Following Intellectual Passions, With Dr. Baruch Kupperman

Barry KuppermanPODCAST EPISODE 299

Click here to watch the video version of this podcast.

Baruch (Barry) Kupperman, MD, PhD, works as a consultant, professor, and benchtop scientist, but finds the most meaning in the dozens of patients he treats each week.

With research interests in dry age-related macular degeneration and drug delivery, Dr. Kupperman has held multiple roles at the University of California Irvine’s Department of Ophthalmology before becoming the Roger F. Steinert Professor and Chair of the department in 2017. Although he spends more time in leadership meetings these days, Dr. Kupperman still devotes time to the pursuit of science and medicine.

OIS host Firas Rahhal, MD, catches up with Dr. Kupperman after a rare two days off to discuss his career path, the current and future state of drug delivery, and what keeps him awake at night.

Dr. Kupperman also discusses his residency and first fellowship (he completed three), which involved treating AIDS patients with retinitis. Administering eye injections to patients weekly—even seeing patients at their homes when they were too sick to visit the clinic—motivated him to help establish a drug delivery unit at UC Irvine to research more convenient ways to deliver treatments.

Listen to the podcast to discover:
• More details about Dr. Kupperman’s background, his work with AIDS patients, and his purposeful detour into neuroscience.
• The evolution of drug development and delivery to date and his views on the current state of drug delivery into the retina. He also names the three most promising long-term developments in ophthalmic research.
• The breadth of innovation happening in Orange County and UC Irvine’s influence in furthering that innovation. The university’s Gavin Herbert Eye Institute spun off several companies, including Glaukos, which developed the first micro-invasive glaucoma surgery (MIGS) device, iStent. UC Irvine is also behind stem cell companies and many others.

Click “play” to listen.

TRANSCRIPT:


Firas Rahhal:
Welcome back, everyone to the OIS Retina Podcast. Thanks for joining. This is again Firas Rahhal a member of Retina Vitreous Associates in Los Angeles, as well as a member of ExSight Venture centered in New York. And I’m super delighted today because I have as a guest, a very close personal friend of mine and somebody I’ve known for many, many years and after homology, one of the longest standing people I’ve known in the retinas space, my great friend, Dr. Barry Kupperman. Barry, as most of you know, is an incredibly successful researcher, clinician scientist and is a million other thing is now the Chairman of the Department at UC Irvine. Barry, welcome to the broadcast. And thank you for accepting our invitation.


Barry Kupperman:
Thank you, Firas. It’s a pleasure to be here. And again, I echo that we’ve known each other forever. And it’s been a pleasure to be your friend.

Firas Rahhal: Thank you. So let’s start with a little bit on your background. That’s always how I like to start. I know your background reasonably well. But honestly, I don’t know what as well, as I’m sure I could have. After all these many times we’ve been together. I know you’ve been on the faculty at UCI for a long time will you tell us how many years you’re the professor and Chairman now and you’ve been a chairman for at least a few years now. Although I always felt like you were the chairman before. No disrespect to those who were the chairman at that time, George barbell.


Barry Kupperman:
MacDonald or nothing.

Firas Rahhal: Very good. You were originally trained. I know you’re a former USC resident here, Doheny. And we can get into that though he was USC. And now sadly, for some there, they’ve departed in that split has occurred. But I also know that you did two fellowships, one with Bert Glaser in Baltimore, and one with our mutual friend and mentor, Bill Freeman, where I also trained at some years later to tell me about the two fellowships why two and what did you kind of extract from either of those two very brilliant, very efficient gods?

Barry Kupperman: I can, thank you so much Firas. It’s always a little embarrassing to talk about yourself. So with all those caveats, or that caveat, I’m happy to share. I kind of had a very, I’m happy, you know, I just was never very process. I was more process oriented and product oriented. And at the time that I went to the fellowship, I was a resident. Doheny as you point out, though, he USC under Steve Ryan and Ron Smith for the chief there for many years. And I was actually he was Bert Glaser, you said but also equally important was with Ron Michaels, I was actually Ron Michaels last fellow the great Ron Michaels ran a surgeon park so on to die the year I was there, sadly, Ray short, and I were the two fellows that year, and he died that year of amyloid cardiomyopathy. So it was really a combination of Ron and Burke who had been at Hopkins forever and then had left to go into private practice, I was actually admitted to the Hopkins fellowship, and then they left but that was a weird time because most of the fellowships at that time had converted to two-year Retina fellowships. And this was one of the last remaining one-year retina fellowships, but I saw an opportunity when they recruited me to do that. And then I also arranged at the same time to do a second year with Bill Freeman because at the time one of my great interests because sort of from a variety of reasons, kind of because it meant something to me from the socio politics of it from the meaning of it was that was still the big battled AIDS era and I was very I became when I started my residency, Doheny the first rotation I had my chance to be with Narsing Rao, which was the Uveitis/ Pathology rotation. And my first rotation in the part of that rotation was to see people with AIDS and this in the AIDS in the CMV retinitis clinic. I was like, epiphany for me as I didn’t realize why I went into medicine exactly, but there was I discovered it. My families from Brazil, I grew up speaking fluent Portuguese and learn Spanish living in California for most of my life. And you know, in LA County, a lot of Hispanic speaking Spanish speaking patients that I could speak for the with them to relate to them. That was a different cultural context socio economically. And then suddenly there was this one-half day a week where it was like, people leave with the exact same interests, you know, art, music literature, so they were gay, and I wasn’t we were the same age, and they were going blind and dying. And so that was a very powerful experience. So that was in the back of my mind throughout my residency. So when I then saw this opportunity to do this incredibly illustrious fellowship that I began at the time I accepted, I thought I was going to Hopkins, I piggybacked with that, you know, Bill Freeman at UC San Diego was one of the great retina CMV retinitis researchers in the world at the time, this is all early, early 90s. So this is before about, you know how Active antiretroviral therapy and the cocktail. This was still a real problem. This was a period of time, interestingly, that they’re predicting, that’s the number one cause of retinal detachments in America was going to be CMV retinitis related retinal detachments and people with AIDS. It was a, it was an era that was taking, you know, it was a huge era. So I went, I thought, you know, cleverly in my mind, I could do this fellowship at Hopkins, which turned out to be in private practice at St. Joseph’s Hospital because they love that Bill agreed very kindly to for me to come in and just do a one-year fellowship with him. As a second-year fellows, essentially at UC San Diego, and it was a very productive year, I wrote a ton of papers with them in fact, when I took the job at UC Irvine, right after that, I still went down once a week to visit with Bill for the first year or two. And we ended up writing, I don’t know, 15-20 papers together, just so many projects came out of that. So that was sort of the rationale why created this is one you get the more traditional training East Coast, Hopkins, etc. and then do the other passion I had, which was learning more about taking care of people with CMV retinitis.

Firas Rahhal: I hear you 100% on your comments regarding UCSD and the CMV retinitis era, I was a fellow there 94 and 95. And it was called an I can’t remember what it stands for. AORU, which I think was AIDS Ocular Research Unit, which we’ll set that up. We, when I was there the two half days a week and I honestly had your point about cultural equivalency is well taken, I literally had doctors flying from around the country to come get into habitual sight off of your objections with me in that unit, who would come every six weeks, because they couldn’t get it locally. You know, they didn’t want systemic therapy. Nice, very short. It was an incredible time in American medicine. And we sort of grew up in that. And I’ve almost forgotten to know how well we’ve done as a medical community with anti-retroviral therapy, it’s incredibly short.

Barry Kupperman: Well, just to take it a bit further as well, that was we were really in the trenches that I would, you know, again, a lot of guests, we gave it off of their injections. But mostly we’re giving guests cycling and fostering those were weekly injections for a period of time, where there weren’t really many individual injections, we were these people would come in every week for injections. And if they didn’t come in, I knew they were either hospitalized, too sick to come in or dead. So I was I would make house calls, I would bring my little kit of injection and go to their homes and give them injection, I have privileges at every hospital in Orange County, to be able to give them their bedside injections of again, ganciclovir, typically, or foscarnet. It was really it was I mean, everything that’s come since then, I mean, what we do now is so meaningful. I’m not gonna minimize all the incredible things we’re able to do with anti-VEGF therapy. But it was different. It was not the same. We were fighting with life and death back then. And again, for those of us of that generation, it was people that again, were it was young men of exactly our same age that again had because of their sexual orientation, they were going blind and dying. It was just it was a remarkable time. And it kind of ended around 2000 went along came behind the active antiretroviral therapy and they suddenly started living and I still have a lot of those people from way back when are still my patients. They’re still I mean, one of my contract and for God’s sakes, I mean, it’s like, they had all gotten that there’s this weird thing I forget what it’s called viatical and weird insurance, they sold it because they had a death sentence, they had a diagnosis that they’re going to die they would sell their life insurance to a company that bought it so they all have money they’re driving Mercedes and Jaguars acceptance suddenly they’re gonna live forever. So those insurance companies lost a ton of money because they give them all this money and then eventually have to go back to work and find jobs because they’re still alive after that transition in 2000.

Firas Rahhal: In good winds are the good guys then.

Barry Kupperman: That’s exactly right. Absolutely.

Firas Rahhal: Barry, and I knew this. You also have a PhD in neuroscience from CalTech, maybe others don’t know this. Tell us about that. Your dad was involved at CalTech professors. It looks, did you originally go intending to be a neurologist, neuroscientist? What was the story with that?

Barry Kupperman: I was always just sort of followed my intellectual passions. I went to Berkeley and discovered biophysics non-equilibrium thermodynamics, the physics of biology, essentially, you know, no entropy would tell us we should be running down, and life runs a sock hill so that became my first intellectual passion. Then I took a I always also took a bunch of time off to travel I sort of three I went to Berkeley for two years, traveled for a year came back and graduated a year later travel for a couple of years. And while I was traveling, I just I was thinking about what interested me and I began to think about learning and learning at a synaptic level. How do we rewire our brains to learn so I began to explore neuroscience programs and applied to grad school from like a little hotel room in Bolivia with no typewriter in those days there’s not certainly no computers have been invented it was typewriters? But I can telegraph my applications to, you know, Harvard Rockefeller, Stanford, Caltech, etc. And with an interest in neuroscience and then end up going to CalTech. Because in that period of time, I spent about a year in Brazil, my family again immigrated from Brazil, I lived there as a child. And I really learned the glories of sort of having adventures but still staying close to home too. And my father was a professor at CalTech for many years professor of chemical physics, he did quantum mechanics of chemical reactions was his thing. So I decided to take the I was offered a position at several grad schools, but I took them on at CalTech because I was in the building then next door, my dad and we’d have lunch together at the Athenaeum know, several times a week, it was a lot of fun, I didn’t live at home, I will have my own place, but it was nice to be there. But then when I got to CalTech hand started doing research, again, looking for synaptic plasticity is the interesting part yet was learning. But it turned out that the part of the brain that we understood the best was the primary visual cortex. And that was the work of Hublin Weasel from off Thorsten visa and David Huber, from Harvard who got the Nobel Prize for that. And so I’m setting under a trainee of theirs who is now the distinguished professor at CalTech and was studying those ocular dominance columns. So I went from, again, it’s an early interest in non-equilibrium thermodynamics to synaptic rewiring to vision because that was the model system that I was using. And as I was enjoying life at CalTech, I was also conscious that it was I was pretty I wanted to see make it be more applied. As much as I enjoyed the basic science research. I thought to myself, this has clinical implications, it would be fun to follow that through. And so then I applied to med schools, and it turned out a month at that time, it’s not even close. But at that time, there was a for 30 years or so there was a program at University of Miami that if you had a PhD, you could get an MD in two years. It was a super accelerated. You started in June, not in September, you went for nine months, six days a week of the basic sciences in February or March one, you had a mock sitting of the boards part one and then you had a one-year core, junior year core clerkships March one to March one, then you had senior surgery, senior medicine, cardiology and a two-week elective and of course, Miami is a perfectly good med school. It’s not great, but it’s very solid, but what it does have its most famous and best department turned out to be serendipitously of course, basketball Marines to do the best department of ophthalmology in the country. Of course, I have a PhD in vision research. So I did a rotation there and it just everything click, and I sort of came back home to Pasadena. I was accepted into USC Doheny, and once again, I lived in Pasadena while I was going to internship and residency there.

Firas Rahhal: So around the dinner table at the Kupperman household, you know physical chemistry, quantum mechanics, statistical thermodynamics, the rest of us were asking Dad, how to calculate an earned run average that’s pretty high.

Barry Kupperman: Interestingly, my parents my mom once accused me of lying when I told that I used to play baseball and literally they were Brazilian immigrants. They had no idea we just want were put on this funny outfit and write down ride my bicycles in those days. There was no parents giving us rides or carpool and that you were on your own. You walked to school; you rode your bike. I had a job in the morning as a curbside laundry pickup for Okay cleaners. I would ride down to about two miles away to go play literally they didn’t know anything. They were you know; they were intellectual immigrants and didn’t pay attention that but it is interesting. They did something right because I have three siblings. I’m the oldest of four. The youngest has Down syndrome Sharon, and so we’ll put her in a different category, but my other two siblings, the three of us, my brother is chair of Emergency Medicine at UC Davis. It has been for 15 years. My sister is a professor in department of ob-gyn does a PhD. I’m head of research there at UCSF for a zillion years and I’ve been at UCI for a million years. So we all went into academics following our parents lead, my mom was a high school chemistry teacher at a private school for girls in Pasadena called Western School for Girls. And my father was at CalTech, and the department can be met and as undergraduates at the University of San Paulo in the chemistry department so they both were chemists. My mom became again a high school teacher. My dad became a world-famous scientist at CalTech.

Firas Rahhal: That’s amazing, amazing underachievers. Clearly Westridge is a great school Tom choose two brilliant daughters both graduated from there and are doing great things.

Barry Kupperman: A class on that science building that in honor of my mother because she was the director of the science department there for like 25 years.

Firas Rahhal: Amazing. Amazing. Let’s talk a little bit about now you know your current work or say what you’ve been up to at UC Irvine I know it’s a long time I don’t mean it nutshell the whole thing but Look, we all know you’ve got great clinical skills. You’re a teacher, you teach fellows, residents, you’re a clinical scientist, you’re a benchtop scientist, which is often not the case that one does both of those scientific endeavors you do, you consult for companies, you’re on boards. You’re doing a lot, man. And it’s really impressive. What do you like the most? And again, as I joked earlier with you in writing, I’m not asking you to pick your favorite son or daughter, but what challenges you in these areas? What do you like, what do you dislike, if anything among all these different hats?

Barry Kupperman: Well, you summed it up well. I really feel very fortunate. I actually graduated and took this job at UC Irvine. When I finished my fellowship in 1992. For God’s sakes, I can’t believe that it’s been now 29 years it went by in a blur and it’s basically my only real job because you know, before that was, you know, little jobs or training programs. So I’ve been lucky enough to have this one job forever. And I just loved it there. It’s been a great environment. I’ve raised you know, a family there. It’s been lived in Laguna Beach for a million years now. We live in Newport Beach. It’s just a dream. wonderful place. UC Irvine was great for me, because I’m very entrepreneurial, and they never really got in my way. I never asked for anything from them. But they also never got in my way, that’s been sort of my secret of success there. I was always kind of a good problem solver, but at the end of the day, but even with my MD, PhD, and all the hats we all wear, it’s still my favorite thing is to be a doctor, I love being with a patient and explaining what they’ve got. I love the surgery. I mean, I love the teaching, the teaching, I have I’ve had the fortune also I was a residency director for 10 years. Then we develop fellowship programs. I’ve got both an American fellowship program and an international fellowship program. So for example, right now my international fellows are from Egypt, Venezuela and Romania. It’s a Brazilian I think maybe arriving Monday, there’s also one from Iran coming soon, one from Armenia coming soon. So it’s just been that’s been a lot of fun as well. So it’s hard. And then of course, all the serendipitous things again, I mentioned that interests that I founded as a resident in taking care of people with AIDS, that was actually a huge thing that happened with industry when I arrived at UC Irvine, by another serendipity not realizing just following your passion and not worrying about where it was going to lead. There was a it was the Gan cipher implant trial and by Kyron vision and my Chairman at the time he was on the board of chi Ron and they closed it to the study hadn’t started yet but they’ve been picked all the sights but i’d arrived they open up the door to let me in to have a site and then close the door again, I ended up being the leader of that program, first interaction with industry and was the one of the only investigator on that New England journal article that of the data presented the data to the FDA, just straight out of fellowship within a few years I was at a time where there really wasn’t that much with industry but one thing that there was in the pharmaceutical industry was aids and CMV retinitis and so I became involved with industry at a very early age so just a lot of things happen serendipitously and all those fun I have to say it’s just been I feel very lucky it’s been again as you say it’s hard to choose which childhood like the best but I find the big one at the end of the day is still being a doctor and sitting with a patient and taking care of them nothing is more meaningful to me than that.

Firas Rahhal: Yeah that says a lot I’m not surprised to hear you say that I feel similarly that with all the different hats we wear in modern medicine, especially one is academic minded and busy doing teaching and these other things, nothing like reattaching retina live and then seeing the patient a month later having it work and having the game the site but that’s still the preeminent thing we do absolutely. What hear you say you started on something I want to touch on it’s very timely because it’s what I wanted to get into with you a little bit on the science side, which is you know, drug and product development innovation and you specifically mentioned the area that I when I think of very Cooperman and science and development, immediately I think about drug delivery, ocular pharmacology, I know you’ve done other things, but you’ve clearly built a name for yourself have a niche in that area. Maybe it started with the Kyron product you were just talking about. Tell us about the back drug delivery. Was it just serendipity? Was it something you wanted to do? How do you decide to solve a particular problems you go to the clinic, see the problem, then go back to the lab, give us a little structure on how the drug development thing came about and your current views of drug delivery into the retina which we of course talk about a lot today.

Barry Kupperman: Right? Well, it’s a great question. A lot of things sort of combined. Again, as I mentioned before, part of what motivated me to come to UC Irvine was its geographic proximity. It was close but not too close to home. My parents I didn’t mention how to beach house them of doing it. So my kids growing up and see their grandparents on my side every weekend. My wife is actually again another interesting site an aside, again, I’m Jewish from Brazil so we’re presuming you’re Jewish and my wife is Thai Buddhist. So our kids are this nice mix of Thai and Brazilian and Jewish and American and, and Buddhist. So her and her family is up in LA. So it’s a nice option if we’re able to see a lot of families throughout that period of time. But during all that period of time have been easier have on another reason to be there was I was I become this fascinated by taking care of people with AIDS and see if you’re right, noticed, and there was really no big player in Orange County doing that. So that was one of the motivating factors as well, professionally while I went there, I was conscious at that time that we were doing injections every week. And these four people it was at that I mean, as bad as the monthly injections are, the weekly ones were even more, you know, daunting. I mean, there was one that I’ll just shoot one little vignette, I still remember it now there’s one guy who must have had very sensor by memory, injecting him some ganciclovir and leaks from a couple of other sites that he’d been injected from the weekend before. And the week before that, it was like though, that watering cam for the garden, it was like, Oh my goodness, poor guy. So again, it was so then suddenly, when I got involved with the drug delivery was like, Oh, this is a solution. It was like another epiphany; this light bulb went off there. And that’s when I became very, very interested in in drug delivery, again, because of the Kylan vision, or gansai cover implant. And that’s when I then we had a very good department of engineering at UC Irvine, fairly new Department of Biomedical Engineering. So I reached out to some of the people there and we set up a drug delivery unit, we have patents in that space. So it became because of the interaction with industry is really kind of this mice, not just serendipity, but collaboration certain sense. It was an interaction with industry that inspired me to do some research, it was very rewarding that way. And so we set up this drug delivery team and to date I still haven’t drawn upon biomedical engineering. Because of all those efforts we did together. We had grad students, we got patents, we had a team of people involved in that it’s kind of petered out. But now and my interest is in me has changed a bit away to more cell culture work and other things in the laboratory that I share with Chris Kenny, researcher, that’s another story. But it was really this drug delivery was inspired by the Kylan vision Gan cipher implant that led me to want to develop my own drug delivery systems.

Firas Rahhal: That’s fascinating. This, let’s say, bridging between ophthalmology and engineering and I’m sure other medical specialties and engineering. This has become somewhat commonplace now and I know you have this connection with engineering department, Mark Humayun has a similar kind of bridge. He has a clean room. In the early days when you were first making those interactions was that common then? Was this something that was thought about and planned was it just sort of a organic evolution of the natural instincts of both departments.

Barry Kupperman: It was, it existed but it was still in its in its very early period. There were some things going on. But there wasn’t as much going on. But it didn’t take long. I mean, our department at UC Irvine So first of all, let’s also want to give kudos again behind you can see our lovely Gavin Herbert Eye Institute and Gavin Herbert to those that may not know it was that he and his father Gavin Herbert, senior and junior, he’s now senior, but he was Junior then founded our Gannett, a little while compounding pharmacy in a storefront in downtown LA that led to the Allergan Empire which of course ended up being sold and now it’s part of Allergan, but um, but again, there was there were things going on for all this period of time, there were interactions with industry, but it was on a much more modest basis. But again, what I want to highlight in our Eye Institute is your mind, we’ve been very entrepreneurial. And in fact, a series of companies have been spun off of technology developed at shriven amongst them, and again, somewhere at that period of time as well. So Rich Hill, a glaucoma specialist for many years and then went into private practice and then actually came back and retired with us a couple years ago, but he founded the Glaucos Eyestand so that little mix device was founded not in this building that still didn’t exist then but on that campus, and we still get patent royalty income from that eye stand to get a company was founded surrounding that and other technologies. We have stem cell companies we have Ron Kurtz, who’s been an incredible serial entrepreneur was in our department for many years. He founded IntraLase and Lens x and now is the CEO of I’m blanking on the name, but he’s been called Calhoun vision. Dan Schwartz, his company with that adjustable iOLs has a new name. Do you know I forgotten the name?

Firas Rahhal: I’m sorry. Yes, I can’t remember the name, but it is.

Barry Kupperman: That was that so he’s still getting Had a little straw, a long history of entrepreneurialism. And again, just this homage to Gavin Herbert, he was the why, why Orange County becoming Orange County is one of the world’s top five or six biotech borders. But it’s number one in a ophthalmic tech. And that’s because Gavin went and moved out again, some of the get 60 years or so go to Orange County. And he was this very inspirational leader continues to be at that age, you know, quite elderly, still an amazing guy still full of ideas. And I meet with him regularly. But he encouraged his executives that had great ideas that he didn’t think fit within the Allergan portfolio to just get off their own companies. And so there’s this whole ecosystem in Orange County of a ophthalmic tech companies, all with Moulton, many of them were founded by Allergan executives, employees. And there was another factor Bill Link was this incredible venture capitalist who’s actually behind Kairouan vision and others, his money and his investments. Let me block us off Glaukos was you know, a lot of it was his investments and several other companies have done that as well. So between Bill Link and, and Gavin Herbert, these were these two towers of inspiration, and entrepreneurialism in Orange County that led to this incredible ophthalmic tech. So UC Irvine recognize that so there’s again, we spun off a bunch of companies, things were happening, but it was very incipient was very in its earliest stages back 30 years ago, and now it’s just blooming like that.

Firas Rahhal: It’s a perfect segue. It’s one of the main reasons your perfect guest for this show. And you’re a heck of a nice guy, and I’d love to talk to you, thank you this kind of interfacing of industry, academia, private sector, private practice, venture capital, this is happening now all the time, the whole OIS meeting and structure is built on this concept. You’ve watched the whole evolution of this because I think as I was coming up, this was a pretty novel thing in the early days of Rogan Product Development. We currently have this system where companies are spun out of university labs is a common paradigm labs like yours, lab, like Mark Humayun’s, many, many others, as you just described, and then become private enterprises with venture backing and ultimately, maybe strategic partnership. This is kind of the progress. Is this the best way to do it? I mean, clearly it works. It’s working for us now. Are there tweaks? Are there other paradigms that you’ve seen or thought of that would be better? Or is this the best way? Is this the final common pathway to product and drug development in medicine or the eyelids?

Barry Kupperman: I think there’s, I think there’s a lot of ways to get there. I think we need to have all of them. I think a lot of stuff comes from university. A lot of that are scientists that are in companies that leave the companies to bad ideas and want to find their own and develop it. And you know, Allergan when it was purchased by activists and still remained Allergan, they kind of abandoned all the internal development to a large extent and went to the sort of open science concept, which I think is quite valid in many ways, because don’t fall too much in love with your own ideas. See what’s the kind of a little bit more cold blooded interact with tech companies, small companies, universities and pick and choose what you think is best. Now with AbbVie having purchased Allergan, I think they I think they have that hybrid model, which I think is probably the strongest they have internal development of products. But also, they’re always their eyes are always open for opportunities to interact with small companies and like they just announced with rejects bio, you saw that licensing agreement they just had announced they have an interest in, we have a clap. We have an interaction with them. We have they fund some of our working they have rights of first refusal for some of our research so they interact with our labs, we have amazing research going on now we’ve ended up I really focused since becoming chair almost five years ago on our basic science and we’re now something like 12th in the country and NIH funding most recently so again second UC system second only to UCSF a smidge ahead of UCLA even and ahead of UC San Diego Davis and our research funding because we’ve been able to bring on a very strong group of researchers including for example Chris Walchesky who does amazing he’s member of National Academy of Medicine and does amazing rental pharmacology we’re that we also have this amazing scientist for sure Ben Muhammad who is another great story he’s French Moroccan moved to France to Morocco when he was a young child who grew up there got a PhD at the pastor Institute has been in our department for 20 years and now he’s got patents he was setting herpes virology herpes infection of the eye and is now developed a pan Coronavirus vaccine and we’ve set up a small startup company called check immune surrounding his you know Pan Coronavirus, meaning and effects. It doesn’t look at those modifiable spike epitopes it’s the more conserved epitopes so it’s a good against direct every type of Coronavirus Which includes many of the strange and common cold are coronaviruses. So that’s come out of our lab, so it’s really been quite an energetic person. But again the companies that interplay between big pharma, small pharma, startup pharma and the universities it’s created this incredibly rich and nuanced and textured ecosystem of ideas and products. I think it’s amazing I think it’s all ideal.


Firas Rahhal:
I totally think it’s amazing in it UCI you guys are doing an unbelievable job and I’m pretty impressed with the entire UC system the number of campuses spitting out amazing products and amazing new biomedical technologies incredible and I’m glad to live in this state and be part of some of those institutions. Do you think I’ll put on my cynical hat for just a second, I want your take on this or do you think because the system is working as well as it is and because these bridges have been formed quite successfully over the last three decades as you just outlined? Is there times now where we have to worry about the tail wagging the dog and people sort of creating products and then finding a need for an idea rather than the other way around? And do we have to worry at all about some of the biases inherent in all of us being part of the system at a high level and how do we ward that off that what your thoughts?


Barry Kupperman:
I understand your statement I don’t really have that cynicism because I believe in the marketplace. I think the marketplace sorts these things out if it’s a crappy product it’s not going to be used very much it might be used and soaked artificially for a while but eventually interest will wait it and also it will be it’ll, but it also does by getting a kind of mediocre market in and unmet need for example to us that inspires others to say ah that’s pretty low hanging fruit I just have to be a little bit better than that. But the product over better and I could have a product, for example not to call it mediocre but the date you know the capam faculty edition and the thing that came out with a palace in Derby notes will they get approval or not one trial showed such a significance with a high degree of significance but still only 21% reduction of geographic after growth over a year. The other one was just borderline non-significant .05 to 6 or something like that. But only like 12% admission. Even if it gets approved that’s a month injection for the eyes it with ga Are we going to want to do it or not. But it does inspire others that will see also of course what Ivar Maya will do with their compliment fine inhibitor. But will there be other things will be inspired to see that there’s the opportunity they’ve paved the road now let’s see, it is first to market. But if it’s not a great product, it becomes. Again, I’ll use the other example Maccujen at first to market. Where is it now? Right? And then of course, be careful again, we thought Rosemount was going to be great. And that was amazing. Until it wasn’t because of safety concerns. And that we’ll see what happens the first time that when it comes up.

Firas Rahhal:That’s a great point. I’m glad to hear you say that actually because I do often wear a cynical hat. But I am also a believer in the marketplace. And you know, Europe does it even more. So that way, it’s easier to get products across the finish line in there. And they often let the commercial market really dictate. And you’ve got a lot of products that come out of there that then often want to come and become licensed here that never even hardly got used in their own region because the market spoke.

Barry Kupperman: I would disagree a little bit with that you’re right, the hurdle to approval in Europe is lower. But then because of all the health care agencies and the way that they are very financially restricted, they get approved, but they end up not being available to people because insurance, our national health insurance won’t pay for it. So I have a different controlling mechanism. Here. It’s harder to get approved because once it is approved, then the insurance companies’ kind of have to pay for it. They have no choice. So it’s a different set that they’re different. So we again so it’s that’s why here we can really have the marketplace sort out there. They’re in a certain sense, it’s the insurance that sorted out, though again, that’s happening more here with effect therapy and all that other stuff that does restrict the use of some therapies.


Firas Rahhal:
That is coming more and more and we’re going to find out in the next decade how much of this step therapy will become trenched. In terms of the science and ophthalmology Retina, we know what some of the obvious areas are that we’re pursuing. You mentioned them dry AMD obviously is a massive unmet need. What are the things, what are you thinking about when you’re thinking about the next frontier after the Great anti-VEGF? You know, we’ve had in the last 15 years, what’s next? Is it the dry AMD, Are there other things? Is it well, gene therapy?


Barry Kupperman:
Well, I would say it’s dry AMD, up to a point I would actually broaden that to say neuro protection. I think that we neuro protection products that can be used in a variety of ways, including in dry AMD. I mean a LeGros product was taken out of it looks like it’s a neuro protectant. Even the company that was spun out of our department j site, every class and his wife, Jean gang, have these human, these human retell on sort of these retinal progenitor cells that are basically injected into the vitreous, and they’re just releasing trophic factors there that right now we’re looking at retinitis pigmentosa only. But those can easily theoretically be applied to disease, other diseases, including dry AMD, because essentially, that’s a neuro protection play. So I think that’s the next phase that will be on. And then probably it’s the gene therapy one, and we’ll have to see how that plays out. And then after that, I think will be the harder challenge. But what we’re getting there, and Mark mine and others are doing a lot of great work on that mess, really taking the stem cells not just to use them as trophic factors, but actually regrow the retina. I think that is the sequence that we’re going to see neurotrophic advances, gene therapy and acid advances and finally, re growing a retina that’s I think we’re going to get there. But that’s probably in the, you know, 10 to 20 year a way range.

Firas Rahhal: That’s an amazing roadmap. And I liked it, I think that makes a lot of sense. And those, those steps all do seem realistic, but long term, I agree. Certainly the full-on replacement of the retina. But I tell patients, there’s realistic reasons to start believing that.

Barry Kupperman: It would be past therapy of the macula, we try to not go to grow a whole retina, but we try to get something lay down into a damaged phobia, macula that would you know, would you know be able to get wired and functional. You know, again, Mark, Humayun is the other way with the silicone foam artificial silicone right now. But again, now the biological solutions in there. And he’s certainly doing work on that as well with he’s got some certain grants in that space, as do others, other have other projects with that. So I think we’re going to get there. A lot of very, very clever people are working on this, but it’s hard.


Firas Rahhal:
I mean, that trial, we treated the patient some time ago, and we’re in a holding pattern now. But in just those 15 cases, the surgery evolved a ton. In those 15 cases. It really was the first of its kind and its phenomenally fascinating science and surgery. Yeah, we’ll see. We’ll see what happens. What about you personally, I only have a few minutes left. You just told us the frontiers, you know, what about you? You’ve had a great run. It’s not ending anytime soon. What do you see for yourself? What do you want to do? in these next five to 10 years? You’re a chairman, you’re doing science, you’re doing clinics? What do you favor coming up?

Barry Kupperman: Well, it’s an interesting point because it’s interesting being in sharing a lot of people aspire to being share, I didn’t really, I kind of saved that towards the end towards the end. So I’ve been here for five years. You know, normally when there’s a five-year appointment for many chairs, certainly the University of California system and they like to renew you, If possible, because it’s expensive. And you don’t want to do it’s destabilizing if too many chairs cycling through. So it’s like and I agreed to do it. I realize even though it’s a five-year appointment, that would be likely that I’d be reappointed what I’d be willing to do for 10 years. And so I will probably do that for another five years. But I look forward to another phase of I mean, I’m giving back to my department, I didn’t rush towards being a chair, but I’m taking on with all my heart and passion. I really have. You know, it’s basically I spend most afternoons in meetings. I have certainly I have when I was a faculty member, I didn’t feel like I had a boss. I never felt like you know, my chair was my boss. Now I feel like everybody’s my boss, the dean is really my boss, but every faculty member if I’m not making their lives better than I’m not doing a good job. So I feel like every faculty member is my boss too. So again, it’s a great I mean, I’m very happy to do it. But it’s I lay awake at night worrying a lot, too. So I look forward to a phase after being chair as well. And sort of finishing, you know, that would probably be the last phase where I kind of conclude some projects and I also want to mention one more thing that’s been one of the great things in my life in academia is finding a great basic science partner. So I was I had this phase where I was doing all this work with engineering and drug delivery and pharma. But in a certain point, I began to say, I feel like I’m doing stuff for other people. I’m helping making farmer products better. What about my own stuff and even though I did have the drug delivery piece, I began to focus on lab work and set up my own lab and I found that again, I was a busy clinician, busy surgeon, a teacher traveled a ton, so I actually found a great lab partner of Cristina Kenny, Cris Kenny. She’s awesome. And she was an MD PhD and ophthalmologists that always had a lab less off more research and less Clinical and then she eventually stopped doing clinical work and is only in the lab. And so we’ve had this, I don’t know 15-to-20-year partnership or she runs the lab, I bring the the our international fellows work at least 50% or more of their time in the lab. But we’ve had this incredible collaboration on these, you know, cell culture, retinal cells and culture and how do they respond to stimuli. So it’s really been a regrowth of our it really inspired me to stay in academics because honestly, I reached a point where I was going to join you, buddy, you know, I was always in conversation with David and Gary Thomas made recipes way back in the day, you guys were always my I had these two, I was so lucky, I had two great options. I had this great job in academics, but I knew but David made it clear if it didn’t work out, give him a call. And there was a period of time around seven years in that I did give him a call and I came that far away from leaving here and joining David. So again, that was always tough, because that’s still a fan today. I love being a doctor most.

Firas Rahhal: Well, it’s never too late, maybe I’ll send you another invite in the next month.

Barry Kupperman: You guys are always paid off. I have to say, and I’ll share this I’ve always there are certain groups, I’ve had a soft spot in my heart for the for the Royal Oak group, I have so many friends there. I love the retinas, surgeons at Cole Eye Center Cleveland Clinic, they’re sort of my one of my favorite academic groups. And then I love you guys, you know, between especially way back when it was a period of time, it was just David Boyer, Gary Thomas. And then along came Roger. And you know, and then you came along and Tom, it’s like nothing but love, you guys are awesome, I would have always happily joined you guys. That was always that was gonna be my other option. I felt like the luckiest guy alive.

Firas Rahhal: That means a lot. It really does. And the staying up late at night, thinking about how to make your department better. And help your faculty is exactly why you are a great Chairman, why you will continue to be a great Chairman, as much as that’s a labor of love for you. And staying up at night isn’t the best thing. That’s why they stay, and you’ll continue to do a great job. They’re lucky to have you. And really as my great friend, thank you for coming on the program I really enjoyed.

Barry Kupperman: Thank you, Firas. It’s been a pleasure. And again, somewhat embarrassing to talk to talk about myself, but maybe there’s some lessons for others too. Hopefully it’ll inspire others to basically follow your heart. Don’t worry about that straight line. I was super curvy. I spent about five years traveling around the world. I got a PhD along the way. But it all worked out. Yes, I was delayed somewhat compared to my peers, but it’s I still made my money, raise my family, have my life. It’s been great. But I’ve been able to smell the roses along the way. I encourage people to do that.

Firas Rahhal: You’re being very humble. For those who are listening. I know this man’s career very well. And he undersold it a lot. Here you are nothing but humble in this conversation. Thank you, thank you doing very, you’ve done a ton. And we appreciate it as professionals that you’re continuing to do so.

Barry Kupperman: Thanks Firas. Again it’s a pleasure and kudos to you and all you’ve done too. I really admire all your efforts, both in your clinic and all your paying attention to the industry in your investments. You’ve also been leading the charge on the on the physician scientist investment, that’s also a very important way to populate our space. So kudos to you as well.

Firas Rahhal: Thank you. Thank you

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Ehsan Sadri
ehsan sadri
Firas Rahhal
Firas Rahhal, MD
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