Ep 61: Guest Inge Marie Svane

Dy gyfly掰掰 o iawn ni ein by Shall e'i hwn a ff Klim anderen yn mewn ac Ylwys a'i Thanksgiving mor o fyny mewn reiau dyn o gydo o People's Cym Find i'wyd mynd yn hylch. Mae'r question specificio i'r own situation, please contact your own permission. Ys podcastu may be available on both audio and visual, so please check your platform. Alright, hi everybody, welcome to Melanoma Matters. I'm Sutn y ffytel. James Rock and High. Thank you so much for taking time out of your schedule for joining us. So perhaps we could get to know you a little bit. Could you tell us about your background, where you grew up, where you did your studies, and how you came to the position that you're in now? Yeah, so yeah, I actually my interest in cancer immunotherapy started out already when I was a medical student. So I've been working with this area, even in cancer therapy for more than 25 years. I made a basic TFT at the university in the in the in the surveillance in the modern modern, not nice and so on, where I kind of documented that it matters whether you have a TFT system or not. It matters how the tumour grew up and how the entity in the city of the tumour. But then I moved out to the clinical world and I started straight into the patients and then my dilemma started out actually like the interaction with the patients very much. So I decided not to go back to the university and instead I tried to establish my own research group at the same time. I was trained as a specialist in oncology. So to quite some years, to do my training because I worked on the time also in the lab myself and when I started the group. Like translation and look at say it, but then some years ago in 2000 and then and and six. I think we started out a group where we joined I was joined by a more basic research group and we we established a center center for cancer. New therapy and then that. So it's a long time ago, but we have been going since then we were like, it's in people when we started out and now we are about 90 people. Some also director of that center but have continued to work in the clinic all the time. And in the clinic, I have responsibility for minimal care. So when I took over the area of melanoma, it was like we didn't have really anything, but we I established the hideous in from the kitchen at that time. I have like the tymosolamide that was your only thing. And I think it was only a couple of years after it ought to go off and yeah, we have the shape on his and so on. So it has been great thing to actually work on in a lower place in the same. And at the same time developing clinical trials testing our own own therapeutic products from our same design and that has been focused on. Cancer vaccine and then very much on the piece of. Yeah, that's great. I mean, I still unfortunately remember that the days of tymosolamide. No, satematos as well. So it's been amazing. I would say that a patient advocacy meeting weekend. And when I was asked to talk about was the other 50% meaning the people who don't get due benefit from checkpoints inhibitors. And obviously, one of the things I talked about was cellular therapy. But before we get into that in detail, I'd love to hear your historical perspective on cellular therapy for melanoma. Because it's not new, right? It's just the guests in the last year or two. It's something we're talking about a lot more. Yeah, how did you see that? Because it's been around for decades really has not. Then for several decades, I mean, the work from the work was in dark school. It's been amazing and we have known that for actually many years. But I think it has been a strategy to move it forward because it's not an easy therapy. You made a lot of the. Technical experience in the lab to be able to produce and manufacture the tea cells combined with this clinical setup with a very. Complete therapy and very intensive one also with a high those team of therapy and the high those in the looking to. So. So I think that some of the reasons why it didn't spread out more fast than it actually did. So they're interested in the commercial side was extremely low until like I went to. Reptid and and land. And it is amazing why that so few centers around the world actually picked it up. We actually visited in Seattle at the time and we decided to put it up and we started out and having the cans it because we thought we should do something else and wasn't there. But then it was very difficult to work with the head and the kinds of things because they are. Very good performance. They just went out to simulated them and we then decided to try to kind of establish it in many moments since then we have been working quite a lot for that. I think it is to say it is a very important point that then you can actually benefit from chasing therapy independently of when we had a check on the people who reflects we deceased and that's so important because inside the patients that we have. Now that we do not really want to do about and how to treat them. So that would be almost my biggest question. I mean we've got data from from love for the role that you did with John Hannah randomize trail variable on trial versus if he. So we can see those efficacy signals that where do you see the price of cellular therapy in the meantime in five years time in terms of lots of therapy. Are we going away we could. Select people out or enrich the people say first on anything. Yeah, I think it's a important point that this is a really highly selective patients and we need to remember that it's not for all cameras. First of all, you need to I mean the age is does actually matter so we're not treating patients above 75 because it's totally worth this variant and so people tell me I'm too. It's really tough and you can. You can be live straight and by the inside effects so I think that's important but also actually but you need to be able to protect the two. But I really have heard the patient and that's not all for me in other patients. Even when the normal people start and the skin when we say no quality on cars is setting. You normally have the most is in the season inside and it can be a rather tough thing to go for. Million of my mother. Metasins and deliver a lot. So there are a lot of limitations on that. In regards to which places to treat. And my opinion at the time being I think that still even though we do not have the same kind of long team. So I think that the side effects from the side effects from T. So therapy as we can experience from the tick on the results. I still think that there's the total level of side effects are lower. We'll take one. So I really would go for tick on the results first line. But there are maybe about cases where we do not treat with this combination. And then mark at least we also use a P. They are one marker. And for those patients it would be more at least I believe to be able to forward the. Season therapy if they progress and the P. One then she tried to go for another. I think it could be in that setting and I think from the Ivan study. As well we have seen that. For all late lines it's around. I mean 36% response rate what they feel for the patients with what the question. It's a bit lower. I wonder if I can ask you a question in gammary about. As we're now using cellular therapy as a potential standard second liner beyond. What do you feel is the next obvious step for us? Should we be genetically modifying our till and having them express shutdown signal, suicide switches. Should we be giving them knockout receptors for TGF beta? Is it the interleukin two portion? Should we do something to adjust that interleukin two? So that you know some groups like aisle 15 some groups like aisle 21 because they promote more of a memory cell phenotype. Or do you think it's from that very first step the tissue procurement getting tissue from biopsy specimens. As opposed to a surgical specimen reducing anesthesia time. You know quantity needed a tissue that kind of thing we're ready. We can make progress in all of these, but where should we be focusing? I was about to say the same thing. And we think we need to move forward in all directions, right? There's a lot of things that we cannot summarize. I mean, both in the way that we prepare and then factor in the T cells, we know that. And we know that we lose a lot of activities when we move from the early cells that we produce like the themselves. And then moving through the very large expansion in the last couple of weeks, we lose a lot of businesses. We can see that the functionality it goes down and for sure we are losing some of the importance and. The physical services, I'm sure. So we could probably do a lot about that. How we kind of start with initial. And manufacturing up with C cells and then in the gut to how we could kind of manipulate them. I also think we have a lot of possibilities. So we are working on a couple of directions here. So we're starting up with a clinical trial now, which has been approved where we are kind of crisper and out. The PD one expression and the T cells. You could say you could achieve the same thing, maybe by combining it with an entity, one entity, but I think what is also important here is that we are only kind of manipulating the T cells, which are concentrated around the tumor activity. So that should hopefully mean that we see less side effects than if we combine it, but it's a point to be so because. If you look at the one of the things that we actually do not that frequently see for the season, so that's also. Side effects is very rare that we see that so in that way there's not a lot to boost by nothing out the PD one right. So we really truly believe that we can maybe have a more focused continuous activation of T cells reacting against the tumor cells by knocking out the PD one on the toes. But other options are as to set also to introduce something and they have also another try working on introducing that seven. But in the also again, a very focused way where it's only when the T cell receptor into act and get activated by the and string in such early. Then it starts producing the I have certain and that is a must meant to be like to begin to protect the patient against the side effects. Because I think we in the setting of T cell therapy, we can't really tolerate most side effects right. It's so intensive for this problem of weeks when they hospitalized that this isn't enough. So whatever we do is it also have to be taking into consideration that we need to. Hopefully, no other side effects, but at least not increasing that. We work together with in a European setting, we have a year grand is it's from also from from Barcelona where they have them. Stateless try will be trying to use another kind of I to. A kind of I to which is again, not activated in the same way systemically in the hope that we can reduce our two side effects because I would say they they are excellent. The most away ones. So I hope I hope that we also in the future will be able to work on the dosing and how we I mean maybe you will look more kind of I to maybe new kind of side of kinds that can. So do society effects then at least also continue the same efficacy. Yeah, I mean that that that sounds great. I mean, one of the things I've been wondering a little bit and I agree with what you were saying that probably for a lot of patients just still going to want to go with the checkpoints inhibitor first of all. And I think that the agents probably going to be well tolerated and if they're sensitive, it's great. You know, they might not need much more treatment, but I want a new argument might be a bit of an example of this, but but also metastatic disease. Where they should be thinking to ourselves quite early on is this patient is really going to get durable benefit from the checkpoints inhibitor or not. Rather than waiting for multiple lines of therapy and then you've got someone who's been on steroids and there are even a suppressant they've got brain mass, but actually in our heads, if you like treating metastatic disease, let's say in the first six 12 months. And you know, you know those data from various sources that were quality response to checkpoints inhibitors will correlate quite tightly with long term outcome, but whether we should say to ourselves, actually, this isn't a good enough response to a checkpoints inhibitor quite early on. And that's where we should be trying to understand more about the place of cellular therapy because I think for that kind of patient, they're probably going to be easier to treat in lots of different ways. And I think you can justify them potentially great toxicity as well from cellular therapy because they failed or they're going to fail checkpoints inhibitors to do. And I think that's plausible it's just me sort of, you know, the optimistic about which way we're having. Hopefully help us out in the future and I mean there's a lot of assessments of biomegospels, all of this kind of explorative and I think we are completely lacking the way we decided and validated the markers and probably we will be working with the profiles in what the mark of other first profiles in the future. Hopefully help us out and help the patient also that we're not offering them condemnation checkpoints, we could see if we can see the way we have a very, very small chance of efficacy and instead move them forward with the two, to therapy. And I think it like for the kind of treatments and later line, they're no one if it is a rate and it's a symbol to help you know it can be extremely difficult to kind of have the pace and ready and then not proposing to aggressively after we have made inhibitors waiting for the tea cells can be extremely difficult. And so, so in then, not here at the moment we have this approval of what I call an early access program, but it is for patient base. So I have to apply the third is for allowance to to keep the tea cell therapy. And we are actually argued that this would be also feasible for patients who have not been treated with the ref making episodes because afterwards it can be like a possible and as you said they can probably they turn out to have been the testers and we have a lot of issues there. Well, this is good. I mean, I think we have the same experience as well, certainly working with like the Lucille and I have answered. So that sort of brings me slightly to another question and from what I can gather you and John Helen as well, I think have access to send it up in reimbursement correct. And that's a struggle. So I mean, it's happening in the US and I feel is what I have to approve or do you think the kind of the regulatory and reimbursement world, you know, more widely in Europe, it just feels a little bit like it's not kind of set up for this kind of thing very well and it's a real struggle. But you know, and you're really close to this. I'd love to hear your thoughts. I think you're strangled and we've been struggling with this. Like I think it's almost serious. Yeah, no laughing. Now if the system is completely untrained for academia, I would say everything is set up for the industry and the endless the chances that you're living. Because you do not have the competence of yourself and we do not have really the right people to help you out because nobody has tried to move forward as an extreme way towards email with this submission of a market of poor education. So even though we have been able to find that consultancy, they haven't got the experience right so there's a sort of helping us out in the level that they have but I mean, we've had decided before and an email they are also challenged by the lack of experience and there's a lot of discussions actually going on in Europe at this time. And I've been approached by we have made a committee around this AT&T, we advanced in the health is as well as a team staff is and they try to kind of begin to also the hospital exemption. That because it's the way that it's it's being used in the different countries in Europe is completely different. So it's interpreted very strictly for example in Denmark and many of the countries in world but in Spain. There are a lot of things like the cut he sells their own CV 19 13 based on this special exemption and they have allowed the second approval. But individually like in Spain and at the same time it was the client in Denmark I was the client applying for a special exemption while gentlemen were well once was approved based on the same data right. And that was very difficult and the whole discussion also about the competition. This is a fair competition through the company. So this is really unfair and how should we put the prize in it? Yeah, there's a lot of things here also I think for within the next. It would be very interesting to see when in the next five years where we will end up where will be where the politically and regulatory and also I mean like to come the collaboration with the company. Thank you. industry, I think there's room for all of us, less really, and how I see it because we have so many pays and around Europe and around the world who need this therapy and it's not near to cover by the industry at the moment. So I think there's a lot of space that we can just try to help with Jada. And I think also it's a pretty thing to have in position also when you're a company. Yeah, so it's slightly discussion of this point of care production as compared to a centralized production also. And I think we're going to move for both ways to do it, I believe. And also to secure excellence, the continued development and research in TISO therapy. You need to have it right next to the clinical research and the academia. Yeah, just feels to know that I know for straightening it's been at least I think I've got some idea about straightening it's been that you have a therapy that can really help patients, jubbly. There's all these other considerations that are coming into it but at the end of the day this is something that really can make a difference to patients. So congratulations to you and John and everybody else on really pursuing this. But it is a point I suppose isn't it that there's all this beautiful clinical and scientific work but actually then to deliver to patients afterwards as a whole load of other considerations. So listen, this is going to be my final questioning and then Satnam, they have to ask other things, but based on what we've discussed, where do you see the prospects for this type of strategy in other solid tumour types and then the data certainly from our events and others in various other settings. Do you think it's going to be a sort of mainstream treatment in other solid tumour types in a part, at least, elective patients obviously, not not everybody. Do you see the promise that? Yeah, I do think you say in some of the patients. I think it's very important data on hitting the cancer and also lung cancer but again lung cancer we need to be able to go through a restriction of the lung, of the lung diseases typically and many other hitting the cancer patients. They are really loving a performance stage as well. You can drag them through the headers, Kim, with the OVNI and I. To sign the way they need to figure out how to increase the efficacy in those patients and decrease the side effects. So for sure and I think for that it's very important in which you started that they tested the incoming donations that check on the HIPAA cells as well. And you can also imagine like genetic modification and also improve the way they may be but we also work this is like really procanically but we're also working on a car. So you actually kind of introduce a car and the disease is during manufacturing. So you have a very potent target and then you combine it with the greatness of the work that's right off the cells and the condemnation of that could maybe be undue to a high efficacy clinical also. I think so you need to we have so many different very exciting tools for manipulating those cells so it will be I think there will be a lot of new strategies out there in the next years. Okay, Satma and the thing else for you. No, I think that was incredible. I mean we even we have been only just talked about a portion of your research out there if you would do that same part. I think you're coming so exciting to see and of course congratulations to you and John and everybody there that's working on this cellular therapy in in Northern Europe. I only know just because it's a pretty monumental date. It was two years ago yesterday that you're new England Journal of Medicine. You know, you're just waiting or where are the other people? How do we get this donations? Thank you so much for coming on our part. Thank you. It was really great talking to you. Wonderful. Okay. Bye.