Good day, everyone, and welcome to Pfizer's fourth quarter 2020 earnings conference call. Today's call is being recorded. At this time, I would like to turn the call over to Mr. Chuck Triano, Senior Vice President of Investor Relations. Please go ahead, sir. Thank you, operator. Good morning, everyone, and thanks for joining us today to review Pfizer's fourth quarter and full year 2020 financial results, our 2021 financial guidance, as well as other relevant business topics. I'm joined today, as usual, by our Chairman and CEO, Dr. Albert Bourla; Frank D'Amelio, our CFO; Mikael Dolsten, President of Worldwide Research, Development and Medical; Angela Hwang, Group President, Biopharmaceuticals Group; John Young, our Chief Business Officer; and Doug Lankler, General Counsel. The slides that will be presented on this call were posted to our website earlier this morning and are available at pfizer.com/investors. You'll see here on slide three our disclaimer regarding forward-looking statements we will make during this call regarding, among other topics, our anticipated future operating and financial performance, business plans and prospects, and expectations for our product pipeline and in-line products, which of course are subject to risks and uncertainties. In addition, we'll be using non-GAAP financial information. Additional information regarding forward-looking statements and our non-GAAP financial measures is available in our earnings release, including under the disclosure notice section and under risk factors in our SEC forms 10-K and 10-Q. The forward-looking statements on this call speak only as of the original date of this call, and we undertake no obligation to update or revise any of the statements. Albert and Frank will now make prepared remarks, and then we will move to a question and answer session. With that, I'll now turn the call over to Albert Bourla. Albert? Thank you, Chuck, good morning, everyone. 2020 was a year like none other in Pfizer's history. With the separation of Upjohn complete, we saw the culmination of Pfizer's decade-long conversion into a pure-play science innovation-focused company. Through our collaboration with BioNTech, we delivered the world's first breakthrough COVID-19 vaccine in less than a year. By harnessing the power of a variety of digital capabilities, we made sure that despite the lockdowns and travel restrictions, we continue to serve patients around the world who rely on our medicines and vaccines. Despite this challenging environment and the incredible amount of resources we devoted to develop a safe and effective COVID-19 vaccine, we generated 8% operational revenue growth for the year from our core biopharmaceutical product portfolio, excluding the revenue impact from consumer healthcare and excluding $154 million in sales of the Pfizer-BioNTech COVID-19 vaccine that were recorded in the first quarter. Keep in mind that this 8% operation growth includes a negative 2% impact due to the slowdown in macroeconomic and healthcare activity resulting from the pandemic. This operational growth was driven primarily by continued strong performances from VYNDAQEL, VYNDAMAX, ELIQUIS, oncology biosimilars, eye brands, Prevnar 13 outside the U.S., INLYTA, XELJANZ, and XTANDI. Basically, all the growth drivers contribute significantly. Full-year adjusted diluted EPS was $2.22, up to 90% operationally from 2019. I would like to point out that revenues and expenses associated with the Upjohn business have been recategorized as discontinued operations and excluded from our adjusted results. Overall, we've had a strong year, which positions us well as we begin to operate as one global focused biopharmaceutical company, which I have envisioned for the past several years. Let me start with a discussion of some of our key growth drivers. VYNDAQEL and VYNDAMAX generated revenues of $1.3 billion in 2020, up 170% operationally. Our disease education efforts continued to support appropriate diagnosis, increasing diagnosis rate to move the 21% at the end of the fourth quarter as compared with approximately 2% before we launched, from 2% to 21%. As of December 31st, more than 20,500 patients have been diagnosed, more than 4,500 patients have received prescription, and more than 8,500 patients have received the drug, including patients who receive the drug at no cost through our patient assistance programs. We continue to see a recovery in new diagnosis since Q3 and the gradual rebound in new patient starts. With the current resurgence of COVID-19, however, we are seeing varying levels of regional lockdowns that could impact this recovery. ELIQUIS delivered another strong performance in 2020, with revenues up 18% operationally to $4.9 billion for the year. In the U.S., strong volume growth was partially offset by a lower net price due to an increased number of lives in the Medicare coverage gap and the expansion of that gap, as well as unfavorable channel mix. Revenues from our global biosimilars product portfolio grew 68% operationally and totaled approximately $1.5 billion for the full year 2020, making them a meaningful contributor to our growth. This was driven primarily by our oncology biosimilars, which grew 203% operationally, generating revenue of $866 million. Global IBRANCE revenue increased 9% operationally to $5.4 billion in 2020. IBRANCE continues to be a leader in the CDK4/6 inhibitor class for metastatic breast cancer. In fact, eight out of 10 first-line HR-positive, HER2-negative metastatic breast cancer patients in the U.S. who are prescribed a CDK4/6 inhibitor receive IBRANCE. This is a testament to the continued benefit IBRANCE delivers to patients with its compelling safety and efficacy profile. Based on the continued strong prescribing patterns, IBRANCE compelling safety and efficacy profile, and more than five years of use in everyday clinical practice with continued positive patients and physician experiences, we remain confident in its future performance of the metastatic setting. Global Prevnar 13 revenues were up 1% operationally to $5.9 billion in 2020. Revenues outside the U.S. grew 13% operationally in 2020, driven primarily by increased adult uptake in certain international markets, resulting from greater vaccine awareness arising from the COVID-19 pandemic. I should note that Prevnar 13 is indicated for the prevention of pneumonia resulting from pneumococcal bacteria, not SARS-CoV-2. Strong pediatric uptake in China also contributed to this growth. ELIQUIS had a strong 2020 performance, growing revenues 66% operationally. For the full year 2020, global XELJANZ revenue grew 9% operationally to $2.4 billion. The underlying prescription demand in the U.S. grew 12% in 2020 compared with 2019, outpacing the advanced therapy market by 9%. We have invested in formulary access in the U.S., which played a vital role in enabling this volume growth. Last week, we reported top-line data from a post-marketing safety study which did not meet the non-inferiority criteria for the co-primary endpoint of MACE and malignancies, excluding non-melanoma skin cancer versus TNFi. We are continuing to analyze the secondary endpoints of the study and will discuss the full data set as well as the potential implications to labeling with the regulatory agents. At this point, it is premature to make an assessment as to what impact this data may have on Xeljanz, of course, patient safety remains our priority. For XTANDI, Alliance revenues for the U.S. were up 22% for the year, and when combined with our royalty income from ex-U.S. sales, totaled $1.4 billion. XTANDI new patient starts grew 12%, bolstered by the successful launch of the metastatic castration-sensitive indication, which is helping patients earlier in their disease who will benefit from a longer duration of therapy. Of course, the biggest story of 2020 for Pfizer was our work with BioNTech to develop and deliver the world's first COVID-19 vaccine authorized for use in developed markets. It took us just 248 days to get from the day we announced our plans to collaborate with BioNTech to the day we submitted to the FDA for emergency use authorization. I couldn't be more proud of how our colleagues stepped up when the world needed us the most. Our ability to move at such extraordinary speed while always maintaining our focus on quality and safety, was the first powerful display of what the new Pfizer is capable of. While we never imagined a pandemic of this magnitude, every action we have taken over the past several years has been to transform Pfizer into an agile scientific powerhouse capable of addressing the world's most devastating diseases, like the one that happened now. The manufacturing and distribution of our COVID-19 vaccine have done very well as well. Not only did we achieve our commitment for 2020, but as of January 31st, we had supplied 65 million doses globally, of which 29 million doses were supplied to the U.S. government. We are continuing to work closely with the U.S. government on our production, release, and shipping schedules to help states ensure Americans receive their first and second doses of the vaccine on time. We have provided the government with a specific forward-looking schedule so they can plan accordingly. We foresee no issues with delivering the commitments we have made and expect to deliver 200 million doses to the U.S. by end of May, two months earlier than our contractual obligation. Because of the dire need to vaccinate more people, we have explored innovative plans to increase the number of doses we are able to produce globally by the end of 2021. As a result, we now believe that we can potentially deliver at least two billion doses in total by the end of 2021. This is based on the updated six-dose label, continuous progress improvements, and expansion at our current facilities, contingent upon adding more suppliers as well as contract manufacturers. We are now approaching one year since the beginning of the pandemic. Based on what we have seen so far, we believe it is increasingly likely that a durable COVID-19 vaccine revenue stream, like is happening in flu, is a potential outcome for two reasons. First, there likely will be a need to boost regularly to maintain high levels of vaccine-elicited immune response. Second, maybe more important, we may need to boost to counter the threat of the emerging mutant strains we have seen with variations in the spike receptor binding domain site. Genetic mutations occur naturally during virus replication and spread. We recently announced results of in vitro studies that show that sera from people who have received our COVID-19 vaccine effectively neutralize a pseudovirus bearing the SARS-CoV-2 U.K. variant spike, and also neutralize engineered SARS-CoV-2s with key mutations from South Africa variant and U.K. variant spikes. We are encouraged by these early in vitro study findings and will continue to monitor our vaccine's effectiveness in preventing COVID-19 caused by the virus strains in circulation. We are awaiting data on neutralization of an engineered SARS-CoV-2 with a full set of mutations from the spike of the South African variant. That said, there is an increasingly probable scenario when it could become necessary within the next two years to boost COVID-19 vaccinated patients with a vaccine encoding a spike variant. One of the reasons Pfizer and BioNTech chose to utilize an mRNA platform is because of the potential for the flexibility of the technology in comparison to traditional vaccine technologies. This flexibility includes the ability to alter the RNA sequence in the vaccine to potentially address new strains of the virus if one ever were to emerge that it is not covered by the current vaccine. Of course, this requires additional development work and regulatory submissions and approvals. Pfizer and BioNTech are preparing for such a possible scenario by working closely with regulatory agencies as well as relevant scientific bodies to enable vaccine technical committees to review data and make appropriate updates to recommendations. Regarding other applications of the mRNA platform, we are advancing plans to deploy this technology for flu vaccines and may explore other opportunities to work on other viral diseases and other therapeutic applications outside infectious diseases. Turning now to our 2021 guidance. I want to share just a few thoughts, as Frank will go into more detail. The midpoint of our 2020 revenue guidance range reflects 6% operational growth compared to 2020 if you exclude completely the impact of our COVID-19 vaccine. While there are signs that COVID-19 may be here for some time, which could result, as I said, in a more recurring revenue stream, we are carving out the COVID-19 vaccine's revenue for now. Frank will provide some context on both our anticipated COVID-19 revenue and margins in his remarks. While the COVID-19 vaccine has created a new cash flow stream, there is no change in our capital allocation priorities. We remain focused on growth initiatives and a growing dividend, though at a slower rate. Now let's turn to the pipeline, which is the engine for the new Pfizer and continues to be one of our great strengths. As discussed during last September's Investor Day meetings, we still see unappreciated potential in our pipeline, particularly in our rare disease, vaccine, and internal medicines R&D portfolios. I would like to start with highlighting the incredible improvements we have driven in our clinical success rates and how they compare with industry benchmarks. Between 2015 and 2020, our Phase II success rates on a five-year rolling average more than tripled from 15% to 52%, which is almost double the 2019 industry benchmark of 29%. Significantly, most of these successes are either first-in-class assets with innovations built on established mechanisms with novel scientific designs. Our Phase III success rate on a five-year rolling average improved from 70% to 85%, 13 points higher than the 2019 industry benchmark of 72%. Our end-to-end success rate more than quadrupled from 5% to 21%, almost triple the 2019 industry benchmark of 8%. I would also point out that while our phase I success rates on a three-year rolling average stayed flat at 48%, this is eight points higher than the 2019 industry benchmark. We believe these metrics demonstrate that through our science, we are selecting assets to move through the research and development process that have the best chance of benefiting patients. This did not happen by accident, but was a result of a purposeful R&D turnaround strategy that we began in 2011. We aim to sustain the success rates, which we believe clearly demonstrate the value of our pipeline. In rare diseases, we achieved two phase III study starts since our last earnings call. On November 23rd, we announced the third participant has been dosed in the phase III BASIS study of marstacimab, an anti-tissue factor pathway inhibitor being evaluated for the treatment of people with severe hemophilia A or B. On January 7th, we announced we had dosed the first participant in our phase III Duchenne muscular dystrophy gene therapy program. The CIFFREO trial is expected to enroll 99 ambulatory male patients, ages four through seven, across 55 clinical trial sites in 15 countries. Our DMD program is the first gene therapy to start the phase III trial with a potential first and best-in-class profile. In inflammation, our unique ritlecitinib, the JAK3/TEC selective oral small molecule, has reported positive top-line results in two phase II studies, one for vitiligo and one demonstrating strong clinical remission rates in ulcerative colitis. Data from both studies will be presented in scientific congresses later this year. Last October, we announced FDA and EMA filing acceptance of our applications for ritlecitinib in patients with moderate to severe atopic dermatitis with a priority review PDUFA date for the FDA in April. There is a large unmet medical need here. Many of the 60 million patients are not well controlled on current therapy or are simply untreated, and we see an attractive opportunity to capture many of these patients. In other words, we are not just looking to convert existing patients from other therapies. In vaccines, the FDA has accepted for priority review the Biologic License Application for our investigational 20-valent pneumococcal conjugate vaccine for adults 18 years of age and older with a PDUFA date expected in June. If approved, we believe the vaccine could provide the most comprehensive coverage against pneumococcal disease in adults compared with the standard of care and other pneumococcal conjugate vaccines in late-stage clinical development. In internal medicine, we are progressing potentially novel treatments that address underlying causes of metabolic diseases and cardiovascular risk. We initiated a phase II-B clinical trial to evaluate repaglinide for the potential to reduce cardiovascular risk and treat severe hypertriglyceridemia. Our phase II diabetes trial for our oral GLP-1 class is enrolling rapidly, and we expect to initiate a phase II trial for obesity shortly. We expect a proof of concept readout in the third quarter of this year, which will inform the next step, the potential pivotal phase III program. In oncology, we recorded robust response rates for BRAFTOVI in the phase II ANCHOR first-line colorectal cancer study and have initiated a phase III pivotal trial. We also achieved a positive readout for talazoparib in DDR plus metastatic castration-resistant prostate cancer in the phase II TALAPRO-1 trial, which gives us increased confidence for a potential positive outcome of the pivotal phase III TALAPRO-2 trial, which has an expected readout for all comers in 2021 and subsequently for the DDR plus subset of patients. We are very excited about elranatamab, our investigational BCMA CD3-targeted bispecific antibody for the treatment of multiple myeloma. In December, we presented encouraging data from our ongoing phase I trial that demonstrated high response rates and manageable safety in patients with relapsed or refractory multiple myeloma, including a few patients who relapsed on or progressed after prior BCMA-targeted therapies. In late January, elranatamab received fast-track designation for treatment of patients with multiple myeloma who are refractory to at least one proteasome inhibitor, one immunomodulatory drug, and one anti-CD38 antibody. We recently initiated the potential registration-enabling phase II trial of elranatamab monotherapy in triple-class refractory multiple myeloma. We anticipate the first patient to be dosed this month. As you can see, tremendous activity. Before I close, I want to say a few words about affordability. As we have said, our breakthrough medicines and vaccines won't do anyone any good if people can't affordably access them. We believe the industry has generated a great deal of goodwill with Congress and public opinion through our COVID-19 treatment and vaccine efforts. We hope we can build on this goodwill by working together on a solution, including making a contribution as an industry through legislation or executive action that results in lower out-of-pocket costs to patients. The status quo simply won't cut it. We look forward to working with the Biden administration and members of Congress from both sides of the aisle to help ensure our breakthroughs are accessible to all. In summary, 2020 was a transformational and very successful year for our company. We look forward to sustaining this momentum in 2021 and beyond. We remain focused on being nimble and investing in our R&D organization so we can build on the strong improvements in key metrics we have seen over the past five years. We continue to expect a revenue CAGR of at least 6% on a risk-adjusted basis through the end of 2025 and double-digit growth on the bottom line. I would note that these projections do not include any potential impact from our COVID-19 vaccine. We remain very confident in our ability to achieve these growth rates because of the strength of both our current product portfolio and our R&D pipeline. At the same time, we will continue to pursue business development opportunities with the potential to enhance our long-term growth prospects post 2025. We will focus mainly on smaller deals that fit within our current therapeutic areas, and as always, we are focused on value generation for Pfizer shareholders, not those of potential acquisition targets. Now I will turn it over to Frank to provide details on the quarter and our outlook for the remainder of 2021. Frank. Thanks, Albert. Good day, everyone. I know you've seen our release, so let me provide a few highlights regarding the financials. We again saw very solid revenue growth for the business in the quarter and the year, which continues to support our projected 6%+ revenue CAGR through the end of 2025. As a reminder, this growth projection excludes any contribution from the COVID vaccine. In terms of the price and volume mix for the year, if I go up of the 8% operational growth we posted, excluding consumer healthcare and the COVID vaccine, our underlying biopharmaceuticals portfolio generated 10% volume growth, offset by a negative 2% price impact. Continued very strong volume overall. Foreign exchange had a slightly positive impact on revenue in the quarter, with a 1% benefit for the full year. While for the full year, we saw an overall negative impact of 1%. 1% positive for the quarter, 1% negative for the full year. Moving down the income statement. Adjusted gross margins were lower in the quarter, mainly due to the negative impact of foreign exchange, product mix, an unfavorable year-over-year impact of cash flow hedging on inventory, and COVID-related expenses. It's important to note that on an annual basis, adjusted gross margin for 2020 was within 90 basis points of 2019 at around 80%. Adjusted SI&A expenses in the quarter were lower by 2% on an operational basis and lower by 10% on an annual basis. There remain two main factors that drive the decrease for the year: the exclusion of consumer health and lower selling expenses due to COVID, and to a lesser extent, the early implementation of a planned reduction in spending associated with our corporate enabling functions. Adjusted R&D expenses grew 24% in the quarter and 15% for the year on an operational basis. This growth was primarily driven by our investment in developing the COVID-19 vaccine. Reported diluted EPS for the quarter was up significantly compared to the prior year quarter, mainly driven by lower asset impairment charges compared to the year-ago quarter. For the year, reported earnings were lower, mainly due to the non-recurrence of the gain on the consumer joint venture formation in 2019. Adjusted diluted EPS grew 17% for the quarter and 20% for the year on an operational basis. I'd add that our full-year adjusted diluted EPS was $2.22, which is below the range of $2.28-$2.38 we had given in terms of new Pfizer financials on a full-year basis. Just want to remind you that we had indicated on last quarter's earnings call that our actual reported numbers would be lower than the guidance, because the guidance assumed a full year of operating without Upjohn, as well as assuming a full-year benefit of transitional service agreement recoveries and lower interest expenses from the deployment of the $12 billion in proceeds to pay down debt. With the deal not closing until November, we only had a small benefit from these factors in our reported 2020 financials. Now let's move to our 2021 guidance. We've provided total company guidance, which includes the COVID vaccine, and then we've provided some additional sub-ledger detail on our assumptions regarding the projected COVID vaccine contribution, so you can also get a read on the business out. In terms of revenue, we are projecting a range of $59.4 billion-$61.4 billion, which includes a foreign exchange benefit of approximately $1.4 billion and at the guidance range midpoint represents operational growth of 41% from 2020. For adjusted COGS, the range is 32%-33% as a percentage of revenue, which incorporates the COVID vaccine gross profit share payment to BioNTech, as well as some other related items that we'll speak to in a moment. On our SI&A, what we see is the impact of increased sales and marketing expense behind key growth brands, as well as for expected product launches by our enabling function cost savings. In addition, we see growth in R&D, which follows along with our pipeline development cadence. I note, given our clinical trial success metrics Albert referenced, we're confident about making sound R&D investments. Adjusted other income or deductions is projected at just over $2 billion of income. In addition to the usual items included here, I remind you for modeling purpose that 3 larger items in terms of income are our GSK consumer healthcare joint venture equity income, ViiV dividend income, and transition service agreement recoveries primarily related to ViiV Healthcare. Working this through with our projected 15% tax rate yields an adjusted diluted EPS range of $3.10-$3.20 or 38% operational growth at the midpoint. This range is a bit higher than what we discussed three weeks ago. It was driven mainly by an increase in our COVID vaccine sales projections since then. Let me offer some assumptions and context on the projected COVID vaccine financial contribution and our collaboration agreement. The Pfizer-BioNTech vaccine collaboration construct is a 50/50 gross profit split. Pfizer will book the vast majority of the global collaboration revenue, except for Germany and Turkey, and we do not participate in China. We continue to expect that we can manufacture up to 2 billion doses in 2021. However, given it is still early in the year, we are not projecting that we will sell all those doses. Ultimately, we may contract for all the doses, but for the purposes for our initial guidance, we primarily included doses that are covered by strong supply agreements with various governments. From this, we currently forecast approximately $15 billion in COVID vaccine revenue, which is what you see here. Given we remain in negotiations for additional contracts, we are not providing the number of doses behind the revenue estimate. Our cost of sales for the COVID vaccine revenue will include manufacturing and distribution costs, a royalty payment allowance, as well as the payment to BioNTech, representing the 50% gross profit split. All in, this yields an anticipated income before tax COVID vaccine in the high 20% range. Let me add that if we contract for the delivery of additional doses during the year, we'll provide a guidance update in our subsequent earnings releases. If we remove the projected COVID vaccine contribution and related impacts on revenue, that results in our business having 2021 projected annual revenue between $44.4 and $46.6 billion. 6% operational revenue growth at the midpoint and about 8% if we include the current favorable impact of foreign exchange compared to last year. In terms of adjusted cost of goods, net of the COVID vaccine, we see a range between 21% and 22% as a percentage of revenues. For adjusted diluted EPS, we see a range of $2.50-$2.60, which represents 11% operational growth at the midpoint. These growth rates are all consistent with how we've been publicly positioning the business subsequent to the Upjohn separation. In terms of reporting our quarterly earnings, we are not going to report two sets of financials, one with COVID and one without, I think the context in terms of the vaccine margins will be helpful in calculating a good estimate of the adjusted diluted EPS impact based on the COVID vaccine revenue we will report in future earnings releases. Let me speak for a moment about our dividend going forward and how it will initially be linked to the ViiV Healthcare dividend once it is declared. To make it simple, let's start with Pfizer's current annualized dividend rate of $1.56 per share. A Pfizer shareholder owning 100 shares just prior to the spin-off would now still own their 100 shares of Pfizer and also 12 shares of ViiV Healthcare, assuming they have continued to hold the ViiV Healthcare shares. The 100 shares of Pfizer would generate $156 in annual dividend income, and currently, the 12 shares of ViiV Healthcare do not generate any dividend income. This $156 in annual dividend income is what we will preserve. Once ViiV Healthcare declares its dividend, we will calculate the annual income generated by the 12 shares of ViiV Healthcare and then adjust the Pfizer dividend so the combined annual income generated from the 100 shares of Pfizer and 12 shares of ViiV Healthcare totals at least that $156 in 2021. For the foreseeable future, we expect our board to continue to support annual dividend increases at approximately this year's level. Obviously, we have no say as to what ViiV Healthcare does with its future dividend. I hope this example is helpful. In summary, we had a strong 2020. The separation of Upjohn is behind us. The business is on track for solid top and bottom-line growth, and we are highly focused on advancing our pipeline, supporting in-market brands, and looking to deploy capital responsibly with a focus on initiatives that can solidify our long-term revenue and earnings growth. With that, I'll turn it back to Chuck. Great. Thank you, Frank and Albert, for the prepared remarks. Operator, at this point, can we please poll for questions? Thank you. Your first question comes from the line of David Risinger from Morgan Stanley. Thanks very much. First of all, congrats on the phenomenal vaccine progress and the benefits that Pfizer is driving for society. That's much appreciated by everyone on this call and beyond. My two questions relate to vaccine prospects and Xeljanz. First, could you speak to how you are projecting vaccine sales for David, unfortunately, you are cutting off, and I couldn't hear you. Can you repeat the question of the vaccine from the beginning? The question is, with respect to the vaccine. Unfortunately, the line is not good, David. We can't hear you. Maybe Dave, you can come back in. Operator, can we move to the next question? Your next question comes from the line of Steve Scala from Cowen. Thank you. I have two questions. In what scenarios would you not sell all 2 billion doses of COVID vaccine Pfizer can manufacture in 2021? Some competitors haven't exactly exceeded expectations, and only a small fraction of global demand has been satisfied to date. It seems as though you'll sell every dose you make, and that the current guidance is going to be way low. Second question is, on the XELJANZ CV study, should we assume VTE tracked similarly to MACE? Given that Pfizer has other JAKs in development, what do you believe are the long-term implications for the JAK class overall, given this recent XELJANZ CV study? Thank you, Steve. Let me take the COVID one, and then I will ask Michael to comment on the XELJANZ first part, and then Angela on the implications from commercial. Steve, we try not to give a low expectation. We try to give a responsible expectation. If you are asking if there is a scenario that we will sell everything? Yes, there is. Also, I would tell you that if that was an open market, which means that physicians and citizens, they have the ability to choose which vaccine they will receive, I would feel very comfortable that we will have the lion market share because we are first, and we are best, as you have clearly indicated, and we have great operations in basically every country in the world. This is not an open market, at least for this year. This year, it is a market that it is controlled by governments appropriately because I think we are in a crisis, as you know. Also it is a market that creates a lot of political pressure, so not always the decisions are sound, solid, and avoiding panic. With that in mind, we have a formula that we try to implement in a responsible way that takes into consideration the contracts that we have, the potential for future contracts, but also takes into consideration the strength of the contracts, takes into consideration the potential for other vaccines to present data. In fact, the reason why we changed our revenue projections, which resulted in $0.10 improvement in our bottom line, it is because we did have more news from the AstraZeneca registration and the way that it is perceived in Europe. We had the news from the Dane data, reported data. We have much better visibility now in the last two weeks on their manufacturing capabilities. All of that resulted in us increasing our projections. Clearly, there are a lot. This is a multidimensional and, let's say, challenge to have accurate projections. Clearly, we are having dynamic changes, which we will follow, and we will update our estimates as time comes. In all honesty, I couldn't responsibly just say right out, we are going to sell everything we can make, the $2 billion, when I have all this dynamic situation that it is evolving. Why don't we move to Mikael to talk a little bit about the MACE on XELJANZ, and then Angela on the revenues expectations. Yeah. Thank you, Albert, and Steve, for the question. As you know, the 1133 study for Xeljanz was a rather unique population with increased CV risk. Xeljanz has been studied in numerous clinical trial and in the market, where a large population have used it in a more general RA population or in ulcerative colitis. In those populations, it has had a very robust efficacy to safety profile. I think RA by itself has more CV liabilities than standard RA patients, and this was a very specific subset. Going to other JAK inhibitors, the next generation of JAK inhibitors, such as abrocitinib in registration for atopic dermatitis, or as Albert reported, ritlecitinib, which is a unique JAK3 TEC inhibitor. Each JAK inhibitor differs by itself. We think both of these two that I mentioned have very encouraging benefit to risk profile. While regulatory agencies have in some instances inferred a general class label across JAKs, I think the experience will tell that abrocitinib for atopic dermatitis has a very compelling efficacy and risk profile, and ritlecitinib for alopecia that's reading out later this year, or for vitiligo and also sclerosis, where we have very encouraging phase II data, again, has a unique profile. I don't think that we should extend 1133 to other JAKs, and I think we also need to look at Xeljanz having a very robust profile in populations that was not a smaller version of the 1133 study. Thank you very much. Thanks, Mikael. Just building off of what Mikael has said, as you know, we have a very robust data set that has been built around Xeljanz for over seven years, 50 different clinical trials, 260,000 patients that are currently on Xeljanz. Of course, a very robust real-world data set that goes along with these 260,000 patients. I think based on all of this, and together with the fact that we are still so early on in our understanding of the A3921133 data as it pertains to Xeljanz, that we feel confident that Xeljanz will remain an important part of the treatment paradigm for RA patients and for patients with PsA and UC as well, and that it has an appropriate and favorable benefit risk profile for this sort of patient population type. Of course, we will share the data with you as we continue to learn more about the study. For now, that's how we feel. I think you had one more question in terms of how do we think about this in terms of impact on our other JAKs. As Mikael said, scientifically, each one of these molecules are very different, and they're all being designed with a different benefit risk profile to match the different disease condition as well as the different patient types. I think, as a result, we continue to be very confident about our JAK portfolio and the investments that we're making in each one of these. We think that what we will be able to deliver are differentiated profiles that will be appropriate and fit for purpose for that condition and for that patient type. Thank you. All right. Thanks for the responses. Next question, please, operator. Your next question comes from the line of Gregg Gilbert from Truist Securities. Thank you. Albert, it seems pretty clear that Pfizer, the stock anyway, is not getting a whole lot of credit for the COVID-19 vaccine. Whether or not you agree that that's fair, I'm curious how you expect to leverage the expertise you've built in this area into areas that investors might view as contributing more to long-term franchise value, regardless of what happens to the COVID-19 part of the story. Then a second vaccine-related question, perhaps for Angela. There's been a lot of focus on your vaccine and others about logistics and supply and coverage of variants. It seems to me that at some point, a key metric, if not the most important metric, will be how many people want to get a vaccine. Curious what your work tells you on that front and whether you plan to get involved as a company in helping drive awareness and demand at some point, or is that not really Pfizer's role to play? Thank you. Gregg, thank you very much. I fully agree with you that I don't think we're receiving a lot of credit, not for the vaccines right now when you see the stock price, but mainly for our basic business and pipeline. This is a business that is growing 6% in double digits. The bottom line, excluding any COVID, clearly deserves much, much higher multiple in this industry. The same comes even more when we speak about the COVID-19 vaccine, I think clearly, people should see much more into that. To your question, how do we plan to use strategically this platform? I believe that the RNA technology has been proven in a glorious way that will have an impact in treating diseases, in preventing diseases in multiple applications. I believe Pfizer has accumulated expertise and knowledge of a decade into one year. Also Pfizer has completed infrastructure investments that will take five years, again into one year. Clearly we plan to use this expertise so that we will be able to benefit more and more patients. I made some comments that within the COVID vaccine, I believe that the dynamics in the COVID more and more indicate the potential that we will have a clearly repeated business. The reasons for that are multiple. Let me start by saying in the beginning, we were waiting to see if the immunity will be durable. We still don't have data about the immunity of our vaccine because it is early, but we do see that the people that have the disease, more and more publications indicate that after several months, their immune response goes down, so there is a need to boost. There are a lot of papers that have been published that indicate even for the new variants. If you have very high level of immune responses, you are protecting against those variants in much higher level than if you have lower levels of these antibodies. That indicates that the need to boost or that you maintain much higher levels is there. Last but not least, it is clear that the scenario that the variants will develop in such a way that they may be escaping very effective protection from the current vaccine, which is not the case right now for us. We will clearly preparing ourselves so that we will produce in a very speedy time and make publicly a statement that needs to be done end-to-end in less than 100 days to provide new booster vaccines that will protect against the new variant. In scenarios like that, and even in scenarios that the COVID will move from a pandemic into more of a normal type of vaccination business, it is very clear that Pfizer will have a key advantage, not only because of the strength of the data, but also because we have developed significant brand equity and trust with the people when it comes to their choice. We have infrastructure and expertise that will help us. RNA is not going to provide only COVID-19 vaccines. We are accelerating our work for flu right now, we are clearly investigating multiple other applications in other vaccines for this RNA technology or therapeutic areas. I believe that our business, excluding COVID, is very robust with robust pipeline. I think COVID has a very good chance that could completely transform the revenue and earnings trajectory of this business starting from now. With that, I will ask Angela to comment on the question about, again, the COVID vaccine. Angela. Thanks for the question. I think what you're talking about is vaccine confidence, which clearly has been a big topic since the vaccine was introduced. I'm actually really encouraged by data that we're receiving on a routine basis that is demonstrating that vaccine confidence is indeed building, and that compared to where we were even a month ago, we've had a significant rise in interest and willingness of the public to get vaccinated. I think a lot of this is driven, obviously, by real-world experience by many people who are now getting the vaccine and having good experiences with them. I think that this will continue. To your question about what is it that we're doing to drive awareness and demand, I think, first of all, we have to understand that right now we are in a period where we are operating under an EUA, the emergency approval. There's guardrails as it pertains to that and what it is that we can do. For sure, we have worked very diligently with many medical and public health societies and institutions to ensure that we are supporting education across the entire country. There recently was even a public service announcement that was launched, where it had our support in conjunction with a number of patient advocacy groups to really educate and to create confidence for the public around this vaccine. In addition to that, at a more specific level, Pfizer uniquely has really supported the healthcare professional community in its vaccination by providing a lot of training, a lot of support to ensure that confidence is gained at the vaccinator site. Actually, just to share that over 30,000 HCPs have been trained by Pfizer alone in the recent month or so to be able to confidently vaccinate people. I think that that's also helping to create confidence. Of course, where we can get most involved and will be able to do even more is once we receive our BLA. We're working towards that, and we will build on the education initiatives that we already have in place, but we'll be able to amplify that even more once we have a full label. Thank you. Thanks, Angela. Good point on the BLA opening up more opportunities. Next question, please, operator. Your next question comes from the line of Terence Flynn with Goldman Sachs. Great. Thanks so much for taking the question, and thank you for all the work you're doing again on the COVID vaccine. I was just wondering, is there an integrated system that's being set up by either the government or governments or Pfizer to monitor instances of vaccine breakthroughs and conduct sequencing? Then what factors and who will ultimately dictate when a change in the potential of the vaccine is needed to cover an emerging variant? How does a consensus emerge on that question? Thank you. Yes. Mikael, would you like to take this question, please? Yeah. There are different organized at the government levels efforts in the U.S. deposition of sequences both to track new strains like the South African and Brazil. As well, among unvaccinated and vaccinated, are deposited in certain databases. There is one initiative in the U.K. Of course, Pfizer has a unique collaboration in real world evidence with the Israeli Ministers of Health, which will allow us to track first real world evidence for our vaccine in the population. As you may know, we are the number 1 to have such data that shows 92%-95% in real world evidence vaccine efficacy, primarily seen initially in an older population. That's harder normally to get this stunning data. It also showed a very low, 0.25, about, for both the 24 and 26 for first and second injection of adverse events. Really well-performing in a large population of millions of individuals. Of course, they will also track if there are breakthrough infections. Now, in general, I think it has been claimed that the South Africa and Brazil variants are more difficult to treat, and vaccines that have lower antibody levels will have much more breakthroughs. Given that the mRNA vaccines have very high antibody levels, and that was, I think, implied in Albert's answer. We expect them to be much more resistant to breakthroughs for longer time. I think data from several labs shows that if you maintain with mRNA vaccine high antibody levels, you will actually protect very well, even against those variants. That suggests, and we are just embarking on such studies, that you could boost with the current vaccine a further time and avoid some of these breakthrough infections that were reported recently in some vaccine studies. That would be our aspiration to demonstrate that by keeping individuals with very high titers, you can really impact, and that can be recorded as you ask in various systems that are now in place in many countries. That could be a very important way to transit into a more sustained protection, sustained business model, where the monitoring allow you to plan when the next boost should happen. Great. Thank you, Mike. Next question, please, operator. Your next question comes from the line of Louise Chen from Cantor. Hi. Thanks for taking my questions. My first question is, if the COVID vaccine becomes routine, how do you think governments and physicians will choose amongst these different vaccines that have received emergency use authorization? How do you think about that 95% efficacy rate in light of mutations? The last question is on your PCV20. If it's approved, what do you expect the ACIP recommendation to be, or what would you ideally like it to be? Do you think there will be any upgrade for those 65 plus due to the additional serotypes? Thank you. Thank you. Why don't we start with PCV20 and Angela, and then we can come back to COVID. Angela? Sure. In terms of PCV20, what we believe our value there is the additional serotypes. In the adults, these additional serotypes are meaningful because it will give us 33% more protection against strains causing IPD in adults and 42% more protection against strains causing IPD for pediatrics. We feel that this is very value creating and provides us the opportunity to really bring an important option into the market that is an upgrade compared to what it is that we have today. To your question about ACIP, of course, we're working closely with the FDA for approval and with the CDC at the right moments in time to get the right recommendation. We believe that the recommendation will be positive as it pertains to PCV20, and we look forward to working with them to achieve that. Thank you. As regards how people could choose or physicians could choose if that is a routine. I believe that if this is a routine, the decision will come as with all other vaccines and the medicines, the strength of the data. I think that this is why I made before the comments that are given that we are first, which means that we are vaccinating a lot of people right now with the first doses. Given that we have such a strong safety and efficacy database in an open choice situation, we would get the vast majority of the share of choices. That I think will come a reality likely after in 2022 when the governments do their whole vaccination scheme. Also in that year, there will be ample, I believe, capacity. Volume would not be a case even if everyone wants to get one vaccine, I think would be enough to make this one vaccine. What about the 95% efficacy in terms of variants? I think we answered that, but Mikael, maybe you want to reiterate once more why the higher the efficacy, the better is not only for the current but also for the variants. Yeah, very brief. It's clear from convalescent plasma studies that now the last couple of weeks been out, and also from plasma from vaccine recipient. Higher antibody levels seem to protect from variants in the preclinical studies from patients. I think it will project into the vaccines with high antibody levels and T-cell immunity, which are an additional protection mechanism, will do very well against variants, and keep boosting them will keep the variants off the population for a longer time before there's any need to shift to a variant-selective. I think the data we have with mRNA vaccine put them really in a unique category, having the strong immune response, the ability to boost, and ability to, if needed, reconfigure. Great. Thanks, Michael. Next question, please, operator. Your next question comes from the line of Umer Raffat from Evercore. Hi, guys. Thanks so much for taking my question. I want to hit up on two different topics. One, as we think about possible new vaccine for the new variants, do you guys have plans in place? Are you working on it right now? Should we anticipate some sort of phase I data by some point this early summer? Has there been a consideration to allocate some of this $2 billion in doses capacity to a new version of the vaccine? Separately, going back to the phase III you reported, it's been a few weeks, and one of the questions I've had is, of the patients that tested positive on the vaccine post dose 2, what did we learn about what mutations those patients had on deep sequencing? What did we learn about their nAb titers and T-cells? I wonder if there's anything we can draw on correlative protection. Thank you. Yeah. Umer, very good. Excellent questions. Mikael, do you want to take the last one and also the first one, and then I can speak then later on the manufacturing piece. With variants, we are embarking on a study which will give a boost after six months and possibly also compare with a 12-month boost. We'll compare the wild type, the current vaccine, with a variant vaccine, likely based on the E484 amino acid from Brazil and South Africa. I think that given the data is so strong with our vaccine, as we alluded to, may very well be that a third boost at the proper time point is sufficient, and we continue to monitor variants. We will be prepared, if needed, with data, as you said, around early summer. Quality protection is something we're working with a lot of scientists, not just looking at data in our trial, but in public consortium with NIH, looking at data across many trials. We will see the outcome. I expect, again, high antibody levels plus T-cell immunity will provide the best durability, and that makes us very optimistic about the unique profile of mRNA vaccine. Thank you, Michael. The 2 billion doses that we're speaking about, it is all clearly for this current vaccine. Clearly also we are working to see if we can improve that even further. Right now, we are at our commitment of 2 billion doses. The reason why we had selected mRNA in the first place was because it simplifies tremendously this type of process. Our ability with this technology to build a new construct of the same vaccine by just changing the messenger RNA within this vaccine, it is really a very simple process in terms of manufacturing and in terms of actually developing it. Now, nothing is simple in biology when we speak about high complicated processes, but relative to any other technology, this is very simple. I wouldn't say that I would anticipate a major, if we have to go to a new vaccine, that we will have a major shake up in our manufacturing capacity. I think overall, 2 billion doses could be maybe a little bit less if we start producing new vaccine, replace altogether the new variants. Altogether, cumulative, the new and the old, if there is a need to do the new. Great. Thanks, Albert. We'll take our next question, please. Your next question comes from the line of Geoffrey Porges from SVB Leerink. Thank you. Thank you very much. I unfortunately will continue a little bit on this theme. Mikael, could you give us a sense of whether you think the so-called South African, Brazilian variants that have similar mutations represent terminal or near terminal adaptation to the virus? Do you think that we will see sort of almost recurring and infinite adaptations that we may have to contemplate adapting vaccines to? Secondly, have you contemplated giving a single dose of vaccine to those who've previously been infected, given what's probably 20%-25% antibody positivity in the U.S. population? Lastly, could your next gen variant vaccine be refrigerator stable? Thanks. Michael? Yeah. Thank you. Yeah. The first strains, like the U.K. strain, was mainly selected for transmissibility to spread quickly. As there were previously infected people in South Africa and Brazil, the new strains have been selected for immune escape, which is the E484 amino acid is the most important. High antibody titers, as alluded to before, from our vaccine seems still to be able to react quite nicely with that strain, albeit somewhat more moderate reduction. We think keeping high titer up in patients will be a very good going forward approach until there is need for a strain change. Now with that concept, keep up high antibody titer, you should immunize whether you have had infection or not twice. That is your maximal titer and allow you to fight off variant strains for as long time as possible before you may need a boost or after some time that there may be any reason to a variant vaccine, as Albert alluded to. We are currently initiating study to understand when a third immunization would be helpful for participants. We will be studying six to 12 months as initial assumption. Of course, we continue to make efforts to make refrigerated-based vaccine that includes lyophilization or possible liquid with a stabilized product. We think end of this year or early next year, we'll have such a product. Excellent. Next question, please, operator. Your next question is from Vamil Divan, from Mizuho. Great. Thanks so much for taking the questions. Maybe I'll just shift gears a little bit off the vaccine. I guess somewhat tied to the vaccine, but a little different angle here. In terms of capital allocation, I think, Albert, I think you mentioned that they would change their strategy, but the vaccine obviously is going to give you a boost to your sales and cash flow, at least in the near term here. I'm just wondering, should we expect Pfizer to be maybe more active and complete more transactions in the coming months to try and boost your pipeline than you otherwise might have been? If not, I guess just maybe you sort of comment on your thoughts around this added cash flow and what you might look to do there. My second question is on VYNDAMAX, where looks like you are having pretty good traction there, maybe better than we thought given the pandemic. Just wondering if you can maybe comment, so where this product is now relative to where maybe you would have expected a year ago sort of pre-pandemic. I'm trying to get a sense, is there a real sort of bolus of patients or you could maybe make more traction with as the pandemic eases, or is you're already doing quite well in terms of gaining penetration into those patients now, so we should sort of expect the same sort of state of uptake going forward? Any thoughts would be helpful. Thank you. Thank you, Vamil, and thank you also for asking something outside COVID that is at least making the very interesting. You're right, the capital allocation, it is the result of a strategy. If anything, the COVID-19 is proving our strategy correct. It is, I think, a demonstration that we do have a research machine that has the resources of a big biopharma and the agility of a small biotech. I don't think that many people would bet that Pfizer would be the first one to complete something like that. This is what we are building in the last few years, and this is the demonstration that we are there. Our capital allocation, we never say never. Right now, the dividend will be maintained. Frank was very clear about it, a growing dividend. It is important thing, part of our investment thesis. We will continue in very intensive rhythms to try to bring in phase II, phase III predominantly programs that through our R&D machine very quickly and very successfully can become medicines and vaccines that could generate revenues that will fill the gap from the 6%, so we can sustain the 6% beyond 2025. Nothing changes. Also, we do have higher flexibility in terms of cash with COVID, clearly, but it is not that we were lacking cash before and we couldn't do basically things that we wanted to do. Now that makes it even more comfortable to do that. Still, I don't think because we have this comfort level, we will do things that do not respect the fact that this is our shareholders' money. We will invest them very prudently. We are not going to spend them. We are clearly ready to take risks when needed and also clearly ready to pay a full price for things that we really want. As I said before, we never say never. Angela, how do you see VYNDAMAX evolving? Was there a bolus? Is it something that you continue growing? What is your views on that? We have been really pleased with what we've seen with VYNDAQEL, VYNDAMAX and the patients that we've been able to diagnose. I think this has gone better than we thought, actually, even with the pandemic. Currently, this last quarter, we were able to diagnose 21% of the population with ATTR-CM. This increase that we're seeing quarter-over-quarter gives us a lot of confidence that our ability to diagnose and the imaging techniques that are being used, the non-invasive techniques, are working really well. I would say the bolus is gone. That was something that was maybe in the first half of the year when we launched. I think where we are now is in a pretty good cadence of using our suspect and detect techniques as well as the ability to refer to imaging centers to get the diagnosis, and I think that our success rate in diagnosis is evidence of this. I think we'll continue to see cadence like this. Of course, there's still massive opportunity 80% more patients still to be diagnosed. We're really focused now on using technologies and different techniques to heighten and to look and to screen more effectively for patients, because once we know that we can find them, they can get diagnosed. That's where our focus is going to continue to be in 2021. Great. Thank you, Angela and Albert, for those responses. Let's move to the next question, please. Your next question comes from Tim Anderson from Wolfe Research. Thank you. A couple of questions. On the mRNA platform, you talk about leveraging that technology in areas outside of a COVID vaccine, and I think you mentioned something like seasonal flu. I'm guessing timelines for any of those types of opportunities would be more normal, and I'm hoping you can give us some idea, just a rough timeline on when Pfizer and BioNTech might launch a non-COVID mRNA vaccine product, totally unrelated to COVID-19. I'm guessing that would be something like five years away at a minimum, but maybe you can shed some light on that. Then second question, just on guidance for 2021 and the other income line, the big number, $2.2 billion, very much above the normal run rate for that line item. You mentioned the consumer JV and ViiV and Viatris all going into that. Only brand-new piece there is Viatris. Can you just give us more details why that number goes so high in 2021? Importantly, what's the run rate for that line item beyond 2021? Thank you very much, Tim. Obviously, Frank will answer the second one and Mikael the first one. Let me also just make an introductory comment before I ask Mikael to speak about flu. I believe the COVID thing has created a new normal. I don't think we are aspiring here in Pfizer to go back in the old normal of developing timelines, even if we were, as you saw before, at the top of the industry benchmarks. Right? If COVID, why not with cancer? If COVID, why not with flu? I think that clearly with COVID, there was the collaboration of regulators that made that also possible, but it was a lot of other things that we have tested and we did differently than before. Our aspiration is that these learnings will be clearly applied to everything in our portfolio, in our pipeline. With that, Mikael, tell us a little bit how you see the timelines. Where are we with the flu? Thank you, Albert, I think you said it well that the type of light-speed approaches with the mRNA platform should, of course, be projected into other areas as well as flu. Tim, you mentioned 2025. I think that it would be more conservative and traditionally realistic goal, we are looking at ways to bring it as a potential product for approval earlier than 2025. Of course, it depends on whether there are good flu seasons with cases coming along or not. I think as life continues with vaccinated folks, flu will take up new momentum. Our aim is ahead of 2025. Terrific. Albert, I'll answer on the other income question. Oh, sorry. Other income. Yep. Yeah. Tim, let me run the numbers first and then I'll answer the question. You talked about the absolute size of the number in 2021 guidance. Remember, in 2020, our other income was about $1.5 billion in adjusted results. It's going from about $1.5 billion to the guidance we gave, which was about $2.2 billion. The major elements in the increase are really transition service agreement recoveries, and that's primarily now as a result of closing the Viatris transaction, higher joint venture income, and then we had some pension expense benefits as well. Those are the pieces that really get us from the call it a billion and a half in 2020 to the $2.2 billion of guidance in 2021. You asked about beyond 2021. I think the way to think about beyond 2021, just in terms of the cadence or the rhythm of that number is the watch item for us will be what happens with the consumer joint venture relative to what GSK decides to do with their portion of that venture. We own 32% of that venture, so we'll have to see what GSK does. Obviously, depending on what they do, that could impact our other income number going forward beyond that. That's the, I'll call it the watch item for us in that line item. Great. Thanks, Mike. Next question, please. Your next question comes from the line of Geoff Meacham from Bank of America. Good morning, everyone. This is Jason on for Jeff. Real quickly, sorry to move back to COVID, but Frank, if you could talk a little bit about the vaccine, at least at a high level, about how the marginal contributions will change over time as manufacturing scales. I just want to get a better sense of the intermediate to longer term if COVID does ultimately transition to more of an endemic versus a pandemic. Secondly, we wanted to ask about next steps for XELJANZ after the recent safety data. Is the assumption here that the label will include these new data? Thanks so much. Thank you very much. Frank? Sure. Jace, let me do it this way. Let me talk about how the current margins work. Then I'll pivot to how they can work going forward. In terms of the current margins, I always start with, we're in a pandemic pricing environment. The one price that we published is the price with the U.S. of $19.50 per dose. Obviously, that's not a normal price like we typically get for a vaccine, $150, $175 per dose. Pandemic pricing. What are the takeaways from that? Obviously, there's the direct material, the labor, the factory overhead, shipping, distribution, then obviously, royalty assumptions we've made, and then the 50% gross profit payment that we pay to our partner, BioNTech. You layer in on top of that, some marketing and sales expense, some medical expense, some R&D expense, and you come out with the high 20s in terms of that as a% of revenue. What we got. That's kind of the existing financials for the vaccine. Let's go beyond a pandemic pricing environment or the environment we're currently in. Obviously, we're going to get more on price. Clearly, to your point, the more volume we put through our factories, the lower unit cost will become. Clearly, there's a significant opportunity for those margins to improve once we get beyond the pandemic environment that we're in. Thank you very much, Frank. Angela, would you like to take also the XELJANZ? As it pertains to the label for Xeljanz, this is something that we don't have any sense of yet. This was a big study. A3921133 was a big study, five years, 4,500 people. We only have the co-primary endpoints that we've shared with you. We still have a lot of work to do in terms of secondary endpoints, subpopulations, and bringing all of this together, to discuss this with regulators. I think we're still a ways off in terms of really understanding what impact it will be to our label. Certainly, we'll keep you posted. Great. Thank you very much. Thanks, Angela. Operator, let's take another question, please. Your next question comes from the line of Ronny Gal from Bernstein. Good morning, everybody. Congratulations on the very impressive progress on COVID. I got two questions, they're both on things that you haven't done. The first one is development of JAKs for RA. Obviously, you've got a really versatile platform for developing JAKs, and especially with an eye to the XELJANZ safety issue, it should be interesting for you to consider a second-generation JAK in that core largest I&I market. Any thoughts about development there? If there is, what will be the requirements for you? The second one is about PD-1 approaches. You are participating in that market somewhat tangentially, if I could put it that way. We've seen a couple of the other large pharma companies like Lilly and Novartis are bringing in PD-1 simply as a base platform for combinations or maybe as a low-cost alternative in the current market. Have you considered that approach? Where do you come out in this issue? I think Mikael and John could provide some insights here. Mikael, why don't you start a little bit with more scientific information, and then John, you can summarize our strategy for JAKs and PD-1 as low-cost alternatives. Yeah. Thank you. Our ritlecitinib, which is a completely unique JAK3/TEC inhibitor, actually in a phase II already did deliver a really interesting profile. We have a study ongoing with that, the phase II ritlecitinib by itself and combined with a second molecule, IRAK4, to see if we can induce a step change improvement in RA. Please recall also that we just communicated that ritlecitinib had really strong data in ulcerative colitis, so that product could grow very strongly in IBD as an option, but we'll continue in RA. I'll say just something on our own PD-1, and maybe John can add to additional things we do globally there. We have a very nice best-in-class PD-1 platform, sasanlimab, that was developed in Pfizer that is subcutaneous and have delivered very nice response rates across multiple solid tumors. We're actually starting a phase III with F1 in bladder cancer, combining with BCG in order to improve outcomes for those patients. Thank you. Yeah. Thank you very much for the question, Ronny. I think Mikael sort of touched on the key points. I think we'd really just sort of highlight that obviously, we have our existing partnership on BAVENCIO or PD-L1. I think you saw in our release that we confirmed recent approval in Europe for a really interesting indication that could be very valuable for patients. As Mikael just said, additionally to that, with our own internal program, which is a PD-1, not a PD-L1, it's a PD-1 sasanlimab. In December, in fact, we initiated the study that Mikael just mentioned. I think the thing that we are very excited about in terms of its potential for sasanlimab is that it's a subcutaneous PD-1. We think that the marketplace for more convenient PD-1s is actually still to be developed. Plainly, PD-1s, given their efficacy data across a whole range of tumors, have enormous potential to be a backbone for the long term. We think that as that market evolves, the opportunity for a PD-1 that has effectiveness, which has been proven across multiple other compounds, but also combines significant convenience enhancements, is actually very significant. We're very excited about sasanlimab, and we will keep you updated with progress as that program develops. All right. Thanks, John. Next question, please. Your next question comes from the line of Navin Jacob from UBS. Hi. Thanks so much for taking the questions, and squeezing me in here. A couple questions for Frank, and one for Mikael, if I may. Frank, just wondering if there was any change in inventory in the U.S. between Q3, Q4 of 2020, and how does that compare to the change in inventory in the U.S. between Q3 and Q4 in 2019? Separately, Frank, the high 20% margins for the COVID vaccine suggests at 100% economics, somewhere between 50%-60% op margin. Wondering, because I know obviously you're investing a ton into R&D, moving forward into 2022, how much could we see that operating margin increase over time as R&D spend lowers? For Mikael, obviously a key question that everyone has is durability of efficacy, which is in part affected by new variants. How exactly is the agency measuring durability of efficacy or requiring manufacturers or developers to measure durability of efficacy? What specific trials and/or endpoints, or how is that characterized, please? Any color would be helpful. Frank? Thanks for the question, Navin. On the inventory, it's approximately three weeks on hand, and roughly the same as it was last year at the end of the year. In terms of Q3 to Q4, no major change in the rhythm of the inventory. It's approximately three weeks on hand. In terms of the high 20s%, it's interesting how you framed the question, because the way I think about it is the R&D spend is not the big driver of what's getting us to that high 20s, which is how I heard the question. It's really the COGS. It's like I said, because primarily it's the pandemic pricing, and then the different layers of the COGS that I answered earlier on in the Q&A. That's really what's driving the lower IBT as a% of margin. I think you mentioned 50%. Based on all the current financials, we're lower, significantly lower than 50% on the gross margin. When you layer in the expenses, you get into the high 20s. Now, to your question beyond that, once again, I think the big factor in it will be the pricing. We'll continue to take the unit cost down as volumes improve. The royalty is what the royalty is. The profit share is the profit share is. Obviously, we're spending R&D, but we'll continue to manage the R&D spend. To me, the big-ticket item there will be what we can do on pricing, and then obviously, the more volume we generate, the lower we'll take the unit cost, and those items will clearly drop to the bottom line. Right. Thanks, Frank. Operator, if we could take our last question at this time. Your final question comes from the line of Chris Schott from JPMorgan. Great. Thanks so much for the question. Just two quick ones here. Maybe on the BCMA bispecific, can you just talk a little bit about how you see these agents fitting in the treatment paradigm? Maybe as importantly, how you're seeing the competitive landscape shaping up. Basically, what differentiation do you see with your program versus others? Maybe just then a follow-up on capital allocation priorities post Upjohn. Share repo, the company's been historically pretty active on that front. Should we think about less or a less relevant role for share repo in the paradigm going forward as I actually think about maybe a little bit higher dividend payout ratio and then some of these priorities to bring in additional assets ahead of the 2026-2028 LOE cycles? Just would love to hear how you see that fitting in the mix. Thanks so much. Sorry, I was muted. Mikael, would you like to take the first question? Yeah. BCMA or elranatamab, we're very excited about that drug, and it had at the high dose, 1,000 micro per kilogram, 83% response rate in a heavily pretreated population. It has showed a significant number of stringent or complete responses. It's given subcu because a very nice tolerability profile. Although it's a field with several entrants, I think we have an opportunity to aim for being absolutely in the first wave here and with a really nice best-in-class profile. We're moving with the first opportunity we see for accelerated approval in triple refractory patients that either have seen no prior BCMA-based treatment or have seen prior BCMA treatment such as ADC or CAR T. We are planning such cohorts to start soon with a potential for registration. We are moving into second and third line in combination with classical IMiDs, and other combination that are used in order to come to first and second-line opportunity, particularly with IMiDs. Thank you very much. Thank you. Chris, as regards the stock repurchases, we never say never to anything, right? We don't want to leave any weapons that we say we never use. Clearly, the share repurchases falls at the bottom of the priorities right now. The dividend is a clear commitment that, of course, we will honor, and we believe there are tremendous opportunities right now to invest in the business. As Frank has said, we have already an authorization from the board that we could exercise at any point to buy back shares, and we could at any moment ask for a renewal, this is not the priority right now. The priority is to make sure that we keep investing for business development and for infrastructure. For example, our COVID franchise will thrive over time, and our R&D machine will get many more programs from the external world that can run through it. Thank you very much. Thank you. Albert, could you add some closing remarks? Wow, time flies. 11:30, my God. Thank you very much for joining us today and for your continued engagement with Pfizer. The new Pfizer is all about two things, science and patients. I think it's the culmination of a bold, decade-long transformation from a diversified enterprise to a more focused and innovative biopharma company. By uniting transformational technology and cutting-edge science, we are pioneering biopharmaceutical innovations to do more than just treat difficult diseases. I think we are curing and preventing them. We believe our success in developing COVID-19 was just the beginning. Thanks to the incredible transformation we have executed over the last 10 years, Pfizer is now advancing one of the strongest pipelines in our company's history. We have 95 potential new therapies or indications in six therapeutic areas, with nine programs in registration, 24 in phase III clinical trials. This means 95 potential opportunities to change the lives of patients around the world. When patients win, we all win. Have a great rest of your day. Ladies and gentlemen, this does conclude Pfizer's fourth quarter 2020 earnings conference call. You may now disconnect.