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Robin Daly
Hello and welcome to the first Yes to Life show of 2024. I’m Robin Daly, regular host for the show which is named after the UK charity Yes to Life that helps people with cancer to find out what they can do to help themselves through education about and inspiring access to integrative oncology, a form of cancer care that looks to support people holistically to help them meet the many and significant challenges of cancer and to make their lives as meaningful and as healthy as possible. Today we’re going to be looking at a rapidly developing field of treatment that has shown great potential in some situations, cell therapy. This is very much an umbrella term that covers a growing range of techniques and to help pick it all apart and find out a little more about what is on offer and to who. I have three expert guests. In the UK I have Prof Fiona Thistlethwaite, Consultant Oncologist working in this field, Finn Willingham, Head of Advanced Therapy Treatment Center Network Coordination, Cell and Gene Therapy Catapult and in the US Brad Heller, Founder and CEO of Achieve Clinic. Welcome Brad, Finn, Fiona to the Yes to Life show. Thank you all very much for coming on today.

Guests
Great to be here. Thank you.

Robin Daly
So the subject of today’s show is cell therapy. It’s a growing field that’s attracting a lot of interest. Even though various cell therapies have been around for many years in one form or another, it’s an approach that’s not so well known. And one I expect many of our listeners would like to know a bit more about. So Fiona, I’m delighted to have you on today. Professor Fiona Thistlethwaite from Manchester, I believe, Christie Hospital. I wonder if you can tell us about your particular interest in cell therapy and maybe also about IMATCH that you’re director of.

Guests
Yes, of course. And thank you for inviting me here today to speak. So I work as an oncologist, a cancer doctor in Manchester at the Christie Hospital. And for many years, I’ve had an interest in using a patient’s own cells and to to demonstrate or to cause any reaction that can have an anti cancer effect. So using a patient’s own cells for a cancer treatment. And and the idea behind that is that if we give the patient’s cells, we can and those cells can react against the cancer. They can kill a cancer cell and go on to kill multiple other cancer cells. So the idea is that we can give a one off treatment for patients and hopefully have a deep response that may have a durable emission and so patients can become cancer free for long periods of time. And we’d be working on that for many years with varying degrees of success, I have to say. So in some fields like in blood cancers, we’ve seen fantastic success with the particular type of cell therapy called CAR T therapy. In the field that I work in, in solid tumors, success is being more limited. But we are starting to see some really positive signals coming through. Hmm. OK. So one of the challenges you can imagine, if we’re using a patient’s own cells as a treatment, it’s incredibly complex. So we have to get those cells, usually from the patient themselves, rather than normal drugs, which are more off the shelf products. So we get those cells from the patient by a process, a complex process, either surgical or going on a machine. So a process called aphelesis. Those cells then have to be transported to the manufacturing facilities often in the US or outside the UK’s borders. And the way they’re manufactured under very specialized conditions and then brought back to the clinical site where the patient’s ready for those cells. We have to give them conditioning chemotherapy before they receive the cells. So just from that description, I’m sure you get a feel of the complexity of this. And for us to be able to deliver these therapies within the NHS, we need to have that infrastructure in place to be able to deliver at scale. You know, this isn’t just a one-off thing. We need to be treating patients week in week out. And that’s what iMATCH is all about, really. It’s about the UK being able to deliver these complex therapies and having that infrastructure in place. Not just the infrastructure in one center like the Christian Manchester, but across the UK, having a network of establishments where we can say to the companies developing these therapies, look, we’re fit for purpose in the UK. We can do these complex therapies and actually attract in clinical trials and the latest cutting edge treatment to benefit our patients, but also to gain that experience within the NHS. So iMATCH is a collaboration across multiple partners, clinical, academic and commercial partners, to scale up that activity, to increase access for patients. And iMATCH is part of a wider network, a network called the Advanced Therapy Treatment Centre network, which is UK-wide.

Robin Daly
So quite a bit of buy-in from a lot of people there in order to make this happen. OK, so Brad, you’re the CEO of Achieved Clinics in the US. I want to introduce yourself and achieve and tell us how and why you’re involved in this field.

Guests
Sure. Thank you, Robin. Great to be here. It’s a really good segue from what Fiona just said about the complexity of going to patients and helping them access these personalized medicines. My background is as a research scientist, I was in the trenches at the bench at a cell therapy company, just the type of company that does make these types of living drugs from a patient’s own tissue in the San Francisco Bay area. It’s all those stereotypes of startup culture that you see on TV are mostly true. It was a very, very exciting experience for me, but something that was really clear from the outset was how difficult these drugs are to make. This isn’t just bench. When you’re literally working from material collected from a patient, the variability that you see from one person to another, how their previous lines of treatment are known, of course it’s intuitive, but it has been conclusively shown to damage the immune cells that are needed to go on and then literally make the cell therapy. Just experiencing that from the research side, I realized there’s got to be a better way to make these drugs. There’s got to be an easier way for these patients to access these types of drugs. I did a little bit of research on my own and resigned and founded Achieve Clinics, which is accessing patients earlier in their disease course and offering them a zero cost option to undergo that cell collection that Fiona mentioned earlier, that ephoresis, also sometimes called a leukophoresis, where you get hooked up to a machine and your white blood cells are collected. We’re doing that earlier to avoid many of those logistical pitfalls that patients suffer when they wait until their disease is sufficiently advanced at the point where they can finally become eligible for these exciting trials that could really help them, or even cell therapies and commercial use that are FDA approved today. Patients are still struggling to access them because they can’t get them until they’re sufficiently sick. It’s a very sad and tragic situation that patients find themselves in that we’re trying to fix. Let’s get those cells earlier unless to help improve your access to that future.

Robin Daly
Yeah, it’s one of the sort of bugbears of your life for patients is that new therapies tend to get put at the end of the line. It goes through all the rest of the stuff first, failing, and you’re getting worse and worse, and then it comes along. And yeah, really promising therapy, wouldn’t it be nice to try it way earlier on and see how well we get on. But yeah, well thanks very much for that. And I also believe you’ve got your eye on UK shows in the future. Do you want to tell us about that?

Guests
Yeah, I sure do. So, one of our very first conversations was with UK’s catapult. And so, we’re really happy that Finn was able to come here and represent catapult. I’m sure she’s going to introduce herself and catapult interest at home. And so, I don’t want to steal her thunder, but our first conversations were very clear that this is something that could really be helpful for British patients. At the present time, there isn’t an increased appetite. I was just at a very large meeting called ASH, the American Society for Hematology, where I actually had a really productive meeting with Sarah Groshian. And she was explaining to us, she’s a British physician as well, a scientist, and an ECL. And she was explaining that there is a little bit of increased appetite to do this so-called rainy day harvest of collecting these cells a little bit sooner in case it’s where patients are a certain lock for future cell therapy. But there’s no capacity or appetite to pay for much earlier risk collections that we think could do the most good. And she’s hoping to advise us with. So, yeah, there’s definitely a plan to kind of expand to the UK with the assistance of potentially with Catapult. Also, one of our new advisors is a CEO of Worry Biotech. This is one of UK’s champions, frankly, and the cell therapy manufacturing space. And so, they’re working on improving the actual manufacturing once you receive the cells. We’re the experts in giving them the cells in the first place and the access to patients. So, this is a whole ecosystem of how these drugs are made.

Robin Daly
I can see that. Okay, yes, over to you, Finn. So you’re head of Advanced Therapy Treatment Centers or ATTC network coordination for catapults, cell and gene therapy in the UK. So could you tell us a little bit about yourself, why you’re doing this work? You could tell us about the ATTC a bit more as well, and also about the relationship between achieving catapults.

Guests
I’ll just give a little bit of context about cell and gene therapy to start with. So we’re an independent innovation and technology organization committed to the advancement of cell and gene therapies in the UK, with the vision to have a thriving industry delivering these life-changing advanced therapies to the world, and to also create powerful collaborations which overcome the challenges and to advancements of the sector. And some years ago now, catapults supported initiatives through the UK government to make funding available. So back in 2018 to establish the ATTCs and create the ATTC network. So there are three ATTCs and Fiona’s already described iMatch. There’s one called Midlands and Wales, as the name might suggest, covers across the Midlands and in Wales, and it actually has got a long reach down into the south and southwest of the UK. And the Northern Alliance Advanced Therapy Treatment Center is based across Scotland and in the north of England and has some reach into Northern Ireland too. So the geography of the network is very extensive. And as Fiona described, we’ve worked really collaboratively, not only within each ATTC, but also across the network to deliver a whole range of projects that are looking at the infrastructure to deliver these medicines and the training to deliver them of scale to patients. And several pieces of work actually around the ATTCs did link into the sort of the capacity or around apheresis, which is such an important process to make sure that there’s starting, you know, good quality starting material for a lot of these products to be manufactured. And so there was a big network project around looking at standardization of apheresis, that process that Fiona described. But also more recently, we’ve done a network project where we’ve actually looked at the apheresis capacity that the UK NHS system has in place at the moment and what the demands will be on that capacity going forward. And we’ve used data provided by NHS England. They’ve done some scanning of the horizon to see what products are coming through the system. And based on that data, it looks like there’s going to be a significant increase in demand on those services up to 25% increase in demand. And therefore it does pose the question, how does the UK respond to that in terms of making sure that we can actually treat the patients that these pipeline products are promising to be available for. And that’s where we work with industry, for example, achieve clinics, we would look to see how we could collaborate to make sure that the infrastructure or the system was geared up to enable that to happen.

Robin Daly
So a complicated hookup of all sorts of skills. Just out of interest, is it very costly, for instance?

Guests
Fiona’s probably better place to comment on that, but I think it’s not insignificant. It’s not insignificant, I mean, for one CAR T product, for example, the actual process of a free system, patients are going on the machine for around four hours, it’s a sort of half day in hospital, they may need additional blood tests, clinic reviews, the actual running and maintenance of the machines and the staff who are extremely well trained to actually carry out the apheresis and then the product then being transferred to the lab. But I think all of that, although there’s a cost associated with it, it’s a small aspect in terms of the overall cost of the therapies overall, it’s running to six figure sums. But I think there’s so many aspects to something like the apheresis in particular that adds to the complexity that you’ve heard about already. So take, for example, the training of apheresis nurses, we can go out and buy a new machine, but if we don’t have the apheresis nurse trained and imposed, we can’t get maximum efficiency out of using that machine. And so I think it’s all of those aspects that add to the kind of time cost as well as the financial cost of apheresis. Right.

Robin Daly
So what Brad is pushing for is that this process is undertaken early on as just to be in readiness for this process at some point. And so literally, this is just a collection, which is then frozen, presumably, is it, for later use if needed? Okay.

Guests
And maybe I could comment a little bit further and then hand back to Brad, because it’s already this idea that when we carry out these complex therapies, it’s for patients where our standard of care perhaps hasn’t worked as effectively as we might want. So many patients with such a type of cancer are cured by surgery or by their initial therapy. And where CAR T comes in currently in the patient pathway is later down the line where standard of care treatment, standard of treatment haven’t been effective. And when the patients have been exposed already, perhaps to several rounds of penis therapy, which impacts on their immune cells, which are the T cells that we require as a starting material for CAR T therapy. There’s absolutely a case to be made that what we want to do is gather those T cells at a point where they’re healthiest, there’s more of them and they are more functional than might occur later down the line. And that’s the rationale for bringing treatments earlier in the patient pathway. Now, it might be that we might, and currently clinical trials are already testing this, to say, actually, rather than waiting till last line for something complex like CAR T, is it more effective if we bring it earlier in the line, second or even first line of treatment for patients with particular blood cancers like lymphoma? But even so, I think that idea that we know we’ve got an effective treatment, but can we make it more effective by starting with better starting material? And that’s certainly a question that’s worth asking. Makes complete sense. Did you want to comment more, Brad?

Guests
Sure. I could say that definitely I go, what Fiona just said, apheresis is, I would say almost any cost is a burden on a newly diagnosed cancer patient, especially in the United States where we don’t have the NHS, something that would be a few hundred dollars could really be challenging for a patient. Apheresis and cell processing and freezing, as Fiona alluded to, is thousands of dollars. But it’s still a drop in the bucket when the entire treatment itself costs three or four or five hundred thousand dollars. And so there’s that kind of disconnect. And as she said, there’s that capacity issue. I guess it’s worth mentioning and backing up for a second for admittedly or mostly lay folks who are listening to this podcast. So the apheresis itself is a technology that’s been around, I think since the 1950s or 60s for therapeutic use. These facilities exist and they’ve been designed to provide a therapeutic value at a certain level of use. The advent of CAR T cell therapies has increased the demand on these pre-existing facilities by, I don’t know, tenfold? I don’t know. We can estimate that some other time, tenfold, maybe twentyfold, maybe they’re swamped. And so like Fiona said, it’s not just buying another machine. Do you actually have the space? Do you have the personnel to work with it and operate it? And yeah, I would definitely echo what she just said. I would also say that I would want to clarify that even though that there’s been the most progress with hematological malignancies, so the leukemia, lymphoma, and we’re very, very excited, especially that the meaning I just mentioned about these therapies beginning to move into first line, you may think, well, then why do we need to achieve clinics? If these things become first line, I’ll be able to get them right away. And so first of all, there’s always going to be the next greatest thing and the next generation is going to be in trials that patients are going to be struggling to access. And secondly, if you don’t have a hematological malignancy, if you have a solid tumor, those options are all in trials. And so there’s still a tremendous need to help those patients who are often diagnosed at a much more advanced stage, because part of the insidious nature of these types of cancers, pancreatic, liver, et cetera, is that you’re actually in pretty good health until something goes wrong. And then by that point, the cancer is too far along. And the standard of care, resection, and some other drugs, add a few months here and there, but don’t really alter the outcome. If you can help that patient quickly access an experimental CAR T, that might work. That still is something that’s a huge value at night. As much as the efficacy boost of using cells that are healthier and using an immune system that has T cells that haven’t been exposed to the previous lines of treatment, as much as that I think is real, and we want it to be real, we’re pretty sure is true. There’s that logistical issue of helping patients access these future medicines as quickly as possible. It’s actually really a logistical solution more than anything else, what we’re trying to provide. We’re trying to do something as quickly as possible for the patients. We’re the most vulnerable.

Robin Daly
Hmm. Okay. Yeah. Understood. All right. Look, a few basics. I mean, quite a few people will have heard about other types of cell procedures that go on, like stem cell transplants, marrow transplants, that sort of thing. Can you just maybe Fiona, just differentiate between those and what you’re involved in?

Guests
Yeah, I can certainly try. So with a stem cell transplant, patients still generally require a phoresis, but in that case, they’re taking stem cells, so a different type of cell from the patient, rather than in our case, what we’re talking about is primarily the T cells. So with stem cell transplant, the stem cells are taken, and they’re not what we call manipulated. They’re not gene-modified or otherwise activated, particularly. The patient then has conditioning chemotherapy, and the cells are given back to the patient. With T cell therapy, with CAR T, it’s different. So the cells are taken away to the manufacturing laboratory, and with CAR T in particular, they’re genetically modified. So the cells are actually infected with a virus, and that virus will cause those cells to express on their surface a particular protein, something called the receptor, that can then target specifically, very specific global cancer cells when they go back into the patient. But not all cell therapies require or utilize apheresis, for example. So in solid tumors, there’s a therapy called TIL therapy. That stands for tumor infiltrating lymphocyte therapy. And that’s actually been submitted recently to the FDA, to the regulatory authority, for them to assess whether this is a therapy that they might be able to approve. And that’s been submitted to the FDA for marinoma. So that’s a type of skin cancer. And with TIL therapy, the differences of the T cells aren’t genetically modified, but they are T cells that are actually grown from the tumor themselves. So usually a secondary deposit in a patient where the cancer is spread beyond the original melanoma. And when it’s spread, the patient undergoes an operation. And the metastasis, the secondary section that is removed, and then it’s chopped up in the lab, and the lymphocytes, those T cells are grown out of the cancer cells. It’s not the cancer cells that are grown in the lab, but the lymphocytes, the T cells. Those T cells are then activated and grown up to billions of cells in the laboratory to enough cells and they’re activated by giving them chemicals called cytokines before they can be given back to the patient. So in that case, it’s a different scenario to what we were talking about where there’s apheresis capacity, but these patients have to undergo surgery. And in that sense, there’s complex aspects to capacity and to ensuring that the cells and the tumor resection, the operation sample is correctly handled. So for example, it’s in sterile conditions and it’s transported at the right temperature to the laboratory, which may be many miles, even on a different continent. And so obviously that’s giving you a feel for some of the kind of different aspects. So there’s the stem cells that are not particularly manipulated in the laboratory. They need to be stored under the correct conditions. But then there’s the more complex end of things like CAR T and telothoracic. OK, well, let’s talk about CAR T cell therapy for a minute now.

Robin Daly
That’s a name that is bandaged around quite a bit and probably quite a few people have heard it, but I doubt that many know what it stands for. I have to look it up. Chimeric antigen receptor cell therapy. Well, it’s not only being able to read it, it’s what does it mean? So does somebody want to have a stab at explaining in the plainest English possible what that’s all about?

Guests
The idea behind this is that we know that T cells in normal setting very often control abnormal cells in such a way that they get rid of any pre-cancerous or cancerous cells before they’ve even formed the cancer. And they do that by homing in on abnormal cells, detecting that they’re abnormal and then destroying them. And the way that they detect them is by interacting with those cells. And the T cells can sense when there’s an abnormal protein on the surface of the cell. So they see this abnormal protein where the T cell activates and then it kills. And we go with a patient’s developed cancer, something’s gone wrong with that process. And the T cells are either not active enough or not getting into where the tumor is. And the idea behind CAR T cell therapy is to say, can we reactivate or can we activate an anti-tumor response by making these T cells so powerful and very specific for the cancer cells? Because we don’t want the T cells to go around destroying normal cells, for example, because that would make the patient very sick. That causes condition called autoimmunity. So, when the T-cells have taken away to the lab, they are actually, as I mentioned, they’re infected with the virus that inserts the DNA that we need it to into the T-cell’s DNA and then it can express, the T-cells then express this chimeric antigen receptor on their cell surface. So, that’s the kind of engineering that has been designed in the laboratory and that we’re able to do this. We genetically modify those T-cells so that they can express on their surface, they have on their surface a new protein or receptor called the CAR and that CAR can detect a specific protein on the cancer cells. Now, the CAR T-cell therapy that we hear about all the time is in blood cancers and most of those are detecting a protein called CD19 which occurs on some blood cancers called lymphomas and some volcanias. So, the T-cells in CAR T-cell therapy have this receptor that can detect CD19 protein on the ligament cells. So, we genetically modify them, we grow up the cells in the lab and then we can give those cells back and those cells can then hold to the areas of cancer within the patients and then they’re activated and can destroy them.

Guests
The power of this technology is that the T-cells, when they’re activated correctly, they’ll multiply and they can go off and kill other cancer cells. So, unlike a normal drug where once it’s killed the cell, it’s destroyed, this can engrass and proliferate so that the ideal is that we only need to give a one-off treatment and that’s the kind of step change that’s different.

Robin Daly
Yeah, so you’re starting a process. So, everything we’ve been talking about so far comes under the banner of immunotherapy which is being heralded very much as the new modality for cancer treatment alongside the more traditional methods. So, any of you would like to put your name to a prediction of how immunotherapy might rank alongside the traditional therapies in say 10 years.

Guests
Wow. Well, I would agree with you that it’s a very, very, very exciting new modality. That’s seen really tremendous impact for many, many patients. I really would see it also as another tool in the oncologist toolbox. And I think this is probably another better question for anyone to go into. But a lot of people ask me, oh, gee, clinics is really just for cell therapies. And that’s really going to be the future. That’s another way of asking your question, right? Robin, is cell therapy really going to be the whole, that’s secure for cancer? Well, maybe. But why do we just have to put all of our chips on one thing? I think we need as many different tools as possible, whether it’s biologics like antibodies, which also is essentially immuno-oncology or small molecules or different types of cell therapies. They’re a genetic material that expresses a synthetic receptor for a cancer molecule. There are also versions of cell therapy where those tools, as Fiona described, that are intrinsic to the tumor are purified. And their ability to detect the cancer that enabled them to infiltrate the tumor in the first place is purified and put into a fresh, clean, new, brand new T cell and grown up to give a different type of cell therapy called GCR, G cell therapy. There are all sorts of versions. There are cell therapies that don’t involve T cells. We should spend hours and confuse all of our listeners with those made from B cells and macrophage and vaccines that involve dendritic cells. It’s so exciting. We all have to be rooting for all of it and we all have to be doing everything we can to be advancing all of it as much as possible because I think all of it is going to work, some of it for one cancer, but not another. So we just have to keep on trying and doing everything we can.

Guests
maybe I could make a few additional comments and to say, where is immunotherapy? And actually, immunotherapy is already part of our armory. So we used to talk about the pillars of cancer treatment, surgery, regiotherapy, 4-1 treatment. Then a force pillar came along in terms of targeted treatments. And actually, I think immunotherapy is already really established as a fifth pillar of treatment. And really, the step change came perhaps 20 years ago when we started to see the emergence of antibody drugs called checkpoint inhibitors. And the way that checkpoint inhibitors work is that they block an inhibitory reaction. So what they do is they reactivate the immune system. So checkpoint inhibitors have been a real step change. We use it all week in week out in our standard oncology practice now. I do on my own or combined with chemotherapies. But the important thing about checkpoint inhibitors to know is that even the highest rate of response that we see in melanoma, for example, half of patients will not respond to checkpoint inhibitors. So for the half of patients that respond, well, that’s great, but for the remaining patients, we need better treatments. And that’s where these newer therapies come in, like the cell therapies. There’s also a new type of immunotherapy that we’re seeing increasingly coming towards a clinic. And that’s something called bi-specific antibodies. And those are otherwise known as T-cell engangers. So you can ask the question of saying, do we actually need to do the complex manufacturing of T-cells and genetically modifying T-cells in the laboratory? Couldn’t we just detonate an enganger in a molecule that physically links the cancer cell to the T-cells that we know are already there and actually connect the two up. And that’s those bi-specific antibodies are actually being used now in the clinic on the verge of becoming part of our standard of care in solid tumors now as well as blood cancers. Problem with those or one of the challenges with those is that they’re big molecules, relatively big molecules. So when you infuse them into a patient, they don’t last very long in the blood system. So we have to give patients often weekly treatments with these drugs. And that’s the almost the consensus end of the spectrum of what we’ve been talking about with cell therapies, where you have a one-off treatment that hopefully will give a long lasting effect versus coming to the clinic for a weekly treatment, it might not need the complexity of a phoresis or coming in for conditioning chemotherapy and a one-off long hospital stay that the CAR T requires, but it is equally, and if not more, a drain on the kind of facilities and the capacity that we have if we’re having to treat patients weak or the full intravenous infusion. And these are all kind of aspects that we need to consider when when we want to help as many patients as we possibly can with these novel treatments.

Robin Daly
Absolutely. Of course, it’s a better result for the patient, something that they put a big effort in and it works is actually a much better result than something where they have to be on maintenance all the time.

Robin Daly
Yeah. OK, very interesting. OK, so can we talk a bit about the challenges that are facing cell therapy? Your organisations are striving to address these. I mean, maybe Finn, you want to tell us what Catapult is doing to support cell therapy innovation in the UK?

Guests
Certainly, I was going to mention, actually, there’s a slide that we quite often use in presentations which weren’t bad to use in the podcast, but it just indicates, it visualizes just how many advanced therapies are coming through the pipeline. And there’s a few dotted in the middle where they’ve actually got through and their license and they’ve been commissioned within the NHS to use. And then there’s an avalanche of all these other products coming through for oncology, but also for other indications, which just shows you the promise of what’s to come. And we’re very mindful of that when we do our work across the ATTC network to see how we can boost the infrastructure. And generally, Catapult will be working with industry and the NHS to support initiatives that help with the readiness for cell therapies, obviously more broadly as well, because we work with advanced therapies such as gene therapies, et cetera. So we might run a pilot program, for example, with a company who might have an initiative around cell therapies, such as a gene clinics, where we bring together partners to collaborate to test out whether or not that particular approach might work. And if it does, then we would look to roll out further across the NHS. So very much the model of the ATTCs is to run something small scale and then disseminate or build the infrastructure around it without giving any more specific examples.

Robin Daly
Great. To the outside of the cost of these things sounds astronomical, but treating cancer is expensive for the stop. So I’m just interested to know how it compares. You know, if you look at, well, what you described is the fact that there’s a fair chance that you can achieve a lot in one session, which might you might spend an awful lot of money maintaining somebody’s health in another way. How does it compare with other forms of cancer treatment?

Guests
Well, I can pick up and just comment on within the UK a lot of the products that have actually been are in use now within the NHS are still gathering data to demonstrate efficacy because they come to the market at a point where there’s some uncertainty about it and it may require several years to continue to gather that data before they can go back and demonstrate that they are cost effective. So we’re at quite an early stage in the UK and I suspect it’s the same in America where we’re still looking for that demonstrable efficacy and cost effectiveness for these products and but they are significantly upfront and more expensive than say another type of cancer, but I’m happy to be corrected by Fiona on that. But if you think about the cost saving across the lifetime of the individual who may be treated, you know, and you take other factors into consideration, then you can make the argument more effectively that actually they’re definitely worthwhile commissioning within the UK.

Guests
The fact that they are not minimally manipulated like the stem cell transplant that we were talking about earlier, they are not considered to be advanced therapies of stem cell transplantation and their costs are much lower because it doesn’t require product to be manufactured in a GMP, a good manufacturing sort of environment. So it brings the costs of goods down, but you could imagine that in the longer term, you can get benefit of scale up. So the cost of goods would come down, you get a more mature sort of supply chain. So you improve the transportation of these things, etc, etc. And you can imagine that initiatives like Achieve Clinics is looking to implement would be part of that whole infrastructure to support. It’s difficult to justify costs upfront like that, isn’t it? It’s investment right at the beginning of a process when some other cheaper process may look like a good option is hard. Fiona, yes. And yes, and just to add to that, what are the challenges for cell therapy? There’s lots of challenges in terms of thinking about that cost effectiveness. So first of all, it’s actually very difficult to do randomised trials with cell therapy. And they have been done. But because you can’t blind a patient, you know, it wouldn’t be ethical to put a patient through this week of chemotherapy and then kind of giving them a placebo cell infusion because the side effects of the chemo, that sort of thing. And also actually, it’s actually relatively small numbers of patients who are fitting well enough to be able to have the cell infusion. And most people going into if you went into a clinical trial, it’s a randomised trial of cells versus perhaps a chemotherapy that you know is going to keep a relatively short benefit if any. And many patients would wait to hear whether which they’re randomised to and quite naturally if they’re not going to randomise to the cell therapy arm, then they choose not to participate in the trial. And so there’s some strategies that you can think about in the trial design to help support that. It’s actually with cell therapy, we often rely on non-randomised trials, unlike most other new drugs coming through where the regulatory authorities would mandate would say you have to do a randomised trial to show that it’s better than the standard of care. So with cell therapy, we rely actually on say, we think this is better because of long-term follow-up and those doable responses that I talked about, you think of a one-off treatment of patients well five years down the line and versus with the standard treatments we knew there are with survival is perhaps measured in months rather than years, you can say there’s clearly a benefit. But we rely then on long-term follow-up and that health economic balance tips towards those therapies where we see long durable emissions. It can be actually very hard to measure and we don’t want to wait for five years to see if patients are still alive if there’s career therapy that’s benefiting them.

Guests
So it comes, there’s some really important aspects there about how we monitor patients and how we continue to document how they’re doing that will feed into those health economic aspects that will really strengthen our case to be able to do the bring more of these therapies to more patients and really justify that cost effectiveness as well as just saying these are clearly effective therapies. One of the things I really like to think about is some of the patients that we’ve treated who have had a long-term remission, we hear about them going back to work and leading normal lives in the community where they can contribute it once again, both social contribution but also actually economic contributions or paying taxes for example in a way that we wouldn’t see and those sorts of nuances really don’t get pulled into the health economic analysis that is done by NICE in a kind of standardized way because they’re incredibly difficult to measure. How do you measure some of those aspects? We’ve got some interesting, for example, really developing really good measures of that through patient reported outcome measures. So those are tools that are to use, they’re called problems and are actually where the patients themselves can record their symptoms, the tools, the activity levels for example and these are just really starting to be developed in fields such as Carti where they perhaps haven’t traditionally been very used in a standardized way in clinical trials for example.

Robin Daly
Well that’s really interesting. Yeah, I think one of the things that’s been more and more in the news in recent years is that survival figures are up but nobody’s looking hard enough at what that survival looks like and for some they have incredibly poor quality of life as a result of the treatments they’ve had. It’s not necessarily anything to do with the cancer, it might be successful from a treatment point of view but they’ve got radiotherapy damage or something which is actually making their life a misery and they’re certainly not a benefit to society, they’re a drain on society in financial terms. So yeah, that’s a very important point to find new ways of assessing success in that way, measuring success and looking more in the round if you like.

Guests
If I may, I think the efficacy that we’re seeing of cell therapies, for instance, only takes into account those patients who receive them. Those patients who are too ill to undergo the cell collection, those patients who pass away while waiting for a cell therapy. Some studies have shown that the so-called brain to vein time, the time at which a patient is referred relative to the time which their cells are collected, at least in the United States, is three to eight months for an advanced patient that is life-threatening. And that’s not factored in to the efficacy of the cell therapy treatment. But I think when you talked about costs earlier, what I’d like to add to that, one of the huge cost drivers for the drug makers is the huge risk that it takes to run a clinical trial and the lost commercial activity that’s realized when the trial takes longer than it should because of the time it takes to accrue patients. So if a patent only is in effect for a certain number of years, but the trial takes an extra year or two because of how difficult it is to enroll patients, that’s a huge amount of money lost and that’s money that has to be made up in these really high prices that are charged patients. And so one of the values that achieve clinics is bringing to the marketplace to our customers who are essentially the drug makers, they’re the ones who are paying us to populate their trials and enabling our free-to-patient model is because we’re saying maybe we can shave off a few months off of your trial time. And that’s an enormous, enormous cost savings. And we can also do so in a way that reduces their risk. As Fiona said, it’s virtually impossible to do a randomized trial for cell therapy. However, we’re collecting and accessing patients in the beginning. So we have a roster of actual patients and all of their health records that they’ve been consented to share with us, so that the folks leading the trials can look at this and use that to very thoughtfully populate their trial. So I’ll stop there, but there are different things that we can do to try and reduce costs, even if it’s just accelerating the pace of clinical development.

Robin Daly
Well, well, look, guess what? We’re out of time. And what a fascinating chat. Just sort of slightly lifted the lid on this sort of amazing hotbed of development that’s going on in this field. Obviously things are moving very fast. Uh, very interesting to have all your different input from different angles on it as well. So, uh, I just want to thank you all very much for coming on today. I’m sure there’s lots of listeners who will appreciate knowing more about this. so thank you very much.

Robin Daly
The promise of some durable remissions is indeed heartening to hear about and is the kind of result every patient is hoping for, a treatment that may be somewhat challenging but that can deliver a lasting result. Whether all the many hurdles can be overcome remains to be seen but developments in this area are certainly worthy of our attention in the next few years. Meanwhile it’s heartening to hear of some roots being created for people to access what could otherwise be the main reserves for the super rich. Wishing you all the very best for the coming year, one in which Yes To Life has some exciting plans I’ll be telling you more about shortly. I’ll be back again next week with another Yes To Life show so please do join me. Goodbye.