In this episode, we tackle these questions while exploring one fundamental issue: Why? Why is it essential to continue innovating to broaden patient access, develop new therapies, and push the industry forward?
Guests:
- Tay Salimullah, Chief Access Commercial Officer at Novartis
- Jason Jones, Global Business Development Lead at Cellular Origins
Setting the scene: progress and challenges in cell & gene therapy
[00:00:05] Stuart Lowe The cell and gene therapy industry is rightly proud of its achievements to date. New approvals are being announced almost monthly, and treatments for indications with much larger patient populations are on the horizon. Though with high price tags and cumbersome manufacturing methods, are we doing enough to ensure that the benefits of these therapies are going to be accessible to all those in need. In order to bring down costs and streamline manufacturing, where should we turn? Traditional methods of process development rely heavily on legacy equipment and labor intensive handling steps. Decisions that are taken early on in a therapy's development can have a dramatic effect on the ability to scale manufacturing. And this can result in considerable time and expense in deploying the processes in production. So today we ask, can new ways of thinking about process development allow cell and gene therapies to scale to meet patient demand? Join me, Stuart Lowe, as we uncover the future of cell and gene therapy. In this episode, I'll be joined by Tay Salimullah and Jason Jones. Tay is vice president, global head of value and access at Novartis Gene therapies, where he helps build global access to cell and gene therapies. Jason is a Global Business Development Lead, a Cellular Origins, an organization that brings advanced robotic automation to the cell and gene therapy industry. In this episode, we set out to answer one question, why. Why is it imperative that we move forward? Why do we need to continue innovating in this field? And in exploring this question. We'll come face to face with some of the issues facing the cell and gene therapy industry, and gain insight into the steps we can take to propel us to where we need to be. I wanted to start this conversation with Tay and get his thoughts on where we are now, where we're going, and of course the why. Hi, thanks for joining us on the TTP Event podcast. It's really good to see you. Could you introduce yourself and say a little bit about what you do at Novartis?
Introducing the guests
[00:02:40] Tay Salimullah Currently, what I do at the AveXis, which was bought by Novartis, a gene therapy company, is I head up there a chief access officer role looking at worldwide commercialization of one time regenerative medicines, whether they be the gene therapy, the proprietary technology. Being part of the executive management team, where really indexed on how we take these 21st century medicines and make them a relevant therapeutic category for patients, families, caregivers around the world in health care systems, frankly, designed for chronic treatment and follow up. [00:03:24]And there, like [0.4s] the polarity, where you have a medicine that potentially can hold a disease in its tracks or change the natural history of the disease. You are dealing with healthcare systems that were really built around ongoing chronic management. So that's what we do, and that's what energizes us every day.
[00:03:43] Stuart Lowe If you think 20 years ago, some of these conditions were more or less a death sentence, and now it isn't. How far are we along that road to being able to treat everybody who needs treatment with some of these new 21st century medicines?
From hope to reality: patient impact of regenerative medicines
[00:03:59] Tay Salimullah It would be disingenuous to say at the point of we've reached summit far from because, look, let's go back a little bit. We work in an area where you work on 90 percent plus rates of failure and learning. So every nine medicines out of ten, potentially won't make their way forward. That shows you that there has to be a mindset of resilience, of once you fail, you have to pick up and restart and make sure you keep driving forward with purpose. Coming back to the area of regenerative medicines, there was some recent data from the Alliance of Regenerative Medicine that basically published [00:04:43]bio has this Accurus [1.0s] published on it that it's 3.5 times likely that you'll see approvals for these types of therapies. These regenerative medicines versus standard drugs, 48 percent in phase one, 65 percent in phase two and 30 percent in phase reverses the standard approvals. And why is that? Because you're really looking at very specific populations. You're looking at the mutations of those populations. You're looking at potentially trials that allow you to not go very broad, but go very specific in terms of the label population. And what is that resulted in just where we react in terms of on our journey to summit is we had five approvals in the space between 2017 and 2022. Only last year in 2023, we had five approvals for gene therapies for DMD, for Hemophilia A, for sickle cell disease too and then one for this condition called Dystrophic Epidermolysis Bullosa. In 2024, we're slated in Europe and the United States potentially to go between 12 and 17 approvals.
[00:06:01] Stuart Lowe After hearing about the potential benefits for patients, I wanted to know more about how healthcare systems are adapting and enabling the commercialization of these therapies.
Commercialisation and healthcare system deadiness
[00:06:13] Tay Salimullah I'm going to do it in two parts. The first part is when I say start with the commercial or the potential in mind, what does that actually mean? That means double clicking into the diagnostic odyssey of what patients and families caregivers go through on a daily basis. So what I'm saying is we want to avoid even pitfalls of the past where products got approved and then they were withdrawn. We're talking, for example, like we're talking about heart therapy that tried to get to Europe and then they couldn't commercialize. We don't want any of that. Right. This is the pain the early innovators have paid for paving the way for others to come.
[00:06:57] Stuart Lowe Yes, exactly. We don't want to have to go down the same path. Right? We want to learn from it.
[00:07:01] Tay Salimullah You got it. You got it. And that's why I hone in on what is the potential or what are you trying to address. And it starts by that deep journey you take one thing. What is it we need to solve for that patient? In the area of spinal muscular atrophy, patients who don't live very high percent of natural history, 80 percent plus don't get to see their second birthday. So how do you make sure that a copy of the SMN1 gene that is then put into the patient helps course correct and ensure that verse is not from history of patient can live a normal course of life. Achieve milestones that you and me may have had as a given, which is sitting and standing, walking and talking, swallowing. So this is really important and that helps you shape the unmet need you're going after versus the standard of care. But let's say, for example, you and me have a bias towards the therapies and we want them to do well. But really we should suppress that bias and say, what is it the therapeutic gain we're trying to achieve in a sector of autoimmune disease or in oncology or inhibitor. And can gene therapy, can cell therapy help us elevate that net therapeutic gain as an enabler? Not the other way around that I have this technology and I'm going after that disease. No, you need to know are you going off to survival? Are you going after making sure that a child no longer needs to sit on a ventilator? And these markers are huge, and I have seen an openness from regulators around the world to try and help manufacturers on that journey and really crystallize what that right development looks like. Then what is the comparator? Because if you don't do all that work upfront, what actually happens is you then get to regulatory approval and say, that's fine. Then you get into the market and what happens is you start hitting all these hurdles where you get compared to standard of care or you get and missed an endpoint. So this is really critical.
Early decisions that shape patient access
[00:09:01] Stuart Lowe It seems like decisions that you make really early on in the development can have a significant impact on patient access downstream. What do you think the key decisions people need to think of when they're developing the therapy? And how does that kind of flow through to whether it's going to be a success or not in terms of the patient?
[00:09:20] Tay Salimullah Very good point. We often say there's two things that make or break these types of therapies. The first is an upstream one, which is very close to what you guys are doing, which is the manufacturing. Right? Can you have producer reproducibility from trial to commercial product? Can you actually scale? Do you have enough material partnerships to actually then make what you need?
[00:09:50] Stuart Lowe As Tay mentioned, in the cell and gene therapy field, the question of patient access is intertwined with our ability to produce the necessary doses at scale. I was interested to hear Tay's perspective on how choices made during process development impact on the ability to scale manufacturing. There's a few things that I'm just going to pull together that might be interesting to look at. Thinking about time to market from bench to bedside, that development pace where you're looking at the processes and you're trying to make improvements, how can you make that part faster? But it's also deciding that the manufacturing scale might be easier, so that it's easier to deliver so that the storage is less cumbersome. I mean, there's all sorts of decisions you could make. How do you need to organize yourself so that process development is streamlined.
Manufacturing and the power of partnerships
[00:10:43] Tay Salimullah Look, there's so many themes in all of that, whether you're working on autologous therapy, allergenic or [00:10:50]simply AAV [1.4s] type intervention. And you already started answering that in a thoughtful way around, you've modulated manufacturing. Then you thought about, okay, we're now [00:11:02]into man [0.4s] or in the clinic. So where do we choose those sites? Because imagine like if you're dealing with monogenic diseases, there is certain disproportionate populations around the world that are impacted. You know, you have to be thoughtful around that as well. Populations shouldn't be an afterthought.
[00:11:20] Stuart Lowe No. Where should you site your trial?
[00:11:23] Tay Salimullah It's exactly the strategic decision and [00:11:27]recu [0.0s] that you need to do and say, how do we make site readiness happen? And because you could imagine that some of these sites will be doing this for the first time.
[00:11:35] Stuart Lowe This is it. So some of the manufacturing processes, they can't be things that you need to have ten years training to be able to operate.
[00:11:42] Tay Salimullah I think partnerships is big for me because through this sort of, I would say, almost a decade of in these platforms. I found that we would never have got to where we got to without the purpose partnerships that we built. And with a for there's two types. One is on the manufacturing side, on the upstream side, on diagnostic side, on making sure therapy can be shipped around the world. And then on the other side with payers, physicians, patient groups. And I think all of that allows you to challenge your bias and be developed solutions that are potentially then going to last and be executed. Otherwise, you're pretty much trying to lead your the blind versus the blind and doing something on your own. And that for me is not very conducive in this space.
[00:12:38] Stuart Lowe How about the diversity of modalities. Right. So people talk about cell and gene therapy. And then you've obviously got engineered cells. You've got gene therapy. But you've also got things like TILs as well. How does the industry cope with the just the sheer diversity, because that's quite difficult to put into a one size fits all biologics or small molecule thinking. Yeah.
Adapting to a diverse therapeutic landscape
[00:13:00] Tay Salimullah It's a good question. But the gene editing and we had the first gene edited sickle cell disease product approved from CRISPR. I think when Novartis is not an inch wide foot deep on the cart platform, and then the next generation platform that they're developing, and then certainly in the AAV space, and then that went to a realization of, oh, we need to improve our game in the capsids and making sure that if we want to get to areas of the brain, how do we do that? Build another partnerships. So often a view that you go a foot wide and an inch deep, or do you go an inch wide and a foot deep?
[00:13:35] Stuart Lowe So yeah, there's a case of elevating, and there's also an approach where you maybe make some pragmatic compromises in order to reach that goal of saying, I do want to treat those 80 percent of patients. I wonder if you've come across any approaches that work particularly well, that or maybe you're surprised that it was done in this way, but proved to be particularly effective.
Patient-centered innovation and global access
[00:13:57] Tay Salimullah So remember I said to you, you may recall in the early part of this discussion a few times, that deeper understanding of what patients and families in the diagnostic odyssey, what did people go through on a daily basis? So about five years ago, we started an effort with the government of Ghana to look at newborn screening diagnostics and access to basic medications, pain vaccines and hydroxyurea. And now it's scaled up to four or five different African countries, multiple partners. The reason was what is the point of having gene therapy or cell therapy for sickle cell if you can't preserve the organs and make sure that Tay and Stuart have access to the basic standards of care? It doesn't make sense because your baseline characteristics will be way worse off if you don't get that when you get the gene therapy. So you have to almost, when I say to go inch wide, foot deep, you have to play the long game. There has to be those elements of I said partnership. But once you understand what you're going after, then it allows you to then tailor your trials and your interventions to ensure that the magnitude of benefit that your interventions can potentially get in the TPP is has a maximum chance of success.
[00:15:18] Stuart Lowe It was fascinating to hear Tay's views on the motivations for adopting new technologies within the pharmaceutical industry. At the end of the day, it clearly has to be driven by patient need. But with new modalities, challenging development and access models. I wondered whether any lessons Tay had learned about fostering innovative thinking within large organizations. What does a big farmer like Novartis get out of the equation, right, to described what of access gets out of it, but what is what is Novartis got out on there?
Big Pharma and the playbook for regenerative medicines
[00:15:58] Tay Salimullah So AveXis Inc now, which is formerly part of Novartis, the parent company. Imagine the journey is you start off in a very small organization. You're very innovative. You are able to take, I would say, create a new playbook for how you develop these, I would call it sometimes Star Wars medicines work and co-create with regulators a pathway to potentially how they will be approved and then work with [00:16:27]HTM regulatory bodies [1.4s] around the world to see how would be evaluated, and then work with patient groups in society to make sure there's an understanding of how these treatments would be used in the real world. And you've got to imagine in the 80s and 90s, early 2000s, and the history of big pharma has been really indexed around small molecules, biologics, vaccines, and they've learned there are and done it extremely well. And they have automated systems that are able to get pills of the past into a pharmacy. But you now have autologous treatment. You have treatments where you need to get the diagnostic right, the tightness of the patient. You need to get make sure that the product is then available,all stuff you guys are familiar with in the card space and even in the gene therapy space. All of this is almost sometimes in reverse. You're thinking about the patient first. Making sure you understand where the patient is geographically, where the physician is at, then you're actually shipping product rather than the products already there. And you know, at times for folks, it can be a nuanced puzzle, but it's actually very energizing and rewarding to try and work with like minded people who are really trying to elevate the industry's impact by bringing these one time, I would say, curative potential regenerative medicines to patients. And I actually thought, honestly, my lifetime warranty moment like this.
Milestones and lessons from Kymriah
[00:18:00] Stuart Lowe It's been very kind of inspirational speaking to you about this and really, you can really tell the passion that you're steeped in the industry. When we look back at history and say, Kymriah being the first cell therapy on the market. Will people say that was a big milestone, that was the start of something. And what do you think people will think about that moment in the future?
[00:18:23] Tay Salimullah Yeah, I think it's a good plan. I'm thinking we are in this sort of polarity of these 21st century medicines in healthcare systems designed for chronic follow up care and Kymriah, for me, it's in some respects it was that first approval that gave the oxygen for others to also say this can happen. But it was full of a playbook of learning. I think, fast forward to 2024 or now in this period of as I said, we've reached nearly, you know, 4000 patients with our AAV and sometimes often from the outside and people say, oh, wow, that's a slam dunk and it's a unicorn at times. And there's different words people use. But all I can say, again, just to bring it to reality that we went country by country, plan by plan. When I say plan by plan, state by state, payer by payer, policy by policy. To make sure that we could provide a opportunity to partner without making someone feel vulnerable and at the same time co-create in a way that would allow and serve as an example for others to come rather than be a reservoir and we say we done this all ourselves. When recently someone in the executive role and a board member said to me, we probably don't need to do some of that hard work now. That was nice, because that actually tells me that now is being received in service of the industry and that for me, I think is a more purpose driven leadership rather than your reservoir, and you take everything for the hero for the day.
Key takeaways from Tay: access, partnerships, perseverance
[00:20:18] Stuart Lowe I really enjoyed my conversation with Tay. It was interesting to hear his perspective on getting therapies to patients and what we need to prioritize to broaden access. Some of my key takeaways from our conversation were. Understanding the patient journey. We can't disregard the impact these therapies are having on the lives of patients. And this is actually driving innovation in health care systems to widen access. The need for partnerships, Tay highlighted that the real path forward involves partnerships across countries, companies and health care systems. Collaboration is key to progress. Perseverance is essential. Tay mentioned that we are far from the summit. While we've made significant strides, we still have a long way to go and must keep pushing forward and innovating. Next, I spoke with Jason Jones to get his perspective on the why. Jason is passionate about the power of automation to scale therapies. Like Tay, he wants to streamline processes to make this a reality. His why is closely tied to his conviction that we should be doing more with automation. He explains how he's finding new ways to augment legacy processes so they can meet the future needs of the industry. Hi, and thanks for coming on the TTP Event Podcast. It's really good to see you. For our listeners, would you mind just saying who you are and and what you do?
The role of automation in scaling therapies
[00:21:58] Jason Jones I'm Jason Jones. I'm the global business development lead for Cellular Origins.
[00:22:04] Stuart Lowe And what does that involve?
[00:22:06] Jason Jones Considering that I'm in the company of biologists and engineers, I describe myself as the talky one. So essentially my role is to maintain and develop current client relationships, bring in new clients, and develop those relationships. We have a lot of partners in the industry, other technology companies. We have a very collaborative approach, so developing, maintaining those relationships to his business and paperwork and anything business development wise around that. The sales that I'm into, into marketing element as well. As typical to a lot of startup companies, a bit of bit of everything. But yeah, anything in terms of the external, well, our industry is viewpoint on us and our viewpoint of that.
[00:22:49] Stuart Lowe I think that's really interesting viewpoint. You're seeing things from start up in the ecosystem, but also you get to talk to end users, like pharma companies and other technology providers as well. Is that a fair characterization?
[00:23:05] Jason Jones Absolutely. It's a proper trans industry point of view. A lot of trans industry touch points, which is fantastic. Because you'll gain from as this conversation as we go on. I've a real passion for this. I've had moments over the last 20, 21 years where I've wondered about being in this industry, but always I return to the fact that this is something along my horizon and that we've got to achieve the things we want to achieve in it.
[00:23:31] Stuart Lowe From where you sit today. Would you say that we are getting quite good at making CAR-T therapies at an industrial scale?
A manufacturing crunch point
[00:23:37] Jason Jones I'll be able to say no, just qualify that. So people say what has changed since in the last 20 years in terms of challenging manufacturing? In some ways a lot, but in many ways not a not at all, in fact, to a disappointing degree. So have we got good at it? I think we've got good at making do, and I think we've got good at squeezing every ounce of potential out of the kind of technology that we use at the moment and of experienced and qualified people in manufacturing facilities around the world now, in terms of what kind of production output we can achieve.
[00:24:16] Stuart Lowe So you're saying you feel like you're ringing out the last few drops from our kind of capability at the moment? What does it look like if we continue down the path that we're on.
[00:24:26] Jason Jones As of this year onwards, actually, we're approaching some kind of crunch point here. I think if there's a [00:24:32]cliff edge. [0.3s] I can always visualize in grassy cliff edge that you're skidding towards and one of those kind of horrible dreams. I think cell and gene therapies going from strength to strength. And I think a lot of the milestones have been achieved this year. I think we're going through transition. It's not slap you in the face, obvious. But we had the big advent of a pre therapies 2016, 2017 [00:24:58]was June various [0.9s] with Kymriah with it's CAR T getting approval and coming of the marketplace. That's fantastic. But really what's happened since, and yeah of course a lot of work but not in terms of approvals. Yeah. And no, in terms of patient access, companies like Novartis and Kite have done incredibly well to ramp up to me as many of their patients as they can. But leukemia and lymphoma is the tip of the iceberg. And I say tip of the iceberg. I don't even know if we knew it was an iceberg, because what's happening now? So with the advent of the approval of Cascade last year, that's a gene modified stem cell therapy for a six hour anemia and transfusion dependent B thalassemia. Those are not small in patient numbers, not really far as it can reach. You add into that, then this year we've had the multiple myeloma CAR T therapies, BCMA Carvykti achieve in second and while putting in respective order third line is second line treatments. We're now at a stage where we need to ramp up to be allowed as an industry to be able to produce tens of thousands of products a year rather than the thousands we've been achieving now. So a log difference minimum.
[00:26:16] Stuart Lowe Take us through our cell therapy manufacturing facility, right now, what does that what does that look like? You paint a picture for us.
From lab to factory: a new vision for manufacturing
[00:26:23] Jason Jones Firstly, it's a clean room. I think we, if we like, say one thing we've achieved. We have managed to close a lot of processes out. On the hall, you might find yourself in the grade C or D clean room these days, but there will still have to be a grade A or grade B, clean room with [00:26:39]a great air [0.3s] and somewhere nearby or an isolator, because still things like raw material preparation essentially needs to be done in a grade A area. Everyone will be gowns, everyone will have been trained to be gowned and and signed off. They've been trained to be gowned. Sterility is still absolutely top most of everyone's thoughts. Everything is [00:26:58]SOP led. [0.5s] You will see pieces of equipment in there. There are those islands of automation like [00:27:04]talking about best [0.2s] and they'll be cell washers in there. In fact, even prior to that, they'll be thawing devices, cell washers, some way of selecting specific cell populations. And there would be a lot of incubation devices, whether it be incubators themselves or different bioreactors, they're off to something fulfilling finishing and then some cryogenic freezers of some description to. All based around an infrastructure of yeah, cleanliness or very specific rates for materials, very specific raised for the personnel inputs and output areas and a lot of warehousing behind all of that as well.
[00:27:40] Stuart Lowe I mean, a lot of that you've described sounds like a laboratory rather than a manufacturing facility. I don't want to denigrate, but there are elements of that where you'd like. Yes. People gowned up working at instruments, not a sort of a 21st century automated manufacturing facility.
[00:27:58] Jason Jones You're right. It doesn't look like, 19th and 20th century lab with smoke coming out of conical flasks, but it's still a laboratory base. And what we need is a factory based layout. What does it look like? I mean, somewhat biased here, but the reason I'm here selling origins. Is that I think the future has to look a little bit more light, probably in most of my conversations, people would use the analogy a lot more of a car manufacturing. It's a pun that I don't think it was even thought of as a pun anymore. Like a CAR T manufacturing [00:28:34]is CAR [0.2s] manufactured, but at least that kind of I mean, I don't think we'll have conveyor belts in clearer facilities, but more the robotic handling of materials, of bringing in materials, of operating those instruments that I say were all on benchtops at the moment and that are all strangely, I showed other automation devices. They're actually designed and built for automating processes that people are handling. Manufacturing wise if you look across the industries. We're very used to manufacturing very complex things high levels. Why haven't we done here selling jeans so far? If we haven't evolved to some degree because there are certain restrictions put on us. Where is it? It's GMP manufacturing. It's risk adverse add necessity. And so and change is risk, right. So we've had to get to a point where the risk of not changing is higher than the risk of changing.
[00:29:33] Stuart Lowe Yeah yeah yeah. So you're saying up to that up to this point, up to this point, the risk of change has been high. But now the risk of not changing is higher.
[00:29:43] Jason Jones Yes, the risk of changing is still high, but the risk of not changing is even higher. So it's always that I don't want to do them out of what they've achieved because it helps. But these pieces of information rely on people to put everything on, move everything to them and between them and to operate. I mean, everything's got a touchscreen and he's a human finger to touch it. We're looking to re orientate some of that cellular origins and make it look a lot more like a cross between car manufacturing line and a smart warehouse. There's two ways you can you can introduce robotics into cell and gene therapy manufacturing and that's you have a fixed robot robotic arm that can do all your manipulations and you bring things to it, which doesn't get you much further, really, than where we were with taking it to individual pieces of equipment or you can have mobile robots that will transfer between all of those different stations of automation. And that's certainly what we believe, and that's how I envisage the future being that we can have, let's say we can turn around from having 20 people in a manufacturing room to having one person in a in an office next to the manufacturing room monitoring what's going on and in that way, and you can run those plants 24/7, 365 days a year, even an extra day on a leap year. And you can somewhat and you can really expand that kind of output. But also you need to do that in a way that if you multiply your output, if you increase your scale, you do have to have a higher degree of quality, because let's say you have something like, a one percent failure rate. You'll then looking at 100 times more output, you've got 100 times more failures as well.
[00:31:31] Stuart Lowe It was exciting to hear about the work Jason and his team are doing to address the scaling issues in cell and gene therapy manufacture. As we've heard earlier in the episode, decisions made in the early stages of development can have a large impact on the ability to scale. I wondered if Jason had any advice for companies at this stage. What would you suggest to somebody who is in an earlier stage of development, who's maybe getting some good biological responses and thinking, how am I going to develop this process? What would you suggest to them in order to set them up for scale in the best way?
Advice for early-stage developers
[00:32:12] Jason Jones I think there's a great capital outlay in any kind of fully automated system and all these things. I used to say what is working with just devices, new instrumentation, there would sit on a bench top, I used to say as early as possible. Because then you're not going to you're not going to change anything later on and you'd already [00:32:30]be using, in fact. [0.5s] It could potentially speed up your process development work as well. With a full automation platform, it's not going to be possible for early therapy developers to invest in that kind of capital outlay and the facilities that would go in. And in fact, how much money would you waste over the subsequent six, eight, ten years of developing your product by keeping it online. It's unreliable. So I would say my advice would be to talk to the manufacturer, as bright as that of the technology that you're using about what their roadway, their pathway to full automation and for example, Cellular Origins coming in from the outside. And we're working with those providers to adapt and integrate their systems into our full automation platform. I would be bold enough to ask those technology providers what the pathway is. If they haven't got one, then they would suggest when you need to produce, yeah, 50,000 products a year for example.
[00:33:26] Stuart Lowe Okay. So actually being willing to go on a journey with your technology providers because you're going to be going on this journey and they need to come along with you, or you need to have the confidence that they're going to come along with you.
[00:33:38] Jason Jones I mean, I could say from what am I experienced that you're on a journey with them anyway, and it's not, it's not an arm length journey either. If you're utilizing technology in your process, your whole in your therapy development, your whole company relies on the therapy. It relies on the quality of that therapy and its success. So you have to be in a trusted relationship with your technology providers. I add that S on purpose. It's normally multiple because you're on a journey together. And like I say, you have to trust your technology provider to maintain the quality and the supply. I would add to that to circle back to how we started this part. I would add to that you need to trust that they have a pathway to full automation and high scale. Yeah.
[00:34:21] Stuart Lowe That leads me to ask a bit about maybe when you are working with some of those devices, working for some of those device companies and trying to place new equipment in farmer companies. How easy is it to deploy brand new technology in a pharmaceutical company? What challenges have you seen?
Technology adoption in pharma
[00:34:41] Jason Jones Easy access, not easy. There are some well-described metrics out there. Technology uptake curves. For example, you have your early adopters, you have your innovators, and you have the main crowd, the [00:34:55]tool man [0.3s] of the curve. And then in the technology lifecycle there's a turn off as well. So technology uptake is well described. I'd say it's a little hard on our industry. So what do you need? You need a piece of technology that moves the needle enough. Especially now that there's a lot of different choices in whatever unit operation you're looking at. Why would you choose one piece of technology over another, is one question. And if something new comes in, what would make you change it to something that you've been relatively satisfied with? It has to do more of what you want, more of what you require, whether that be now or later. So I would say usually that would mean don't touch the biology, but potentially you can make your process quicker. It could potentially you can have more viable cells at the end of it maybe. But on the whole probably you're going to want to be able to make more and more of those products through that technology as you go along. And it's got to move the needle. Otherwise, why do it?
[00:35:55] Stuart Lowe Help me make this argument then adjacent to say, look, planning for scale is the needle mover that you need to consider early on. How would you phrase up more eloquently.
Planning for scale
[00:36:07] Jason Jones If every developer has to think about where they want to be? Undoubtedly is treating patients. But is it patients in a clinical trial? I don't think so. I don't think that's the endpoint of anybody's journey. It's about treating as many patients as there are really that can benefit from the therapy, and having as big an impact on the medical world as you can. Making human life a bit more bearable in disease cases. Making life a bit fairer for those families whose children or loved ones or whoever are suffering for whether it be cancer or terrible human diseases, or whether it be. I've always thought, especially in oncology, that cancers often limit their genetic predispositions, but often it's a roll of the dice.
[00:36:55] Stuart Lowe For sake of argument, we have a few facilities in the future now, where it is fully automated, control by one person, looks much more like a car manufacturing plant. Do you foresee any bottlenecks now coming into the manufacturing process or as a result of that manufacturing process? What's the next hurdle?
Future bottlenecks beyond manufacturing
[00:37:17] Jason Jones That final vision. And by the way, I don't think I'll ever be like just one person running a production factory about it, but certainly a lot fewer than that could be. You know, I think. I certainly think with some of the technology we're looking at now around implementing robotics, implementing industrialization technology from other industries, finally into [00:37:40]supply chain. [0.3s] We could get to a point where we've nailed the manufacturing. We have greater standardization, greater reproducibility, that we have a greater depth of data around the process because everything is everything's digital, right? Every millimeter movement of the product or materials through the process is recorded. Yeah, we could nail all of that. We could get it down to near to zero process variability. We will, of course, still have the inherent variability in the patient product or the donor product. But the bigger, more immediate worry after we've nailed manufacturing, that's not going to be no work is that everything around it. The easy one, a lot of people talk about the analytics. All right. So you're producing more products. Okay. That's great. You're doing well at that. But how do you quality control? How do you analyze the product?
[00:38:31] Stuart Lowe Yeah. Suddenly a QC labs receiving 100 batches a day rather than as one.
[00:38:35] Jason Jones So I do have some hope in that. I think we've got to think smart about it. We got to utilize technologies again. But there is a lot out there now.
[00:38:42] Stuart Lowe In Covid, there was a lot of open collaboration between pharma companies, universities, institutes, manufacturers, equipment companies. Are you calling for something like that? Do you think that would help us get over this hump in the next two to five years?
Collaboration as a catalyst for change
[00:38:57] Jason Jones Yes. In short, it goes back to my kind of daydreams where I think about what if we all just put the resources we need into this for a short amount of time, which would actually probably cost a lot less to. It probably is. I say it probably isn't going to happen. It's not going to necessarily happen in any kind of methodical.
[00:39:14] Stuart Lowe Yeah, yeah.
[00:39:15] Jason Jones But I would say it's organically beginning to happen one way or another. It's almost takes a sort of facilitator out there. To some degrees, I do see the technology we bring into the industry as being that facilitation, the outside of a jigsaw puzzle, that we can then fit the other bits that already exist into. And actually the partners we're working with technology developers in the field around all different process and instrumentation, sort of being very open, very warm to essentially what is a common goal that we can implement more automation to achieve more scale, and that we're working solely on my day to day work now, I'm working a very collaborative way with a number of partners, and there will be more as we go on to achieve what you were just talking about with the therapy of developers involved as well.
Looking ahead: the future of cell and gene therapy
[00:40:10] Stuart Lowe Clearly, Jason has a lot of belief in the power of technology to enable cell and gene therapies to reach their full potential. So I was interested to hear what the future looks like to him. So we're recording in 2024, and this seems to be the year where we're getting a lot of approvals in cell and gene therapies. We already know more than ten years on from some of the first patients, and they are effectively cured of their cancer. Is it a done deal if we if we finished some of the cell and gene therapy development, we're good to go, right?
[00:40:48] Jason Jones I don't think many people really up to their armpits in the industry is gonna, is going to say that. There's so much more work to do a lot of which we've discussed. But from the source outside looking in, I have heard that term used actually, or at least inferred that, well, cell and gene was a success. Right. Let's invest in oligonucleotides. So let's bring out new grants around M&A production. What fantastically policy areas is plus cell gene therapy a success? No. We've really not even come out of the beginning of it. We've got so much more to do in terms of approvals to come, challenges around manufacturing to bring the cost of goods down. But we have to reduce the cost of these therapies or potentially we can afford health authorities who can afford them now, but then I'm going to be able to afford them when there are 100, 200 approve therapies on the [00:41:47]Indian. [0.0s] Is it a done deal? I almost react quite violently when I hear that, and especially around funding organization and more sort of national broadly, like bioprocessing organizations, Let say no.
[00:41:58] Stuart Lowe We've come so far. Don't stop now.
[00:42:00] Jason Jones It's short termism exists and politics exists. And in many walks of life and I exist somewhere around medicine, medical development and biotech. No, it's not a done deal. We just so much more today. We've got more to invest to make the returns, what they should be, whether that be around the good that we can do with patients for patients and their families, or whether it be the bottom line dollar, annual return of investment. I'd say we don't have much further to go before we can reach more patients. That kind of means that the again, the financial returns are going to be so much higher. I hope we enter into a new kind of period of positive feedback around that now. Is it done? No way. But it looks so promising that we'd all, we'd be foolish to turn away now. And yeah, please keep the interest and the investment coming into the area.
[00:42:55] Stuart Lowe What's your kind of like best case scenario? What's your best case vision for the future, in say, ten years time? Where might we be?
[00:43:03] Jason Jones It could even be 20 years. But we'll have successes on the way. And, well, I want to see us, cell and gene therapy should be accessible to everybody that requires them. Getting to a point where if you have a certain type of leukemia, lymphoma or myeloma and you try standard treatments, then you can then get a therapy that that you should respond to the probability why you should respond to. I'd like to get to a point where we have that option for many more patients. Hundreds of thousands of patients.
[00:43:35] Stuart Lowe It doesn't seem fair to have any other ambition.
[00:43:38] Jason Jones If it can benefit patients than it should do. And I'll say again as well, not to just think about the patients, but their families and friends around them. If if it's a matter of if it's a disease and it's life or death and not even that, actually some of the autoimmune diseases, the standard of living for some of these patients is really appalling, that you can make such a difference to so many patients with a kind of medicine that really didn't exist 30 years ago. I don't really, would be unbiased. I've spent my professional career in this field, but it would be what we're all working towards. I think it'd be a revolution of kinds, certainly medicine.
The why of cell and gene Therapy
[00:44:20] Stuart Lowe It was great to get Jason's perspective. Here are my three takeaways from our discussion. The technology we need already exists. Much of the technology required to further automate our processes is already available from other industries. We just need to adapt it and continue to innovate. The time is now. It's crucial that we lay the groundwork for the next steps immediately, or we risk additional development effort that adds cost and could hinder innovation. It's about partnerships. As the industry matures, technology developers and therapy developers are going to need to collaborate to eliminate bottlenecks and streamline processes. As we heard from both Tay and Jason. The why of cell and gene therapies is the incredible potential they have to make a real difference to patients lives, but we cannot continue to develop life changing therapies in isolation without paying attention to the means of producing these at scale. Thanks to the work of people like Jason, Tay and others, we are changing the mindset of the industry to enable more collaboration and create an environment for innovative solutions, which should help ensure widespread patient access. Thank you to both Tay and Jason for joining the podcast today and sharing their insights. In the next episode, I'll be exploring how out of the box thinking can decrease costs and increase the speed of development. And at the end of these two episodes, I hope you'll feel closer to understanding the why and the how that are driving progress and investment in the cell and gene therapy industry.
