Welcome everyone, thanks for joining us virtually for our first of two sessions where we will share some exciting updates from Pfizer's portfolio and R&D pipeline. Today's program will be a combination of pre-recorded prepared remarks and then, of course, live audience Q&A sections. Today we'll hear from members of our executive leadership team, as well as leaders of our internal medicine and vaccines teams, the two therapeutic areas in focus for today's session. We will have a Q&A session following each of the therapeutic area presentations. The presentation at today's Investor Day includes forward-looking statements about, among other things, our anticipated future operating and financial performance, business plans, and prospects and expectations for our product pipeline, our in-line products and product candidates. By their nature, all these statements about future events and expectations for our pipeline products are forward-looking.
Each forward-looking statement contained in these presentations is subject to risks and uncertainties that could cause actual results to differ materially from those projected in such statements. Additional information regarding these factors are included in the slide entitled Forward-Looking Statements and Other Notices and under Risk Factors in our 10-K and 10-Qs. The forward-looking statements in this presentation speak only as of the original date of the presentation, and we undertake no obligation to update or revise any of these statements. The slides that will be presented during this session will be posted on pfizer.com/investors after each session. You can also find speaker bios and today's agenda on a separate tab at www.pfizerinvestorday.virtualeventsite.com. Again, there'll be time for Q&A via the operator following each business unit's presentation. Now we're going to play a video that articulates our commitment to science.
[Presentation]
Now I'll be handing it over to our executive leadership team. Today we'll hear from Albert Bourla, our Chairman and CEO, who will speak to the broad transformation that has been in place at Pfizer and how it will make a difference. Mikael Dolsten, our Chief Scientific Officer and President, Worldwide Research, Development and Medical, who will speak to how our R&D organization has evolved to become a highly focused and agile leader in science and identify for us some of the exciting breakthroughs that may be available for patients. Rod MacKenzie, our Chief Development Officer, who will speak to some very important metrics regarding our R&D productivity.
Angela Hwang, Group President, Biopharmaceuticals Group, who will speak about our commercial organization and provide detail as to the drivers of our projected 6% plus revenue CAGR from the time of the close of the Upjohn Mylan transaction through the end of 2025, and importantly, quantify our current view as to peak sales potential for selected pipeline assets that could drive growth well beyond 2025. I'll now turn it over to Albert Bourla.
Welcome, and thank you for joining us today. We are thrilled to introduce you to the new Pfizer by doing a deep dive into the scientific engine and culture of innovation that we expect to drive our growth for the next decade and beyond. Over the next two days, we will share our excitement about our pipeline, including some of the projects about which we are very excited, but with which you might not be as familiar. It is this pipeline that makes us confident that following the completion of the pending Upjohn Mylan transaction, we can drive at least 6% revenue CAGR over the next five years and continue to deliver longer-term top-line growth beyond that period. With the separation of Consumer Health last year, and the expected separation of Upjohn later this year, we are significantly transforming our company.
We are evolving from a diversified enterprise to a more focused and innovative biopharma company, from a scientific fast-forward to a first-in-class scientific powerhouse, and from growing EPS through large-scale M&A and share repurchases to a company with organic growth at our core, supplemented by bolt-on acquisitions where and when they make sense. We believe this structure not only makes Pfizer more relevant to patients, but will also earn a higher PE multiple. A transformation of this magnitude could not happen within one or two years. It started in 2010 when my predecessor, Ian Read, recognizing that our historic R&D productivity lagged the industry, set a priority to strengthen our scientific engine. This 10-year journey resulted in a dramatic turnaround of our R&D organization.
The increased R&D productivity, as well as the depth and breadth of our pipeline, gave us the confidence to move so quickly over the past year to transform into the new Pfizer. The new Pfizer will be very different. It will combine the agility and innovative spirit of a biotech with the scale of a big pharma. To be successful, a company like this needs to have a purpose that inspires all its employees, a small set of clear strategic priorities, and a culture that allows innovation to flourish. Last year, we launched what we call our Purpose Blueprint, the roadmap that will guide our company for the foreseeable future. It includes, on one page, all the why, what, and how of Pfizer. Our purpose, which is breakthroughs that change patients' lives, represents the why we exist and do everything we do.
Our bold moves represent the what we need to do to be successful. Unleash the power of our people, deliver first-in-class science, transform our go-to-market model, win the digital race in pharma, and lead the conversation on science and reputation. Every plan we develop, every action we take, and every dollar we spend is aligned with these five bold moves. Finally, our values represent the how we do things. Our new Pfizer's culture will be characterized by courage, because breakthroughs favor the bold. By excellence, because we can only change patients' lives when we perform at our best. By equity, because every person deserves to be seen, heard, and cared for. By joy, because we take our jobs seriously, not ourselves. In order to prevent our scale from becoming an impediment to innovation, we organized Pfizer into six vertical integrated business units.
Each of these units possesses deep scientific, commercial, and patient experience expertise that make them uniquely effective to address the distinct needs of the patients and physicians they serve. We see these six business units as six individuall biotechs within Pfizer. Each of them is led by a triad consisting of a chief scientific officer, a chief development officer, and a global commercial president. They manage their units independently within the boundaries of their assigned strategic priorities and budgets. All the operational decisions of each business unit, regardless of whether they are scientific or commercial, are made within the unit. This allows for greater agility, speed, and executional excellence. It is this operating model that allowed our vaccine business unit, for example, to move so fast with the development of their COVID-19 vaccine candidate, and our hospital unit with the development of their antiviral protease inhibitor candidate.
These biotechs compete with each other for capital and resources for their internal and external projects. These resources are allocated by a committee of five executive leadership team members, which applies the same criteria to both internal and external programs. We have removed all previous incentives that were favoring internally versus externally sourced science. This operating model was implemented in 2016 and has resulted in better decision-making regarding which projects we pursue and which we deprioritize. To realize our full potential as a more focused and innovative biopharma company, we must also radically simplify the ways in which we work and the interactions between our business units and corporate functions. Bureaucracy and innovation are like oil and water. They don't mix well together.
Over the past several months, we have worked to reimagine the way we work and begun to redesign major corporate processes with an objective to radically simplify them. Going forward, we will also reduce the number of interfaces we have between our core and enabling functions from 16 to five, and will consolidate our shared service centers from 20 to six. These changes will create a more nimble and efficient company, improve our ability to get things done, and right-size our corporate expenses to our smaller revenue base. To ensure our culture of innovation continues to flourish, it also is essential that our incentives align with the focus on science and our pipeline. That's why we have made an important change to our short-term incentive plan for all colleagues who are bonus eligible.
Going forward, the funding of the variable compensation, which is approved each year by the compensation committee of the board, will be based on both our financial performance and the success of our pipeline. Previously, only our R&D colleagues' compensation was impacted by our pipeline performance. This sends a clear message to our entire organization about how important the success of our pipeline is. As a purpose-driven, science-based biopharma company, and in line with our values, we are committed not only to delivering strong financial results but also to ensuring that environmental, social, and governance principles are hardwired into our DNA. We recognize the adverse impact climate has on health and are proud to have achieved a 23% reduction in greenhouse gas emissions from 2012 to 2019.
That's ahead of our science-based goal to achieve a 20% reduction by 2020 and builds on the progress we have made to reduce emissions by approximately 55% since 2000. In 2019, we conducted also our first global pay equity study. The study confirmed that Pfizer has equitable pay practices between women and men globally, as well as between minority and non-minority colleagues in the U.S. Our annually elected board of directors is comprised entirely of independent directors other than me, with more than half of them being from diverse backgrounds based on gender or ethnicity. To signify our commitment to ESG, we recently renamed the board's corporate governance committee to become the governance and sustainability committee, which speaks volumes about our board-level interest and involvement to sustainability.
As we evolve into a world-class, science-based biopharma, we also have strengthened our board of directors by infusing more global business leadership and scientific expertise. Since 2019, we have added to our board four highly accomplished directors. Dr. Scott Gottlieb, special partner of the New Enterprise Associates, resident fellow of the American Enterprise Institute, and the 23rd commissioner of the FDA. Mr. James Quincey, chairman and chief executive officer of The Coca-Cola Company, the world's largest non-alcoholic beverages enterprise. Dr. Susan Hockfield, professor of neuroscience and president emerita at MIT. Susan was the first woman and the first life scientist to lead MIT as its 16th president. Dr. Sue Desmond-Hellmann, board member of the Bill & Melinda Gates Medical Research Institute, a former CEO of the Bill & Melinda Gates Foundation, and the first female chancellor of the University of California, San Francisco.
With these additions, we clearly strengthened the scientific depth of our board while maintaining a balance of strong financial, business, and scientific expertise, together with our longer-serving board members, Professor Helen Hobbs from the University of Texas Southwestern and Professor Dan Littman from NYU. Our board now includes five highly accomplished scientists that form one of the best science and technology board committees in our industry. Each not only has spent their career focusing on a different therapeutic area, including metabolic diseases, immunology, cancer, neuroscience, and clinical medicine, but they also greatly complement one another in terms of early science, clinical development, and regulatory expertise. Each of these actions have been essential to our transformation. We think that now is the exact right time for the genesis of the new Pfizer for many reasons. First, our existing portfolio of innovative medicines and vaccines continued its strong growth.
Last year, it generated 8% operational revenue growth, and for the first six months of the year, it generated 9% operational growth. We have a long runway of high-performing, patent-protected brands with no significant LOEs anticipated until 2026. We expect a five-year revenue CAGR of at least 6% on a risk-adjusted basis following the completion of the Upjohn separation and continued growth beyond that from the next wave of our patent-protected portfolio. Should we be successful with our COVID-19 vaccine and antiviral programs, we will obviously update this projection. Our adjusted EPS during that same five-year period is expected to grow in the double digits. Investment in Pfizer shares today provides healthy dividend income that we expect will continue to increase. Our pipeline is as strong as it's ever been, with 89 projects spread across six targeted therapeutic areas, with four programs in registration and 23 in phase III.
Last but not least, we have the financial strength to supplement our internal pipeline where appropriate with external business development. As we have already said, we are biased towards phase II and phase III-ready assets. Now let me offer a few points regarding our longer-term revenue growth view. The sell- side community expects $18 billion-$20 billion in lost revenue during our LOE period, which is expected to begin in 2026, six years from now. We have a similar expectation in our longer-term forecast. On a risk-adjusted basis, we see our current pipeline excluding any revenue from a COVID vaccine or treatment and excluding any future business development revenue as serving to at least replace the LOE revenue expectation. We are eager to show you why we think this is the case over the next two days.
In closing, we believe we have taken the steps to create the focus and culture needed to drive our success as a science-driven company. What you will see over the next two days is the Pfizer of the next decade. I believe you will walk away with the new appreciation of the value our science can deliver to patients, to society, and to our shareholders. We look forward to showcasing our people, our culture, and our science. With that, let me turn it over to Pfizer's Chief Scientific Officer, Mikael Dolsten. Mikael.
Thank you very much, Albert, and welcome everyone. In this next session, I would like to share with you Pfizer's own turnaround over the past decade or so and our journey to get here. I will also review our robust and innovative pipeline with an emphasis on what we see as promising but underappreciated assets. Along with most of our peers in the early 2000s, Pfizer found itself following a volume-oriented R&D strategy that sought to get as many shots on goals as possible. During the period leading up to 2010, our R&D efforts were thinly spread across 10 key therapeutic areas, seeking to advance as many programs into the clinic as possible. By 2010 year-end, we had 104 NMEs in the clinic, predominantly small molecules. Our major R&D sites were located outside of major scientific hubs, isolating our R&D colleagues, and our decision-making was often siloed.
In 2011, we embarked on a significant R&D turnaround effort focused on reinvigorating our innovative core. As part of the turnaround, we made a conscious decision to focus our resources on five key therapeutic areas where we felt we could make the greatest impact. In addition, we shifted away from a volume-based development strategy to one in which we focused on high-quality NMEs. We recorded 54 NMEs in second quarter 2020 and broadened our modality base beyond small molecules. During this time, we also co-located our R&D sites in scientific hubs, which enabled us to better attract scientific talent in our core therapeutic areas. The impact of our turnaround was profound.
Our decision-making became more integrated with enhanced objectivity and a high bar for success and Pfizer began racking up successes that included first-in-class blockbuster therapies developed internally at Pfizer, such as XELJANZ, PREVNAR, IBRANCE, and complemented by partnership or acquisitions of molecules from external sources, including ELIQUIS with BMS, XTANDI from Medivation, which have significantly benefited millions of patients around the world. Over the next few minutes, I would like to take a deep dive into each of these elements, describe the impact they've had on our success, and how they've put us in an outstanding position for success well into the future. The success of this strategy is reflected in the substantial improvement that we've seen in phase II trials.
In the three years leading up to 2017, Pfizer's phase II success rate, which is defined by successful transition into phase III, was 17%, which was well below the industry median and put us in the bottom quartile. I'm proud to say that today we have tripled our phase II success rates on a three-year rolling average, going from 17% in 2017 to 47% in 2019 to currently 53% in 2020 year to date, and we're now among industry leaders in this metric. Between 2015 and 2017, for every successful phase II to phase III transition, Pfizer needed six to seven readouts. By 2019, Pfizer was achieving one successful transition into phase III from every two phase II readouts. Another measure of success is survival rate from first in human to approval.
These two have significantly improved with 76% relative increase since 2015 and have surpassed the industry peer group. 2015, Pfizer had 5% end-to-end success rate versus industry 10.6%. 2019, Pfizer is at 8.8% versus industry at 8.3%. Another factor in our success was the decision to concentrate on five therapeutic areas where there's great unmet need and a strong biological foundation, and where our expertise and capabilities can be leveraged to improve the likelihood of success. Our five core therapeutic areas include oncology, with a focus on targeting cancer vulnerabilities and drug resistance. Inflammation and immunology, leveraging our world-leading experience in cytokine biology. Vaccines, where we can leverage our industry-leading experience to develop high-impact bacterial and viral vaccines. Rare disease, with a key focus on the molecular pathology of genetic diseases, and internal medicine, where we now focus on metabolic dysfunction and cardiovascular risk.
Along with our sharpened focus in five key therapeutic areas, Pfizer's broadened its scientific and clinical toolbox to tackle diverse disease pathophysiology. We expanded our core technology platforms beyond small molecules and monoclonal antibodies to include conjugate and engineered vaccines and AAV gene therapy. We have gone beyond that and have been focusing on building novel emerging platforms, which includes protein degraders, expanding our small molecule expertise, multi-specific biologics like bi and tri-specifics, RNA vaccines like our potential COVID-19 vaccine in partnership with BioNTech, gene expression modulators, which include zinc fingers in ALS, translation and splicing acting drugs in cancer, such as PRMT5 or eIF4E. Artificial intelligence, multi-omics, and epidemiology, which utilizes big data, real-world evidence, genomic profiling, and enhanced epidemiology information to guide early decisions.
To place Pfizer's R&D at the forefront of the evolving biopharmaceutical base, we have co-located our key R&D facilities in globally recognized scientific hubs. Together with our focus on science, locating to these hubs has enabled Pfizer to attract top scientific talent and effectively leverage the collaborative environment such locations naturally offer. Our therapeutic area hubs are distributed in scientific centers of excellence, including for oncology, La Jolla, California, and Boulder, Colorado, inflammation and immunology, rare disease, and internal medicine, Cambridge, Massachusetts, and vaccines, Pearl River, New York. Our science and technology centers include small molecule centers at Groton, Connecticut, and Sandwich, U.K., large molecule centers at St. Louis, Missouri, and Andover, Massachusetts, and new modality gene therapy sites at Chapel Hill and Sanford, North Carolina. These efforts have yielded an innovative pipeline that has positioned Pfizer to be a leader in the next wave of therapeutic breakthroughs.
We are confident that we're on the right road and have set an ambitious goal to put up to 25 breakthroughs in the hands of patients by 2025. In short, up to 25 by '25. 2026 to 2028 opportunities include a significant number of potential breakthrough medicines across our therapeutic areas, and we're exploring potential acceleration paths to enable the earlier approval of these medicines. There are a total of 62 key programs shown on the slide, which included 38 key assets that could potentially contribute to up to 25 by '25, and 24 key assets shown in the 2026 to 2028 timeframe. More than 70% are beyond phase I, and more than 35% are in phase III registration or recently approved. There is strong contribution from all TAs, with oncology being the main contributor, 29%, followed by immunology and inflammation, 20%.
Our internal medicine portfolio sees its initial potential launches in the second half of this decade and includes multi-billion potential blockbuster opportunities in the peri-2026 phase. If we look at up to 25 by 2025 cohort in terms of non-risk-adjusted peak sales potential, we see approximately $35 billion-$40 billion in revenue. This includes PCV20 revenues, and as you know, it's a potential replacement for PREVNAR 13. We recognize these will not all achieve peak sales in the same year and are subject to attrition, but this should give confidence in the overall size of the opportunities we see. Of the $35 billion-$40 billion, major contributions are coming from vaccine, rare disease, followed by immunology and inflammation.
Achieving up to 25 by 2025 will require a combination of developed or Pfizer-generated molecules and external partnership BD deals. Of the 62 programs shown here, close to one third are part of business development and bolt-on M&A. We will continue to look for breakthrough bolt-on assets and deals, which will further bolster our pipeline. In the next two days, our scientific leaders will present therapeutic area deep dives covering nearly half of these assets. These programs were predominantly chosen based on expected launch by 2025, clinical data we're excited to share, assets we believe are underappreciated assets by the analyst community. I want to highlight our near-term catalysts among the programs you see in the potential slide. They include up to 10 potential approvals, 10 anticipated pivotal study readouts, and 10 anticipated early-stage clinical readouts by 2021.
Up to 10 potential approvals include key programs like a COVID-19 vaccine, abrocitinib in atopic dermatitis, and PCV20 valent adult vaccine. Up to 10 potential pivotal readouts includes key programs like ritlecitinib in alopecia, XTANDI and TALZENNA combination in TALAPRO-2 study in prostate cancer, and IBRANCE/PATINA study in double-positive hormone receptor and HER2 positive advanced breast cancer. Up to 10 potential early-stage clinical readouts include key programs like BCMA, bispecific in multiple myeloma, Lyme disease vaccine, and topical brepocitinib in atopic dermatitis. Finally, I would like to introduce our highly accomplished scientific leadership team, James, Nick, Mike, Kathrin, Bill, and Morris, who have a strong record of drug hunting abilities and proven history of translating pipelines into products that can help millions of patients. Across these therapeutic area CSOs, we have more than 1,000 scientific publications and more than 50 years of Pfizer work experience.
Thank you very much for your attention. I will hand over to Rod.
Thank you, Mikael, and thank you to everyone for joining us today. It's my pleasure to take you through some of the very impactful ways we've been revving up our clinical development engine in recent years, and how we're continuing to reduce our cycle times across development. To get us started, let's go back to 2015. Quite frankly, we were in a poor spot in terms of our operational performance metrics and nowhere close to where we knew we should be based on our talent and experience. You can see some examples here. We were bottom quartile with double-digit rankings. Needless to say, that's not where we expect to be. Well, if we fast-forward from 2015 to 2019, I'm pleased to say that we've moved to the top quartile. More important, though, than the ranking is what that ranking reflects.
As you can see, we've achieved very significant reductions in cycle times across the board, ranging from 18% to more than 50% in some cases. We're in a much better place today. I'm pleased to report that we expect that trend to continue through 2021 and beyond. Here you can see that we expect to further reduce these key cycle times by up to another 60% by the end of next year. How did we get here? We focused on three key dimensions of performance. The first was the most important. It was to build an integrated, patient-centric development organization with a deeply embedded culture of performance, quality, and continuous improvement. The second dimension was to put all of our colleagues to work on all of our processes, systems, and tools with a strong focus on internal and external innovation. It really was optimization on steroids.
With the first two foundational elements in place, the third dimension was, and it still is, reinventing the way we operate with a laser focus on quality and cycle time reductions. To give you a sense of the ambition we have, we're in the process of taking out a further two and a half years from our average times for end-to-end clinical development. Let me spend a few minutes on each of these three dimensions, and let's start with organization culture and our people. Our first action was to consolidate all of our clinical operations. Back in 2015, these were somewhat fragmented and sitting in different parts of Pfizer. All in all, we took four different organizations and brought them together under one leader. From the outset, global product development has been an organization which is obsessed with patient centricity, quality, speed, cost, and simplicity.
In other words, all the elements of operational excellence. What does it mean to be patient-centric? Remember that every participant in a clinical trial is a volunteer. All of them are pioneers in science and medicine. Patient centricity is primarily about building trust in the communities that we work with. Recently, you may have seen that we've made a public commitment to enrolling clinical trial participants who reflect the racial and ethnic diversity of the countries where we operate and better represent the epidemiology of the diseases we're addressing. More specifically, we are keenly aware that we must build trust in the communities that continue to suffer from racial injustice and socioeconomic disadvantage, and that have good reasons to mistrust the healthcare system. This won't happen overnight, these are important principles that we're holding ourselves accountable to. We're also working to build awareness.
Today, far too few people know what clinical trials are available to them. We need to make it much easier for them to find information and to make that first connection with clinical trial sites. Finally, when someone participates in a clinical trial, it needs to be less burdensome. For example, fewer visits to sites means less need to take time off work, and fewer invasive procedures means just a better experience for everyone. This is what it means to be patient-centric. It's really about doing the right things, which is at the heart of why we're doing all of these things. By doing the right things, we will also enhance the quality of our clinical data sets because they will better reflect the real population in clinical practice.
Any organization is only as good as its people. I'm pleased to say that we have one of the most experienced and talented groups of clinical development leaders in the industry. Between them, James, Bill, Mike, Brenda, and Chris, have played key leadership roles in bringing more than 30 medicines and vaccines to patients, with cumulative lifetime revenues in the region of $150 billion. These are leaders who have done it before, and they have a state-of-the-art clinical engine now to work with. I know that we can trust them to deliver the pipeline that you will hear about throughout this meeting. The good news is you don't have to take my word for it, because you will hear from each of these leaders during the meeting. Let's now look at the second dimension of performance, and that's operational excellence.
When we created our organization, we spent a full year examining every aspect of our clinical development operations and optimizing them. The work was entirely done by volunteers across the organization, more than 700 of them, in 44 work streams. The result was very significant improvements in operational performance. For example, we saw reductions in cycle times, in some cases up to 30%. In addition, we created cost efficiencies that allowed us to reinvest approximately $750 million back into the portfolio. In addition to optimization of our processes, we recognize that we can't change the practice of clinical trials without the type of experimentation that leads to innovation. We're beginning to see the fruits of that now. We're conducting, for example, a decentralized trial where we're bringing the entire study to patients. They can participate in the trial without ever leaving their home.
We believe this is the first regulatory grade study, which is completely remote in that way. If we do, we'll scale that approach up in other studies. Another example is automated clinical documentation, which will reduce the time it takes for authors to review documents, allowing colleagues to focus on higher-volume work. Finally, in this dimension of operational excellence, we placed a premium on being externally focused. Collaborations with other innovative companies are really important to us. For example, we're working with TrialSpark, a young, energetic company based in New York City who provide infrastructure to doctors and clinics who have not traditionally conducted clinical trials. We gain access to patients we couldn't otherwise reach.
With Ochsner Health , we have access to a first-rate, extensive, and growing network of hospitals that use electronic health records, enabling the seamless transfer of anonymized data into Pfizer databases. As a founding member of TransCelerate, we're helping harmonize industry practices, thereby facilitating patient centricity by providing our clinical trial partners a similar experience no matter which sponsors they're working with. Let's move now to the third dimension of our transformation, which is laser-focused on reducing cycle times. As you know, in the world of patented medicines and vaccines, the faster we bring our breakthrough products to patients, the better we fulfill our purpose and the better we meet the goals of our investors. There's a perfect alignment between these two things. When we began our work, on average, from a first in-human study start to an approval, took us about nine and a half years.
That's too long for everyone. We looked very carefully at every moment of that timeline. We took apart every transaction, every technology, every process, every human-to-human interaction, and every tool. We looked minute to minute to understand in great depth how our time was being spent. In the end, we decided to split those nine and a half years into two buckets. The first bucket was what we felt was operationally addressable. For example, white space where really nothing is happening, decision-making time, and the time to recruit our clinical studies. All of that's addressable. We have control. The second bucket is what we felt was operationally fixed, where we have less control. For example, regulatory review periods or the study period of a trial.
If we're studying a medicine for a year in a trial, no matter how quickly we recruit that study, it cannot take less than a year. In other words, the two buckets were based on what we have strong control over and that which we have little control over, at least in the short term. When we added it all up, the addressable time turned out to be 5.2 years. We set ourselves a breakthrough goal to reduce that by a full two and a half years by the end of 2021. I'm pleased to say we are making great progress. Here, you can see the cadence of the actual and anticipated reductions in average cycle times. Up to and including 2019 are actuals. 2020 and 2021 are projections. I'm very confident we'll continue to do well. How are we doing it?
We're working in five areas, you can see the relative contributions here. The first is in changing the investment profile of our programs. As Mikael described to you, with our phase II success rates going up, our confidence in making earlier investments in programs is getting higher. That, in turn, reduces white space while we wait for clinical trial supplies for pivotal studies. On the average, we think by about eight months. We've also speeded up our study starts, which accounts for a couple of months. Now, the clinical trial recruitment phase is the single longest cycle time we have when you look across the entire continuum. By moving faster in recruitment, we expect to gain up to an average of five and a half months. On the back end of studies, we're moving much faster from the last patient in the study to the database release.
We expect that to contribute an average saving time of three months. The biggest impact is in the automation of processes. Right now, every aspect of clinical trials is very human-intensive and requires many manual processes and transfers of data and other information. Through automation, we're creating an environment where data can flow directly from a patient into an electronic database and on into Pfizer systems after anonymization, and to populate clinical trial submission documents without them being touched by human hands. Because automation can positively impact every aspect of end-to-end clinical development, we anticipate that the overall automation of processes will contribute nearly one year to our cycle time reductions. Let me finish by showing you how we are putting all of this to work.
I thought you might like to see how this new clinical development engine and our culture of operational excellence at Pfizer has come together in our COVID-19 vaccine work. Tomorrow, you'll hear in some detail a full description of Pfizer's overall COVID-19 response. Just to give you a little bit of a preview, you'll see here that from the time we had the first approved protocol for our potential COVID-19 vaccine to the first subject first visit was only 12 days. When we received regulatory approval to start our phase II-III study, we had our first subject first visit two hours later. We had 6,000 people dosed in the study in just 18 days and more than 20,000 in just 35 days from the start of the study.
I think you'll agree that these are extraordinary timelines, and these timelines would not have been possible without the culture of operational excellence that we've been building. Let me finish with LORBRENA. This is an important medicine for non-small cell lung cancer that took less than five years in clinical development, under half of our previous median, and significantly shorter than the industry median of the day. LORBRENA is a lifesaver, and it's a life prolonger. It was discovered by our own scientists using state-of-the-art medicine design, developed with patient centricity and quality and speed, and with love and respect for the patients that we serve. Well, that was a whistle-stop tour of our transformation journey in clinical development.
There's no question in my mind that we now have a clinical engine that will deliver the portfolio that you will hear about in this meeting and to deliver it with quality and speed. Thank you for your attention. Now it's my pleasure to turn it over to my colleague, Angela Hwang, Group President for Pfizer's Biopharmaceuticals Group.
Thank you, Rod, and hello, everyone. I am pleased to be here today to review the Biopharma portfolio with you. As you saw in Mikael's and Rod's presentation, our pipeline is robust and has great prospects from an unmet need and a market perspective. What you heard from Mikael was a broad review of our pipeline until 2028. During this presentation, I'm going to focus on 2020 to 2025. What I see is a business that has the potential to deliver 6% CAGR or more in the next five years, and this is a function of three things. First, a strong in-line portfolio that's already delivering strong growth today and will continue to grow. Despite the impact of the pandemic, which drove a downside of $250 million, Biopharma in-line brands grew 9% in the first half of 2020.
The momentum in our current portfolio is strong, and the seven in-line products, namely IBRANCE, XTANDI, Oncology Biosimilars, BRAFTOVI, MEKTOVI, VYNDAQEL, ELIQUIS, and XELJANZ, are expected to drive 50% of the revenue growth over the next five years. Second, the potential of 25 launches by 2025, including nine potential blockbusters that have a total of $15 billion in non-risk adjusted revenues in 2025. Third, no significant LOEs anticipated until 2026. We have a unique portfolio of medicines and vaccines housed in seven business units, each with commercial capabilities and resources that are focused specifically on their therapeutic areas and customer needs. Having all of the business units within one Biopharma Group also gives us unparalleled scale and capital allocation ability. This combination allows us to achieve both focus and leverage across the BU and is what makes our commercial model unique and competitive.
Our commercial engine and our capabilities gives us great confidence to deliver best-in-class launches for every pipeline product to come. Let's introduce the business units. The seven units are led by my outstanding leadership team, our global presidents. Together, they comprise $41.6 billion of revenue in 2020, this being the midpoint of our 2020 guidance. Each of these leaders have deep expertise within Pfizer. They bring unique experiences and capabilities to Biopharma. They work side by side with the chief scientific officers and chief development officers that Mikael and Rod already introduced to you, and they shape and advance the pipeline in addition to their commercial responsibilities. We call this group of three the Triad, and together they create and execute on their respective parts of the end-to-end strategy for each business unit. This is also the group who will be discussing the pipeline with you later this afternoon.
Each of these business units is a leader in the market segment they operate in today, and all of them have deep pipeline potential. Let's start with internal medicine. Today, it is a business unit that is $9 billion in revenue. In the pipeline are six potential first-in-class medicines. We have deep expertise in cardiology and primary care. Those capabilities will be leveraged by our pipeline assets in hypertriglyceridemia and obesity. Vaccines has the potential to become a top two player in the next few years, especially if the COVID vaccine is successful. You will hear more about the potential of our COVID vaccine tomorrow. Currently, this vaccine is not reflected in the $6 billion of vaccine pipeline potential that we believe we have.
I&I has a leading medicine in XELJANZ. We have one of the largest targeted JAK portfolios across the industry with 12 potential NMEs across 24 indications. We feel we are well positioned to maintain leadership in I&I. The Rare Disease BU will be the only company with three phase III gene therapy programs building on the momentum of exceptional launches like the one that we've seen with VYNDAQEL. Our Oncology BU has been a strong growth driver in recent years and will continue to contribute to Biopharma's growth, with up to 14 approvals of NMEs and indications by 2025. The Hospital BU is a leader in sterile injectables and anti-infectives and is focused on building out its pipeline with innovative molecules and platform technologies. This includes three NMEs, namely the ATM- AVI asset and both the IV and oral protease inhibitor.
Our Emerging Markets BU encompasses all the products from the six business units and commercializes those products in over 100 countries. Our Emerging Markets footprint is one of the largest in the industry, with significant scale. In 2020 alone, over 140 product launches are expected. This is the roadmap of how we plan to achieve our 6% revenue CAGR from 2020 to 2025. 50% of the revenue is expected to come from the seven in-line brands. Together, these seven brands have the potential to contribute $8 billion of incremental revenue by 2025. The other part of our growth will be led by our pipeline. Non-risk adjusted, the revenue potential for this in 2025 is about $15 billion. The assets we're showing here are either in phase III or will be by the end of this year.
Risk adjustment gives the pipeline about $8 billion, making up the other 50% of our revenue growth. We have three mega blockbusters in abrocitinib, DMD gene therapy, and ritlecitinib. Abrocitinib and ritlecitinib have more than $3 billion in peak revenue, and DMD gene therapy more than $2 billion in peak revenue. We also expect PREVNAR 20 to be a mega blockbuster, we're not factoring this into our incremental revenue growth because we see this replacing PREVNAR 13. These expected launches are not only a contributor to revenue growth in 2025, they also help BioPharma to fuel the growth through the LOE period that begins in 2026. This is truly an exciting portfolio and one that is meaningful for every single BU. Never in the 23 years that I have been here have I seen as exciting a launch and growth story as the one that we have today.
When you consider that this growth is off a +$41 billion space in 2020, it's all the more significant. It doesn't stop here. We continue to pursue business development, which will drive incremental revenue growth to what we are discussing here today. Over the next five years, this is the cadence of launches that you can expect. As you can see, each business unit has a role in contributing to Pfizer's growth. I won't go through and name each of these now, but as you can see, there are the following themes here. We have a strong vaccine portfolio that includes the potential of a COVID vaccine later this year. The investments we've made behind our rare disease portfolio and gene therapy gives us a consistent series of launches until 2025.
The depth of our JAK portfolio, which builds off the strong foundation of XELJANZ, expands into new disease areas like dermatology. Let's get into some specific details around a few of our growth brands to help show how we see their future growth potential. VYNDAQEL has seen exceptional performance in ATTR-CM and should be close to a billion-dollar global brand by the end of 2020. We're seeing strong launches across the world. Today, just in the U.S. alone, we have diagnosed approximately 15% of all ATTR-CM patients. This is remarkable given the short period of time since the product has been on the market and the challenges that we've seen from the pandemic. We previously talked about peak diagnosis rates for rare diseases being in the range of 30%-50%.
With the momentum we have, we would expect to drive a higher than average diagnosis rate for a rare disease. We also expect peak diagnosis rates to occur earlier than we originally thought if we follow the shape of the curve. XELJANZ. We believe in the growth potential XELJANZ has. In a heavily rebated class like this one, we have to contract. These contracts we executed over the last 18 months helped us to gain access to an incremental 64 million lives. With any contract, there is a lower net price. This has had a negative double-digit pricing impact over the last several quarters. This gained access is a major driver of XELJANZ's excellent volume growth. We expect in 2021 and beyond for the volume impact to significantly outpace any pricing impact.
Since launch, we have consistently grown volume over 30% a year, excluding the impact of COVID recently. As for the JAK class, we see the entrance of competitor JAKs as being a positive. In the U.S., 32% of all new-to-brand advanced therapy scripts are now from JAK. Given the high unmet need in rheumatology and UC, the attractiveness of an oral therapy and a significant biologics market that can still be penetrated, this gives us great growth potential in the JAK class. We look forward to launching ankylosing spondylitis to further strengthen our leadership in rheumatology. AS continues to have a significant unmet need for the 1.7 million adult patients in the U.S. and the E.U. We have a strong field force footprint and deep customer relationships, giving us a competitive advantage in rheumatology.
In the phase III trial, XELJANZ was found to be an efficacious and safe oral option for those who had an inadequate response to NSAID, meeting both the primary and the secondary endpoint at 16 weeks. Data was submitted as an sNDA to the FDA. We expect our PDUFA to be the second quarter of 2021. Oncology biosimilars portfolio is an exciting one and is now the largest in the industry, with six biosimilars approved, including mAbs, as well as supportive care products. Over the next several years, we expect the growth of our oncology biosimilars to be driven by global launches and increasing utilization, especially here in the U.S. IBRANCE is the leading CDK4/6 inhibitor in metastatic breast cancer. In the U.S., IBRANCE holds an 87% share in first-line CDK use. We expect to defend our market-leading position.
Oncologists view IBRANCE profile favorably, with over five years of patient and physician experience. Real-world data recently shows a statistically significant benefit of 32% in overall survival. We conducted research with KOLs and oncologists as recently as July and August, and consistently, prescribers reiterated their positive view of IBRANCE as the leader in metastatic breast cancer now and in the future. Since the category is large, growth will naturally moderate as it's difficult to maintain the same growth on such a large and growing base. Despite the monarchE results, we do not anticipate an impact on IBRANCE prescribing in metastatic breast cancer. We expect patients treated with a CDK in early breast cancer to be retreated with a different CDK if they progress to metastatic.
Currently, Pfizer is aware of at least five studies evaluating CDK after the CDK usage, with results anticipated in the late 2022, early 2023 timeframe. We remain confident in IBRANCE leadership as the preferred CDK in metastatic breast cancer. We believe we have a best-in-class commercial organization in Pfizer BioPharma. We have breadth and depth of therapeutic areas with a proven track record of capital allocation that drives growth. Our strengths are founded in our disease knowledge, legacy of customer relationships, and execution excellence. Everything that we're doing today is directly applicable to launching our pipeline. We've also demonstrated that we can set new standards for launch with industry-leading capabilities. This is evident in our recent launches such as VYNDAQEL and our oncology biosimilars, and we will do this again if we're successful with our COVID vaccine.
The Triad structure integrates our commercial, clinical development, and research organizations, allowing us to introduce commercial insights early in the development process. Our end-to-end capabilities also help us to be a partner of choice in business development, and we've seen this play out successfully, as in recent examples like Array and BioNTech. Strong fundamentals position BioPharma for continued growth. We have seven key inline drivers. We have limited LOEs. We have a commercial engine that delivers customer focus and global scale with capabilities that are directly applicable to our pipeline. We have a prolific and exciting pipeline that is truly focused on breakthroughs. These are the reasons why we are confident we can deliver 6% or more revenue CAGR from now till 2025.
I know you will enjoy hearing from our Triad team about the strength of our pipeline and how we will fuel the next stage of growth in BioPharma. Now, Chuck, back over to you.
Thanks, Angela. Now we're going to take a break, so please stand by and we'll resume in 10 minutes with a presentation from our Internal Medicine leadership team.
[Break]
Welcome back. Now we're going to move into our Internal Medicine program. To kick it off, we'd first like to share a video featuring Roger Ortega, a NASH patient.
I felt kind of tired and exhausted that day that it all happened. I found myself passing blood and vomiting blood. They took me into the intensive care, and the doctor came and told me that he believed I had NASH, non-alcoholic steatohepatitis. Prior to that, I had been diagnosed with type 2 diabetes. I don't drink, didn't smoke, but I was morbidly obese. I weighed over 300 pounds. With healthier behavior, I believe I have slowed it down, obviously. I hope that they find a cure for it, or at least something that will negate it, and for future generations, not just mine.
I'd like to turn it over to the Internal Medicine triad.
Hello and welcome. Internal Medicine has a legacy of discovering, developing, and commercializing best-in-class therapies. Many of these are not only household names, but they've been the backbone of Pfizer's long-standing success. Through our focus on cardiometabolism, Internal Medicine is well-positioned to continue to address diseases that impact patients on a massive scale. We're pleased to discuss our R&D strategy with you today. We're excited to share data on several development programs that we believe have either first-in-class or best-in-class potential. Here's the team presenting today. Between the three of us, we have over 75 years of internal medicine experience. My name is Mike Gladstone. I'm the Global President of Internal Medicine. James Rusnak is our Chief Development Officer. He leads both the Internal Medicine and the hospital categories.
Morris Birnbaum is our Chief Scientific Officer in Internal Medicine. Let's take a closer look at our expertise and our reach. Internal Medicine drives innovation that diagnoses, treats, and prevents the most prevalent healthcare challenges facing our societies. In 2019 alone, we reached approximately 59 million patients. First, we have an aging population with chronic metabolic conditions that are at an epidemic level. Second, the diseases we focus on, such as obesity, cardiovascular disease, and type 2 diabetes, these are some of the largest cost drivers in our healthcare systems. We've got an unmatched track record in developing and commercializing massive primary care medicines like ZOLOFT, LYRICA, LIPITOR, NORVASC, and ELIQUIS. While some companies have backed away from CV med, Pfizer continues to invest here because we recognize the tremendous unmet patient need that still exists. We've got an industry-leading footprint in cardiology and primary care.
That means we know the healthcare providers, we know the patients, and we know how to get medicine into the hands of patients that need them. Our experience and reach make us a compelling partner. We strategically engage with other industry members in order to complement our already strong portfolio. Our footprint with PCPs will also be an advantage when we launch tanezumab. We're excited about tanezumab as a potential first-in-class non-opioid treatment for patients with chronic pain due to moderate to severe osteoarthritis who've experienced inadequate pain relief from other analgesics. Our regulatory applications for tanezumab are under review by FDA, EMA, and Japan's PMDA. We're looking forward to FDA's decision in December later this year. Now I'll turn it over to Morris to introduce the Internal Medicine R&D strategy. Morris?
Thanks, Mike. Our Internal Medicine pipeline strategy addresses the increasing global burden of metabolic disease. Because of the incredible advances in the treatment of life-threatening diseases, people are living longer, and this, coupled with increased food intake and sedentary behavior, has led to a worldwide epidemic of obesity, and with it, what we at Pfizer call the dysmetabolic state. This dysmetabolic state, the hallmark of which is insulin resistance, puts people at risk for diabetes, non-alcoholic fatty liver disease, and cardiovascular disease. With our expertise in cardiometabolic conditions and our deep commitment to use this knowledge in the development of novel therapies, Internal Medicine is well-positioned to make significant contributions to the fight against these global epidemics. To address the needs of so many people with cardiometabolic diseases, Internal Medicine has assembled a novel, science-driven, and balanced early- and mid-stage pipeline that spans multiple diseases and indications.
We currently have nine medicines in active clinical studies and more following in the clinical pipeline made up of potential medicines discovered and developed in-house. Today, we would like to share exciting data and development plans for several investigational therapies. We'll focus on our combination of ACC and DGAT2 inhibitors for NASH, two drugs that were recently given INN of clesacostat and ervogastat. we'll also talk about danuglipron, the INN for our small molecule oral GLP-1 receptor agonist for diabetes and obesity. First, we'd like to bring you an update on vupanorsen, a promising potential treatment for cardiovascular disease that we acquired through an in-licensing agreement with Akcea and Ionis.
Thanks, Morris. vupanorsen is a great example of our strategy to identify external opportunity to further strengthen our internal portfolio. vupanorsen has shown promise in early studies of reducing atherogenic lipoproteins that could help reduce residual CV risk. Cardiovascular disease continues to be the leading cause of death and disability worldwide. Elevated levels of LDL cholesterol are an established risk factor for coronary heart disease. Substantial CV risk remains even after levels of LDL-C have been lowered by statins and PCSK9 inhibitors. You'll see that here in the FOURIER study with PCSK9 inhibitor of evolocumab. The residual risk here shows that we need to address other risk factors beyond LDL-C, such as non-HDL-C and triglyceride-rich lipoproteins. We estimate that over 6 million U.S. patients are at a high risk of a major CV event despite already being treated with statins.
James's going to talk more about the role of vupanorsen and how it can play a role in addressing this residual risk. James?
Angiopoietin-like 3, or ANGPTL3, is a protein produced and secreted by the liver that is a key regulator of lipid and cholesterol metabolism. Individuals with a genetic loss-of-function mutation in ANGPTL3 have lower lipid levels and a reduced risk of coronary artery disease by approximately 35%-40%. Amongst its functions, ANGPTL3 regulates lipoprotein lipase, or LPL, and endothelial lipase, or EL, controlling the conversion of VLDL to VLDL remnants. VLDL remnants are thought to be highly atherogenic, pro-inflammatory, and can be directly inserted into the arterial wall without modification. It has been proposed that on-statin CV risk is strongly associated with these VLDL remnants.
We believe vupanorsen, an investigational antisense oligonucleotide which leads to enhanced clearance of VLDL remnants, will result in reduced cardiovascular risk as the reduction of ANGPTL3 causes increased production and clearance of these VLDL remnants, as well as reductions in triglycerides, LDL, non-HDL, and other lipids. A large meta-regression analysis that includes 49 trials with 375,000 patients showed that a reduction of non-HDL in addition to triglycerides, is strongly associated with a lower risk of major cardiovascular events, as demonstrated on the chart on the left. The charts on the right are from Akcea and Ionis' phase I-B study in healthy volunteers with elevated triglycerides. Once-weekly doses of vupanorsen led to dose-dependent reduction in non-HDL cholesterol and triglycerides. At the recent ESC Congress, Akcea presented results from a II-A study of vupanorsen in patients with non-alcoholic fatty liver disease, type 2 diabetes, and hypertriglyceridemia.
The phase II-A study evaluated a lower dose range than the earlier phase I-B study. It met its primary endpoint of triglyceride reduction and several secondary lipid parameters. While the overall phase II-A result met the primary endpoint, the maximal effects on some lipid parameters, particularly non-HDL-C, were not as robust as originally observed at the higher doses of the phase I study. Pfizer is leading the development of vupanorsen moving forward with a focus on cardiovascular risk reduction. We are initiating a phase II-B study to complete additional dose ranging in patients representative of our planned phase III population. The phase II-B study will be initiated later this month and is a placebo-controlled trial in 260 patients with elevated non-HDL cholesterol and high triglyceride levels who are on stable statin therapy, plus or minus ezetimibe. We are collaborating on this study with the TIMI Group.
It will assess the safety and efficacy of different doses of vupanorsen, along with assessing the safety and efficacy of the same monthly dose of vupanorsen given at different dosing intervals. Our phase III program will include a large-scale cardiovascular outcome study, which will enroll patients with elevated non-HDL cholesterol who are at increased risk of cardiovascular events. Two additional phase III studies will support a severe hypertriglyceridemia indication and will seek to demonstrate superiority of vupanorsen to placebo and to VASCEPA in reducing triglycerides, LDL cholesterol, non-HDL cholesterol, and ApoB. In closing, we're very encouraged by the human genetic data that demonstrates loss-of-function variants of ANGPTL3 having a reduced incidence of coronary artery disease and the early data that we've seen with vupanorsen. We see great potential for vupanorsen as a new approach for patients who need additional treatment to lower their on-statin residual life-threatening cardiovascular risk.
Now, I'll turn it back to Mike to introduce our NASH program.
Thanks, James. Before we move on to NASH, I want to take a minute to highlight the potential opportunity with vupanorsen. Subject to approval, we'll launch in 2025. The indication will be severe hypertriglyceridemia. This is for triglyceride levels above 500 milligrams per. Over 2 million patients fall into this category. The larger unmet need and also the larger opportunity for vupanorsen are in cardiovascular risk reduction. We'll launch that indication in 2028. We estimate that there'll be over 6 million statin-treated patients with significant residual risk by 2028. This means triglyceride levels above 200 milligrams per deciliter or other risk factors, including elevated non-HDL-C. Vupanorsen will be an add-on therapy to statins plus other lipid-lowering agents. The goal here is to further reduce residual CV risk. We're really excited about its potential. Let's take a look at NASH.
NASH is a serious and growing condition for which there are currently no FDA or EMA-approved treatments. Our expertise in metabolic disorders, coupled with our differentiated approach in NASH, will enable us to develop breakthrough medicines for patients. While a lack of treatment and a validated non-invasive diagnostic leaves some question about the prevalence of NASH, I want to be clear, this disease has significant consequences, it carries a growing burden for patients and healthcare systems. NASH significantly increases morbidity, it's one of the leading causes of liver transplants in the U.S. By the way, the severity of hepatic fibrosis is defined in stages, they range from F0 or no fibrosis to F4, which is cirrhosis. Evidence suggests that significant to advanced fibrosis, that's stages F2 and F3, are associated with both liver-related and all-cause mortality.
I'll turn it over to Morris to tell us more about our NASH strategy in more detail.
NASH pathogenesis is complex and multifactorial, involving fat accumulation, inflammation, liver scarring, and, if left untreated, progression to life-threatening liver failure or cancer. At Pfizer, we view NASH as fundamentally a metabolic disease. We believe that by targeting core metabolic pathways, we can drive the fat out of the liver. By doing so, not only prevent NASH in susceptible individuals, but actually reverse the inflammation and fibrosis in patients who already have the disease, ultimately preventing the life-threatening downstream consequences of NASH. Let's take a closer look at the key biochemical pathways we are targeting with our potential first-in-class therapeutics. Acetyl-CoA carboxylase, or ACC, catalyzes the first step in the synthesis of new fat and is a key regulator of fat oxidation, making it an attractive therapeutic target for hepatic fat reduction.
Additionally, emerging preclinical and clinical evidence suggests that ACC inhibition may have direct effects on reducing inflammation and fibrosis. At the other end of the pathway, diacylglycerol 2, or DGAT2, is the enzyme that catalyzes the terminal step of lipid synthesis, the production of triglycerides, which is the form of fat that accumulates in the livers of NASH patients. Interestingly, inhibition of DGAT2 has an indirect effect to shut down those genes that encode the enzymes of fat synthesis. Though we don't understand how this happens, it is important to the rationale for combining the DGAT2 and ACC inhibitors. First, let's take a look at the early clinical profiles of each of these inhibitors when used as monotherapy.
Here are the results from a phase I study of our potential first-in-class DGAT inhibitor, ervogastat, in subjects with NAFLD, that is, individuals with excess fat in the liver but no signs of NASH. As you can see in the bar graph, treatment led to a dose-dependent decrease in liver fat, with a higher dose achieving a 40% reduction in fat in just two weeks, compared to a 10% decrease in response to placebo. The ervogastat reduced circulating triglycerides, an important risk factor for cardiovascular disease and pancreatitis. Let's take a look at what happens when ACC activity is inhibited. Like DGAT2, inhibition of ACC also reduces liver fat. In a 16-week study in patients with NAFLD or presumed NASH, ACC inhibition with clesacostat reduced liver fat by more than 60% at the highest dose tested, again, with a placebo-dependent decrease of less than 10%.
clesacostat also caused a 40% in ALT, a circulating marker of liver injury. As shown in the panel on the right, the marked decreases in liver fat were accompanied by a significant increase in serum triglyceride, a recognized consequence of ACC inhibition. ACC has such a profound effect on steatosis and has the potential to directly reduce inflammation and fibrosis, we sought a way of mitigating the increases in serum triglycerides while maintaining or even enhancing the positive effects of ACC inhibition. As I described earlier, because of the indirect effects of DGAT2 inhibitor to reduce the levels of enzymes essential for fat synthesis, we reasoned that by adding it to the ACC inhibitor, we might suppress the increase in circulating triglycerides. We're pleased to share with you today the results of a phase II trial evaluating the combination of our ACC and DGAT2 inhibitors.
These exciting data were recently presented at the International Liver Congress. As shown in the panel on the far left, after six weeks treatment, both DGAT2 and ACC inhibitor monotherapy reduced hepatic fat in subjects with NAFLD, with the combination offering efficacy comparable to ACC alone. As shown in the second panel, a larger proportion of subjects achieved a greater than 50% liver fat reduction on the combination relative to DGAT inhibitor on its own. Now let's take a look at what happened to serum triglycerides. As shown in the far right panel, as expected, the ACC inhibitor increased circulating triglycerides, while the DGAT2 inhibitor offered a slight reduction. Importantly, the combination of the two agents yielded a fasting triglyceride profile indistinguishable from placebo, completely correcting the adverse effects of ACC inhibitor monotherapy.
Shown in the table at the bottom of the slide, the ACC DGAT2 inhibitor combination significantly reduced the number of times fasting triglycerides rose above the threshold levels of 400, 600, or 800 mg/dL , again producing a profile comparable to placebo. These are very exciting data, as they reveal a potential way to realize the efficacy of ACC inhibition and still maintain a favorable safety profile. The early ACC and DGAT2 inhibitor data are highly encouraging, currently the only definitive way to evaluate NASH efficacy is by assessing histological changes in a biopsy study. We have progressed both the DGAT2 inhibitor monotherapy as well as the ACC DGAT2 inhibitor combination in a phase II-B liver biopsy study, which began enrolling this past June. The outcome of this study will guide which candidate or combination progresses to phase III.
Unfortunately, there isn't enough time today to discuss the emerging data for our KHK inhibitor or other early innovative approaches. Nonetheless, I hope you got a sense of our commitment to NASH, our excitement about our novel metabolic approach, and the many different ways we are attacking the problem. We are rapidly progressing a robust pipeline of first-in-class agents designed and developed within our own laboratories. We believe that the strong scientific rationale for these mechanisms will increase the likelihood of their success as NASH therapies. Mike and James will talk about another area of significant patient need, type 2 diabetes and obesity, and discuss our small molecule oral GLP-1 program.
Thanks, Morris. The obesity and type 2 diabetes epidemics represent the largest medical challenges confronting the world today. We believe there's a significant opportunity to reach many more patients with our potential first-in-class, small-molecule, oral GLP-1 RA, danuglipron. The numbers here are astounding. 650 million obese patients today, less than 5% of them have been treated with medicine. The cost of managing the 200-plus comorbidities associated with obesity is significant. We know for most patients that diet and exercise simply are just not enough to make a meaningful difference. When you look at type 2 diabetes, about half of the patients remain undiagnosed. About half of those that have been diagnosed still are not at their HbA1c treatment goals. The end result here drives significant cost to the healthcare systems.
The GLP-1 class is a proven mechanism of action that offers compelling diabetes and weight loss efficacy with cardiovascular benefit. However, the current injectable GLP-1s are underutilized for type 2 diabetes. That's why our scientists set their sights on identifying a breakthrough approach to managing these conditions with a small molecule oral GLP-1 RA. The compelling phase I data we shared with you in June leads us to believe that we have a potential breakthrough treatment on our hands for both obesity and type 2 diabetes. I'll turn it over to James to share more about this exciting program. James?
The discovery of non-peptide, small molecule GLP-1 receptor agonists has been a significant challenge. Pfizer Internal Medicine has remained committed to this pursuit, however, due to the large patient need and the promise that a true small molecule agonist holds. Our phase I data suggest that danuglipron will yield a differentiated profile that is expected to deliver potent benefits on blood sugar and weight loss, safety and tolerability comparable to the peptide GLP-1 class, good oral bioavailability with no food or dose restrictions, and unlike the peptide-based oral GLP-1, danuglipron may be suitable for both monotherapy and combination therapies. Let's have a look at the data. This is very exciting phase I data, and it was shared in an analyst briefing in June of this year. This is an inpatient study conducted in subjects with type 2 diabetes on stable metformin background.
For the higher doses, subjects were titrated for the first two weeks and then stabilized at the target dose for the second two weeks. We observed robust reductions in fasting plasma glucose and hemoglobin A1c at all doses. This study was only four weeks in duration, so the changes in hemoglobin A1c likely have not reached maximum effects. Study subjects experienced robust reductions in body weight at higher doses. danuglipron was well-tolerated in the study with an adverse event profile that was consistent with the GLP-1 class. I would also like to proactively address the questions we've heard on GI tolerability. As expected, we did observe dose-dependent increases in GI-related adverse events, including nausea, diarrhea, and vomiting.
When looking at GI tolerability in this study, it is important to keep in mind that this was a short, four-week, phase I study where we utilized an aggressive dose titration scheme to reach the higher doses. On average, uptitrations occurred every two to three days. This aggressive titration was required because we sought to evaluate doses for at least two weeks at steady state. As a result, the tolerability data from this study is not comparable to more typical phase II and phase III data reported with other agents where longer and slower titration schemes were used. In fact, our upcoming phase II studies, dose titration will occur at weekly or biweekly intervals. These studies will titrate more slowly and are of a longer duration, they will provide a more representative picture of the tolerability profile of danuglipron.
Based on the phase I results, we are poised to continue to progress our oral small molecule for both type 2 diabetes and obesity and have an ambitious program in place. Our aspiration is to develop the most efficacious oral therapy for type 2 diabetes and develop the first small molecule oral GLP-1 receptor agonist for treating both obesity and type 2 diabetes. We are also exploring this asset in NASH, and we believe danuglipron may ultimately be best utilized in combinations with one of our other NASH assets. I'll now turn it back to Morris to help close us out.
We began today's discussion by describing how the modern lifestyle has led to an epidemic of diseases that share as their basis the dysmetabolic state. We also shared with you how Pfizer Internal Medicine is building on the newest science to develop an innovative pipeline to treat some of the most prevalent health challenges facing society today and over the next decade. While many other companies are exiting the cardiometabolic area, we chose to double our commitment, recognizing the tremendous impact of these conditions on human health and the economy, and understanding the responsibility of Pfizer to make a real difference in such a challenging but important area of healthcare.
With Pfizer's deep knowledge of the basic biology of human metabolism, our years of experience in the discovery, development, and bringing to patient of therapies for cardiometabolic disease, and our passion for turning that knowledge into first-in-class or best-in-class medicines, we are confident in our ability to address multiple diseases stemming from the dysmetabolic state. In doing so, we have the potential to improve the lives of millions of patients and make a significant positive impact on society. On behalf of James, Mike, and the more than 7,000 Internal Medicine colleagues working every day to advance breakthroughs that change patients' lives, we thank you for your time and attention and look forward to answering your questions.
Great. Thanks. Now we've got James, Morris, and Mike available here ready to answer your questions about the portfolio and the pipeline. Operator, at this point, can we please now call for questions for the Internal Medicine triad? Thanks.
Yes. If you would like to ask a question, please press star, then the number one on your telephone keypad. We'll pause for just a moment to compile the Q&A roster. Your first question is from the line of David Risinger with Morgan Stanley.
Yes. Thanks very much. Thank you, Chuck and team, for hosting the sessions. We really appreciate it. Chuck, I don't know if it's appropriate or not, but I wanted to ask about the higher-level pipeline projections. Just to confirm, the $35 billion-$40 billion pipeline peak, is that in 2030? The 50% risk adjustment, is that the average risk adjustment for that pipeline that you're assuming? With respect to the team that just presented, I just wanted to better understand a little bit your philosophy with respect to developing assets, considering the competitive landscape. For example, as you think about NASH, could you talk about that competitive landscape and Pfizer's positioning and time to market relative to other companies?
In addition, with respect to the oral GLP-1, if you could speak to that as well, how you assess the competitive landscape and how you make decisions on the appropriate level of investment spending in light of those considerations. Thank you so much.
Yeah, David. Chuck here. Your first question, before I turn it over to the IM team, that's the $35 billion-$40 billion represents potential peak sales. Now remember, not every potential compound has peak sales in the same year. If we normalize and said at peak for each compound, that's where you get that number as opposed to a single estimate for a given year. That's if you said all of them achieve peak sales in their respective years where they would be hitting peak sales, that's where we see the potential. Again, we're not pinpointing that to a specific year. That's in a sense totality and really on a continuum basis. Regarding risk adjustment, yes, as we look at each compound, we assign each compound a different risk adjustment based on what we've seen in terms of the data so far.
Our view is the reality, as we all know, is you either have a compound or a compound fail. It's either a zero or you have a successful compound. That's how we're looking at this, rather than to say somewhere in the middle, some will win, some will lose. That's what the risk adjustment does. That's when we take this as a totality of the pipeline, just to give you all a sense of what we see in the situation where they were all successful and hit peak sales. From that point, we would take a general risk adjustment. In that sense, let me leave it there, and then I'll turn it over to Mike to moderate with his group here on your specific internal medicine questions. Thanks, David.
Thanks, Chuck. I think we'll start out with the competitive set situation, and I'll ask Morris to start there, and then I'll follow with GLP-1 and commercial considerations. Morris?
Thanks. Thanks for the question. You're absolutely right. We're not in the first wave of potential NASH therapies, but we do have the advantage of seeing what's happened before us, and I think the message is very clear. We know the results of the study so far. They've been largely disappointing, and we interpret that as validation of our underlying philosophy, which is the only way to effectively treat NASH is by going at those core metabolic pathways. Honestly, the late-stage clinical trials that have failed have not addressed that strategy. They've largely been repurposed drugs that were initially developed for other diseases and were now switched over to a NASH therapy. Yes, we're not first, but we're still pretty confident based on the results of other studies.
Also, I should say, based on the human genetic results that have come out over the last couple of years, again, validating the metabolic basis of the disease and really providing reinforcement that our metabolic strategy ultimately will have the most efficacious outcome.
Thanks, Morris. The big challenge remaining here is screening, diagnosis, and monitoring of NASH. This is still a very big opportunity. It's been estimated that there are 18 million NASH patients in the U.S., and roughly about 30% of these patients have cirrhosis stage F2 and 3, which is what we're targeting. There's a wide range of opinions as to what the external community thinks will be the diagnosis and treatment rate. The range is somewhere between 20% and 75% expected diagnosis rate for F2 and F3. We believe that our assumptions are on the more conservative end of that. At the end of the day, this is a pretty large opportunity for us, and as this landscape evolves, so will we in terms of our assumptions. We think we're well prepared to bring a competitive product to the marketplace here.
Let's shift over to GLP-1. I think the important thing to keep in mind here is that if you look at type 2 diabetes treatments, the GLP-1 has about a 44% share of the non-insulin diabetes dollar sales in the U.S. They only have about a 9.6 share of the total prescription. We think the treatment gap here is due in part to the limitations available with the current GLP-1s. It's in their route of administration. They're either injectables or they're very difficult to take with significant food restrictions. We believe that the opportunity here with danuglipron is significant if we achieve our target profile and we have an oral product that delivers potent reduction of A1c and body weight without food restrictions, and it can be combined with a lot of other compounds.
If it hits its target profile and it's approved, we believe it'll be as competitive as the best-in-class agents in the GLP-1 class. With that, James, do you have anything else to add on GLP-1?
Yeah, Mike. Thank you very much. I think the GLP-1 opportunity is very exciting. Again, what we're striving for here is to be the most efficacious oral treatment for diabetes and a treatment for obesity. I think what's exciting about the data that we've seen to date, while it's been short duration, at steady state after two weeks, we have a HbA1c reduction that is comparable to what is seen with marketed agents at three or six months. We know that it takes quite a while to stabilize the HbA1c over that time period. We do anticipate that we will get additional efficacy data over that intervening time period in phase II and phase III studies. I think that this will allow us to demonstrate superiority in the oral agent class.
It's also exciting because we can use danuglipron in combination with other agents, not only for diabetes, but also potentially for NASH and really close that treatment gap that you spoke about earlier, Mike.
Thanks, James. I think we can go to the next question.
Your next question is from the line of Umer Raffat with Evercore. Umer, your line is open. Okay, our next question is from the line of Louise Chen with Cantor.
Hi. Thanks for taking my questions here. I had a few. First question is, how much upside to that 6% CAGR do you think we could see if your COVID-19 vaccine is successful and revenues turn out to be recurring? Secondly, on NASH, how long do you think your studies have to be to show a reversal of fibrosis? Do you think combo therapy will be more effective than monotherapy here? Any thoughts? Last one, just on this oral GLP-1, how do you think about oral versus injectable and how that debate will play out? Thank you.
Okay. I'll turn the CAGR question over to Chuck, and then we'll go to NASH with Morris on the length of the study and combinations. Chuck, I don't know if you want to comment on that first question.
Sure, Louise. We've said that if we're successful with the COVID vaccine, that is something you would then make any appropriate updates to the 6% plus CAGR. We're not making that update today, but certainly if the time comes, we will let you all know how that changes our thinking. Thanks, Louise.
Morris Birnbaum, we can go to you to talk about the length of the studies needed for reversal and/or combination. Thoughts on combination.
Thanks, Mike. Let me start with combinations. There's been a lot of enthusiasm in the NASH field for combinations and it's rational in the sense that most metabolic diseases end up with combination therapy. They're complicated multifactorial diseases, and NASH falls within that class. We are going to be testing combinations for a number of the agents, some you've heard about today, going forward. Ultimately, whether we end up with a combination or we can get enough efficacy with monotherapy will be determined by our phase II biopsy studies, and we'll make a decision off of that. We're certainly open to combinations and agree that it might be necessary, but the data will ultimately tell us. I'll turn it over to James to talk about the clinical plans for NASH.
Thanks, Morris. Yeah. Currently, we have the DGAT and DGAT-ACC combination in a phase II-B study. The primary endpoint of that study is a biopsy timed at 48 weeks. We believe that a 52-week to 72-week biopsy for phase III will be appropriate and will be guided by our phase II data as well as other data as it emerges in the field.
Great. Now, as we turn to move over to oral GLP-1, how will the oral versus the injectable game play out? I'll probably have a few words, then I'll kick it over to James to see if you have anything to add. It's still early. I think one of the big challenges here with the utilization with the GLP-1 is for administration, as injectable, and the only oral out there has significant food interactions. We think the advantage here will be that we can deliver a targeted profile. We can have a product that doesn't have the food restrictions that are currently available or the inconvenience of an injectable, and this product can be combined with other compounds. James, is there anything else to add there?
Yeah, Mike, I think that while speculative, there is some real promise for an oral agent. That's because an oral agent actually is a true small molecule, gets absorbed in the intestines, where GLP-1 is endogenously produced and GLP-1 receptors reside. Subcutaneous injection, while it certainly can reach those areas, wouldn't necessarily reach to the same extent. Of course, the other oral agent which is available gets absorbed through the gastric wall. That may be a potential theoretical benefit for this oral agent. Morris, anything else?
No, I think we covered it well, James. Just to reiterate, it's a controversial field. There's no doubt that there are receptors outside the brain, and those receptors are in the portal complex as well as the wall of the intestines in the plexus. It's also pretty clear that these get activated with an oral when you take food because GLP-1 is secreted from the intestines. There is some reason to believe and some data to support the idea that a gastrointestinal absorption of an activator will lead to a differentiated response. If anything, it's been associated with the satiety response after a meal. We'll see. We have to do the experiments, but at least there's a basis to be optimistic about getting a different profile with an oral drug than an injectable.
Thanks to both. I think I'll probably just end off and say the weight loss efficacy of the currently approved therapies for type 2 diabetes is limited, with single-digit reductions in body weight, and we need to do better than that. Obesity also needs to be understood as a metabolic disease instead of a lifestyle issue, and this is going to require some market development. Pfizer's got the history and understanding of what it takes to bring a medicine like this to market, and we're working with that to be market ready. Thank you for your question. I think we can probably go to the next one.
Your next question is from the line of Chris Schott with JP Morgan.
Great. Thanks so much for the questions. My first was on vupanorsen. Can you just help us put the efficacy here into context relative to other products on the market? I guess specifically, are you expecting the benefit driven from this drug to be largely triglyceride-lowering in terms of the driver, or do you think there's other elements of the profile that will also drive the CV outcomes benefit for this product? My second question was just on tanezumab, just as we're approaching the approval of that drug. Just the latest update about how you're thinking about the commercial opportunity here. I guess given the need in the market balanced against some of the safety profiles that we've seen emerge with that one. Thanks so much.
Great. Thanks, Chris. James, if you can start off with vupanorsen, then I'll follow back with the tanezumab question.
Okay, we see the opportunity with vupanorsen to be addressing a lipoprotein and residual cardiovascular risk in a broad perspective. We do believe that there's a substantial opportunity beyond just triglyceride lowering. Vupanorsen reduces non-HDL cholesterol in a dose-dependent fashion. Akcea, in their phase II-A study, studied a lower end of the range, which was initially studied in the phase I program. What we intend to do in our phase II-B study is actually expand out those ranges beyond what was studied in the phase II-A trial to really understand the efficacy that we can derive on non-HDL. Non-HDL is tightly linked to cardiovascular risk reduction, and we'd be seeking to take that data and design a cardiovascular outcome trial to show that in patients that are already receiving very efficacious and lipid-lowering therapy so that we can reduce their cardiovascular risk largely through non-HDL reduction with vupanorsen.
Morris, anything else to add on that?
Yeah. Thanks, James. Increasingly, we're basing our prediction on how these drugs are going to work on human genetics. We do have a lot of information on the phenotype of individuals who are deficient for ANGPTL3 protein. Yes, there's a marked decrease in triglycerides, but equally important, there's a decrease in non-HDL cholesterol, as James said, but there's also a decrease in LDL cholesterol. Importantly, the decrease in LDL cholesterol is by an LDL receptor independent mechanism, which gives knocking down ANGPTL3 the potential of lowering LDL cholesterol further, even when maximally treated with one of the drugs on the market, both of which work through the LDL receptor. There's a lot of reasons to believe that ANGPTL3 is going to reduce cardiovascular risk by multiple mechanisms.
Great. Thank you for the question. I'll answer the question about the tanezumab opportunity. I guess when we think about tanezumab opportunity, first we can think about the unmet need. There's a large unmet need in osteoarthritis, and we think tanezumab can play an important role. When we think about it in the U.S., we've got 27 million people with osteoarthritis. 11 million of those have moderate to severe osteoarthritis. Couple that with the fact that 80% of these patients have tried and failed three or more analgesics. There haven't been any new classes of medicines in this category for over a decade. You put those factors together, there's a lot to be excited about tanezumab, and we're looking forward to hear from the FDA about our BLA in December of this year. Thanks for the question. I think we can probably go to the next one.
Your next question is from the line of Geoff Meacham with Bank of America.
Hey, guys. Thanks for doing the event. Just had one question on R&D strategy and one on NASH. For Albert or Mikael, on the strategy, I know you guys have raised the pipeline success rate. What would you say mostly drove that? Was it broader deployment of biomarkers? Was it a more dynamic clinical trial design? Is there an opportunity to further increase your phase II and ultimately phase III success rate? On NASH, I know the long-term approach, as mentioned before, is likely combo therapy with two or three mechanisms. Is there one that you view as foundational, and how would you characterize the FDA environment for NASH, just with respect to shortening the studies and maybe more rapidly de-risking in the clinic? Thank you.
Thanks for the question. This will be our last question. With that, I'll turn it over to Morris to talk about NASH and combinations, and then I'll ask Chuck to see if there's any comments on the first.
Great. Thanks, Mike. I think at this point, it's too early to commit to one therapy that we're particularly optimistic about. Obviously, you heard about the excitement of being able to inhibit ACC1 and to a fairly large degree and not be concerned about the increase in triglycerides. We're very excited about that. As always, we're going to have to see what the biopsy studies show. As we mentioned earlier, we've got a number of different mechanisms, independent mechanisms coming through the pipeline. We will find out which works the best. Right now, we're very excited about our lead studies, which are the ACC/DGAT combo and DGAT2 inhibitor alone. James, do you have anything to add on the clinical side?
I think that the question regarding the acceleration and FDA, I think that FDA has been very responsive to all of our interactions, and this is an emerging field. This is a field that we're looking for that initial standard of care to be developed. I think that right now the field is still open.
Great. Thank you. Chuck, any comments on the first question? A little bit broader than the general medicine.
Yeah, sure, Mike. Geoff, of course, we're always trying to have continuous improvement here. I think it's a combination of those factors that you referenced. As Rod pointed out in the presentation, we took a hard look at some of the areas where we were below average, identified those issues and took very specific steps to improve them. I think it's a combination. Yes, we're always going to continue to see ourselves improve, but a lot of progress made there. It really is, I think Rod and Mikael pointed out, a very different scientific organization here driven by a whole different set of parameters and really a different way to assess our success and a lot more accountability here, certainly. Thanks for the question, Geoff, and thanks for your questions.
We're going to move into our vaccines program, and we'll transition there. Before we do that, we'd first like to share a video featuring Emma Harris, who's a former RSV patient.
Knowing that Emma was going to be born with Goldenhar syndrome was a little daunting just because the previous flu season was horrible.
She started getting very lethargic. She was sleeping all the time. That's when the cough started. When the doctor came in and they did the test, she immediately was like, "Yes, she has RSV. Let's go to the hospital right now.
Dear scientists, there is nothing more perfect in the world than a brand-new baby. I was unprepared to hear our pediatrician say that Emma had RSV at 10 days old and needed to go to the ER. In those moments, she needed the care and attention of nurses and doctors. We want to thank you for the work you are doing that will help the most delicate little miracles in our lives. I hope there's a day that a scared mommy never has to watch the nurse suction their tiny little baby. Motherhood is scary enough, your work may help it not be as scary.
I'd like to turn it over to the vaccines team.
I am Nanette Cocero, President of Pfizer Vaccines, and I am thrilled to be joining you this afternoon to share some of the exciting work our team has underway. There is certainly no more relevant time to be discussing the profound importance of vaccines to society as the world has been turned upside down by what we are very familiar with now, the COVID-19 pandemic. Yet, we're also driven every day by the personal stories and the experiences of families like the one you just watched in the video. It is personal for all of us, and for me, it is especially because, like baby Emma, my son Javier contracted RSV when he was only two months old. Thankfully, he made a full recovery and today is a thriving 24-year-old, but it was a scary and difficult time for our family.
The potential to bring forward a vaccine that can help other families is what drives me and inspires me every day. I'm also inspired by our vaccine team, which includes experts and leaders in vaccine research and development, infectious disease epidemiology, medical affairs, and vaccine commercialization. You're all familiar with our flagship product, PREVNAR, and several of the leaders with you today were instrumental in bringing this vaccine to millions of people around the world. I am joined for today's presentation by Kathrin Jansen, our Head of Vaccines Research and Development, and later for the Q&A, you will meet Luis Jodar and Bill Gruber, who round out our vaccines leadership team. We and the thousands of vaccine-focused colleagues working beside us every day have a true passion for helping to protect lives and meaningfully impact public health through the power of our vaccines.
Since the acquisition of Wyeth just over a decade ago, Pfizer has worked with focus and rigor to build the capabilities that have allowed us to quadruple the number of vaccine programs we have in the clinic, and most recently, to move quickly and effectively to take on COVID-19 virus. Our efforts over the last 10 years have transformed Pfizer's presence in the vaccine space from the PREVNAR company to an end-to-end global vaccine leader anchored in three key strengths, innovation, portfolio breadth and depth, and scale. We have invested significantly in our vaccine infrastructure, and today we operate one of the most sophisticated and reliable supply chains in the industry, enabling us to deliver more than 1 billion vaccine doses since 2010 and without stockout. We also continue to fuel our research and development engine. Currently, we have nine programs in active clinical development.
Dating back to PREVNAR 13, we have received 10 Fast Track designations and three Breakthrough Therapy designations, underscoring the innovations they represent and the unmet medical needs that they address. Best of all, with our robust pipeline, we are now aiming with regulatory approval to deliver six innovative breakthrough vaccines by 2025. Another way to look at this is that with regulatory approval, we expect to be able to launch more than one innovative vaccine every year for the next five years on average. These six vaccines by 2025 include the four phase III assets you see outlined here in red. These are the candidates we will focus our discussion on today. Our next-generation pneumococcal conjugated vaccine candidate, PCV20, in development for adult and pediatric populations, and our potential first-in-class C. difficile, pentavalent meningococcal, and RSV maternal vaccine candidates.
Also included in the six by 2025 are our Lyme vaccine candidate in collaboration with Valneva and our COVID-19 vaccine candidate in collaboration with BioNTech. These programs will not be discussed in detail today. We're looking forward to sharing more on our COVID-19 vaccine tomorrow and on Lyme in the near future. Before moving on, I do also want to underscore how much progress there has been with our pipeline in the last six months alone. The slide you see today looks quite different from the version you would have seen had we held this meeting back in March. Since that time, we have initiated five new phase III trials and added the phase II Lyme program to our pipeline.
We are incredibly proud of the momentum we're building, even in the face of a uniquely challenging year. With this strong pipeline, in addition to our current portfolio, we are working towards protecting more than three-quarters of a billion additional lives by 2028. We expect to deliver sustained growth year-over-year, to be a strong contributor to the long-term growth goal of the overall company, while making a profound impact on global public health. This represents an acceleration of our growth profile compared to our recent past, driven by the six anticipated vaccine launches between now and 2025. Bottom line, we have the infrastructure, we have the expertise, and we have a passionate and committed team to successfully deliver against this growth goal. What drives us the most are those three-quarters of a billion lives across the globe that are depending on us to make it a reality.
With that, I'd like to turn it over to Kathrin Jansen.
Thank you, Nanette. My name is Kathrin Jansen. I'm Senior Vice President and Head of Vaccine Research and Development at Pfizer. I'm passionate about vaccine R&D, have focused my scientific career on improving public health through the development of high-impact vaccines, such as GARDASIL while at Merck, and PREVNAR 13 and TRUMENBA at Pfizer. As noted by Nanette, today I will review our five late-stage programs, starting with our third generation pneumococcal conjugate vaccine, PCV20, which aims to address the unmet pneumococcal disease burden in adult and pediatric populations. We established our leadership in the area of pneumococcal conjugate vaccines first with the introduction of PCV7 in the year 2000, followed by PCV13 in the 2009, 2010 timeframe. PCV7 and PCV13 had a tremendous impact on public health, reducing the global pneumococcal disease burden. We knew that we could do more.
Streptococcus pneumoniae remains a significant cause of disease and death globally for adults, infants, and children, as you can see here, with an estimated 500,000 deaths a year in adults and 320,000 deaths annually in children. To help further address this considerable burden, we now are advancing a 20-valent pneumococcal conjugate vaccine in adult and pediatric populations. Based on our estimates shown here, we believe that PCV20, once approved, could provide the most comprehensive coverage against pneumococcal disease in both adults and pediatric populations compared to the standard of care and compared to other pneumococcal conjugate vaccines in late-stage clinical development. Of course, also with advantages of a PCV that induces immune memory, lasting protection, and particularly in older adults, proven efficacy against non-bacteremic pneumonia.
If phase III is successful and receives regulatory approval, PCV20 adult will provide 33% more IPD coverage, and PCV20 pediatric will provide 42% more invasive pneumococcal disease coverage than any other pneumococcal conjugate vaccine in late-stage clinical development. I'm thrilled to present for the first time today the clinical data from our PCV20 pediatric phase II study, based on which the FDA granted breakthrough therapy designation on August 17th. Licensure of PCV20 pneumococcal conjugate vaccine requires demonstration of comparable serotype-specific immune responses to PCV13 for the serotypes in common. As you can see here for our pediatric four-dose regimen, immune responses across serotypes are indeed comparable. We also see substantial immune responses for the additional seven serotypes not in PCV13 that mirror those seen in PCV13 and for which efficacy was demonstrated previously.
These data will be presented at IDWeek next month. Registration for PCV20 pediatric is targeted for late 2022, and potential approval is targeted for mid-2023. These milestones are tracked closely to assess any potential COVID-19 timeline impact. Now to turn to our PCV20 adult vaccine. I'm very excited to share that we are close to the finish line. The PCV20 adult submission is on target for early October, with the potential approval expected mid-2021. Our team is looking forward to sharing the Phase III results from our PCV20 adult vaccine next month as a virtual presentation at IDWeek. Next, I'd like to update you on our Phase III C. difficile vaccine program. C. difficile is a potentially life-threatening disease that has been recognized by the CDC as an urgent public health threat and is classified by WHO as a priority pathogen.
C. difficile infections cause symptoms ranging from diarrhea to life-threatening inflammation of the colon and affect mostly older adults. This is a disease that can truly be everywhere. It is highly contagious, given that it is transmitted through heat-resistant spores. In the past, it was thought that the disease is mainly hospital-acquired. That is no longer the case. We now know that community-associated infections are on the rise and represent about half of all C. difficile infections. Compared to shingles, which can be prevented by a two-dose vaccine that is recommended in the United States for adults 50 and older, C. difficile causes a higher number of annual deaths in the United States and has a higher cost to the healthcare system, as shown here. Our vaccine candidate is composed of two inactivated toxins, toxin A and B, that have been inactivated through genetic and chemical detoxification procedures.
Shown here are our phase II proof-of-concept data that give us high confidence in our ongoing phase III program. Our bivalent vaccine induces high toxin-neutralizing antibody responses after three doses, as shown here for toxin B. You can see that the responses control and then persist at substantially elevated levels above baseline. Similar responses observed also for toxin A. What is the relevance of these phase II data? The majority of vaccinated subjects had antibody titers that exceeded the serum levels of a monoclonal antibody licensed to protect against recurrence of Clostridioides difficile disease. Our phase III CLOVER study is an endpoint-driven study that is fully enrolled. As publicly reported, endpoints are accruing slower than originally anticipated.
Given our confidence in the vaccine and in consultation with the FDA, we have added additional interim analysis to our study, and we expect to have the first interim analysis occurring at the end of this year. The next program I would like to share with you is our pentavalent meningococcal vaccine, or in short, penta, a vaccine designed for the broadest meningococcal disease coverage. It is heartbreaking when we hear stories of how parents watch their child suffer from the serious consequences of meningococcal disease. There are currently separate vaccines for meningitis ACWY and meningitis B with separate recommendations, which is very confusing to healthcare providers and parents. This is unfortunate because only 17% of U.S. adolescents receive at least one dose of a MenB vaccine, and far fewer receive the full schedule of meningococcal vaccine needed for protection.
We think we can do something about this confusion and help simplify the schedule to protect more adolescents and young adults. Through our acquisition of the effective meningococcal ACWY vaccine, Nimenrix, we have an excellent opportunity to combine it with our own meningococcal B vaccine, TRUMENBA, aiming to provide one pentavalent vaccine to help address meningococcal disease caused by serogroups A, B, C, W, Y in adolescents and young adults. Assuming clinical success and FDA approval, we envision a future schedule with our penta vaccine that would only require three doses, shown here in light blue, compared to the four doses in current schedules. If we are successful, this simplification should avoid confusion and help ensure comprehensive protection from this potentially deadly disease in larger numbers of adolescents and young adults. In addition, Pfizer could potentially be the leader in the meningococcal U.S. market.
To show that we're on track to potentially achieve this goal, I like to share new clinical data from our penta phase II proof-of-concept study. Shown here are the immune responses of penta in dark blue bars compared to TRUMENBA in light blue and MenACWY in gray. Similar to pneumococcal conjugate vaccine, meningococcal vaccine licensure requires demonstration that penta, again in the dark blue bars, has comparable immunogenicity to MenB and ACWY vaccines. We are pleased to show you here that penta, indeed, in almost all cases, induces comparable, if not better, immune responses than the comparators. Given these data, we believe that if reproduced in phase III, such data will help support licensure and put us in a good position to offer a more comprehensive pentavalent meningococcal coverage to help prevent this devastating disease. Additional results from this study will be presented at IDWeek next month.
Our phase III study start occurred on June 17th, 2020. As you can see on this timeline, we believe that if phase III indeed is successful, a BLA filing of the penta vaccine could potentially occur in early 2023. I now like to switch to RSV, a vaccine candidate that we believe can revolutionize how we think about protection of newborns from infectious diseases through maternal immunization, a new frontier for vaccines. For too many newborns, respiratory syncytial virus, or RSV, can cause severe respiratory disease, causing families to experience fear, anxiety, and despair as they see their newborn babies struggling to breathe, as you saw in the video played earlier in our session. RSV disease is particularly devastating in newborns, causing approximately 1.4 million hospitalizations in those less than six months of age, and unfortunately, death in many newborns across the globe.
There is currently no cure or vaccine, the standard-of-care treatments that exist today simply are not enough for this vulnerable population. Scientists and researchers have worked on the development of an RSV vaccine without success for over half a century, including Pfizer. Based on a discovery by Jason McLellan and his team in 2013, we now know that while we all had the right vaccine target, we all had the wrong structure. The left-hand side panel shows the vaccine target antigen that was the root cause of all prior failures. This structure, or the post-fusion structure of F, is not the predominant form that exists on the virus and not the structure that antibodies must bind to neutralize the virus. Instead, note the structure on the right, the pre-fusion F form, which is the right form and is the target of most naturally produced neutralizing antibodies.
The reason the pre-F structure was so elusive for so long is that pre-F is extremely unstable. Like a spring-loaded device that flips into the wrong form after the slightest trigger. Using our protein engineering expertise at Pfizer, we used our numerous inventive protein design and engineering capabilities to optimize the stability of the pre-F form and lock it down. Based on our clinical phase II data in healthy women and men, we believe that we have the most stable and immunogenic vaccine candidate for a maternal vaccine. Compared to prior attempts with our pre-F vaccine candidate, we see never-before-observed fold rises of RSV neutralizing antibodies, over 15-fold for RSV A and 18-fold for RSV B in women of childbearing age, compared to the mere two- to three-fold rises seen prior with post-fusion F or insufficiently stabilized forms of F.
Having these high fold rises to both subtypes is critical, as RSV A and RSV B circulate almost at equal rates in any given RSV season. What do these data mean, though? We modeled efficacy data from an RSV monoclonal antibody to estimate the fold rises likely needed for substantial protection. While rises from prior vaccines were not sufficient to achieve meaningful protection, and our model actually predicted this, we believe that our vaccine fold rises suggest a high probability to demonstrate substantial efficacy in newborn babies. These data provide us with confidence that our vaccine candidate, if proven successful in phase III, could be the very first maternal vaccine licensed, and most importantly, would offer protection for the most vulnerable population from RSV in the first days, weeks, and months of life.
Our phase III RSV study began on June 18, 2020, with pregnant women receiving a single vaccine dose between 24 and 36 weeks of gestation. This study is on a Pfizer accelerated pathway to bring faster forward promising vaccine candidates. Due to COVID, we are tracking the RSV disease epidemiology very closely to understand any potential impact on our timeline. We do have an interim analysis built into the program at 50% of cases. If efficacy was met at the interim analysis, the submission could occur as early as mid-2023, based on our current timeline projections. To summarize our late-stage vaccine portfolio, we have built a robust and exciting vaccine pipeline with the potential to launch six innovative vaccines by 2025. The five you see here on the slide, plus our COVID-19 vaccine candidate, which I look forward to discuss with you in detail tomorrow.
With that, I would like to hand it back over to Nanette. Thank you.
Thank you, Kathrin. As I talked about earlier, our work in the pneumococcal space is well-known. Today, in addition to hearing about our next generation PREVNAR vaccine, PCV20, you have also heard about phase III assets such as PCV20, RSV maternal, and meningococcal pentavalent vaccine candidates. You have gotten a closer look at these disease areas, the compelling data we have generated to date, and an overview of clinical timelines. Additionally, I wanted to share some information on how we are thinking about the commercial opportunity of these three assets. For PCV sales, the prevalent population ranges from 90 million-130 million people, depending on the ACIP recommendation that we receive. We anticipate vaccinating up to 5% of the target population each year in the U.S., ultimately reaching nearly half of those 90 million-130 million people on a cumulative basis.
We also expect 100% market share for the first four to five years before competition potentially enters the market. For RSV maternal, we anticipate a strong market uptake among our population, which is the number of pregnant mothers based on the annual birth cohort. We also expect to maintain a 60%-70% of the RSV maternal vaccine market, given our lead over the competition and our projection that there will be complementary usage of maternal immunization and monoclonal antibodies. Finally, within the total meningococcal market, we expect to push current penetration rates even higher to what you see here with the potential introduction of our pentavalent meningococcal vaccine. We anticipate our share of the pentavalent market to range between 40%-55%, yielding peak sales in 2029. By now, I'm sure you all can see why we're so excited about our portfolio.
We're entering a new era for Pfizer vaccines that will be driven by these six breakthrough vaccines. 2020 is a pivotal moment in our journey, not only because of COVID-19, but because of how we have accelerated and expanded our pipeline overall. We are incredibly proud of how far we have come in the last 10 years, and yet, even more important and exciting, where we're heading in the next 10 years. The best is yet to come. Thank you all for your time and attention, and now I'll turn it back to Chuck to get us started with the Q&A session.
Great. Thanks, Nanette. Certainly a lot going on in the vaccines area. We're going to get ready to move to the Q&A session for the vaccines team. Just a reminder, we're going to have a separate COVID section tomorrow with Mikael, Angela, and Kathrin presenting on COVID, then Albert will join for the Q&A session as well for that tomorrow. If you can hold your COVID questions until tomorrow, this way, the vaccines team can talk about all the other vaccines that they've just gone through. With that, operator, could we now please poll for questions for the vaccines team? Thanks.
Your first question is from the line of Vamil Divan with Mizuho Securities.
Hi. Great. Thanks for taking the questions. I do have some COVID questions. I guess I'll save those for tomorrow. One on your pneumococcal franchise and one on the meningitis side. Just in terms of the pneumococcal franchise, I guess I'm curious on how you think about the sort of near to midterm commercial look for your franchise, because Merck does seem to be a little bit ahead of you with their vaccine, the 15-valent. I can see why yours is maybe a better vaccine and maybe the leader over time. Maybe if you could talk about how you see the next one to three years playing out if Merck, if they want to get to market ahead of you, especially in the pediatric setting.
On the meningitis side, I guess we've been surprised by the relatively limited uptake for your current vaccine. You did seem to give pretty bullish sort of projection in terms of market share and penetration. I guess maybe if you can dive a little deeper into that. I know there's a 3-shot series instead of a 4-shot series, but what I guess maybe drives your confidence there in terms of that? Is that the main driver in terms of why you think there could be a lot more? I guess I'm just trying to understand that one a little bit more to see why this one might turn out to be a bigger opportunity than what we've seen so far. Thanks so much.
Well, thank you for your question. I'll begin with the question on Pneumo. We are confident that we will be maintaining our leadership position given our strong history of safety and efficacy, and expect to be 12 months behind our competition for the pediatric space. For the adult space, we are going to be coming to market by mid-next year, which is right head-to-head with competition. While current timelines indicate a potential 12 months in the pediatric space, we are leveraging our clinical expertise to explore closing this gap, just as we did with the adult vaccine. PCV13 efficacy, and even more important, the safety, are well established and recognized among physicians and patients, this is why we expect physicians to be very comfortable continuing prescribing PCV13 in the period before PCV20 potentially launches.
As you mentioned, both PCV13, I mean PCV20 adult and pediatric do add additional coverage, 42% additional coverage in the pediatric space and 33% more coverage in the adult space.
For all these reasons, we are confident that we will maintain our leadership in the pneumococcal space, short-term and long-term. To your question on the meningitis. We are also confident and very excited about this opportunity to address the current patchwork, like Kathrin mentioned, which is complicated and inconsistent recommendations. In order to simplify the vaccination schedule along allowing more adolescents to be fully protected with the five additional serotypes. This will give us A, B, C, Y, W, which covers the majority of the meningococcal devastating disease. Because of our timing, that this is ahead of our competition, as first to potentially launch, and based on strong phase II data that Kathrin mentioned, we do see a high probability for phase III success and licensure.
By entering the market in the U.S. first, we do anticipate maintaining a strong share of the market, resulting in a blockbuster commercial opportunity. To the third question on the three-shot series, I will pass on that question to my colleague, Luis Jodar. Luis, please.
Yes, Nanette. Thank you very much. Yes, I think as Kathrin and Nanette said, there are now a patchwork of recommendations. Just to remind everybody, at 11 years of age, there is a dose of the tetravalent vaccine and a booster dose at 16 years of age, and those are routine recommendations. Those are the former ACIP category A, and the uptake is very high. I think you've mentioned why you were thinking that the two doses for MenB at 16 years of age, the uptake is a little bit lower, and that's for a number of reasons, but presumably because it's a category B or shared clinical decision-making. What we are expecting when the pentavalent is introduced is to reduce the four current shots into three shots and going to the universal or routine immunization.
Both at 11 years of age after the pentavalent-containing vaccine, and then two doses to replace the three doses in the 16 years of age. For that reason, we are very confident that the uptake is likely to be very high, and even higher than the current tetravalent uptake right now. Thank you. Back to you, Nanette.
Thank you, Luis. Operator, next question, please.
Your next question is from the line of Geoffrey Porges with SVB Leerink.
Thank you very much. Appreciate the question. A couple for Luis. I just want to follow up on the question about pneumococcal conjugate and how do you expect the ACIP to handle the time difference between the availability of the package for your data and then your competitor's data? Is there a threshold where the ACIP will lump them together and just take a vote and issue a recommendation? Is that six months, three months, one month? Just trying to figure out whether there'll be a switch in the recommendation to your competitor's product and then theoretically a switch back to yours, assuming the pivotal trials are correct. A question for you, Kathrin. It's something that I'm sure is near and dear to your heart, but do you need a proprietary adjuvant system?
We've been surprised with the performance of all the supplier-derived adjuvants. I know you're headed towards mRNA. Do you think that that's something you would like to have in your portfolio and toolkit given all the opportunities you're looking at? Thanks.
Excellent. Well, thank you for your questions. You did my job. Luis will take the first question, and Kathrin will take the second question. Luis, please.
Sure, absolutely. About the timing of ACIP. Well, first of all, of course, I cannot speculate around what the ACIP is going to do, but that's an interesting question, and I think I would answer it in two ways. First, for adults, I think as you've heard Kathrin, we are sort of filing in October the PREVNAR 20. Again, we'll see how it goes, but in principle, we expect that licensure will be in mid-2021. Now, we do not know whether Merck is going to be up there or not. The idea would be that both vaccines would be either looked into the guidance and recommendations for June 2021 or in October 2021. That I think is pretty clear that both vaccines in adults are going to be sort of recommended at the same time.
As for the pediatrics, well, right now, we are one year behind. I think as Kathrin mentioned, we are trying to do our best to shorten that gap as much as possible. If we shorten that gap to less than one year, it might seem prudent to have a sort of a holistic review of the recommendations of pediatrics just together. Really that would depend on the gap between the two vaccines, and unfortunately I cannot give you whether it's three months or six months. It would be one or two ACIP meetings, I would say, as a difference. Then I pass it to Kathrin.
Thank you, Luis. Thank you, Geoff, for your question about the adjuvants. We actually have been working for a long time on the evaluation of different adjuvants. Our strategy has been to invest in a focused manner in new technologies such as adjuvants when we believe that the current approaches may not be sufficient to develop a successful vaccine. Actually, case in point is our collaboration with BioNTech on a seasonal flu vaccine. We believe that BioNTech's RNA platform may address the current shortcomings of seasonal influenza vaccines and provides a platform that we believe could provide better protection each year.
Thank you very much. Yes. Thank you, Kathrin. Operator, ready for next question, please.
Your next question is on the line of Terence Flynn with Goldman Sachs.
Great. Thanks for taking the questions. First, it is kind of a follow-up to a prior one with respect to the 20-valent market opportunity. Do you guys see that as more of a straight conversion opportunity, or is there actually a chance you could expand usage and grow your revenues over time in that segment above and beyond PREVNAR 13? One on the messenger RNA platform. How are you guys thinking about that more broadly? Is that something that, again, as you think about your partnership there, you do see a broader range of opportunities, and maybe you could talk to us about that? The third question is just on the C. diff vaccine, any way to lower the number of injections there needed from three to less than three? Thank you.
Okay. I'm going to start with C. diff question and pass it on to Kathrin, please. I'll take the PCV 20 question. I'm so sorry, but I did not get the second question. Can you repeat it?
His line is closed.
Okay. All right. Let's go then to Kathrin. Can you please then address the C. diff question on the number of doses, and then I'll address the PCV 20 question.
Yes. Thank you very much, Nanette, and thank you for the question. As you know, of course, we are very excited about our collaboration with BioNTech and the RNA platform, and you will hear much more about this in our session tomorrow. Given the exciting data that we are seeing out of this technology, you are absolutely correct. We are thinking about widening the platform to encompass additional disease targets. That is in addition to the influenza vaccine. This is something that we are working on, but we haven't decided yet on the details of those additional programs. We are also working in the context of the seasonal influenza on an RNA platform that is called self-amplifying RNA, that we believe has the best chance of success to develop a more potent seasonal influenza vaccine.
This self-amplifying RNA could potentially be very potent, and we believe that there may be an opportunity to make this a one-dose vaccine.
Thank you. Thank you, Kathrin. Now to the PCV 20 question. We are confident in the potential of PCV 20, of course, given the augmented coverage that we have mentioned. Yet, we also do recognize that there will be a period where we will have both PCV 20 and PCV 13. While our strategy is to transfer all of our PCV 13 business to PCV 20, there will be a period where we have both because the registration timeline is not the same for every country, especially for the emerging market countries. There will be a period of time where we will have PCV 20 in the U.S. and in Europe, and we will still have PCV 13 in emerging markets. Thank you for your question.
Nanette, perhaps you can point to Bill. Bill, I think there was a question about the three doses versus two doses of the PCV20 clinical program. Perhaps you want to elaborate that?
Yeah. Maybe I can just speak to that briefly. Obviously, if the C. difficile efficacy trial, the CLOVER trial, demonstrates efficacy with a three-dose regimen, there is the potential by showing that an immune response with a two-dose regimen spread six months apart. If that shows a comparable immune response, there's the potential for a two-dose regimen to be part of an indication. It's a good question, and it's something that we're interested in.
Okay. Thank you. Thank you, Bill. We're ready for the next question, operator.
Your next question is on the line of Seamus Fernandez with Guggenheim.
Oh, great. Thank you for the question. Just a couple. First on the pneumococcal conjugate. Just wanted to get a better understanding of the threshold, particularly in the pediatric patient population that's been demonstrated with your 20-valent. Historically, I think that the threshold that had been established by regulators was the .3 or .35 microgram per ML target for the antibody threshold. I'm just wondering if that threshold has been achieved with all of the 20 serotypes. As a separate question to that, if it hasn't been achieved but non-inferiority has been clearly established to PREVNAR 13, is it possible that the agency's bar has shifted to some degree, given the efficacy with PREVNAR 13? The second question I have is actually around the RSV program. Can you help us understand two questions?
Number one is passive vaccination with an antibody like nirsevimab, which we saw recently published in The New England Journal, versus maternal vaccination. Can you help us understand the advantages of maternal vaccination over potential passive vaccination? separately, just in terms of the percentage uptake that we typically see with maternal vaccination, what would be the estimated acceptance? it would seem like that might be more challenging versus a passive vaccination approach. Tjanks so much.
Thanks, Seamus. Thank you very much for your questions. The first two questions on non-inferiority, I think that Kathrin, you can take those, and Luis could probably then also add to that. I will take the RSV questions. Thank you. Kathrin.
Thank you. Just as I described earlier, the polysaccharide conjugates vaccines will be licensed against existing pneumococcal conjugate vaccine. PCV20 will be licensed by demonstration of non-inferiority to PCV13 for the serotypes in common, and then also using the 0.35 threshold for the seven additional serotypes. What we have demonstrated so far, what you have seen here, are data from our phase II study. That study was not powered to actually demonstrate non-inferiority. When we go to the adult program, that study was our phase III data, and that study was powered to demonstrate non-inferiority.
What regulators do, and what we have done in the past with PCV13, because of the large number of statistical non-inferiority comparisons that we have to do, and for PCV20, that will be 20, we have established precedent that if by chance one or more of the serotypes would miss the non-inferiority margin, that regulators will look at additional data and take the totality of the data into consideration. That is actually a very wise decision if you want, because we have seen exactly the same for PCV13 when we compared it to the original PREVNAR 7.
We found that two of the serotypes did indeed miss the non-inferiority margin. Other data, such as fold rises, the reverse cumulative distribution, and how the extent to the midst of the non-inferiority margin were all taken into consideration as well as functional antibody, which led to the licensure and approval of PCV13. What turned out then in real life after the vaccine, PCV13 that is, was rolled out, that the serotypes that actually did miss non-inferiority were very effective and continued to be effective after the use of the PCV13 vaccine. We expect to receive something like this in the phase III program, in our pediatric phase III program, that we would expect and believe that the same approach would be used to license PCV20 for the pediatric population.
Okay. Luis, for the RSV question. For RSV.
Yeah. Maybe I start. I think just should discuss some of the advantages. Luis can put into context how a monoclonal- the vaccine, assuming both are successfully approved, could coexist. From our perspective is it is our intent to, and we have designed the RSV Maternal Program, to really address the global unmet medical need of RSV in newborns up to 6 months of age, where we really do see the highest unmet medical need. The second advantage of a vaccine approach is that you do induce a, what we call, polyclonal RSV neutralizing antibody response. That is in contrast to a monoclonal that only targets a single epitope on the virus. When you think about this, the RNA viruses, even though they're more stable than flu, nevertheless, they do mutate, and we have already seen a number of mutations that are circulating.
There's not just one strain. There is a high liability of the monoclonal to actually lose effectiveness should the epitope that is recognized by that monoclonal change over time. Luis, if you would like to discuss though how a monoclonal can be used in the context of a successful maternal vaccine, please.
Sure. Thank you, Kathrin. Seamus, I think your question was about, okay, suppose that you have the monoclonal and the vaccine with similar characteristics, how do they coexist together based on ACIP recommendations? Again, we are very confident about our approach, and I think Kathrin has summarized it well, our approach with our RSV vaccine for the ACIP. Again, I cannot speculate how the ACIP and the CDC is going to decide to make these recommendations. The way that we are seeing it is that it seems to us that an structured recommendation makes more sense than just having two recommendations with two different providers, two intervention groups, two target populations, pregnant women or kids, and then two time points as well.
At the end of the day, what we believe is that if safety and efficacy is demonstrated, then there's going to be a universal recommendation for pregnant women. Then the monoclonal will be a complementary intervention, either for a high-risk group or either for unvaccinated or for older age populations. That's how we see this playing out. Thanks very much. Back to you, Nanette.
Thanks, Luis. Yes, just to address the last piece of the question, which is regarding the uptake of RSV in the maternal space, we are very confident that our penetration estimates given the strength of the data that we have today, we do believe that we can reach the 60%-70% market share, especially because RSV is the number 1 cause of hospitalization in infants younger than 6 months old, and the treatment is really limited to only fluids and oxygen. We do believe that with appropriate education and awareness as well as continued strong clinical results, all stakeholders, including pregnant mothers, will see the value that the RSV vaccine is bringing. Thank you so very much for your question. We have run out of time. Thank you to the panel for answering all the questions.
Again, thank you for the audience for all your great questions. Now I pass it on back to Chuck.
Great. Thanks, Nanette. Thanks everyone for your engagement today. A couple things. We'll certainly look forward to reviewing our other therapeutic areas within the organization tomorrow. As a reminder, that'll be inflammation and immunology, rare disease, oncology, and then the COVID section. As a reminder, tomorrow's session is going to begin at 10:00 A.M. New York time. If you refresh your screen, you'll see at the top a survey. If you could take a moment to fill out the feedback survey, we'd certainly appreciate that. We look forward to reconnecting with you all tomorrow. This will end today's session. Thank you.