Rob Rothman: Hello OIS Podcast audience, happy to be speaking with you again. For those of you who have not listened to any of my previous podcasts or have no idea who I am, my name is Rob Rothman. I am a Practicing Glaucoma Specialist in New York. I am also the Co-Founder and Co-Managing member of InFocus Capital Partners, which is an ophthalmic focused venture capital fund, we have a 13-asset portfolio, and we have recently, for the most part concluded the investment period for this one, I have been an active participant with OIS for many years as a panelist and a participant in many ways, and I have recently taken on an additional role as a Podcast Interviewer, which is, undoubtedly been the most fun role that I think that I’ve had here. So, with that as a backdrop, I would like you to welcome today’s guest, who is the Founder, Chairman and Chief Executive Officer of IACTA Pharmaceuticals, Damon Burrows, I will also, full disclosure, make the audience aware that InFocus Capital Partners does have an investment with IACTA, but this interview is purely based on the fact that Damon is one of the most fun guys that I’ve interacted with, during my time in the venture capital business. So, Damon, with that as backdrop, welcome to the podcast, and thank you for taking the time to be with us today.

Time: 02:01

Damon Burrows: It’s a pleasure, thank you so much for having me.

Time: 02:04

Rob Rothman: So, I want to sort of get into a little bit, you know, these podcasts are very sort of loose when I do them. I don’t have a structured format, which you know, but I want to get a little bit into your background, because this is a recurring theme, I think, nowadays, that people from the legal world are taking on responsibilities at the helm of early startup stage companies and Life Sciences. And for me personally, as an investor, when we are looking through the management diligence, it’s an important one for us to know that somebody’s got some background in legal, as I say the majority of roadblocks that are controllable end up happening on the regulatory and legal side of the business. So, maybe you can just walk us through a little bit of your background. I know you’ve had a long history in the pharmaceutical world, sort of your educational history, where you came from, all that stuff, just so the audience knows who you are.

Time: 03:05 – Legal Career in Washington, DC and joining Roche

Damon Burrows: Sure, no, thank you. Yeah, so I was a lawyer by training, started in Washington, DC, working for a law firm in the Health Law Group. I worked for a lot of doctors, hospitals, health clinics, and really counselors around compliance issues, and that was sort of where I got my teeth in law. And then, because of the big healthcare practice that we had, it turned into life sciences as a subcategory that we started supporting quite a bit. And I remember a phone call I got, I was sitting in Washington, DC, and a headhunter called me and asked, ”what do you like about what you do?,” and I said, “well, look, I love the clients, I love the science, the thing I don’t like is the travel.” You can tell I was traveling all over the country and, he said, ”what if I could get you in a company, and give you visibility to the scientists and all the things that you love, and you wouldn’t have to travel?” And I said, “that sounds amazing, let’s do that.” And, so, not long after that, I was on a call with Roche, and they were hiring a regulatory lawyer for Hoffmann-La-Roche’s Nutley, New Jersey office, and they said, “we’d really like you to come on board,” and I said, “well, does it concern you at all that you’re hiring a regulatory lawyer and I know nothing about regulatory?” I was a compliance lawyer. And they said, “no, that doesn’t bother us at all. And I said “well, it bothers me a little bit”, and they said, “don’t worry about that, if you got the compliance stuff, it’s fine.” And I literally went there as a regulatory lawyer, and I learned from scratch everything about being in life sciences.

Time: 04:45 – Working at Roche

And I say, I will say, to their credit, Roche is a special company, I was fantastically lucky to be there, but the way they had their lawyers set up, you’re a lawyer really soup to nuts for the entire business. So, everything from early stage, formulation, R&D oriented through clinical trials, all the way through commercialization. So, one lawyer got full visibility to all aspects of the lifecycle, and I was absolutely enamored with life science. And, so, that became really my passion. And, so, while I loved the R&D and the development side, and commercialization, really all of it, and, so, but that, that was what got me into life sciences, and from that point forward, I knew that’s really all I wanted to do.

Time: 05:35 – Leaving Roche

So, when Roche was acquiring Genentech, taking them private, I had a choice, it was either move to South San Francisco and become 1 of 100 plus lawyers, and I didn’t know what I would do, right, or, at the time, Allergan was hiring a Chief Regulatory Counsel, this is five years after I’ve been in house, and I thought, like, yes, I am a regulatory lawyer now, right, so sure. And I really, really was impressed with the leadership at Allergan, and that’s what brought me to Southern California. I had the choice, and I chose Allergan, and what a good choice that was, because it was my exposure to eye care and, really, eye care became a big part of what I did from that point forward. So, my path was probably atypical, I would say a regulatory lawyer specifically is a really small niche, there aren’t a lot of regulatory lawyers in the world that are in-house, but absolutely fantastic in terms of visibility, and it really got me excited about life sciences, and at that point, it really became the only thing I wanted to do.

Time: 06:36

Rob Rothman: So, when you got to Allergan, though, your responsibilities became a lot more diverse, is that correct? I mean, you obviously took on a much larger role there because you have, again, from my personal experience with you, this incredible compendium of knowledge regarding management of operations when it comes to the pharmaceutical industry, not just regulatory compliance. So, what happened at Allergan that sort of changed to your perspective on what you want them to do?

Time: 07:04 – Joining Allergan as Chief Regulatory Counsel

Damon Burrows: Well, Allergan was just absolutely a joy, because when I remember the day I showed up at Allergan, there was a queue of people standing at my door wanting to talk to me. Hi, I’m Damon, and, you know, there are three or four people standing there waiting to hold papers in front of me and, so, I’ve never been more needed in my life than that. But it meant that it was visibility to every kind of a problem one would have, right, from a technical standpoint, manufacturing standpoint. The way that we had things structured at Allergan, I was the Chief Regulatory Counsel for R&D Globally, so that meant I had full visibility to the entire R&D organization around the world, Chief Regulatory Counsel for all of the health authorities, and I sat on the North American leadership team for commercialization. So, I really was actively counseling all business units, whether it was how to get something paid, whether it was how to promote something, whether it was a counterfeit issue, everything around the company, and I didn’t have to do a lot of the things that I would have had to do at Roche, right, there were no contracts review. So, it was a fantastic job. And then, as we moved forward, I ended up building a team that reported to me, and then we had actually lawyers in the weeds working and supporting all aspects of the business. So, I would say that I was fortunate in terms of visibility to what the business does. But, I also was able to really determine what makes a great pharmaceutical executive, what makes a great person of great execution, and that heavily influenced how I then was recruiting for IACTA, because the people that I work with that I trust, that execute really well, those are the people that I was keen to hire.

Time: 08:51 – Leaving Allergan

When Allergan sold a number of years ago to Actavis, I was in a situation where, well, what am I going to do? You know, we were a Top 10 company in the world and I was the Chief Regulatory Counsel, there are only nine other jobs in the world like that, those aren’t exactly available, right? So, what do you do, and there really wasn’t a company I wanted to work for at the time as an employee, and, so, in the end, we really liked the idea of taking what we were good at, and trying to focus just on that. If you recall, at the time, Actavis had announced they were no longer going to focus on early-stage drug development, right? They were going focus on late stage, well, sound business plan, and, of course, you know that’s a great way to go, but that wasn’t how we built Allergan originally, right, Allergan was built on taking things, getting them into the clinic, seeing, you know, market making in many instances, and that was what I wanted to focus on. So, we founded IACTA really with the idea that we wouldn’t do what everyone else is doing, we would do something very different, and focus on early-stage drug development, and hopefully fill a niche that, you know, was unmet. And that was sort of the vision, originally, it morphed over time and turned into a lot of other things, but the vision of what we wanted to do, was really what we were great at, which is formulating drugs, getting them into the clinic, and getting new data.

Time: 10:15

Rob Rothman: So, but, tell me, just I think maybe you just glossed over it a little bit, and I think maybe it’s probably an important thing to spend a few minutes on, which is that transition from this corporate world where you had, you know, this multilevel of responsibility, sort of job description that take you into all aspects of pharmaceutical development from, you know, science all the way through marketing, licensing, you know, the whole the whole gamut and then you end up sort of at IACTA. So where is that inflection? How does it go from Big Pharma to IACTA?

Time: 10:51 – GC at Allergan

Damon Burrows: So, it’s a great question I did skip over. When Allergan sold, I became General Counsel of a pain company called Scilex. And not long after I was there, in about a year, it sold to Sorrento. So, we were at a non-opioid pain company, that I was the General Counsel of and, at that company, there was a lot of BD evaluations we did. One of them I thought was very interesting, it was not a part of that company, there was an ocular drug that we evaluated. They had a pain product and an ocular drug. The ocular drug was really interesting. I don’t know if you know this, but I lead the defense of Restasis^®, when a bioequivalence guidance had been issued, Sesha Neervannan and I co-lead a defense and the project team on that effort. And so I was very…

 

 

 

Time: 11:44

Rob Rothman: It was very successful. I mean, that was a successful defense, there is the bioequivalence requirements for Restasis^® are incredible. So, you know, that’s why you’ve managed to keep generic, pretty much out of the market, I guess, for the most part, correct?

Time: 11:55

Damon Burrows: Well, so that’s the end result that there hasn’t been someone able to demonstrate a bioequivalence, but the reality is, it’s incredibly challenging to deliver a hydrophobic drug like cyclosporin into the eye, and the ways in which that was formulated, it was a very elegant formulation, and very specific. And so we knew from all of the iterations of making that drug, how difficult it was to try and make something similar to that drug. It’s just a very complex formulation. So, our team of scientists, absolutely brilliant, our regulatory team was brilliant, and our legal team was brilliant, and we were able to put together very concrete real-world examples with data that showed these differences.

Time: 12:37

That was a very successful effort. It was also baptism by fire about how complex ocular formulations are and can be. So, we wanted to build on that. I found an asset that we quite liked, that was really novel. We loved, because of our Chief Scientific Officer, Orest Olejnik, we really love complex formulations, because of Restasis^® and getting something formulated. That’s obviously one example. But the reality is, there’s a whole host of really novel interesting delivery platforms that can be harnessed now, that just were not available over the years. If you think about the many things that were evaluated, if some of the technologies were available now, back then, we would have had, we think, many other successes. So, it’s in our view, a very exciting time for ophthalmology. And so, this was the beginning thought process around, well, what should we do? Let’s harness some of the new tech, right, of delivery systems, let’s go for things that no one else is going for, or novel formulations that we can, you know, innovate. And I will say I didn’t fully appreciate the investor community, and what was and wasn’t favorable at the time. So, I thought, scientifically, a reformulated cyclosporin would have been a brilliant, brilliant program, and I had many people ask me why we were doing that.

Time: 14:05 – IC 265

We continued to work and look for other assets, and I must say, over time, we were able to identify a new platform that is very differentiated, which we now call IC 265. And IC 265 was really, for us at the next step of okay, well, cyclosporin sort of has been done, even if you differentiate it on a formulation, what is really going to change the game for dry eye, for example. So, the idea of having the something that is truly potent and really specific, as an inhibitor, was very attractive to us. And so, we went from thinking, okay, well, we’ll make the best cyclosporin, to really evaluating this NCE that is a SYK Kinase inhibitor. IC 265 is now in Phase 2. So, we’re doing a Phase 2 program beginning at the end of this year. That program, I’m very excited about because it is a very novel, and very tolerable anti-inflammatory. So, one of the big challenges for anti-inflammatories historically has been tolerability. And so having something that’s easily tolerable is, and fast acting, we think is very, very exciting. We look at it more as a platform. We are doing a dry eye model, and we’ll have a readout on that in the next year. But we really are interested in harnessing the SYK Kinase Inhibitor for a number of uses. We think having a potent anti-inflammatory that could potentially minimize or lessen the use of steroids where steroids are not effective or have consequences can be very positive. So, as I said, we morphed from sort of one drug into NCE. We’re very excited about that platform, we’ve now moved that into the clinic. And then, just recently, we’ve in-licensed another platform that we’re very excited about, which is an ocular analgesic.

 

 

Time: 15:51

Rob Rothman: We’ll get there in minute. So let’s look. I want to save that for later because I think that’s a very compelling part of the IACTA story, but let me go backwards again. So basically, I mean, I made it, tell me if I’m saying this incorrectly, but you were working in Big Pharma, you’ve come across these assets, you’re like these would be amazing, maybe there’s a market for this, I’m going to leave, start a company, and figure out how to turn these assets into a real sort of viable company in the ophthalmic space, is that a summary of the thought process going so far, just so you know, I mean, this is the part that’s so fascinating to me, and it’s always been fascinating. It’s sort of like, you know, IACTA was sort of born from, you know, all of the companies that we come across in the hundreds of companies that we diligence as a venture capital fund, have well intentioned people will have a real good idea about what they think is a perceived need in ophthalmic space. But the way that IACTA sort of did it was a very, you know, a little bit of a differentiated pathway, and I think I want, so you know what I’m asking? I mean, you know.

Time: 17:04

Damon Burrows: It’s a good question. So, unlike the brilliant scientist that has a passion, and knows exactly that we’re going change the world with this one idea, that is not me, right? So, I am not the brilliant scientist, of course. I didn’t leave Allergan and say, I’m going to change the world, that was not the case. Allergan got sold, which meant I was free, right? So, Allergan is newco Allergan with Actavis, and I was, for the first time in my career, without a job and able to do anything I wanted to do. It was only after that exit, of all the sort of original executives under Doug Ingram and David Pyatt that we, you know, everyone is sort of free. And so, the idea was, we have this incredible talent pool, and why not do what we were great at, which is taking other people’s brilliant technology, getting it into the eye, and build a company.

Time: 17:57 – What is different about the people in IACTA

Rob Rothman: So, that’s a part that’s great, that’s the part that’s great. So that’s the part that people I don’t think realizes that it’s not just somebody who finds a molecule or develops a molecule or out-licenses a molecule in some ways, this is going to be great because of the science around it, you took the people who are basically running one of the largest ophthalmic pharmaceutical companies in the world and sort of put them into a new entity.

Time: 18:18 – How IACTA operates and brings in assets globally

Damon Burrows: We did that well, over time, right? It took quite a while, but that was exactly the vision, the vision was we have an ability to execute. We know what works, we know what makes a difference, and want to do that. Now, I will say that with this idea, I sort of ran into a brick wall in the United States at times because people said, you know, who are you? Damon Burrows regulatory lawyer, I found them, but I found a lot of receptivity overseas, I found in Europe and in Asia, a lot of receptivity. So, as we were partnering, we didn’t take just a US focus, we look really at around the world, what is special and interesting. And I must say if you think about what we’ve done, we’ve been able to use a global perspective about drug development, and then bring assets into different markets. So, we like to acquire something that is both novel, has global rights available, and it’s usually, ideally, has a formulation challenge that we can help solve. So, we can value add a program, as opposed to just paying money for it and bring it in and, you know, moving it forward. If there’s some particular challenge that we can bring value to, that is a very nice fit for us. And that’s actually been the case for a couple of the programs that we’re moving forward.

Time: 19:38

Rob Rothman: Right. So now let’s talk about IACTA now because, you know, obviously I think that’s what excites us and sort of where your passion is at the moment, any order you want, but I think it’s important to discuss your team because, you know, the rock star nature of who’s involved with IACTA and the quality of the people that have, have come to help you sort of, on this journey. And, then I think the clinical programs, ideas that you have for bringing value to investors is also somewhat exemplary, and I think you’re going to need to spend some time talking about that. So go nuts here, I will interrupt you as little as I have to.

Time: 20:19 – How to build a network of world class experts, how we built IACTA – Steve Johnson and Orest Olejnik

Damon Burrows: So, the first two sort of core members of our executive team were Steve Johnson and Orest Olejnik, right, so, when Steve and Orest, you know, were post-Allergan, they had approached me to be their general counsel for their own start-up company doing an ophthalmology play, right. And, so, I knew at the time I was doing IACTA, and I wasn’t interested in that, but knew that was something they were doing. And when I was strategizing, well, okay, I’ve never been a CEO before, I’ve never been a founder before, I need some help, right? So, I pick people’s brains. I got some really good advice from a guy named Len Brandt. Len said to me, “you need to pick the very, very best people in the world, not, you know, around, but in the world, and surround yourself with them. Whether they’re available or not, doesn’t matter.” And I said, well, that sounds nice, but I don’t have some big stack, you know, I can’t just recruit people, I don’t have an HR function. He said, let me be clear, and you know, laid that all out. It was fantastic advice, because in my mind, Steve and Orest, I knew they were not available, because they were working on something else, because they had approached me. But I took his advice, and I called Steve. And I said, Steve, here’s what’s going on, here’s the idea, here’s what I want to do, and when I think about R&D operations, you know, I worked for Steve, Steve was the Global Head of R&D operations for Allergan, run hundreds of trials all around the world. And, so, when it comes to execution, Allergan was extraordinary at executing on clinical trials. So, when I think of who do I want in that seat running operations, number one, Steve Johnson. So, I called him, and I said, Steve, you know, this is the idea, are you interested? He said, actually, I’m very interested, because this one asset that we were looking at, they couldn’t attain, ultimately, it just didn’t work out. And, so, they were very eager to do something entrepreneurial, have exactly the same vision of let’s harness this sort of drug development expertise. And, so, but he said that we need Orest, obviously, and I said, of course, and so we talked to Orest, the three of us chatted, and Orest is amazing. Orest is, I would say, one of the greatest ocular formulators in the world. So, he was successful at formulating time and again, for Allergan. It was one of the big core strengths we were fantastic at and Orest led that effort. He’s just brilliant.

Time: 22:50 – What is special about IACTA – R&D, Formulation

So, Orest, when we’re talking about strategizing how to solve drug development problems, like a formulation, it could be a novel technology, could be an application, could be, you know, any of the various excipients right use, but the art of getting something that just sort of fits the profile of what you need for ocular drug formulation, he’s brilliant. And so that’s really what we started to build around, we were looking for assets where we could add value, and that was sort of the core. What happened from that point on, is we were very fortunate, and we were able to partner with ORA clinical. ORA, of course Orest knew the founder of ORA all the way back before either was in big companies, right? They worked together 40 years ago. And, so, we are big fans of ORA and ORA had believed in us, and early on invested in IACTA. So, even though we had a very small team, we had great depth of reach in terms of asset identification. And then once we would identify an asset, our ability to look at it, evaluate it carefully, and then assess its potential, I think we’re very good at, this is precisely what Orest and Steve were very good at at Allergan.

Time: 24:09 – Expanding the team – Eric Carter and Yogesh Bahl

So that really became for us the beginnings of IACTA, and since then, I’m happy to report we’ve actually added a number of other team members. Most recently, we’ve added a wonderful Chief Medical Officer, Eric Carter. Eric was, I was his lawyer on the medical Risk Management Committee (at Allergan), so the committee that oversaw all human clinical trial safety, I was his lawyer and worked for him. And then of course, he was the head of development for Allergan. So, we approached Eric, and when we were talking to him about some of the programs in particular, the ocular analgesic program, Eric got very, very excited about what we were doing. And we were able to convince him to join us as our Chief Medical Officer. So, I’m proud to report we now have, you know, Steve Johnson, who ran R&D operations, Orest Olejnik, who ran formulations worldwide, and Eric Carter, who ran development worldwide for Allergan on our team. I am merely the recruiter, but what they are a rockstar team. In addition, we recently hired a non-Allergan CFO that I am absolutely thrilled with named Yogesh Bahl. We’d been doing private money investments up until now and had been very excited with that, but we’re now sort of positioning ourselves for greater, bigger things and, so, we brought Yogesh on, he is absolutely wonderful, and we’re in the process of, of making a lot of structural improvements and changes because of his leadership. So, I’m beyond thrilled about the team and I think when it comes to knowing ocular drug potential and how to execute on it, I would put us up against anyone.

Time: 25:52

Rob Rothman: Yeah, I would agree, I mean, a fascinating consolidation of Big Pharma talent into, you know, much smaller, smaller and sort of efficient package, and that’s, obviously one of the things that at least brought, you know, InFocus into the mix, besides the clinical programs, which we’ll talk about in a minute, but it’s great guys, and they’ve all been a pleasure to speak with and to listen to and to talk to on a regular basis, and it’s pretty impressive, so good job recruiting, I guess. So, tell us about the clinical programs, because, you know, again, I think that IACTA is, you know, one of those companies that’s on its way to being, you know, a bigger player in the ophthalmology, pharmaceutical space, and, you know, multi-platform technology here that I think is going to be very successful, so I think people should hear whatever you’re willing to discuss regarding where you are clinically.

Time: 26:49 – IC 265 and Licensing Deal with Zhaoke Ophthalmology

Damon Burrows: Sure, and we have been pretty quiet up till now about a lot of this stuff. The way we went about our clinical strategy didn’t require us to be so visible and public on some of this. But we are at a point now where that’s changing. So, we’re very excited about the IC 265 program, we made an announcement that our global dry eye franchise, we partnered with Hong Kong based company, Zhaoke Ophthalmology on a licensing deal where we outline since our IC 265 rights to them for China and Southeast Asia, we were absolutely thrilled to pick them up as a partner, my co-founders Will Pedranti and George Ng have worked for many years with Lee’s Pharma, and this is a Lee’s Pharma subsidiary, so we know them very, very well. They’re a fantastic group of people, very, very focused on execution and have a long-standing commitment to ophthalmology. So, with their support, we’ve actually kicked off not just a US study, but we will be doing a multi-regional study in China and in the United States. That is very exciting. It begins enrolling in just a few months. I don’t want to say much more than that, but stay tuned, because that one’s gearing up right now. Like I say, the IC 265 platform, being such a novel, potent anti-inflammatory, we’re excited about it as a platform. So, certainly, the dry eye model is exciting. It had already been an allergy model, where you saw very nice redness reduction, and you saw a very nice anti-inflammatory effect, pronounced, strong anti-inflammatory effect. But most importantly, very, very tolerable, right, an easily tolerable anti-inflammatory, that’s exciting. That’s exciting because, what you can do with something like that, when you’re talking about a heavily inflamed eye, something that’s an irritant is of course working against your ultimate goal of bringing down inflammation. So, a tolerable anti-inflammatory, we think is very exciting, and we think that the applications of it in allergy and in dry eye, which we’ve announced, are very promising. But honestly, beyond that, we have research programs that we have not yet announced that will evaluate its benefits, even at the back of the eye. So, I think that there are, that program in particular, as a platform, we used the China partnership as a de-risking strategy, to move it faster into the clinic, and really have an ability to move it into a number of indications, is the goal. So that program I’m very excited about and we’ve made announcements about that. The newest addition to the IACTA family is the one that everyone’s sort of buzzing about. And as much as I love the IC 265 asset, we have picked up an ocular analgesic platform, that I can’t tell you how excited I am about it. There’s a company in France that figured out a way to harness this enkephalin natural analgesic biological activity, and enhance it, and that is a story into itself. I’ll back up there, and before I jump into the whole Pharmaleads and Denki story, let me see if you have any questions about the IC 265 program.

Time: 30:05

Rob Rothman: No, I mean, we you’ve already told people about the kinase inhibition, multiple potential applications, both front and back in the eye. So, we’ve got that. People need to hear about Denki.

Time: 30:18 – The story about the Denki program

Damon Burrows: Yeah. So, I was at a bio conference in Philadelphia, which we’ve all done, right, you go to these partnering conferences, 30 minutes, and I sat down and after a surface anti-inflammatory, our next big category that we were looking for something was an analgesic, and that was sort of just top of my list, there are a couple of things that are on my wish list, but that one was number two. And so having already got anti-inflammatory in hand, I always tell people, if you have anything in this category, we’re on, we’re looking for it. And I sat down with Tanja Ouimet, and Tanya, says we happen to have an ocular analgesic, and I’m like, Oh, well, would love to know more about it, and she’s like, it’s fantastic. It’s nontoxic, it helps with reduction in pain in the eye, and acts as an anti-inflammatory as well. I’m like, thinking to myself, no you don’t, like, sure you do, you may think you do, but you know, sure, sounds good, I’d love to talk to you, exchange information. So, we brought it back to our guys, and we started looking at it. And, you know, interesting. And as we looked at it more and more and more, it was everything she said, and it was even more than that. Something that I think is one of the most promising programs I’ve seen, personally. So, if you think about what we have in terms of available options for ocular pain, there’s almost nothing, right? There’s almost nothing you can use. You go to the doctor, I remember going to my ophthalmologist, I had pain in my eye and I said what in the world can I have? This was years ago. And they said, well, there’s really nothing. We have something that can numb the eye, but we can’t give that to you, you have to do that here in the office, and we’ve got really nothing we could give you at the time. And I thought to myself, how was that possible, right? How is it possible that there’s not something you can put in the eye?

Time: 32:13

And, so, I actually had some great conversations with the founder of ORA, Mark Abelson, about this sort of vision, a dream of finding something that would be a, you know, for lack of a better word, Tylenol for the eyes, something that generally can just use for ocular pain, and it just doesn’t exist. And when you think about like, what should we go for, what’s the targets, what are the categories, the feeling was, it can’t be a steroid, that’s an anti-inflammatory, it’s not, that’s precisely what you’re trying to avoid. The NSAIDs on the market have this sort of toxicity associated with it so that, for surgeries, at least, it’s not optimal in that regard. And then, if you’re looking at other an NSAID or a steroid as your pain strategies, both of those categories don’t seem to fit, so it really needs to be something else, and other NSAIDs don’t seem to work So, Mark had said to me, it’s got to be something, it’s not this, it’s not that, it’s not that, but its got to be something else, what that’s something else is, we don’t know.

Time: 33:15 – Mechanism and non-toxicity of Denki

Fast forward to me sitting with Tanja, and hearing about this, I’m like, well, it is something else. Let’s dig into it. Our team was really intrigued by the mechanism. I’ll tell you a little bit about the mechanism. But most importantly, about its nontoxic effects. So, it’s a very elegant drug system that’s being evaluated really for systemic pain, right, so they have a whole program around drugs that would be used throughout the body for different uses. But we were very keen on understanding what it would be if it’s used for the eye. It was discovered that there are, of course, opioid sensors, receptors in the eye, that do get hit, you have an enormous amount of pain, because of the ocular sensitivity and result. So, if there’s a way to block the pain signal at the surface, or at those receptors itself, it could be huge, right, for many indications, both acute as well as chronic indications. And, so, the way this works is your body has a natural peptide, called an enkephalin, and that enkephalin, when there’s pain, is naturally released by the cells, and with that release, it’s very effective. So, your body naturally fights pain, and we know this because there are disorders that people who are overexpressing enkephalins can’t feel pain.

Time: 34:34

So, it’s a very, very potent analgesic. It’s natural, and it happens without any sort of interaction by an outside force or drug or stimulant. So, that’s sort of the state of affairs. This discovery about enkephalins was very exciting, it happened in the 1970s, and many companies have been working on trying to find ways to capture that enkephalin analgesia without success, and that’s because not long after the enkephalins are expressed, there are degrading enzymes and, in this instance, Aminopeptidase and Neprilysin, or NEP and APN. These two metalloproteinase enzymes break down the enkephalins fairly quickly. And, so, while the enkephalins are effective because they’re broken down so quickly, it doesn’t provide a long enough sort of analgesia for many conditions like a surgery for example. But what the researchers discovered at Pharmaleads, is that if you inhibit not just one, not just Neprilysin, but if you inhibit both Neprilysin and APN, you have a dramatic elongation of the half-life other than enkephalin. Well, that’s exciting because people have been working on that for a very long time. And, to their credit, brilliant scientists that they are, they engineered a molecule that can, with one molecule inhibit both NEP and APN, and that is our IC 800. So, IC 800 is a drug that isn’t itself an agonist, it doesn’t hit the receptors in any specific way. What it does, is it actually inhibits the degradation of enkephalins in the eye, and so you have this natural analgesia that is happening by the body and instead of that analgesia getting diminished over time through degrading of these enzymes, you block the degradation, we have an elevation of enkephalins and as a result, an improved analgesia. It’s very exciting. And the math…

Time: 36:37

Rob Rothman: I had to say that’s the best science description I’ve ever heard a lawyer give, a nice job Damon, actually, I think even I understood that I think most people will, but that was fantastically done. So again, sorry to interrupt.

Time: 36:48

Damon Burrows: I’ve been trained, very well by Tanja and Herve at Pharmaleads, they have come walk me through it a 1000 times. But, so, one of the things about my role at Allergan, I’m really a champion of scientists, like, so, I love science, and I love these scientists. So, for me really being able to understand how to make an impact and how to make a difference, it’s a scientist, it’s not me, right? But getting, harnessing, this information, this technology, and then bringing it into the clinic, solving the formulation issues associated with it, and getting the result out of it, that’s where we are. So, they had an absolutely brilliant result in animal models. So, there were five separate animal models that they put the Denki drug into, and this is in, you know, ocular animal models about pain, and in all fine, the result was a resoundingly positive result. So it’s that story, the scientific story is very exciting.

Time: 37:53 – Formulation and POC for Denki, use for acute and chronic conditions

But there was a need for us to solve the formulation issue associated with how you get it in a formulation in a stable way into the eye, and that was something that we, our expertise, thanks to, you know, IACTA and ORA, we’re able to solve. And so we just in-licensed this program on the 31st, or last day of last year (2020), so the very beginning of this year (2021), and we’ve already made very good progress on the formulation solutions. And, so, we’re now approaching, we think we have an ability to get a number of POC studies, the first ones that we will do, we’re going to evaluate this in surgeries, so we’re going to look at it in PRK, crosslinking, and LASIK, and see how it performs in all of those. The vision, the reason we’re going after a number of POCs, we’re looking for very broad labeling, as this drug has, it doesn’t have toxicity associated with other programs. So, we’re really going for a broad application for acute pain. So, that’s the reason we really want to have a number of different proofs of concept to be able to talk to the agency and with success, ask for a broad label, and because we think it’s a game changer for surgeries. What’s interesting is while analgesia is a big unmet need, everyone’s familiar with the anti-inflammatory story. Interestingly, this program appears to have very nice anti-inflammatory properties, which in the POC studies, we’re going to evaluate more closely. But then, it’s the third element that makes this something that really raised eyebrows with our team, and that is that it appears to be very pro-wound healing. So, as opposed to being toxic to epithelial cells, this drug will have a benefit to improving the healing. So, it really lines up nicely. If you have an analgesic, anti-inflammatory pro wound healing drug, there’s never been a drug like that. It’s just unprecedented. And so that’s why I say for us, this is the one that you’re, I think a lot of KOLs that have had a chance to look at the data and really understand its impact, has said two things. One, it would be very impactful for surgeries, right? So acute pain, it would be a solution for acute pain that doesn’t exist.

Time: 40:00 – Denke, use for pain associated with dry eye

But then on the even larger scale, the promise of what it may be able to do in chronic conditions, such as neuralgia, or dry eye, there’s nothing in the world approved for pain associated with dry eye. And, so, it’s a very nice story because as opposed to the signs and symptoms that one goes for an anti-inflammatory dry eye disease claim, we think you could use our IC 265, you could use Restasis^®, etc., But, ultimately, if you want to have pain associated with that dry eye condition, it’s an alternative that looks very, very promising. And, so, that program is very, very exciting and, like I say, you start a drug development program with targets, and you de-risk them, you get the POCs, and you move it forward. But, the ultimate vision, that original sort of idea, right, of what does good look like for this drug, we would want to swing for the fences, and obviously find ways to conquer pain generally, right? When you think about all of the uses of an analgesic, it’s very hard to think of all of the ways, because pain is ubiquitous, right? And so having something that doesn’t create numbness, does help with reduction of inflammation, but dramatically lowers pain, we think is a game changer for ophthalmology.

Time: 41:17

Rob Rothman: Well, so does InFocus, so, you know, there you have it. And, you know, I think that the pathways or clinical programs that you have, ongoing now and planned, are absolutely looking for solutions to problems that currently have not been fulfilled, you know, the true unmet need, is really where IACTA is leading. And both products are novel, at this point, and hopefully going to be disruptive, and I think that anybody who’s interested in speaking with you, after they listen to this will be fascinated to learn how much money you’ve done this with. So, another great part of the story, so…

Time: 42:02

Damon Burrows: We’re scrappy, we’re a scrappy company.

Time: 42:07

Rob Rothman: Very, very scrappy.

Time: 42:08

Damon Burrows: But I think what we’re doing now is we’re sort of setting the stage for being a lot more visible, a lot more public. So, yeah, until now, we were very sort of quiet.

Time: 42:18 – Closing summary

Rob Rothman: Well, I think that with that, you know, I think we’ll sort of wind down in a little bit, and I think that, you know, one of the reasons why I was very interested to have you do this is I think that anybody who listens to this, whether it be from the investor side, or the science side, will be excited to hear about these things, and as you come out of, you know, not what I would consider to be true stealth mode, maybe it’s more of a semi stealth mode of operation, and people start to realize the things that you are pursuing, the things are going to be a lot of excitement for you and for IACTA as a company, because not only are these projects, you know, incredibly needed, they’re also incredibly promising and are showing unbelievably, you know, positive early data. And I think that your enthusiasm for them, and when people realize who’s involved and who’s working on, they’re going to understand, you know, how important IACTA is going to be the future of ophthalmology, I think that’s going to come across very, very clearly to them. And hopefully this podcast is something that you’ll use, and people will listen to you and sort of embraces, you know, here we are, here’s what we’re doing, you know, get ready, and, and I think that’s the message that sort of came across here today. So, I think we’ll shut it down now so that don’t get yelled at for being too long again. And I want to again, thank Damon Burrows, the Founder and CEO of IACTA Pharmaceuticals, looking forward to great things from you, and IACTA in the future. Thanks for taking the time with us. And thank you to the OIS Podcast audience for listening in.

Time: 43:41

Damon Burrows: Thank you so much for having me.