Welcome, everyone, and thanks for joining us virtually for our first of 2 sessions, where we will share some exciting updates from Pfizer's portfolio and R and D pipeline. Today's program will be a combination of prerecorded prepared remarks and then, of course, live audience Q and A sessions. Today, we'll hear from members of our executive leadership team as well as leaders of our internal medicine and vaccines teams, the 2 therapeutic areas in focus for today's session. We will have a Q and A session following each of the therapeutic area presentations. The presentation at today's Investor Day include forward looking statements about, among other things, our anticipated future operating and financial performance, business plans and prospects and expectations for our product pipeline, are 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 ks 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 on pfizer.com/investors after each session.
You can also find the speaker bios and today's agenda on a separate tab at www.pfizerinvestorday.
Virtualeventsite.com.
Again, there will be time for a Q and A via the operator following each business unit's presentation. Now we're going to play a video that articulates our commitment to science.
When we want to send opinions from disease,
ask science.
It will make the breakthrough. Because science is relentless. It never gives up. It keeps asking questions until it finds what it's looking for. Clients want to cure people more than any disease wants to exist.
Just ask me once it's always been.
A
and again until the final of the day through it isn't done. We believe that you enjoy everything you need
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. Michael Dolsten, our Chief Scientific Officer and President, Worldwide Research Development and Medical, who will speak to how our R and 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. Rob McKenzie, our Chief Development Officer, who will speak to some very important metrics regarding our R and D productivity and Angela Wong, Group President, Biopharmaceuticals Group, who will speak about our commercial organization and provide detail as to the drivers of our projected 6% plus revenue tagger 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 2 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 Abjorn Mylan transaction, we can drive at least 6% revenue CAGR over the next 5 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 1st in class scientific powerhouse and from growing EPS through large scale M
and 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 1 or 2 years. It started in 2010, when my predecessor, Jern Reit, recognizing that our historic R and D productivity lag the industry, set a priority to strengthen our scientific engine. This 10 year journey resulted in a dramatic turnaround of our R and D organization.
The increased R and 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 the 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 saves patients' lives, represents the why we exist and do everything we do. Our bold moves represent what we need to do to be successful. Unleash the power of our people, deliver 1st in class science, transform our go to market model, win the digital race in pharma and to lead the conversation on science and reputation. Every plan we develop, every action we take and every dollar we spend is aligned with this 5 bolt move.
Finally, our values represent the how we do things. Our new Pfizer's culture will be characterized by courage because great growth favor the goal My 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 and by joy, because we take our job seriously, not ourselves. In order to prevent our scale from becoming an impediment innovation, we organized Pfizer into 6 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 6 business units as 6 individual 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 allows our vaccines business unit, for example, to move so fast with the development of their COVID-nineteen vaccine candidate and our hospital unit with the development of the antiviral protease inhibitor candidate. These biotechs compete with each other for capital and resources for the internal and external projects. These resources are allocated by a committee of 5 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 re imagine the way we work and began 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 15 to 5.
And we'll consolidate our sub service centers from 20 to 6. 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 and 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 build on the progress we have made to reduce emissions by approximately 55% since 2000.
In 2019, we conducted also our 1st 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 United States. And 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 4 highly accomplished directors. Doctor. Scott Gottlieb, Special Partner of the New Enterprise Associations, President Fellow of the American Enterprise Institute and the 23rd Commissioner of the FDA. Mr. James Quincy, Chairman and Chief Executive Officer of The Coca Cola Company, the world's largest non alcoholic beverages enterprise Doctor.
Susan Fockfield, Professor of Neuroscience and President, America at MIT. Susan was the 1st woman and the 1st life scientist to lead MIT as its 16th President. And Doctor. Sue Desmond Hellman, Board Member of the Bill and Melinda Gates Medical Research Institute, a former CEO of the Bill and Melinda Gates Foundation and the 1st 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 Littmann from NYU. Our Board now includes 5 highly accomplished scientists that form one of the best Science and Technology Board Committees in our industry. NIMS 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 And we think that now is the exact right time for the genesis of the MiFIs 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 1st 6 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 5 year revenue CAGR of at least 6% on a risk adjusted basis following the completion of the absence separation and continued growth beyond that from the next wave of our patent protected portfolio.
Should we be successful with our COVID-nineteen vaccine and antiviral programs, we will obviously update these projects. Our adjusted EPS during that same 5 year period is expected to grow in the double digits. Investment in Pfizer, sir, 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 6 targeted therapeutic areas, with 4 programs in registration and 23 in Phase 3. Last but not least, we have the financial strength to supplement our internal pipeline where appropriate with external business development.
As you have already said, we are biased towards Phase II and Phase III ready assets. And now let me offer a few points regarding our longer term revenue growth view. The sell side community expects $18,000,000,000 to $20,000,000,000 in loss to revenue during our LOE period, which is expected to begin in 2026, 6 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 situation.
We are eager to show you why we think this is the case over the next 2 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 2 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 showcase in our people, our culture and our science.
And with that, let me turn it over to Pfizer's Chief Scientific Officer, Michael Dorsey. Michael? Thank you very much, Albert, and welcome, everyone. In this next session, I would like to share with you Pfizer's on the 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 and D strategy that sought to get as many shots on goals as possible. During the period leading up to 2010, our R and D efforts were extremely spread across 10 key therapeutic areas, seeking to grant as many programs into the clinic as possible. By 2010 year end, we had 104 MEs in the clinic, predominantly small molecules. Our major R and D sites were located outside of major scientific hubs, isolating our R and D colleagues, and our decision making was often siloed. But in 2011, we embarked on a significant R and D turnaround effort focused on reinvigorating our innovative core.
As part of the turnaround, we made a conscious decision to focus our resources on 5 key therapeutic areas, where we felt we could make the greatest impact. In addition, we shifted away from a volume based development strategy to 1 in which we focused on high quality NMEs. We recorded 54 NMEs in Q2 2020 and broadened our modality base beyond small molecules. During this time, we also co located our R and D sites in scientific hubs, which enable us to better attract scientific talents in our core therapeutic areas. The impact of our turnaround was profound.
Our decision making became more integrated with enhanced objectivity and a high barter success. And Pfizer began racking up successes that included 1st in class blockbuster therapies developed internal advisors such as Celliant, Prevnar, Ibrance and complemented by partnership or acquisitions of molecules from external sources, including Eliquit with BMS Xtandi for 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 have had on our success and how they have put us in an outstanding position for success well into the future. The success of this strategy is reflected in substantial improvement that we've seen in Phase II trials. In the 3 years leading up to 2017, Bison's Phase 2 success rate, which is defined by successful transition into Phase 3, 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 2 success rates on a 3 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 2017, for every successful Phase 2 to Phase 3 transition, Pfizer needed 6 to 7 readouts. By 2019, Pfizer was achieving one successful transition into Phase 3 from every 2 Phase 2 readouts. Another measure of success is survival rate from first in human to approval.
These 2 have significantly improved with 76% relative increase in 2015 and has 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 5 therapeutic areas where there is great unmet need and a strong biological foundation and where our expertise and capabilities can deleveraged to improve the likelihood of success. Our 5 core therapeutic areas include oncology with a focus on targeting cancer vulnerabilities and drug resistance inflammation in 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 5 key therapeutic areas, Pfizer has 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. But 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 specific, RNA vaccines, like our potential COVID-nineteen vaccine in partnership with BioNTech gene expression modulators, which include zinc fingers in ALS translation and slicing as in drugs encounter, such as PRMT5 or EIFF4U. Artificial intelligence, multiarrhythmics and epidemiology, which utilizes big data, real world evidence, genomic profiling and enhanced epidemiology information to guide early decisions. To place Pfizer's R and D at the forefront of the evolving biopharmaceutical experience, we have co located our key R and D facilities in globally recognized scientific hubs.
Together with our focus on science, locating these hubs has enabled Faiza to attract top scientific talent and effectively leverage the collaborative environment such location naturally offers. Our therapeutic area hubs are distributed in scientific centers of excellence, including for oncology, La Jolla, California and Boulder, Colorado inflammation in immunology, rare disease and internal medicine, Cambridge, Massachusetts and Vaccines, Padreav, New York. Our science and technology centers include small molecule centers at Grosston, Connecticut and Sandwich, UK large molecule centers at St. Louis, Mounisui and Andover, Massachusetts a new modality unit 30 sites at Kitt Creek 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 that has enabled a 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 1 and more than 35% are in Phase 3 registration or recently approved.
There is strong contribution from all TAs with oncology being the main contributor, 29%, followed by immunodial inflammation, 20%. Our internal medicine portfolio sees its initial potential launches in the second half of this decade and includes multibillion potential blockbuster opportunities in the peri-twenty 26 phase. If we look at up to 25 by-twenty 5 cohort in terms of non risk adjusted peak sales potential, we see approximately $35,000,000,000 to $40,000,000,000 revenue. This includes TCV20 revenues and, as you know, is a potential replacement for Prevnar 13. We recognize these will not all achieve peak sales in the same year and our study expectation, But this should give confidence in the overall size of the opportunities we see.
Of the SEK 35,000,000,000 to SEK 40,000,000,000, major contributions are coming from vaccine, rare disease, followed by immunology inflammation. A ceiling up to 25x25 will require a combination of developed of 5 gs generated molecules and external partnership PD deals. Of the 62 programs shown here, close to 1 third are part of business development and bolt on M and A. We will continue to look for breakthrough bolt on assets and yields, which will further bolster our pipeline. In the next 2 days, our scientific leaders will present therapeutic area deep dives covering another 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. Finally, 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-nineteen vaccine, eversitinib in atopic dermatitis and PCV-twenty valent adult vaccine. Up to 10 potential pivotal readouts includes key programs like with next to me in alopecia, Xtandi and Telcena combination in TELACORE 2 study in prostate cancer and Ibrance PASEMA study in double positive, homorcept and HER2 positive advanced breast cancer.
ASC-ten potential early stage clinical readout includes key programs like these may iotherapy in multiple myeloma, Lyme disease vaccine and atopic repositinib in atopic dermatitis. Finally, I would like to introduce our highly accomplished scientific leadership team, Jeff, Nick, Mike, Kathleen, Sam and Morian, 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 areas 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. Now I will hand over to Rod.
Thank you, Michael, 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 quarter. More important though than the ranking is what that ranking reflects. And 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.
So we're in a much better place today. And I'm pleased to report that we expect that trend to continue through 2021 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. So how did we get here? We focused on 3 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 steel oils. And then with the first two foundational elements in place, the 3rd dimension was and it still is reinventing the way we operate with a laser focus on quality and cycle time reductions.
To give me
a sense of the ambition we have, we're in the process of taking out a further 2.5 years from our average times for end to end clinical development. So 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 4 different organizations and brought them together under one leader. And 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. So what does it mean to be patient centric? Remember that every participant in the clinical trial is a volunteer.
All of them are pioneers in science and medicine. So 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 they have good reasons to mistrust the healthcare system. This won't happen overnight, but 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. We need to make it much easier for them to find information and to make that first connection with clinical trial sites. And 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. And 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. And 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, Jim, Bill, Mike, Brenda and Chris have played key leadership roles in bringing more than 13 medicines and vaccines to patients with cumulative lifetime revenues
in the region of $150,000,000,000
So these are leaders who have done it before and they have a state of the art clinical engine now to work with. So I know that we can trust them to deliver the pipeline that you will hear about throughout this meeting. But 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 2nd 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. And the result was very significant improvements in operational performance. For example, we saw reductions in cycle times, in some cases up to 30 percent. In addition, we created cost efficiencies that allowed us to reinvest approximately $750,000,000 back into the portfolio. But 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.
And we're beginning to see the fruits of that now. We're consulting, 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 1st regulatory grade study, which is completely remote in that way. We hope to see a significant increase in retention of participants in the study.
And 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 value work. And 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 With Ochsner Healthcare, we have access to our 1st rate extensive and growing network of hospitals that use electronic health records, enabling the seamless transfer of anonymized data into Pfizer databases.
And as a founding member of Transcelerate, we're helping harmonize industry practices, thereby facilitating patient centricity by providing them with our clinical trial partners a similar experience, no matter which sponsors they're working with. Let's move now to the 3rd dimension of our transformation, which is laser focused on reducing cycle types. 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 9.5 years.
That's too long for everyone. So we look 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 look minute to minute to understand in great depth how our time has been spent. In the end, we decided to split those 9.5 years into 2 buckets.
The first bucket was where 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 2 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. And so we set ourselves a breakthrough goal to reduce that by a full 2.5 years by the end of 2021.
And 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 and 2020 2021 are projections, but I'm very confident we'll continue to do well. So how are we doing? We're working in 5 areas and you can see the relative contributions here.
The first is in changing the investment profile of our programs. As Michael described to you, with our Phase 2 success rates going up, our confidence in making earlier investments in programs is getting higher. That in turn reduces weight space, while we wait for clinical trial supplies for pivotal studies. On the average, we think by about 8 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 5.5 months. Then 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 3 months. However, the biggest impact is in the automation of processes.
Right now, every aspect of clinical trials is very human intensive and requires many, 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. And because automation can positively impact every aspect of end to end clinical development, we anticipate that the overall automation of processes will contribute nearly 1 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-nineteen vaccine work.
Tomorrow, you'll hear in some detail a full description of Pfizer's overall COVID-nineteen response. But 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-nineteen vaccine to the 1st subject first visit was only 12 days. Then when we received regulatory approval to start our Phase twothree study, we had our 1st subject first visit 2 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 LARGRIENNA. This is an important medicine for non small cell lung cancer that took less than 5 years in clinical development, under half of our previous median and significantly shorter than the industry median of the day. Laubrina is a lifesaver and it's a life prolong. 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.
We expect to continue to get better, but 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. And now it's my pleasure to turn it over to my colleague, Angela Wong, 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 Michael'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 Michael was a broad review of our pipeline until 2028. But 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 5 years. And this is a function of 3 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 $250,000,000 biopharma inline brands grew 9% in the 3rd half of 2020. The momentum in our current portfolio is strong and the 7 in line products, namely Ibrance, Xtandi, Oncology Biosimilars, BRAFTOVI, MEKTOVI, VINZICAL Eliquis and Xeljanz are expected to drive 50% of the revenue growth over the next 5 years.
2nd, the potential of 25 launches by 2025, including 9 potential blockbusters that have a total of $15,000,000,000 in non risk adjusted revenues in 2025. 3rd, no significant LOEs anticipated until 2026. We have a unique portfolio of medicines and vaccines housed in 7,000,000 years, each with commercial capabilities and resources that are focused specifically on their therapeutic areas and customer needs. Having all of the business units within 1 biopharma group also gives us unparalleled scale and capital allocation abilities. 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 give us great confidence to deliver best in class launches for every pipeline product to come. So let's introduce the business units. The 7 units are led by my outstanding leadership team, our Global President. Together, they comprise $41,600,000,000 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 Michael and Rod already introduced to you. And they shaped and advanced the pipeline in addition to their commercial responsibilities. We call this group of 3 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 $9,000,000,000 in revenue. And in the pipeline are 6 potential 1st in class medicines. We have deep expertise in cardiology and primary care and those capabilities will be leveraged by our pipeline assets in hyperthroglyceridemia and obesity.
Vaccines has the potential to become a top 2 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 $6,000,000,000 of vaccine pipeline potential that we believe we have. INI has the leading medicine in Xeljan and we have one of the largest targeted JAK portfolios across the industry with 12 potential enemies across 24 indications. We feel we are well positioned to maintain leadership in I9.
And the rare disease BU will be the only company with 3 Phase 3 gene therapy programs, building on the momentum of exceptional launches like the one that we've seen with Vintacal. 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 infective and is focused on building out its pipeline with innovative molecules and platform technologies. This includes 3 MMEs, namely the ATMAbi asset and both the IV and oral protease inhibitor. Our Emerging Markets BU encompasses all the products from the 6 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 7 in line brands. And together, these 7 brands have the potential to contribute $8,000,000,000 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 R15 1,000,000,000. The assets we're showing here are either in Phase 3 or will be by the end of this year. Risk adjustment gives the pipeline about $8,000,000,000 making up the other 50% of our revenue growth. We have 3 mega blockbusters in agaracitinib, DMD gene therapy and buprenosine.
Abro and buprenosine have more than $3,000,000,000 in peak revenue and D and D gene therapy more than $2,000,000,000 in peak revenue. We also expect PCV20 to be a mega blockbuster, but we're not factoring this into our incremental revenue growth because we see this replacing PCB-thirteen. And 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. And when you consider that this growth is off a $41,000,000,000 plus base in 2020, it's all the more significant. But 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 5 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 make 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 have made behind our rare disease portfolio and gene therapy gives us a consistent series of launches until 2025. And the depth of our JAK portfolio, which builds off the strong foundation of Celgene expands into new disease areas like dermatology.
So let's get into some specific details around a few of our growth brands to help show how we see their future growth potential. Brinsacao has seen exceptional performance in ATTR Centimeters and should be close to $1,000,000,000 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 Centimeters 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 rate for rare diseases being in the range of 30% to 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 the 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 64,000,000 lives. But 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 on Celgene's excellent volume growth. We expect in 2021 and beyond for the volume impact to significantly up pace any pricing impact. Since launch, we have consistently grown volume over 30% a year, excluding the impact of COVID recently. As for the Jack loss, we see the entrance of competitor Jacks as being a positive.
In the U. S, 32% of all new to brand advanced therapy scripts are now subject. 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 life. We look forward to launching ankylosing spondylitis to further strengthen our leadership in rheumatology. AS continues to have a significant unmet need for the 1,700,000 adult patients in the U.
S. And the EU. 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 NSAIDs, meaning both the primary and the secondary endpoints at 16 weeks. And data was submitted as an sNDA to the FDA and we expect our PDUFA to be the Q2 of 2021.
Oncology biosimilars portfolio is an exciting one and is now the largest in the industry with 6 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 specific inhibitor in metastatic breast cancer. In the U.
S, Ibrance holds an 87% share in first line CDK use and we expect to defend our market leading position. Oncologists view Ibrance profile favorably with over 5 years of patient and physician experience. And real world data recently showed a statistically significant benefit of 42% in overall survival. We conducted research with KOLs and oncologists as recently as July 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 molecule 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. And currently, Pfizer is aware of at least 5 studies evaluating CDK office CDK usage, with results anticipated in the late 2022 early 2023 timeframe. So 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's 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 ZYNDECAL and our oncology biosimilars and we will do this again if we're successful with our COVID vaccine.
The client structure integrates our commercial, clinical development and research organization, allowing us to introduce commercial insights early in the development process. And our end to end capabilities also help us to be a partner of choice in business development. Strong fundamentals Strong fundamentals position biopharma for continued growth. We have 7 key in line 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. And 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 taper from now till 2025. I know you will enjoy hearing from our trial team about the strength of our pipeline and how we will fuel the next stage of growth in biopharma. And now Chuck, back over to you.
Thanks, Angela. So now we're going to take a break. So please stand by and we'll resume in 10 minutes with the presentation from our internal medicine leadership team. 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. So they took me in into intensive care, and the doctor came and told me, that, we believed I had NASH, nonalcoholic steatohepatitis, a product 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.
With healthier behavior, I believe I have slowed it down, obviously. I hope that we find a cure for it or at least something that will negate it and future generations, not just mine.
Now 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. And 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 and D strategy with you today. We're excited to share data on several development programs that we believe have either 1st in class or best in class potential. So here's the team presenting today and between the 3 of us, we have over 75 years of internal medicine experience. My name is Mike Gladstone. I'm the Global President of Internal Medicine and Jim Rusnick is our Chief Development Officer.
He leads both the internal medicine and hospital categories. Maury Birnbaum is our Chief Scientific Officer in Internal Medicine. So let's take a look closer look at our expertise and our reach. Internal medicine drives innovation that diagnosis, treats and prevents the most prevalent healthcare challenges facing our societies. And in 2019 alone, we reached approximately 59,000,000 patients.
1st, we have an aging population with chronic metabolic conditions that are at an epidemic level. 2nd, 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 system. And we've got an unmatched track record in developing and commercializing massive primary care medicines like Zoloft, Lyrica, Lipitor, Norvasc and Eliquis. And 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. 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. And 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, PMA and Japan's PMDA and we're looking forward to FDA's decision in December later this year. Now I'll turn it over to Maury to introduce the internal medicine R and D strategy. Maury? 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. Now 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 novel, science driven and balanced early and mid stage pipeline such as multiple diseases and indications.
We currently have 9 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 DGAAP2 inhibitors for NASH, 2 drugs that were recently given INN of clusacastat and ervulcostat. We'll also talk about damugliprim, the INN for our small molecule oral GLP-one receptor agonist for diabetes and obesity. But first, we'd like to bring you an update on buprenorphine, a promising potential treatment for cardiovascular disease that we acquired through an in licensing agreement with Akcea and Ionis.
Thanks, Maury. Lupinorcin is a great example of our strategy to identify external opportunity to further strengthen our internal portfolio. Lupinorcin has shown promise in early studies of reducing atherogenic glycoproteins 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.
However, 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 4 year study with PCSK9 inhibitor of avelocumab. 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 6,000,000 U. S.
Patients are at a high risk of a major CV event despite already being treated with statins. Tim is going to talk more about the role of buprenorphine and how it can play a role in addressing this residual risk. Jim? Angiofoetin LY3 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% to 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 buprenorphine, 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 net of 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 1b study in healthy volunteers with elevated triglycerides. Once weekly doses of buprenorphine led to dose dependent reduction in non HDL cholesterol and triglycerides. At the recent ESC Congress, AKCEA presented results from a 2a study of buprenorphine in patients with nonalcoholic fatty liver disease, type 2 diabetes and hypertriglyceridemia. The Phase 2a study evaluated a lower dose range than the earlier Phase 1b study. It met its primary endpoint of triglyceride reduction and several secondary lipid parameters.
While the overall Phase 2a result met the primary endpoint, the maximal effects on some lipid parameters, particularly non HCLC, were not as robust as originally observed at the higher doses of the Phase I study. Pfizer is leading the development of buprenorphine moving forward with a focus on cardiovascular risk reduction. We are initiating a Phase 2b study to complete additional dose ranging in patients representative of our planned Phase 3 population. The Phase 2b 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 adazitamone. We are collaborating on this study with the Timi Group.
It will assess the safety and efficacy of different doses of RupaNoris along with assessing the safety and efficacy of the same monthly dose of buprenorphine given at different dosing intervals. Our Phase 3 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. 2 additional Phase 3 studies will support a severe hypertriglyceridemia LDL cholesterol, non HDL cholesterol and LDL cholesterol, non HDL cholesterol and APO B. In closing, we're very encouraged by the human genetic data that demonstrates lots of function variance of ANGPTL3 having a reduced incidence of coronary artery disease and the early data that we've seen with buprenorphine. We see great potential for buprenorphine 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, Jim. Before we move on to NASH, I want to take a minute to highlight the potential opportunity we think the most. Subject to approval, we'll launch in 2025. The indication will be severe hypertriglycerideemia.
This is for triglyceride levels above 500 milligrams per deciliter. Over 2,000,000 patients fall into this category. The larger unmet need and also the larger opportunity for buprenorphine are in cardiovascular risk reduction. We'll launch that indication in 2028. We estimate that there'll be over 6,000,000 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 HCLC. Flupinarsen will be an add on therapy to statins plus other lipid lowering agents. Now the goal here is to further reduce residual CB risk and we're really excited about its potential. Now 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 the 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 and it carries a growing burden for patients and healthcare systems. NASH significantly increases morbidity and it's one of the leading causes of liver transplants in the U. S.
Now by the way, the severity of hepatic fibrosis is defined in stages and they range from F0 or no fibrosis to F4, which is cirrhosis. Evidence suggests that significant to advanced fibrosis that's stated F2 and F3 are associated with both liver related and all cause mortality. Now I'll turn it over to Maury to tell us more about our NASH strategy and pipeline. 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. And 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. Acetylcholine 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 reward, DGAP2, 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 DGAP2 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. But 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 the Phase 1 study of our potential 1st in class dGAT inhibitor or vogastat 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 2 weeks compared to a 10% decrease in response to placebo. In addition, the voristat reduced circulating triglycerides, an important risk factor for cardiovascular disease and pancreatitis. Now let's take a look at what happens when ACC activity is inhibiting people. Like DGAT2, inhibition of ACC also reduces liver fat. In a 16 week study in patients with NAFLD or presumed NASH, ACC inhibition with clizacrastat reduced liver fat by more than 60% of the highest dose tested, again with a placebo dependent decrease of less than 10%.
Clizacostat also caused the 40% in ALT, a circulating marker of liver injury. However, 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. Since ACC had such a profound effect on steatosis, it has the potential to directly reduce inflammation of fibrosis. We saw in a way it can mitigate 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 PGAT2 inhibitor to reduce the levels of enzymes essential for pracq 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 DGAAP2 inhibitors. These exciting data were recently presented at the International Liver Congress. As shown in the panel on the far left, after 6 weeks treatment both DGAP2 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 DGAP 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 DGAP2 inhibitor offered a slight reduction. Importantly, the combination of the 2 agents yielded a fasting triglyceride profile, indistinguishable from placebo, completely correcting the adverse effects of ACC in the pure monotherapy. Further, as shown in the table at the bottom of the slide, the ACC DGAP2 inhibitor combination significantly reduced the number of times fasting triglycerides rose above the threshold levels 400, 600 or 800 milligrams per deciliter, 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. While the early ACC and DdGAC2 inhibitor data are highly encouraging, currently the only definitive way to evaluate NASH efficacy is by assessing histological changes in the biopsy study.
Hence, we have progressed both the dGAT2 inhibitor monotherapy as well as the ACC DGAT2 inhibitor combination in a Phase IIb liver biopsy study, which began enrolling this past June. The outcome of this study will guide which candidate or combination will progress with Phase 3. 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 1st 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. Now Mike and Jim will talk about another area of significant patient need, type 2 diabetes and obesity and discuss our small molecule oral GLP-one program. Thanks, Maureen. 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 1st in class small molecule oral GLP-1Ra, vinaglifron.
The numbers here are astounding. 650,000,000 obese patients today and less than 5% of them have been treated with NASH. 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. Now the GLP-one class is a proven mechanism of action that offers compelling diabetes and weight loss efficacy with cardiac asthma. 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 or
GLP-1Ra. The compelling Phase 1 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. Now I'll turn it over to Jim to share more about this exciting program. Jim? The discovery of non peptidesmallmolecule GLP-one receptor agonist 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 1 data suggests that anyglutron will yield a differentiated profile that is expected to deliver potent benefits on blood sugar and weight loss, safety and tolerability comparable to the peptides GLP-one class, good oral bioavailability with no food or dose restrictions and unlike the peptide based oral GLP-one, danegliplipron may be suitable for both monotherapy and combination therapies. Let's have a look at the data. This is very exciting Phase 1 data and it was shared in ANA's 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 1st 2 weeks and then stabilized at the target dose
for the 2nd 2 weeks.
We observed robust reductions in fasting plasma glucose and hemoglobin A1c at all doses. This study was only 4 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. Saniglipron was well tolerated in this study with an adverse event profile that was consistent with the GLP-one 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 4 week Phase 1 study where we utilized an aggressive dose titration scheme to reach the higher doses. On average, up titrations occurred every 2 to 3 days. This aggressive titration was required because we sought to evaluate doses for at least 2 weeks at steady sleep. As a result, the tolerability data from this study is not comparable to more typical Phase 2 and Phase 3 data reported with other agents where longer and slower titration schemes were used.
In fact, our upcoming Phase 2 studies, dose titration will occur at weekly or biweekly intervals. Since these studies will titrate more slowly in or of a longer duration, they will provide a more representative picture of the tolerability profile of antibody response. Based on the Phase 1 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 1st small molecule oral GLP-one receptor agonist for treating both obesity and type 2 diabetes. We are also exploring this asset in NASH and we believe denglutbrone may ultimately be best utilized in combinations with one of our other NASH assets.
I'll now turn it back to Moray 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 to dysmenabolic 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 health care. 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 1st 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 by millions of patients and make a significant positive impact on society. On behalf of Jim, 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. So now we've got Jim, Maury and Mike available here, ready to answer your questions about the portfolio and the pipeline. So operator, at this point, can we please now poll for questions for the internal medicine triad? Thanks.
Your first question is from the line of David Risinger with Morgan Stanley.
Yes. Thanks very much. And thank you, Chuck and team for hosting the sessions. We really appreciate it. So, Chuck, I don't know if it's appropriate or not, but I wanted to ask about the higher level pipeline projections.
So just to confirm, the $35,000,000,000 to $40,000,000,000 pipeline peak, is that in 2,030? And the 50% risk adjustment, is that the average risk adjustment for that pipeline that you're assuming? And then 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. So 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? And in addition, with respect to the oral GLP-one, 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.
Yes, David, Chuck here. So your first question before I turn it over to the I'm team, that the $35,000,000,000 to $40,000,000,000 represents potential peak sales. Now remember, not every potential compound has peak sales in the same year. So if we normalize and set at peak for each combo, that's where you get that number as opposed to a single estimate for a given year.
So that's if you said
all of them achieved peak sales in the respective years, they would be hitting peak sales. That's what we see the potential. But again, we're not pinpointing that to a specific year. That's in a sense totality and really on a continuum basis. And then 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.
But our view is the reality, as we all know, is you either have a compound or a compound fail. So it's either a 0 or you have a successful compound. So that's how we're looking at this rather than to say somewhere in the middle, some will win, some will lose. So that's what the risk adjustment does, but that's when we take this as a totality of the pipeline just to give you all a sense of what we see in these situations where they were all successful and hit peak sales. And then from that point, we would take a general risk adjustment.
So in that sense, let me leave it there and then I'll turn it over to Mike to kind of moderate with his room here on the specific internal medicine questions. Thanks, Dave. Thanks, Jeff. I think we'll start out with the competitive situation and I'll ask Maury to start there and then I'll follow with GLP-1 and commercial considerations. So Morrie?
Thanks. And 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.
And you know the results of the study so far have been largely disappointing. And we interpret that as validation of underlying philosophy, which is the only way to effectively treat NASH is by going at those core metabolic pathways. And quite honestly, the late stage clinical trials that have failed have not addressed that strategy. They've largely been repurposed drugs, drugs that were initially developed for other diseases and we're now switched over to NASH therapy. So yes, we're not first, but we're still pretty confident based on the results of other studies.
And 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, Maury. The big challenge remains here in screening diagnosis and monogrammed NASH. And this is still a very, very big opportunity. It's been estimated that our 18,000,000 NASH patients in the U.
S. And roughly about 30% of these patients have fibrosis stage F23, which is what we're targeting. And there's a wide range of opinions as to what the external community thinks will be the diagnosis and treatment rate. And the range is somewhere between 20% 75% expected diagnosis rate for us. We believe that our assumptions are that we're conservative than 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, but we think we're well prepared to bring in competitive products to
the marketplace here. Now let's
shift over to GLP-one. And I think the important thing to keep in mind here is that if you look at type 2 diabetes treatments, GLP-one got about 9.6 share of the total prescription. And we think the treatment gap year is doing part because the limitations available at the current GLP-1s. It's similar to administration. They're either injectables or they're very difficult to take with significant food restrictions.
And we believe that the opportunity here with anaglutide 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 other compounds.
If it hits its target profile
and it's approved, we believe it will be competitive as competitive as the best first in class agents that we have, best in class agents in the GLP-1 class. So with that, Jim, do you have anything else to add on GLP-one? Yes, Mike. So thank you very much. I think the GLP-one 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 today, while in short duration, at steady state after 2 weeks, we have a hemoglobin A1C reduction that is comparable to what is seen with marketed agents at 3 or 6 months. And we know that it takes quite a while to stabilize hemoglobin A1c over that time period. So we do anticipate that we will get additional efficacy data over that intervening time period in Phase 2 and Phase 3 studies. I think that this will allow us to demonstrate superiority in the oral agent class.
It's also upsetting because we can use danglucarone in combination with other agents, not only for diabetes, but also potentially H4 and H and really close that treatment gap that you spoke about earlier, Mike. Thanks, Joe. Hope we can go to the next question, sir.
Your next question is from the line of Omar Raffat with Evercore.
Okay.
Your next question is from the line of Louise Chen with Cantor.
Hi. Thanks for taking my questions here. So I had a few. First question is, how much upside to that 6% CAGR do you think we could see if your COVID-nineteen 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?
And do you think combo therapy will be more effective than monotherapy here, any thoughts? And then last one just on this oral GLP-one, how do you think about oral versus injectable and how that debate will play out? Thank you.
Okay. So I'll turn the CAGR question over to Chuck and then we'll go to Nash with Maury on the length of the study and combinations. So Charles, I don't know if you want to comment on that first question. Yes, sure, Louise. So we said we have 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.
So we are not making that update today. But certainly, if the time comes, we will let you all know how that changes our thinking. Thanks, Louise. In the morning, press 2, can you talk about the length of the studies needed for a marginal indoor combination, top line combination? Let me start with combinations.
There's been a lot of enthusiasm in the Nashville for combinations. And it's rational in the sense that most metabolic diseases end up with combination therapy or complicated multifactorial diseases and NASH falls within that class. So we are going to be testing in combinations for a number of the agents, some you've heard about today, going forward. But 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. But 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 Jim to talk about the clinical plans for NASH. Thanks, Maury. Yes. So currently we have the dGAT and dGATACC combination in a Phase 2b study. The primary endpoint of that study is a biopsy timed at 48 weeks.
We believe that 52 week to 72 week biopsy for Phase 3 will be appropriate and will be guided by our Phase 2 data as well as other data as it emerges in the field. Great. Now as we turn to look to move over to oral GLP-one, How will the oral versus the injectable game play out? I'll probably have a few words and I'll kick it over to Jim to see if you have anything to add. It's stated earlier, I think one of the big challenges here is the utilization of the group volumes, it's for administration, it has injectable.
And the only oral out there has significant food interaction. So we think the advantage here will be that we can deliver a product that doesn't have the food restrictions that are currently available or the inconvenience of an injectable and this product will be combined with other compounds. So Jim, is there anything else to add there? Yes, Mike. I think that while speculative, there is some real promise for an oral agent.
And that's because an oral agent is actually the true small molecule gets absorbed in the intestines where GLP-one is indogenously produced and GLP-one receptors reside. Subcutaneous injection well and certainly can reach those areas wouldn't necessarily reach to the same extent. And 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. Maury, anything else?
No, I think we covered it well, Jim. Just to reiterate, that'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 intestine complex. And so and it's also pretty clear that these get activated with an oral with oral when you take food because GLT-one is secreted from the intestines.
So there is some reason to believe in some data to support the idea that a gastrointestinal absorption of the of an activator will lead to a differentiated response, if anything, it's been associated with the satiety response after a meal. So 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, Kipul. And I think I'll probably just end up in saying 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. This is going
to require some market help
and the price has got a history of understanding what it takes to bring imediapine's life business to market and we're working with that. 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 JPMorgan.
Great. Thanks so much for the questions. My first was on vuprenorphine. Can you just help us put the efficacy here into context relative to other products in the market? And 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? And then my second question was just on tanezumab, just as we're approaching the approval of that drug. Just a little bit 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.
And this is all Preston, if you can start off with Bupo and then I'll follow back with the same exact question.
So we see the opportunity
of buprenorphine to be addressing a live of protein and residual cardiovascular risk in sort of a broad perspective. We do believe that there is a substantial opportunity beyond just triglyceride lowering. Rupinarsen reduces non HDL cholesterol in a dose dependent fashion. And AKCEA in our QA study, studied a lower end of the range, which was initially studied in the Phase 1 program. What we intend to do in our Phase 2b study is actually expand that dose range beyond what was studied in the Phase 2a trial to really understand the efficacy that we can derive on non HDL.
Non HDL is tightly linked cardiovascular risk reduction and we'd be seeking to take that data and design a cardiovascular outcome trial to show the inpatients that are already receiving very efficacious lipid lowering therapy so that we can reduce the cardiovascular risk largely through non HDL reduction with bupomarsen. Maury, anything else to add on that? Yes. Thanks, Judah. Increasingly, we're basing our prediction on how these drugs are going to work on human genetics.
And we do have a lot of information on the phenotype of individuals who are deficient for atropoint like 3 protein. And yes, there is a market decrease in triglyceride, but equally important, there is a decrease in non HDL cholesterol, as you can say, but there's also a decrease in LDL cholesterol. And importantly, the decrease on LDL cholesterol is by an LDL receptor independent mechanism, which gives knocking down antiguoin LR3 the potential of lowering LDL cholesterol further even when maximally treated with 1 of the drugs on the market, both of which work through the OBL receptor. So there's a lot of reasons to believe that entry point like 3 is going to reduce cardiovascular risk by multiple mechanisms. Great.
Thank you for the question. I'll answer the question about the Seneca Lab opportunity. I guess when we think about Seneca Lab opportunity quickly to think about the unmet need. There's a large unmet need in osteoarthritis and I think we think Sanazepam can play a important role. We think about in the U.
S. We've got 27,000,000 people with osteoarthritis, 11,000,000 of those have moderate to severe osteoarthritis. Couple that with the fact that 80% of these patients have tried and failed 3 or more analgesics. There haven't been any new classes of medicines in this category for over a decade.
We put those factors together, there's a lot
to be excited about tanezumab and we're looking forward to hear from the FDA of our BLA in December this year. So 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 and D strategy and one on NASH. For Albert and Michael, 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? And is there an opportunity to further increase your Phase II and ultimately Phase III success rate? And then on NASH, I know the long term approach, as mentioned before, is likely combo therapy with 2 or 3 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 derisking in the clinic? Thank you. Thanks for the question. And this will be our last question. So with that, I'll turn it over to Maury 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 as 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.
So we're very excited about that. But 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. So we will find out which works the best. But right now, we're very excited about our lead studies, which are the ACC DGAT combo and DGAT 2 inhibitor alone.
Jim, do you have anything to add on the clinical side? I think that the question regarding the acceleration in 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. And 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 Gerald Martin? Yes, sure, Mike. So yes, Jeff, of course, we're always trying to have continuous improvement here.
So I think a combination of those factors that you referenced. We took as Rob 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, very specific steps to improve them. So I think it's a combination. And yes, we're always going to continue to see ourselves improve, but a lot of progress made there. And so it really is, as I think Ron and Michael 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.
So thanks for the question, Jeff, and thanks for your questions. Now we're now going to move into our vaccines program and we'll transition there. And before we do that, we'd first like to share a video featuring Emma Harris, who's a former RSV patient.
Knowing Emma is going to be born in full season, it's a little daunting just because the previous 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, you have our she has our
Dear scientist, there is nothing more perfect in the world than a brand new baby. So I was unprepared to hear our pediatrician say that Emma had RSV at 10 years 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 when they're expecting their tiny little babies. Motherhood is scaring us, but your work may help it not be as scary.
Now I'd like to turn it over to the vaccines team.
I am Nanette Coucero, 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-nineteen pandemic. Yes, 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 2 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. And 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 webinar, 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 Kathleen Janssen, our Head of Vaccines Research and Development.
And later, for the Q and A, you will meet Luis Hodard and Bill Gruber, who ramp out our vaccine leadership team. We and the thousands of Vaccines focused colleagues working besides 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 Gaius 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-nineteen virus. Our efforts over the last 10 years have transformed Pfizer's presence in the vaccine space from the prevalent company to an end to end global vaccine leader anchored in 3 key strengths: innovation, portfolio breadth and depth and scale. We have invested significantly in our vaccine infrastructure.
And today, we operate 1 of the most sophisticated and reliable supply chains in the industry, enabling us to deliver more than 1,000,000,000 vaccine doses since 2010 and without stock out. We also continue to fuel our research and development engine. Currently, we have 9 programs in active clinical development. Dating back to Prevnar thirteen, we have received 10 Fast Track Designations and 3 Breakthrough Therapy Designations, underscoring the innovations they represent and the unmet medical need that they address. Best of all, with our robust pipeline, we are now aiming with regulatory approval to deliver 6 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 5 years on average. These 6 vaccines by 2025 include the 4 Phase 3 assets you see outlined here in red. These are the candidates who will focus our discussion on today. Our next generation pneumococcal conjugated vaccine candidate, CCD20, in development for adult and pediatric populations and our potential 1st in class CDP field, pentavalameningococcal and RSV maternal vaccine candidates. Also included in the 6 by 2025 are our Lyme vaccine candidates in collaboration with Valneva and our COVID-nineteen vaccine candidate in collaboration with BioNTech.
These programs will not be discussed in detail today, but we're looking forward to sharing more on our COVID-nineteen vaccine tomorrow and online 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 6 months alone. This 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 5 new Phase III trials and added the Phase II life 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 3 quarters of a 1000000000 additional lives by 2028. We expect to deliver sustained growth year over year and 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 6 anticipated vaccine launches between now and 2025.
Bottom line, we have infrastructure, we have the expertise and we have a passionate and committed team to successfully deliver against this growth goal. And what drives us the most are those 3 quarter of a 1000000000 lives across the globe that are depending on us to make it a reality. And with that, I'd like to turn it over to Katherine Janssen.
Thank you, Nanette. My name is Katherine Janssen, Senior Vice President and Head of Vaccine Research and Development at Pfizer. I'm passionate about vaccine R and D and have focused my scientific career on improving public health through the development of high impact vaccines such as Gardasil while at Merck and Prevnar13 and Trememba at Pfizer. As noted by Nanette, today I will review our 5 late stage programs starting with our 3rd 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 2,009, 2010 time frame.
PCV7 and PCV13 had a tremendous impact on public health, reducing the global pneumococcal disease burden. But 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 variant 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 vaccine 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 nonbacteriumic pneumonia. If Phase 3 is successful and receives regulatory approval, PCV20 adult will provide 33% more IPD coverage and PCV20 pediatric will provide 40 2% 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 17. 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 4 dose regimen, immune responses across serotypes are indeed comparable.
We also see substantial immune responses for the additional 7 serotypes not in PCV13 that mirror those seen in PCV13 and for which efficacy was demonstrated previously. These data will be presented at ID Week 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-nineteen 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-twenty 21. 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 force. 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 right and represent about half of all C. Difficile infections.
Compared to shingles, which can be prevented by a 2 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 health care system as shown here. Our vaccine candidate is composed of 2 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 3 doses, as shown here, for toxin B.
You can see that the responses plateau and then persist at substantially elevated levels above baseline. Similar responses observed also for TOXINAE. So what is the relevance of these Phase II data? The majority of vaccinated subjects had antibody titers that exceeded the serum levels of the monoclonal antibody license to protect against recurrence of CDK cell 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 1st 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 C with separate recommendations, which is very confusing to health care providers and parents.
This is unfortunate because only 17% of U. S. Adolescents receive at least one dose of a meninge B vaccine and far fewer received the full schedule of meningeococcal vaccines needed for protection. But 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, mimemrix, we had an excellent opportunity to combine it with our own meningococcal B vaccine to remember aiming to provide 1 pentavalent vaccine to help address meningococcal disease called Part Aire Groups ABCWY in adolescents and young adults.
Assuming clinical success and FDA approval, we envision a future schedule with our penta vaccine that would only require 3 doses shown here in light blue compared to the 4 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 are on track to potentially achieve this goal, I'd like to share new clinical data from our Penta Phase II proof of concept study. Shown here are the immune response of penta in dark blue bars compared to Tremendra in light blue and then ACWY 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 iZEVIC next month. Our Phase III study start occurred on June 17, 2020. As you can see on this time line, we believe that if Phase III indeed is success for, a BLA filing of the penta vaccine could potentially occur in early 2023. I'd 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 1,000,000 hospitalizations in those less than 6 months of age, and unfortunately, deaths in many newborns across the globe. There is currently no cure or vaccine, and the standard of care treatment that exists 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 the discovery by Jason McCallum and his team in 2013, we now know that while we all have 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, 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, biose 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 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 near 2 to 3 fold crisis seen prior with post fusion F or insufficiently stabilized forms of F. Having these high fold rises to both subtypes is critical as RCA and B circulate almost at equal rates in any given RSV season. What do this 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 RT in the 1st days, weeks months of life. Our Phase III RSV study began on June 18, 2020, with pregnant women receiving a single vaccine dose between 24 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 time line.
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-twenty 23 based on our current timeline projections. To summarize our late stage vaccine portfolio, we have built a robust and exciting vaccines pipeline with the potential to launch 6 innovative vaccines by 2025. The 5 you see here on the slide, plus our COVID-nineteen 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, Catherine. As I talked about earlier, our work in the pneumococcal space is well known. Today, in addition to hearing about our next generation Pembinar vaccine, PCV20, you have also heard about Phase 3 assets such as CVP0, RSV maternal and meningococcal pentavalent vaccine candidates. And you have gotten a closer look at these disease areas, the compelling data we have generated to date and an overview of clinical time line. Additionally, I wanted to share some information on how we are thinking about the commercial opportunity of these three assets.
For CVCIL, the prevalent population ranges from 90,000,000 to 130,000,000 people depending on the ACIP recommendation that we receive. We anticipate vaccinating up to 5% of the target population each year in the United States, ultimately reaching nearly half of those 90,000,000 to 130,000,000 people on a cumulative basis. We also expect 100% market share for the 1st 4 to 5 years before competition potentially enters the market. For rasimha turnoff, we anticipate a strong market update among our population, which is the number of pregnant mothers based on the annual birth cohort. We also expect to maintain a 60% to 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.
And finally, within the total remaining coco 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% to 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 6 breakthrough vaccines. 2020 is a pivotal moment in our journey, not only because of COVID-nineteen, 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 because 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 and A session.
Great. Thanks, Lynette. Certainly, a lot going on in the vaccines area. So we're going to get ready to move to the Q and A session for the vaccines team. And just a reminder, we're going to have a separate COVID section tomorrow with Michael, Angela, and Catherine presenting on COVID and then Albert will join for the Q and A session as well for that tomorrow.
So 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 brought through. So with that, operator, 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. So one on your pneumococcal franchise and one on the meningitis side.
So just in terms of the pneumococcal franchise, I guess I'm curious on how you're thinking about the near to mid term commercial outlook 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. But maybe if you could talk about how you see the next 1 to 3 years playing out if marketing, like it's on market ahead of you, especially in the pediatric setting? And then on the many data side, I guess, we've been surprised, I guess, by the relatively limited uptake for your current vaccine. You just seem to get pretty bullish sort of projection in terms of market share and penetration.
And I guess, I just 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 is that the main driver in terms of why the uptick would be a lot more? Or I guess I've been 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.
Okay. Well, thank you for your question. And I'll begin with a question on NUML. And 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. And for the adult space, we are going to be coming to market by mid next year, which is quite head to head with competition.
While current pipeline 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. CCD13 efficacy and even more important, the safety are well established and recognized among physicians and patients. And this is why we expect physicians to be very comfortable continuing prescribing CCD13 in the period before CCD20 is actually launched. And as you mentioned, both CCD13 I mean CCD20 as well as pediatric do add additional coverage, 42% additional coverage in the pediatric space and 33% more coverage in the adult space. So for all these reasons, we are confident that we will niche, we are also confident and very excited about this meeting to address the current password, as I mentioned, which is complicated and inconsistent, recommendations.
In order to simplify the vaccination schedule, a lot more allowing more adolescents to be fully protected. We with the 5 additional stereotypes, this will give us AABTYW, which covers the majority of the meningococcal devastating disease. Our timing because of our timing, that this is ahead of our competition, at first, to potentially launch And based on strong Phase II data that Catherine mentioned, we do see a high probability for Phase III success and licensure. And 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. And to the third question on the 3 shot series, I will pass on that question to my colleague, Luis Jogar. Luis, please.
Yes, Melanie. Thank you very much. So yes, I think that, Carlos and Melanie, there are now a patchwork of recommendations. So just to remind everybody, 11 years of age, there is a dose of the detravatant vaccine and a booster dose of 16 years of age, and those are routine recommendations. Those are the former ATIT Category A, and the uptake is very high.
I think you've mentioned why you were thinking that the 2 doses for Menh B 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 Category B or share clinical decision making. So we are expecting when the ventabayment is introduced is to reduce the 4 current shots into 3 shots. And go into the universal or routine immunization, both at 11 years of age after the surveillance containing vaccine and then Tudo received to replace the 3 doses in the 16 years of age. For that reasons, we are very, 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, Naele.
Thank you, Luis. Operator, next question please.
Your next question is from the line of Geoffrey Forges with SVB Leerink.
Thank you very much for taking the question. A couple for Luis. I just want to follow-up on the question about pneumoconjugating. And how do you expect the ATIP to handle a time difference between the availability of the package for your data and then your competitors' data. So is there a threshold where the ATIP will lump them together and just take a vote and issue a recommendation?
Is that 6 months, 3 months, 1 month? Just trying to figure out whether there'll be a switch in the recommendation to your competitors' product and then theoretically a switch back to yours assuming the pivotal trials are correct. And then a question for you, Catherine. It's something that I'm sure is near and dear to your heart, but you need a proprietary adjuvant system. We've been surprised with the performance of all the supronin derived adjuvants.
And I know you're headed towards mRNA. But 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. So Luis will do will take the first question and Catherine will take the second question. Luis, please.
Sure, absolutely. About the timing of AT and T. Well, first of all, of course, I cannot speculate around what the AT and T is going to do. But that's an interesting question. And I think I would answer it in
2 ways. First, for adults.
And I think as you heard, Catherine, we are sort of fighting in October the PPD 2020. So again, we'll see how it goes. But in principle, we expect that life insurance will be in mid-twenty 21. Now we do not know whether America is going to be up there or not. But the idea would be that both vaccines would be either moved into the grade and recommendations for June 2021 or in October 2021.
So 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, there is we are a year behind. But I think as Patrick mentioned, we are trying to do our best to shorten that gap as much as possible. And if we shorten that gap to less than 1 year, it might seem prudent to have a sort of a holistic review of the recommendations of pediatrics just together. But really that will depend on the gap between the two vaccines.
And unfortunately, I cannot give you whether it's 3 months or 6 months. But it would be 1 or 2 ATIC meetings, I would say, as a difference. And then I'll pass it to Catherine.
Thank you, Louis, and thank you, Jeff, 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 adjuvant when we believe that the current approaches may not be sufficient to develop a successful vaccine. And 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 provide the platform that we believe could be provide better protection each year.
Thank you very much. Yes, thank you, Kathleen. Operator, ready for next question, please.
Your next question is from the line of Terence Flynn with Goldman Sachs.
Great. Thanks for taking the questions. First, it's kind of a follow-up to a prior one. With respect to the 20 balance 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 Prevenar 13?
And then 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? And then the third question is just on the C. Diff vaccine, any way to lower the number of injections there needed from 3 to less than 3?
Thank you.
Okay. So I'm going to start with the Siggi's question and pass it on to, Sikafim, please. And then I'll take the CCD20 question. And actually, I'm so sorry, but I did not get the second question. Can you repeat it?
Okay. All right. So let's go then to Catherine. Can you please then address the CD question on the number of doses? And then I'll address the CTB-twenty 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. So given the exciting data that we are seeing out of this technology, you are absolutely correct. We are thinking about widening our platform to encompass additional release targets.
So that is in addition to the influenza vaccine. So 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, Catherine. Now to the we are confident with the potential of PCV20, of course, given the augmented coverage that we have mentioned. Yet, we also do websites that there will be a period where we will have both PCV20 and PCV13. While our strategy is to transfer all of our PCV13 business to PCV20, There will be a period where we have found because the registration time line is not the same on every country, especially for the emerging market countries.
So there will be a period of time where we will have CPD20 in
the U. S. And in
Europe, and we will still have CPD still have PPD 13 in emerging markets. So thank you for your questions.
Perhaps you can find to Vida. Vida, is there a question about the 3 doses versus 2 doses for specific clinical program, perhaps you want to elaborate that?
Yes. So maybe I can just speak to that briefly. So obviously, if the C. Difficile efficacy trial, the CLOVER trial demonstrates efficacy with a 3 dose regimen, there is the potential by showing that an immune response with a 2 dose regimen spread 6 months apart, if that shows a comparable immune response, there's the potential for a 2 dose regimen to be part of an indication. And so it's a good question, and it's something that we're interested in.
Okay. Thank you. Thank you, Bill. And we're ready for the next question, operator.
Your next question is from the line of Seamus Fernandez with Guggenheim.
Great. Thank you for the question. So 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 3 20 balance.
Historically, I think the threshold that had been established by regulators was the 0.3 or 0.35 microgram per ml target for the antibody threshold. So I'm just wondering if that threshold has been achieved with all of the 20 serotypes. And then as a separate question to that, if it hasn't been achieved, but non inferiority has been clearly established to prednisone thirteen, Is it possible that the agency's bar has shifted to some degree given the efficacy with predn-thirteen? And then second question I have is actually on around the RSV program. Can you help us understand 2 questions?
Number 1 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? And then separately, just in terms of the percentage uptake that we typically see with maternal vaccination, What would be the estimated acceptance because it would seem like that might be more challenging versus a passive vaccination approach? Thanks so much.
Thanks, Carol. Thank you very much for your questions. The first two questions, and then for Nishal, I think that Catherine, you can take those and you could probably then also ask that. And I will take the R and D question. Thank you, Catherine.
Yes. Thank you. So just as I described earlier, the polysaccharide conjugates vaccines will be licensed against existing pneumococcal conjugate vaccine. So PCV20 will be licensed by demonstration of non inferiority to PCV13 for the stereotypes in common and then also using the 0.35 threshold for the 7 additional serotypes. So 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. So 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 2020, we have established precedent that in if by chance 1 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. And that is actually a very wise decision that we want because we have seen exactly the same for PCV13 when we compared it to the original Prevnar7. We found that 2 of the serotypes did indeed miss the noninferity margin, but then other data such as fold rises, the reverse cumulative distribution and how the extent to the mix of the non inferiority margin were all taken into consideration as well as functional antibody, which led to the licensure and approval of PCV13.
And what turned out then in real life after the vaccine PCV13 that is was rolled out, that the stereotypes that actually did miss non inferiority were very effective and continue to be effective in after the use of the PCV13 vaccine. And we expect, should we see 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. Maybe I'll start and let you discuss some of the advantages and then Luis can put into context how a monoclonal vaccine, assuming those are successfully approved, could coexist. So from our perspective, it is our intent to and we have designed the R3 maternal program to really address the global unmet medical need of R3 in newborns up to 6 months of age where we really do see the highest unmet medical need. So one of the advantage of a vaccine is that the protection of the newborn starts at birth because it's actually provided by the mom.
The second advantage of a vaccine approach is that you do induce a what we call polyclonal RSV neutralizing antibody response. And that is in contrast to a monoclonal that only targets a single epitope on the virus. And when you think about this, the RNA viruses, even though they are more stable than flu, nevertheless, they do mutate, and we have already seen a number of mutations that are circulating, so there's not just one strain. And there is a high liability of the monoclonal to actually lose effectiveness should the epitope that is recognized by that monoclonal change over time. And so, 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, Catherine. And Sienna, I think your question was about, okay, suppose that you have the monoclonal antibodies, similar characteristics, how do they coexist together based on AT and T recommendation? And again, we are very confident about our approach. And I think Kathleen has summarized it well, our approach with our RSV vaccine for the ATIB.
Again, I come back without the ATIB and the CDC is going to decide to make these recommendations. But the way that we are seeing it is that it seems to us that a structured recommendation makes more sense that just having 2 recommendations with 2 different providers, 2 intervention tools, 2 target populations, pregnant women or kids and then 2 time points as well. So at the end of the day, what we believe is that if safety and efficacy demonstrated, then there's going to be a universal recommendation for Western women. And then the monoclonal will be a complementary intervention, either for high risk group or either for unvaccinated or for older age population. That's how we see this play now.
So thanks very much. Back to you, Vanessa.
Thanks, Dominique. And 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% to 70% market share, especially because R and D is the number one cause of hospitalization in infants younger than 6 months old and the treatment is really limited to only fluids and oxygen. So we do believe that with appropriate and awareness across continued strong clinical results, all stakeholders, including second presenters will see the value for that RSV vaccine in the infraving. So thank you so very much for your questions.
We have run out of time. So thank you to the panel for answering all the questions. And again, thank you for the audience for all your great questions. And now I pass it on back to Chuck.
Great. Thanks, Nanette. And thanks, everyone, for your engagement today. A couple of things. We'll certainly look forward to reviewing our other therapeutic areas within the organization tomorrow.
As a reminder, that will be inflammation and immunology, rare disease, oncology and then the COVID section. And as a reminder, tomorrow's session is going to begin at 10 a. M. New York time. And then if you refresh your screen, you'll see at the top a survey.
So if you could take a moment to fill out the feedback survey, we'd certainly appreciate that. And we look forward to reconnecting with you all tomorrow, and this will end today's session. Thank you.