Transformation in Trials
A podcast about the transformations in clinical trial. As life science companies are pressured to deliver novel drugs faster, data, processes, applications, roles and change itself is changing. We speak to people in the industry that experience these transformations up close and make sense of how the pressure can become a catalyst for transformation.
Transformation in Trials
How Cell and Gene Therapy Manufacturing is transforming Life Sciences with Jason Bock
What if a pharmaceutical company can be deconstructed and re-assembled in a new configuration? This is already happening in cell and gene therapy manufacturing. Join us for an enlightening conversation with Jason Bock, the founder and CEO of CTMC, who has been at the forefront of this intersection between clinical research and manufacturing. Discover the unique challenges of setting up a manufacturing network for autologous cell therapies and how this relationship between clinical and manufacturing sites differs from traditional methods. Jason shares his journey of moving to MD Anderson Cancer Center, setting up a biotech firm, and transforming the supply chain, thereby expediting product development.
Imagine the thrill of cell therapy advancements and the potential for cures in a single dose! Uncover how the trailblazing minds at CTMC and MD Anderson have submitted six INDs in the span of just 18 months. Half of these are MD Anderson invented therapies, while the rest are biotech invented products. Alongside these exciting developments, we also delve into the implications of such revolutionary treatments on the healthcare system. Understand the challenges that lay ahead in terms of making these potentially curative treatments widely accessible. Tune in for this riveting discussion on the transformation of healthcare, offering a glimpse into the future of medicine.
Guest:
Jason Bock
________
Reach out to Sam Parnell and Ivanna Rosendal
Join the conversation on our LinkedIn page
Welcome to Transformation in Trials. This is a podcast exploring all things transformational in clinical trials. Everything is off limits on the show and we will have guests from the whole spectrum of the clinical trials community, and we're your hosts, Ivana and Sam. Welcome to another episode of Transformation in Trials Today. In the studio with me I have Jason Bock, who is the founder and CEO of CTMC. Welcome, Jason.
Speaker 2:Thanks so much for having me, Ivana.
Speaker 1:And today the topic of our podcast is going to be the link between manufacturing and clinical research in cell therapies. But before we dive into the specifics of this topic, could you tell us more about how a pharmaceutical company would usually go about building up manufacturing capabilities?
Speaker 2:Sure.
Speaker 2:So it's a particular challenge for especially autologous cell therapies to move a product from the research stage into the clinic.
Speaker 2:So, putting aside all of the FDA interactions and the like, just to set up the manufacturing network for, let's just say, a typical CAR T, you would need to find a manufacturing site to manufacture the virus, the cell therapy, then hire a CRO to set up a network of clinical sites and then they would manage the coordination of trying to enroll patients in a dose escalation part of that study and shipping the starting material, which is the patient's starting material, to the manufacturing site, getting a slot organized in the manufacturing site and then going through that manufacturing and then getting the product back to the clinic and having the patient line up with. When that happens, then you would have another site which would be doing, or another CRO which would be doing clinical correlate analysis to analyze the results from that study, and so overall a really complex logistics and coordination to understand how a clinical study is performing and to get to clinical proof of concept. So much more challenging, I think, in autologous cell therapy than other modalities such as small molecules or antibodies.
Speaker 1:And can you tell us more about why it's specifically trickier in this specific space?
Speaker 2:Yeah, so with especially autologous cell therapy, the supply chain literally starts with the patient. So each dose is manufactured patient-specific, starting with patient material as the starting material of either a phoresis product or potentially even a sample of their tumor, and so this creates a different kind of relationship between the clinical site and the manufacturing site than other more traditional modalities, small molecules or antibodies. Your supply chain just starts with raw materials cell bank perhaps, and that can be located anywhere in the world, and then you just check the product to the clinical site and they can enroll the patients and have the product sitting on the pharmacy. When we're manufacturing patient-specific batches, that connection between the clinic and the manufacturing is different.
Speaker 1:No, I understand. If the patient is part of the manufacturing value chain, then they just are closer together than in the traditional therapies.
Speaker 2:Yeah.
Speaker 1:Well, I was curious. How could this be different If you are not to go through the regular Cerebro approach, where you would have this supply chain nightmare of all these different partners? How else could you do it?
Speaker 2:Yeah, so I mean that's why I moved down to Houston and started working at MD Anderson Cancer Center.
Speaker 2:So as background, I had 20 years developing various therapeutics, bringing those products into the clinic and through to global commercialization mostly protein therapeutics and antibodies and there we had a very centralized supply chain that could be global.
Speaker 2:We actually manufactured products in Korea, had them filled, finished in Germany and then distributed all around the world. But I became really intrigued about five years ago with the regulatory approval of CAR-T's and the tremendous impact they were having on cancer care and the potential they had to really transform all of healthcare in many ways. And yet the manufacturing and this supply chain that we talked about was gonna be a real challenge, and so, coincidentally, some of the leadership at MD Anderson, through friends of friends, were talking to me and said why don't you come down to MD Anderson and we try and figure this out together with some novel approach? And so I thought that was a really intriguing idea. So I'd left my large pharmaceutical organization that I had been at for 10 years and moved down to Houston about four and a half years ago to start something new to specifically address this challenge, and so within MD Anderson we built a biotech that, at least for the initial way, was for MD Anderson invented products.
Speaker 2:we could handle that whole supply chain and so we acquired a local cell therapy development manufacturing facility that was quite a good size 60,000 square feet with 14 clean rooms built to really industrial standards. We were able to recruit a tremendous leadership team and staff, now up to about 85 people, and build capabilities to work with MD Anderson researchers who had come up with novel cell therapies. We were able to industrialize them, work through a regulatory strategy with them, develop a manufacturing process, click clear and IND and initiate a clinical study at MD Anderson to bring these products from research proof of concept. Hey, we think we have something that cures cancer. Advice to see how well it works in patients and see if we can actually impact patient care.
Speaker 2:So, interestingly, we set this up initially internal to MD Anderson, and then a number of biotechs reached out to us and heard what we were doing and said, hey, don't keep this all to yourself, we need this help too, and can you work with us on the same model to help us develop our product? We've got this really great product in the research labs. We haven't built out a clinical development organization or regulatory CMC can you help us do all of that? And so we formed some really great partnerships with companies with tremendous technology, such as obsidian therapeutics, ksq therapeutics and March biosciences, as well as others, to do exactly that.
Speaker 2:Where that whole network complicated network of CROs and CMOs and clinical sites and manufacturing sites, we can basically handle all of that for our partners and co-develop their products with them. What we found is much quicker, with lower risk, especially on the execution side, and in a very robust way to high quality. So we filed six INDs over the last 18 months and have five more INDs planned in the next 18 months. So it's been a very exciting busy time, but really excited to have this vision of what we could do. So we're trying to get those results of simplifying things, making them robust, lower risk, quicker and getting them into the clinic and seeing how well these potentially transformative therapies can work in patients.
Speaker 1:Well, I do wanna unpack that a little bit. So it means that what you've essentially done is build out the manufacturing capabilities for cell therapies specifically, and you can work with different kinds of biotechs that come to you, but for this critical phase of clinical development and manufacturing also, you are their partner in making sure that they get from point A to point approval. Hopefully. Is that correct?
Speaker 2:you understood, yeah so yeah, exactly like you said, people come to us typically when they have good pre-clinical data and I said we wanna see how the wellness works in patients and basically everything they need to do from that point through getting the product into patients, getting 10, 15, 25 patients of clinical data we can do for them. And then about a year and a half ago we spun this organization out from MD Anderson. It's now a joint venture between MD Anderson and National Resilience. Resilience is a very ambitious company focused on manufacturing technologies and developing a commercialization network, and so we work very closely with Resilience to transition partners, after they've gotten clinical proof of concept, into the resilience network to commercialize the products. And so really, just as you said, we can go from mice to commercialization all in a connected way. And in this emerging new modality, when there's so many challenges and so hard to put together this network, it seems like it's really caught on and been very effective in developing these kind of cell therapies.
Speaker 1:I think it's a very interesting development because basically you're deconstructing the pharmaceutical company from being this beast that's entwined to saying, well, there are actually different things that you can be good at and specializing in this specific area, and kind of being, I believe, in the pre-call. We also call it like the train tracks for different kinds of trains. Trains are the drugs.
Speaker 2:Yes, yes, exactly.
Speaker 2:I've really seen over my more than 20 years in therapeutics development the value of partnerships.
Speaker 2:A lot of these things are really hard, and it's hard for one organization to be good at all of them, and so what I found is finding partners who are really good at different aspects of this make for accelerating these products having an impact on patients, and so research companies that come up with very novel innovations that can impact cancer are great at that.
Speaker 2:Then we're really good at turning those research concepts into a therapeutic that can be developed and then, as I laid out for you, commercialized. And then that's also just another beginning of after you get a product to be, la too, find the right patient populations to market and grow that market and make it available for as many patients as possible. That's what large pharmaceutical companies are really good at is post-approval. They do all the other stuff to get products to be commercial along the way. But especially with cell therapy, especially with it being a relatively new modality, it's not like there's a very broad expertise set out there. We've managed to pull together a really highly competent organization that's quite good at this stuff, and so we can really help our partners accelerate their therapeutics development.
Speaker 1:I would be curious to learn more about some of the factors that make your organization successful at this. Is it skills? Is it specific backgrounds? Is it just how you arrange that people work together? What's your secret sauce?
Speaker 2:There's a lot of components to it Because we were able to build this from the ground floor. We really think holistically about what are the limitations or what are the bottlenecks, but things slow down therapeutic development. Really, having a high degree of competence and science is critical. That's why, when we built this organization and why I was excited to come to MD Anderson is we were able to recruit very highly competent scientists, even professors, who have a depth of experience in the science of cell therapy, and couple those with industry-experienced people who understand more about regulatory science and industrialization. We intentionally put together this kind of hybrid organization that was very focused on science-based but focused on bringing products robustly into the clinic. It all starts with the people. That's the most important thing. More manufacturing facility is really important. We were able to acquire this facility that was built at very high quality, designed as a clinical manufacturing and launch site for bellicom pharmaceuticals. That facility allows us to control the environment very well and have the best equipment and the like. That's another prerequisite.
Speaker 2:Then, underlying all of that in terms of partnerships is how you partner. We have a very differentiated partnership model that tries to deal with all the important business stuff up front but then gets out of the way and allows the scientists from both organizations to focus on making the right choices for that therapeutic to move as quickly as we can, as robustly as we can, and not have to constantly worry about change orders or out of scope. These are really complex products. The scope is going to change constantly. Some, to be honest, some organizations build their business model around that that we're going to start with a really small scope and then we'll just change it along the way and we'll make a lot of money based on all these changes that companies have to pay for. We take a very different approach that we put together a holistic scope to get partners from research to clinical data. It's basically one price that's fixed. We also share in as we see value created in those products. We share in that value that's created as well.
Speaker 1:That does sound like a better recipe for success in partnership than the other model, because you're in it together, so you're both dependent on the outcome.
Speaker 2:The best way of saying it is aligned incentives. If you create a business model where your incentives aren't aligned, then it can work for a little while. Everyone, even the best of people, can try and make that work, but eventually there's going to be a conflict based on misaligned incentives. What we really try to do is holistically think about it. Meet our partners where they are different stages of their company and align our incentives so that we're incentivized to make the most robust product for them, not cut any corners, but as well move as quickly as we can and get that product into patients which is very much aligned with their goals as well.
Speaker 1:Jason, I'm curious. You have the beautiful Houston background behind you. How much does Houston play a role in what you're doing here?
Speaker 2:Thanks for mentioning. Behind me is the Texas Medical Center. It's actually the largest medical center in the world. More patients are treated here in the few square miles behind me than any place in the world. As we started the conversation about the different kind of relationship between patients and the manufacturing the clinic and manufacturing it just made total intuitive sense that if we're going to do something disruptive like this, let's base it right next to the largest medical center in the world. It's integral to what we do.
Speaker 1:That makes sense. It's funny, in this very digital virtual world, proximity sometimes still matters.
Speaker 2:Yeah, I mean literally. There's a shuttle bus that goes every 15 minutes between the MD Anderson Clinic and our building and can bring patient samples to us. So when we're making an infusion product, we can, as needed, coordinate with the clinic, say we're on our way over and we bring the product directly to the patient bedside, literally to their bedside. The other great thing that I can just say about cell therapy because it's patient, the patient is so integrated in it is they can really excited about cell therapy, because cancer is such a horrible disease and it's really like your body is betraying you, because it's your own cells that become cancerous and can, unfortunately, potentially kill you, and so it's very, it's a lack of control.
Speaker 2:They're like this body that I've lived with for all my life is now repelling against me. But then the ability to take their own immune cells, bring them into the manufacturing facility, engineer them, soup them up, rev them up and then re-infuse them to the same patient.
Speaker 1:Patients get super excited about it and are like okay, when am I getting my cells?
Speaker 2:When are they coming back from vacation and let's fight this cancer together.
Speaker 1:And so that's a beautiful way to put it.
Speaker 2:Patients get really excited when they would call up and say, okay, we're bringing the product over. Lots of times they ask our team to take a selfie with them or something before the infusion, and so it's fantastically rewarding.
Speaker 1:I love that image that the cells have been on vacation, they've rested up, they're ready to get back in there.
Speaker 2:Yeah, that's what we colloquially call it that we give the cells the club bed treatment. Let them rest, rejuvenate and then get back in there and fight the good fight.
Speaker 1:I also want to hear more about these six INDs that you have submitted in 18 months, because that is a high concentration of INDs in a very short amount of time. How did you go about that? But also, are they for some of the same originators? Are there all different inventors of these six? I would be happy anything you can share about that.
Speaker 2:Sure, some of them we've announced publicly, some of them we haven't. About half of them are MD Anderson invented therapies that we've developed and then brought into the clinic for indications such as melanoma as well as CRC. Then the other half is biotech invented products that we co-develop with our partners and bring those into the clinic. There are different modalities. Some are TIL, tumor infiltrating lymphocytes, some are CAR T's, against different targets and for different indications. We're fairly agnostic At this point. We're primarily focused on cancer indications, although we've started to think about some other indications for cell therapies as well.
Speaker 1:I would also be curious to learn more about the cell therapy space in general, because often I do hear that it's applied in cancer treatments of different kinds. What is happening in the space? What's new and exciting? What are you excited about?
Speaker 2:The thing that I'm most excited about, I would say, is this modality. That's been around for a while, but I think it's going to be at an inflection point. This is what I mentioned before tumor infiltrating lymphocytes. This concept was originally developed under Steve Rosenberg at NCI, maybe even a little longer than 30 years ago, and has been consistent in terms of showing clinical efficacy in solid tumors, which is an area that cell therapies have struggled with. However, there's been a struggle to really industrialize them and bring it through FDA interactions through to commercial product.
Speaker 2:The company that's furthest along with that is a company called Iovance and they're due to hear back on their commercial application from FDA early next year. That's with un-engineered TILS. I think the writing right behind that is a wave of engineered TILS where we've taken these products and give them to overuse that phrase give them the super med club, med treatment, where we not only rest them and rejuvenate them, but then we engineer them to have additional fitness or resistance to the tumor microenvironment, give them even more tools. When they go back and are infused they have even a better chance. We have partnerships with both Obsidian Therapeutics and KSQ Therapeutics on TIL modalities that hopefully those companies will have news coming up that they'll be excited to share.
Speaker 1:That is exciting. This is why I love the space. There are so many new exciting things happening where just a couple of years ago we couldn't even imagine that it could have happened.
Speaker 2:Yeah, I really think there's some of these buzzwords that get overused transformative but to me, the biggest difference with cell therapies is not only their efficacy but the fact that they're single dose and potentially curative treatments.
Speaker 2:There's so many patients who are on their sixth line of treatment have been essentially cancer patients for a big chunk of their life, maybe 15 years. Every six weeks they come back and get another treatment and another round of chemo and it holds the cancer at bay, but they're still cancer patients. But then with cell therapy, with the single dose treatments that can be curative patients then who are five, 10, 15, 20 years without another treatment, and so not only is it curative, not only is it life extending, but single-dose it, so those aren't cancer patients anymore. They're back to spending their vacations actually going to fun places and not spending vacations. Oh, okay, I have to take off a week every six weeks to go to the hospital and get another round of chemo because I'm so sick from that. The quality of life is so critical, and that's what one of the great things and how cell therapies can be transformative.
Speaker 1:And that is truly transformative.
Speaker 2:Yeah, I mean let's say it was your podcast, right, and so it's going to be a challenge to work through this transformation, because our whole healthcare system is set up for okay, come in every six weeks, get your infusion, we'll keep monitoring you. Let's go on to the second line now. Let's do combination with this and that the whole system is built around that. And if you move to a system where you may have to come into the hospital for a week, get your infusion, but then after that it's just checkups, it's a whole different model. And while I hear a lot of concerns about the cost of these individualized, personalized therapies and we do have to work on that and I think we're at the very early stages of just driving that cost group down but on the other hand, if you're carrying cancer, I think there's an economic case that people have in their lives back is very valuable. I mean you can't.
Speaker 1:You cannot put a price tag on that. Yeah, yeah.
Speaker 2:And if you did put a price tag on it, it would be worth a lot, true, true, as opposed to all those costs that is associated with ongoing care for cancer patients.
Speaker 1:How would this? It does definitely impact healthcare. I'm just thinking about patients who are not in Houston and may not be in as fortunate circumstances to be in a vicinity of a world class facility that can develop these kinds of things for them. How do they get this sort of treatment?
Speaker 2:Yeah, I think what, what you know, the setup we have here in Houston is great for those super cutting edge treatments to be able to try very novel things, very powerful, powerful treatments that you know can have some side effects and the amazing doctors in the industry to be able to mitigate those side effects and have the therapy meet its full potential. But then our goal is to continue to develop these as where we understand the therapeutic window, where we can know how to mitigate any adverse events and then make them more widely available to. You know, a wide population outside of Houston and other academic medical centers.
Speaker 1:And I think that'll come.
Speaker 2:You know, we're really still at the early stages of this field and those kind of innovations will come from the manufacturing side, but as well just coming up with how we engineer the cells to not only be efficacious but safer as well, as well as how to administer those and mitigate the clinical adverse events and how to treat these patients. It's different kind of adverse events that we have with other kind of therapeutic modalities.
Speaker 1:Can you share any of the kinds of adverse events that are experienced?
Speaker 2:So yeah, I mean some of the adverse events that can be is it's basically an overactive immune response.
Speaker 2:We're putting in supercharged up immune cells and just like when you get a vaccine and basically stimulate the immune system and you feel terrible for a few days. This is even more direct that you're putting in cells that are like supercharged up. It's almost like a nuclear warhead to attack cancer. So there's a big immune response. But I would say, to give you a specific example of how you know, technology and product development can address that One of our early partners of city and therapeutics.
Speaker 2:Their technology is to regulate the cell surface expression of IL-15. Il-15 serves to stimulate and promote the proliferation of T cells and basically propagate immune response. But obsidian technology is they can give a small molecule which causes that IL-15 to be demonstrated at the cell surface and yet when they take the small molecule away, it reduces the level of expression. And so you can modulate, based on a patient's response, to turn the T cell response up or down in a tunable way. And that's just a novel technology that will allow doctors to essentially increase the therapeutic window and find the right way of having the therapy be efficacious but not toxic.
Speaker 1:That's really cool. That's sort of very impressive. I do want to ask more about your facility. You've mentioned a couple of times that you're very pleased with the facility that you have. What makes a great facility for manufacturing cell therapies?
Speaker 2:Yeah, Well, there's a lot of things. It's basically the way it was laid out to assure that we can control the environment very well, have enough space. I think one of the simplest things is enough space for the operators to be able to have the right equipment laid out so they're not too confined. And this facility was built with quite large clean rooms that allow us to put the right equipment in the right places, have the right number of operators and not have to have any trade-offs. And then, as well, the environmental control systems for HVAC is really important too, because we want to control the temperature, the humidity and the particle counts in the environment, and I don't know whether you've ever been to Houston, but it's really important to control the humidity and the temperature. It can be a little hot here and a little sticky, but felt out very robust environmental controls. And then the last aspect that's not exactly tied to the facility but is equally important is your quality systems.
Speaker 2:And we're in the progress, and one of the reasons we partnered with Resilience is they're at the forefront of digital quality systems, and so we're implementing a number of very robust quality systems. That allows us to maintain control of all the patient samples moving through the facility, have them be uniquely identified, have it be impossible to have patient mix-ups and yet maintain a high level of quality compliance that meets FDA expectations.
Speaker 1:That is important and digitizing that process helps a lot.
Speaker 2:Yeah, there's just a tremendous amount of data that's produced. When I commercialized an antibody, a number of antibodies, we would typically have maybe six, maybe eight, maybe 10 clinical batches for the entire eight-year or so clinical development. They were large batches. They produced enough to treat hundreds, not thousands, of patients. For cell therapy we make eight batches per product in a month and there's probably 100 to 200 to 300 batches that we produce for a particular product before it would reach commercialization, and so managing that amount of data with all the INDs we talked about, really requires robust electronic systems, digital systems.
Speaker 1:Well, that makes me very happy. I am in the technology space in Life Sciences so I'm like, yay, it's part of our business now Technology that enables us to do our good work in Life Sciences.
Speaker 2:Couldn't agree more. Couldn't agree more.
Speaker 1:I am curious to hear your opinion, jason, because what you're doing is changing or maybe even reconfiguring Life Sciences as we know them. Could you anticipate that something similar could be done in other areas of Life Sciences where, basically, we have other entities that work across the product, companies, or something similar?
Speaker 2:Yeah, I mean, one of my main drivers is just to constantly challenge the status quo. So it doesn't mean understand the status quo. It was developed for a reason, but then look for ways to make that better, and so I'll tell you this and then I'll answer your question.
Speaker 2:What I saw in cell therapy was a lot of people doing things the same way as we did antibodies or small molecules, and it was sort of just well, that's how we do things. But if you zoom out and for all the things we've talked about over the last half hour or so, it's a different supply chain and so why don't you think differently about it? So just challenge that status quo, think about it from first principles what are the challenges in this particular field and what makes the best sense to arrange the pieces to solve those challenges? And that was the whole concept with coming down to everybody understand where typically academic centers were, where innovation happened, but then it spun out into biotech.
Speaker 2:And then they handled the industrialization and clinical development. But because cell therapies are such a clinically based modality and that you're infusing live cells into a patient and having to track how they react, the clinic is much more center of where that development occurs. And so it made sense to sort of shift and bring the manufacturing closer to the clinical development and base more development around the clinic. And so what I always, when I talk in various audiences and things, is just challenge people to ask these questions of why, what makes sense, and to just be intentional about how you think about things and don't take it for granted oh, this is just the way it's always done. Is there a better way? And I think if you have that kind of challenging always challenging or understanding the why, then you can come up with disruptions that help with transformation, drive transformation.
Speaker 1:Well, I couldn't agree more, and I think that there are still lots of opportunities out there. And it all starts with asking well, how else could we do this and could we do it better?
Speaker 2:Yeah, exactly.
Speaker 1:And that's a perfect segue to the question that we always ask our guests on the show, and that is if we gave you the transformation in trials, magic ones that has the ability to change one thing in the life sciences industry, what would you wish for?
Speaker 2:Let's see. Well, I'll keep it focused to life sciences. I mean, if I could make Houston 15 degrees cooler during the summers, that would be really fantastic, but that may need a bigger wand, I think. To be honest, it would be just what we talked about before. I think having people have an open mind to figuring out creative and different ways of solving some of these challenges and then being willing to create innovative partnership structures to solve those challenges in unique ways, that's what I've been so it's one of the things that I enjoy so much about the world here is finding novel products and then working with great partners on how to move those as quickly as we can to have the greatest impact on patients.
Speaker 1:That's a well. I hope that's that wish comes true. And, Jason, if our audience have any follow up questions or would like to learn more about what you do, where could they reach out to?
Speaker 2:The easiest way is to find me on LinkedIn, jason Bach, bismboy, ock, as well as our website, ctmccom. Oh, awesome.
Speaker 1:This was a lovely conversation. Thank you so much for coming on the show, Jason.
Speaker 2:I really enjoyed the conversation. Thanks so much for having me.
Speaker 1:You're listening to Transformation in Trials. If you have a suggestion for a guest for our show, reach out to Sam Parnell or Ivana Rosendale on LinkedIn. You can find more episodes on Apple Podcasts, spotify, google Podcasts or in any other player. Remember to subscribe and get the episodes hot off the editor.
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