 is our next panel, which is on oncology. And it's always one of the most exciting panel of this annual event. And this year we have a prototype biopharmaceutical leader and a very old colleague and friend of mine, Elise Rison, who will be moderating the panel. I've known Elise since my day one in industry, which is in 2001. Elise has served in leadership roles that have focused on delivering medicines to patients at Merck at EMD Serono and most recently at Celgene. Elise is now CEO of her own biotech company, TechComic. And I'll tell you, Elise, when I first met you in the summer of 2001, when I was interviewing for my first position in industry at Merck, I was inspired at what a physician scientist could be in industry. And I'll also admit that I was a little bit intimidated by you at the time. So with that said, I'll hand it over to you and you can introduce your great panel. Thank you, Andy. I think I've heard other versions of that story from you as well, but that's for another time. So good morning from the West Coast and I am thrilled to be able to moderate this panel. I think it's gonna be an incredibly engaging panel if it's anything like the rehearsal that we had, which was supposed to be half an hour and we had to cut off after 60 minutes. So with that, we really have a wonderful and varied panel today. I'm gonna let everybody introduce themselves really, really briefly. We'll start with you, Sam. Hi, I'm an immunologist. I found an Mclone and have a number of cancer drugs on the market like herbitux and cyramsa. I then founded other companies like Mira and Cadmone. And I'm now the chairman and CEO of Equilibrate. Carrie. Sure, hi, I'm Carrie Brownstein. I'm currently the chief medical officer at Selectus, a gene editing and cell therapy company in New York. And I'm previously a pediatric oncologist who've worked at a number of companies and I had the pleasure of meeting Elise about two years ago and she's been a wonderful mentor and I'm really thrilled to be here today. So thanks for inviting me. And Vivek. Hi, I'm Vivek Ramaswamy. I'm the founder and executive chairman today of RoyVent Sciences and glad to be part of the panel. Bruce. Bruce Chabner, I'm originally at the National Cancer Institute for a number of years and then at Mass General and then had the pleasure of working with Elise at EMD Serono. And Phillip. Hi there, I'm Phillip Larson. I'm the global head of research and early development at TAPIRA Pharmaceuticals. All right, so let's start in keeping with the meeting theme which is from N of one to N of a billion to talk about cellular therapy, which we are clearly now more closer to the N of one than we are to N of a billion. So what is it gonna take and what do you think the advances are really gonna be that makes cellular therapy more accessible to more patients in more tumor types and how close are we with off the shelf therapy or other new innovations? Maybe Carrie, we'll start with you. Sure, thanks for that question Elise. I think you're absolutely right. The autologous cell therapy space has really been an N of one situation where companies and even the academic centers are making bespoke therapy for individual patients and it's been working mainly in hematologic malignancies and has not really seen much yet in the world of solid tumors. And I think what we're doing here at Selectus with gene editing and making off the shelf allogeneic products is really going to be the revolution when we get there in that this is the only way we're gonna be able to make cellular therapies available and economically available to larger proportions of patients throughout the world. So I think we're getting there. I think it's still somewhat early days but I do think that there's been significant progress and I'm sure I'd love to hear what other people's thoughts are but there's so many companies now working in this space where we're using healthy donor cells to make large scale batches of cellular therapies that then can be available to so many more patients and the data while it's still early are incredibly encouraging. And I think showed that at least in the space of hematologic malignancies right now that the off the shelf versions of these therapies can be as effective if not potentially more. We'll see how that goes and be available in the near future to more people. Anyone wanna comment on the data that was shown by fate at ASCO with NK cells and whether you think that they may be as effective as CAR-T, safer than CAR-T, will you get the durability? Anyone have a view on that? Yeah, I guess. Go ahead. Okay, well, at least to my perspective is probably safer from the perspective that the risk and the toxicity you need to manage when using T cells is somewhat unpredictable and would probably require more T cells especially if you go into solid tumor therapy whereas the NK cells based on the data we've seen so far seems as a safer bet but obviously the challenge here would be can you have sustained efficacy and will you ask to be able to have a lasting effect or to the effect exhaust? And I think that's one of the issues we'll have to understand better before we can say NK versus T cells. I'm of the school where it may have to be both. We know that the cytokine IL-15 is such a critical cytokine in the oncology field and I believe that what it does very beautifully is expand both NK as well as CD8 T effector memory cells and therefore we may see in the future a convergence of both. Wow, I can't even imagine the manufacturing complexity. No, that's a whole other story and the cost. How about for solid tumors? There have been some recent setbacks especially with some safety issues. The TME has been brought up as one of the major obstacles. Do we think that we're making headway there? How many years away are we from cellular therapy and solid tumors? Well, there's certainly a lot of experiments going on clinically. I know there's a thyroid cartoon that's now in the clinic and our people are putting in a glioblastoma directed CAR-T but the question is whether you can really get an effective and selective response without killing normal tissue and what would the antigen be? I think there's a lot of work to be done there. Yes, I mean, I think the solid tumor space is incredibly challenging but I do think it's surmountable. I think that to your point Bruce, 100% agree the hard thing with just about everything other than lymphoma and myeloma is the fact that most targets are expressed also on normal tissues that you actually need as opposed to B cells. So finding those targets so you can selectively have a CAR-T or other type of cellular therapy that is going to selectively hit your tumor is incredibly challenging. That said, there are other mechanisms that I think people are working on. There are the TCR type of therapies which might be more specific. If we're trying to, there's also some gating strategies that some companies are using that might be helpful as well. So I think there's ways going forward. I think the other piece of the puzzle is as you pointed out, the tumor microenvironment and the incredible issues with getting over what's going on in the microenvironment. And I think again, with gene editing, hopefully if all of this can be sorted out, being able to secrete cytokines and other inhibitors so you can overcome some of the obstacles in the tumor microenvironment may be a way of getting cellular therapies into the tumors and potentially getting them into the tumors selectively as opposed to normal tissues. So there's lots of strategies out there that are just gonna take a lot of work to get there. And also we have the issue of it being much closer to an N equals one than to the a million. It is tough. And so... One of the advances that potentially could get us closer, I think, and in the million and that would really substantially make the manufacturing less complex or some of the companies that are starting to now form around in vivo car where you basically use either a virus or another vector to actually make the car in vivo. And I think, I don't know, do people think there's any hope of that and how long will it take for us to get there? I think we're a long ways away. I think that in vivo gene editing and putting viruses in that are specific enough is a whole other world. And look, Steve Rosenberg has been doing work with TILS for a very long time, very pretty work. And yet it's closer to an N equals one than N of a million. So let's switch to other topics in oncology. The last decade, cellular therapy aside has been just such an incredible decade of innovation and oncology. It's just been phenomenal on so many different fronts. So I'm curious from all of you based on ACR and ASCO, what do you think's most exciting going forward? I don't know, the back we haven't heard from you yet. You want to start? Well, I mean, most exciting is an absolute statement but it may be something that we haven't talked about in a direction that I think is exciting and kind of goes to your question about solid tumors in that, yes, part of the reason why we're not going to maybe see the same promise in solid tumors in the near term for cell therapy is because of some of the inherent challenges we just discussed. But some of it may also be due to the promise of other approaches outside of cell therapy in addressing solid tumors and the opportunity cost of entering or planning a trial may actually have to be measured against the best available approaches elsewhere. So there's an optimistic side to it too. I kind of am pretty optimistic in particular about the promise of targeted protein degradation and the advances that we have seen and being able to take this from being a, you know, I call it a new modality, a new modality of therapeutics that now is moving from just having degraders that target the active site, which is sort of 1.0 of the protack, the greater revolution to actually realizing the promise of targeting binding sites on the target protein that go beyond the active site, which actually opens up the druggable landscape far beyond just degrading something by sticking to the same binding sites as an inhibitor. That's where version 1.0 is right now, but we're seeing a lot of companies be able to make the transition to actually find new binding sites on proteins. You know, we're planning possibly to have a discussion about KRAS, but I think that not only with respect to KRAS, but with respect to a whole range of previously difficult to drug or undruggable proteins. This is, I think, one of the exciting areas for solid tumors and all tumors to come. So, you know, that's what I would say. It's an optimistic note when we look at this, it's a little bit like a hydraulic pump system where if we press on one place and it becomes a little more difficult, cell therapy with respect to solid tumors, you know, the opportunity pops up, you know, elsewhere and we have to look at these things in the context of investigators looking to pursue trials in a given patient population. It's a measurement against the opportunity elsewhere and that's part of what, part of the reason why I think we won't see as much advance in the near term with respect to, you know, cell therapy in solid tumors is because we have great opportunities to look at therapeutic advances elsewhere. The nice part of this is that we have good clinical examples of these things working. So, we know that, you know, this is a very plausible therapy now, practical therapy, but designing it for specific protein targets is the challenge and not killing people in the process. I think Bruce is right. The challenge is specific targets and the interesting thing will be how we use them clinically and how we put together combination therapies that make sense from the point of view of specific tumors. That's going to be a big problem. If you think about RAS, maybe Vivi can talk to this a bit, but if you're trying to degrade RAS, how do you protect normal tissue, which depend on RAS? Right. So, we've got a question coming in from Syed Cosme. Let me turn it over to Syed that's related to what you were just talking about, Bruce. Syed, you're on mute, Syed. Take yourself off mute. Yeah, sorry about that. Thanks, Liz. Yeah, so sort of related to what just Vivek and Bruce mentioned. I mean, we know that the approval of Lumacros has really opened the door to a new field in cancer development. But if you look at what may happen from here on, what was your perspective on the future of this field, especially in the context of developing resistance to Keras agents? So as Vivek pointed out, our follow on new compounds with dual activity of target inhibition and degradation, the answer, I mean, potentially combinations may be considered, but what can we learn from CK in gastric cancer or BRAF, MEK in melanoma to further improve on Keras therapies? Well, I can comment a bit on this because it's really part of the whole story of targeted therapies where the mechanisms of resistance may be somewhat different between agents, but in general involve mutations in the target or amplification of the target or the development of alternative pathways and all that is known to happen experimentally with Keras inhibitors. And the question is how much of that we'll see. I'm sure we will. I mean, the response rates in the clinic are now 35 to 40%, they're not 100%. And these disease control only lasts several months. So we have a long way to go with Keras and I think the answer is either better agents but also agents addressing some of the specific mechanisms of resistance, particularly alternative pathways and combination therapies also, I think we mentioned that earlier. So there's a long way to go with Keras in terms of making it really an effective therapy at this point. It's a marvelous advance, but it's early. And I think you're already seeing companies start to have extensive combinations. Combinations we ship to EGFR anticipating the type of resistance that everybody knows is either happening already or will happen with treatment. Yeah, the example would, yeah, we had an example with BRAF where the combination with a MEK inhibitor made a huge difference in terms of duration of response. And the same thing could happen. I mean, it's really the same pathway but maybe a little more complex. Now, and Bruce is absolutely spot on. It's really the same pathway. And a lot of these things are part of a network that bypass mutations in an incredible way. So what we need to do is figure out ways to make sure that we know what's going to happen when we hit Keras or when we hit EGFR, et cetera. And how to use all the different networks to bypass effective therapies. And that's going to be very, very important. We knew that in the infectious disease world, Elise. As you know, we did it very quickly with viruses. I was just going to point out a couple of, probably a couple of obvious points to people who are on the panel, but maybe worth stating anyway is what we've seen in Keras despite the celebration by I think some important breakthroughs in the so-called G12C, that they're relatively short duration responses to date. And there might be, there might just be too many escape mutations. And I think that there's kind of a couple of axes. One is binding the on and off form. And then the other is sort of to be able to go pan Keras mutant while also sparing wild type, which are of course inherently intention with one another. So if we think about a couple of those axes of down or on versus on and off state both, while also being able to hit pan mutant while sparing wild type, that's definitely a tough cat to skin. I think that a couple of points that I would make on the escape mutation points is if we probably serve ourselves well to have a clear eye lens to the different kinds of escape mutations, right? There's mutations that may be outside of the target protein of interest, maybe outside of Keras, but in the pathway, then there are mutations actually specific to the protein itself. And I think what approaches we take, you know, combination therapy versus not depend on which class of escape mutation or escape mutation, even as it applies to the pathway, even if not the protein, you know, I think that those are just framing comments, but I think that the implications of directions that you might see as more promising or not, depend on which of those you're talking about. Which I think, in the back, I think all of the above will occur, which I think will speak to the fact that it's gonna get really into precision medicine, which for each patient, you're gonna have to understand what those escape mutations are or what pathways to target the next round of therapy for them. At least probably remembers way back when, or maybe she doesn't, that Ed Scholl tried to play with a RAS inhibitor at Merck that everyone had huge, felt huge promise for. And yet it wasn't something that was going to work because every cell, as Bruce said, was going to be affected and it was a disaster down the line. And then we learned that, inhibitors of EGF receptor bypassed functionality with K-RAS and with SARC. It's complicated, but we're gonna figure it out. Yeah. Well, I think the message is that, performing translational research in patients receiving these drugs is very important. And this is something that we were unable to do with chemotherapy, but now we have many more tools for doing this. And this is essential in learning about how to make this work. But I think there are some positive, there are, yeah, go ahead. There are some positive learnings from other mutated oncogenic signaling molecules. For instance, the Intreg family, where if you address very specific mutants, you can get an extremely high response rate and yet have a very, very good tolerability. So I think being an optimist, I think there's reason to believe that you will be able to find chemical matter that really addresses the mutants or mutants interacting with other players like BRAF and what you already mentioned. So I think it is possible because there are other examples of precision molecular oncology that really works out. Maybe it's not a single patient, but a reasonable handful of patient who would benefit from that. Let me, I'm gonna take one more question right now before we go to the next topic from the audience. Philippe Lopez Fernandez, you've got a question. Yes, hi Alice, a question to you and your panel. There are now several ADCs on the market with strong results. And I'd like to know where do you see the best possibilities to further improve ADCs to significantly boost efficacy and safety? Would you go multi-specific or multi-payload or in contrary, try to be more targeted or specific? You've hit some of the important points. I think also understanding linker technology has been so important in this field because without a linker that's degradable within lysosomes but stable outside, you get into a lot of clinical toxicity. We still have clinical toxicity with these drugs. They're not as specific as we would like, but also defining the right payload. So there are recently some very nice examples of radionuclides attached to antibodies that are working in prostate cancer and they're not antibody linked or some of them are. Others are linked to just receptor proteins, but that's another really interesting possibility. I think one of the things I've thought about though and you brought it up to Leeds and that is that it's really hard to expect single entities, secure cancer, single therapeutic modalities. So I think with all of these, ultimately we're gonna reach combination therapies, perhaps with immunotherapy, perhaps with chemotherapy, perhaps with multiple ADCs in order to really achieve long lasting effects. I think one of the great things, Bruce again, is absolutely correct. It's going to be combination modalities and the oncology field has always played in the combination modality fashion. I think that ADCs are tough, but we've already seen great examples of real responsivity in the HER2 field. There's responsivity in other areas. I believe that there's greater responsivity again in the hematological area than there is in the solid tumor area. And we still have to learn to navigate that. It is not an easy road to navigate, but it's going to be one that's necessary. But I believe that in the hematology field, we've seen great results and in breast cancer. And I think we're starting to go beyond that. You've got some of Daiichi Senkyo's new ADCs. It really looks like they've got a lot of promise across a wide way of solid tumors, TROP2 and other TROPs. You know, this is a new field, really. There was one trial at the recent ASCO meeting that perhaps did not get as much attention as I think it truly deserves, was Novartis trial with the Lutegium label, PSMA, antibody, which actually shows you that you can get a fairly decent response in patients who have tried everything. And what is remarkable is that the tolerability for that modality seems to be pretty good, at least compared to the ADCs. And the HER2 story is really interesting that the antibody that Shannon was talking about works against cells which have down-regulated the expression of HER2. Amazing. I'm going to cut us off for a second because there's still a few topics and we don't have a lot of time left. Let me switch to the following, which is great successes, fast development in oncology, what can other fields take away from what's been done in oncology? Vivek, you wanna start with this one? Yeah, sure. I mean, I think that we can't, there's a little gauche to sort of say, but I do think that there is a lesson to be learned and a discussion to be had amongst the people who aren't on this call at the FDA, who I think ought to learn the lessons that came from being, I think a little bit more permissive in leaning ahead on when evidence supported the use of biomarkers to be able to support approvals, to be able to decide where one trial was required, required rather than two, where the risk-benefit trade-off for patients was ultimately in favor of making a therapeutic available. This was an individual at the FDA who made a value judgment that I think wasn't necessarily made with the calculus of saying that that's going to unlock an innovative revolution in the private sector, though it did have that impact, though it did have that effect, but it was individually on a case-by-case basis, this was what made the most sense for this compound taking patient interests into account. And I think that, I think people in other divisions of the FDA can take inspiration from that. And I think that, yes, there are a lot of lessons that we ought to talk about in terms of thinking about trial design, the better use of biomarkers to be able to select patients for the right kinds of trials that we ought to learn as lessons too. But if there was one pan industry, pan sector lesson to take away, if I had to take just one, I would love to see other division heads at FDA take the same inspiration from for the past year as maybe others have more controversially recently in the case of, let's just say, the Attic-Eni-Mab's approval, which I think maybe we ought to talk about at some point, but I think could be a red herring and a smoke screen that distracts us from actually a valid discussion that we still ought to have from other division directors who can more constructively and in a more applicable way take some of those same lessons that Pazder led the way with. Any other comment? I think that I would say there's great lessons that can be applied for instance, doing studies with if you've got an indication that has a low placebo response as you do in cancer, where you can look at multiple indications and single arm studies looking for signals. I think that you can do that. I think there are places where maybe oncology can learn from other fields. And safety and dose finding, I think are probably those. And I think you've seen the FDA start to go in that direction. As we move away from chemotherapy as the sole treatment in cancer where maximal tolerated dose was the way of doing it. Maybe a push towards really trying to find the optimal dose. And I don't know, before we go to the last topic, if anybody wants to comment on that aspect of it. I think there are ways to accelerate, especially understanding PK better for some of the newer generation of molecules that are not either cytotoxic or genotoxic where you can really hit the ground running by optimizing your understanding of your molecule, even in healthy volunteers before you go into patients because it's so much easier to recruit these people. And then you can have a much better understanding of where to start your dose when you go into cancer patients. I would say that's an under evaluated and under utilized way of accelerating your first inpatient, I believe. I think one thing I want to. Yeah, I point to one short point and that is that we had a real problem with our original targeted drugs and they weren't getting into the CNS and we've learned to get drugs in that have been very effective in some of the lung cancers and breast cancer patients but particularly in lung cancer. I think that's a lesson for the people that are interested in CNS disease. I was just gonna add one other. I'm sorry, go ahead. Go ahead. I was just gonna add one additional point I think is and this is somewhat controversial but the idea of surrogate endpoints or what actually, maybe not even surrogate but what actually are the endpoints that are meaningful? And I think that one of the challenges is an oncology is survival has been the only meaningful endpoint for a very, very long time and then there's surrogates of survival but is that really what all drugs need to be achieving in oncology? Is that really the only thing that's important? And I'm not sure that that is and I think that that's something that needs to be worked through a bit. I mean, Kerry's so right about that. Yeah, totally correct. Really understand what surrogates mean. So sometimes surrogates are perfectly good to get a drug approved and not perfectly good for the patients as far as outcome is concerned and then other times they are. So we have to learn that in what is translational medicine. As Bruce said, I'm always suspect when somebody says look at these animal studies because I view each human being as an inbred strain of mouse and it is very, so we have to really try and understand how to do translational medicine. What quickly lessons to be learned in our adaptive design models that we use in oncology, how to use them right across the board in other indications and how to try to understand and converge all of these things so we can be better at getting drugs to patients. Yep. Okay, last topic and hopefully our sponsors are gonna let us go a little bit over since we started late because I know this is a topic that everybody wants to talk about. Cost and access in oncology. How do we increase access, decrease costs while still spurring in an important innovation in the field? Who wants to go first? Well, I'm gonna go first on that because it's here and here to my heart and I argue with Peter Bach about it at Memorial all the time. I believe that we're going to be running into a headstorm of different types of people, patients, legislators, even the agency as to what we can charge and how we do it. But I have a point of view about this that is the following. When we see that drugs give us a three month survival edge or a seventh month edge or a one month edge and they get approved and people say, but it only did this. When we look at that data, what we understand is that X amount of the patients really survived 20%, 15%, they were the responders, they lived for years or longer. The rest just didn't respond. And so what we need to start thinking about in a very, very thoughtful way is charging for when it works. And if we do that, no one's going to be angry about what we charge. They're going to be our allies because we're going to be showing that in 15% of the patients, they respond forever or at least three years and we have a real change in outcome for populations. That's who we need to charge for. And that's what our partners in the paying field will be happy about. And so if we do that, we will change the paradigm for how we look at what we're charging, the amount and when we do it, it'll be a new world and that's what we need to do. Although Sam, I think some of those payment type strategies are already happening in Europe. The other thing is there's a little bit of a natural way that that happens anyway, except for CTLA-4 where it's only given a couple of times and you pay upfront. For most of these therapies, it's the monthly cost. And so if you fail fast, it costs much less than for those patients who go on for prolonged periods of time where the payments continue. Well, except for the fact that there's some patients that will live longer, keep getting drug, even though the drug isn't having an effect. The patient is living longer. We've got to look at real responsibility in patients. In cancer. I think the other answer to this though is better patient selection. I think we're failing in that regard now. If you look at checkpoint therapy, we just have very crude ways of trying to select patients with PBL-1 maybe. But we don't know what the antigen is that the patient's immune system is responding to if we could select patients for specific therapies better. We would be, that would make a big difference. The other big problem though is that 60% of the world can't afford our drugs, 70%. I mean, cancer, we design these exotic therapies which are so expensive for an American and Western European population and maybe Japan and maybe China. But the rest of the world can't afford it. And it's really a sad situation where you know, in Africa we're stuck now with trying to get chemotherapy to patients, let alone immune therapies and targeted drugs. I wanted to just- Good back, I'm going to ask you a question. Because you think in a very innovative way and try to do things differently. Are there ways that we're not, industries not using to decrease the costs of drug development? Because obviously the costs afterwards are related to costs that go into drug development. What more can we be doing there? Yeah, so I just want to take an opportunity to offer one jointer on the last comment and then I'll come back and I'll leave that to answer your point, Elise, which is, I think in the space of oncology, it's an obvious point, but I don't think enough people recognize the fundamental dilemma. I agree with everything Bruce said about patient selection, but there's a basic difference between the drug pricing dilemma in something like a cure for chronic hepatitis C virus and a cure for a particular form of cancer and it's this. It's that when you cure chronic hepatitis C you're actually saving the system money downstream. When that person was going to live a long life anyway, but was going to go on and live a longer life that resulted in potentially really expensive downstream therapy, even intervention, that wasn't pharmacotherapy, in form of liver transplant at the limit, liver cirrhosis, hepaticellular carcinoma, which of course then raises oncology related costs of its own. And I think the difference in curing cancer is that you're actually making people live longer without actually that future cost saving downstream and that's part of the point. And I think that in some ways in the oncology pricing debate, that is a basic fundamental point we just are gonna have to make a value judgment ground that I think we can, I don't think so we're hiding from it about patient selection, those are important tactics, but I think it sort of evades a fundamental dilemma at the heart of oncology drug pricing as opposed to hepatitis C cure to therapy pricing. For example. So Vivek, I must say that in some cancers as we're now using immunotherapy in positive ways in non small cell lung cancer and in melanoma and in other cancers, those people are going back to work, those people are living lives. So they may not downstream have a high cost because of a liver transplant, but they are now part and parcel of going back to work in society. And way back when Amgen first priced erythropoietin, they used as a pharmacoeconomic model, the fact that people that were undergoing kidney dialysis were going back to work the next week, paying taxes, making money, and being part and parcel of society in a positive way. Yeah, I'm not disagreeing with that. I'm not disagreeing with that. That is very important. I think this is on the side of greater cost pressure on oncology or not, but I do think that we owe it to the discussion to have a clear eye view of what the fundamental difference is about drug pricing. Absolutely. But one other thing to point out though, I think is important, and we're not gonna be able to talk about this with the minimum of the time, but it's the cost of the drug development itself. And I think that, you know, that's a huge whole other complicated factor. So to the point of trying to get things to people all over who can't afford it, or maybe there's no business case, for example, and some companies won't even bother developing something because there's no business case. So the point of these things is, it's one to bring up in pediatrics, for example, there's never a business case. And therefore, nobody wants to develop drugs, and now they just have to. And I think that there's a challenge. It's because it costs more to do the studies than it's gonna do, you're ever gonna make back. So how do we fix the whole model of drug development, such that you can actually price drugs in a way that are affordable? And I don't know if that's the answer. That's the FDA also. So we should have a whole discussion next year on what Kerry just brought up, because that is a 20 minute panel. And with that, I know we're out of time now. I wanna thank everybody so much for the engaging conversation. And I don't know if I'm turning it back to Andy or Karun. Andy. Well, it was supposed to be Karun, but I wanna step in and thank you, Elise, and this panel, really just an incredible discussion. And it's so rich and not surprising given that 40% of the molecules in the aggregate pipeline of industry fall into this space. It's also the space where, as you all have mentioned, we see the most progressive science, the most progressive policy and regulatory frameworks, but also the space where we see the greatest number of failures. So we still have a really long way to go. And Elise, the last thing I'll say is, you did a great job in moderating this panel. And up until the very end, you were able to keep our beloved Sam Waxall in check until you got into pricing and access. And then Sam went on to do it so fast. That's why we did pricing last. Thank you all very much. And I will turn it back to you, Karun. Thank you, Andy. Thank you. Thanks, Andy. What do I tell you? You had it very well. And no, Sam is a good sport. Like he doesn't mind, he's got deep knowledge, but I think we need to have another summit where only we have one speaker, which is Sam, and we help him for the entire day. So can you please put the poll slide? The poll is starting. The question is what innovation will have the biggest impact on increasing access to cell therapies? 16th, start the poll. Welcome back, everybody. And thank you very much for participating in our poll. A big thanks again to Elise Reisen and just an absolutely terrific oncology panel such an exciting area of science, policy and really leading edge. Before we go to the next panel, if I could please ask you to put up the results of our polling question. Terrific, thank you very much. So the question that you all took on and we've got another neck and neck answer, what innovation will have the biggest impact on increasing access to cell therapies? And there were two answers that came in essentially tied. One was simplified manufacturing processes. And the second is the successful development of allogeneic cell therapy. So thank you again very much for participating in the poll.