Transforming Cancer Drug Development in the UK: Perspectives and Breakthroughs

Hello everybody and welcome to Crowncast. This is the podcast from Crown Bio, which aims to discuss the emerging trends and breakthroughs and viewpoints in oncology drug discovery. So it's bringing you some interesting conversations from scientific experts from across the globe. My name is Rejendra Kumari and I'm Executive Director for Integrated Solutions at Crown Bio, and I'll be your host for today's podcast. So I'm based in The UK. I've been with Crown for over twelve years and it's been it's a great privilege today to have two of my colleagues based here in The UK who will be giving us their insights into drug discovery and development from a UK perspective for today's episode. My first guest is Sarah Wagner. She serves as the Senior Director of Business Development within the Commercial team at Crown Bio. And since joining the organisation in 2019, she's played a pivotal role in engaging with a broad spectrum of clients across The UK and Europe, providing strategic support throughout all phases of drug discovery and development process. And my second guest is Brian Miller, joined the UK team in 2019 and currently serves as Director of Scientific and Technical Operations at Crown Bioscience UK and plays a pivotal role in executing and delivering drug discovery projects across different indications and therapeutic modalities. So I'm really looking forward to getting your perspectives on drug discovery in The UK, but before we do, just tell us a little bit more about yourself and what you enjoy about your role. Sure, so before joining Crane, I've moved from Germany to The UK to pursue a PhD at the Nottingham Trent University, where I worked on prostate cancer metastasis to identify novel biomarkers of disease progression. In parallel, I also worked on a project on acute myeloid leukaemia. Since joining Crown in 2019, I very much enjoyed a collaborative journey together with our customers, seeing them from a very early start, from the very first early essays to a late stage and even seeing those compounds move into the clinic. It's very exciting to be part of these journeys. So my background is on oncology. Following my PhD at the University of Leicester, I worked on two postdoctoral fellowships, the first at the University of Toronto and the second at CRUK. These were focused on in vitro and in vivo models of colorectal and pancreatic cancer. I then joined the CRO field in 2015 and have worked for Crown since 2019, where I currently serve as Director of Scientific and Technical Operations for our UK site. That's fantastic. So you have some great exposure into how drug discovery and development is shaping in The UK through all the different interactions with a wide range of biotech pharma and start ups. So let's start. So can you tell me how has the role of a UK based CRO evolved in the recent years in supporting these drug discovery programmes from early stage to right through to clinical trials? Over the last years, CROs have changed from a specific solution provider commonly to a more an integrated provider from a very early stage where you have your customers maybe in an in vitro setting to move on to later stages, translational biology and even into the clinics. I think you can find nowadays a partner that helps you through the whole journey. I think it's a very good point. I mean, what I found is that more and more clients are realizing the value of outsourcing work to CROs. And a good CRO will become your partner and will build a strong relationship with your company. And this strength of relationship and the strength of communication is crucial for making the most out of the client CRO relationship. Yeah, that's a really good point. And so do you think there are advantages of working with CROs within The UK? Are there any particular advantages or challenges that come with operating within The UK sort of regulatory and funding environment? I think being in The UK is a fantastic place to be for a CRO or for any researcher. The UK is such a vibrant place with we have the Golden Triangle, Cambridge, Oxford, London. We do have regular spinouts. We have big pharma companies that are still based here locally and certainly also a very, flexible approach from the from the UK government, very supportive with funding bodies such as Innovate UK or excellent centers such as the the Catapult Environment. I think it's it's offering a great opportunity for anyone wanting to perform research here. Certainly, Brexit, there have been a few challenges, but I believe these becoming smoother and are overcome with every month that we are progressing. And also, if you're based in The UK or within Europe, offers you a great opportunity to work with someone that's in the same time zone as you. So you have a very direct connection to someone. You can take up the phone. You can you can ring up your partner where you don't have an issue. That's maybe someone sits in The US or in China where you have a different time zone that could potentially delay communication. I think the other advantage as well, if sickly for in vivo studies, any in vivo studies are conducted in The UK are going to be performed to the very high standards of animal welfare. And I think that's, you know, a real advantage to run-in these studies because I'm a firm believer that you get the best science when strict welfare standards are upheld. And at Crown, we are very, very proud of our gold standard welfare, that we follow for all of our animal studies. Yeah, do see in my role agreeing with you, Brian here, I do see in my role regularly more and more interest on the very stringent animal welfare guidelines that are there. And this is just something that comes up more and more, also looking at potential replacements of animal studies, but it's very, very keen and key for our customers nowadays. Yeah, that's great. The three R's is really important to many companies, just in The UK but broadly as well. So in The UK the standards are very high and a lot of effort is made to ensure the studies are conducted, maintain high animal welfare but also critically gets high quality scientific value from the studies. So I mean there's a lot of innovation that goes with also improving the three R's as well as experimental studies. So let's maybe kind of focus on some of the innovation that's coming out. So what do you think are the key technologies that are emerging or transforming oncology research within the CROs? I can see two very common themes that are developing and are being utilised more. One is certainly a stronger focus on substituting of in vivo work, such as through organoid technology. I think this is offering a great option, have very representative models available without the use use of animals. We can see also there's a strong uptake. It's also seen with the FDA two point o, Act that this is just something that is more widely accepted nowadays, and is also more widely used. At the same time, I believe also AI, we all we all hear about AI and I believe this is giving us a great potential and exciting time to be in. I think we all need to see what a journey brings us with AI, but I believe it has a great potential in performing in silico approaches that we may just can substitute or replace certain actual experimental lab work that we're currently offering. And I think it's very exciting because it's just going to accelerate the drug discovery process. I very much agree with that. I think I'm very excited by the prospect of what AI can offer in the coming years. I mean, we're already seeing it, you know, have an impact on, you know, predictive drug design. And I can see, you know, huge potential with data mining, data interpretation, I think is going to be a real crucial part of drug discovery moving forward. How we're talking about data, I believe it is very, very critical on how this data is being handled and processed, because I believe there are so many companies, providers nowadays offering data, but data, I think, is a very broad definition. So we need to very much be careful about what type of data we're talking about, how this data is processed. Because if it's been processed in two different facilities or different approaches, the interaction and the mining approaches may not fit or may not work. So I believe it is very, very crucial to uphold very strict standards on the data processing, data formatting, and also keeping this data consistent across facilities, across companies to really use this value of the data. And what sort of other technologies do you think are helping refining some of the animal work as well? I mean obviously upstream the organoid is helping maybe refine downstream work, but when we're doing animal studies what sort of technologies have really been part of your exposure that you think is helping make these animal models more relevant to the clinic? I mean, think we've seen a lot of progress with particularly humanised mouse models in recent years and as these have increased in complexity and patient relevance, I think they've given a lot of opportunity to run very clinically relevant studies for clients across a number of different cancer indications. But if also the use of additional tools with these animal models actually increases the value of the material data generated, so including aspects of just tumor sampling and then the routine analysis of omics sequencing, mass spectrometry analysis, you just really use everything you can get from a single study and increasing I mean reducing costs. These kind of things are becoming a more commonly adopted. I think it is just makes it more valuable what you generate and also the animal that has been used. You can really get more information out of these samples. So you do a lot of, imaging in The UK. Can you tell me a little bit more around what the technology is available? We've got different imaging platforms. So we have an IVUS platform available, and this is principally used for bioluminescence imaging, but also has capabilities around fluorescence imaging. I also have an ultrasound platform available which has two main uses. Firstly, we perform a lot of our orthotopic implantations using ultrasound guided injection, and this has the advantage of being much better for the welfare of the animal. So it's much less invasive than traditional surgery, and the animal recovers, much faster. And it also is quicker than traditional surgery as well. So it also allows us to implant larger studies for for our the topic models. And the second use for ultrasound is in tumour measurement. And this is particularly useful if we're working with material such as PDX, which is not suitable to label with bioluminescence or fluorescence, we can still do in life measurement of tumour volume using an ultrasound platform. That's great. Mean, there's some fascinating areas of technology that's really kind of shaping drug discovery today. I'm just going to go back to one of the points you made earlier about how there's a lot of teamwork and interconnection between the sort of different entities within The UK. There's a real sort of ecosystem at play here. So what's your opinion perspective on how different institutions work together? So UK government initiatives or funding bodies like Cancer Research UK, other institutions or infrastructure supporting research such as mentioned Catapult before. And these are really kind of shaping how the different roles, the different sort of entities play together, including CROs, how they work together. So how do you think they work together well in The UK? Think there are different aspects. For example for Innovate UK or Funding Buddies, commonly want to have a commercial collaborator involved in this. I believe was to progress the programme faster. Then you have aspects such as Catapult initiatives which are offering expertise in a field that's commonly not every CRO already any researcher can actually have and you can tap into their vast knowledge in this field. And I believe through the collaboration across funding bodies, researchers, potentially biotechs, they're also collaborating with our large pharma companies, getting access to their knowledge. It's just offering a great potential to progress their compounds through the clinic or to the clinic. I think we all have to work together because no one can be a specialist in in every single topic. And I think just this this flexibility to work with whoever you would like to partner who has this capabilities is just something unique I've seen in The UK. And it's just... Yeah. Think it's very, very true. And The UK has recently rejoined the Horizon programme as well. So there's now opportunities for, you know, UK companies to also be involved in European wide consortiums also. Yeah, that's great news. Yeah, there's a lot of, like I said, interconnection and that sort of research ecosystem. And with that in mind, sort of looking ahead, how do you see the landscape of oncology drug discovery shifting in The UK in the sort of, you know, five or ten years time and what do you think the role of the contract research organisations have in shaping this future? Yes, I'm actually really excited by, I think, lot of the prospects that are coming out over the next five, ten years for drug discovery in The UK, I'm seeing a lot of exciting progress on personalised medicine. I think there's a lot of potential around cellular therapies as well, particularly CAR Ts. I think we're going to see a lot of exciting developments there. And as well, I think the prospects for treatments such as oncolytic viruses and radiopharmaceuticals will give us great, great opportunities coming up. And CROs will be at the forefront of supporting clients to drive this forward and drive this innovation. Yeah, I can see CROs to take a very strong position in future in the next five to ten years, considering that many new companies are virtual companies. They need a trusting partner to progress their medicines into the clinics. Whether it's in a preclinical space or in a clinical space, this partnership will take a more central role in future. That's a really good point. So Sarah, I just want to expand on that. So, I mean The UK is thriving with new startups, new ideas, new innovation. So, we see a lot of, virtual companies, startup companies who are requiring that expertise. Like you say, no one organisation holds all the expertise, so they need different partners, to work in that space. So they really rely on the sort of CRO partnership. So what advice would you give to those small startup companies or smaller companies to get the most out of their collaboration with CROs? I think the best see your trusted CRO as a partner rather than a service provider. CROs commonly have fantastic scientists. They've seen a lot of compounds go through their hands. They have this experience. Just listen to them. They commonly have to experience. They can help you and advise you on maybe how to adjust the design of your of your study or what additional points or experiments you should conduct to make this a bigger package. However I do also recommend be upfront and transparent. Share with them what are your goals? Where would you like to get to? When would you like to get to there? When what is your timeline? When do you need these these results for potential new seed round? Just interact and and work with them as closely as possible. Many of us are scientists. I'm a scientist myself, and we actually very much enjoy working together in a new and exciting adventure with you. I completely agree with that. And I think, you know, choosing a CRO with a strong collaborative culture is is, you know, very, very important. And as Samara says make full use of them and their expertise. I'm a great fan of meetings, particularly in person meetings, go visit the CRO, meet the wider team. If you're doing an in vivo study, go see your animals, see how your study is being conducted. A good CRO wants to build that partnership with you and will be very transparent with you about your work and how the study is conducted. So that's really good points there and Brian I just want to again maybe expand a little bit more because you talked about how working with different therapeutic modalities like oncolytic viruses, cell therapies, radiopharmaceuticals those types of modalities really require a close partnership and a very local partnership. Tell just us a little bit around maybe why that is and how, you know, being in The UK really facilitates those companies working with those therapeutic modalities. Yeah, particularly for test materials such as viruses or cellular therapies, I think there's a lot of advantages of working with a local provider. In particular, it takes all the uncertainty out of shipping and customs requirements if you are working with someone who is local to you. So you mentioned earlier the models becoming more sophisticated, such as the humanised systems and using imaging to do orthotopic and metastatic disease modelling. How do you ensure the ethical standards are maintained and the quality of those models? Yes, it's a very good point. I mean, particularly if you're working with humanised models and you're working with primary human tissue, it's really crucial to ensure ethical use of that tissue. At current bioscience we do have a human tissue authority license and we have all the processes in place to ensure that the tissue that we are using is being used in a way that's consistent with consent given by the original donor. In terms of animal welfare, do have strict standards for our welfare requirements. We work under our home office project licenses and we're regularly inspected by the home office. And we do have, you know, a team that works within Crown to ensure full compliance with all, you know, animal welfare legislation, and ensures that we are code the highest possible standards of welfare in all of our studies. And I think another thing that's actually crucial in terms of data integrity is ensuring you have a strong QMS system in place. And this ensures that the highest possible quality standards are maintained and also helps guarantee data integrity. And working with the companies at different stages, obviously there's discussions, early discussions that are had with the customers to understand their projects. So Sarah, you're very heavily involved in this stage and then it's moved to the operations team. So it's a real team effort here in The UK and like you said, it's a close partnership with the customer as well. Do you want to kind of talk a little bit around the communication or how you operate within Crown UK and also with the customers on a day to day basis to ensure their studies are being communicated on? Sure, so I'm acting as a first point of contact within the company. Commonly I'm at the forefront. However, what I very much enjoy and very like to do is to get our scientific team involved as early as possible. While I do have a PhD in oncology myself, I do think the more experienced scientists we can have in these early stage discussions, the better the outcome will be. Also for customers that we're working with regularly, we do already have a designated study team. I would say I quite enjoy taking the study team directly with me to the customers. We visit them directly to ensure we're all on the same page and there's nothing missed in our communication from the handover from the study discussions to the actual study execution. Yeah, completely agree with Sarah's point. I think that we have got a really good collaboration between the commercial team and the operations team at Crown, And I think that's really, really crucial, I think, to providing the best possible services to our clients. So CrownBuyer actually operates internationally. So how does The UK fit into this sort of global strategy and how does that benefit the partners that we work with and the clients who need different services for oncology drug discovery? I can see over the last years that there's been more of a drive to buy local, shop local, have a local point of contact. Within The UK or within Europe, you have people like me who are actually based physically in in The UK and also our team that is locally available to you. The choice of going local can be various. It could be because of logistics. It could be off because of funding sometimes, such as in a way you innovate UK grants are very much specific to business conducted in The UK or because you would like to adhere to certain standards that are more commonly applied in Europe. However, we understand that not everything will be available everywhere. But at Coronavirus Science, we for example offered the solution also to perform work in another facility such as outside in The US, where they're very much specialized on on biomarkers or other systems. However, we can still keep that central point of contact and the communication for you in Europe, which many find very, very useful to them. Because as I said before, you can just take up your phone and call your study director just half them at the same time zone as you. Yeah, I completely agree with that. Mean, at The UK site we work very closely with the other CRAN sites and it's great to be part of this global company and to be able to draw on the expertise that the other sites offer as well. Something we do in multiple studies is we actually manage them from The UK, even though some of the work may be performed elsewhere within Crown. We found that's been a very successful way to make the full use of Crown's capabilities available to our clients. I think we should also highlight here, when we're running work at different facilities, we want to make sure that our customers have the best team on their study and on the specific work. We can see sometimes certain markets, you may have already established a different facility, and we really want to make sure you get the best out of the experiments that we conduct. That's great. I mean that really is a huge benefit to have not only just a local team who handles all the communication, the logistics, but an international based team that also can then support studies further. Real integrated offering here. So that's a really sort of exciting area because Crown has grown and grown and it's meeting those client needs. Like you say Sarah, it's important that we understand, have those discussions with the customer as early as possible to understand exactly what they need and then find the right solutions. And it doesn't matter where those solutions are, you'll be the team in The UK that's helping coordinating all those different integrated offerings across the globe. Okay, great. Any final remarks or comments or advice for our listeners? Personally, as I said before, a partner, not only a service provider. I think that will make your journey the most exciting and the most successful route. And I also personally, I'm actually very excited on where we are at the current stage with all these new technologies that are becoming available from organoids to AI to the more routine use of sequencing or mass spectrometry. I just feel there's such a potential that we're just tapping into. And over the next years, this will just be a great big adventure. And I believe it will help us to bring new medicines to our patients or to patients faster. And I think that's our ultimate goal. Yeah, we've recently launched a strategic partnership with Medicine Discovery Catapult to deliver radiopharmaceutical studies to our clients. And what I'm finding is there's increasing amounts of interest in radiopharmaceuticals and the exciting potential of them in oncology. So I'm very, very excited by the prospects in the coming years of working with Medicines Discovery Catapult to deliver those studies for our clients. Well, mean, that's absolutely exciting. There's some real advanced technologies that are being employed to really help our UK customers in progressing their agents forward to help our patients. So thank you Sarah and Brian for a great conversation today. I really enjoyed and appreciated your perspectives on drug discovery in The UK and some great advice as well from you both. I think it's really nice to see the faces who will be interacting and helping those projects move forward. Obviously there's some great things happening, great technology that's been utilised and your enthusiasm really makes it easy to work and understand how they can be applied to the different projects. So I look forward to seeing you soon in person. I hope you have a great rest of your day and then to our listeners as well, thank you all for tuning in today. I hope you have enjoyed today's conversation and found it interesting. If it was and you want to hear more, then don't forget to subscribe to Crowncast on YouTube, on Spotify or via Crown's website. So that's at crownbio.com/crowncast. Until next time, have a great day.