First in Human Episode #1 featuring Dr. Dhaval Desai

Episode 1 of First in Human features Dr. Dhaval Desai, SVP & Chief Development Officer at Iveric Bio. First In Human is a biotech podcast that interviews industry leaders and investors to learn about their journey to in-human clinical trials. Presented by Vial, a tech-enabled CRO. Episodes launch every other Tuesday.

Simon Burns: Congratulations on the GATHER2 topline results, to kick us off.

Dr. Dhaval Desai: Well, thanks. I mean, you know, it’s been a, what? Two years now that, this has been in the making and it’s super exciting whenever you do anything for the first time. And this is the first time our field’s ever seen that two positive primary endpoint met studies in geographic atrophy. And while it’s a super exciting time for us, it even more so for treating physicians and patients. So, I think there’s a lot to be excited about, so thanks for your kind words.

Simon Burns: Absolutely. I’m sure it’s been busy. Well, to kick us off let’s start with quick introductions. I’m Simon, co-founder and CEO of Vial. Vial is a next generation and technology-enabled CRO that has started and is on a mission to reimagine clinical trials and make them faster and more efficient for sponsors. And super thrilled to chat with you today Dhaval, of all things, clinical trials and and get your advice for fellow biotech companies who look at your results recently and go ” Whoa. How can I do something similar in my company?” do you mind introducing yourself super quickly?

Dr. Dhaval Desai: Yeah. Sure. I’m Dhaval Desai, I am the Senior Vice President and Chief Development Officer at Iveric Bio.

Simon Burns: So, to kick it off, say, you know, exactly that case we talked about, biotech company comes to you, says, you know, “Phenomenal job running, that trial. What should I know? What are the kind of pitfalls to avoid? How should I go about it?” Oftentimes, we hear this and people go, “I don’t know the first thing about protocol design or site selection or picking a CRO. There’s a whole ton of questions these companies are asking and, you’re, on the short list of experts here. What would you tell them?

Dr. Dhaval Desai: Well, first and foremost, hit your primary endpoint.

Simon Burns: [laughs]

Dr. Dhaval Desai: And, you know I’m, a little bit facetious when I say that, but it’s, it really goes back to answering a question that you know that you can get an answer to. And answering it and, asking it in a manner where the trial that you’ve designed is set up to give you that answer. So many times we see protocols designed in a manner that, there’s no way that for any given question that a sample size of this will be able to give you a definitive answer. So you’re doomed to fail before you even start. So making sure that all of your basic assumptions are around, what the main question is and will you be able to get to it through a conduct of a study, that’s gotta be locked up from jump street.

And a lot of companies make the mistake of not doing that and they wind up at the end of the study saying, “Well, you know, we were underpowered to show X, Y and Z results.” Or, “We asked the wrong question.” Or sometimes, they don’t even go to the regulatory authorities to ask, is this an approvable endpoint, which is really scary. But it’s just getting the blocking and tackling of a study right, right? So that’s first and foremost.

The second part is, are you asking the relevant questions? Right? We’ve seen specifically in our field a number of studies that have delivered what we consider, you know, positive primary endpoints, only to find out that, that’s great but there’s really no use for that in the clinical spectrum of how we treat patients. So are you asking relevant questions?

The third I would say and, probably the biggest one is make sure that you’re using qualified experts to help you and guide in your protocol design. Right? And I’ll, give you a, close to home example. In our studies with Zimura, one of the adverse events that we know happened with complement inhibitors is the development of CNV. Well, we used what we call as our visionary committee and these are the top experts in the field of retina to really guide us on how should we monitor for this, how should we really ensure that no patient is left you know, uncaught or slips through the net when they develop CNV, and they helped us design a comprehensive protocol, which we think is a best in the retina methodology in how to evaluate CNV.

 So three things, make sure you do all the blocking and tackling right, make sure you’re asking relevant questions and make sure you use the right experts when it comes to helping you design critical pieces of your protocol.

Simon Burns: I love that best in retina protocol designs. You, gotta trademark that now t-shirts or something. Okay. So we, talked about the pre-kick off of the trials. Say your, trial is operating you’re live in your sites and data’s coming in, how does your philosophy change when you then refocus on what works and fits for biotech companies there?

Dr. Dhaval Desai: Well, so, execution is always king, right? And, the first thing [00:05:00] that we always, any trial that I’ve ever run is always been around watch it like a hawk early, right? And, the main reason for that is that all of the mistakes, whether at a site level, at a sponsor level, they typically happen early and those, if you’re not watching it, those can perpetuate and wind up going for a very long time. If you’re watching it closely, you can put a cap in place, correct whatever mistakes are there and really have minimal impact on ultimate results, conduct, etc. So first is watch it early.

The second part is, and this is one that a lot of sponsors missed, pay attention to your study coordinators. They are the lifeblood of any study. Enrollment, conduct, and specifically retention. Where you spent a lot of time, money, effort in getting these patients in, you wanna keep them in. Missing data, dropout, all of that is not good for the ultimate outputs. Even if you’re positive, right? The FDA will ding you for something like that. The key to doing all of that, PIs are important, but any good PI will tell you that the, engine to this study is a study coordinator. So that’s the other thing.

The final piece of it would be do things in real time. Right? So don’t put off cleaning data, monitoring for PDs uh, all of the other stuff that seems mundane, do it in real time. Cause if you wain until the end, you could wind up with a big mess on your hands that you need to clean up. Also, doing it in real time shortens the time from when you have last patient, last visit to database lock and if you shorten that, you shorten the time to first interpretable results and eventually, submission, and everything else, that’s a domino thereafter.

So those are three actual trial conduct pieces of it. The other pieces around whether or not you’re using a CRO. And if you’re using one, to choose the right one. Right? Specifically in our field, we’ve seen examples of when picking the wrong one, cost a company a pivotal program. On the flip, using the right one has saved a trial when there were critical errors that were made during the conduct. And so, if you’re going to use a CRO like most small biotechs do, you gotta make sure you pick the right one.

Simon Burns: You guys are working with a lot of cutting edge modalities which make the trial quite different. I’m curious, any kind of specific nuances that you either kinda came up in running the trial or that you would advise some of these new AAV gene therapy trials that are coming up, what’s different and what’s unique? What did you learn running this trial in particular?

Dr. Dhaval Desai: Yeah. So, for gene therapies in particular, we haven’t actually kicked off any here at Iveric, but my Vice President of Clinical Development used to be the Chief Medical Officer at Advera, so we know a thing or two about gene therapy clinical trials.

And so, just around gene therapy, right? The challenge is, generally around three big buckets. First is the delivery, right? Most of these therapies are subretinal delivered, which you know, is a break from your traditional intravitreal drug delivery. It requires special surgical skill and while most retina specialist are trained in doing subretinal surgery it’s not something you do routinely, right? So there’s an extra training aspect to that.

The second piece is the dose that you deliver. Right? You don’t know like you do in a typical intravitreal drug delivery study what exact dose you’re doing ’cause it’s delivered in a manner that’s really non-traditional using vitrectomy machine.

And then, the third big challenge around those is managing the AEs and specifically, every gene therapy study we’ve seen today jut had some sort of intraocular inflammation issue. And getting to the right cocktail for the type of inflammation that you’re seeing, is an art. And it varies from study to study and it varies from compound to compound. So those are the three big ones that if you’re running gene therapy studies, you absolutely wanna have an eye to, because they all have a critical piece in whether or not a study succeeds or fits.

Simon Burns: One of the things we think a lot about is the, key challenges and pain points in, clinical trials and in particular, where technology could be applied to impact those and improve trial operations. Kick us off first with what are the challenges that still are quite stressful when you’re running a trial and two, where do you think there’s opportunity for technology to make an impact?

Dr. Dhaval Desai: So the biggest challenge that we always face that I would argue that probably any sponsor faces for a study is anything that requires us to be at a clinical site. And these include things like study nation, study initiation inspections, source data, monitoring, anything that requires a physical presence at a clinical site. And when we think about digital tools that could potentially in technology [00:10:00] that can solve for that, right? If you think about the fact that most of our clinics these days are busier than ever. We live in a world where HIPAA, especially here in the United States, when you know when you walk into any clinic, there is HIPAA issues potentially all over the place.

And then thirdly, it seems like there’s a new communicable disease around the corner every day now. You gotta figure out how to solve for this thing and we have now video-enabled iPads that we offer every site. If we can move to source data verification electronically, that would be a huge boon. And very frankly, I don’t understand why we haven’t gotten there yet. We have all the tools to never have to step foot into a clinical trial site. Yet very few solutions kinda offer that, right? The touchless trial if you would. And I think if we could solve for that, it would cure the biggest pain points and the things that actually take up the most amount of time when you’re thinking about study startup, study conduct, study closure. Those are the things that kind of, scheduling being on sites, scheduling, this would cause us the most pain. And if we can solve for that, I think that’ll be awesome. I think it saves us time, money, dollars, etc.

Simon Burns: Totally. Could not agree more. It’s crazy visiting a lot of these clinics in person, like we’ve had the chance to do. How that the clinical side of the business is running on electronic systems and it’s only on research that they’re still capturing everything on paper… 

Dr. Dhaval Desai: Yeah. Yeah, which is amazing because, again, right, we have the tools.

Simon Burns: Absolutely. Yeah. Let’s jump into a segment called overrated, underrated. I’m gonna give you a series of topics. You’re gonna tell me whether these topics are overrated or underrated. The first is the size of the opportunity in GA, overrated or underrated?

Dr. Dhaval Desai: So I think for sure it’s underrated. And I’ll preface that by saying, it’s not just because we’re working in the GA space now, but I’ve had the opportunity to launch a number of first-in-class therapeutics and what we always find out is that the opportunity is always less than what we thought. And the reason mainly because is that most of these patients have learned to live their life without any sort of hope. And once you offer that glimmer of hope, to be treated for what was a previous untreatable disease, they come out of the woodwork. And, the history of therapeutic development is wrought with those examples.

Think about Gleevec, right and, Novartis, you know, the thought would to be a small niche drug, was never ever even gonna get developed. But once it got developed, it was one of the most successful oncology drugs that was ever created. And it’s mainly because the patients came out and they sought out treatment. And I think we’re gonna see the same thing in geographic atrophy. If you don’t believe me, close your eyes and try walking around for a minute. And that will tell you everything that you need to know about how important site is.

Simon Burns: Seriously. Along the same lines, Iveric is also working in IRD. Same question, overrated, underrated, the opportunity in inherited retinal diseases?

Dr. Dhaval Desai: I think it’s gonna be underrated because I think there’s some of these IRDs that are really kind of attractive targets that we just haven’t quite figured out yet, either the, gene in question is too big, we haven’t got the vectors right, but at some point, science always catches up. We’re gonna get these vector issues figured out. And we’re gonna figure out how to take, for example, the gene for Stargardt’s and get it into one of these therapeutics.

And I think at that point, we’re really gonna see that field blossom, so I think it is underrated. We’re just waiting for science to catch up on just the basic blocking and tackling of delivering gene therapy.

Simon Burns: And speaking of science catching up, there’s some, very early stage work on CRISPR, and CRISPR’s impact on whether it’s AMD or some of these other retinal diseases. What do you think of CRISPR, overrated, underrated as a future next generation therapy modality?

Dr. Dhaval Desai: I think when it comes to science, it’s always hard to say overrated. Especially when the technology like CRISPR is in its infancy. The only caution I have with CRISPR is that it is a little bit scary to know that you’re gonna turn something off forever, right? And you know, we’ll see. Right? Like with anything, this first bit of it will be a little bit bumpy, and then, as science gets better, as we get smarter about what we did right and what we did wrong, I think you’ll see an evolution of that and then, it’ll turn to an opportunity that’s really robust. So I think it’s underrated for sure.

Simon Burns: And last question for you. The markets have been quite punishing XBI, private capital funding, markets, etc. Extending the scope of the conversation here from ClinOps to ClinDev, how do you advise earlier stage peers that are not yet dealing with things like topline positive results? How do you advise them on, thinking through capital allocation, clinical development strategy, and then, the tough climate room?

Dr. Dhaval Desai: It’s a great question. I think the first thing is, and everybody is guilty of this, don’t bite off more than you can chew. Right? I think [00:15:00] that is a critical piece of what biotechs tend to do wrong. And that is trying to be more than just one drug development company or two drugs or three, depending on your size. Do what you know you can do well and do it that way.

The second is that you always have to balance the clinic in Wall Street. There’s no doubt. It’s something that small biotechs struggle with. The key piece of advice is, don’t ever let that balance get it too far skewed in either direction. You can’t be such a purist that you ignore what Wall Street has to say, and you can’t cater to Wall Street that you ignore your science. So, keeping that balance intact is what’s critical for small biotechs.

And then, the third piece of that is really around executional excellence. One of the big things that small biotechs struggle with is time and money. If your science is good, you can always get more money. But it doesn’t matter how good your science, you’ll never get more time. Execute with flawless excellence, pick the right partners, and the rest will be there for you. So those are the three things when you’re talking about Wall Street and the clinic that I think every small biotech needs to kinda keep in mind.

Simon Burns: Well it’s been phenomenal chatting. Thank you so much for giving us advice today and congratulations again on the success. Excited to see the continuation of your programs go through the clinic. We’ll be watching closely.

Dr. Dhaval Desai: Thanks, Simon, and good luck to you. It’s it’s really exciting to see what you guys are doing over there at Vial.

Simon Burns: Thank you so much.

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