volume of overall cases has meaningfully increased since the emergence of Omicron, and we have seen the total number of hospitalizations increase as well. While we would all prefer to put this pandemic behind us, we expect Veklury to continue to play a critical role in 2022 and beyond.

As you would expect, hospitalizations remain a key indicator for in-patient Veklury sales, and we are seeing higher hospitalizations in geographies with lower vaccination adoption, including certain parts of the U.S. as well as Eastern Europe.

Additionally, I’m very pleased to highlight that the FDA recently approved the sNDA filing for the use of Veklury in the outpatient setting for patients at high risk of disease progression. This approval was based on data generated in the Phase 3 PINETREE study, further solidifying the credibility, importance and role of Veklury.

Now Veklury will be available to help even more patients earlier and reduce risk of hospitalization for COVID-19. Next, as shown on slide 9, total HIV sales were $4.5 billion in the quarter, up 8% sequentially driven by favorable inventory and pricing dynamics as well as changes to our gross to net estimates in Q4 2021.

For the full year, total HIV sales were $16.3 billion, down 4% year-over-year, primarily due to the Truvada and Atripla LOE, in addition to pandemic-related impacts and pricing dynamics. The expected impact from the LOEs, which amounted to $1.3 billion, was offset by continued Biktarvy growth.

Excluding the sizeable LOE impact, HIV total product sales for the full year grew 4% compared to 2020 despite the ongoing pandemic headwinds. We now expect the Truvada and Atripla loss of exclusivity impact to be minimal going forward as the headwind dissipates starting in Q2 of this year.

In HIV treatment, we continue to see signs of market recovery although the U.S. market declined 1% sequentially in Q4 following two quarters of sequential growth. On a year-over-year basis, the overall market in Q4 was up 1.5% in both the U.S. as well as the EU5, despite screening and diagnosis rates still below pre-pandemic levels.

As you know, favorable dynamics play out in the fourth quarter of every year in HIV, and 2021 was no different with some year-end inventory stocking and favorable seasonal pricing as well as changes in our gross to net estimates in Q4 2021.

As you think about 2022, I’ll remind you of the normal HIV inventory build-up in Q4 and the New Year reset for patient copays and donut hole payments. Given these factors, along with the favorable pricing dynamics I just mentioned, we expect the sequential decline in Q1 ‘22 to be greater than Q1 ‘21.

Nonetheless, we expect a strong year overall in HIV and expect continued growth in subsequent quarters. Back to Q4, Biktarvy had another record quarter with sales of $2.5 billion, up 11% sequentially and 22% year-over-year. On slide 10, you can see that Biktarvy U.S.

treatment market share has increased over 5 share points in 2021, reaching 42%, which is the highest share that any complete regimen has ever achieved in this market. For the full year, Biktarvy sales were $8.6 billion, growing 19% from 2020, and Biktarvy remains the leading prescribed treatment for naïve and switch patients in the U.S.

as well as number 1 in naïve in EU5. Descovy revenue for the fourth quarter was $473 million, up 9% quarter-over-quarter primarily as a result of favorable seasonal pricing and inventory dynamics as well as continued demand.

We expect Descovy revenue to continue to be driven by PrEP as Descovy has maintained about 45% of overall PrEP market prescriptions in the U.S. We will continue to ensure access to support physician choice, and expect growing demand and market expansion to offset the impact of increased commercial contracting.

Overall, while near term growth continues to be impacted by local pandemic-related social restrictions, we are encouraged by the growing PrEP market. In Q4, the overall PrEP market grew 4% quarter-over-quarter, and 31% year-over-year.

Looking forward, we believe lenacapavir, our investigational longer-acting PrEP offering, could potentially catalyze the market well beyond the 25% penetration rate in PrEP that we see today. Moving to slide 11, it’s clear that HCV continues to be the part of our portfolio most impacted by the pandemic.

Although there was some slight quarter-over-quarter recovery in market starts in the EU5, U.S. market starts declined, resulting in flat total starts overall. While Gilead market share increased modestly on a sequential basis in both the U.S.

and the EU, this was more than offset by unfavorable pricing dynamics, resulting in Q4 total sales of $393 million, down 8% sequentially and 7% year-over-year. As you can see on slide 12, our HBV and HDV franchise reported record quarterly revenues of $265 million, up 7% sequentially due to seasonal inventory and favorable pricing.

The 9% year-over-year growth was primarily driven by Vemlidy demand. Total fiscal year sales for this franchise were $969 million, up 13% year-over-year. Hepcludex reported $12 million of sales in Q4 in Europe, with $37 million in 2021 sales since our acquisition in late first quarter.

Hepcludex is currently available in Germany and France, in addition to a number of early access programs in countries such as Austria, Italy, and Greece. In 2022, and as part of our comprehensive commercialization plan, we expect to finalize reimbursement for launch in a number of major European markets.

In the U.S., we filed a BLA in November and FDA granted priority review for accelerated approval, with a PDUFA date set for the third quarter and an Advisory Committee meeting that will be scheduled in the coming months.

Moving to oncology, first with Trodelvy on slide 13, global sales were $118 million in the fourth quarter, up 17% sequentially and up 84% year-over-year compared to full Q4 2020 sales.

This reflects growing adoption of the second line metastatic TNBC triple-negative breast cancer indication, which was noted as a preferred regimen in the NCCN Breast Guidelines updated in September. We are also starting to see stronger, unaided brand awareness which is resulting in continued market share growth.

In second-line TNBC, Trodelvy now captures approximately 1 in 4 new starts in the U.S. We have expanded our oncology footprint globally, including tripling our U.S. headcount to further accelerate penetration of Trodelvy and prepare for our potential HR positive and HER2 negative launches.

Additionally, EU approval for Trodelvy was granted in late November 2021 and we have already seen strong momentum in France and Germany since their launch. We plan to launch in a number of new countries following key reimbursement decisions this year.

Now, on slide 14, on behalf of Christi and the Kite team, cell therapy Q4 sales of $239 million reflected 47% year-over-year growth, an 8% increase sequentially. For the quarter, Yescarta sales of $182 million were up 41% year-over-year driven by continued demand in relapsed or refractory large B-cell lymphoma and follicular lymphoma.

Tecartus sales of $57 million in the quarter reflected 68% year-over-year growth based on growing global demand for relapsed or refractory mantle cell lymphoma and early contribution from adult acute lymphoblastic leukemia in the U.S.

As a reminder, FDA granted Tecartus approval in adult ALL in October and in just the first few months of launch, there has already been strong demand that we expect to continue in the coming quarters given the high unmet need.

Full year cell therapy sales of $871 million reflected 43% year-over-year growth driven by continued LBCL and MCL demand globally as well as the new launches.

The strong growth we’ve seen with these recent launches reinforces our belief that cell therapy adoption will continue its positive momentum as more physicians understand the benefits for appropriate patients and therefore increase referral rates to treatment centers.

Merdad will elaborate later, so I’ll just quickly mention the impressive data Kite presented at ASH in December, 43% overall survival rate after five years in third line LBCL patients. The Yescarta data at ASH not only highlighted the long-term real-world safety and efficacy profile in third line LBCL, but also in earlier lines of therapy.

For ZUMA-7 data in second-line LBCL, FDA has set a PDUFA date of April 1st when we hope Yescarta will be granted approval. In the meantime, the Kite team is ramping up manufacturing capacity to meet the anticipated demand. Kite expects the new Maryland facility to begin commercial operations by Q2.

Combined with the Amsterdam and El Segundo facilities, we expect to increase operational capacity by up to 50% by the end of this year. Christi is here with the team and available to take questions on cell therapy during our Q&A. In closing, our oncology sales were $1.25 billion in 2021 and we expect robust growth in the coming years.

With that, I’ll hand it over to Merdad for pipeline updates..

domvanalimab, an Fc silent anti-TIGIT antibody; AB308, an Fc active anti-TIGIT antibody; etrumadenant, an adenosine receptor antagonist; and quemliclustat, a small molecule CD73 inhibitor.

Together with Arcus, we expect to share ARC-7 Phase 2 PFS data in the second half of 2022, which will include data for the zimberelimab monotherapy, zim and dom doublet, as well as the zim, dom and etruma triplet arm.

We look forward to sharing data when available and are very excited to collaborate more closely with Arcus to accelerate future development plans. On slide 23, you can see that Gilead’s portfolio now encompasses 55 clinical stage programs, nearly doubling since 2019.

Given the exciting potential of our portfolio across virology, oncology, and even early stage inflammation assets, this is just the beginning. Our teams are committed to advancing the most promising programs that will help transform patient outcomes, and we look forward to sharing our progress with you over the coming quarters and years.

With that, I’ll hand it over to Andy..

Thank you, Merdad, and good afternoon, everyone. It was a strong close to 2021, driven primarily by strong HIV and Veklury revenue in the fourth quarter. For the full year, and excluding the impact of the LOEs, HIV grew 4% year-over-year, driven by the continued outperformance of Biktarvy, which achieved record U.S.

market share of 42%, and sales of $8.6 billion, up 19% from 2020. Oncology was another highlight from both a pipeline and revenue perspective, with full year cell therapy sales of $871 million growing 43% from 2020, and Trodelvy sales of $380 million in its first full year.

By 2030, we anticipate our oncology franchise will represent at least a third of our total revenue. Before I get into the normal P&L review and 2022 guidance, I want to address the EPS results for this quarter upfront. Slide 25 highlights two sizeable expenses that occurred after we gave our last guidance in October.

First, and subsequent to the exercise of Gilead’s opt-in to four Arcus assets in December, our fourth quarter results reflect a net charge of $625 million, recorded in R&D. This charge reflects our $725 million option payment recognized in Q4 less $100 million that was previously accrued.

This impacted our EPS by about $0.38 in Q4 and for the full year. Second, and as part of a legal settlement with ViiV and related parties, we have agreed to make a one-time $1.25 billion payment, in addition to an ongoing 3% royalty for future sales of Biktarvy and the bictegravir component of bictegravir-containing products in the United States.

This royalty extends until October 5 of 2027. The $1.25 billion payment is recorded in our fourth quarter results and reflected in our cost of goods sold. This charge constituted an approximately 17% impact to gross margin in the fourth quarter, and it impacted our EPS by $0.80 for Q4 2021 and the full year.

Going forward, we expect the impact of this new royalty to be approximately 1% on our gross margin, starting in the first quarter of 2022. Excluding these items, and their combined $1.18 impact, our full year non-GAAP EPS would have exceeded the guidance range that we set back in October, helped by stronger than expected Veklury sales.

Moving back to our quarterly review on slide 26, fourth quarter revenue in our base business included HIV product sales growth of 7% year-over-year and 8% sequentially. Veklury sales were higher than expected due to start of the Omicron surge.

Non-GAAP product gross margin was 70.5%, impacted by the legal settlement that I referenced earlier, and non-GAAP R&D was impacted by the Arcus opt-in, resulting in non-GAAP EPS of $0.69 per share.

Our non-GAAP effective tax rate for the fourth quarter was 32.2%, reflecting tax expense related to uncertain tax positions, an increase in valuation allowance, as well as the impact of discrete tax benefits related to legal settlements with tax authorities in 2020 that did not recur this year.

For the full year, on slide 27, total product sales of $27 billion grew 11% driven by Veklury. Excluding Veklury, total product sales were roughly flat at $21.4 billion as growth in Biktarvy and oncology offset the $1.3 billion impact of the Truvada and Atripla LOEs in the United States.

I touched on the main P&L impacts in the fourth quarter discussion, but will highlight that our non-GAAP effective tax rate for 2021 was 20.4%, despite the higher effective tax rate in the fourth quarter. Moving now to slide 28.

Our 2022 guidance assumes that the recent Omicron surge represents the only major COVID-19 wave for 2022, and that our HIV business will continue to recover from the pandemic. With that in mind, we expect Product Sales in the range of $23.8 billion to $24.3 billion.

Excluding Veklury, we expect product sales in the range of $21.8 billion to $22.3 billion, representing growth of 2% to 4% for our base business year-over-year. Relative to Q1, I’ll remind you to expect HIV revenue to decline sequentially.

This is a normal dynamic for HIV due to inventory and seasonal pricing impacts, and you’ll recall last year HIV revenue declined 14% sequentially in Q1 ‘21 from Q4 of 2020. For Q122, we expect a larger sequential decline, given the favorable Q4 ‘21 changes to gross to net estimates that Johanna mentioned earlier.

Nonetheless, we expect a strong year overall for our HIV business and continued growth in the subsequent quarters. Looking beyond Q1, we expect the impact of the Truvada and Atripla LOEs will be largely behind us starting in Q2, and we look forward to accelerating growth in our HIV business during the remainder of the year.

For the full year 2022, we expect Veklury sales of approximately $2 billion. This assumes, as I previously indicated, that Omicron will represent the only major surge for the year, with Veklury revenue heavily weighted in the first quarter.

That said, the pandemic continues to be dynamic, and we will update you on our Veklury expectations on a quarterly basis, consistent with our recent practice. Moving to the rest of the P&L.

We expect our non-GAAP product gross margin to be approximately 85% to 86%, consistent with our historic guidance and allowing for the 3% royalty associated with the legal settlement. For non-GAAP operating expenses, we expect R&D to decrease by a mid-single digit percentage compared to 2021 levels.

This decline is driven by the net $625 million charge related to the Arcus opt-in in the fourth quarter of 2021. Excluding this, we expect full year R&D expense to increase by a mid-to-high single digit percentage compared to 2021 levels. We expect SG&A to be approximately flat on a dollar basis compared to 2021.

Our non-GAAP effective tax rate is expected to be approximately 20% this year. Finally, we expect our non-GAAP diluted EPS to be between $6.20 and $6.70 for the full-year, and GAAP diluted EPS to be between $4.70 and $5.20. On capital allocation, our priorities have not changed.

We continued to invest in our business while, at the same time, we returned over $4 billion in 2021 to our shareholders, through dividends and share repurchases. In addition, we repaid $4.75 billion of debt in 2021. For 2022, we plan to repay $1.5 billion of debt, of which, we repaid $500 million this morning.

With that, I will invite the operator to begin the Q&A. Thank you..

[Operator Instructions] Our first question comes from the line of Geoff Meacham from Bank of America..

Dan or Andy, maybe a higher level strategic question. I wanted to ask about your comments regarding long-term oncology sales.

And the question is, are you comfortable with the aggregate assets in the portfolio? Do you think you’ll need to be more aggressive on BD either to drive more near-term growth or looking longer term to have higher impact assets?.

Thanks, Jeff. Thanks for the question and teaming. I’ll start and then hand it over to Andy. So, yes, I mean, the guide that we gave at JP Morgan was that we are confident in our ability to grow and to also have oncology by 2030 be at least a third of our overall revenue on top of a solid HIV business and virology business overall.

I think, the answer to the question, Geoff, is we believe we have everything in-house to be able to fulfill on that commitment today.

I mean, the number of options that we have with Trodelvy, with magrolimab, with the Arcus assets and with Cell Therapy from an oncology base provides tremendous opportunity for us to look alone and in combination of that portfolio in the coming years.

And that specifically leads to the more than 30 clinical trials we have ongoing right now in our oncology portfolio. And our guide that this year will start at least another 20 in the oncology space. So really, that’s the armamentarium behind our commitment and our growth.

Of course, we’ll continue to be opportunistic around business development and look for supplemental options out there that can complement this portfolio as a course of normal business as any healthy company should. Having said that, we really do have enough in-house to be able to fill up on that commitment.

So, with that, Andy, I may have stolen all your thunder, but I’m sure you’ll have some additional perspectives..

Yes. Geoff, thank you for the question. I think it’s an important question, especially in the context of the magrolimab clinical hold that maybe underpinning the question specifically. But the answer is relatively simple. We have a very strong set of assets already.

The guidance that we provided at JP Morgan does not actually include all of the assets or all the indications for all the assets. So, there’s a lot of ways for us to get there. We have complete confidence in where we’re going, and we don’t expect to change our BD strategy as a result of any of the recent developments.

We’re actually really excited about where we are. And there’s a lot of upside to that of other assets, whether it’s some of the earlier Arcus assets or the Tizona or Pionyr assets, as examples, provide additional options for patients.

So, when you talk about high-impact assets, I would just summarize by saying, we already think that we have a great portfolio of high-impact assets in oncology, we’re incredibly pleased with what we’ve put together and nothing that’s happened recently has changed that in any way. So, thanks for the question..

Our next question comes from the line of Mohit Bansal from Wells Fargo..

Maybe a question for Merdad.

So, in the light of new data that are emerging in HR positive and HER2-negative breast cancer, do you have any updated thoughts on how to think about overall survival in the treatment and control arms for TROPiCS-02 vis-à-vis the expectation or the assumptions in clinical trials, which I think, if I’m not mistaken, 12 months for the control and 16.5 months for the treatment? So, how should we think about OS? Thank you..

Thanks, Mohit. Directly over to you, Merdad..

Yes. Thanks, Mohit. It’s a great question. And I think as I mentioned in my call, I think we’re excited that we’re going to be able to share the first interim analysis from the OS as well when we do the readout here for the PFS. So, I do think we’ll look at both at the same time.

You’re absolutely right that there are developments in the HR-positive space, but I continue to believe, and I think that the impact on both PFS -- on PFS in particular here, but also OS continues to be, I think, if we see something in the ballpark of what you just described, we’re confident that that remains incredibly clinically relevant for people suffering with HR-positive HER2-negative.

It is, as you state, an increasingly competitive area, but we do think that that remains a key milestone for patients if we can achieve that..

Our next question comes from the line of Cory Kasimov from JP Morgan..

I wanted to follow up as well on the TROPiCS-02 study.

And maybe, Merdad, can you talk about how you see the potential significance of this convergence of events that you alluded to when thinking about both progression-free survival and overall survival? Did you see any implications from this, or is this kind of moving along the lines as you would have expected it to?.

Yes. Great question, and thanks for asking it. I think I’m very reassured I would not read anything into this other than the fact that we’ve been, as you can imagine, keeping track of the PFS events and the OS events all along.

And we’ve now gotten to the point where those OS events have occurred in a time frame that allows us to look at both of these events at the same time. I don’t think it really says anything about -- I think what you’re getting at is does it have any implications for the underlying positive or negative or anything like that.

And I really don’t think there’s any way to interpret that right now. It would be pure speculation to think that there’s some underlying driver of bringing those endpoints together. And actually, it’s not that unexpected. It’s a little bit closer than we thought it would be, but not by that much. So, I wouldn’t read too much into it.

I’m just excited we’ll be able to do it. It will be a more robust look. And I think as I’ve said before, we think the regulators are going to want to see those robust looks at the OS to help them with sort of, in a sense, supporting the PFS endpoint..

Our next question comes from the line of Brian Abrahams from RBC Capital Markets..

I wanted to better understand the potential signals from magrolimab. I think you guys have said that you haven’t observed any clear AE trend.

I was curious, where is the disconnect versus what the FDA and investigator concerns are here? And maybe talk a little bit about the potential path to resolution, what additional safety data would be needed and your level of confidence you will reach a resolution? Thanks..

That’s great. Thanks, Brian..

Thanks, Cory. Yes. So look, I think the way to think about it is some of -- there have been a couple of events that the agency wants to make sure that they have a chance to look at the overall safety profile. I remain blinded to the safety data.

So, what is going on is we are gathering the safety data, and we’re going to share it with the FDA and with the data monitoring committee. I can tell you that we feel that these are temporary challenges right now and we’re going to work through resolving it as quickly as possible.

I don’t think these challenges really shake our confidence for the portfolio overall and our overall strategy hasn’t changed. We’re really committed to the macro development program, and we think that it really continues to have the potential to really address -- an important unmet medical need.

The only thing I’d add is, remember, these are very generally pretty sick patients. And with that underlying illness, I think it’s appropriate to be cautious to make sure that we’re striking the right balance as we go forward.

But we’ll work through it by looking at the overall safety at the overall safety profile, Brian, and make sure that we are able to resolve those issues with the FDA..

And Brian, we’ll keep you informed as that evolves. We have obviously a lot of patients on magrolimab that continue to be served by magrolimab. So, we have a sense of urgency in working with the agency around this..

Our next question comes from the line of Salveen Richter from Goldman Sachs..

You referred to the Arcus portfolio.

Can you just comment on what you’re most excited about outside of TIGIT and when you might start the triplet study?.

Sure.

Merdad, why don’t you start on that?.

Sure. I think in addition to the TIGIT asset, as you know, the adenosine portfolio, if you will, the 2 molecules, the 2 inhibitors of adenosine, both in terms of the synthesis inhibitor, CD73, as well as the receptor blocker are really interesting to us.

They’re early programs, but we think that there is a real potential for those assets to provide significant upside to treatment, both in terms of where -- in lung cancer, where we think there’s some -- the trial that’s ongoing that is looking at the addition of adenosine inhibition to TIGIT plus PD-1 as well as in some of the indications that Arcus is evaluating with monotherapy in particular, pancreatic cancer.

So, I think for us, there are a number of opportunities there and the broad potential of adenosine inhibitors to add on to immuno-oncology in general and TIGIT plus PD-1 in particular really strike us is a really great opportunity that hopefully as the data mature, we’ll be able to share more and really underpin the optimism we have around where those programs are headed..

Right. And I think there was a question around when to start the....

And then the triplet study, yes, we’ll -- we haven’t announced that yet. We need to work through some details. Thanks for reminding me, Dan. We’re working through some approach.

Really, the question here for us is how to go from the doublet, where we’re really looking at a TIGIT inhibitor being an unapproved agent, right, and then potentially bringing in a second unapproved agent.

So we have to work through in a sense, the regulatory complications of how we have to sequence and stage those studies to allow us to assess the contribution of components such that we can move forward aggressively.

So, we’re working really closely with our adenosine colleague -- our adenosine colleagues, our Arcus colleagues, and we’ll work through the regulatory pathways to make sure that we can get to a robust base Phase 3 trials with those. So, as we do so, we’ll certainly share the timing in the pathway..

And Salveen, the only thing I’d add on top of Merdad’s eloquent response is the potential to combine this attractive portfolio for markets with other medicines that we have within Gilead, including Trodelvy and possibly magrolimab and others, so his combination of having access to a PD-1 2 TIGIT compounds to adenosine combined with Trodelvy provides a rich opportunity to look at rational-based combinations.

And we’ll be getting more into that as we do a deeper dive in oncology as a starting point in April. And then obviously, throughout the year, we’ll continue to update you on that. And it’s one of the major reasons why opting in early was important to us because we can work really fluidly now across a very rich portfolio.

And with the additional expertise and colleagues from Arcus, it really expands all of our potential and clinical science and beyond..

Our next question comes from the line of Michael Yee from Jefferies..

Maybe back to Merdad on Trodelvy, appreciating that I know there’s a lot of focus on this interim OS. I would love to give you the opportunity to perhaps frame expectations at an interim. Interims have different connotations and there’s different interims at different percent of events that have accrued.

So, could you just explain what percent of events this interim is based on? Do you actually expect to hit stat significant, or do you just expecting a trend of a few months? Maybe just talk to that a bit, because I think there’s different implications of just an interim..

Yes. Thanks, Michael. And maybe just a suggestion, as you answer, Michael’s specific question, it might be helpful for the whole audience to hear again kind of your overall view of the potential success of this indication..

Yes. Michael, it’s a great question. And I think, thank you for asking it. So, as a reminder, I think from a PFS standpoint, the primary endpoint of the study, we believe we’re really well powered to detect a difference there. And as I’ll remind folks, we did redesign the study a year ago in order to power the study adequately for OS as well.

I would -- I think as excited as I am that we will be able to report out that first interim analysis, Michael, you’re absolutely right on that. I would not expect statistical significance at this first interim because it is relatively early in the time frame that we’re seeing.

So, my expectation is that again, pending a positive outcome that we are well powered to see a PFS improvement at a statistically significant level. And the OS will be supportive data at that point that will give us directionality as to where we’re headed.

And then hopefully, subsequent to that as the events accrue, we’ll see where we’re headed with OS and down the road. It’s a great question..

Our next question comes from the line of Ronny Gal from Bernstein..

Switching over to talk a little bit about Yescarta. Can you tell us if there’s already impact, the use of Yescarta in second line, or is it still ahead of us? And you’ve mentioned you’re increasing your capacity by 50%.

Are you currently capacity-constrained or demand-constrained? Essentially, will all that demand be used if it comes on line?.

Yes. Thanks, Ronny. And as I turn it over to Christi, let me just say how many patients we’ve been able to impact with cell therapy in 2021, and that being just the beginning, I think, of our promise for the future.

We certainly invested in the manufacturing capacity to anticipate demand and success in the second-line, and Christi can go into the details with you. Christi, over to you..

Thanks, Dan. Thanks for the question.

Yes, we’re very excited about not only the second-line, which is the most important to help the most patients, but the continued success of third line plus with the five-year data that was presented at ASH where year four, you saw 43% of patients still alive, and at -- 44% of the patients still on life of four years and 43% at five years, which I think you heard Merdad say.

So, based on those as well as new indications coming out, we’re really seeing an increase in demand. Our capacity, we’re well positioned. We have the El Segundo manufacturing site here in California. Amsterdam was approved during COVID and with up to its capacity by the end of last year.

And now, we have the Maryland site, which will be going online in the first half of this year where you’ll see our automation as well. So, not only increasing capacity, but also the ability to reduce costs.

So, things are coming along nicely in terms of our ability to deliver, and we still have that reliability of 97% success when we give the cells back, which is so critically important to patients. So, not a capacity issue.

We had a transparency, a couple of issues last year where we had a scheduling issue where physicians were asking for the exact same slot all at the same time. And we quickly addressed that and no longer have that concern. So, we’re doing well and preparing for, hopefully, what we’ll see is helping a lot more patients stay live a lot longer..

Thanks so much, Christi. And overall, Ronny, we’re expecting about a 50% increase in capacity over the course of 2022, so continued investment there..

Our next question comes from the line of Colin Bristow from UBS..

On magrolimab, maybe could you explain why the multiple myeloma and DLBCL trials were also on hold given they’re not in combination with aza? And then, just somewhat related to that, the $1.50 in acquisition-related expenses in the ‘22 guide, is there any component of that, that’s related to the Forty Seven acquisition..

Great. So I’ll have Andy answer the second. Maybe you want to touch base on the first, Merdad, also telling about the stage of those 2 trials..

Yes, it’s really important to -- I think this may have not been entirely clear. First of all, I think -- look, I think whenever there’s a safety question, the agency is going to err on the side of being cautious. And so we’ll work through with them on how to go forward. And I agree in those studies, we are not combining with azacitidine.

So again, I think as we share the data and the analysis with the agency, hopefully, we can come to resolution sooner than later. And it’s important to note that for the multiple myeloma study, we actually hadn’t really started enrolling patients at that point. So I think that was one consideration.

And by contrast for the DLBCL study, that is completely enrolled. So, the partial hold there actually doesn’t have much of a practical impact on that study because we’re going to continue dosing the patients who are already enrolled in that study.

So, I think -- remember that the way it works is maybe the context here, the holds are placed on an IND, not on a study-by-study basis, generally. So, this was a hold to the IND. And so, that’s sort of the context to think about it. I’ll hand it off to Andy to answer the second part of the question..

I’m not sure that I fully understood the question, but what I can tell you is none of the -- none of the updates that we provided in terms of the onetime fourth quarter expenses nor none of our 2022 guidance has anything to do with expenses.

So you and I can maybe talk separately to understand what your question is specifically, but there’s nothing related to or the Forty Seven acquisition that was either part of our fourth quarter update, year-end update or part of the 2022 guide specifically..

Thanks, Colin. Happy to take that up separately, too..

Our next question comes from the line of Hartaj Singh from Oppenheimer..

This is just a question on Veklury. You’re starting to get a pretty consistent franchise there. I mean, unfortunately, COVID-19 is still out there. Various experts have indicated and even some of the companies we cover, we’re going from a pandemic to an endemic kind of state over this year into next year.

How do we -- how do you think of Veklury going forward? I know it’s difficult to give guidance there, but you’ve got a year and a half worth of data underneath your belt.

How are you thinking of hospitalizations going forward, whether that’s through breakthrough infections, or do you see as unvaccinated individuals get less and less that hospitalization will concomitantly decrease? Any thoughts there? And then, assuming the oral program gets approved, how do you see remdesivir IV and then the oral option working together going forward? And again, thanks for the questions, and a really nice quarter..

Thanks, Hartaj. So, I think Johanna can start with some of the pandemic -- endemic and then Merdad could also comment a little bit on the forward portfolio. But please, Johanna, over to you..

Thanks, Hartaj, for the question. Basically, what we’ve seen since the very beginning is how that Veklury sales truly track to the hospitalizations. And we’ve seen that most recently again with the Omicron surge.

What we did see as well is the fact that -- despite the fact that Omicron seemed to may be less severe impact, unfortunately, the number of cases were much greater and therefore just the pure absolute numbers of hospitalizations went up. And so, we’ve tracked every single time pretty much in line, parallel to the hospitalization rates.

And we assume that will continue. We do think the hospitalizations will get impacted by some of the oral compounds, even some of the outpatient use of Veklury, but also neutralizing antibodies as well as the oral treatments as well like the PI from Pfizer. And so, we do think that will decrease hospitalizations over time.

The one thing we had assumed maybe about a year ago is we really thought the vaccination rates would continue to rise and they didn’t. They basically stabilize at around the 60%, 65% rate. And of course, there are variances across the country.

So, what we’ve seen is the use of different treatments as well as the vaccinations -- the vaccination rates are really dictating a little bit kind of the hospitalizations and therefore, the Veklury usage.

And yet again, in the December, January time frame, we’ve really seen Veklury play a critical role here for these hospitalizations, also having to do with the fact that many of the other previous agents that were on the market were no longer effective against the Omicron variant. And we haven’t seen any of that.

We’ve seen very strong efficacy with Veklury, which has also helped that.

I think most recently, the outpatient data that’s just come out in addition to the indication really plays a critical role when there are surges and hospitals are overcapacity, so that they really can look at outpatient setting with Veklury, and we think that will just kind of play hand in hand.

And I would propose, as I turn it over to Merdad to address the oral piece of the puzzle, I actually think you need both.

I think you need the oral setting, so more players in the oral setting is critical and you still need hospitalizations because, unfortunately, as this -- if it does become endemic, I do think you’ll see a steady rate of hospitalizations as we go through, and that’s where Veklury plays a critical role.

Merdad?.

Yes. Thanks. And I guess, I’d make two points. The first is, is very early days with the oral program. And so, I would keep that in mind. We just started Phase 1. So, a lot of things can happen. And so I would just keep that in mind. Obviously, if things go well, we’ll move as aggressively as possible. And I agree with Johanna.

I think that there will always be a role for both oral and IV therapies. There will be a -- what we’re seeing now, I think, in terms of how folks are approaching it is that as availability of oral therapies becomes broader, they’re used relatively early in the course of disease.

Many people may progress and/or not get treated early enough and end up in the hospital. And at that point, I think that’s where that hospitalized or carry hospitalization more severe disease is where the role of IV therapies is going to come in, Veklury in particular is going to come in.

So, I have too much to add to what Johanna said, but I do think there’ll be a role for both in the long run..

Hartaj, just to complement what Johanna and Merdad said, I think we clearly see that as this becomes endemic that there’ll be potentially a need for multiple mechanisms in the outpatient setting.

So, that’s one of the reasons why approaching it from a preliminary standpoint as well as to a protease standpoint, we think could make sense over the long term for resistance patterns.

And the last thing I’ll say is I think what we’ve seen this, whether it’s pandemic or endemic, remdesivir is going to firmly trench now as a standard of care in the hospital setting. And so, as goes hospitalization, so will go remdesivir over time, and we think that’s going to be an important part of our ongoing business and our benefit to patients..

Our next question comes from the line of Carter Gould from Barclays..

I wanted to come back to Trodelvy but a little bit more from the commercial and strategic angle and wanted to -- just sort of the decision to triple the sales force at this point, ahead of TROPiCS-02, is that decision dependent upon positive data from TROPiCS-02, or could that potentially be revisited, depending on that outcome? And then, specifically around sort of what you’re seeing in -- with the sales, it seems like the growth on an absolute basis quarter-on-quarter does seem to be sort of slowing a bit.

Can you maybe just talk about how the real-world duration of use has maybe evolved, and if that’s sort of in line with what you saw in the studies -- in the pivotal studies? Thank you..

Thanks, Carter. Right over to Johanna, please..

Sure, Carter. Thanks for the question. Just a couple of things. One is the footprint, the geographic footprint that we’ve just initiated and that ramp-up and the tripling. It has really maybe three objectives. One is to further support our initial launches of both metastatic TNBC triple-negative breast cancer as well as bladder.

So, that’s definitely number one, and that is here and now. the potential to support a potential indication in HR positive, which is what you were referring to. And the third one is also setting up for the future success of our total oncology portfolio.

So, assuming positive data, of course, is what we’ve decided to go for, but having said that, even if that didn’t play out, this is the right team for the future for Gilead Oncology. So that was the first part of your question.

The second part of your question about the growth slowing, I actually think we’re quite pleased, actually, as we got into Q4, what we’ve seen is the share really drive up post NCCN breast guidelines update in September. And so, we had good data point of share.

The last data point we have is October, and that’s the 1 in 4 that you heard me talk about earlier. And so, that’s doubling from where we were in April. So, we were at about half of that share in second line. And now we’re at about 24%, 25% share in second line. So, a real nice growth on that front and definitely more to come.

I think there’s an incredible opportunity for Trodelvy in this patient setting, especially with the high unmet medical need and the incredible OS data that we have with Trodelvy. So more to come on that..

Terrific. Thank you so much, Carter. We can take one last question, everybody. Thank you..

Thank you. Our last question comes from the line of Matthew Harrison from Morgan Stanley..

Just one clarification and one question. So, for Merdad, can you just clarify, it was unclear to me from your comments whether the FDA had asked for the OS data, and that’s why you were including this interim now for the filing or if that had been your plan all along. So, if you could just clarify that would be great.

And then, second, any comments you can make specifically around the stocking tailwind as well as the gross to net tailwind that you have from HIV in the fourth quarter? Thanks..

Thanks a lot, Matthew. We’ll go to Merdad and then Johanna..

Yes, very quickly. I think as I mentioned, we did upsize the study last year for OS because we’ve always believed, especially in HR-positive that having OS data are going to be important to support a file. It’s not the primary endpoint, and we think it’s going to be important supportive data to go.

So, that didn’t really have much to do with this confluence of events here. It’s a fortuitous event in terms of timing here that will support our data. So hopefully, that answers....

The FDA did not ask for it..

The FDA didn’t specifically ask us for it. No. It’s always -- we’re always going to take a look at OS with the first PFS data cut at this point in order -- instead of doing a look and then an interim, we’re just going to do the PFS and the interim at the same time..

Thanks, Matthew.

Johanna?.

And Matthew, the second part of your question around the Q4 piece of the puzzle. So, as you well know, right, as you go into Q4, you usually have a bit of a seasonal inventory build in the subchannel play. And then, of course, that bleeds out in Q1. So, that’s one piece of the puzzle.

In Q1, the other difference is, of course, you increased your co-pay support, your donut hole coverage and so all those pieces and your payer mix kind of changes in your first quarter.

Having said that, in addition to that, there was some favorability in Q4 of 2021 from a gross-to-net standpoint, which will then create an even bigger kind of decline in Q1, and that’s what we were referring to. So, hopefully, that helps a little bit. It’s a onetime thing in Q4.

And it’s just more around the comparison versus Q1 over Q4 as we get through the first quarter, and that’s what I was trying to signal..

Great, Matthew. And I just want to, before I turn it over to Jacquie, thank all of you for joining from our perspective. We are really excited about the build that we’ve had at Gilead over the past two years and the team and the people that we have on board.

We’ve got a lot to do this year, and we’re really teed up for a good strong year and a strong decade ahead with this portfolio. With that, Jacquie, over to you, please..

Thank you, Dan, and thanks to our operator, Gigi, for your help today, and indeed to all of you for joining us. We appreciate your continued interest in Gilead and hope that you can join us for our Virology Deep Dive scheduled for Thursday, the 17th of February. Thank you..

This concludes today’s conference call. Thank you for participating. You may now disconnect..