Esmé Walters: Hello and welcome to Cancer Connections, a new podcast from Cancer Research Horizons, which takes an in depth look at the expert ecosystem vital to helping us beat cancer. Cancer Research UK is the world's largest charitable funder of cancer research. As the charity's commercial arm, it's Cancer Research Horizons' job to maximise the impact of that research by turning discoveries into marketable treatments that reach patients with cancer. A huge part of that work happens through our expert network, a community of business, scientific, clinical, investment, and industry leaders. In this trailer episode, we'll be introducing you to the voice behind the series, your host, Parker Moss, and hope to give you a sense of what to expect from the conversations ahead.

Parker Moss: Thanks Esme, it is so good to be here. I cannot wait to get stuck into this Cancer Connection series. We've got some really brilliant guests lined up and I think it's a really positive thing to be doing So yes, I'll tell you a little bit about myself. I've got a... rather unusual background for someone working in this field. So my training was in theoretical physics and philosophy. That was my degree. had no to biology. I didn't even do A-level biology. ⁓ I into private sector working in ⁓ deep tech and telecom, and I was happy, busily away And then my life changed

Esmé Walters: Parker, thank you so much for joining us today. We are absolutely delighted to have you on board as the host of our new podcast, Cancer Connections. Now, throughout the series, you'll be sitting down with members of the Cancer Research Horizons Expert Network.

Parker Moss: very dramatically in about 2012 when my middle daughter at the time, Vanessa, who was four years old, was diagnosed with stage four neuroblastoma, for those unfamiliar ⁓ is one of the pediatric cancers that you really do not want to get. I up living on the wards in Great Ormond Street Hospital in London ⁓ My and I slept nights between us on that ward.

Esmé Walters: to delve into the human stories and connections that are really driving patient impact. But before we get started, we wanted to give listeners the opportunity to get to know you. Can you please walk us through your background and also what drew you into healthcare in the first place? You mentioned your board role at Cancer Research Horizons. Can you tell us a bit more about how you've worked with us and Cancer Research UK over the years?

Parker Moss: and I started. reading cancer research papers. actually was invited by the hospital to come and lead their technology strategy. So I actually started working in the NHS at the time. I remember reading Bob Weinberg's, Hallmarks of Cancer in 2012 and pretty quickly falling love with the field. And soon after my daughter died in 2017, I moved into the sector via a role in

Esmé Walters: I think you've painted a good picture of how Cancer Research Horizons helps bridge that gap between discovery and patient benefit. And with that in mind, what are you seeing in the cancer discovery landscape that gets you the most excited?

Parker Moss: venture capital investment with F prime and in that role I just focused on cancer, the tech bio thesis on machine learning and then I went back into industry, back into the public sector and I've done a whole range of things since then. ⁓ been on the Health Technology Board, I've been on the Cancer Research Board for seven years now

Esmé Walters: Three really great examples there. Now, the depth of your experience across the whole oncology ecosystem, what would you say is the most challenging aspect of translating all of this exciting and breakthrough science, like the in vivo expression of drugs that you mentioned, into real patient benefits?

Parker Moss: I led the commercial and also the cancer program at Genomics England for years and generally done whole range of things that me from living a patient ward, ⁓ working with cancer charities, working industry, working with doctors and scientists. So I'm a generalist, but with a north star and a real passion for this industry.

Esmé Walters: As you know, this podcast is called Cancer Connections. Why is making connections across the oncology ecosystem so important? Perhaps now more than ever.

Parker Moss: I was first introduced to the really chair of Cancer Research Horizons, Peter Chambré about...

Esmé Walters: I think you've really hit the nail on the head with it takes a village to bring a cancer drug to market. Can you give us an example where bringing the right people together, whether that be scientists, clinicians, investors or partners, made a real difference to progress?

Parker Moss: eight years ago and a year later he invited me to join the board. So I actually have just had my final board meeting after hitting my term limit at about seven years in. it's an absolutely fascinating part of the charity that I think not many people are familiar with. So, know, Cancer Research Horizon's role is really to convert Cancer UK funded science into patient And it does in a whole lot of ⁓ complicated ways. ⁓ helps functionally. discoveries that come out of the basic research. ⁓ helps license the IP for some of those discoveries. On we form and we fund startups to spin out those discoveries into companies. Sometimes ⁓ instead discoveries to be partnered with pharma or biotech and we set those up as well. ⁓

Esmé Walters: Throughout this series, you'll be speaking with members of our expert network. What excites you most about the conversations you're going to have? And if you could choose one thing, what do you hope listeners take away from cancer connections? Thanks, Parker. It's been great to hear more about the stories, both professional and personal, that have shaped your career across the oncology ecosystem, and we are so excited to hear the conversations that you'll have with our experts across the series. Thank you for listening to the trailer episode of the Cancer Connections Podcast. Subscribe now on Spotify, Apple Podcasts, or wherever you get your content to join Parker for our first episodes with one of the incredible experts from our network.

Parker Moss: Increasingly what we're doing is we're actually progressing the most promising drug discovery our in-house biotech which is called Therapeutic Innovation that was only formed a couple years ago. so all together CRH invest the 400 million that CRUK spends every single year ⁓ on cancer research we're constantly focused on patient need that is the kind of North Star that guides us ⁓ But also make sure that we focus on the difficult areas of cancer, like pediatric or brain tumors, which have proven be ⁓ both a scientific a commercial market failure in the past and without charitable investment probably just wouldn't receive ⁓ enough investment to make impact. just the most exciting time. If you'd said to me a ago that 2026... was gonna be a real breakthrough year in cancer research. I'm not sure I would have believed you, I don't know what's been in the water, but something has happened in the last six months, which has got us all really revved up. And a lot of the announcements were made in AACR this year, And would love to just mention a few of them. There's been a massive breakthrough in in vivo of drugs. ⁓ And I'm thinking of particular examples here. ⁓ So finally, it seems personalized cancer therapeutic vaccines are working. ⁓ been a strong signal that they've been in melanoma for a few years now, but BioNTech with MSKCC, so the Sloan Kettering Cancer Center New York, finally that we're getting ⁓ lasting remissions in one of the challenging cancers. and that is pancreatic cancer ⁓ that's really significant because unlike is a highly mutated hot tumor, pancreatic cancer is a cold tumor. So the fact that it has worked there really suggests that ⁓ it might work in other cold tumors brain and many of the pediatric cancers. So that that is thrilling. A second area that's really close to my is in vivo expression of CAR T therapies. ⁓ Now is a major break. It matters to me because my daughter Vanessa actually died on a phase one car T So I saw really up how toxic how complicated and slow ⁓ the design and manufacturing process of car T's are And the breakthrough in in vivo car is just thrilling and it's not just for cancer In fact, it may well break through first in immunology ⁓ and then move into cancer ⁓ But essence of it is instead manufacturing these complicated chimeric antigen receptors ex vivo in bioreactors and based on T cells taken from the patient. ⁓ big idea is that you use either mRNA in a lipid nanoparticle ⁓ a virus vector with a DNA vaccine ⁓ generate the protein that will reprogram the patient's T cells in the body. ⁓ that means that you should be able to do that without lympho depleting the patients or without wiping out their own T cells. ⁓ you may not have to give them such a high dose, causes a whole lot of toxicity, including cytokine release storms, because you may, be able just dose them every month, the toxicity and increasing the durability. ⁓ So that's a massive thrill. it's second example of drug that is essentially made inside the body. And then the last example ⁓ that I would be remiss not because it is just so and so unexpected, is that an incredible company. America called Revolution Medicine ⁓ has finally many many years of all of us trying managed to drug RAS mutation. ⁓ So I think people listening to this podcast will know that RAS affects about 30 % of all cancers, about 50 % of colorectal cancers ⁓ and 90 % pancreatic cancers. So it has been one of the major holy grail targets that we've been going for, but it's just been impossible to drug It's a huge and very smooth binding pocket without any kind of hooks for small molecules to ⁓ lock onto. ⁓ what this incredible company has managed to show ⁓ that they could drug a protein that was already present in most of our cells, a protein called cyclophilin. ⁓ it's using a small molecule, to ⁓ reform the shape of protein cyclophilin and that remodeled cyc cyclophilin becomes key that unlocks the RAS mutation specifically in the RAS on position and stops these RAS addicted from constantly proliferating. So it looks like we going to be at a drug RAS and that could really really change outcomes. ⁓ So when you when you of those three discoveries that just all have been brought clinical trial in the last six months and then you combine that with ⁓ major breakthroughs manufacturing. ⁓ Where I'm working the moment, I think we might be able to bring down the cost of manufacture nucleic acid drugs like ⁓ formulated mRNA by ten 20x in the next few I think we're going see that 2026 is the beginning of a wave major new breakthroughs that will not only increase survival, but also will really the cost and the toxicity. of drugs. So I'm feeling really fired up about the cancer market this year and I just can't wait to speak to some of the experts in the field to hear their take on the market. I think it is an challenge. Some people say ⁓ getting drug to a patient is like landing a space rocket on the moon. I actually think it's probably harder than that. In fact, from the perspective of a molecule going through the body to the target site of a cancer cell, it actually has to travel proportionally much further than a spaceship has to travel to the moon. And through a much more hostile environment, it's not traveling just through air and vacuum, it's traveling through of the most hostile, ⁓ and ⁓ environment, which of the insides our bodies and our blood systems. ⁓ So it's an incredibly challenging task and think very few people outside of our industry understand the true heroism of these drug discovery and target biology experts bring drugs to market. ⁓ the thing about it is it's not just one ⁓ single thing. ⁓ have to so many things right to bring a successful to patients. ⁓ So first have to off with exquisitely selected target biology. ⁓ And no matter how good drug if it's targeting the wrong thing in the body. for example, if it's targeting a passenger and not driver of cancer, the thing is wasted. So you've got to get your target biology right. ⁓ Then you have to have chemistry, which doesn't just bind the target, is non-toxic soluble stable and all of the rest of it. ⁓ That's the whole challenge of lead optimization, both small and large molecule And then even when you have your development candidate and is ready to go through through IND approval, there's then a huge risk, which you have to design exactly the right trial ⁓ to that new drug candidate patients. ⁓ And many, many target drug combinations have to to patients because people have ⁓ just not done a great of designing a trial that ⁓ evidences the well. So you've to design your phase and then your phase two and your 3 trial and that is not just hard but it's expensive so you've got to find investors to come on the journey with you and that means telling a story and that means hitting the road and doing hundreds and hundreds of investor meetings that not all scientists are well suited to doing or inclined to do so the money is a massive challenge. ⁓ finally you have to get through regulatory approval which is not easy and even once a great drug ⁓ achieved regulatory approval ⁓ have to get it's and then you have to convince doctors to actually use the Drug So you've just got to do a huge number of things right to get a drug to market. Cancer is the worst of all the modalities from that perspective. 95 % of all cancer drug discovery. programs fail. It's hugely, expensive. Attrition-weighted, costs over a couple of billion dollars to bring a drug to market. And despite the advances of AI, it's still taking 10 to 15 years to do so. So the dedication it requires for a team of people to get it there is just incredible. And I think that these cancer researchers should be celebrated. And I really hope that this podcast can be part of celebrating their just enormous achievements. Yes, I think that networking within any industry is generally understood by most people, but it is particularly important in drug discovery industry and ⁓ even so in the cancer discovery industry right now. So I in my previous answer, I gave you a sense of how it really takes a village to bring cancer drug to market. ⁓ But what I mention is the cultural differences between all of those different skill sets. So target biologists, chemists, ⁓ manufacturers, regulators, clinical trialers, investors, they really do have to work together. Often they come from very different backgrounds, often with very different temperaments. And to get a team of people to be single focus for not just a couple of years, but often 10 to 15 years on a single, single drug candidate and getting into patients is a massive challenge. And that requires knowing each other, liking each other. understanding where each other are coming from and that requires connections. So I think that's the first thing ⁓ to say. But it's important right now in cancer because ⁓ one of things that I would say ⁓ we have demonstrated in cancer and this is no longer up for debate is that ⁓ few of complex and particularly metastatic cancers are going to be ⁓ cured through single So not a single drug. ⁓ It is increasingly combinations that are being bought. together to cure cancer and that may well be for example this Razon inhibitor that I mentioned earlier, combined with a cancer vaccine, combined with a checkpoint inhibitor, may well be required to generate and lasting remissions. And so that to happen, ⁓ not only the different disciplines have to work together, but different companies, different startups and academic labs, and also Big Pharma, all have to work to bring these combinations to market. So I think now is a particularly critical time that we put ⁓ connected across the ⁓ both in the UK but also internationally. I'll upon an example when I was working at Genomics England. So at Genomics England, ⁓ we had the of whole genome sequencing, ⁓ a load of cancer patients. did deep sequencing of ⁓ both their germline their tumors. And we were sitting on ⁓ 100 petabytes of data across ⁓ a range of cancers. the same time, I had the privilege to be working with some of the best academics in the country and also people in the top pharma companies around the world. ⁓ I remember a couple of years ago studying of the algorithms that one of our top academics in Cambridge was working on. ⁓ And had created an algorithm could predict a whole genome a particular epigenetic feature called homologous recombination deficiency. ⁓ Now this flavor of HRD was not the normal coding based. type of genomic instability. This was specifically a type of HRD driven by promotomethylation. it suggested that there a whole subpopulation, in this case of women cancer, ⁓ who if had their whole genome sequence, ⁓ you could this promotomethylation driven homologous deficiency and potentially drug them a class of drug a inhibitor. ⁓ And at the time, we were working some of the pharma companies who were in the pop business and several of them had new pop inhibitors ⁓ to market ⁓ just by making that observation which just simply required having access to the data the people. I able to bring those three communicatives together, so the genomes from Genomics England, the algorithms from this brilliant academic, the asset owners in the pharma companies, to work on a project to trial and get access to this class drug to a new sub-population of patients that had not really been identified before, mostly whole genome sequencing hadn't. been widely adopted. That still hasn't come to market but it is ⁓ promising that it might do so soon. That just a classic example of how making a connection could really impact patients over a of years ⁓ and how don't have to be an expert you could just be a generalist like me to do so. ⁓ So I'm hoping that this podcast series will generate that type of connection ⁓ just by who are passionate about the field and are curious about asking questions and bringing in great minds together. Yeah, there are experts in our ecosystem who are working in just the most elegant areas of science, but who really get to tell their stories. ⁓ so this not going to be a technical research series, but I do want to ⁓ surface a bit of the science ⁓ and show little bit of the wonder ⁓ of what is inside the wet labs and also the computational to people who are maybe to this academic and bio... tech community. I really want to get the kind non-specialist listeners to hear the voices of these real scientists to get a sense of the energy and the momentum and the excitement of working in cancer research in this really extraordinary time. So I'm just looking forward to surfacing the science and also exposing some of the people who are my personal heroes. I think it's such a great opportunity to hear the voices of the because, you know, most people ⁓ confront either in very formal presentations in research seminars or via highly formalized and quite impenetrable research papers and research posters. And frankly, it's just not a very approachable field from the outside. ⁓ So the one I would like to do is just make it clear that these great scientists are approachable people. can call them, you can speak with them, you can bring them ideas, you can bring them investment and can connect them with each other. ⁓ So I can do anything just to increase the level of approachability for some of the great scientists in ⁓ our Cancer Research ecosystem ⁓ and share some the passion and the excitement of the science as well then I think this podcast series will have done its job and I'm really looking forward to on that journey. ⁓ Thank you Esme, I can't wait to get started.