Pfizer : Oncology Innovation Day Transcript

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EDITED TRANSCRIPT

Pfizer Inc To Host Oncology Innovation Day

EVENT DATE/TIME: FEBRUARY 29, 2024 / 6:00PM GMT

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FEBRUARY 29, 2024 / 6:00PM GMT, Pfizer Inc To Host Oncology Innovation Day

CORPORATE PARTICIPANTS

Adam Schayowitz Pfizer Inc. - Head of Product Teams, Portfolio & Program Management, Pfizer Oncology Akos Czibere Pfizer Inc. - Therapeutic Area Development Head for Hematology-Oncology, Pfizer Oncology Albert Bourla Pfizer Inc. - Chairman of the Board & CEO

Chris Boshoff Pfizer Inc. - Executive VP & Chief Oncology Officer

Dana Kennedy Pfizer Inc. - Therapeutic Area Development Head for Genitourinary Cancer, Pfizer Oncology Francesca M. DeMartino Pfizer Inc. - Chief IR Officer & SVP

Jeffrey Settleman Pfizer Inc. - Chief Scientific Officer, Pfizer Oncology

Megan O'Meara Pfizer Inc. - Head of Early-Stage Development, Pfizer Oncology Roger Dansey Pfizer Inc. - Chief Development Officer, Pfizer Oncology

Scott Peterson Pfizer Inc. - Head of ADC Discovery and Cancer Immunology, Pfizer Oncology Suneet Varma Pfizer Inc. - Commercial President, Pfizer Oncology

Thomas Powles University of London and Barts Cancer Centre - Professor of Genitourinary Oncology

CONFERENCE CALL PARTICIPANTS

Akash Tewari Jefferies LLC, Research Division - Equity Analyst

Andrew Simon Baum Citigroup Inc., Research Division - Global Head of Healthcare Research and MD Carter Lewis Gould Barclays Bank PLC - Research Division - Senior Analyst

Courtney Breen Sanford C. Bernstein & Co., L.L.C. - Senior Research Analyst, US Biopharma Christopher Thomas Schott JPMorgan Chase & Co, Research Division - Senior Analyst

David Reed Risinger Leerink Partners LLC, Research Division - Senior MD & Senior Research Analyst Evan David Seigerman BMO Capital Markets Equity Research - MD & Senior BioPharma Research Analyst Louise Alesandra Chen Cantor Fitzgerald & Co., Research Division - MD & Senior Research Analyst Stephen Michael Scala TD Cowen, Research Division - MD & Senior Research Analyst

Susan Chor BofA Securities - Equity Research Associate

Terence C. Flynn Morgan Stanley, Research Division - Equity Analyst Trung Chuong Huynh UBS Investment Bank, Research Division - Analyst

Vamil Kishore Divan Guggenheim Securities, LLC, Research Division - Research Analyst

PRESENTATION

Francesca M. DeMartino Pfizer Inc. - Chief IR Officer & SVP

Welcome, everyone. Good afternoon, and thank you so much for joining us today, both here at our New York headquarters and online. I'm Francesca DeMartino, Chief Investor Relations Officer for Pfizer, and it is my great honor to kick off a day we've all been waiting for, our Oncology Innovation Day.

Before we get started, I want to remind you that today, we will be making forward-looking statements in discussing certain non-GAAP financial measures. I encourage you to read the disclaimers in our slide presentation, which are also shown on the screen in the room. In addition, the full transcript and video recording of today's event will be posted on the Pfizer IR website, once available, approximately 48 hours post event.

One final note for those in the room, you should have received your unique WiFi access information when you picked up your badge. Please see a member of the IR team with any questions.

We have a robust agenda today, which we've developed to provide you with a comprehensive overview of our new Pfizer Oncology organization. Throughout the afternoon, you'll hear directly from our new Pfizer Oncology leadership team. This team represents top talent from Pfizer and Seagen and is leading our new chapter in the fight against cancer. You'll gain insights into our portfolio, technology, new data and key catalysts and hear why we believe the combination of Pfizer and Seagen is more than the sum of its parts.

To start the day, our Chief Oncology Officer, Chris Boshoff, will unveil the strategic vision for our new Pfizer Oncology organization, followed by presentations on our opportunities in GU and thoracic cancers. Of note, we are pleased to welcome Dr. Tom Powles, a world authority in urothelial cancer, who is joining us to showcase several Pfizer programs focused on UC.

After a short break, the afternoon will continue with presentations on breast cancer, hematology oncology and next-generation approaches to therapy development. We'll end with a commercial outlook.

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FEBRUARY 29, 2024 / 6:00PM GMT, Pfizer Inc To Host Oncology Innovation Day

You'll note that we have built in 2 Q&A sessions, one before the break and one near the end of the day. We'll have a panel on stage during each session for you to ask your questions related to the preceding presentations. We ask that you please keep your questions relevant to the panelists on stage and related to the presentations you just heard so that we can have the most productive discussion.

The first Q&A session will focus on our oncology strategy, GU and thoracic presentations. The second will focus on our breast, hematology oncology, next-generation and commercial presentations. We'll conclude our event with summary remarks from our Chairman and CEO, Dr. Albert Bourla.

For those attending in person, a reception will follow. Our goal is that you will leave today with an appreciation of the tremendous opportunity we have in Oncology and an understanding of the anticipated catalyst-rich months and years ahead.

Chris Boshoff, who leads our new organization, will be our host for the afternoon. Trained as a medical oncologist, Chris joined Pfizer in 2013 following more than a decade of experience leading academic cancer research. At Pfizer, Chris and his team have delivered numerous cancer medicines from Phase 1 to global approvals, including more than 10 FDA Breakthrough Therapy and European Medicines Agency prime designations.

And now as Chief Oncology Officer, Chris leads end-to-end Oncology R&D and while his background speaks for itself, after 4 months at Pfizer, I can personally attest that Chris is an exceptional leader, a wonderful colleague and friend, and we are really fortunate to have him at the helm.

Joining Chris as speakers today will be several members of his new Pfizer Oncology leadership team: Roger Dansey, our Chief Development Officer; Megan O'Meara, Head of Early Stage Development; Jeff Settleman, our Chief Scientific Officer; Suneet Varma, our Oncology Commercial President; and as I mentioned, Dr. Tom Powles. Chris will introduce our speakers throughout the day, and these leaders will also be joined during the Q&A sessions by additional Oncology leaders and experts.

So with that, let's get started.

(presentation)

Chris Boshoff Pfizer Inc. - Executive VP & Chief Oncology Officer

Welcome, everyone. Welcome. It's a great pleasure to have you all with us here at the Pfizer headquarters. Just over 2 months ago, we actually closed the acquisition of Seagen. And on behalf of the whole leadership team, we're excited now to unveil our new Oncology organization to you today.

Over the next few hours, we'll do a deep dive into our expanded portfolio, our clinical development plans and our capabilities. We will also share more about our strategy, which is assigned and designed to drive significant innovation and growth through 2030 and beyond.

You've heard about a lot now about Pfizer Oncology's renewed focus. As a new organization, we have a bold vision that aligns with Pfizer's purpose. Pfizer's purpose: breakthroughs that drive -- breakthroughs that change patients' lives. Our vision is to accelerate breakthroughs that will help people with cancer globally live better and longer lives.

This drives everything we are doing and reflects our personal mission to improve the lives of people with cancer. Our vision is ambitious, but rightfully so, because as you all know, cancer remains one of the greatest health challenges of our lifetime.

For the first time, 2 million people in the U.S. are expected to be diagnosed with cancer this year. Globally, around 20 million people received a cancer diagnosis in 2022 alone. Approximately 10 million people around the world died from cancer in 2022, and just over 600,000 deaths are expected to occur in the U.S. this year.

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FEBRUARY 29, 2024 / 6:00PM GMT, Pfizer Inc To Host Oncology Innovation Day

We believe advancing the global fight against cancer will have a tremendous impact on society. And that's why so many companies in this industry are working towards delivering new breakthroughs for people with cancer. In fact, the oncology market is projected to increase to up to $500 billion by 2030.

This year, Pfizer is celebrating our 175th anniversary. We have demonstrated the ability to innovate with urgency, and billions of patients globally have been treated with one of our medicines or vaccines.

Seagen has pioneered the technology and development of antibody drug conjugates, so ADCs, which are emerging as a very, very important tool in the fight against cancer. Over their 25-year history, Seagen developed deep technological expertise to become an industry leader in the ADC field.

And today, nearly half of all the FDA-approved and marketed ADCs use a unique linker payload system developed by Seagen. That's why bringing these 2 companies together has been so exciting for us.

By combining our respective strengths, experience and heritage, we are uniquely positioned to deliver additional breakthrough cancer medicines to more people around the world. As a newly combined organization, our expertise and collective capabilities are now amplified to deliver even more impact for patients than each company could do by itself.

Beginning with expertise. We are bringing together the best from both organizations. We have an exceptionally talented team with extensive experience in oncology.

Innovation. Our pipeline has now expanded significantly. And we are focused on flawless execution, delivering the next generation of breakthroughs.

And lastly, scale. We're poised to have a true global impact. Our new Oncology organization leverages the breadth and depth of Pfizer, including our industry-leading commercial and manufacturing capabilities, to drive broader patient reach.

Before we dive deeper into our future, I would like to briefly touch on what we have been able to achieve over the past decade. Pfizer has been growing Oncology for about 20 years. With the establishment of the first Oncology business unit in 2014, we've emerged from a niche player to a bona fide leader today.

Leading up to 2023, we established a solid foundation with numerous innovative medicines that became new standards of care in several cancers. In fact, our medicines reached just over 2 million patients with cancer last year, which includes our innovative medicines, biosimilars and cancer therapies from Pfizer's hospitals and hospital unit.

We've also seen outstanding revenue growth of our Oncology business over the last decade at a CAGR of over 19%, outpacing the industry average of approximately 10%. With the acquisition of Seagen, we believe our industry-leading portfolio is positioned for strong near-term growth.

We now have 4 additional approved medicines, all of which are first-in-class in their respective indication, and all 4 have demonstrated overall survival benefit. Mid to long term, our early-stage and late-stage development programs have doubled, representing significant future opportunities.

We are at an inflection point of our leadership. We expect to impact many more lives of patients with cancer over the next 5 years plus, aiming to double the number of patients treated with our innovative cancer medicines by 2030.

Leading up to the close of Seagen, we had several months to undertake integration planning and ensure a seamless transition on day 1. The Pfizer Oncology organization, which includes the U.S. Oncology Commercial division and end-to-end global R&D, is designed to improve interaction and collaboration across all functions, from early discovery all the way through to commercialization, facilitating quicker decisions and to accelerate execution.

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FEBRUARY 29, 2024 / 6:00PM GMT, Pfizer Inc To Host Oncology Innovation Day

Here's our new Oncology leadership team. Any organization is only as good as its people, and I'm pleased to say that we are one of the most experienced and talented groups of oncology leaders in the industry, with nearly 300 years of oncology experience across academia and industry between these leaders combined. These are leaders who've done it before, and they have highly experienced teams working with each of them.

Retention of talent has been critical for us with this integration. And today, we have approximately 50-50 participation of Seagen and Pfizer colleagues in the combined new organization. These colleagues are united around our vision to accelerate breakthroughs for patients with cancer. Our integrated Oncology organization is now fully operational.

To further illustrate the executional excellence of this team, I'd like to highlight 3 examples of how we've rapidly delivered transformational medicines to patients, starting with LORBRENA, which is our third-generation ALK inhibitor for metastatic non-small cell lung cancer. LORBRENA is a small molecule that was discovered by Pfizer scientists using state-of-the-artstructure-based drug design. This is a medicine that took less than 5 years in development, significantly shorter than the industry median at the time.

Moving on to ELREXFIO, which is our BCMA-targeted bispecific antibody in development for multiple myeloma. ELREXFIO was first developed by Pfizer scientists, and we significantly accelerated the clinical development time lines. The start of the first pivotal trial, MagnetisMM-3, to ELREXFIO's first FDA approval took less than 2.5 years.

And lastly, moving to PADCEV, which was developed by legacy Seagen scientists in partnership with Astellas. The recent expansion of PADCEV to locally advanced or metastatic urothelial carcinoma was a tremendous feat in speed.

Receipt of the top line report from the groundbreaking EV-302 trial to FDA approval took less than 3 months. And this is a remarkable feat in terms of time lines and a testament to what we believe is PADCEV's groundbreaking clinical value, but also the unbelievable talent of the team that delivered PADCEV to the FDA.

Pfizer is consistently ranked by the Center for Medicinal Research on multiple cycle time metrics using -- and the latest metric from them places us #2 in the industry for oncology. And importantly, across combined legacy Pfizer and legacy Seagen, we have secured 8 FDA approvals for 8 cancer indications in the last 3 years alone.

These examples of rapid execution are great representation of what Pfizer and Seagen were able to achieve as individual companies, but together, we believe our strengths are multiplied. It is also critical to have the resources and scale to deliver these breakthroughs to patients globally.

Pfizer has an extensive global manufacturing footprint with 10 of our sites manufacturing oncology products on 3 continents compared to Seagen's 1 manufacturing site. This robust internal network is critical to ensure agility and responsiveness and puts us in a solid position for growth as our portfolio expands.

In fact, we have 6x the capacity for vial volume for ADC production to what Seagen had alone. We also have 7x more bioreactors for biologics. And we have a supply channel presence in over 100 countries, enabling us to reach large patient populations around the world.

Another example of our amplified impact is through our medical and commercial organizations. We have increased in size and numbers. We have tripled the size of our customer-facing colleagues in the U.S. compared to Seagen alone. And Pfizer has commercial footprint in more than 100 countries compared to 17 for legacy Seagen.

We have cross-trained now our field force, which means we should double our share of voice in key tumor areas. But just increasing size isn't everything. As both Pfizer and Seagen have been building our leadership in oncology for many years, we have each built strong relationships with physicians and customers in our key tumor areas.

Our newly combined presence across both medical and commercial will expand the breadth and depth of our engagement with health

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FEBRUARY 29, 2024 / 6:00PM GMT, Pfizer Inc To Host Oncology Innovation Day

care providers in both academic and community settings. And lastly, we have the ability to leverage Pfizer's large-scale medical and commercial platforms and capabilities, including our chief marketing offers, to ensure a surround-sound approach with digital channels, analytics and tools.

Let's now move to our strategy. To guide us, we have a new impactful strategy in place. We are focused on 3 main modalities where we have significant depth, world-class capabilities and expertise, small molecules, antibody drug conjugates and bispecific antibodies, including other immuno-oncology biologics. This gives us the ability to combine and adapt modalities to improve outcomes.

For our therapeutic areas, we're building on the cancer types where we have already established presence and where we can further develop our leadership. [These are] across hormonal subtype, genitourinary cancer, including prostate; and urothelial cancer, including bladder cancer; hematology/oncology, including multiple myeloma and certain lymphomas like Hodgkin's disease; and thoracic cancers, which include lung and head and neck cancer.

Within these areas, we're initiating parallel earlier-line trials where the addressable population is the greatest, aiming to both accelerate a new wave of breakthroughs and move approved medicines into earlier lines of treatment. We will continue to also develop targeted therapy opportunities where we believe we can have a true impact, for example, BRAF-positive or HER2-positive colorectal cancer. You will hear much more about our tumor-specific strategies from our speakers today.

Through our strategy, we believe we are positioned to drive transformational global impact through 2030 and beyond. We have the potential to increase the number of blockbuster medicines in our portfolio from 5 today to 8 or more in 2030. We shall provide insight into these 8-plus opportunities today.

With our R&D focus, we anticipate having a tenfold increase in the proportion of revenue from biologics by 2030, presenting potentially more durable revenue opportunity and potentially improved outcomes for patients. These will set the stage for our ambition to double the number of patients treated with our medicines by 2030. We will share further detail of how we plan to achieve these goals through our presentations today.

To close, I'd like to highlight our overall portfolio. As you can see, we have a deep and diverse pipeline, spanning our core modalities and key tumor areas that underpin our strategy. You will hear more about each of these tumor areas and many of these exciting pipeline opportunities during our presentations today.

And with that, we will now transition to our next session on genitourinary cancer, beginning with a reminder of what drives each of us each and every day.

(presentation)

Chris Boshoff Pfizer Inc. - Executive VP & Chief Oncology Officer

Prostate and urothelial cancer are 2 of the most common cancers impacting patients in the United States, both with significant unmet needs. In prostate cancer, close to 300,000 new cases and 35,000 deaths are projected in the U.S. this year alone. And with urothelial cancer, bladder cancer, up to 83,000 new cases are expected this year and 17,000 deaths.

These continues -- there continues to be obviously high unmet need for both types of cancers. In turn, there's a lot of activity in this space, and with many of the industry activity pursuing new treatments for both prostate and bladder cancer.

The prostate cancer market is projected to increase to $26.5 billion by 2030, and the urothelial cancer market is projected to more than triple to $17 billion by 2030. Pfizer has a long heritage in improving outcomes for people living with genitourinary cancers, and we now have an industry-leading portfolio with many exciting opportunities ahead.

Starting with bladder cancer. Our portfolio is anchored with the groundbreaking benefit of PADCEV in patients with locally advanced or metastatic tumors, with opportunities to move to earlier lines of treatment with ongoing Phase 3 studies in muscle-invasive bladder

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FEBRUARY 29, 2024 / 6:00PM GMT, Pfizer Inc To Host Oncology Innovation Day

cancer.

In metastatic disease, we are developing a novel HER2-directed ADC, disitamab vedotin, which has shown very promising early clinical data. The ongoing pivotal program is evaluating disitamab vedotin in the subset of patients with HER2-positive disease, both high expressers and low expressers, with planned registrations in second line as monotherapy and in first line combined with pembrolizumab.

Finally, in nonmuscle-invasive bladder cancer, we are evaluating the combination of sasanlimab, our subcutaneously administered PD-1 antibody, with BCG to improve outcomes for patients with high-risknonmuscle-invasive bladder cancer. To share more about this portfolio I'd now like to introduce 2 of our speakers for this session.

First, I'd like to formally introduce Roger Dansey, who is our Chief Development Officer. Roger joins us from Seagen, where he was President of Research and Development. Previously, Roger was therapeutic area head of late-stage oncology at Merck, prior to that, clinical development leadership at Gilead and Amgen.

Roger holds an MD from the University of the Witwatersrand in Johannesburg, South Africa. And he brings unmatched oncology clinical drug development experience to Pfizer as well as the industry gold standard for executional excellence.

And then I'd also like to welcome Dr. Thomas Powles, who is professor of genitourinary oncology at the University of London and Barts Cancer Center. Dr. Powles is the Head Investigator for the PADCEV EV-302 trial and a world-renowned urological oncologist. We're happy to have him here today to share his perspectives on the exciting data from PADCEV and bladder cancer as well as additional medicines we have in development for bladder cancer.

I'll now turn it over to Dr. Powles. Thank you.

Thomas Powles University of London and Barts Cancer Centre - Professor of Genitourinary Oncology

Thanks, Chris. It's really kind of you. Thank you for inviting me, and it's nice to see you. Chris asked me to come today, and I jumped at the chance. I live in London. You can see by my accent, probably. And the reason I came was because I think we are at a pivotal moment in oncology. We've not been at a point like this for some period of time.

I was involved in the immuno-oncology transformation and partly involved in the targeted therapy transformation. And I think we're going through one of those transformations at the moment, and I wanted to describe what my views are of those. I'm very lucky in that respect.

I've led 23 big randomized trials in my life. Some have been successful, most have not. But I'm going to describe today the one that has been most successful, which was presented recently at ESMO. PADCEV, enfortumab vedotin, is what I call it, is an antibody-drug conjugate. It targets Nectin-4.Nectin-4 is expressed on almost all urothelial cancers. And patients with advanced urothelial cancer have a really poor outcome, meaning survival of about a year historically.

PADCEV, it binds to the system. It's internalized rapidly. It is then degraded by the lysosome. And from there, MMAE, the microtubule disrupting agent, is activated. And at that point, it triggers apoptosis. It also causes cell cycle arrest through the endoplasmic reticulum. There's the immunogenic cell death also. So that's the second mechanism. And thirdly, it's important to recognize that MMAE is permeable and can cross the barrier into other cells and trigger another apoptotic process.

The drug itself, therefore, is a really attractive target for urothelial cancer, but potentially other cancers also. This is the study which I led, and I think it was -- at the time we designed it, we felt it was ambitious. It turned out that, that wasn't the case. We were right to be ambitious.

When we designed it, we knew that enfortumab vedotin was associated with responses in patients who are heavily pretreated. We know that -- well, I felt it was probably the most active single agent that we had, but you might be aware that we've struggled to combine drugs with immune checkpoint inhibitors in urothelial cancers previously.

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FEBRUARY 29, 2024 / 6:00PM GMT, Pfizer Inc To Host Oncology Innovation Day

So we did Phase 2 work, and that Phase 2 work showed response rates in advanced disease of 70%. That was a little bit unprecedented in urothelial cancer, who are used to about 40%, but Phase 2 data can be misleading. And so it was important to do this large randomized Phase 3 study.

The randomized Phase 3 is a classic 850-patient,first-line metastatic urothelial cancer, enfortumab vedotin, PADCEV plus pembrolizumab, KEYTRUDA, the 2 drugs together versus standard chemotherapy. During the conduct of the trial, the control arm changed the -- we allowed the introduction of avalumab. 31% of patients got avalumab in the control arm. That's actually quite a high proportion of patients.

The endpoints, dual endpoints, progression-free survival and overall survival with some secondary endpoints around safety and response. You can see from here, these are the primary endpoints of progression-free and overall survival. And they are overwhelmingly positive, with a 45% reduction in the risk of progression or death, and a 53% reduction in the risk of death.

These are, by far, the most impressive data we've ever seen in urothelial cancer. In fact, it's the first time we've beaten frontline chemotherapy, gem/cis or gem/carbo, in urothelial cancer. And to beat it by 53%, the reduction of risk of death of that proportion was unprecedented.

The control arm actually performed really well in this study. Historically, as I said, the median survival going back in other trials like DANUBE was more like 12 to 14 months. So this really was exceptional data. It's also worthwhile noting the CR rate, complete response rate, was 30%. We've never seen anything like that before. And that's why we're so excited about moving this into the perioptic setting.

It's important to also recognize that in this study, we enrolled all comers. We enrolled patients, irrespective of their PD-L1 status, cisplatin eligibility, which I think will become a thing of the past. But we've got very obsessed in urothelial cancer with whether a patient has cisplatin or carboplatin. It's my feeling that the drugs have more similarities than differences. Other people disagree with me on that issue.

But this was an all-comer study for the entire population. And it's likely because of these results -- historically, not all patients have been offered chemotherapy in urothelial cancer. The outcomes have been modest. It's quite toxic. I suspect the pie will increase. I think more people will be offered EV-pembro that were previously being offered platinum-based chemotherapy.

Adverse events are really important part of everything that we do. They're super important for patients, too. EV-pembro was given until progression, platinum-based chemotherapy given for 6 cycles. You can see here, actually, the grade 3 or 4 adverse events were less frequent for EV-pembro than for platinum-based chemotherapy, 70% versus 56%.

My experience with platinum-based chemotherapy and of my colleagues is not fantastic. It's associated with quite bad renal toxicity. In fact, if it was developed tomorrow, it probably wouldn't get off the ground because you've got to give IV fluid beforehand for 4 hours, then you get the platinum. We have developed 3 antiemetic drugs to control the nausea and neutropenic sepsis.

I've got a patient at the moment in our hospital who's on their third cycle. The cancer is growing, the neutrophil count is 0.1. They've got infection, they're on IV antibiotics. It's a complicated regime to give. Unfortunately, the dose is different from that. It is associated with adverse events. Skin toxicity in the first 3 or 4 cycles and peripheral neuropathy, which increases at cycle 6 to 12.

My experience, my personal experience of this, and I'd spend a lot of time speaking to people in rooms not dissimilar to this about adverse events of drugs is that it's manageable. In fact, I think it's easier to give them platinum-based chemotherapy. I think dose delays and interruptions are required.

An early recognition of new toxicity is really important. When we go to med school and oncology school, we're taught for years about adverse events of chemotherapy. And then when new drugs arrive, we're supposed to just pick them up immediately. I think we need to think more carefully about that. But I think this is a total regime. I think it's going to be very widely used throughout the world.

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FEBRUARY 29, 2024 / 6:00PM GMT, Pfizer Inc To Host Oncology Innovation Day

The data made a huge splash at ESMO. I was lucky to present it. I made less of a splash. The data was amazing and spoke for itself. We got 2 standing ovations, which is a rather unusual thing and made me quite anxious at the time. Why did it make such a big splash? It made such a big splash because we've never seen something like this before.

Unlike pancreatic cancer, I think when we beat gemcitabine in pancreatic cancer, it will be a similar moment. It's taken such a long time and has been so frustrating to see these patients come, struggle and then die of their disease.

That's just the first part of the story because the story in urothelial cancer is going to continue. And I got a feeling the story might get better. We really need to cure more of these patients. We don't yet know about some of the durability issues of EV-pembro. I think the median overall survival will turn out to be about 3 years, at 36 months. There's a bit of instability in that curve.

But the CR rate of 30% is really intriguing. I have treated maybe 20 or 30 patients with the combination. And we have patients who we've given 4 or 5 cycles, too, some 8 or 9, and they've got into durable remissions. And we stopped some of the drugs in some of those patients, and the cancer's not come back.

If we give these drugs to patients at the time of their operation when half of them are cured with cystectomy alone, with or without adjuvant nivolumab, I think we might be able to increase the cure rate further. And I think we might be able to cure of some of these patients with systemic therapy alone.

And I hope it's going to be 30%, 40%, dare I say it, 50%. I don't know what's going to happen. But I'm very excited about these 2 trials, one in cisplatin eligible, one in cisplatin ineligible. One of them is enrolling, one of 'em completed enrolling. You can see here the date of '26 and '27 when they're expected, but we'll probably get some interim analysis results potentially before then.

Disitamab vedotin is a drug which I'm also excited about. I've got personal experience with this drug as well. We've treated about 20 patients. And I can tell you, it's also a very active antibody-drug conjugate. Disitamab vedotin has a mechanism of action which is -- it's targeting HER2. It's distinct from some of the other HER2-targeted therapies. It's actually internalized more quickly than trastuzumab. And the reason for that is it binds to a different epitope.

It also has MMAE as a payload. So the mechanism of action in terms of the microtubule disruption, the immune component and potentially a good partner with immune therapy, but also the bystander effect obviously applies as well. And there's a table there looking at other HER-targeted therapies and how this may compare.

This drug is approved actually in China, and it's used in gastric cancer, and it's also used in urothelial cancer. As I said, it's a HER2-targeted therapy. It looks like that there is some enrichment in those patients who heavily overexpress the biomarker. But you can see actually here, the vast majority of patients have expressed HER2. And on top of that, the response rate is about 50% in heavily treated urothelial cancer.

Now remember that enfortumab vedotin dosing was 40%. So now I'm not a great one for comparing Phase 2 studies, but I'll just say that this drug is active. We've given it to our patients. It's active. The adverse event profile, because it's targeting HER2 and not Nectin-4, is a distinct toxicity profile, perhaps less skin toxicity, in my opinion.

The high rate of durable responses that we've seen with monotherapy is actually increased again when we combine it with an immune checkpoint inhibitor. This is toripalimab, not pembrolizumab. This is Chinese data again. And you can see here both from the waterfall plot and the spider plot that there will be deep durable responses.

I think the point that I'd kind of like to make is that I'm not convinced that all partnerships with ADCs and immune checkpoint inhibitors is going to be synergistic or additive. But it looks like MMAE may be a good partner, a good payload partner. We saw that in EV-302. We may be seeing that with disitamab vedotin also. As you can imagine, there's an ambitious plan for disitamab vedotin.

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FEBRUARY 29, 2024 / 6:00PM GMT, Pfizer Inc To Host Oncology Innovation Day

Chris (inaudible) which I was -- which I'm bought into.

I'm also bought into the strategy for this agent. As a single agent, it has an accelerated approval with -- sorry, has breakthrough status with the FDA. But it's also being explored in a Phase 2 study to confirm that monotherapy activity. Our site is taking part in that study at the moment. And we're enjoying using the drugs, and we're seeing deep responses, as I said.

It's also being explored in a frontline randomized Phase 3, a trial design not dissimilar to the EV-pembro trial, which I just previously showed you. (inaudible) developed subcutaneously, which is different from the other immune checkpoint inhibitors, which have been developed intravenously. Although some have data or more data subcutaneously. It's a potent PD-1 inhibitor. It has high receptor affinity, and it's a drug which is being explored in nonmuscle-invasive urothelial cancer.

I described advanced disease, and I talked about enfortumab vedotin and pembrolizumab and disitamab vedotin. I talked about that muscle-invasive setting, where we do the cystectomy to cure patients. And we hope that by giving EV-pembro neoadjuvantly, we're going to cure a significant proportion of patients.

And now earlier in the disease, nonmuscle-invasive urothelial cancer, where patients normally just have cystoscopy to scrape away their cancer, the standard treatment for 40, 50 years, perhaps longer, it's actually been BCG therapy. It's an immune therapy. No one knows exactly how it works, which I think is intriguing. But if you go on PubMed, you'll find 100 different ways in which it may work.

But you also know that in this nonmuscle-invasive space, pembrolizumab currently has a license. But in those patients whose cancers have progressed after BCG, this is a more ambitious plan than that. This is to go earlier in this high-risk population. BCG is the control arm. BCG is given as an initial therapy and a maintenance therapy for a period of time. You'll be aware there's a BCG shortage from a global perspective.

In this study, it's 3 arms: it's BCG plus sasanlimab, BCG plus sasanlimab but no maintenance period of the BCG and then BCG alone. I think this is an exciting study. We're hoping to see the study readout in the not-too-distant future. It's an ambitious plan. And as Chris described earlier, the Pfizer Group has a very ambitious strategy.

I'm now going to turn it over to Roger to do prostate cancer. Thank you very much for your attention.

Roger Dansey Pfizer Inc. - Chief Development Officer, Pfizer Oncology

Okay. Good afternoon, everyone. It's great to be here. And I would like to just reiterate what Chris said from a sort of an ex-Seagen side. I'm extremely excited. I mean, we have 2 organizations that already are a level of high excellence. We've brought them together. This idea of best of both is extremely appealing.

And more importantly than anything else is the portfolio is really, really meaningful in terms of what we can potentially do to help people. That's our North Star. That's our driving force in terms of why we do this every day is to make a difference in patients' lives. And certainly, for me, it's very exciting to see all of these programs, great science with good people. Hopefully, we'll bring forward some great medicines.

So turning our attention to prostate cancer, which really can be broadly divided into castration-resistant and castration-sensitive disease with actually large addressable populations across this continuum of disease. Our portfolio is anchored by XTANDI. It's the only antigen receptor-signaling inhibitor, which is actually approved across the prostate cancer continuum.

As we seek to further improve outcomes for men with prostate cancer, we are building on that foundational drug, XTANDI, with the next generation of combinations. We have 2 novel combination approaches: TALZENNA, which is our PARP inhibitor; and mevrometostat, our EZH2 inhibitor, both of which are being combined in development trials with XTANDI. And these 2 will be the focus of my presentation.

However, before we get that, I'd like to remind you just what an advancement XTANDI by itself has been in prostate cancer. I think you can appreciate when you look at the weighted evidence on the slide and demonstrated by all the graphs showing improvement in

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