The Radiopharmaceutical Revolution: Driving Precision in Treatment

So hello, everyone, and welcome to CryonCast, the podcast from CryonBio, which discusses the emerging trends, breakthroughs and viewpoints in oncology drug discovery and development. Hopefully bringing you some interesting conversations from the scientific experts from around the globe. My name is Rejendra Kumari, and I will be your host for today's podcast. And I'm very excited with today's topic, which is on radiopharmaceuticals. And this is gaining a lot of attention for precision medicine. And we recently announced a strategic global alliance between Medicine Discoveries Catapult and Crown Bioscience to really support the growth in this area and to integrate our collective capabilities in translation biology to help accelerate the development of novel radiopharmaceuticals. So today I have the privilege of speaking with Doctor. Juliana Maynard, who has been with MDC since 2019 and is head of translational imaging with over twenty years of experience in translational imaging and therapeutic precision medicine. Giuliana is an expert imaging scientist and has worked with a wide range of imaging modalities, including PET, SPECT, CT, ultrasound and MRI, and has a strong research background, which is demonstrated by the numerous publications across various diseases and therapeutic areas. So thank you for joining us today, Juliana. Welcome to Crowncast. It's great to have you join us today and I hope you're doing well. Thank you. That's really amazing and really exciting to be here today and I'm looking forward to being part of the podcast and sharing, all of the work we've been doing, in this really exciting space of physician radiopharmaceuticals. Yes, I'm really looking forward to learning more about radiopharmaceuticals. But before we do, just tell us a little bit more yourself and how you got into the field and your role at MDC. So I've been part of Medicines Discovery Catapult for just over eight years now. I lead all of our translational research activities, both from our preclinical imaging and therapeutics as well as our clinical total body PET programme. And prior to joining the catapult, since finishing my PhD, I've been very interested in imaging science as a whole. I worked for AstraZeneca for just over ten years in their translational imaging team, which then led me to the creation of setting up a commercial imaging service for the broader drug discovery community, which then brought me into the catapult where we really strive to provide these technologies to our partners, to our innovators, to really showcase drug discovery and the outputs that it can have. We get really excited develop and describe a bit more today. That's fantastic. And it's great to hear that these types of expertise, services and expertise, which is not not common or accessible in industry is available for drug discovery, like you say, and it's quite unique and powerful sort of treatment options for patients. So could you tell us a little bit more around about those radiopharmaceuticals and what promise they hold, especially in comparison to those other targeted therapies and what advantages they bring to patients? Radio pharmaceuticals themselves, they stand apart from those other targeted therapies because they just don't work to block a biological pathway, which a standard pharmaceutical might look to do. They actually deliver that energy directly to the cancer cell. So instead of relying on that biochemical inhibition, what they use then is the targeting molecule that can carry that radioactive isotope directly to the tumour itself, and then once it binds it can emit that radiation directly into the tumour to destroy the cancer cell itself. So you know, and it's also sparing that healthy tissue as well. So you know it's essentially radiotherapy as a normal cancer therapy but in a molecular form that's able to reach those tumours anywhere in the body, which really importantly includes those micro metastases that might not ordinarily be targeted by normal radiotherapy in its simplest form. And I think because mainly many radiopharmaceuticals are theranostic, what you can do is you can use both the radiopharmaceutical to image and treat it at the same time, so you can see exactly where the drug's going, and then you can deliver that therapeutic dose with position. So you've got that accuracy, the visibility and the potency, which makes four-three together be so impactful for actually how it can treat patients. Yeah, so there's a lot of differences in comparison to those other therapeutic modalities and very precise, you say. So what is that? What does that mean for patients? How do they benefit from this? I think for patients as a whole is that we can literally precisely treat that cancer, but at the same time while reducing the burden of treatment. So often sometimes with a cancer therapeutic, it's not tolerated well, but also we can see those treatment effects and how they're going to work. So unlike chemotherapy, that will affect the entire body. What the radiopharmaceuticals do, they deliver that tiny, tiny amount of radiation to the tumour cells, you know, really means that there's fewer side effects for the patients and offers a much better quality of life for them, which is very important for the patients and for their families, as well as you know the outcome to treatment. And because it can directly target those metastatic sites, that's something that surgery itself can't do. So you know it's really making it much more accurate, more tolerated and more personal, which does a huge impact for patients and their families. And it also just gives real hope where other treatments just simply can't or have reached their limits. That sounds great. I mean, this is I mean, you've been in the field for twenty years, so is nothing new. This is, but it is still advanced technology. Why do you think it's now it's becoming so strong and at the forefront? Why is there a focus in this therapeutic area? So I think why it's so important now and where it's really kind of come to the forefront and to fruition, because for the first time, the science, the technology and the infrastructure have all aligned at once, which is pivotal to the success of the mainstream use of these. So we've known for decades that by being able to deliver radiation directly to a cancer cell could be really, really powerful, but we might not have had that isotope supply chain. We might not have had the chemistry nor the imaging technology and some of those imaging technologies like toasted body PET that's coming to the forefront. But that's all changed now, so now we do have better reliable isotope production. We've got access to more isotopes, the molecules themselves are better, so there's more targeting precision molecules available. With those advanced imaging technology like total body PET, we can see in the whole body where these agents go to. So clinically we're already seeing outstanding phenomenal results in cancers like late stage metastatic prostate cancer and neuroendocrine cancer, where we're showing that that approach truly does work and those results are game changing. So there are some real unique and distinct differences and like you say, advances in technology that's really enabled this space to flourish. And those differences in those with in comparison to other therapeutic modalities, it sounds like this needs a distinct sort of ecosystem to support the development. So how do you see regulatory agencies shaping the development and the approval pathways for radiopharmaceuticals? Yeah, that's such a really big and important part as well. So, you know, everybody is investing heavily in this space and I think we definitely need to have that collaborative approach with those regulatory agencies. So within The UK itself we're seeing real momentum from both the MHRA, how we're working with them, and also how we're working with the NHS around radiopharmaceuticals themselves. The MHRA is developing those clear regulatory pathways that recognises the unique nature of the therapies themselves, that it is a radioactive asset, and how you know we can work to get that regulatory piece to be safe for the patient, which is so important, but how we do that in a way that we can get NHS deployment in a rapid time that we need for our patients. And you know the NHS is actively integrating those diagnostics into cancer care, and that aligning I think between both the regulators and the healthcare system is critical, and we play a key role there in being that neutral broker, bringing the two together, because then it means you've got that faster clinical translation, but also a more streamlined approach for the patients who need the treatment, and a coordinated push together to make The UK a leader in radiopharmaceutical innovation in a worldwide place. Yeah, that's think it's really important having that ecosystem and within The UK that's flourishing and working with different sort of organisations coming together. And in this case as well, with, you know, Crown Bioscience and MDC coming together, how does this partnership address some of those critical needs in the field, but also on a sort of global space, I suppose, not just in The UK space? Absolutely. And I think, you know, it is a global partnership and we're hugely excited about it and how we can grow that into the future as well. So I think what brought Crown Bioscience and Metis Discovery Catapult together first of all was that shared vision to close the major gap in radiopharmaceutical ecosystem, know the bridge between discovery and clinical translation. So Crown Biosciences themselves, they have deep expertise in that preclinical oncology models. And MDC, we have quantitative imaging, we have radiochemistry, we have the infrastructure, the isotope handling and the translational development. And by combining the two of them together, that creates that integrated pathway right the way through from having the isotope to actually validating the target itself, and right the way through to first in human readiness so that it can go through that clinical trial commercialisation. And that partnership I think identifies the biggest challenges that industry face by turning those radiopharmaceutical ideas into clinically and commercially viable radiotherapy, only that we can do it faster, but also with greater confidence that it's actually going to work in the clinical situation and that we've characterised that pre clinically the best humanised way through this partnership. Yeah, so I think some really key points there. And just to kind of pull out that, you know, how do these drug discovery, these innovators benefit from this unique combination of MDC's expertise in radiochemistry, having the infrastructure, like you say, and then also Crown Biosciences translational models. That's something that's very unique, isn't it? Yes, hugely unique. I think that's where innovators can benefit enormously here because the partnership itself brings the best of both of the worlds together. So where we have our deep expertise in the radiochemistry and the isotope labelling, Crown Bioscience themselves, they have the translational models, we have the translational imaging, all of the imaging technologies that give that clinical output to test those therapies and those biologically relevant systems. And I think by combining those strengths, the innovators can move from what they have in terms of their molecule design to in vivo proof of concept far more efficiently, and for them it's reducing their risk for their investors, it accelerates their timelines, and it makes the kind of data that their investors need, but also the regulators take notice of to be able to take them through to IND and through into clinical trials. Yeah, that's it's really kind of interesting how there are so many components to this and it has to all kind of fit together. So it's great that we are leveraging the expertise and the capabilities as individual organizations and bringing them together. But, you know, looking forward, how do you see this collaboration evolving as the radiopharmaceutical field itself matures? Yeah, no, absolutely. And I think the collaboration will grow from strength to strength. And I think it will evolve into that true end to end innovation platform. Know, we have that already, but we can expand and grow and develop that. Whereas right now we're focused on bridging discovery translation, but as that clinical pipelines expand, can support everything from novel isotope development right the way through into early phase clinical trial readiness, biomarkers, understanding clinical effects of treatment. And whilst we're moving through that journey together, we can build those shared data sets that we're already generating. We can look at the predictive models, we can combine expression with the therapeutic effect and we can move that through into translation and we can integrate the imaging outputs that we're seeing into those workflows, you know, to accelerate those into the clinic. So ultimately what we're trying to create is that sustainable ecosystem where we're building the scientific innovation that we're creating now. We're looking at the clinical access and the patient access and keeping it all connected. We can look at models of resistance, know, we can really pull apart and be ready one step ahead as to how that radiopharmaceutical is evolving at a biological level. And I think that's exactly where that partnership is heading. As you say, it's an international partnership. We want to be worldwide leading in this space and doing that together. Yeah, that's really there's some really key things that you said there, but I mean, just focusing on that workflow that you mentioned and the timelines. So can you just kind of describe or walk through that journey of designing the radio pharmaceuticals from the sort of molecule to model? How does that work? I think it's a fascinating journey when you look at how you design a radiopharmaceutical because it starts with choosing the biological target, it starts with choosing the disease area and choosing something that's uniquely expressed only on cancer cells. And then next the chemist will then design that molecule. It can often be a peptide or an antibody and then that homes in onto the target. Then having that radioactive isotope, that's all about the next stage then of actually using that precision radiochemistry to create a compound that will both find and treat the tumour. From there it's then tested in those translational models to confirm that the chemistry is correct, that it will hit and target the right cancer cells, and then not only targeting the cancer cells, but that it will deliver the dose of radiation that we believe it will, and more importantly it clears safely through the body so we're not seeing any off target effects. So you know that brings us one step closer to a therapy, you know we can see it, we can see where it goes through, that it binds to its target, we can see that it's pathophysiologically working, we can see it's safe, and we can see that it's applicable to go into clinical benefit and that it's a surrogate patient benefits for treatment. So you know, it's a really, really exciting journey that you know, each step along the way in that journey is pivotal for the success of the radiopharmaceutical into man. Yeah, so there's quite there's lot of there's a multi step process, isn't it? So just focusing on that sort of early stage, you know, there might be some challenges in developing some of those radiopharmaceuticals, not everything can be made hot. So how does MDC's expertise kind of help overcome this and help the client to kind of navigate this space? Yeah, and you're completely right. Developing a radiopharmaceutical is incredibly complex because if it is a radiopharmaceutical it has the radiation in there. You're dealing with very short lived isotopes, you're dealing with strict regulatory controls, and the challenge of proving that they're safe, and also targeting accuracy all at once, And we want to help overcome those barriers by being predictive in those questions to provide the specialist infrastructure and expertise that most innovators don't have access to, you know, to give access and to have our ability of our radiochemistry lab technology capabilities, you know, to feed into that regulatory guidance and translational models, to move those therapies faster and quicker, but also to be predictive of how we can work those through in the next year. How can we show that those therapies, are safe in the long term? How can we demonstrate and feed into that regulatory documentation that we can then broaden how they're being used in different disease areas, treat patients earlier and not just in late stage cancer? So really making sure that we can ensure that we are keeping those position based radiopharmaceuticals as broad as we can, such that every patient can benefit from the amazing piece that they can be. At Crown, we're talking about the sort of making the translational models. We have a lot of different preclinical tools in vitro and in vivo. So you have the PDXs, CDXs, the cell line models, the organoids and syngenoids, as well as more complex systems like the humanized mouse models. So how do these specifically enhance that predictive value of the pharmaceutical development? That's what translational point of the development phase. I think those models are absolutely critical in that they will give researchers a much more accurate picture of how their radiopharmaceutical will behave in real patients, because the models themselves, as you say, they're so broad and they're ranging, but they replicate that human tumour biology. We can look at the immune response that's so important, the tumour microenvironment, know, the dosing can be targeted, we know what the minimum effective dose can be because it's in its humanised form, and it's making that translation into the clinic far more predictable and effective. It's de risking those phase one clinical trials. The models themselves have got such great intra and inter tumour heterogeneity, they're so well characterised that you can make critical decisions based upon those molecules and the models and the data that's coming out of that to feed into investor packages, but also into IND submissions to go into those clinical trials with confidence. So really is leveraging the expertise on both sides in radiochemistry, developing the radiopharmaceuticals and then downstream selecting the right models so that we really do get the right information, like you say, for those IND packages. So I'm just moving on to the sort of other sort of components that are important as well around the sort of translation and imaging. Why is and we talked about this a little bit, why is the translation component so important in this space? And that collaboration that we have, it helps bridge that preclinical research with the clinical outcomes. Can you just talk a little bit more around that? Certainly. So I think that translational component is so, so critical and vital because it's turning what is essentially a really opportunistic lab discovery into real time clinical therapies. Because the radiopharmaceutical demands such precise validation, understanding how they behave in living systems is really, really important, but pulling that back and you know really understanding and characterising it across the whole body, understanding how different organs are having that interplay, how we can also use radiopharmaceuticals in combination with other therapies, know is really really important, and I think it really brings that bridge between the clinical stage, the patient, and also you know being a laboratory desk based activity. So I think that is the critical and the vital part, and imaging that in real time. I think our collaboration bridges that gap, as I said, you know, it links the advanced models with their translational imaging expertise to then deriving an effective treatment for patients. So the diagnostic imaging then is often paired, like you mentioned, with the So how does MDC integrate those different imaging technologies with the evaluation of the therapeutic entity to really kind of provide the whole picture, the complete picture? So what will be the outcome of this? Yeah, so at MBC we're hugely fortunate that we have the diagnostic and therapeutic based imaging capabilities where we can integrate that into our projects, into all of our programmes. So we can use PET, positron emission tomography and SPECT, single focal emission tomography, to track exactly where that therapy is going. We can then understand the concentration, actually how much has reached the tumour, but also importantly the persistence, how long does it stay there, does it stay within the tumour. And I think that real time imaging links those insights into molecular design with the patient impact. It also leads to patient stratification. We can do smarter dosing, we can do better targeted treatments, we can look at that and we can combine that with standard radiotherapy. So you know we can do numerous imaging based technology assessments within the same subject as well, and then really linking that how it can lead then to more successful treatment outcomes. Because translationally and preclinically, are using those clinical imaging endpoints, we can take that information and then actually predict how that's going to work in the clinical situation. Yeah, so really kind of linking that preclinical very closely to the clinical outcome. That's fantastic and really is very innovative. And like I say, it's based on that technology. So then looking ahead, then what further innovations or new approaches do you see on the horizon for radiopharmaceuticals in the sort of next three to five years? I think the next three to five years is going to be such an exciting journey. I think there is so much more to come here. I think we'll see major innovation in radiopharmaceuticals themselves, the targeting ligands for different types of cancers and other disease areas that they can treat. We will see growth in the isotopes as well, not only from beta emitting isotopes, we've seen a huge growth in demand in the alpha emitting isotopes, that they can target double stranded DNA. Isotopes like lead two twelve, astin two eleven, you know, we can see on paper they've promised, actually getting access to them and putting them in real world translational and clinical trials will drive the tomorrow of the isotopes and how they can be. We've got artificial imaging, not only from artificial guided imaging that can personalise treatment in real time, but in how that can characterise probes and their ability to be successful as a radiopharmaceutical. Alongside that, think advances in the chemistry and how we streamline that production and how we can also use combination treatments. So by taking radiopharmaceuticals to deliver a therapeutic punch and then combining that with immunotherapy, potentially a small molecule inhibitor, really understanding how we can target that will derive powerful new ways to target and destroy those cancer cells, not only more effectively, but at a permanent level and actually have much more longer patient outcomes and patient free survival. So that sounds promising. I mean, there's a lot of opportunity here, a lot of data that's going to be generated, that's going to be very informative and understandably why there's so much focus in this area. So if you had one, if you had to share like one takeaway, I suppose, for biotech and pharma companies, what would that be? I think my biggest takeaway for biotech and also for pharma companies is that you know radiopharmaceuticals themselves, you know everybody can see the promise that they have, but they are no longer experimental. It's not just a vision, it's not just a dream, we're ready to scale. So everything is in place, the science is there, the infrastructure, the regulatory clarity, it's all ready to go. And I think what we really need now is that bold collaboration, working together, partnering early, really driving forth that pipeline, that translational science to decrease their development and accelerate their progress. And I think those that are investing now, they will shape the next wave of precision radiopharmaceuticals themselves, how we work together, and I think ultimately what we're going to show is that where we've done before, we've treated cancer, we've tried to treat cancer. We don't just treat cancer. We want to see it, we want to target it, and we want to treat it and defeat it at the molecular level, ultimately to derive much more longer term outcomes and patient free survival. You. That's amazing. That's going to be such huge benefit to our patients and the future of treating oncology. So thank you, Juliana, for a great conversation today. Really enjoyed and appreciate your perspectives on radiopharmaceuticals. And it's great to hear all about the advances, the innovative approaches in imaging, in radiochem, and also the animal models that really kind of are enabling the different isotopes to be used in such a precise way to tackle cancer. So it's been very informative talking with you. I look forward to catching up with you in person soon. Thank you. Thank you so much for having me. It's been an absolute pleasure and yes, very much looking forward to seeing you soon as well. Thanks. And to our listeners, thank you all for tuning in today. We really hope you've enjoyed today's podcast and found it informative and interesting. And if you want to hear more, then you can subscribe to Crowncast on YouTube, on Spotify or via Crown's website at crownbio.com/crowncast. 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