This episode of the Business of Biotech begins with a personal story about my dad and the standard of care in bladder cancer, before shifting to the work that Dr. Bobby Reddy and his team at ImmunityBio are doing to change that standard of care. They're painfully close. Dr. Reddy, Chief Medical Officer at ImmunityBio, gives us a long look behind the curtain at the commercial preparations the company is making as its lead Phase 3 candidate, Anktiva, nears the goal line in non-muscle invasive bladder cancer (NMIBC). From grassroots engagement with physicians and urologists to making a global press to share clinical results, Dr. Reddy offers plenty of insight into biopharma commercial readiness, and good reason to hope for nearly a million NMIBC patients in the U.S. alone.
You've listened along for years -- now you can watch along, too! Go to bioprocessonline.com/solution/the-business-of-biotech-podcast, where you can put faces to voices as you watch hundreds of interviews with the world's best biotech builders. While you're there, subscribe to the #BusinessofBiotech newsletter at bioprocessonline.com/bob for more real, honest, transparent interactions with the leaders of emerging biotech. It's a once-per-month dose of insight and intel that you'll actually look forward to receiving! Check it out at bioprocessonline.com/bob!
This episode of the Business of Biotech begins with a personal story about my dad and the standard of care in bladder cancer, before shifting to the work that Dr. Bobby Reddy and his team at ImmunityBio are doing to change that standard of care. They're painfully close. Dr. Reddy, Chief Medical Officer at ImmunityBio, gives us a long look behind the curtain at the commercial preparations the company is making as its lead Phase 3 candidate, Anktiva, nears the goal line in non-muscle invasive bladder cancer (NMIBC). From grassroots engagement with physicians and urologists to making a global press to share clinical results, Dr. Reddy offers plenty of insight into biopharma commercial readiness, and good reason to hope for nearly a million NMIBC patients in the U.S. alone.
You've listened along for years -- now you can watch along, too! Go to bioprocessonline.com/solution/the-business-of-biotech-podcast, where you can put faces to voices as you watch hundreds of interviews with the world's best biotech builders. While you're there, subscribe to the #BusinessofBiotech newsletter at bioprocessonline.com/bob for more real, honest, transparent interactions with the leaders of emerging biotech. It's a once-per-month dose of insight and intel that you'll actually look forward to receiving! Check it out at bioprocessonline.com/bob!
I'm Matt Pillar, host of the Business of Biotech podcast, and if you're listening to my voice right now but not seeing my face, maybe you haven't heard that we've launched a new Business of Biotech video cast page under the Listen and Watch tab at bioprocessonlinecom. There you'll find hundreds of videos of my interviews with biotech builders, categorized by topic, like finance and capital markets, regulatory discovery and manufacturing. Don't try it if you listen while driving, but be sure to check it out when you get where you're going. Go to bioprocessonlinecom, hit the listen and watch tab and choose business of biotech in the dropdown. So here's a personal story to kick off today's episode.
Matt Pillar:For the past five years or so, my dad has had non-muscular invasive bladder cancer Benjamin Davies, who's a professor at the University of Pittsburgh School of Medicine, chief of urology at UPMC and program director of the Urologic Oncology Fellowship there. At each visit, dr Davies tells my dad's stories while he runs a cystoscopy to assess the lining of my dad's bladder. The last few times we've been to visit, my old man is at a clean checkup, but that's not always the case. On several occasions, dr Davies' scope has revealed cancer's return. Those appointments are followed by a transurethral resection to remove the cancerous tumor cells in my dad's bladder, followed by several weeks of intravesical chemotherapy to thwart its return, and the frequency of our visits ratchets up to three-week intervals. That's the standard of care, and while it's kept my dad in the game, it's neither physically nor mentally convenient. Whether or not the cancer has returned is a gamble, often a losing one, as recurrence rates in resectable bladder cancers are incredibly high.
Matt Pillar:I'm Matt Pillar. This is the Business of Biotech, and my guest on today's show is a man whose company is very, very close to changing the standard of care paradigm for people like my dad. Dr Sandeep " is chief medical officer at Immunity Bio, whose lead candidate an interleukin-15 super agonist fusion protein the company calls ANKTIVA is squaring up for a likely approval this year. On today's episode, we're going to learn about Dr Reddy and that candidate, how he shepherded it to the goal line, how the company is preparing for commercial success and more. Dr Reddy, a heartfelt thank you, not only for the work that you're doing, but also for joining us today on the business of biotech.
Bobby Reddy, M.D.:Yeah, thanks for having me, Matt. You know sorry to hear about your dad, but I'm glad that you know he's alive. Today, when we have new therapies coming we hope plenty of new therapies coming it's much better, you know, options and opportunities for patients.
Matt Pillar:For sure and I appreciate that. My dad, by the way, is doing considerably well. He's doing well in between these treatments. But, as I said, you know, for a guy of his age it's not just physically holding taxing, but it's also mentally taxing to go through the not knowing and then the knowing and then the repeat procedures. So it's really exciting for me personally to see development and progress in this space. I want to start out getting a little we're going to get to know you and what led you into this space in a little bit. But I want to start with the candidate itself and I want to kind of pick up on. I understand that you've been working on this candidate pretty much since it was considered developable. Tell us a little bit about your history with N803 or ANKTIVA aware of it about 2017 or 18.
Bobby Reddy, M.D.:I think they had presented some of their early data, their phase one data, and there was a whole slew at that time of therapies that were in development, looking at how we could bolster the immune response, and checkpoint inhibitors had been out for a while. I had been a practicing oncologist for many years and I had used checkpoint inhibitors and what we saw with that class of therapy is tremendous, tremendous improvements over where we worked before. For example, in lung cancer. You know we would almost never see a five-year survivor who had metastatic disease, and now it was. I wouldn't say routine, but you know it's relatively common to see people that were three, four, five plus years out, um, and so there was a real, there's a story there. But we also saw the majority of people relapsing. So the question was okay, what can we add? What's coming down the pipeline to forestall those recurrences, delay them and possibly prevent them? So the whole theory was can you boost the immune response just enough to get over that threshold, right, that relapse threshold? And the thought was well, there's secondary immune checkpoints. So the checkpoint inhibitors, like pavrolizumab or the volumetritopdivo, those were the first ones approved and they block PD-1. There's other checkpoints. So the thought was okay, can we target those other ones? And so ongoing clinical trials are happening. But the second theory was can you just non-specifically boost all of the immune response, get more out of the T-cells you have? You know, the T-cell's working, it's killing the cancer, but then it stops working. Is it because those T-cells become exhausted the word we use technically is exhausted, they're tired, and can you boost that? And there's good data to say that that can happen.
Bobby Reddy, M.D.:So when I was in training, I trained at City of Hope and we did hematologic transplant, bone marrow transplant, but we also were a center for high-dose interleukin-2 and high-dose interferon for kidney cancer and melanoma, and that is a very, very, very toxic therapy. But at the time I don't want to date myself, but you know 25 plus years ago there wasn't a lot of other options and so you know we would give people very high dose therapy, would make them very, very sick and if they, you know, sufficiently recovered, there was a small percentage less than 10% who would be cured of their disease. So it's very exciting. So the promise was there, but those were very toxic medicines and we were trying to do it all on its own.
Bobby Reddy, M.D.:So the theory was maybe you could go with something that's less toxic and add it to something else that's already working, so you don't have to be as toxic and you can still get the benefit. So the theory was there. So they presented their data and immediately what struck me when I saw the data was this concept of wow, this is actually what we've been waiting for, something that isn't going to kill the patient with toxicity but could add to what we already have. So it was a very rational and, I would say, attractive concept. So I immediately got involved and started talking to the team there and followed their work and then eventually, when I joined the company, started to promote that and push that forward in terms of our pipeline.
Matt Pillar:Yeah, how did your first exposure to the molecule happen? Just give us a little bit of context, like, did you meet them at a conference or did you have some colleagues there? How'd that kind of come to fruition?
Bobby Reddy, M.D.:Yeah, yeah, so I did. I met them at a conference and it was a small kind of. It wasn't one of the big ASCO conferences, a smaller conference, so it was the kind of situation where you could actually go and talk to the presenters and so the data was being presented from the bladder program and what was striking is in the early phase one, they saw responses. And traditionally, when you're doing a phase one clinical trial, what you're looking for is to establish safety and a dose to go forward and you don't expect to see responses. And what they saw was responses in all of the nine people that were treated. So that was, you know, wow, a nine out of nine, 100%. Now, I'm not traditionally someone. I'm not a urologist by training, I'm a hematologist, oncologist. I don't treat bladder cancer or non-muscle invasive bladder cancer, so 100%. I said, okay, that's pretty exciting, but what would you expect? So I went and I talked to the presenter and I said, well, what would you expect? And they said, well, we would expect to see maybe 80%, but not durable. We would expect that BCG works and exactly the story that you've already given right, it works, but it's not durable, that at some point you'll relapse from that the majority of people relapse.
Bobby Reddy, M.D.:So I said, okay, well, what do you think? He said, well, 60%. We would think that at two years, 60% might still be in remission, 40% would relapse, but we have 100%. So we think something's happening there. Yeah, okay, it's a good story. I'm intrigued. Tell me more. And you know, we just we started corresponding and I became very interested because I could see and I was, of course, selfishly not thinking about bladder cancer, because I don't treat bladder cancer I was thinking, well, what about solid tumors and lung cancer, pancreas cancer, et cetera? And that's, you know, that's the thought would be. It would be very similar.
Matt Pillar:Yeah, and I should note at this point, dr Reddy, that you know obviously the lead candidate, the one that's closest, is your bladder cancer candidate. Obviously, I have a bias, but you've got a much deeper and richer pipeline. We'll talk a little bit about that later on. You know where these therapies go next and what other cancers you guys are looking to target. When you joined so you officially joined the company in what? 2020? Correct?
Bobby Reddy, M.D.:Yeah, right around COVID times.
Matt Pillar:Right around.
Bobby Reddy, M.D.:COVID times. Yeah, it's an interesting time to make changes right. What was your charge when you officially joined the company? Yeah, I mean it was exactly so to shepherd the NA-03 program forward. So I mean backing up the company, as you mentioned, as a whole series of assets that are in various stages of development and I would sort of vibricate them into sort of three key pillars. So one pillar is the N803 or ANKTIVA program, the second is the cell program, the natural killer cell program, and the third is the vaccine program. So my charge at that point was really integrating the three. So clinical trials that would integrate the three. And specifically I was focused on the vaccine program and the anti-dose three program.
Bobby Reddy, M.D.:And I had come from a prior background. The last two companies that I worked for were diagnostic companies and we were focused on doing next-generation sequencing. So Karis Life Sciences and Nant Health, and we had built this bioinformatic pipeline to identify mutations. But the purpose of identifying those mutations was to ultimately use that information to build better cancer therapies and specifically a cancer vaccine. So, coming to Immunity Bio, the whole purpose was to identify these mutations, create vaccines and then bolster that vaccine immune response with a drug like NNO3. And we've done some early work and we're moving towards that. But along that journey we saw really profound early benefit, as I mentioned, from the phase one and then into the phase two and early on in the phase two and turned our attention to okay, this is a product that in and of itself is going to work. We don't need to add a vaccine, we are adding BCG. I mean it works in combination with BCG.
Matt Pillar:Right.
Bobby Reddy, M.D.:And so we said, all right, let's prioritize that because we can get that out, we can get that to patients earlier and we know it can help people and it appears to be safe at that time. Certainly, the further studies have indicated it's very safe. So, you know, really doubled down on our efforts to move that more rapidly.
Matt Pillar:Yeah, yeah, yeah, and you were willing to embrace that shift in your anticipated responsibilities.
Bobby Reddy, M.D.:Yeah, yeah, yeah, sometimes, you know you can't always, you know. I say it's like you're the captain of the ship, but you have to go where the wind takes you. So the wind was taking us there. Yeah, you know, I say it's like you're the captain of the ship, but you have to go where the wind takes you, so the wind was taking us there.
Matt Pillar:Yeah, there'll be time for tacking the ship later, that's right. That's right. Yeah, when you joined in 2020 officially. So my job here and we have a limited amount of time to do this, so I'm going to give up the reins to you to lead a little bit, because what I want to do is I want to get a story. I want to hear the story about where the molecule was when you joined and the progression that's led us to the point where we're looking at an anticipated approval here this year. So where was it when you officially joined the company and took on that responsibility?
Bobby Reddy, M.D.:Yeah. So it had gotten through. As I mentioned, they had started their phase one. They had basically completed accrual in their phase one. The phase two programs were submitted to the FDA, they had been reviewed and they'd been approved and we were starting to enroll in those trials. Unfortunately, as I said, it was COVID and that was a whole different universe for clinical trial operations. It was challenging to be able to complete the normal sort of course of business in terms of monitoring of the trial, startup, training of the investigators, even patients coming in. There was times I mean we now look at it in the rearview mirror, but at the time, you remember it was pretty scary. So if somebody had a non-lethal disease in terms of their bladder cancer, at that point let's say it's in remission they were saying I don't know if I want to go to the hospital right now to have a procedure for something that's non-lethal, when there's a chance I could go, be sitting in the hospital and get a lethal infection.
Matt Pillar:Sure, it certainly resonates. I mean the personal story that I tell about my dad. Like we did that through COVID, we were traveling down to Pittsburgh, you know, going into the hospital and going through all the protocols during that. So it resonates entirely. Anyone who was dealing with a chronic condition during that time or enrolled in a clinical trial can certainly relate.
Bobby Reddy, M.D.:Yeah, so it was tough, but you know, so we had to look at, you know, the new technologies that have become available and the way that all of us adapted to that. So the use of remote monitoring, the use of more telemedicine capabilities to be able to collect the data and stay on top of it. So that was you. So at that point that's where the program was, and then it was also we were starting the solid tumor program, so we're getting into lung cancer and pancreas cancer as well.
Bobby Reddy, M.D.:From the bladder perspective, it was also a time and it's been an ongoing history of something called the BCG shortage.
Bobby Reddy, M.D.:So that started roughly around 2016 in the United States but has been on and off essentially throughout, and it's highly location-dependent, meaning, at a given moment, in a certain reach of the United States, there may be acute shortages of BCG supply, whereas at others there isn't and it just sort of moves around.
Bobby Reddy, M.D.:And so this has been a challenge because, as part of our clinical trial, we provide the BCG, so we're only given a certain allotment and we buy as much as we can, because we want to put more people on trial, and we have a good problem, and our problem is this the people on our trial are doing well, so they stay on, but that means they're consuming all of our BCG. So there was that issue of trying to manage the supply and the demand and thinking about how strategically we could open the trial at certain locations. So in that sort of complex milieu we were able to push forward and complete the phase two BCG unresponsive trial and we really prioritize that. And now we're pushing our resources into the BCG naive population. The reason we did the BCG unresponsive is that's a single arm trial, whereas the other trials randomized. So if you have limited BCG supply, you know I can get to the finish line faster in a single arm than a two arm and that's really how we prioritize it.
Matt Pillar:Yeah, yeah. And that BCG unresponsive trial can you share with us? I mean I've read some of the statistics and some of the results of those studies Can you share with us? I mean I've read some of the statistics and some of the results of those studies. Can you share with us some of the successes you've seen there?
Bobby Reddy, M.D.:Yeah, absolutely. I mean this is now public data. We were able to publish this late 2022 in New England Journal of Evidence. The first author is Kareem Chamey. He was the lead accruer from UCLA and Sam Chang was the second lead accruer and he said Vanderbilt, and what we showed is, when we give BCG to people who basically, you know the BCG is unresponsive In other words, they had a full course of BCG and a full course of maintenance BCG and yet their cancer has recurred.
Bobby Reddy, M.D.:If we give them back the same BCG but add N803 given directly into the bladder. For people with carcinoma in situ, which is one of the higher risk we have in bladder cancer non-muscle-beating bladder cancer we divide it up into low risk, intermediate risk and high risk. So this is considered high risk disease, high risk for recurrence or progression. In that population. What we saw was a 71% complete response rate at any time. Now what does any time mean? It means that when you get the drug, as you know, you get the drug a couple weeks in a row and then you come back to be reevaluated after three months with that cystoscopy in the office. If, at that point in time, you've achieved a complete response, you've got a complete response. Funder.
Bobby Reddy, M.D.:One of the unique aspects of our clinical trial design was we also allowed what's called re-induction. So in normal clinical practice of medicine, people will get a course of BCG six weeks in a row and then be evaluated six weeks after that. So it's a three-month period of time. If they haven't achieved a complete response, you can give them another course of BCG, because sometimes you need more time for your immune system to really kick into gear and this has been shown and this has been demonstrated historically. So we allow that. So we give another six weeks of BCG and then we give the 803, the N803 ativa. We call it. N-803 is the shorter chemical name for it. The long chemical name is painful. It's nogopendicin in bacchuset alpha, so we'll just say N-803.
Matt Pillar:I'm sure you've said that several times, but I still give you credit for nailing it just now. It is a tongue twister.
Bobby Reddy, M.D.:So what we do is we give that second course and we'll achieve a remission, a complete remission in about half of that additional group. So that gets you about 55% up front and another half and you put those two together and you get to a 71% where the cancer has effectively completely gone away. And that's without surgically removing it. That's just the drug going into your bladder, essentially killing the cancer.
Bobby Reddy, M.D.:So, that's good. That's good. But the important thing, as I said earlier, is not that it works, because we know BCG works. It's does it keep working Right. And what's exciting is we're seeing duration here. So in the published paper the median duration was over two years, but we have now updated data and we have press release where we, in our filing with the FDA, we've extended this beyond three years, and so that is as I said in the very beginning.
Bobby Reddy, M.D.:What was exciting for me was immunotherapy as a class was really different than chemotherapy. When I was in training, the only thing we had was chemotherapy and we were starting to do, you know this, high-dose interleukin and high-dose interferon. But chemotherapy works. It kills cancer, but then the cancer comes back and then ultimately our patients succumb to the disease. So what's exciting here is when the immunotherapy works. It's training your own immune system to continuously fight that cancer and prevent it from coming back, and that leads to this long plateau of durability, which it's too early to say. We don't want to say the C word, but we hope that's indicative of a cure.
Matt Pillar:Yeah, yeah, it's incredible, and I mean just contrasting that with the standard of care that I described and that so many bladder cancer patients have experienced. I mean, I believe it's one of the top five most common cancers in the United States, particularly among men. Am I getting that right?
Bobby Reddy, M.D.:Sadly, it is far more common in men than women. However, women tend to have a worse prognosis. They get diagnosed later. So it's important that women and you know female urologists and urogynecologists who specialize in this for women are aware, so that we don't have that delay in diagnosis so maybe we can have at least the same outcomes or better outcomes for women.
Matt Pillar:Yeah, yeah. But as I was saying, I mean, just contrast it with the standard of care. It's cause for great hope. Your activity leading up to the BLA was this had you had experience with BLA submissions in prior roles?
Bobby Reddy, M.D.:No, so in my prior life I had done a lot of work in terms of regulatory submissions for devices. As I mentioned, I come from two diagnostic companies. We had a FDA. We had the only at that point we had submitted and got approved. The only FDA cleared whole exome to our normal sequencing test, which was a really high complexity. In a past life at Keras, we had relatively simple devices and had worked with many, many companies that were working on companion diagnostics. So moving into the drug product world was quite different. So this has been my first BLA experience and there's a lot of similarities, right, but there's a lot of differences as well.
Matt Pillar:Well, you're the perfect person to answer this question and answer it to the perfect audience, because the bulk of our audience are folks who are in perhaps discovery, preclinical, very early stage, and many of our listeners, like you, haven't had the opportunity to work through a BLA submission. So I guess I'd just ask you to maybe share some introspection and thoughts on that process, how it went for you, maybe some learnings and advice that you'd offer to someone stepping in a role, just like you did back in 2020 and seeing this through.
Bobby Reddy, M.D.:Yeah, I think I mean. The first thing I'd say is you have to have a good team. You can't, like, no one does this alone. Obviously it's a massive undertaking. You need a really good team. You have to have a solid team that has knowledge and experience. They're people that you trust and can work with, and I'm fortunate to have that supportive network. The chairman of our company, patrick Tsumshan that's one of the key reasons I had come to the company is Patrick has tremendous experience and knowledge, has had multiple drugs approved, not just at the path we should take and there might be okay, there's two or three or four other options and let's think about that and discuss that, and that resource is tremendously valuable. I think without that team it can't be done.
Bobby Reddy, M.D.:I think the second thing I would say is device and drug are different, so you have to sometimes unlearn what you know. Experience is always helpful. Knowledge and experience is always helpful, but you always have to be open and willing to say oh, we did it this way, but we have to consider doing it that way instead if we're going to be successful. So having that internal flexibility is important, but the regulatory landscape in general is pretty slow to move and change and so you kind of understand your playing field. But you have to know in advance things can change and you have to try to build and feel safe. So, in terms of a program development, you have to anticipate.
Bobby Reddy, M.D.:Not only are there going to be competitors, but the regulatory landscape could shift. So, for example, when we started the program, one of the key things was that in bladder cancer there was guidance from the FDA that a single arm trial could be adequate for this indication. But we also know that, for example, for papillary disease. So I mentioned carcinoma and cytotrophic. But for papillary disease we ran a phase two single arm and the FDA said, well, that's nice, but you need to do a randomized trial.
Bobby Reddy, M.D.:So we've built it in that program, we know what that looks like and we can go to that once we complete our other studies because, as I mentioned, there's only a limited amount of BCG and, knowing those things, having early conversations with the FDA, having frequent interaction, we were fortunate we had achieved breakthrough designation and I would say, anyone in drug development, if you can get it, take it, because the ability to have frequent, meaningful dialogue with regulatory agencies, health authorities globally, is going to help tremendously. Sometimes it seems like, oh, that's, oh that's, you know, an extra burden? Absolutely not. It's certainly helpful and can steer you in the right direction. Even when you think you're going in the right direction, you might find that you're actually lost in the woods. It can get you back on the path.
Matt Pillar:If you can get it, take it. So what went into getting it Like in your experience? What did Immunity Bio need to do or choose to do to achieve breakthrough designation?
Bobby Reddy, M.D.:Yeah, I mean, when we took a look at the interim analysis, we saw a tremendous signal for both efficacy and safety and we reached out to the agency and asked the question of is this appropriate for possible breakthrough designation? And in that submission, what, beyond this preliminary data set, do you want to see? And they were actually very helpful and gave us feedback about what was going on in our other programs and what data they would like to see from those, and together we sort of moved forward. We put together that package we presented to them and they gave us breakthrough. And I think it's very telling because the regulatory agencies really are there to help.
Bobby Reddy, M.D.:I mean, their charter is to have new therapies safe and effective new therapies available for the American people, and so they want you to succeed. They want because any company, anybody in development, if you can come up with a better mousetrap, that is a benefit to the American people and that's their job. So they want you to succeed and they're there to help you get there as quickly and as safely as possible, because that's the key. We want to make it safe for the patients that are out there. We also want to make it fast because unfortunately, you know, people are sick, people are having practiced, having been a practitioner who's joined industry.
Matt Pillar:I talk to MDs all the time who joined industry, but it's, I guess, more rare for those MDs to get back to a point through industry, through drug development, where they get to feel the patient impact that you're so close to feeling again right as an MD, like back in your. I mean, I don't want to make assumptions here, but in your soul of soul, your mind, of minds, right, you were a practicing physician, in fact, you were chief of staff at Los Alamitos Medical Center, were chief of staff at Los Alamitos Medical Center. Two-part question One how does that experience sort of feed your worldview in industry? And then two, I guess just some personal, how does it feel at this point for Dr Bobby Reddy to be on the cusp of having that sort of patient impact again?
Bobby Reddy, M.D.:Yeah, no, it's super gratifying, right, but I mean, as I said, I'm just a small cog in a big machine. I recognize that I try to do my part. It takes a big, big, big village to make this happen. Having said that, you know one of the reasons that I moved away from practicing? Because I, you know if you'd asked me 30 years ago. Well, you know, you're exposed to research and that exposes your mind to new questions and new opportunities, and I was very fortunate.
Bobby Reddy, M.D.:My location where I trained and then where I worked, was Southern California. I was close to the San Diego biotech corridor, which was again at this period of time you know we're talking late 1990s, early 2000s was really starting to explode, not just in terms of new novel therapeutics but specifically diagnostics around sequencing technologies Early it was PCR and then later sequencing and so I had an exposure to that and I was a consultant for many of the big companies and it just led me into that world. And there was a point where I said I can probably do more with my knowledge and expertise by crossing over and really trying to move the needle there than here, and I think at that time also we were seeing a bit of a change in the way that medicine was being practiced, where there was a lot more consolidation of medicine into large entities with very defined sort of pathways and algorithms and a little bit less of the sort of. What I was looking for was really precision medicine, which I would also argue is personalized medicine, which I still passionately believe in, I think, in terms of cancer, where an understanding of the given individual, their specific genome and how that interacts with their tumor process, because cancer is different than, say, an infectious disease. An infectious disease, that's an external organism that we need to eliminate, but the cancer is you. Technically that's you and it's transformed. So it's definitely smarter than an external organism and it's much more complicated and difficult. So we have to have that fundamental understanding of both the host and the disease, and so we were sort of moving away from that. I felt like I could do more by sort of crossing over into industry and so I went in that direction. But definitely it's gratifying to see, you know, hopefully, an approved product get to market so it can help more patients. But even in the clinical trials, when we see good responses, when we see complete responses and some difficult to treat tumors pancreatic cancer, glioblastoma.
Bobby Reddy, M.D.:It's very exciting. It's early, it's small. We need more. You know there's certainly plenty of opportunity. I don't think anyone's on the cusp of curing cancer, but if you'd asked me 20 years ago when I was in training, or 30 years ago, is that a reality? Is that something that's going to happen in your lifetime? I would have said no, and now I wouldn't say that I think it is a reality, I think it's a possibility. I think we're getting closer. We're seeing so many advances with cellular therapy, with CAR-Ts and now TIL therapies being approved that if we can bring all these pieces together, we have the tools that can really transform and change the trajectory for most patients. It's a really exciting time.
Matt Pillar:Yeah, it sure is. Unfortunately, this is where I want to shift a little bit into sort of commercialization efforts. Unfortunately you can. Where I want to shift a little bit into sort of commercialization efforts. Unfortunately you can have all the tools in the toolbox but a lot of therapies struggle with commercialization and some of that is self-inflicted. I've seen plenty of biopharma companies, and even big pharma companies, suffer some self-inflicted fate at the commercialization level. So I'm curious about that. I want to ask you a few questions about sort of what your role has been as CMO in the lead up to commercialization efforts, what those efforts look like and how you anticipate ensuring the post-commercial success of the therapy. So maybe start, if you wouldn't mind, dr Reddy, maybe start with I'm curious about, like what is at this stage in Immunity Bio's, you know sort of trajectory what is the CMO's role in pre-commercialization efforts?
Bobby Reddy, M.D.:Sure, yeah, I mean I think that the key role is to continue to advance sort of the medical communications aspect of it. So knowledge and communications in terms of the presentations that we're making, the data that's being presented, publication strategy. So we recently, a few months ago, we had a paper on the quality of life that was seen in the phase two, the pivotal trial for which we're going to be commercialized, showing that there is essentially no decremented quality of life with the drug when added to BCG and these BCG unresponsive patients and we know historically people do very badly because ultimately their bladder is getting worse and worse with all these surgeries, as you mentioned, multiple TURVTs, and then certainly if you progress to have your bladder removed, your quality of life decreases. So it's exciting to see the quality of life can be maintained and you're not having toxicity-related decrement in your quality of life, for example. So it's things like this where getting those messages out there and then helping to lead the medical affairs effort, academic physicians working to establish collaborations in new areas of research, whether it be preclinical or clinical, that are not necessarily what the company is doing. We have company-sponsored trials, of course, areas that we think are the next opportunity for an approval. But that doesn't limit who we are as a company. We like to think that no pun intended, but that the science is in our DNA and that we're really looking at what works.
Bobby Reddy, M.D.:Again, our founder, patrick Sun Chung, is an MD by training. He's a physician. He's not looking at things necessarily from is this going to bring the most immediate, highest commercial return? He's looking at, is this going to be the best thing for a patient? If this was my patient, how can we best treat their disease? And when we take that lens, we might do some investigator initiated trials. That might seem wait, how does that fit in your strategy? But it does, because our strategy isn't limited to just promoting the one product. We have several, as you mentioned. We have several products in the pipeline and can we bring those forward? And if we knew that the one product could cure bladder cancer, we would be done. But we know it doesn't. So, and that's our goal we need to cure, we need to really drive to that cure. 71% is a great number, but it's not 100%. So that's really my charge is can we take've got this one? That's pre-commercial?
Matt Pillar:getting ready to become commercial. You've got another one that I think is just entering phase three and then some mid-clinical candidates. What is the commercialization effort and the assemblance of a medical affairs effort? What does that do to a company immunity, bio, size, organizationally and how do you manage through it?
Bobby Reddy, M.D.:Well, it's a culture change, right? It's different to go from a free commercial company to a commercial company. You know, we've started having compliance training for everyone in the company so they understand the rules and regs, understanding things like the Sunshine Act I mean, these are all things I'm familiar with from my background but for others in the company, even people who are in manufacturing, for example, to understand, oh okay, what is this? And I think these are all good things for them. The second piece is that, as we bring on the commercial enterprise, we shift to look at how we, as I said, not just medical communications but all communications, how we communicate the message of who we are in the United States in terms of our healthcare delivery system, is making sure that there is a positive formulary determination, a positive coverage determination, we think, for this product when approved, because certainly, if it's not being paid for, it's not going to be given to any patients, right? So it's important that that value proposition is realized.
Bobby Reddy, M.D.:You mentioned something earlier about the frequency of bladder cancer.
Bobby Reddy, M.D.:I think what's maybe scarier is that bladder cancer is actually the most expensive cancer to treat in the United States and the underlying reason and you hinted at it is the chronicity you know.
Bobby Reddy, M.D.:So in a way that's a good thing. I mean, it's very bad to have, say, lung cancer, because people aren't living long, but with bladder cancer they're living a long time, but they're living with their disease and with the side effects of their disease and multiple treatments, multiple surgeries, and all of that adds up over time. And then there's a big surgery, sometimes at the end of that, which is to remove the bladder, which is a huge, very expensive surgery, and then the downstream cost of that. So you know, as a society, one of the things that we look at is, you know, if we can even have a small dent in that, if we can take away 5% of people losing their bladder, it could be huge savings to the health plans and to the United States as a whole. So it's an exciting opportunity that to see if indeed, can we actually not only make new medicines, but can we make new medicines that are affordable for everyone in the country. It can't be just for the 1%, it has to be for everyone.
Matt Pillar:Yeah, yeah. How do you communicate? I mean, these are some complex equations, complex projections. How do you communicate that to the stakeholders who need to hear it?
Bobby Reddy, M.D.:Yeah, so it's. I mean, it's the old fashioned way of boots on the ground and face-to-face meetings. You know we're meeting by Zoom, but you know, one day I'd love to meet you face-to-face.
Matt Pillar:We'll make it happen.
Bobby Reddy, M.D.:Zoom I spent I joke that, you know, I just spent my entire day in Zoom land. So I don't, you know, I don't know where I am physically located because I'm in Zoom land, right, but I think there's no better way than actually just getting out there and discussing with people and answering their questions face-to-face. That's why I was happy to be able to talk to you. And then the second thing, as I mentioned earlier, is publications. I mean, there's nothing better than having a peer-reviewed, peer-refereed journal where someone else it's not me saying it, it's not the company saying it this is data, objectively, it's been vetted, it's true, you can trust it.
Matt Pillar:And then people can make their own conclusions from that data. I'm looking at the clock here, dr Reddy. I can't believe how much time has passed already since we started talking. I want to be respectful of your time, so I do want to shift a little bit and discuss what the manufacturing paradigm looks like in a pre-commercial organization like Immunity Bio right now. What is your approach? Are you manufacturing in-house? Are you outsourcing? How do you anticipate maintaining supply?
Bobby Reddy, M.D.:Yeah, so for N803, we currently are outsourcing the manufacturing. We have a long-term goal of being able to potentially bring that in HAPS. Initially no, and with the current CDMO we have contracts to be able to supply plenty of drug, I mean one of the other drugs in this space. There were some issues in terms of being able to manufacture and produce that. We do not anticipate that being an issue at the time of launch. We'll have enough drug for anybody who needs it. I think that's an important thing. As a second piece, though, that I will add, we have other components to our organization, which I said was the cell therapy. That's something which-how is a little bit different, but close enough that we can translate it to being able to bring in other drug production under one roof but across different locations that we own and maintain. So that's our ambition for N803, but initially it is through an external manufacturer. But we do not anticipate any type of supply chain disruptions or shortages. We should be able to produce adequate drug supply.
Matt Pillar:Yeah, that brings to mind another question. I wanted to ask you about the intent from the outset. Now I know that you've only been with Immunity Bio officially for like four years now, but you've got a history beyond that. So many preclinical and early clinical companies that I talk to when we talk about like beginning with the end in mind, companies are increasingly transparent about their intentions. We're going to take this thing through phase two and then we're going to work like hell to sell it off and then we're going to start another project, but we never want to go commercial. We're never going to manufacture. Was it always Immunity Bio's intent to take drugs to the finish line and potentially manufacture them in-house and become a full service biopharmaceutical company?
Bobby Reddy, M.D.:Yeah, I mean, I would say that that's you have to. I mean, you're right, you could plan that. That's not your intent, but if you plan that way, then you're sort of painted yourself into a very tight core. Instead, our plan was like we want to have all the options available. We want to be able to do this. We're planning for long-term success, not just for this but, as I said, for the other products. We don't intend to be a one and done enterprise. Having said that, we are a public company and we have fiduciary responsibility to listen to offers. So if someone out there wants to throw us a very attractive, very gaudy offer, I think we would be absolutely poised to listen to that. But at this point, we do have the capabilities to do it ourselves. We're confident in that, have the capabilities to do it ourselves. We're confident in that, and that is our plan, not just for today, but for tomorrow and really the foreseeable future.
Matt Pillar:Yeah, we do get a healthy crop of VCs and folks in the finance community who listen to the show. So there you go. Hopefully they're hearing the message. In the time that we've got left, let's talk a little bit about the other programs that are coming on the heels of N803.
Bobby Reddy, M.D.:Yeah, so I'll start with the cell program. I mean, we have two lead candidate cell products. One is autologous, one is allogeneic. So the autologous program is in phase one. Currently we call it MSANC. What we're doing there is it's memory cytokine, enhanced natural killer, cell memory-like, and so the idea is that we take your autologous cells for resupplation and then we expose them to a variety of cytokines, one of which is the N803 IL-15 product, and we get a differentiated cell out of that. It's more effective at killing and because it's autologous it may persist longer and go on being able to exhibit long-term you know durable tumor control. It's early, it's phase one. I have no data to discuss at this point, but you but I'm hoping that maybe by the end of the year in something like ASH, we might be able to present some public data.
Bobby Reddy, M.D.:The other program is a little bit more mature, which is the allogeneic cell, and that's now basically in its third edit. So we started with something called the NK92, which was a patient-derived cell. Line is a patient-derived cell line and normally NK cells have a ratio of killer inhibitor molecules on their cell surface and normally the ratio is 50-50 in sort of yours and mine and average NK cells In this individual patient the ratio is 95-5, favoring the kill, and so it's a very potent cell. That cell line was then immortalized and some edits were done. So the first edit was to introduce an endogenous IL-2 receptor so that essentially the cell could feed itself, it could self-propagate and self-stimulate. Number two we added a high affinity CD16 receptor. Cd16 partners with monoclonal antibodies, so this would enhance the ability to have ADCC, or antibody-dependent cytotoxic killing. And then the third added recently is the CAR. So the CARs that are in clinic right now are PD-L1. And so we have an alternative potentially to checkpoints. And then the second is CD19. So that phase one is just getting ready to kick off and I'm very excited about that because we've seen, of course, cd19 CAR T-cells have transformed the way we treat ALL, for example, or refractory lymphoma. So a CAR-NK cell could be a very attractive bridge to a CAR-T cell.
Bobby Reddy, M.D.:You know, when I was treating patients we'd send them off and you'd have to wait for the CAR-T cell to be produced. And that's a very sort of emotionally difficult time for the patient, the family who knows that that person is actively progressing usually. And then sometimes we give them largely ineffective chemotherapy. We know it's ineffective, but we have no choice. We're trying to do something to bribe us time. And then the worst case scenario is small minority percentage, but it still happens. It's getting better, but it still happens. They cannot produce CAR T cells. So this will give us an option in those patients. So it's very exciting. It's very early, it's just getting ready to open, but I'm very hopeful. That's the cell program, then the vaccine program.
Bobby Reddy, M.D.:We have a second generation adenovirus, though different than, say, the Chadox or Johnson Johnson adenoviruses from COVID. The key with the second generation is we've eliminated something called E2B. The key with the second generation is we've eliminated something calledchallenge. But with this, because you've eliminated that viral fiber, we can give it again and again and again. And in a phase two trial in colorectal cancer where we give an adenovirus with a CEA insert, we actually saw 13 months of overall survival in people who had failed standard of care, basically third-line patient, third and fourth-line patients, which is comparable to what's out there now. It's actually better than, say, even the more recent approval of Bevacizumab and Lonser in that setting.
Bobby Reddy, M.D.:So we think that there's certainly an opportunity, particularly if we partner that with N803. And so right now the NCI is doing a trial in patients with Lynch syndrome as a cancer prevention using the adenovirus to CEA plus N803. So that's an exciting opportunity for us to get it to prevention and use that information to help inform another trial in colorectal cancer. So these programs, if we put them together you can see there could be overlapping synergies and in fact we did that in pancreatic cancer where we gave all of these together and what we saw in late-line pancreas cancer. In a trial called Quilt88 that we presented at ASCO last year we saw a doubling effectively of overall survival in people with third-line pancreatic cancer. So it's a single-arm trial, it's not randomized, but we got survival to go beyond six months and historically in that setting it's about three months. So proof of principle that the concept works. And now we're going back to the drawing board and see if we can refine it, make it a little bit easier to satisfy some regulatory requirements and move that program forward. Yeah.
Matt Pillar:Yeah, share with me just a couple of thoughts on sort of the. I mean, obviously it's a very diverse but at the same time kind of interwoven approach, right, many modalities, a lot of overlap. Share with me some thoughts on how a company organizes to be able to swallow that ocean to use a bad cliche right Like to have the, the IP, the, the personnel, the skill, the talent, uh to to be able to to kind of maneuver through and, I guess, maintain the vision for how the, how all of these different uh approaches come together, cause I, you know, I I'm just saying like I talked to biotech founders and CEOs every day of my life and not everyone's cut out for that.
Bobby Reddy, M.D.:Yeah, I mean, I think it's definitely challenging. Some of it is we're fortunate, I mean when Patrick so I'll just back up the company itself Immunity Bio was produced with the merger of Altor with E2Bix, with Globimmune and with NatCell, and so you have different pieces, different strengths, being brought to the table, and what that allows you to do is retain certain strengths and lose certain other things that maybe aren't strengths. So you build through this kind of approach and you get to, I think, a situation where the whole is definitely greater than the sum of its parts. And Patrick had been building this for 10, 12 years.
Bobby Reddy, M.D.:It's not an overnight. It's like the old story of an overnight success, but it was 20 years in the making. So this is years and years of bringing people in who could do the IP part, who could do the contracting, who could do the science, who could do all the other pieces finance, et cetera and it's finally coming together. But, as I said in the very beginning, it's a big team. It really is. It's a big team. We have several hundred employees and that's how we can achieve. What we've achieved is partly it's through his vision and his determination, but everybody rowing in the same direction.
Matt Pillar:Yeah, all right. Final question, and then I promise I'll let you off the hook. You're talking like. Here's the content. You're talking directly to an aspiring CMO who is contemplating, or has already stepped into, a role similar to what you stepped into four years ago. You know what's your. The questions may be cliche, but what's your, what's your pithiest advice for said aspiring CMO? Yeah, pithiest advice.
Bobby Reddy, M.D.:Well, I guess you know, don't give up. No, I think the key is honestly and I have to say it's just be humble and ask questions, you know, recognize that you don't know what you don't know, and be willing to take advice or input from a lot of people around you and people outside the company. It's amazing how, as I said, people want you to succeed. They really do, because we're not making a better widget, we're trying to make a better treatment for human beings, so people actually do want you to succeed. Whether it's Xtrella, you're going to be able to find input. You solicit that input and you have to carefully weigh that. But it's much better to get multiple sources of input and data and then make an informed decision than assume that you know the answer. And sometimes, a lot of times, I would say I think I know the answer, but I double check, triple check, and sometimes it does change and that becomes and those are big aha moments that you don't know until you know. So that would be my pithiest advice. I appreciate that.
Matt Pillar:Like I said, I'll let you off the hook, but I want to thank you both professionally and personally. Like I said, the work that you're doing is near and dear to my heart and I appreciate the time that you've spent with us and our audience and sharing the insight so transparently, and we'll be keeping an eye on things. Hopefully you'll agree to come back post-commercialization, maybe a year down the road, when we've got stories to tell about the product and the market.
Bobby Reddy, M.D.:Sure thing. I would appreciate that, matt, thank you. Thanks for the time and the opportunity.
Matt Pillar:Thank you for joining me, dr Reddy. So that's Immunity Bios. Dr Bobby Reddy, I'm Matt Pillar and you just listened to the Business of Biotech. We're produced by Life Science Connect and its community of learning, solving and sourcing resources for all manner of life sciences professionals. I invite you to subscribe to the Business of Biotech podcast anywhere you listen, leave us feedback and a review, and be sure to subscribe to our monthly Business of Biotech newsletter at bioprocessonline. com/bob. In the meantime. Thanks for listening.