Translating A New Discovery Into A Novel Cancer Therapy With Grid Therapeutics' Ned Patz, M.D.

0:04Welcome back to the business of biotech. I'm your host, Ben Comer, chief editor at Life Science Leader. And today I'm speaking with Edward or Ned Patz, MD, co-founder and CEO at Grid Therapeutics, a privately held clinical stage biotech developing novel therapies for cancer, including its lead candidate GT 103, the first completely human derived antibody therapy. I'm excited to have Ned on the show today to talk about the process of transferring a new discovery made in his lab at Duke University into a company, Grid Therapeutics, and into clinical development. We'll talk about Ned's early experiences as a biotech co-founder and leader, including how he funded and staffed the company and progressed GT 103 into human clinical trials.

0:50And we'll get his advice for other academic biotech founders looking to turn discoveries into new medicines. Ned, thank you so much for coming on to the show.

0:59Edward Patz: Oh, thank you so much for having me, Ben. Delighted to talk to you. Glad to have you here. As we do on the business of biotech, I want to start out with your background, Ned. You earned an MD at the University of Maryland, worked in academic medicine for nearly 30 years. You completed a residency at Brigham and Women's Hospital, which is one of Harvard Medical School's teaching hospitals, and then returned to Duke, where you'd previously earned a BS in physics as an undergrad to lead your own lab in Duke's radiology department. First off, Ned, why did you decide to switch from physics to medical school?

1:40Edward Patz: Oh, well, that's an interesting question. And I've thought about it, but I think the simple answer is that when I, you know, when I went to college, I wasn't sure what I wanted to do. I was always interested in math and science. I became very interested in physics. I thought it was fascinating. I liked medicine. But the honest answer is I didn't have a clue of what really a physicist or a physician would really do and what the options were. So I think early on, I decided, well, let me take a little more explanation and look at both. And the first opportunity I had after college was I got a call.

2:17Edward Patz: I got a wonderful offer from a man named George Brandenburg, who was the director of the high energy physics labs at Harvard, to work with actually Rory Schwitters, who was one of the high energy physicists in their group. And it was an amazing opportunity with these really smart, fun people. And so I decided to first explore physics and it was fantastic. I mean, it was challenging. It was interesting. It was unlike college where you are given a problem and they know a solution. They gave me problems and I got to work on lots of things. But I always had an interest also in medicine. So at the same time, I made the decision I was going to apply to medical school.

2:55And fortunately, I got in.

2:58Edward Patz: And after I had been doing physics for a little while, I decided I would go to medical school and see how that was. I went to medical school the first two years from work coursework, which I did not like particularly. And actually, for the first three years that I did, I did both. So I tried to actually do both physics and medicine. And I think I finally realized these are two very different fields, very complicated, and that I'd have to grow up a little bit and focus and do one. And during my third year, third or fourth year of medical school, I did a rotation where you do clinical rotations.

3:33Edward Patz: I did one in radiology. I did it at the Brigham, this core rotation. And I realized these radiologists were unbelievable. They were spectacular. They were great physicians. They interacted with every single different field from medicine to surgery to OBGYN. And they knew a tremendous amount of medicine. And in particular, several individuals were just wonderful. So I made the decision I would do a residency and apply for residencies in radiology. And again, I was extraordinarily fortunate. I got a position. I was offered a position at the Brigham and I did a residency there and which was fantastic where I met some great people.

4:18Edward Patz: And that's how I decided that that was the course I was going to then take from then on. Were there similar, I guess, kind of physics and biology writ large? I mean, what what were some of the like key differences? And I don't know if that's what led you to switch to medicine. And it sounds like you, you know, you saw some things right in front of your face that were very impressive to you. People actually practicing medicine. So I'm sure I had had part of it or had something to do with it. But it's it happens. But I don't see all the time people going from like a physics undergrad into medical school.

4:51And I'm just and if you're thinking about both of those fields, you know, is there is there anything that kind of, you know, called to you from from from biology versus physics? other than what you've already said?

5:05Edward Patz: Yeah, I think that, first of all, as an undergraduate, I did almost exclusively physics. I think I only had one biology course during my entire time as an undergraduate. I was much more interested in the math and science part of that rather than biology at that time. But then when I was introduced to a little bit of the biology in medical school, I found also the biology. What was common between them and what I often then later would tell the grad students, It wasn't so much about what type of science or what project you were working on. It was much more of an idea of the process. How do we do science?

5:39Edward Patz: How do we look at problems? How do we take challenging problems and actually look at it and think from first principles and go deep into something and to study it? And how does biology and science and math, how do we look at the scientific process? And you can do that whether it's in physics or in biology. again i had to make a choice between them they were both how to learn the process of science how to be very rigorous do the right controls how to construct the right experiments i was very interested in research so physics to me then part of the issue was it was more just the research aspect whereas in medicine i could actually do both i could actually see patients and i like seeing patients and doing clinical work which i did up until i retired very recently.

6:27Edward Patz: I was a full-time guy, a full-time clinical load as well. So I know a lot of clinical medicine, which is really important, I think, to what we've actually done in the clinic and how we've actually translated. So we knew what the real fundamental clinical problems were. I lived it. I lived these every day. And then take those and then try to say, this is a real challenge. This is a cool problem. Now, how do I actually address it and answer it? Okay. So you really liked that application aspect that you - Absolutely. And the translation. And now in medicine, it's the translation into really taking some basic science, going deep, understanding from first principles and translating it to what I can then see, which I know is going to help me in the clinic.

7:07Right, right. And so then you moved into, you had a residence in radiology, I think you said. Did you know at that point that you wanted to focus on cancer, early cancer detection, lung cancer, or did that come later on?

7:22Edward Patz: I think that came, again, I never really understand how these come. It's like if you turn right or if you turn left out of a door, you may get an answer, right? And I think that came by the fact that during my second year of residency, there was a thoracic radiologist, the head of thoracic radiology at the brink of time, a man named Bob Pugach, who was just really an amazing person. He was a bit outrageous, which I liked. But he was a brilliant radiologist and was very clinically oriented and just thought differently. And I got along very well with him. And he wanted me, even during my second year of residency, to do a fellowship.

8:04Edward Patz: I didn't know whether I was going to do thoracic, abdominal, neuro. I didn't know. And then I got a call from the chairman at the time who called me as office says, well, Bob really likes you. your second year residence, but it's a four year residency during your fourth year. We'll let you do a fellowship and then even offer you a faculty position if you decide to do thoracic, I'd like you to stay. And I was like, well, I don't know. Again, I wasn't that sophisticated. I said, well, that sounds good to me. And I wanted to stay in Boston. And I loved I was both at the Brigham and the Farber at the time because we did cover the Dana Farber.

8:39Edward Patz: And so that's how I became interested in thoracic. And then from there, I started looking at some of the different features and some of the different problems that we were solving. And cancer was a big issue. And I thought cancer biology was extraordinarily interesting. Not that I really knew much about it at that time. So then you after you complete that program, is that then you you go back to Duke and you're the head of your own lab at that point? Is that right or am I missing some in between steps there? Well, there are some slightly different steps. I wanted to stay. I was offered a faculty position at the Brigham, which I did, and I made a commitment to.

9:19Edward Patz: I was in a relationship with a woman who is a molecular biologist at Harvard, and she actually wanted to leave. I didn't want to leave, to be honest with you. I've been there before. Okay. So you understand. I mean, they're only just loving money, and it wasn't the money part at this point, and I wanted to stay. I did what every mature person would do is I then we made the decision then to go to Duke because as a scientist, she wanted to depend to start her independent lab and be very independent of where she had been a postdoc at Harvard Medical School. And so she really wants to go to Duke, but I had made commitments to stay on the faculty.

9:57Edward Patz: And then what I did was I grew my hair long and I showed up to Duke with a ponytail. And and that's how we was then I was recruited to come also down there to be one of the thoracic radiologists. and of all places. It's interesting that I will tell you one sort of funny story. When I was in physics and I had several professors there who wanted me to stay. And I did actually as an undergraduate, I was fortunate. I got to do some of my graduate coursework and I was offered to stay as a grad student there. And I said, no, I really am going to go to Boston. And one of them who had been at Harvard and been in Boston says, oh, well, then you'll come back.

10:32Edward Patz: And I was thinking to myself, there's not a chance as well I'll ever come back to Durham if I'm in Boston. And about 11 years later, I came back and I ran into him and he said to me, oh, Ned, you're back. Are you visiting? I said, no, I'm a faculty member. And the first thing he said to me, see, I told you, you come back.

10:55Edward Patz: And so but it was a great experience and was a wonderful place to be as a radiologist. How would you describe the early focus areas of your lab at Duke? And maybe you could tell me, you know, how what kind of precipitated the discovery of a novel antibody that could become a novel cancer therapy? Well, this was many years worth of work and was a long sort of process. To put into context, when I was doing thoracics and I was one of the thoracic people at the Brigham, we also started, there was a surgeon who came back to start a thoracic surgery program and thoracic program at the Brigham at that time.

11:40Edward Patz: And I got quite involved with that. That was both, again, at the Brigham and the Dana-Farber. And so I would read films at both and I became very interested. I would sit back. I would listen. He would take me. This is a man named David Sugarbaker, who is a great surgeon. He was a resident a couple of years ahead of me and then went off to do a fellowship. But he would take me to the OR. I do mediastinoscopies and thoracotomies with him. I do extraplural pneumonectives because he wanted me to understand how that worked. So I became very interested actually in cancer at that time. um i so that was my initial interest in cancer when i went to duke um i did not know that i was going to start a lab or do anything else but we it was very fortuitous we did have what was known as a pet scanner and at that time nobody else knew i had never heard of the pet scanner they were using it for cns and for cardiac purposes there was no studies in oncology and one of the residents had showed me a study which they were doing cardiac and in the corner they showed something light up and i took a look i said wait what is this and i took a look then at the films and i knew that they the chest x-ray i knew they'd had a resection a sublobar resection that it looked like it could have been uh we didn't know what it was and i didn't know anymore but something lit up there and i went back and started studying this and realized something lit up and i said what is this and then i started looking at the other films and i realized it It was lung cancer.

13:08Edward Patz: It was probably recurrent lung cancer. And from that one day, I said, I don't know what this technology is, but I need to we need to develop this. And I wrote the chair and the head of nuclear medicine and said, I want to do some studies. So we did the first studies in the world in oncology in PET. Wow, interesting. OK. Yeah. So it was fascinating because nobody had done it. I went to meetings and I was the only one ever talking about it. And so I got invited to a lot of meetings. We wrote some of these really initial studies doing this. So I became very used in PET imaging, but I knew we could do it better after doing this for a while, that there were better ways of doing it.

13:43Edward Patz: So I went to the chair and I said to him, I want to start a lab. I'd done some basic science. It was in physics, but I want to do some. And we can do this better. And I've got some ideas. Again, this is a problem. I could solve it. And I'm at an academic institution. So that's what started. Again, it was sort of interesting. And he was very supportive of me. He says, I absolutely support you. I will give you no time off the clinical schedule. I don't have any funds and we don't have a space, but I'm really supportive. Yeah, right. So, but from then I did, I started writing grants and I got my first postdoc.

14:20Edward Patz: We got a grant, a small grant. And there was space actually at that time at Burr's. Welcome, I talked to somebody because they were doing some similar science. And that started. So we started doing a lot of work in molecular diagnostics, molecular imaging, trial to design novel imaging agents. And then that evolved into doing biomarkers. And from the biomarkers, it evolved into how can we answer some of these questions, such as early stage lung cancer where 50 % will occur. And we just don't know which ones. Radiographically, they look the same. Pathologically, they look the same. Genomically, and are there other ways?

14:54Edward Patz: So we were looking for biomarkers. And that's how this whole idea came along and migrated because most Most of the lab focused on, so I ran a lab and we got fairly large and we had grants to do this. And I had graduate students and postdocs. And actually, I will mention my first postdoc was a guy named Mike Campa, who is an unbelievable scientist. And I hired him. He was the first one. He's still working with me to this day, 30 years later. And he's just invaluable. And he's done all the basic science. I only had the crazy ideas. So you made this discovery of this completely human antibody. Can you give me a sense of like when that happened?

15:37And then I guess what prompted you to decide, hey, we need to like found a biotech company to develop this and make it available to patients? Right.

15:49Edward Patz: So what we did, we were studying at that time the process to understand. I was very interested, as you first mentioned, on the process of early detection. And to really understand early detection, I think you need to understand the process of metastasis. Because 90 % of disease will recur and metastasize, and that's what kills the patient. So we really went back to the lab and trying to understand how metastasis works. And we did a lot of work. One of the grad students looked and we were looking at because it's extraordinarily well orchestrated. It is not capricious. It's, you know, they go to it.

16:28Edward Patz: They're very tropic. And we wanted to understand this from basic principles. And we were looking at some of the signaling molecules at that time in the lab of how tumor cells were signaling and how they are controlling this and what other cells that they were potentially co-opting the normal cells, the host cells, to help them promote metastasis. And then I had this, again, a crazy idea because part of my lab was also working on biomarkers. And I will mention one other person in my lab who was with me almost 20 years, Liz Gotland, who was also a scientist as a faculty member who was also just completely invaluable and still, again, today works with me.

17:08Edward Patz: So she was helping on part of the lab and Mike was on part of the lab. And so I combined them. And one part was looking at antibodies. And we were looking at antibodies as biomarkers. And the other part was looking at metastasis. So I asked this question. I said to them at lab meeting, our lab meetings were very open and animated. And I said, is it possible what we showed in the animal models is that we could block metastasis with a drug? We knew which signaling molecules. We found this out. So is it possible that we can pharmacologically block this, which we showed? And we use small molecules.

17:45Edward Patz: We also use antibodies. So I asked the question then, is it possible some patients actually develop antibodies against some of these signaling molecules and it blocks metastasis? It was a very simple question. And everybody looked at me and says, no, this is really not, you know, nobody's done that before. We would doubt it. Why would an autoantibody do that? I said, I don't, let's just take a look. And we took a look and that's how we started. And we found literally doing what was known as an immunoblot where we took proteins down on the gel and we probed it looking for antibodies against those tumor proteins.

18:18Edward Patz: And sure enough, we, and we were completely agnostic as to what the targets were, even though we knew some of the signaling molecules in the mice. And we found some bands on a gel and we isolated the proteins. We figured out what it was. And we said, wow, there is this autoantibody seen in these early stage non-metastatic patients because we selected out for those patients. And we controlled it against those who had metastasis, who developed metastasis, who never had this antibody or virtually never had the antibody. And we said, well, is it good? is it not only a therapeutic, I mean, as a diagnostic, but also potentially could be therapeutic.

18:55Edward Patz: So all of these connecting these areas were unusual. And even one of my collaborators said, well, how would you think of that thing? And I said, well, remember, I wasn't trained in molecular biology, even though I've been doing cancer biology for a long time. We just thought outside the box and asked a question, are there antibodies which actually could be controlling and really controlling the disease that patients produce and helping us have this very distinct, not only phenotype, but these distinct outcomes that we're seeing. Yeah, right. And then so at that point, once you had verified this discovery that you made in the lab, is it your immediate next jump is we got to found a company?

19:38And how did you think about that? How did you actually take that first step?

19:42Edward Patz: Yeah, no, it wasn't about finding, going and doing a company, I wanted to translate it. I wanted to, I was an academic, I'd been in academics my whole career. And I really wanted to translate that into patients. I didn't want to spend 20 years from what I understood would take for a drug to do this. And I said, I really want to do it. And let's move forward. Just to hand this off to a drug development shop and let Absolutely. Absolutely. But there's slightly more. So first of all, you have to understand that we did then some of the preclinical work. One of the most interesting is I went over to my colleagues in the Duke Human Vaccine Institute.

20:26Edward Patz: So we found the antibody. We knew what the target was. Now we really have to develop a drug. So I went over to my colleagues in the Human Vaccine Institute who developed a lot of this really interesting technology for broad neutralizing antibodies in HIV. Bart Haynes ran it and Bart has been a longtime colleague of mine. Tony Moody and Larry Liao were working there. And I said to them, is it possible? So they would pull out patients who had autoantibodies. They could pull out the actual B cell, which made that antibody from the patients and they could clone it and sequence it. and make that antibody.

21:02Edward Patz: And I said, is there any way we could do this in cancer? We know the target we want. We'd actually epitome mapped it down to an exquisitely specific 8 amino acid domain because I wanted exactly what the patients made. I didn't want off-target effect. I wanted to create really what I consider would be a tumor-specific antibody. And they said, well, we've never done it before, but we have the technology. So we tried a couple of times. And actually, after the second time that we tried it, where we literally took single B cells, we put them in single wells, we cloned the immunoglobulin genes and we sequenced it and we put it back into a mammalian cell and we made antibody and we tested it.

21:39Edward Patz: And this was one of the eureka moments I had was we tested it against exactly the target. We then had the cleanest, exactly the antibody the patients made directly. That's why it's a human drive because it was directly from the B cells. I did make a chimeric where we just injected the protein into a mouse and humanized it. we had the sequence of what the real patients were actually making. Yeah. That was really cool. The problem is then we tried to, just as you say, to hand it off, but nobody would license it. Nobody would even look at it. It was a novel target. We had identified this target, which was complement factor H.

22:16Edward Patz: It turned out that when we subclassed each of these patients, meaning we looked at the antibody class and their different classes, it was an IgG3. Nobody had ever made an IgG3 before. And I was very rigorous and demanding about finding the exact target and the exact class and what the patients were doing. And there's some other features which I haven't been able to do, but we're trying to do it the best we can. But it was an IgG3. It was a novel target. Nobody had done this before. And so it was a very hard sell in biotech for anybody to want to license. They said, well, you get more data, but I needed funding to do this.

22:52Edward Patz: And even writing grants was very difficult on this proposition because it was so different than anybody else had done. Yeah, right. Well, I want to come back to GT 103 and talk a little bit more about complement factor H as a target. But before we get there, maybe we could start with or before that, just talk a little bit about grid therapeutics and how that got started. And maybe maybe you could explain, Ned, the tech transfer process. So when you decided, like, you know, it's time to take this discovery, move it into a company, was that a process that you were involved with? Did you have to I assume you had to license the technology from Duke, right?

23:35Edward Patz: Yeah. So I went to Duke had a tech transfer office. They were a little bit in flux at first. And then they they hired a woman, Robin Razor, who was just wonderful to work with. I mean, she's great. And they made it. She made that very easy. We came up with a standard agreement. Again, I was an academic who was like, fine, whatever you really want to me. I didn't. It was about getting this drug into patients. I think this was a really unbelievable drug. And we couldn't license it. So then we decided I did write a small grant at that time to do kind of the DCRI, the Clinical Research Institute. It was started by Rob Califf.

24:15Edward Patz: And Rob had been a colleague of mine for years. He was a cardiologist. He's a phenomenal physician, by the way, a phenomenal cardiologist. And I'd known Rob for many years, and I talked to him about this because he had lots of experience. And he said, yeah, you need to take him to the clinic. And I wrote a small grant, and the DCRI gave me some money to get really a program manager who helped me really get a construct of what we needed to do from IP to regulatory to commercialization to clinical development. and we formed a plan around this. And we got some ideas about what it would take. Now, the funding piece, which the biotech of businesses we're talking about now, the business of biotech really wasn't part of that because I didn't understand that piece very well at the time.

25:06Edward Patz: I was used to writing grants, but we got a lot of the infrastructure actually formed and we knew what it would take and we got some costing done. But that was a very small amount. It really only helped form some of the ideas. And I had no idea we wanted a company. But since we couldn't license it, we started forming what it would take to either write grants to do it through Duke. Although Duke's a nonprofit, it's not obviously a commercial entity. And I had to really get it out of Duke. We had a license agreement that then if we wanted a company, so we decided we would, the only way to do this was to form a company.

25:41Edward Patz: And that's how we sort of started Grid. Although, again, everything's interesting. We were a different name before and somebody else came in the space. There was confusion. So we ended up changing it to grid. Oh, what was the initial name? The initial name was Q, Q Biologics. That was because we took Qs from the native immune system and somebody else came along. It was very similar and they were getting ready to do an IPO. So we decided to have a name such as grid. It was easier to pronounce. It was simple. It was monosyllabic. And we were off the grid. We were totally off the grid from what anybody else was doing.

26:12Edward Patz: Right, right. Right. So we at that point, we formed a company and actually through one of my colleagues, we found an initial investor. And that's how we decided we would we would form this company and we would move forward. And we had a general plan of what to do and what we needed to do. And the investor came along, said yes. And actually, the investor, the initial investor who came along, and this is a totally different story, said they had two real conditions. One is they wanted to fund the entire thing. Fine. Oh, solo. Okay. Solo. Okay. And the second is they wanted me to come along with it.

26:53Edward Patz: And they wanted my help and they wanted my input. I was the, you know, I ran the lab. I was one of the people who discovered it. Again, I have to give credit to the lab and to the DHVR. This takes a lot of people to do it. Yeah. I mean, it was a big, you know, it was extensive science to do to get all this. So we started a company and that's how basically Grid was formed. So you were it sounds like you were kind of pulled into that CEO. I absolutely was pulled in. Yeah. And because I believed in it, you know, it was part of my course. I'd been doing clinical mess. I know how to take care of patients.

27:31Edward Patz: I still read films. I still can take care of patients. But I wanted a different challenge at this point. And this was and I believed in it. And so I was pulled in. I said, you know, this is an interesting opportunity. Yeah. So now you're the CEO of a biotech company. Thinking back, you know, Ned, to those earliest days, what, you know, what were the I'm sure you were, you know, drinking out of a fire hose, trying to learn as much as you possibly could. Um, is there, as you think back about those early days, um, as CEO, um, is there, is there anything that you wish, you know, someone had told you about running a biotech company or, or a kind of singular challenge that you didn't anticipate?

28:14Uh, how would you describe those early days?

28:17Edward Patz: Well, I wasn't only, only drinking out of a fire hose. I was sipping out of a cocktail, uh, straw to try to get oxygen. So, you know, they told me this would be the most difficult thing I ever did. And I I I'd like to think I have a lot of energy and enthusiasm and I'm very passionate about it and very focused. But this was extraordinarily difficult. I did not realize all of the challenges and skill sets that you would need. I mean, I am totally back to my college days where I was naive to what I wanted to do and what was happening. I still feel very naive about this. What I tried to do is surround myself with the best people I could.

28:58Edward Patz: I'd like to work with good, smart people. I've been so fortunate to have had that happen. So I really didn't understand almost all of it, to be quite honest with you, Ben. I just didn't know what this would take, the energy, and then ultimately really the capital. A lot of this comes down to the funding, which is still an interesting piece for us. I mean, it's still been a real challenge for us to get the right partner in here. Unfortunately, our initial partner, they breached contracts. So then I had to go out and try to scramble to get funding. I mean, we were literally out of capital within six weeks and we'd already committed, you know, to manufacturing.

29:43Oh, man. Yeah.

29:44Edward Patz: So that was very hard. I was very fortunate. And again, we had a board of advisors and one of which on our board of advisors is a very close friend of mine who's a wonderful and just amazing person, a guy named Dave King. And Dave was the CEO of LabCorp at the time, but he'd been a friend of mine for years and given me lots of advice. And I called him up one day. I said, I don't know what to do. You got to give me some advice. He goes, let's meet. We met for breakfast one morning at seven o 'clock. I'll never forget it. And I told him the situation, he said, we'll figure this out. And he helped me construct a plan.

30:19And we then got the funding to keep going.

30:23Edward Patz: It doesn't keep it kept us going through the first rounds. And now we're still trying to continually looking for the right partners and how to strategize to make this really a successful business, not only because we have GT 103, which I think is phenomenal, but we have this whole idea of platforms and how we do additional assets as well. Yeah. And I want to ask you about GT 103. There's an investigator sponsored study that's in phase two. But maybe, you know, at a high level, Ned, could you maybe explain what makes GT 103 and complement factor H, you know, a unique approach to targeting cancer?

31:01You know, it sounds like it's something so different that you couldn't easily, you know, get people to just kind of jump onto it because it was so new, right? Right.

31:10Edward Patz: Yeah, no, it's still extraordinarily difficult that it's not a target that I know of. One other group was going after it. I know they're not now. It's different. It's not your typical membrane-bound target. It's not your oncogenic driver. It's not a lineage marker. And it's not necessarily a membrane-bound protein. It does bind to the tumor cell surface. So A, it's a very different target. B, nobody's gone after it before. So the target itself is not well-known in the cancer space. However, it's an incredible target because it binds to tumor cell surface. It binds to all cell surface. It just binds to the tumor cell surface differently than it does to normal cells.

31:53Edward Patz: And opens up. And once it binds, it opens up actually a cleft, what we call a cryptic epitope, which is not seen in a normal soluble protein, which is floating around in the body. it recognizes tumor cells. It recognizes lots of different tumor cells, including, I will mention one of the areas which I've become very interested. My wife is a pediatric oncologist and she's much better. This is the woman you moved to Duke for, right? No, it's not. Oh, a different woman. I moved to Duke for somebody, but my wife and I had been married for 30 years and she's a pediatric. I met her actually at Duke, but she then trained at CHOP up in Philadelphia.

32:31Edward Patz: And she's a much better scientist than I am. And in clinician, but we talk about these things. And so we've actually become interested because in pediatrics, there's a lot of unmet need there too. So we talk about it also, and we've been doing some studies and we're thinking about clinical trials in pediatrics as well. Oh, excellent. Because it's really, so it's seen all solid tumors actually use this mechanism. So it's not unique. It really is a tumor protective protein. So if you can activate it and take off that shield, that it protects it. And not only do you take off that shield with an antibody, but we allow the properties and the mechanisms by which antibodies, you know, use to function, meaning that the part of that antibody has an effector domain, meaning it really is active.

33:19Edward Patz: And we use that to not only kill the tumor cells, but that'll help drive this adaptive immune response. That's what really is quite unique about this antibody, that not only can it kill it, and you don't have to kill every tumor cell, but you do have to learn. And what we've learned to do is initiate and turn on the immune system to turn on to drive CD8 T cells, which can then come and recognize additional antigens on that specific tumor to drive this durable response. So that's what really gives it. It's got an exquisitely tumor-specific epitope. We don't see any off-target effect, and we can not only kill the cells but drive an adaptive immune response.

33:57Is there a biomarker or a patient selection angle for GT103?

34:04Edward Patz: We don't know yet. I mean, we're still early on in the game. So we did a phase one trial really just for safety and tolerability in advanced stage lung cancer patients, and the drug was extremely well tolerated. tolerated. I mean, we had no safety events that were great for five toxicity. Nobody was taken off of the drug, as far as I know, for any drug-related event. And then we did a phase two trial in IO-resistant non-small cell lung cancer. Again, some really interesting results in that trial. In particular, it's interesting because we started out looking for patients. We had patients with non-metastatic lung, who had lung cancer, but that non-metastatic disease never progressed.

34:48Edward Patz: One of the most interesting features we've now really tried to focus on is that even in our phase two trial, we completely abrogated metastasis. It looks like almost 90 % reduction relative to what a historic dose. Virtually nobody developed any new sites of metastasis. They all had stage four disease, meaning metastatic disease, but they didn't develop new sites of disease. So it gives us a really, really interesting way to clinically develop this drug in a very different space because there are no drugs approved for inhibition of metastasis at this point. And metastasis is occurring in the lymphic system primarily.

35:23Is that right?

35:24Edward Patz: No, metastasis can go anywhere. You can have visceral metastasis, meaning it goes to the, so lung cancer goes, you know, will go to the adrenal glands, to the bones, to the brain. very well, again, orchestrated. And different tumors will go to different sites. And they also go to, they can initially go to the lymph nodes or even go to the lymph nodes later, but they can go to any place in the body. Okay. You just referenced clinical programs, but I just want to spell these out a little bit. You've got two clinical programs testing UT103 right now. What can you say about the indication selection for those two programs, maybe first off?

36:03Edward Patz: You know, at this point, you'd ask, and I failed to answer your question, that the biomarkers, we've collected a lot of biomarkers. I did a lot of biomarker work early in my career. I know a lot about this. We collected a lot. We just honestly did not have the resources to process it and do all the work that we wanted to do. I have collaborators all over the world there. I work with a group in Paris who are complement biologists, and because this is complement factor H. And it actually, the way the antibody kills is what's known as complement-dependent cytotoxicity. So we're looking to do all that work at some point in the future.

36:36Edward Patz: Again, we're still really early on, but we've got a lot of ideas. The patient selection at this point, we just don't have enough data. We did a phase one trial for safety and tolerability. We did a phase two trial in combination with Keytruda and, you know, from Merck's pembrolizumab. And we've analyzed that data. We actually have a smaller program in specific mutations. And you asked for biomarkers. We did recently publish a paper on a specific mutation called STK11, which is about 10 to 15 % of all lung cancers. And we found that they meet, which is a very recalcitrant tumor. And we found that those patients may be more susceptible to our drug.

37:18Edward Patz: So we do have just a small investigator-sponsored trial right now, although we had a call last week, and I've now got five other sites who are potentially interested because they found the data so interesting. So we're trying to move that along as well. So we're looking at biomarkers. We don't have a selection, and it's very hard to know right now. But again, because this is ubiquitous and almost all tumor cells use the same mechanism, we will have to really study and figure out what the appropriate biomarkers and who the appropriate population is. On the investigator-sponsored phase two, you mentioned this in combination with Keytruda, the Merck checkpoint inhibitor.

37:58Are there any kind of strategic pros or cons with investigator-sponsored studies versus company-run trials? I mean, you don't have to pay for it. That's a huge benefit. Right. Or not all of it. But is there any you know, maybe how did that how did that come together? And, you know, what are you what do you like or dislike about investigator sponsored studies?

38:19Edward Patz: The investigate. So to begin with, again, when we started this whole program and I had some funding to sort of construct what we were going to do, it was really a matter. Honestly, it was a matter of cost. If we were going to do it, I couldn't. It's much more capital intensive to do a full sponsored clinical sponsored trial. We just didn't have the capital to do that. I had investigators who were interested. There are some downsides that you don't get to have as much control. And even during our phase two trial, we knew the metrics that we knew very early on the metrics were the traditional metrics of ORR were not appropriate.

38:59Edward Patz: were actually completely misleading in this drug for various reasons. And we wanted to change it. It was like, no, you can't do anything till we do an interim analysis. We'll do an amendment at that point. So even though we knew it was wrong and it would be looked at in different ways, we didn't have as much say in it. But we did could at least get some data doing it that way for the capital that we had to then hopefully be able to get the additional finances we would need than to do a more traditional industry-sponsored trial. Got it. I saw on the website, I wanted to ask you about AI. I saw on the website that Grid is using AI in various ways to analyze data.

39:43I know I read, but how would you, I guess, describe AI as a tool, Ned, in the discovery and development work that you're doing at Grid? Yeah.

39:53Edward Patz: The AI, it's more, I would say, a computational program than just AI per se. We use AI for looking at synthetic controls to really comparing our, because part of the objection we've had so far as, well, you've done single arm trials. That's all we could afford. That's the way this is early on in drug development. I mean, if you look, honestly, in my opinion, if you look relative to drugs, even such as Catruda, at this stage of development, we look really, really good. And so we have to, we weren't able to just jump into randomized trials. So we would use the AI agents as helping us design synthetic controls, helping us design trials, helping us look at the clinical program.

40:39Edward Patz: We do use a computational program to then, we now have migrated our platform. and we've got some really interesting candidates right now, which again, just require capital, but we've got, we chose the top five that we want to move forward in doing this. And we use a computational program to do that rather than doing the way we did originally, we discovered GT103. It's fundamentally the same by getting, deriving human-derived antibodies, and we will have to use some of that same components down the line, But we do the computational end of first to actually find the antibodies that we may be interested in.

41:15Edward Patz: We believe this is going to rapidly help us then design trials and design novel tumor therapeutics. Got it. I meant to ask this earlier, but QNowGrid, did you initially found the company or co-found the company in 2014 or 2016? What year was it? Do you remember? Well, I don't really remember. I've been working on, I think our first publication on this was about 2014. We thought about it. I honestly don't remember exactly when Q came along. It came along when we then had somebody, an investor who said, okay, yes, we didn't have the funding to do anything. And when an investor came along, they said, we need a name.

42:03Edward Patz: And that's when we did it. And it was around the 2015, 2016 timeframe, as I remember. Okay. So fair to say, though, that you've been a going concern for a decade now. We have. If you had asked me 10 years ago, Ben, about this, I would have said, oh, there's not a chance. And I would have had no idea I'd be talking to you and doing what I'm doing right now. But I have learned a lot. Yeah. Oh, I bet. Well, let me ask you a couple of questions about the company. How many full-time employees work at Grid right now? We are still only a virtual company. They're what I would consider three full-time, but we have the whole capacity to do everything.

42:44Edward Patz: We have a wonderful CMC consultant. Well, not really a consultant, but he works with Grid, Pat Gearing. I mean, he's just amazing. We have regulatory, we have IP. So we have the full, we have clinical development, we have medical monitoring. So we have the full capability of doing everything right now. But because it was more capital efficient, we, you know, we're doing it this way to turn on and turn off when we, when we need people, because we just don't need the full time people, you know, personnel at this point. And it was too capital intense to do it that way. There's been some major swings in biotech funding.

43:21at the biotech funding environment since, you know, 2018. It was pretty good, you know, before COVID. It was been really bad for a couple of years. Now it seems to be getting a little better, at least depending on what kind of areas you look at. But what could you say, Ned, about how your financing strategy has changed over time? And are there specific, you know, kinds of funding or partnerships that you're focused on right now?

43:52Edward Patz: Well, you're so right. I did not really think about all the macroeconomics would affect this. As an academic, I thought, well, if we have a great drug, everybody's going to want to come. And I didn't really understand the ecosystem and the landscape. I mean, that's the truth. So things change a tremendous amount. I've seen plenty of companies come and go. Yeah. They bought, they sold. even I will tell you nine months ago I went to a colleague of mine a very well known cancer biologist and I said look we've got these great data nobody wants an antibody right now in his opinion you really need a CAR-T or a bispecific or something else so we went out and he introduced me to somebody who does cellular therapy and we actually made a CAR-T and we transduced it with our antibody because it's so specific And there are not many really tumor-specific antibodies that you could put on a CAR-T.

44:52Edward Patz: And we did some preliminary work and it works. It works really, you know, just in vitro. And we haven't done it and I couldn't spend the capital to do it. And I went back to this friend of mine, you know, a few weeks ago and I said, look, we even made a CAR-T. He goes, oh, that was nine months ago when I told you that. It's very different right now. So there have been successes and failures and that certainly changes the funding environment. I think we are looking at all sorts of options. We want, we made, you know, I will say I will take full responsibility of making a snake of not vetting our initial investor well.

45:26Edward Patz: Again, they breached contracts, so we had to go out. We have some wonderful investors. I mean, all of our investors are wonderful, and they've been very supportive of the program. But we really are trying to now find strategic partners and institutional investors who want to do something a little different and want to be more transformative. We're not the next kinase company. We're not the next generation of anything. I never could do that. That's just not me. And so we need somebody who really wants to be transformative and take this a very different way. It's early on in this drug development.

45:58Edward Patz: But I think we have the science is incredible behind it. And there's so much. I mean, this is really 30 years of work boiling down to understanding of how we got here right now. So we're looking and we were taught we're actively funding right now. And we'd be delighted to talk to anybody who finds this type of program interesting. I read an interview with you, Ned, from 2023, suggesting that you'd like to find a new CEO to kind of run the business side of grid so that you can spend more time focused on the science. is that is that something you know that you're still looking for like are you still trying or you know hoping to step away from the the ceo role or are you now set to stay in that position for a while no i'm not i i'm definitely not set to stay in this position i am set and i made a commitment to um for um i will say you know i always say i made commitment to all our investors and the people who've worked with me to get this done, but more to the patients.

47:00Edward Patz: I truly believe this is a really good program and a really unbelievable drug. So I am absolutely committed to seeing this done, whether it's the CEO role, if nobody else wants to come in, it's been hard. I've tried to get other people coming. We haven't had that large capital where I could offer a large package. It was more, we'll take the equity and it's fine. But I want to find the right person who shares our vision of doing something different and the culture which we've now created around grid and the people I work with. And I've got amazing investors and collaborators and board members who have been so supportive and keep telling, I said, I want to step away.

47:39Edward Patz: They said, no, no, you're doing a great job. I said, but I can't do everything I want to do. And it really takes more skill sets than I have. So I'm open for discussion. You know, somebody came in and says, let's build this team. I'm like, oh my God, I couldn't think of anything better. But I am committed. Particularly, I still wear, The first hat I wear is as a physician scientist and as a physician to take care of patients because I've seen patients for many years. I know I take care of them. And I really think we need better drugs than cancer. I know we hear there's there are a lot of interesting drugs out there, but we still see a lot of patients dying of cancer and we need better drugs out there.

48:16Edward Patz: And I see the toxicity. We need safer and better drugs. And I think we've got a way of moving this forward. So I am committed. But whoever wants to come along, come on and talk to me and I'll be delighted. You can have a lot of it. You can have a lot of the stuff that I do. I mean, I open the windows and I close the doors and I sweep the floor. So I'll do everything. When you're small, you got to be a bit scrappy and innovative. Absolutely. And I think it's admirable. It seems like what you're saying is you're going to stay in that role and you're going to uphold your commitments until, you know, someone better, you know, shows up, you know, to take that over.

48:50I get it. I wonder, is there anything that you think the biopharma industry or biotech investors get wrong about physician scientists, about scientist founders?

49:04Edward Patz: You know, I really don't know because I've never been in that role. I still don't get a lot of the biotech investors. I've never really lived in that space. OK. I can call. Look, I can call scientists all over the world. I have collaborators all over the world and physicians who I know who do lung cancer in particular. I mean, I go to these meetings any place. I mean, my kids love to travel. And almost any place I go, I say, oh, I know such and such. They can, you know, somebody everywhere. And I do, but they're not the biotech. They're the people that I've really spent most of my career with.

49:37Edward Patz: Scientists, right. The scientists and the physicians. And I can do that. I really still struggle because I don't have a good sense of what the physician scientist who goes to founder really does and looks like and how everybody else has conducted themselves. Everybody, as my wife and I always joke, you know, everybody else, I've got to be myself because everybody else is taken. And I just can't know. And I haven't figured it out, because if I would, then I probably wouldn't be in this situation where I'm still trying to figure out how to really to try to really go out and and show people and convince them that what we're doing is really an amazing program.

50:23Well, in our final couple of minutes, maybe, Ned, you can tell us what's next. Is there specific data, specific milestone that you're most focused on right now? What's next for the two clinical programs that you're working on?

50:43Edward Patz: Right. So I think foremost, again, we are out there fundraising, trying to get sufficient funds to really move the clinical program forward. OK, so the funding needs to come before the next clinical trial starts. Is that right? Well, it does. And it does. You know, I'm moving forward with them. We've written grants. We've written SBIRs. I'm talking institutions who are very excited about this drug. So we may go back and do some more investigator-sponsored trial where they said they'd be able to keep us going. We do have one trial in SDK 11, which is open right now at Roswell Park. And they're funding it.

51:18Edward Patz: We're providing drugs. We do have drug. So we can do additional trials if we have this. So we are moving GT103 forward, which we're going to do. And both in lung cancer, we're looking at some other solid tumors. I've had other people come. They want to do it in bladder cancer. They want to do it in pancreatic. They want to do it in breast. But we're trying to stay focused. And pediatrics as well, as I mentioned. And we've written grants in that. and then the next thing i'm still working quite hard on we have some new ideas for the assets and we have uh we decided we'd focus on five and we have those so we're moving those forward we honestly now we thought about this at first but we have an idea about how to develop a vaccine out of this whole program which would be really interesting and cool yeah and and because we could select out, particularly in my field of lung cancer, we have screening, but that only includes the high risk and there are plenty of non-smokers who develop lung cancer.

52:21Edward Patz: And so we have ideas about how to develop a vaccine out of this whole program. So I'm constantly talking to collaborators. I'm still sort of in the discovery mode of that while we're trying to move GT103 forward, while we're trying to actually raise and get the right partners to help us come in and sort of build up the business, the business side of things and get the funding to do all this. Well, Ned, thank you so much for coming on the show. Best of luck to you and the company. I really appreciate it. Well, thank you so much for having me and taking the time to talk to me. Appreciate it. Yeah, it went by quick.

52:54We've been speaking with Ned Pats, MD, co-founder and CEO at Grid Therapeutics. I'm Ben Comer, and you've just listened to the business of biotech. Find us and subscribe anywhere you listen to podcasts and be sure to check out our weekly video cast of these conversations every Monday under the Business of Biotech tab at lifescienceleader.com. We'll see you next week. And thanks as always for listening.