Business Of Biotech
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Business Of Biotech
Dye Drug Conjugates For Cancer With Lahjavida's Lyle Small
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On this week's episode, Lyle Small, Founder and CEO at Lahjavida, a dye drug conjugate start-up, talks about creating the famous color-changing technology that turned the mountains blue on cold Coors Light beer cans, to launching a dye-drug conjugate startup developing targeted cancer therapies. Small talks through Lahjavida's early preclinical work and the ongoing animal studies he hopes will secure an IND filing by 2027, his experience with scaling up manufacturing of new technologies, and his approach to leadership and company culture.
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Welcome back to the Business of Biotech. I'm your host, Ben Comer, Chief Editor at Life Science Leader, and today I'm excited to speak with Lyle Small, founder and CEO at Lahjavida, a company developing dye- drug conjugates to more precisely target cancer with chemotherapy. Lyle is a successful company founder. His first company, Chromatic Technologies Incorporated, or CTI, made the Rocky Mountains turn blue on the front of the Coors Light can. Once the beer inside got cold enough. Americans over 35 years old will know exactly what I'm talking about. Lahjavida is Lyle's first foray, however, into the life sciences sector and I'm excited to learn about how the company came together, what the overlaps are between commercial dye manufacturing and drug development, the challenges that he's encountered so far and his plans to get to an IND filing by 2027. Thank you so much for being here, Lyle.
Lyle Small:Thank you, good to be here, Ben.
Ben Comer:I have to start with CTI and Coors Light, but maybe, Lyle, you could talk a little bit about your experience founding that company your first, I believe, and where you got the idea for making products talk to customers.
Lyle Small:Yeah, it's a little bit of an odd path. I guess everybody has an odd path. I thought I was going to be an engineer at one point, trained in bioengineering as an undergrad at Cornell and got acquainted with thermochromic materials early on while I was in college and followed that passion through my college years and decided that, rather than get a regular job, I would begin a startup and see how far it took me, I don't know. I guess it's 32 years later. Here we are. I guess it's 32 years later, here we are. So yeah, before graduation we incorporated the company. My parents were pretty dismayed to hear that Lyle had chosen to do a startup right out of college, but it turned out okay.
Ben Comer:Yeah, so you started up the company. You've been very successful as your first company. When did it occur to you that it might be cool or useful or interesting for a product to tell a customer when it got cold?
Lyle Small:have been around for a long time. Far back as the mid-70s people, you know, folks in Japan actually figured out how to microencapsulate these dyes to get them to change color. The problem was always that the size of these microcapsules was way too big and it never really was a viable option for the kinds of printing that I thought would be interesting. So the idea that you could have something that could make a can or a bottle talk to a customer wasn't a new one. But we were the ones that actually figured out the technology that enabled it, which was make the stuff on the inside of these microcapsules a lot better and make the microcapsules themselves more stable and the right particle size. Yeah, that sort of thing. You know, if we could possibly do this thing, wouldn't it be great?
Lyle Small:If you know watching Coors Light commercials, you know you were probably familiar with the time when the commercials about the cold terrain of Coors Light racing through the Arctic. You know they were all about cold because a warm Coors Light isn't great. All about cold because a warm Coors Light isn't great. They wanted to own that space. And watching these commercials because I'm a big basketball fan, all during the playoffs one year, I thought you know what? We should figure this out. We need to take another look at how we could reduce the particle size enough to get our stuff on a can, and that led to six years of toil and failure before we figured it out In 2006, I think was when they first adopted it in the UK.
Ben Comer:So how did it actually go down with cores? I'm sorry, I'm very curious about this go down with Coors.
Ben Comer:I'm sorry. I'm very curious about this. It's something that really sticks out in my memory, kind of along with hypercolor t-shirts, which I'm going to show my age on that one. They were popular in the 90s but have mysteriously disappeared. But you're based in Colorado. I mean, was it just kind of you know, coors was, you know in your backyard and was where you wanted to take it? How did that evolve, like, how did you actually get that meeting and, you know, ultimately win that business?
Lyle Small:So, like most entrepreneurs, I have a healthy ego and I thought you know why wouldn't they talk to me. Thought you know why wouldn't they talk to me. I just get on the phone and say, hey, I've got something I think could change your business, and was told to go away for several years. You know they're like thanks, son, but we've got it under control. But eventually they get tired of hearing from you. They realize you're not going to go away. It's a fairly common story, right? You knock on the customer's door enough and they finally let you in.
Lyle Small:The guy doing innovation for Coors was a really fantastic gentleman that kind of put his arm around me and said all right, I'll humor you for a day or here's an hour, give me your pitch and I painted a pretty good picture. Didn't have a product at the time. Of course you know, or like imagine if you will uh, the Coors Light can changing colors and it was actually their insight that they could tie their core brand message of the the mountains on the Coors Light can to color change. You know, when the mountains turn blue, it's as cold as the Rockies. That was not my idea. That is all Coors Light and I give them all the credit and you talk about courage. Right, you got this new startup. These guys are teeny, little company. They're not far away so they're convenient, but they're a tiny, tiny company.
Lyle Small:We had sales under $3 million a year at that point, primarily doing checks, receipts and coupons. Color change that showed your check was an original. That was our primary technology. That was our primary technology. They took a big bet on us, of course, did a lot of testing and confirmation that it would work over the years, but it was a mix of determination on our part and really impressive innovative thinking on the part of the Coors Light brand team that said you know what? Let's see if this could happen. If it could happen, I think it could be impactful for our business. They talked the CEO into it once they started seeing some real stuff happen and his eyes lit up and said I think it's brilliant, make it happen. And that really pushed things into the stratosphere. You know we got the resources and the press time that allowed us to perfect the technology.
Ben Comer:I want to get to Lajavita in just a second, but I have one more question about CTI. I suspect that you know the Coors contract was a game changer for the company. When they finally said yes, you know, you had to. You had to scale up somewhat significantly. I would imagine Can you can you talk? You know, first of all, you know how did you convince them that you could supply enough of the materials to to make this work, and then how did you do it to make this work.
Lyle Small:And then how did you do it Right so well? There was no convincing Coors Light. We had to prove it right. You know, like I could tell whatever story I wanted Us.
Lyle Small:Being able to ship thousands of pounds of ink to go on aluminum cans every month was something we had to demonstrate, and had to do that prior to them putting a single can in the market. So the scale up was complex, because the only way for us to create microcapsules that would work was for us to do the microencapsulation, and we had a very specific process. So scaling that from a little beaker to a giant tank was a trick that took years right. So we started in 2003 and the first cans in the UK were in 2006. So there was this three year period where we were trying to really demonstrate that scale was possible, and there are 30 plus manufacturing steps in this, because we micro encapsulate and it's in a waterborne environment. And then we have to teach these capsules to be happy in a solvent-based environment of a metal decorating ink. The capsules themselves have to be very specific in terms of their stability, because that solvent could destroy them and that's usually the problem with these systems. So the complexity alone took years to work out and then scaling each one'm sure that your listeners are familiar with in the drug business.
Lyle Small:But it taught me a lot of lessons about that process and that you can't take anything for granted. You got to write everything down and teach people on the on the manufacturing line how to do it. These guys are the ones that got to execute and some of them haven't gotten out of high school right. So you have to make it straightforward. It has to be repeatable. You have to have a way to confirm that it's right, because you could have a tank full of stuff that's worth $3,000 for a single batch and if it's not right, you could turn that $3,000 into $10,000 of waste by taking it to the next step right. So you got a QC all along the way, and you know this is common in manufacturing.
Lyle Small:But I think that the unique part of what we had to do was the size of our business and the degree of complexity. You know it's kind of like building a transmission or something you know. Lots of steps along the way and we failed dramatically at times and had to throw a lot of product away that didn't meet our standards, and that is always a tough choice for a small company, but one that taught me some crucial lessons. The mountains have got to turn on, they've got to have the right color, at the right temperature in the right environment every time, every day, or we're cooked and it would be a big black eye for Coors Light.
Lyle Small:So that focused the mind. You know I had a lot of very long days for many years to get it to work right, but it was. Once you had it dialed in and we got up and running. It transformed us and actually allowed us not only to provide basically free research and additional innovations years later with Coors Light, but it funded the topic we're going to cover today, which is La Llevida. We would not have gotten into cancer research if we did not have the revenue generated by the Blue Mountains and Coors Light.
Ben Comer:And yeah, I said Americans over 35 will definitely remember this, but it wasn't just Americans. They were sending this product into the UK and perhaps other markets as well, all over Europe.
Lyle Small:Yeah, we're in 30 countries.
Ben Comer:Wow, okay, well, yeah, let's switch over to Lajavita. What circumstances prompted you to, you know, pivot into life sciences with this initial idea of combining dyes with gold nanoparticles for cancer?
Lyle Small:So I've made clear we're in the dye business and I was looking for a dye researcher and created some of the first dyes for the what do you call them? The film, the photographic film, instant photography Sorry, that's the word I'm looking for. Yeah, yeah, so he did instant photography. Sorry, that's the word I'm looking for. Yeah, yeah, so he did instant photography. Then, of course, kodak blows up and he starts working in invisible dyes for the FBI and for other security applications, where you print something that's invisible and then you take a special light or special goggles and you can identify it. He also undertook an effort with some folks at Georgia State to develop a dye that bound selectively to cancer cells, and they worked on this thing for years, filed a patent in 2006. And the point was to inject it into a patient, travels throughout the body and only binds to cancer cells, and then, when you open up a patient to remove their tumor, the surgeon can use special goggles with a special lamp, because the tumors will glow green and then so the surgeon will know where to cut, and that's still a big challenge for surgeons is figuring out where the edge of the tumor is when you're inside a person. Well, this was going to solve that problem and they were working with Harvard and did a lot of work on this. And he showed me this on a Friday. I said fantastic, congratulations. He showed me the picture of a mouse with a glowing dot on its rear flank, which was a tumor. It's called a xenograft tumor for a mouse in colon cancer had this colon cancer tumor and it was glowing bright red. And he said this is going to change cancer treatment because doctors are going to know where to cut, how far to cut. And I said this is going to change cancer treatment because doctors are going to know where to cut, how far to cut. And I said man, that sounds awesome, looking forward to seeing the miracles. You work on the Coors Light can and other applications.
Lyle Small:And then two days later, I was watching a 60 Minutes program about a guy named John Kanzius K-A-N-Z-I-U-S. You can find it on YouTube. They did this program where this guy had the idea to inject gold nanoparticles into tumors and then put patients in front of radio wave machines to heat up the gold, because radio waves pass through us every day harmlessly but when they come in contact with metal particles, the particles vibrate and heat up and you can kill tumors. He was showing that you could raise the temperature inside of a hot dog, for instance. You know he was putting this hot dog in this radio wave machine that had gold nanoparticles in it and he said you can practically cook the hot dog in one spot and leave the rest of the hot dog temperature unchanged. And he said this would be perfect for tumors. And he's right. Hyperthermia in cancer treatment is well established nowadays and it is excellent. It's one of the best ways to kill tumors. You get six degrees of temperature increase and the tumors, the cancer cells, die.
Lyle Small:So we thought at the end of this program they're talking about the solution. And they said so how would this work? Would you just inject it? And he said no, what we really need is a targeting mechanism. And it was kind of like this shot out of the blue, you know, like this is just too weird. I just saw a targeting mechanism two days ago. This dye could be attached to these gold nanoparticles potentially. I mean I didn't know if it was possible, I didn't know enough about the dye or anything. And so I went in the next Monday and asked John about this and he said well, in theory, absolutely.
Lyle Small:So we filed a patent and I started working with Georgia State to take their dyes and attach them to gold nanoparticles, which are very common, and then, after two years and more money than I want to admit to having spent, because my children are in college now, we failed miserably. You know that money was just poof gone and I gave up for two years but turns out, I hired another Kodak chemist that kept going. We decided that we revived this project. That's another long story. It's one of those stories about you know, like this thing just ate at me. You know we're moving ahead, growing the CTI part of the business, but in the back of my mind I just could not let this whole idea about a cancer treatment that would be brand new to the world and transform cancer care Like it was this and people nerds know what this is about. Right, if you're listening to me and you're in innovation, then you get something under your skin and it just gnaws at your amygdala, right, it's just this thing you dream about, you think about it, and so I'm like taking this as a sign. I guess we should keep working on this.
Lyle Small:And I had a chemist that told me that he could make this tumor targeting dye and it turns out he could. So that's when we started all over again, filed more patents and actually got something that would work Hypothetically. We got this tumor targeting dye attached to gold nanoparticles would attach itself actually more effectively than the pure dye, to dozens of different types of cancer. And then we were putting these cancer cells in radio wave machines and cooking them and killing them. It was brilliant.
Lyle Small:We had mice xenograft, mice models that were taking up these gold nanoparticles and these dyes and were heating them, shrinking tumors. It's brilliant. And then, you know, an engineer on our team said if you scale this up, you're going to have problems because the device is going be require so much electricity, it's going to cost 20 million bucks and you're going to need four of them in every hospital. It really is as an investable technology. You got a problem. That was 2019. So this is a journey that takes hours to really describe, but that's what led us to doing the same thing with chemo drugs, and that's where we are right now.
Ben Comer:Now, when did you, at what point did you actually found and launch Lajavita?
Lyle Small:Lajavita was founded in 2018, after we started shrinking tumors and, you know, actually heating up gold with dye attached to it, selectively binding these to all kinds of different cancer cells, and seeing these mice with glowing xenograft tumors. You know it was okay. We've got to make this something new. This was before we figured out that you couldn't really invest in it. But 2018, we found La Llevida because we saw so much potential. Right, we had solved all the big problems, except for the device. We had solved all the big problems except for the device. A human-sized radio wave machine was just going to be a hill too big to climb for a little company like ours.
Ben Comer:Where did the name La Lla Vida come from? I've been saying it wrong. By the way, I think I said La Javida last time.
Lyle Small:That's all right. Yeah, I have created a name that no one can pronounce Another problem with us nerdy types. So Laia, vida means the gift of life in two different languages. I have a special place in my heart for Finland and Brazil, and so this is the Laia means gift in Finnish and vida means life in Portuguese.
Ben Comer:And you funded this company initially just from proceeds at CTI. Is that right? Have you brought in additional investors at this point, or what are your plans, I guess, in terms of funding right now?
Lyle Small:Yeah, of funding right now. Yeah, so CTI spends about. We spend about 15% of our revenue on innovation, so we have 35 unique technologies to the world that no one else has. We are an innovation-driven organization, so this was just another research project. Within CTI, we generally have eight to 10 projects going at once.
Lyle Small:This was one that I was trying to keep in the background for a while. You know, we're just going to let Ray play around that's the chemist's name Play around with the dyes and the gold nanoparticles in its free time. We'll hire an engineer here and there to see about heating up the gold. So this was funded. We put in about three and a half million dollars of CTI's own money before we spun it out Actually, to date we're probably about three and a half. After we spun it out, it was about $2 million. So total of three and a half million dollars over the course of that 10 or so years. And eventually we spun out that we started this company but it was still relying on CTI for funding and doing all the basic research. But in 2023, we decided okay, we're going to spin this out, transfer the technology completely. It's going to stand on its own. We're ready to go out into the marketplace and raise some seed capital. So we had some non-dilutive funding from local foundations here that love the idea of targeted chemotherapy or hyperthermia with gold nanoparticles. They put money into us to the tune of about a million and a half dollars on top of the money that we had put in, and now we've raised another in this most recent seed round that we're trying.
Lyle Small:We're now at the stage where we can do pre-IND studies. Our IND enabling work is beginning now with Syngene, who I'm sure your listeners have heard of. They are off and running the early. You know this is. You heard it here first. The last couple of weeks we have they've been repeating the work that we did in the prior three years on cancer cells.
Lyle Small:We showed very high efficacy on three different cancer cell lines in previous work. That work was confirmed by Syngene. So when you get a test result you feel like you've got confidence in it. You've repeated it several times. But when another company gets exactly the same results, another research group gets exactly the same results in Bangalore, india, it's hard to argue with those results. And so we're getting equivalent efficacy to pure chemotherapy drugs. Nanomolar IC50 numbers, so highly toxic to cancer cells, very selective uptake and once we start doing the animal studies we've already done four animal studies ourselves on lung and colon cancers we're going to start doing those animal studies here in the fall and we're going to file an IND in 2027. We think we can get an approval sometime in that year.
Ben Comer:And you're, I guess the focus right now is on linking the dye to chemo to establish chemotherapy products and improving their precision. You're not still working on gold nanoparticles at this point. That's exactly right.
Lyle Small:So we've set aside gold nanoparticles. It's still being. Actually there's some studies being done by the local university because we got an engineer there who's ecstatic about hyperthermia, especially in prostate cancer. He's found that you can double the heating with the same energy when you attach these dyes to gold nanomarticles. I'm named in a biotech article, which is kind of funny, for this particular approach. It works well. But he's focused on that, our company.
Lyle Small:We've discovered that we could take about 40% of the existing chemotherapy drugs that have ever been developed and attach them to this tumor-targeting dye and make them safer and more effective. The dye uses a completely different mechanism of action compared to antibodies. So antibody drug conjugates, as everyone in biotech knows, are the hottest thing right now. There's a ton of these things in human trials there's 15 that have been approved by the FDA and antibodies target specific cancer cell types. As I'm sure all of you the people that are listening know. Antibodies identify specific epitopes on the surface of cancer cells. The antibody attaches to those on the surface and then this cancer cell takes the whole thing into itself and, once inside, the cleavable linker, based on the chemistry of the cancer cell, releases the chemo drug. So antibody drug conjugates have been around for a long time, since the early 2000s, and each one is worth over a billion dollars. Some of them are worth a couple billion. Each one is worth over a billion dollars, some of them are worth a couple billion.
Lyle Small:This most recent acquisition by Pfizer of Cgen really demonstrated the value of antibody drug conjugates. They have a tremendous. They've done great things for patients and we think that our approach is like antibody drug conjugates, only better. We think there's more potential in this approach than antibody drug conjugates. That is an audacious statement. I understand that I am part of a company that we believe can attach 40% of all chemotherapy drugs to a single dye that will work on dozens of different cancer types. This dye has bound selectively to over 30 different types of cancer. Same dye because it uses a different mechanism of action. That mechanism is well-established, but it's fascinating that this thing will work on so many different types of cancer. But because it will, we've got the opportunity to kind of come in and supplant antibody drug conjugates.
Lyle Small:And why would I say that? Well, antibodies have their issues, as those who know the business well, I didn't know anything about antibody drug conjugates until I got into this, but antibodies are hard to make. It turns out Really tough to manufacture Once you make them. They're not very stable. They're huge molecules so they don't cross the blood-brain barrier. They're problematic from a side effect standpoint. Many of the most recent ADCs that have been in human trials have failed because of side effects. They've either phase one or phase two. They're failing and often it's because of unpredictable immune responses. Antibodies cause immune issues. They also have other issues. There's actually an acquisition made recently. I can't remember who bought the company, but all that company does is identify the side effects of antibodies side effects of antibodies. That's because antibodies are a problem. Antibody drug conjugates have been and are fantastic. However, they aren't the end goal. They have real problems that our solution does not yet appear to have right.
Lyle Small:This dye is a simple molecule that has shown zero toxicity. We have demonstrated over and over again in fairly large animal studies using small nude mice models, no impact of toxicity from the dyes themselves. And actually we're not finding free chemotherapy in the bloodstream of these animals, so no free chemo drug is being released systemically. The dyes themselves do not show toxicity. We're getting 32% weight loss from pure doxorubicin, for instance. That's common.
Lyle Small:Doxorubicin is called the red devil because it's such a horrible chemotherapy drug but it's got a $1.5 billion market because doctors love it. It shrinks tumors but it also really messes up patients. Tumors, but it also really messes up patients. You get more than I think. The number is 350 milligrams per kilogram of body weight of doxorubicin Lifetime dose. Your odds of permanent cardiotoxicity is over 40%. You go over 400 milligrams and you run the risk of giving your patients a heart attack at the rate of 60, 70% Really big problems with doxorubicin.
Lyle Small:When we attach doxorubicin to our dye, all those toxicities go away. We're getting an average weight loss of 4.5% from a cohort of nine different mice, compared to 32 percent weight loss with the pure doxorubicin, and that's. I mean that that alone is a massive step forward for cancer care If we can eliminate or at least significantly reduce these kinds of side effects. Now doctors don't have to worry about that. 350 milligram per kilogram lifetime dose you can. Dose reduction for doctors for oncology docs is one of their biggest problems. In order to save the life of their patient, they have to back off on the medicine. With our approach you don't. You can continue to give the dose that's going to affect the tumor for as long as you need to.
Ben Comer:And because it's only affecting the tumor.
Lyle Small:Exactly, yeah, it waits until it gets to the tumor. Once inside the tumor it cleaves Same cleavable linkers that are used in antibody drug conjugates. So the linker is not new. The chemotherapy drugs, of course, are not new. The dye has been studied for since 2006 and has never shown any toxicity. It is not FDA approved, but a relative of it is approved, and we think that this thing has a very good shot at getting approved by the FDA because there's there just no toxicity signals your lead candidate.
Ben Comer:You know, after you get through animal studies you're not ready to decide on which chemotherapy agent you know you might prioritize for development.
Lyle Small:We've got. So it's a great question. We've got four DDCs that have been created and every one of them worked. Two different dyes and two different payloads. So Two different dyes and two different payloads. So SN38, which is the active form of the prodrug, arenotecan, and doxorubicin. Attach both of those to our dye to two different dye molecules, and all four of these things bound selectively to cancer cells, killed cancer cells at a very high rate, shrunk tumors in mice in both lung and colon cancer. So all of them were successful, but the doxorubicin with one specific dye was the most successful. So so far that's our lead.
Lyle Small:Now we're repeating all this work with Syngene. It's going to take a few months. I don't like that. I'd rather have it be done now, but a couple of months in the grand scheme of things is not that long a period. Then we'll take it into our IND enabling work.
Lyle Small:I think that we have a fifth compound that stands a really good chance of becoming our lead and that is a compound that uses a brand new payload called MMAE. There are four different ADCs, antibody drug conjugates, that use MMAE as a payload. Mmae is 10 times more toxic than doxorubicin, so this thing cannot be used without severe protection. Right, you have to have it bound to an antibody or, in our case, bound to our dye, so that it travels systemically, it's stable, but once it gets inside the tumor, the MMAE is released and it's proven to be a highly effective payload, as you can imagine. I mean, this thing is lightning in a bottle. We're talking about picomolar IC50 numbers. This thing is toxic, really, really hot. So we're thinking maybe this thing would take the lead in some of our early studies. But we'll find out.
Ben Comer:Well, that's really interesting and exciting. I wanted to ask you a question about animal studies and the IND enabling work that you're getting started on. It's a topic that we don't talk about that much on the podcast, but every biotech builder is going to have to go through those phases and so as someone who is somewhat new you know relatively speaking, I guess to the life sciences sector Lyle, you know give me a sense of you know what it takes to do those animal studies. You've done some internally. Now you're working with Syngene to maybe repeat or expand that work. You'll go into your IND enabling studies. Give me a sense of like you know what was unexpected about that, what some of the challenges have been and maybe like a kind of ballpark cost of you know what it will take to get you through those IND enabling studies.
Lyle Small:Yeah, so I'm cheap.
Ben Comer:I do not like spending money and it has served me well over the years. However, once we got to a point where we had seen enough of the cell, information.
Lyle Small:There's only so much. You can do with two dimensional modelsdimensional models, and those mice are pretty expensive. I've heard, oh my goodness, shocking. I think it's the, you know, the teeny little mouse is 300 bucks, you know. Uh, I, I believe that's what it costs. That's just for the mouse, that's not the house or feed or any of that stuff. These, these vivariums are just crazy. So you have to have, let's say, at least nine mice per cohort. So this group has to be housed and fed in a very controlled environment. And then you got to grow the cancer cells in petri dishes for a period of time until you get large enough to inject into the mice. And then you grow these tumors. An individual, very basic mouse study has run us on the order of 80 to 100 thousand dollars. So that's, you know, one control and one test group. If you want to do more than one test group now, you know, just add, add another $50,000 onto each one of those things.
Lyle Small:They run real money, in other words, four or five weeks and, um, that doesn't include the time for the write-up. We worked for a long time with the Cancer Center drug development folks at CU Anschutz here in Colorado. Really fantastic team of professionals Was very pleased with the work that they did with the gold nanoparticles, beginning in 2017. In 2017. They did some early stuff with the chemotherapy conjugates in 2022. Since then we've taken it out and working with a couple of different CROs, but in all cases, in order for them to make any money, they've got to charge significantly. So we were in a luxurious spot where we had set aside, as I said, 15% of our revenue goes toward R&D, and so we were able to fund this to the tune of several million dollars over the course of several years over the course of several years. But at this stage, in order for us to have the kind of data that is going to be persuasive for the FDA, we got to raise about, let's say, between five and eight million dollars. We've raised a million and a half of that so far. From you know local visionaries I'm actually one of them. I will say I put in some of my own cash and so I'm coming in with the same deal that everybody else is, but we're trying to raise money wherever we can. It is tough to get venture capital interested at this stage, as your listeners may be familiar with Just in general. It's hard to get venture capital interested at this stage, as your listeners may be familiar with Just in general. It's hard to get early venture money for oncology in particular, however well, you add to that the overarching problems in the biotech business problems in the biotech business. However, we think that this is a big enough idea that family offices and interested individuals will find this highly compelling. You know the hope of transforming chemotherapy and, one day, possibly small molecule targeted therapies that's, two thirds of every cancer patient gets one or the other either chemo or an SMTT. That hope is just too compelling for early stage investors to pass up. We're a small company but we've got a really impressive team that's done this before. Syngene has obviously done this hundreds of times and so, even though we're coming out of the ink business, we have a group of people that can make it happen.
Lyle Small:I don't have a PhD in molecular biology. I've got a bioengineering degree. I know something about cell biology and I'm learning more about biotech every day. It's, as you can imagine, quite an experience for a guy with ink under his fingernails to come into the biotech field. But you hire good people that have the right experience and the path is fairly well established. That's one of the beauties of the FDA.
Lyle Small:The downside is that the FDA is going to protect patients and there's a very specific process. It's incredibly expensive, incredibly time consuming, but it's not a black box. That's what I love about it and it either passes or it doesn't. It either makes patients' lives better or it doesn't. And if our solution doesn't make patients' lives better, then the FDA should tell us to go away. Make patients' lives better than the FDA should tell us to go away. So I'm not.
Lyle Small:I don't necessarily have a problem with the 80 to a hundred million dollars we're going to have to drop on pre-IND enabling and then IND enabling and then human trials between now and 2031.
Lyle Small:But that it's a big hill to climb and right now we got 1.5 million of the 90 million we're going to need. If we can raise another 5 to get to human trials and that IND is accepted by the FDA, that's going to increase our valuation and make raising the next 20 to 25 million viable for phase one. Phase one goes well and I am highly confident that phase one will go well because this thing is not toxic. You know, we just see it over and over again these mice are just fine after the end of these studies, and I think that you know. Of course humans are different than mice but based on the conversations I've had with people, we have a lot of confidence that phase one is going to go well and then phase two is 30, I'm told, 30 plus Once we get through that. Now the company is a new entity and we're on a completely different plane and I think venture capital will find us an interesting target.
Ben Comer:Are you considering I mean assuming an improvement in the public markets? I mean, have you thought about an IPO, like when that might occur?
Lyle Small:down the road Depends on the market. You know phase two is going to be 2029 and 2030. So by that time I'm hoping that the blood in the streets will subside a little bit you and everyone else in the sector.
Lyle Small:Yeah, right, yeah, that the IPO market will calm down a little bit. I'm open to IPOs if it makes sense. Being a public company is something that makes me nervous. I've got this pretty serious independence streak that I don't like answering to people other than shareholders. And if I've got 10 shareholders, fine. If I've got a hundred thousand shareholders, uh, that now you have a ring in your nose, as they say. You know you've got. You got other people telling you, um, what you need to do with your life day to day, and that doesn't sound really great to me. But if it's required to change cancer treatment, I'll do it.
Ben Comer:Yeah, yeah. You mentioned the importance of just a few minutes ago of hiring good people and I wonder what you might say about, you know, the next hires that you will need. I don't know if you'll need like a regulatory person to cope what I was gonna say.
Lyle Small:Yeah yeah, yeah, no regulatory is um such a key? There's so few people I've found that uh that are out there that want to join small startups with a keen understanding of the inner workings of the f. As long as we can get the right kind of help at this stage to help us identify our lead and identify our indication. I've been listening long enough to smart people talk about these two topics to know that this isn't easy. Choose well your lead compound and, based on that lead compound, there's interplay between the lead and the indication. It isn't necessarily the biggest market that you should go after for your lead compound. It is the market that you can assemble patients most readily from right, yeah, right. Where do you find these patients? How much is each patient going to cost you to attend to, to take your compound? How is this going to be run over time? These are all big questions that are top of mind right now, because we have to begin with the end in mind, and this kind of brings up another point that I should make.
Lyle Small:You know you're called the business of biotech, even though I'm not a biotech CEO. It's business, and when I think about how La Llebitia can be successful, the question is always what is the consumer need that's being met by your company? Does your mission fill an important need by customers? And now, in this case, the complexity is ridiculous because it's not just patients and patients' families, but it's doctors and insurance companies, it's the federal government, it's big pharma should be one of our customers at some level, because this is a platform recently, but we're just talking about an augmentation for existing chemotherapy that just turns it off while it's circulating in your body so that it doesn't destroy your healthy tissues and then lets it go once it gets to the cancer cells.
Lyle Small:So this, the thinking about how a business needs to run, are all the same whether it's biotechnology or IT or software or ink or selling pizzas. Rate. Building a team of people that can serve those needs effectively and efficiently every day and make consumers thrilled that you exist in the world that is what business is all about. That's capitalism, and I think that we're pretty clear. It's never been more obvious, right, what the value proposition is for a product than what we're bringing to the table here.
Ben Comer:We talked a little bit about you know you shared some of your experiences scaling up CTI. Obviously, you're going to have to do some. You know, scale up as the assets progress at La Javita, but you're also going to have to scale up your management team. We've talked about, you know, hiring potentially a regulatory person. Maybe we can do a little bit of recruiting here. Lyle, I'm curious about how you would describe your management style as a leader and maybe you know how your colleagues and staff would describe you.
Lyle Small:This is a dicey question, so, but it's the only question right For me personally, how I recognize the importance of the role that I play. And that is that. That leads me to my first critical point. With anybody that joins our executive team, the most important thing that anyone brings to a team is the ability to introspect Right. This is this is true whether you're talking about a family, you're talking about a football team, you're talking about a team where you work or an organization the ability for you to look inward and say what is my role here in this organization, how do I make this group better and where am I falling short and can I take, accept feedback? So when folks join our team, you know I've I'm a type A right, I'm pretty intense, I get into it, and some people, because I talk like a football player, I played a lot of football. Some people, because I talk like a football player I played a lot of football I am competitive, I am here to win, and sometimes that intimidates people and I don't mean to be intimidating, but I recognize that I have to moderate that because I am part of a group and helping people feel comfortable in that group, comfortable to tell me the truth, as they see it, is one of the most important functions that I play. I want to have a group of people that are willing to tell me what's on their mind, and they're not going to do that if they're nervous, right. So they're also not going to do it if they think that the people around them aren't going to support them. So, getting the best out of people, especially when it comes to the type of work that we're doing at La Vida, we have to have an environment where people are prepared to disagree and have significant conflict, but not personal conflict. How do we have healthy conflict where the best ideas always win, where no one takes things personally if their idea isn't the winner? But getting good ideas on the table of all kinds and then kind of beating the hell out of them, you know like will your idea survive? The gauntlet of this team that's what I'm most proud of is creating a group of individuals that can be good friends and also be able to say, no, I don't like that idea because of this, this and this. I think we should do this for these reasons. That's how companies ultimately win.
Lyle Small:So when I interview folks for a leadership position, I am searching for indications of four different personality traits that I have found are incredibly valuable and incredibly rare. The first one is humility, as I alluded to Right, and humility is not some, you know idea of self-loathing or you, you. Humility is insecurity, somehow. Humility is an accurate assessment of who you are and a recognition that you should continually be reassessing who you are, what you're good at and what you're not so great at. And then curiosity, so, and that kind of feeds this introspection Curiosity about yourself first, but also curiosity about what's in the heads of the people on the team. Curiosity about what you, what other people, are saying and why they're saying it. Curiosity about what motivates others customers, team members, the marketplace. And then the courage to accept the truth that you find as a scientist, you're always looking for the truth, right, and you sometimes don't like the truth.
Lyle Small:The truth was that our gold nanoparticle idea was a shit show waiting to happen. You know it was going to be a failure, as much as I loved it. I love the idea of hyperthermia. It was my baby. I had thought of that. I watched the Kansia show. I had to let it go.
Lyle Small:Courage is required to say I was wrong. Courage is required to say we have to pivot. Even though we love this idea, it's not going to work. Courage to say I've been fighting for the wrong thing this past two months and I have to apologize to this person, you know, because maybe I mistreated them or whatever. That takes courage. It takes courage to do the right thing when it's uncomfortable.
Lyle Small:And then, finally, kindness, and this one, you know, I always like to think that I'm kind, but if I come across to someone as overbearing, then kindness requires that I perfect, but that you're striving each day to be a little bit more courageous, a little bit more humble, a little bit more kind and a little bit more curious. I want you on my team Because you got to be smart to have a PhD, right. You got to be smart to have to have be a professional at the highest level in biotech. That's a given. But smart people are also uh easy to find. It's hard to find people that are uh, going to let the the truth always went out, whether it's happens to be their idea or not.
Ben Comer:Well, um, that is an excellent place to end it, I think. Lyle, thank you so much for being on the show and telling us about just sharing your experiences. I really appreciate it. Thank you, ben, it's been a pleasure. We've been speaking with Lyle Small, founder and CEO of La Lla Vida. 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 new weekly videocasts of these conversations every Monday under the Business of Biotech tab at lifescienceleadercom. We'll see you next week and thanks, as always, for listening.
