Episode 53
In this episode of the Ori Spotlight Podcast, Jason C. Foster welcomes Hong-Ming Hu, Founder and Chief Scientific Officer of ImmuXell Biotech, together with Ori’s Founder and Chief Scientific Officer, Farlan Veraitch, to explore what it takes to bring TCR-T cell therapy to solid tumors, from discovery science to the first patient dosed. Drawing on more than three decades in cancer immunology and adoptive cell therapy, Hong-Ming shares how a novel retroviral vector, one-step transduction and automated manufacturing on our IRO® platform took ImmuXell from process installation to first patient dosed in around four months.
Together with Farlan, they unpack the economics behind cell therapy’s cost of goods, the case for de-skilled, decentralized manufacturing, and why flexible routes like China’s IIT pathway, paired with smarter, data-rich process development, are essential to widen patient access and move solid-tumor cell therapy from a handful of patients to many.
Watch on YouTube: https://youtu.be/LKUyWHEOed0
Further Information
Episode transcript
This transcript has been processed with AI software; please be aware that it may contain inaccuracies and may not be entirely precise.
Jason Foster: Hello and welcome to the Ori Spotlight Podcast. This is your host, Jason Foster. I’ve got some special guests with me today. Many of you will know Farlan Veraitch, our founder and Chief Scientific Officer. And we’re lucky to have Hong-Ming Hu, Founder and Chief Scientific Officer of ImmuXell, with us as well. So welcome, Hong-Ming and Farlan.
Hong-Ming Hu: My name is Hong-Ming Hu, and I’m the Founder and CSO of ImmuXell, in Shanghai. Very nice to talk to you here.
Jason Foster: Thanks, Hong-Ming. And Farlan, welcome back, you’re a multi-time visitor to the Spotlight.
Farlan Veraitch: Thanks, Jason. I’m excited to be on this one, particularly with Hong-Ming. Really excited about today’s conversation.
Jason Foster: Me too, I’m excited to have both of you. As some of you will know, we recently announced our collaboration publicly. It’s been going for about five or six months now, and we’ve reached a very exciting milestone: together with Hong-Ming and his team at ImmuXell, we’ve treated the very first patient with a product manufactured under GMP on the IRO system. I’ve personally been working towards this for the seven years I’ve been with Ori, and Farlan, it’s been ten or so for you, working towards getting that first patient treated. So it’s a very exciting milestone, and we’ll talk much more about it today.
But if we can, I’d like to start at the beginning. Hong-Ming, would you mind introducing yourself and giving us a bit of your background? I know you were in the US for around thirty years doing cancer research and T-cell therapy before moving back to Shanghai. Could you give the audience a little of your background and tell us about your career journey?
Hong-Ming Hu: Thank you, Jason. As you alluded to, I’ve been in this field for almost thirty years. In 1994, I joined a lab where I started working on TIL therapy with one of the early pioneers of immunotherapy. From there, we began to learn how to do adoptive cell therapy and to understand how T cells recognize tumors. We learned a great deal from that early work, and I was later able to use that technology after coming back to China to treat patients. Now we’re taking on a new challenge, working with Ori to scale up and reduce the cost of production. We’re really happy to be able to do that, and we treated our first patient just two weeks ago.
Jason Foster: Exactly. And I think you mentioned that, in the follow-ups, the patient is responding as you’d expect at this stage. Just for clarity, it’s a pancreatic cancer patient, is that correct?
Hong-Ming Hu: Yes. We’d been doing this with our own manual process and were already seeing exciting early results, but we realized that manual production was going to be a major bottleneck. So we felt that scaling up and reducing cost was the way to go. With this first patient, we’ve shown we can do that, and we’re very happy to continue, moving to this kind of automation and seeing the safety and efficacy of the cells we infuse.
Jason Foster: Yes, exactly, we’ll come much more into that later. But let’s back up one step. Tell us a little about ImmuXell’s focus. You’re focused on solid tumors, and the audience will know that solid tumors have historically been much harder to treat than liquid tumors. You’ve got a unique method to target the KRAS G12V mutation. Tell us how you ended up with that target, and what’s unique about ImmuXell’s approach.
Hong-Ming Hu: Let me start with TIL therapy. We’d been doing TIL therapy for a while without really knowing what the major T-cell response was targeting. But in one patient early on, we found it was targeting the KRAS mutation, and we realized that might be a good target. KRAS is a known oncogenic driver, and it’s more difficult for the tumor to escape than many other tumor-associated antigens. KRAS mutations are also more frequent in pancreatic cancer, so it made me think we could use adoptive cell therapy for one of the most difficult-to-treat cancers.
When we cloned one particular T-cell receptor in the context of HLA-A11, we thought we might find more patients in China. So in 2021 I came back to China and set up a lab to clone more T-cell receptors from Chinese patients. We were very lucky: we identified our first T-cell receptor and treated the first patient. As you probably know, China has the IIT system, which lets us quickly run a small patient trial with a new CAR or TCR therapy, so we ran that IIT trial just three months after our first discovery. We saw a very exciting response, the first patient had a complete response lasting eight months, and that laid the foundation to keep pursuing this target. Right now we’re cloning more T-cell receptors against the mutation, including G12V and G12C. So we think we’re in a unique position to do this therapy, not only because there are more patients in China, but because of the speed at which we can test a new T-cell receptor, a new manufacturing process, and other targets.
Jason Foster: Thanks, Hong-Ming. It’s a really interesting history, you moving back to China and identifying the opportunity to accelerate development using the Chinese IIT system. Let’s delve into that a little more, because I think it also connects to how we’ve been able to move so quickly together as a partnership. You’d begun testing your unique approach via the IIT system over the past year or more, and, am I right, you’d treated something like 12 or 13 patients before we started working together, iterating as you went. So tell us a bit more about that. You’ve got a unique target in the KRAS G12V mutation, but you also have a unique vector, if I understand correctly. Is that right?
Hong-Ming Hu: Yes, that’s a very good point. We’re always thinking about how to reduce cost. There are two major costs in cell therapy for CAR-T or TCR-T: one is the material cost, mainly the viral vector, which is significant; the other is labor. As a biologist, I wanted to use our knowledge to reduce the viral production cost, so we focused on retrovirus. Retrovirus is a little different from the lentivirus that most people use. We’re able to create a stable cell line that produces the virus continuously, which makes it easier to scale up and reduce cost later on.
The other innovation is making the system target the T cell directly, by engineering an antibody that specifically recognizes and activates the T cell, the CD3 antibody. After about a year and a half of optimization, we modified our retroviral vector so that it can not only activate the T cell but, at the same time, transduce the activated cell. We call this one-step transduction. Retrovirus typically doesn’t infect non-dividing cells; here it only transduces activated T cells, because we’re using the antibody to activate and transduce in one step. In the end, that also gives high efficiency, because only activated T cells are transduced. We were then able to couple this with our IRO bioreactor to do that one-step transduction, a really beautiful marriage between the viral platform and the automated system. It consistently drives down the two big costs of cell therapy: the viral vector and labor.
Jason Foster: Absolutely. Farlan, maybe I could bring you in. We’ve worked with a couple of partners using retrovirus, but not many, most use lentivirus, as Hong-Ming said. Can you speak to how the collaboration has worked over the past year? Hong-Ming and I first spoke early in 2025, and then you began talking at a CSO-to-CSO level and went out to Shanghai a couple of times. Talk us through how we built the partnership over the last year or so.
Farlan Veraitch: As everybody knows, Ori has a laser focus on driving down the cost of goods and enabling scale-up, whether centralized or decentralized. My first meeting with Hong-Ming was incredible. Every single piece of data he showed me had a little box in the top right-hand corner of the slide showing the cost of goods associated with that run. I thought that was radical coming from a discovery team, and I found it genuinely inspirational. He was innovating around the core biology of the transduction and activation step in order to drive down the cost of goods and the cost per run, making the manufacturing process simpler and more elegant, with fewer steps. One thing we haven’t mentioned is that even in the virus manufacturing, Hong-Ming was thinking very carefully about the cost of the virus, innovating on the manufacturing process for the virus itself, to make sure it would be cheap.
When I came into the picture, we started to marry the biological and manufacturing innovation Hong-Ming was driving with IRO’s ability to de-skill, reduce the footprint, and multiplex, so you can manufacture a lot of doses in a very small space, as well as our ability to push manufacturing into lower-grade rooms. Over an hour-and-a-half, two-hour session, it dawned on both of us that if we brought these two elements together, we were sitting on a combined technology offering with some pretty radical implications across the board.
Jason Foster: I think you told me at some point, Hong-Ming, that your process originally had around ten unique steps, relying on the bags and flasks that are used very widely across the world. When you mapped your process onto the IRO system with Farlan, those ten steps reduced to about six, including your novel vector. Tell me how you were thinking about the efficiency gains. We’ll come to what actually happened once we started working together, but as you were thinking about it, what were you hoping to get out of the collaboration? Certainly COGS reduction and reducing the human-resource burden must have been top of mind.
Hong-Ming Hu: Our goal has always been to make the product at the hospital bedside, and for that the process needs to be really simplified, simple enough that a nurse or a non-PhD technician can operate it. A complex CAR-T production typically involves a leukapheresis step, isolating the T cells with beads, then activating them with another set of beads or antibody, then de-beading, washing, adding the virus, transduction, and washing again. That’s a lot of steps, and it’s very complicated. Each one is a point at which errors can occur, and the transduction efficiency can be variable. So we felt that step needed to be simplified.
We thought that if we could eliminate that separate bead-activation step and simply add the virus directly to the leukapheresis product, we could do everything in one bioreactor, without changing the vessel in between and without washing. That gets us much closer to making bedside manufacturing possible.
Jason Foster: Absolutely, you touched on a couple of key points there. Part of our underlying thesis at Ori is to de-skill the labor required. On the average process, we reduce the amount of labor by at least 60%, and, importantly, the other 40% is de-skilled, so you can use a technician-level operator rather than a PhD immunologist, who’s in short supply, or a nurse who already has many other responsibilities. It’s about de-skilling the process, but also being able to run it outside the clean room. Because IRO is a closed system, you wouldn’t need a high-grade space in the hospital to manufacture, and that’s a critical element to broadening access and operating in a decentralized model, which has real benefits in a large country like China or the US, where patients often have to travel long distances to get treatment. We wanted to test some of this thinking as we moved forward with the partnership. If I recall correctly, we installed the systems in your lab, one in the PD lab and one in the GMP lab, around December 28, almost at the end of last year.
Jason Foster: That’s right, some of our team spent Christmas in Shanghai with you. We trained your team on the ground there in a week or so, and then the work started: mapping your existing process onto the IRO system and optimizing from there. Farlan, maybe you could walk through that process, and Hong-Ming, I’d love your perspective on how it went. It all happened in a relatively short space of time. Farlan, if you don’t mind.
Farlan Veraitch: Everything moved incredibly quickly. We got an instrument out to Shanghai, two instruments, actually, and did our IQ/OQ installation in Hong-Ming’s lab, setting up one instrument in their PD lab and one in their GMP lab. The team at ImmuXell were trained very quickly on how to use the IRO instrument, it took about a day or two, and Hong-Ming’s team were up and running the process they wanted to take into the clinic basically a couple of days after the instrument was installed.
That’s the key first thing: how quickly you can go from installation to running. Every moment is absolutely critical, we’re in a rush across the board. How quickly can you go from installing an instrument to running a process in a GMP setting? That happened incredibly quickly, and we were all sitting together on Teams, in Shanghai and in London, looking at the biological output as the run progressed, the cell numbers, the oxygen profiles, the transduction efficiencies. In a very short space of time, we had a good feel for how IRO was performing with Hong-Ming’s process.
Jason Foster: Hong-Ming, you and I were discussing this not long ago. Tech transfer usually takes nine to twelve months, even if you’re moving quickly, transferring your underlying manufacturing technology is often a complicated process. When you first saw how quickly our two teams were able to get up and running and start generating biological results, was that surprising for you? I don’t know what your expectations were, but I imagine it was a surprise compared to what people normally expect.
Hong-Ming Hu: I was personally surprised it was so smooth and so fast. I used to be a CSO at another company, and when we tried to move our production process from one site to another, in the same city, it took us a year. It’s very difficult, even within the same company, between different manufacturing sites. Here, we were moving something from another country, it was completely new to us, we’d never run a closed, automated system before, and we’d added complexity by using a new virus, not our old generation. So there were two different challenges, and being able to do it in four months is amazing.
I think it speaks to the robustness of the machine. It’s not only flexible, it can be adapted to different protocols and different viruses, it’s also very robust, and it works with any kind of cell. We’re doing TCR-T, which usually requires one or two more logs of cells than a typical CAR-T, and we were still able to generate enough cells for the patient after about four or five runs. We tested it in different conditions and could generate enough cells for TCR-T for solid tumors. That speaks to how reliable, and yet flexible, the system is.
Jason Foster: You threw a lot at us. We had a new virus, and we hadn’t done a huge amount of work with retrovirus, Farlan; a little, but not a lot, and we had a TCR that requires a lot of cells and a long process. One thing the audience might not appreciate yet is the kind of collaboration your team has with a partner like ImmuXell. As you said, we were monitoring the run data remotely, because it’s a connected system, from London, talking with Hong-Ming’s team every day about what was happening, offering ideas. We also did some work with our computational fluid dynamics model along the way, to see if we could optimize mixing. Maybe just describe how that collaboration works in practice.
Farlan Veraitch: The process Hong-Ming just described is not a simple one. We have a novel virus that’s never been used before, and on top of that the virus is responsible not only for the transduction but also for the activation and the selection. This is where IRO really flexed its muscles. It was able to deliver a process that was very gentle at the front end, but required some very complex biology on day zero, to do all of those things simultaneously. At the same time, as Hong-Ming mentioned, with these therapies you need to get to a lot of cells. So you go from a very gentle early-stage process to one where, in an ideal world, you’d have a stirred-tank bioreactor to grow up enough cells to reach dose, and that’s really where our system was able to help: doing all of those things in one single container.
To get something that complex working quickly, it was tremendously important to have our team in London and the team in Shanghai working together. In London, we have a very experienced, highly skilled fluid-dynamics team, because at the heart of this is: how do you mix the cells with the different viruses? How do you get the cells out of the lag phase and growing? And how do you then reach those very high cell numbers, all in the same system, using different mixing regimes for each of those tasks? Our team in London worked side by side with the team in Shanghai, and we were also running biological runs in London, where we have a very skilled T-cell biology team. That close working was aided by the fact that IRO is cloud-enabled: as we run, we get real-time information about what’s happening in the bioreactors, so both teams could react from one day to the next as we saw how each run was going.
It’s not just the technology, it was the coming together of the two teams. The scientists on both sides are very talented, and the leads in Hong-Ming’s team and in Ori’s team were able to accelerate together. They had the technology, both the virus and the manufacturing system, which enabled them to move at that pace. That’s a summary of how things went, and the underlying reason we were able to move such a complicated process so quickly through PD to a point where we could start thinking about putting it into the clinic.
Jason Foster: So the collaboration continued through the first three or four months of 2026, from its origins at the end of December 2025. There were maybe four or five test or optimization runs, PD runs, to really understand how the two systems, ImmuXell’s innovation combined with IRO, could be optimized together. And then, sometime in April, Hong-Ming, you and your team felt comfortable starting the process to manufacture for the first patient.
Your program, the IIT program, is targeting solid tumors, specifically pancreatic cancer, but potentially also colorectal cancer in the future, or maybe already. How did you approach working with the investigators across China? Talk me through the patient-selection process you go through, and what actually happened in manufacturing. I know you ran your standard process and the IRO process in parallel, talk me through that work.
Hong-Ming Hu: First of all, we work with top hospitals in China, in major cities, with leading experts in what we call digestive-system tumors, pancreatic, colon and liver. In China there are very many patients, and for pancreatic cancer in particular there’s no good option, so once patients develop metastatic disease it’s not hard to get the doctors excited about a new approach. We set up our system in one hospital that sees more than a thousand of these patients a year, and decided to work with them.
One of the benefits of the IIT route in China is flexibility. Usually, once you’ve set up a production procedure and a protocol, it’s quite difficult to change or improve it. Within an IIT, we can still build in flexibility: when we find something we believe works better or more efficiently, we can run a comparability study in the lab, and as long as we can show it’s comparable in terms of the quality of the cells and meets the safety standards we routinely apply, we can use it. We typically make two batches for each patient, and if they’re comparable we can infuse. I think the FDA is now also moving towards not requiring extensive studies for a phase-one trial, and allowing the process to be flexible as long as the batches are comparable, so we have that advantage. It really speeds things up, we can generate data quickly and, using the Ori system, bring the new cells into use.
For the first patient we saw a very similar expansion profile, it was safe, the patient had no problems and no additional side effects. We typically see the safety advantage of TCR-T relative to CAR-T, and we were able to convince the PI to proceed. Now that we know it’s safe, we hope to follow up with more patients over the next few months.
Jason Foster: So when we manufactured the dose for the patient, that was late April, early May 2026, two of the things we most often work towards with our partners are higher transduction efficiency and faster cell growth, because to get to those higher yields, particularly transduced-cell yields, you need both. Your normal process is a couple of weeks, about twelve to fourteen days? What did you observe when you ran the two parallel processes, one in your legacy flask-based process and one in the IRO system? What did the team see as you went through manufacturing?
Hong-Ming Hu: Our data is still early. We compared bags, G-Rex and the Ori bioreactor, and from our first few batches we feel they’re at least comparable. As long as we have the right conditions, the cells expand well in all three systems, and, as Jason said, in the Ori system it’s faster. We’re still optimizing. Farlan has already pointed out many ways we can improve transduction, and because the virus is completely new it needs a different kind of mixing, which we need to study carefully. We think the efficiency can get even better, but so far it’s comparable to our standard protocol and works a little faster than our typical bag or G-Rex system.
Jason Foster: Excellent, that leads to the next question: the future of the collaboration. Where do we go from here? We’ve identified another patient or two we hope to treat in the IIT, and Hong-Ming just mentioned the additional optimization we want to do. Farlan, maybe you could lead on the next steps with Hong-Ming’s team from the Ori side.
Farlan Veraitch: The most exciting thing about this collaboration for me is understanding how process improvements affect not just cell growth and transduction efficiency, but also measures of efficacy. We’ll be doing some in vivo tests to look at the killing capacity of the cells we manufacture under different conditions, and we’ll also have clinical data coming from each patient. So as we iterate and improve the manufacturing process, we’ll be getting that all-important functionality data, both in vitro and in vivo. That’s critically important, because in this field efficacy hasn’t always followed what you’d logically expect, so it’s very important to have that data feeding into your understanding of the manufacturing process during PD. For me, the IIT system is the ideal platform for developing cell and gene therapies, because you have that all-important functionality information to inform which direction to take the process in.
Jason Foster: And Hong-Ming, from your perspective, where do you want the collaboration to go? I know you have an ambition to file an IND later this year and to treat many more patients. Tell us about that, and how Ori can support you.
Hong-Ming Hu: There’s a really important point about what we can see in terms of the cell and how it relates to efficacy. So far, from what I understand across CAR-T and TCR-T, we still don’t know the critical quality attributes of the cell. We don’t really know the right dose or the right phenotype, we still don’t have clear answers to those questions. This is where the collaboration could help. With our old bags or G-Rex, we didn’t collect much data, but with the bioreactor we have real-time monitoring and we collect all the data. One day, perhaps, we combine that with a machine-learning or AI model that can identify the critical quality attributes of the cell, and that can guide how we improve our process. That’s one collaboration I’m very excited about, and it’s very important.
The other thing I’d like to see is whether we can build an integrated platform, bringing together our virus, the bioreactor and possibly a robotic arm, to see whether we can run in a decentralized system. In a country like China, that could greatly reduce the cost of delivering cutting-edge cell therapy to a much wider population, not just a few wealthy patients. So the first goal, on the scientific front, is to understand what kind of cell we need to generate; and the second is to deliver to more patients at reduced cost.
Jason Foster: Absolutely. Farlan, this is one of the themes you like to talk about, the ability to modularize and scale up, and then add robotic automation on top to really reach those tens of thousands of doses. Pancreatic cancer has, I believe, around 40,000 patients diagnosed a year, that may be a US number rather than global, but either way it’s very large compared with what we produce today as an industry. Last year, in 2025, the whole industry produced something like 12,000 doses, at least with the approved products in the US. So how does the vision Hong-Ming just articulated fit into Ori’s ambition to scale up production in the future?
Farlan Veraitch: Hong-Ming and I are totally aligned on scale-up. The ability to add a layer of robotics onto multiplexed racks of IROs really opens up the ability to generate a very large number of doses in a small amount of space. What’s really exciting in China at the moment is the way cell and gene therapy manufacturing facilities are being embedded into new hospitals from the very start. For me, that’s going to drive access across China and will serve as a model for the rest of the world too. Ori’s ability to work in PD, as we discussed earlier, but also to be multiplexed depending on the room you’re in, whether you’re in a room in a hospital, or in a large facility for centralized manufacturing where you can apply robotics, means all of those scenarios are well suited to the Ori platform, and I can see it being adopted in all three modes in China.
This is exactly what we want to do: process development and therapy development using tools like IRO; scaling up manufacturing so therapies can be delivered in clean rooms in hospitals across China; but also having a system where, if we want to centralize manufacturing and use robotics to hit those high numbers, we can do that as well. It’s so exciting to have a therapy developer working hand in hand with advanced automation to deliver what I think this field needs: combined discovery and manufacturing platforms. When you bring those two things together, you have the ability to develop the blockbusters of the future.
Jason Foster: One of the takeaways from our recent visit to see Hong-Ming and his team in Shanghai and around China was a brand-new hospital we visited, a 3,000-bed hospital with an embedded 800-square-meter cell therapy manufacturing facility inside, purpose-built to deliver localized manufacturing. Access is constrained in China because of cost, as it is everywhere. From the numbers I saw, the approved Western products that have come to China have treated maybe 2,000 patients in total over the five to seven years they’ve been available, but there are around 2,500 different IITs happening across China, and hospitals like the one we visited, and innovative companies like ImmuXell, are driving that innovation. Ultimately patients need access to these therapies, and the market will find a way to deliver safe and effective medicines for them.
I’m proud to be aligned with a partner who shares our vision of enabling widespread patient access to these life-saving cell therapies, and impressed with the incredible momentum you and your team have at ImmuXell and the innovation you’re bringing, for very difficult diseases, as you said earlier: pancreatic cancer, colorectal cancer, liver cancer. These diseases don’t have good treatments today, and patients often have a grim prognosis when they’re diagnosed, so this offers hope to them and their families. Thank you for doing that, and thank you for your partnership.
One last question: what does the future hold for ImmuXell? I think you’ve got a potentially exciting other partnership ahead, and you may be taking on a bigger role. Can you tell us a little about that?
Hong-Ming Hu: ImmuXell is a five-year-old company, and I’m very proud of what we’ve been able to do so far. We’re lucky to have a collaboration like Ori, and lucky now to have partners who can help put us on the international stage. We’re going to file a new IND, hopefully very soon, in the United States, and in collaboration with the UK, and maybe Europe too. As a company, we’re looking to move into overseas markets, so we’re very happy to have that support. One goal is certainly to push our pipeline forward.
The second is to build the platform: that’s my dream, to build an integrated system, as we’ve been discussing, that combines our discovery and biology platform with the engineering platform. These days, with AI, we can pioneer in that area and deepen our understanding of the biology and the cells we’re making. Over the next couple of years, we’ll see our products reaching patients, and we want to build something that can be used not only by us but offered to other cell therapy developers too, so that the platform can help bring a cutting-edge product to more patients. That’s our goal for the near future.
Jason Foster: That’s a great point to end on. Thank you, Hong-Ming, so much, for that, and for your partnership. We look forward to working together in the future.
Hong-Ming Hu: Thank you, Jason. It would be great to have you come to China again.
Jason Foster: I’ll see you in a few months, we’ll be there, so looking forward to it.