Good evening. Um I'm um I am a native Buffon high school and um spent 23 years doing research in cancer immunotherapy at Sloan Cutter and Cancer Center in New York City. A year and a half ago, I made the fateful decision to come back home as many of us from Buffalo often do. And so my return here has as much to do with Josh Allen as it has to do with Roswell Park. Um And I welcome you to tonight's program. And the, the point of tonight's program is that um we uh have investigators from Mosel Park and we want to introduce you to where we certainly think cancer therapy is headed in the direction of utilizing the immune system, a manipulated immune system to recognize cancer cells and to eradicate disease. We are largely, this is a trend that largely started at places like University of Pennsylvania, but also Sloan Cutter and Cancer Center, um where we developed this technology called chimeric antigen receptor T cells or car T cells. Um This technology much to my surprise, even though I was the one that cured all the mice with this technology, um was technology that we moved into the clinical setting. Uh Marco Davila, who is here tonight as well, um was my fellow at the time and we found that when we treated our first five patients that had relapse and refractory A L L adult patients who have a horrible prognosis, we were able to get all five of them into perhaps not entirely durable but complete molecular remissions. Um This meant that immunotherapy which has been around for, for, for, for decades, this was a new avenue where we looked at T cells and other components of the immune system, other than antibodies to, to target cancer cells in our patients. We uh had a very active and robust program in New York and I assumed that I would never come back to Buffalo or anywhere else for that matter. Um I faithfully decided to uh hear Candace Johnson, our CEO out um came to a visit at Roswell Park and in the, in the past years, whenever I'd be recruited somewhere, I would always ask myself one simple question is, can I do here what I can do in New York? And the answer is always no, this was the first time I walked away from Roswell, so impressed with, with the institution, so impressed with the resources that not only could I convince myself that I could come back to Buffalo and do what I could do in New York. But I actually, and this is true to, to to form, could convince myself that I actually could do more here than I could do um in New York. And so, um, with those very long opening remarks, um I, I welcome all of you uh here in the room and those that are, are online uh to uh to this session, which we're calling the New York State Therapy Consortium, uh which I will explain in a couple of slides moving forward. And, um as the MC, I guess I have the honor of giving the first talk. Um I would ask that everyone um hold their questions until the end of the session. Um those online can, can submit them online. Um And we'd be happy to have a, a form after all of our speakers to, to answer any questions that you may have. So I'm going to illustrate really kind of what I did in the first, what we did in the 1st 1.5 years since I got to Buffalo um developing uh cancer immunotherapy at Roswell Park. Um As I pointed out when I first came to visit, I was much surprised, very pleasantly with the infrastructure that was already there and that's largely thanks to my predecessors, be it or, or um or probably even much more importantly, uh Candice Johnson. So when I interviewed, um I told uh anyone that cared to listen, that if you bring me here, um Our goal is to become a global destination for cell and immune based therapies. Um And what does that mean? That means that we are going to have the capacity. Our plan, our timeline would be another 34 years to be able to provide any patient from anywhere that has relapse or, or factory disease clinical trials that could potentially uh provide help or allow us to learn about optimizing immunotherapies. The uh this will be uh made possible by the fact that while we had a capacity to make some of these cell products, we fully expect in the next year, year and a half to markedly expand our capacity uh to generate these highly complex therapies and ultimately to create a pipeline where we can do every aspect of a very complex system to generate and to conduct these clinical trials that would otherwise require years and many long wait lines uh to, to conduct uh aspects of um in the uh through, through uh through private companies. And as a result of this and our ability to work with in uh with industry, we fully expect that both industry as well as uh uh academics will be markedly attracted to, to work with Roswell Park. And again, to allow us to become this destination, not just in western New York, which of course is very important for our patients, but in New York State um in the United States and, and globally. So what is this technology um that attracted me to Roswell or that attracted Roswell to me, it might be a better way of saying it. Um we call the chimeric antigen receptor T cell uh technology, uh chimeric antigen receptor because it is a chimera. Uh it's made up in part of a antibody targeted to a protein that may be expressed on the, on the tumor surface CD 19 is the go to one that has FDA approval uh followed by a transmembrane domain, followed by a T cell receptor, uh zeta chain signaling domain. So this is a classic uh car anti uh car protein. We can take that gene that makes this, this Frankenstein like molecule. And we can put that into a retrovirus or a lent virus. And then we can take a patient's own T cells that we activate in uh uh in a GMP facility. We can infect it with viruses that contain that gene replication, uh uh incompetent viruses. And now that T cell that would otherwise ignore a tumor cell that has the target antigen on its surface now expresses this car or this chimeric antigen receptor, which now enables uh this T cell to recognize the tumor cell as foreign and eradicate the T cell. We were able to do this in New York City. This is actually a trial that uh uh doctor um when he was a fellow um uh initiated uh at Sloan Kettering. Um We actually had a prior trial for C L L and, and then Marco took that trial changed all the CS from the C L L to A S for A L L and then declared that he wrote a clinical trial, which of course wasn't true. But as you can see here, the prognosis for adults, especially with multiply relapsed and refractory A L L is, is dismal anywhere from 3 to 5% long term survival. And as you can see, we had a tail on the curve on a significant number of our patients, several of whom are still alive today after infusion with these chimeric antigen receptors, this led to uh and I am sorry if this slide looks boastful. I keep meaning to take it out, but I just can't bring myself to do so when we reported the first five patients, all of whom went into remission, um we actually uh got a lot of press attention. The New York Times covered it on the front page. This subsequently led to enhanced reputation for, for Sloan Kettering as a place for cell therapy. And subsequently that that technology was licensed to a biotechnology startup called uh Geno Therapeutics, which when it opened was the highest or most successful IP O for a biotech company. The reason why this is relevant is because this is a model that we're going to try to replicate at Roswell Park. We're in, we develop the technology in our laboratories, we demonstrate efficacy uh in our patients. And then subsequently, we are able to generate and enhance the name of the institution. Uh Not to mention the funding that the institution will then have to invest back to our cell therapy program. So where, where do we go? Uh When, when I got here, what, what was the plan? Um Well, the first thing is laying down a foundation, a clinical foundation where we can run clinical trials and what has happened uh 15, 20 years ago, um we would have bone marrow transplant uh services where, where we, where we conducted bone marrow allogenic bone marrow transplants or autologous bone marrow transplants. Um And with the uh uh with the advent of cart cell therapy, uh the transplanter is immediately voiced that they were the original cell therapists and therefore, uh car T cell therapy should fall under under their umbrella. Now, we don't actually necessarily agree with this. Um And so uh what we now have at Roswell is a T C T service. Doctor Davila is put in charge of that and the eventual goal is to take classic bone marrow transplant into one service and cell therapy, which would be T cells and, and, and its variants uh into a separate service. And the rationale for that in part is because we don't expect to, to level off uh car T cell therapy with hematological malignancies, which would would keep it fine in, in, in the T C T service. But obviously, the plan is to expand this uh technology to solid tumor malignancies and establishing a standalone cell therapy service allows us to recruit uh solid tumor uh experts into that service. So it becomes a hybrid service that it doesn't just have transplants, which it certainly will, but it additionally will have solid tumor uh uh attending that are expert in different uh other more common malignancies that can then participate in these trials. So, two years ago, when I first came to visit Roswell Park, uh we actually did have a GMP manufacturing facility and that is kind of the, the the the the the cornerstone of any type of cell therapy that an academic center would like to um develop, which means that we can make these chimeric antigen receptor T cells and a bunch of other cellular products as well as make the viruses that we use to infect these uh these cells in our own facility. Uh The amount of work that's involved in creating a facility and the amount of cost that's involved in creating such a facility is, is quite immense and having sat in on, on, on meetings where, where we developed our next generation GMP facility at Cutter. There are people that get very excited about these regulations and I'm not one of them. So when we got here, we actually did have a facility that was run by uh and still is run by uh Doctor Klinsky, uh who works on dendritic cells, which is another type of cellular immunotherapy and uh the the brains behind the operation being Joanna Stanton, who had experience in industry, as well as in academia on how to make these cells under strict GMP conditions. We had a cell production facility. As you can see there at the top, this facility was built back in 2012, 2013. It's four rooms which is, which is good, but, but still by most standards, somewhat modest. And then at another site, a vector production, this is where the viruses can be made under GMP conditions, um which was two rooms. So we had a total of six rooms. Um and we actually had approval and, and FDA approval to allow us to make cell products that we could then safely infuse into patients when I got here. Uh They, there was a plan of expanding or building additional rooms and they showed us the, the second floor of the C C C building and, and they came to my, the, the architects came to my office and said, well, here we can build another eight rooms. And I, and I looked at the floor and I said, well, what else are we using this floor for? And they said, well, nothing that I know of. I said, so can you see how many rooms we could fit in if we got the entire floor? And it turned out to be 14? And we were very fortunate that um we are now in the process of starting construction of these additional 14 rooms. In addition, we were very uh fortunate that we were able to uh that, that the state, the Empire State Development Fund came to us and said, we heard you're making this facility, we'd like to help. And that made the process, especially with the board, all that much easier. So we're very happy to say that we'll build up an additional 14 rooms that gets us to 20 GMP rooms, which not that, that's what we were aiming for, but puts us a full five rooms ahead of Sloan Kettering, which is a institution that's five times the size. And in fact, we looked into what other academic centers have, have centers that are equivalent. It's not Dana Farber. Um It's not University of Pennsylvania. In fact, the only place that can equal us and I'm not sure that they have virus production capacity would be the city of hope, which is out on the west coast. So we uh in addition, uh especially when when doctor Davila came uh started working on, on uh further uh uh making this a uh nuts and bolts operation. So the second floor of that building is, is is gonna be the new facility. The third floor is gonna be entirely dedicated to immune monitoring. And in fact, we were very uh delighted that we were able to recruit Peter Malak who not just a leukemia expert but also uh expert in in clinical laboratories that will run that facility. We're gonna have the capacity to, to, to do all the quality controls that we want. Um And we're also looking to see if we can make plasmids under GMP or G LP conditions which otherwise would take six months. And Marco, what's the price for A, for a G LP plasmid $200,000? And we can probably do that for uh significantly less. Um And so what that means is that we're not just building a facility to increase our capacity. What it means is that we now have capacity to full capacity to take what we discover in the laboratory and move it into the clinic and giving our patients uh a promise of, of potentially a better outcome. But in addition to that having 20 total rooms also gives us the capacity to reach out to smaller biotechnology companies that may have very interesting technology but not the wherewithal to go through private companies to make all these different steps. And so we're trying to attract on top of it, industry sponsored trials where in the facility we'll be able to generate revenue. But more interestingly, we anticipate being quite competitive with, with who we select. And so we will only run trials that we think um have, have, have worth to, to offer to our patients. So with all this additional building, uh obviously, the, the, the the the leadership uh significantly increases um as the deputy director. Um I have total uh ultimate oversight um of that facility. Um As I mentioned earlier, Doctor Pavo Klinsky, um is uh stays at, at, at, at the top of the line as far as being the, the scientific director, uh Marco, uh who I've mentioned now 12 times, Marco, um well, came from and uh he will serve as the medical director that he is serving as a medical director of facility and very fortuitously. Uh Chris Choi who um had worked at Roswell before went into industry, um worked at uh kite uh as well as most recently at CRISPR. His wife didn't want to leave Buffalo, which we're very fortunate about and we were able to recruit him to be the technical director. There's probably only at best a handful of people in the country that are more knowledgeable about, about this technology and uh and all the technical aspects that that it involves these uh uh these three, the scientific, technical and medical director will work very closely with each other, but also will allow us the ability to, to um to become very attractive to the multitude of biotechnology companies that I work on this technology. I will say this um without dating myself too much. But about two decades ago, when I started working on this as a fellow myself in, in Michelle Sala's lab at Swan Kettering, um there might have been 10 labs in the entire world working on this technology. Um Now there are over 300 companies in China alone dedicated to T cell technology. So there are a lot of startups with a lot of very interesting ideas. Many of them will not actually get to the clinical stage because they're going to run out of funding. It is our goal to, to select out those that have the most interesting, scientifically, the most interesting technology and to help them run their trials and help them succeed. So this is kind of the model that we're looking at. Um internally. Obviously, we're recruiting folks so that, that we develop the technology at Roswell, we do the manufacturing at Roswell and we treat the patients at Roswell. Another another approach which I alluded to earlier is to work with industry. Now, some industry doesn't have the finances to be able to make the cells and run the trial. So we will engage them at a very early stage of their development. They will introduce to us very interesting technology and multitudes of ways that they make the mice survive longer. Um And, and then we will be the conduit that will allow them to test whether, whether in fact their promising technology can help our patients. And then the third approach um uh which which is also quite viable is working with industry because we will become again a a for, for, for cell therapy. Our, our clinicians are gonna be very expert in how to handle and manage these patients that can be complicated. And so we'll work with larger industry that make their own cells and we will engage with them to enroll uh our patients on their trials. And in that case, the manufacturing occurs at their own stand alone facility, but the patients get treated at our facility. Now, as you can see here at the bottom, we have a blue box here called the Empire State Cell Therapy Consortium. I guess that's um that was the clever name that we call this uh this symposium tonight. But we also realize that that if, if we want to move this technology forward, the the the trick is to not just to develop the technology, but it is to run these early phase trials and accrue these patients as rapidly as possible, learn as much from what these trials tell us so that we can then go back and say if it worked, why did it work? And if it failed, why did it fail and then go back and do the next trial? And what that means is that we can't have trials that stay open for 234 years because we just can't accrue patients. And so this type of technology is of interest to a multitude of academic centers, not all of whom have the fortune of having the GMP facilities that we have. And so we've engaged and are in the process of developing what we call the Empire State uh Cell Therapy Consortium. And right now, we're looking at the University of Rochester, obviously, but also at Mount Sinai, uh uh N Y U Cornell and Columbia and, and leadership at all those institutions have demonstrated a very significant interest. And what would happen in that situation is that we would open the trial, we would make the cells at Roswell. And all, all these institutions will have this trial open at their own respective center so they can give their patient populations opportunities to get this type of therapy. Um And so that also will allow for rapid accrual, rapid analysis. And again, the cycle continues until we optimize this technology and, and give significant benefit to our patients. Now, I've mentioned that we, we are looking at uh um at, at recruiting scientists as well. Uh This is a very creative and innovative field. Um Every time we open up a high end uh journal, uh we find that that people come up with very, I I think clever may not be the right word but, but but very innovative ways of, of finding ways of overcoming obstacles that this technology currently uh suffers from. And if you give me another two hours, I could wax poetic about what those issues are. Just suffice to say we need to bring scientists into Roswell to help uh come overcome some of these issues. And we were very fortunate with the 11 day Power Play. Uh That's the ows who, who, who developed uh the 11 day power play that we got funding through them to, to build up a, a laboratory complex, which is the fifth floor of that same building where the monitoring occurs and where the cells are made. So it's all within one elevator ride. Um uh As far as access goes. And this allowed me when I first came to, to ROS to recruit a doctor and uh and we have several other recruits that were very excited about um to uh to, to help move this technology forward. Um With that comes uh an additional aspect uh which is technology transfer. And uh this is Patrick Emmerling who runs our technology transfer uh uh office. It, it's one of those things that when I first came to interview, I immediately wanted to talk to tech transfer. I think Marco did the same when he came to initially interview and that that is would be perplexing under for, for most recruits. But Mark and I both have experienced uh the downside of, of, of poor tech transfer uh um support. And the reason why tech transfer is so important is that these are very, very expensive of trials. And there probably are 11 of three ways in which, in which way you can actually um develop the technology treat the mice and then actually treat patients. And, and one way of generating money to treat patients is through philanthropy. The second way is if the institution is kind enough to give some of their own money to you to develop their own technology, and that's not what Kettering did. And the third approach is to license this technology to, to, to, to companies that then in turn, ask you to run the trials uh with their funding. And so technology transfer is extremely critical to taking this type of technology, which is at least at, at the, at the, at the initiation, extremely expensive. And again, uh why not write grants? Because there is no grant mechanism uh to run that offers enough money to run these trials. I think when we first wrote our first trials 20 years ago, we we, we, we put in the budget that it would cost $15,000 per patient to, to treat these patients and that just fit into an N I H budget. But we knew we were actually lying to, to the federal government about that the actual cost can be anywhere from 100 to 100 and $50,000 per patient. So, if you want to treat, uh and that doesn't include making the virus, et cetera. So we estimate uh a bare bones um uh hometown discount cost to run one phase one trial that will treat anywhere from 12 to maybe 24 patients to be uh well in excess of $3 million. Um And so again, it illustrates what's so great about Roswell Park is that infrastructure actually exists. Um And, and on top of that, uh uh the, the philanthropy and, and what this, what Western New York and I knew this growing up, Western New York reveres Roswell Park and deservedly so, and hopefully even more so, moving in, moving forward, that allowed us to additionally be able to conduct trials that where if we can't license the technology, we have philanthropic funds that allow us not just to build a laboratory space as you saw with the 11 day Power Play, but in addition to actually run these clinical trials, which again are, are, are high risk but extremely high reward. And so um just reiterate the goals to become a global destination. And I I will say also in a year and a half, not, not, not only have we expanded our capacity. Um We've been very fortunate that we've, we've submitted uh uh multiple grants. Tina is here today who who has helped us do, do all of that um to, to move some of these clinical trials uh in and, and help our patients. Um But, but we are um with the recruitments that we've made in the first year, year and a half, we now have people from very high end in, in uh uh academic centers um asking if, if, if there are any slots available um uh to come work at Roswell. Um And that's not uh without signing uh two uh too cocky. Um That wasn't the case two years from now and, and with recruits like male and, and uh um and, and uh and we actually have now become a very attractive center for people that are interested in this technology. And so, um with that, I think I will, I will stop.
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