Pfizer Inc. (NYSE:PFE) Goldman Sachs 44th Annual Global Healthcare Conference Call June 13, 2023 11:00 AM ET
Company Participants
William Pao – Chief Development Officer and Executive Vice President
Conference Call Participants
Chris Shibutani – Goldman Sachs
Chris Shibutani
Good morning, everybody. Let’s start on time. I hate to penalize people who are on time, especially in the morning. So welcome to day two, the Goldman Sachs Healthcare Conference. Hope everyone had a very positive and productive first day experience. Jet lag is kind of a bummer, but off we go.
Very pleased to have Pfizer join us this year. And in particular, a year under the belt Chief Development Officer, William Pao. William, thank you for joining us.
William Pao
Thanks for having me.
Chris Shibutani
Unfortunately, Dave Denton, the CFO, couldn’t be with us here, so we’re really going to focus a lot on the pipeline. I know, obviously, for Pfizer and for investor communities, there’s a lot of big picture questions here, but I think personally that this can be an interesting snapshot to really focus on the expertise of the person who’s joining us for this conversation. After all, they’re on the brief side, anyway.
So I always like to also start again, because you’re a relatively new face to the Pfizer side. You have a long history at some very distinguished academic institutions and a lot of top shops, especially in the cancer space globally. So tell us a little bit about your background, your professional journey.
William Pao
Okay. Yeah, Chris. So basically, MD, PhD I was in the lab of Adrian Hayday at Yale, where I studied the functioning development of mirroring gamma delta T-cells. Then did internal medicine in Cornell Medical oncology at Memorial, did a postdoctoral in the lab of [indiscernible], where then we and others found EGFR receptor mutations as the genetic basis for why EGFR tyrosine kinase inhibitors work in only 10% of lung cancer patients. Then also found the T790M mutation, which mediates resistance. So I have a patent on that with Memorial and some other people.
Then I had my own lab at Memorial, where I saw patients help run trials and do research, and then got recruited to Vanderbilt where I eventually became the Division Chief there of hematology oncology. Continued to see patients run a lab, help run trials, help AstraZeneca develop osimertinib. Also co-founded my Cancer Genome, which is an online tool to enable genetically informed cancer medicine.
Basically then in 2014, got recruited to Roche to head up oncology drug discovery there in the pharma research and early development unit, the pRED unit. And after four years became the head of all of pRED, helping not only in oncology, but immunology infectious diseases, ophthalmology, neuroscience and rare diseases. And then basically joined Pfizer last year as the Chief Development Officer.
Question-and-Answer Session
Q – Chris Shibutani
Okay. Great. So obviously incredible background in terms of the academic experience, very relevant clinical experience as well, nested to a great extent. Obviously Roche and Genentech and the discovery side of it. So there must have been — basically you’ve been surrounded by a lot of smart challenging people perpetually and so your time at Pfizer is actually at quite a crucible for the company. Thinking about everything that’s happened. Obviously, there’s a lot of moving parts here in terms of what we know the portfolio. A lot of the LOEs coming in the back end of the decade long comes COVID, completely changes the trajectory, the revenue profile, almost creating two companies in essence, right? And investors have a lot of debate. We won’t focus on that with you. I’ll try not to torture you too much, although I will be asking you from like your development standpoint. Sort of like what could come next in terms of developments from a clinical perspective.
And then there’s this pipeline of assets, layered on top of a base business, including things that you’ve acquired, things that have been developed, et cetera. Very importantly, and I kind of have made an analogy with investors, that it’s like being handed this, is that a blocked bag or this pouch, let’s call, it a velvet pouch full of all these coins and the Street is sort of perceiving that there’s a lot of nickels and dimes and therefore the task is to sort of find where are the quarters, where’s the [indiscernible] dollar in here?
So a lot of progress points, a lot of things that could add up and to try and get conviction around that. So I’d like to make sure that we — in our discussion, given your expertise, circle in on some of the pipeline aspects here.
And I think the highest profile opportunity here, that is very time relevant from the standpoint of where we are is the vaccine business, but particularly the next iteration of opportunity. It threads in COVID, but obviously focuses on RSV. So tell us a little bit about where you see we are with the RSV vaccine opportunity. It’s really at this juncture now where we have quite a bit of conviction in terms of the profile. We don’t know everything. And like all great scenarios in the industry and for investors, it’s kind of a two-horse race currently in the leadership, and there’s others that follow as well. So obviously clearly dynamic opportunity. Perhaps outline for us where you see your RSV vaccine in a way that’ll help us understand how we can relevantly compare and contrast with the GSK product. That would be very helpful to start.
William Pao
Sure. So we have the RSV vaccine. It’s a protein based vaccine, and we’ve had multiple readouts, including older adults, where we’ve shown great vaccine efficacy against lower respiratory tract infection. We also have great result in maternal immunization, which then protects newborn babies. So right now we’re very focused on — basically, we passed the VRBPAC for the Older Adults. We anticipate the ACIP very shortly and then approval, and then later on this year similarly for the maternal vaccine, we anticipate approval and then an ACIP recommendation.
So we feel very confident in the vaccine efficacy of our respiratory syncytial virus, most notably, vaccine. Most notably, it also has a very good safety profile. So you may remember we’re un-adjuvanted, and so we have high vaccine efficacy, but the reactogenicity is very tolerable. And we think that will make a huge difference in terms of acceptance by patients and participants across the globe. So — and we’ll be the only ones with the maternal vaccine as well.
Chris Shibutani
When we think about the overall profile, no product is perfect, pros and cons, relative advantages and disadvantages. But at this juncture, I think investors are thinking about what is the uptake going to look like? How big can these get? What’s the ultimate market share?
So from a clinical development leadership standpoint, as you look at this version of the RSV vaccine that you have, that’s going through these key gating factors that will then become the product that’s unveiled commercially to the public for the first time. Where would you say the key strengths are that are relevant from the commercialization standpoint, and where might they possibly still be able to improve as a function of putting on your R&D hat and saying, okay, well the next iteration of this, where else can we go? Strengths?
Same question on potential shortcomings, because as I said, obviously no product is a perfect profile for such a heterogeneous population, so talk about both of those.
William Pao
Yeah. I mean, I think, obviously, we don’t like to compare against any other products because we’ve never had a head-to-head comparison. But as I said before, we have a very high vaccine efficacy, both in the Older Adults as well as in the maternal immunization. We’ll be the only ones with an indication, assuming regulators approve that in the maternal immunization indication. And then, again, we have a very tolerable safety profile.
So in terms of acceptance by people getting it, we think that they’ll — first of all recognize that respiratory syncytial virus is a serious infectious disease problem. We heard last year on the news, not only did you have COVID, but increase in cases of respiratory syncytial virus. It does cause significant hospitalization and death, particularly in Older Adults as well as infants, particularly in the newborn period of zero to six months of life. And so we think we’ll have a very differentiated product that’s accepted by the community.
Now, in terms of the next steps, we have, as Mikael Dolsten has communicated earlier this year, plans to do additional studies in patients at high risk from 18 to 60 years old, as well as from two to 18 years old. So we feel that those at higher risk for RSV will be amenable to immunization as well to protect them from hospitalization and death.
Chris Shibutani
One and completely answered question as of yet from a data reveal standpoint is on durability of the benefit here. I think there’s scenarios where we could possibly be dosing on an annual basis, which has an inherent sort of public health commercial logic versus compelling enough durability to perhaps make it every two years. Help us understand sort of how we should be understanding what the ultimate outcome of that data scenario and commercial implications could be.
William Pao
Well, again, the study is ongoing, particularly in Older Adults, but at the VRBPAC we did release two-year data where we showed I think about a 70% continued vaccine efficacy there. So we’ll have to see how the data play out. But it’s possible you could imagine a scenario where it’s in — every two year vaccine. Although, then possibly the people who are at high risk may want to go for an annual vaccine. We’ll have to just see how the data play out.
Chris Shibutani
Fair answer from the development guide. Ultimately, the question I think investors will be looking to explore as well is given that potential for flexibility on the dosing or different scenarios for populations, there’s a bit of a pricing question that would come out, which I’ll agree is probably not fair to ask you, but nonetheless is something that’s quite relevant. And if you had to guess what you think makes sense, again, from the arc of including being a clinician and taking care of patients, your wishlist would be once a year or once every two years.
William Pao
Well, I mean, I think we have to do what’s medically correct, so there’s no wishlist in terms of the commercial value. I think we do what’s medically needed and fulfills beyond that medical need.
Chris Shibutani
Okay. Fair and safe. Let’s go on into the vaccine portfolio here and think about flu. And here again, we’re trying to actually flex the mRNA based platform. Talk about the data that you have thus far, and your views of likelihood of success for this opportunity. Because there’s some nuances to thinking about flu picking strains, advantages, et cetera. So talk to us about the profile of your product, and how you think it could stack up.
William Pao
Yeah. Sure. So we have mRNA vaccine in development for flu. We haven’t revealed a lot of data, but internally we’re still — we’re very excited on what we see. As you mentioned, it’s a more complicated virus in the sense that we have two against — two components against this A strain as well as two components against the B strain. And to get vaccine approval, you need to have vaccine efficacy against both the A and the B strains.
So what we did announce was that we opened an additional study in the Southern Hemisphere this year in the Northern Hemisphere, just by chance, there were very, very few B cases. And so we’ve expanded in the Southern Hemisphere to gather not — additional B cases. And hopefully by the end of this year we’ll be able to release additional data.
Theoretically, an mRNA vaccine has lots of advantages over a protein vaccine, for example. An mRNA vaccine, first of all, you can much closer to the time of launch, decide on what the strains you want to have. So for COVID, for example, last year with the Bivalent vaccine, we were able to go from construct to launch within less than a hundred days. With a protein vaccine that usually takes eight to nine months or so. So with the shorter time period, we think you can get match the strain much more readily and then potentially have a much higher vaccine efficacy.
So before COVID also, the standard for flu vaccines used to be about 30% to 50% vaccine efficacy and still about 50% of Older Adults would get the vaccine. So with COVID now we know with the vaccines that we’ve developed, they have 80% to 90% efficacy, and we would hope to see high rates of that as well. You also get some advantages with the mRNA vaccine. Not only do you elicit a B-cell response, but you also elicit a T-cell response.
Chris Shibutani
So you made some interesting sort of anchor and adjust type of references to the COVID vaccine. One aspect of that was this element of urgency and actual declared emergency on this. And perhaps the rate limiting step on being able to come up with another vaccine that was more targeted toward the strain with the less than 100 days was in that environment from a scientific manufacturing, regulatory sort of fervor and willingness to accept and sort of turn things around.
Is that dynamic that pacing, that pacing that tone still valid today and on the forward when we think about flu, it certainly seems like it would be an advantage in this scenario, but is that practical, or should we anticipate some tempering of that tempo?
William Pao
Well, first of all, for COVID, just since we’re on the topic, we just very shortly this week, we should know what the strain selection is for the fall. So that is becoming entrenched in terms of picking the strain in June and then having it ready for launch in September in less than a hundred days. And Pfizer’s committed to having the next strain available. And we think that for flu, pending the data, if the vaccine efficacy is that much more superior, then certainly I think the paradigm shift will occur compared to protein vaccines.
Chris Shibutani
Yeah. And you mentioned paradigm shift. With the COVID vaccine, I mean there were probably audible gasps in terms of the level of efficacy profile that was demonstrated. We were in a whole different realm. It was like going from immuno-oncology to precision medicine, kind of the 30 50 to north of 80 and all of a sudden 80 was clearly a B minus, didn’t cut it. Is that level of efficacy hurdle the right way to think about for flu?
William Pao
Yeah. Again, I think we’ll have to see what the data show, but historically, the vaccine efficacy of protein-based — flu vaccines has really only been in the 30% to 50% range. So we think north of 50% will be already a significant advantage.
Chris Shibutani
Right. But the 90% for COVID, is that valid as an expectation setter for the flu side, or are there other parts of the equation here?
William Pao
I think, it’s early days. So again, there’s four different strains that we have to protect against. We’ll have to see what the data look like. But north of 50%, I think is a good estimate for being an advantage for the mRNA vaccine versus the protein vaccine.
Chris Shibutani
Okay. And then you said something in partly in passing, but is worthy of observation, this whole Northern, Southern Hemisphere dimension to it, and they’re just stopping to not be as many cases, et cetera. That’s part of the epidemiologic challenge. You’re trying to be able to predict that. And so the mRNA platform seems to be more nimble in that regard. How much does that impact? What are expectations should be in terms of what the profile and flu could be?
William Pao
I’m not sure I understand the question. So essentially if we can match the strain better, closer to the time, then we think we’ll have a higher vaccine efficacy.
Chris Shibutani
Okay. But in terms of timing, perhaps, can you discuss anything about the Phase 3 readout? I think the preliminary guidance has been about for the second half of this year. Do you expect that will continue to be the case for the data and that we could be thinking about the 2024 into 2025 season as the one that we hit the ground running commercially?
William Pao
Yeah. So we hope to release data by the end of this year. And hopefully we’ll have ready — we’ll be ready to launch by the 2024/2025 season.
Chris Shibutani
Okay. All of these vaccines, you’re looking to combine them. There’s an inherent logic to doing so. But scientifically, not as straightforward. Can you talk to us a little bit about the key considerations in terms of clinical development and anything about how the product profile might look? Is there any vulnerability of some additive changes when you combine these particularly COVID with flu and then potentially in addition COVID plus flu plus RSV?
William Pao
Yeah. I think ultimately, for convenience sake, for patients, we think a triple vaccine would be where we ultimately want to go. So you could get a one stop shop, one injection, you’re protected against COVID, RSV and flu. But to get there, we need to not only have the singletons, but then the doubles. And so yeah, we do have a COVID flu study ongoing as well as an RSV flu study ongoing. So in terms of the regulatory agencies what they want to see is not only efficacy, but also safety and tolerability. So we need to demonstrate that for both components of the vaccines. And then for new vaccines, it’s likely that the regulatory agencies would want at least a year of data before approving a combination. So for example, with the flu vaccine, assuming we launched in 2024/2025, we think we have a combo ready for the following season. But right now, those studies are ongoing and we look forward to seeing the data.
Again from a scientific point of view…
Chris Shibutani
Right. Exactly. I mean, we’re combining mRNA based platforms from protein based. And so get a little geeky for us and help us understand what some of the risks and things that you need to make sure that you accomplish and demonstrate when you’re actually doing the work to combine the vaccines.
William Pao
Yeah. I mean, you need to understand if they’re compatible, you need to understand by formulation. For example, if you combine a protein-based vaccine like RSV with an mRNA vaccine, you need to make sure that the protein component doesn’t degrade the mRNA component and vice versa. Obviously, if that happens, then your vaccine efficacy would drop for one of the components of the vaccine.
For a double mRNA vaccine, basically it comes down to how much mRNA can you actually give a patient by, and not only have good vaccine efficacy, but good tolerability. So we do know that the higher doses you go with mRNA vaccines, you can get more reactogenicity. So those are just some of the things that we have to think about.
Chris Shibutani
You specifically made — do you want to make sure that they don’t degrade the relative components. What evidence do you have thus far, either in early preclinical or early clinical work that you can share to give us some perspective in terms of what that potential is?
William Pao
I think it’s fair to say that we wouldn’t be in the clinic if we had any issues pre-clinically with them.
Chris Shibutani
Okay. And then when we think about the arc of the clinical benefit, each individual vaccine component has some degree of durability of the benefit which can change, or which can also be different between the two components. So how do you see that potential combination and the durability of benefit when you combine these playing out in terms of what, for instance, a clinician will tell a patient that this is appropriate for?
William Pao
Yeah. Again, I think it’s early days in terms of how long the vaccine efficacy will last as just as we discussed. I think some of it will depend on how fast the virus mutates. So for example, with COVID, we know that it seems to be at least a biannual strain kind of shift, which is different from flu, which seems to be more of a seasonal thing. So basically we know that you can get one flu vaccine and that usually protects you for the season. Whereas with COVID, the virus continues to mutate. And so even if you had immunogenicity and immune response to the initial vaccine, if the strain changes enough, you still need to get a potentially a new vaccine. And then RSV appears to mutate at a slower rate. So I think we’ll just have to see how it plays out ultimately with the data.
Chris Shibutani
Okay.
William Pao
But the triple play is mainly for the convenience. I think patients are willing to get one. We’ve seen with COVID and flu that people will get a shot in both arms. But if you could ultimately have one shot that protects you against three and you don’t have to go to your doctor or the pharmacy multiple times, we think that’s the most convenient for patients.
Chris Shibutani
Okay. Let’s shift a topic to something that actually became — interestingly headline generative in spite being data that had already been presented and this is in the obesity space and diabetes with the Oral GLP-1. Talk to us about the two assets that you have, and what kind of data we might expect to see in the second half of the year.
William Pao
Sure. So I think you all know we have two GLP-1 receptor agonists both danuglipron as well as lotiglipron. Danuglipron was developed earlier, and so we have more patient data on that. And that was the recent publication where we showed significant decrease in hemoglobin A1C, fasting plasma glucose, as well as weight loss. And then we have lotiglipron, which is earlier in development. It just came later essentially. So the main differences at a very high level, danuglipron is given twice a day. Lotiglipron is given once a day. And so right now both of them are in development. For both molecules, we did do rapid titration to get to proof-of-concept and show that we actually had significant decreases in fasting plasma glucose as well as weight. But both studies now are looking at monthly titration, and ultimately to pick the right dose and schedule to move forward to the Phase 3s. So for danuglipron, we hope to have data by the — and lotiglipron, we hope to have data by the end of this year and then danuglipron by early next year.
Chris Shibutani
Okay. So the BID danuglipron is a first quarter or early 2024, whereas the Q Day loti, the one that’s a little bit further behind in terms of overall development will have data, some perspective, because it seems as if the communications have been about having these two horses in the race and ultimately making a decision to lean in more one versus the other. And so will the datasets have some aspect of comparability in terms of the N, the kind of the protocols, the dosing ranges that are studied? A lot of nodding on your part.
William Pao
Yeah. No, I think we would — we’re doing the studies particularly so that we can pick the winner, so to speak. Again, we want the best dosing schedule with tolerability in terms of the main side effects in this class of molecules, which are the GI symptoms, nausea, vomiting, diarrhea, and then obviously want safety. And then, we want to pick the best molecule to move forward.
Moving forward is a huge investment, right? So we want to make sure that we have the right molecule when we move forward with the ultimate studies in both type two diabetes as well as obesity.
Chris Shibutani
And obviously there’s other leading players out there, Lilly, Novo, developing orals, et cetera. What kind of profile would be adequate in your mind in terms of committing to a continued investment? Obviously the market opportunity is potentially vast. Pfizer was very explicit in their December analyst meeting, identifying the full scope of this, putting a $90 billion number out there in terms of the broader market. And here you have these two assets that are poised, one will eventually move forward. What is kind of the bogie or the threshold level that you’re going to use to decide which one will go forward, and also how it will compare at a comparable time point of development of other products that are out there?
William Pao
Yeah. Sure. So — yeah, we did put out there that it was $90 billion market and even some analysts since then have gone even higher. I think an oral small molecule GLP-1 receptor agonist will be a new class. We do know from market research, for example, that many people would prefer an oral versus an injectable. Also, most of the injectables are given by endocrinologists, and there are a limited number of endocrinologists. Whereas if you had an oral that was safe and easy to give, you could get to all the primary care physicians just like they prescribe statins.
So I think the profile ultimately we want to match is to be equivalent to the injectables just the single class. But it’s possible that — we’ll just have to see what the data look like and what’s accepted by patients and caregivers. But ultimately, we would like to have a profile very similar to the oral injectables of the single class.
The other advantage for example of a small molecule is that we don’t have any fasting requirements. So that could be an advantage over the oral injectables. And then we’ve also seen that the peptides are very difficult to produce, basically with high cost whereas the small molecule will — should be easy to produce, mass produce and the cost of goods would be much less.
Chris Shibutani
One of your favorite phrases, we’ll just have to see how the data readout, and it’s one of my least favorite responses. So we’ll just keep on asking you going forward. As you think about designing the Phase 3 program, the reality is that there’s going to be products that are out there. There’s expanding concept of segmentation of the market. Also, there’s hypotheses about how these therapeutics will work in the obesity market in particular with kind of a thought of an induction in maintenance kind of thing, standard mirroring that we see in all sorts of like chronic diseases, metabolic, immune mediated, et cetera.
So with that in mind, help give us a sense for the William Pao view on strategic Phase 3 development, given where you are and where the market is, and where you’d like to eventually be at the end of those studies.
William Pao
Yeah. Again, you’re not going to like the answer, but depending on the data, obviously we would like to get into type two diabetes as well as obesity. I think if you have an oral small molecule, there’s also possibilities in the future where you could have an injectable followed by an oral. There’s lots of different kinds of parameters that can come into…
Chris Shibutani
But to be clear, you guys do not have an injectable that’s in the clinic, or in terms of thinking about a portfolio….
William Pao
That’s correct.
Chris Shibutani
…priorities on the oral.
William Pao
Yeah.
Chris Shibutani
Okay. And so as a result, are there particular segments of the — to get to that 90 and to actually also get to the high single digit billion potential scale revenue number that was put out and print on the slides of the December meeting. Again, is there a thought of where will these patients come from? Is it just a matter of muzzling share and grab because there’s so many numbers? Or is there a particular profile, again, you as head of clinical development thinks is smart, is stealth, could position you for an opportunity that could give you some sort of competitive advantage to be able to grab that?
William Pao
Yeah. Again, I think the — if we want to move into type two diabetes as well as obesity, there may be other indications that are secondary to obesity such as sleep apnea or other things that are consequences of obesity. Again, though, I think we have to get primary approval in both type two diabetes as well as obesity before considering those additional areas.
And I think one other advantage, again, if you can get the primary care physicians, you can really have an advantage, and then their Pfizer’s powerhouse marketing team can really help get market penetration. You probably remember that last year we did reorganize the biopharma organization to have primary care, specialty care and oncology. So within the primary care business, we already have molecules like the CGRP antagonists for migraine. Paxlovid is in there, many other molecules, and having a GLP-1 in there would also be an advantage.
Chris Shibutani
And then again, as a clinician scientist in your background outcome studies, when we’re thinking about what seems to be very logical derivatives biologically, clinically with weight loss and potential benefits, cardiovascular outcomes, sleep apnea, et cetera, what is your view on sort of the most likely outcomes trial type scenario? What makes sense to you that you would come to the table at the committee at Pfizer and say, okay, if we get to this point where we’re figuring out an outcomes trial, here’s what I think is the smart approach for us to take. Because there’s a lot of directions you could go. What would William Pao sign off on?
William Pao
Yeah. Well, there’s what William Pao would sign off on, and then there’s also what regulators would require, and particularly, for example, in type two diabetes, they would require cardiovascular outcome studies. And then we’ve seen also an obesity that the area.
Chris Shibutani
Right. So specifically for the obesity side, what are the directions that you would want to go? Because if you look and sort of see what the two leaders are in that space, they kind of mapped out slightly different strategies with that. What’s the slightly different strategy that you think would be smart?
William Pao
Yeah. I would say, Chris, we’re not ready to disclose that.
Chris Shibutani
I’m not going to ask you again. Okay. You’re not going to want to sit up here with me next year, are you? That’s okay. That’s fine. I’ll try to be nice.
Let’s move on to some aspects. We’re just coming on the back end of ASCO, your former Memorial Sloan-Kettering guys [indiscernible], very distinguished, time at that — at MSK, elranatamab. You guys are in the mix by specifics here. Seems like a tremendous opportunity. A lot of different players that are out there. Talk about this asset, certainly it’s fitting within a landscape where people want to see what is the monotherapy profile and what is this opportunity and combinations given the serial treatments and the multiple, multiple combinations of this patient population. Tell us specifically about elranatamab profile so that we can distinguish it from the other bispecifics that are out there.
William Pao
Sure. So elranatamab, we’re very excited about that molecule. It’s a B-cell maturation antigen, CD3 T-cell bispecific. So it’s an antibody basically that brings a myeloma cell together with a T-cell and then the T-cell kills the myeloma cell. Multiple myelomas, as you know, is a huge burden, big hematologic disorder for which the — there’s still huge medical need. So we have a release data both at ASH as well as ASCO this year, about a 60% overall response rate, but a very tolerable safety profile. Notably, we have predictable cytokine release syndrome, which is the main side effect of this class of medicines with no grade three cytokine release syndrome.
Compared to — we feel that our MM3 study, the main one for which we should get approval later this year does have a much better reflection of real world patients. For example, we can go down to platelets of 25,000, a creatinine clearance of 30, performance status of two. We have many more patients with extra medullary disease, and we have many patients who are even penta refractory in terms of treatment.
Also this — at ASCO, we just released new data showing that it works post BCMA treatment. So whether you’ve had a BCMA CAR T-cell, or a BCMA ADC, we showed a 50% response rate. And notably as a single agent, again, we haven’t reached — for those who responded, we haven’t reached a median duration of response or a median overall survival. So we continue to see very, very promising efficacy there.
I would note that we have got breakthrough designation and prior review, despite another agent being there on the market. And I think that’s an independent validation of the excitement about the molecule. So we do plan to move into earlier lines. We have multiple studies ongoing. So we have triple class refractory, which assuming regulators approved, actually we got later this year. Then we’ll have double class exposed — study in double class exposed patients. And then moving into first line, we’ll have a study in transplant ineligible patients as well as first line maintenance studies. We even plan to potentially move into earlier lines and then do a number of combinations, some of which we’re not ready to disclose.
Chris Shibutani
It’s really setting up, obviously the natural evolution is to migrate into earlier lines of treatment. CAR T has been doing this with quite impressive data. And there’s kind of this decision dynamic often of what is the real ROI on investing in some of these earlier studies and when can you get there? In particular, how do you feel about these earlier line opportunities, which are really, in many respects, the brass ring, more patients longer duration of use, et cetera? For a bispecific compared to the CAR T profile, what kind of data needs to be presented? What does the profile need to look like to be able to go nose to nose or nose ahead of CAR T?
William Pao
Yeah. Yeah. I think this — the efficacy of the CAR T-cells, the chimeric antigen receptor T-cells is very impressive. However, it takes a lot of personalized treatment as well as manufacturing, et cetera. And there’s still limitations to that. I would note that I recently saw some market research, which showed that even the BCMA CAR T-cells have maybe 2% market share, whereas [indiscernible] already has 7% market share in the third line setting. So even if short introduction, it’s already surpassed the market share of CAR T-cells. Also, notably CD19 CAR T-cells have been on the market since 2017, as you know. But none of them have gotten to first line yet. And in second line, I think they only have about 6% market share.
So I think just given the manufacturing and other challenges, it will be very — and the cost, it’s going to be challenging to get to first line. Whereas if you have a T-cell bispecific that’s an off the shelf option antibody that’s available throughout the globe, I think it’s just going to be much more convenient.
I did forget to mention, for elranatamab, we also have a unique hospitalization schema for our step up dosing. So we have three step up, three doses in the step up dosing, 48-hour hospitalization just for the first dose, 24 hours for the second dose, and zero hours for the third dose. And we think compared to the competitors, that’s going to allow you to treat double the number of patients actually by having such a short hospitalization requirement. So again, compared to CAR T-cell, that’s also a huge advantage.
Chris Shibutani
Yeah. I think the rubber meets the road as you just described with the clinical actual administration requirements, physicians getting comfortable with that. So we appreciate that detail. Less than a couple minutes left, I just want to do some quick…
William Pao
By the way, also on CD19, CAR Ts and lymphoma, so again, they haven’t had any competition and only recently most inotuzumab should get approved as well as encorafenib. So I’m looking forward to seeing the CAR T versus T-cell bispecific issue play out in the next several years.
Chris Shibutani
Okay. Good. And I gave a fair amount of time to elranatamab because when we were over in headquarters last month, Angela, the Chief Commercial, picked this out as sort of like making the podium beyond some of the other stuff that we talked about. So very quick hits. TALZENNA was also data at ASCO, HR mutated subpopulation. Discuss your confidence that the combination will ultimately receive a broad label in spite of that optimal performance.
William Pao
Yeah. So at ASCO we released data on the combination of TALAPRO plus enzalutamide in metastatic castration resistant prostate cancer in those with homologous recombination repair gene mutations, which account for about 25% of the population. So the data were very specifically significant. And we do expect a label at a minimum in the HR — gene mutated population compared to just BRCA 1 and 2. That’s going to be we think about 20% to 25% of the population, whereas BRCA is only about 10% or less of the population.
Right now the overall survival data as we announced is immature. So we’re waiting for that and we ultimately are confident that assuming regulators approved, that we could get an overall — an all-comer population down the line.
End of Q&A
Chris Shibutani
Okay. Felt like we just took a sliver even the pipeline in the portfolio. And I feel like there’s pros and cons, some disadvantages to that, but I do appreciate the opportunity to go more in depth on some of the near-term and kind of the higher profile needle movers. We’ll just consider this another chapter in the — dialogue that you and I will have in various forums. So thank you for being a good sport. We look forward to a continued progress.
William Pao
Thanks Chirs.
Chris Shibutani
Thanks.
William Pao
Okay.
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