Andrew Brackin: Hi, I’m Andrew Brackin. The co-founder of Vial. Vial is a next generation CRO that uses best in class clinical operators and technology to deliver a faster execution of trials. Today I’m here with Dr. Leng. Dr. Leng, why don’t you go ahead and give us an introduction and where you’re located.
Dr. Theodore Leng: Thank you so much for having me on today . I’m Ted Leng. I am a faculty member at Stanford University in the Department of Ophthalmology at the Byers Eye Institute at Stanford. I’ve been practicing here for about 13 years. I also am the Director of Clinical Trials and Translational Research in this department.
Andrew Brackin: Wonderful. Thanks so much. I’m gonna dive into our first question, Dr. Leng. You’ve contributed significantly to the field of Ophthalmology with over 172 publications over your career. Can you tell us a little bit more about the most exciting project you’ve participated in?
Dr. Theodore Leng: Well, I mean, it’s hard to pick out one project over the career to really focus on, but I think if I had to pick one, I’m going to go for something that’s a little bit future-looking, and that would be stem cell research. So I’ve been involved in, stem cell research for, now for over 10 years. And while I am working on some translational work from bench to bedside in our own laboratory here, I’ve also been able to partner with some industry sponsors through those years.
And in the 2013-2014 timeframe, I was part of a Phase 1/2 clinical trial where we transplanted adult neural stem cells under the retina to treat geographic atrophy and age-related macular degeneration, and I thought that was a really exciting therapy. And I really do think that this type of regenerative medicine is the future for macular diseases.
Andrew Brackin: I completely agree. So what indications are you currently working in, in your clinical trials?
Dr. Theodore Leng: We have a wide range of things that we’re working here at Stanford. There are the very common things, neovascular AMD, advanced dry AMD, diabetic macular edema, retinal vein occlusion. A lot of uveitic diseases as well, ocular oncology. So we’re doing a lot of different things. And these are all just in the retinal space, which is my primary specialty. But my colleagues are also doing trials in ocular plastics, glaucoma, corneal diseases. And even pediatric ophthalmology and neuro-ophthalmology.
Andrew Brackin: Lots of exciting things going on there. As you’ll know with the discovery that we now have the alternative route of IP administration in the suprachoroidal space. This discovery has not only allowed us to study the benefit of this route, but the various techniques to most safely and effectively deliver it. Can you talk about the benefits of the suprachoroidal space?
Dr. Theodore Leng: I’m actually really excited about this approach. I think if you talk to the people that were involved in the early days, it’s a very exciting development story from a medical device standpoint. And being here in the heart of Silicon Valley and, very involved in innovation ecosystem here. It, was a very collaborative effort between the manufacturer, the laboratory, and the clinicians that were actually using those devices. And they did a lot of back and forth, and working closely with the engineers, and it was, it’s a really great kind of case study of how devices should be designed and made better. So I think that was one thing that was really exciting for me to hear from the people that were involved.
But I also think that it’s a great approach to getting investigational products, and ultimately approved products, into the eye. Because when you look at delivering new products and therapies there’s a science which is obviously very, important. But more importantly is the adoption of that technology once it’s out there. And, the device that was designed and the way that we get it into the eye is very close to what we’re doing right now with intravitreal therapy, which we do thousands and thousands of each year , as individual physicians.
So to use this device, to inject medications into the suprachoroidal space, it’s very familiar for us as physicians. And while there is one product currently on the market a anti-inflammatory steroid for uveitic macular edema that’s out there, as you were mentioning, there are a lot of other products in trials right now to treat every indication that I mentioned before, whether it be AMD or diabetes, or, or even cancer of the eye, actually. Once those products make it all the way through the regulatory process, and using this very familiar platform to get it into the suprachoroidal space, I think it’s [00:05:00] going to help with adoption and just, everyone using it for the benefit of our patients.
Andrew Brackin: So what indication are you most excited about with this type of administration?
Dr. Theodore Leng: [laughs] I think that remains to be seen, to be honest. I’m a pragmatist at heart. While I do participate in clinical trials because I want to move the science forward, ultimately those trials allow our, regulators to make sure the products are safe and effective. And once that’s, been, shown to a certain degree of reliability, then it comes into the market where we get to use it in a hands-on fashion with individual patients. And every patient is going to respond differently. A lot of our patients don’t look like patients in clinical trials. And so there’s an element of real world analysis that has to happen post-approval. While there are multiple indications out there, like very common indications, like neovascular AMD for example or diabetic macular edema, which are being treated with these suprachoroidal therapies. I think once it gets approved, I’m just going to use it and we’ll see how it works in my patients. I take that approach with many therapies that come out. I do ascribe to the earlier adopter label. And I like to use a lot of a new product when it first comes out just so I get first hand experience about, you know, the pros and cons of anything that comes out.
Andrew Brackin: Okay, great. We’re gonna switch gears a little bit here this past week, Vial posted an article about GCP – good clinical practice. In line with this focus, what are some ways that you would advise to a physician thinking about getting into clinical research in regard to GCP and how do you in you ensure good GCP for your practice and for the clinical trials that you participate in?
Dr. Theodore Leng: I think, is a really important topic. GCP is just the all-encompassing label or way we, name what we’re doing while we’re running clinical trials. And the two most important things are patient or subject safety as well as generating really high quality data for submission to regulatory agencies, where that’d be the FDA or other ex-US agencies.
And I think, you know, none of us who are investigators ever want to cause any sort of adverse outcome or harm to the patient. And, by ascribing to the GCP guidelines and getting trained in them, we ensure that both us, as a principal investigators, who are ultimately responsible for the conduct and operation of the trials under our protocols, as well as our staff understand all the procedures and protocols that need to be followed in order for our subjects who, not only potentially benefit from the therapies that we’re testing, but also be as safe as possible. So I think GCP guides us to keeping our subjects safe.
And then, on the, regulatory aspect, I think the data that gets sent in to FDA and other regulatory agencies has to be as clean and reliable and trustworthy as possible. So again, the GCP guidelines help us come up with the procedures and the protocols to ensure that the data is as clean and reliable as possible, so that when it is collated and aggregated and given to the regulators, they will have the best data in front of them to make decisions regarding the safety efficacy of the potential treatment.
The second part of your your question was, what do we do to make sure that GCP is followed in our sites. And, I think that’s one of the key responsibilities for any principal investigator, especially if you’re thinking of getting to trials or currently in trials, it’s always something I think that should be in the back of your mind. Because as I had mentioned earlier, the PI is ultimately responsible for how things are run. And we have to make sure that our staff is, well trained. And also believes in the same philosophies.
I think that’s where it all begins, is actually just coming to a common understanding of the goals and the values as we embark on any sort of project such as clinical research. If everyone’s aligned on the common goals and what we want for our subjects and our patients, then we can then overlay these kind of guidelines and policies and procedures to achieve those goals. And so, I think just having regular chats with your staff, and making sure that everyone is up to date on their training will allow us to comply with GCP and, ultimately help, you know our subjects and, their patients.
Andrew Brackin: That’s very important. I think the next question is also in line with GCP as well. As you know, many sites participate in a number of competing trials and although that’s not ideal, it’s often mitigated. How do you handle this issue at your site [00:10:00] and how do you choose which study is best suited for your potential subject?
Dr. Theodore Leng: I think there’s multiple ways of approaching the competing trials problem or concern. As you were mentioning, there’s multiple sponsors and companies that are exploring similar indications.
And they’ll often times want to approach the same site for these trials because they have been really great sites for them in the past or have a strong track record of success. And it, makes sense for them to do so. One way of approaching this is to have different PI’s be the investigators for different trials. So I might be the PI for sponsor one, and my colleague will be PI for sponsor two. And that will allow us to recruit from our own patient pools in certain trials. Therefore, you don’t have a real conflict of interest there. And alternatively, you could also have your referring physicians, your other partners in your group alternate referrals into each trial, assuming they have similar visit structures and administration routes and so forth. And that’s one way of getting around the kind of competing trials, is this, and then, another way of doing it is to just be very mindful of, balance. So if you have, like trial A, and you’ve already recruited seven patients to that trial, and trial B, which is the same medication, but it only has two. You might want to pause trial A and, try to backfill trial B until you level the two. And this is assuming that you have a a belief that the trials are, comparable going into this. And I don’t think that any of us who are PI’s would want to be involved in two trials where we believe that one trial or one product might be superior to the other product. And that, obviously would have introduced another source of bias in their recruitment process.
Andrew Brackin: Right? Exactly. I certainly appreciate your input and love talking to you about various clinical trials as we like to do in general. But I wanna dig into the challenges that you face at a site level. Where do you think we should focus our time and resources to improve research and how it’s conducted and delivered.
Dr. Theodore Leng: I think one of the pain points for any site is just getting a trial started. So, there’s a lot of back and forth that happens between the, site meeting the PI or the clinical research assistants, and the, CRO, the contract of research organization and the sponsor. And sometimes there’s a lot of, it’s almost like a game of telephone. This sponsor says something to the CRO, which then they forward to the PI. There might be a small change or request that’s needed, and that goes back up the chain through the CRO as a middle man.
And often times, we lose days or weeks or even months in that process. And that can be frustrating for both the PI and the sponsor to have to do that. So anything we can speed up, the communication process, even in just terms of operational time. But there could also be efficiencies that could be garnered using technology approaches as well, to help make everything more transparent and visible. And notifications and other things can also help make the communication a bit more fluid between the two parties.
Andrew Brackin: Right, and that ties directly into my next question. In knowing Vial’s vision for reimagining clinical trials with technology. What excites you most about partnering with Vial?
Dr. Theodore Leng: Well I think what’s most exciting to me is, I think Vial’s just taking a fresh new look at this this whole industry. And coming from a different perspective and, being able to look at areas where there could be improvement. For example, in this communication piece I brought up. And then of course, there’s probably a lot of operational efficiencies that can also be improved upon, in the execution trial. Whether that be from recruitment of course, [laughs] every sponsor wants to recruit more rapidly for all their trials. And so, anything we can do to shorten that recruitment process and enrollment process would be really appreciated by, all parties.
And then increasing communication along the follow-up visits with our participants. With monitoring visits there are a lot of different areas, I think, that could potentially have room for improvement. And I think a company like Vial coming in and taking a, fresh look at these different elements of trials and hopefully trying to improve upon those is really exciting to me.
Andrew Brackin: I really appreciate you being here today. Dr. Leng, thanks so much for answering all my questions and I appreciate all the feedback you’ve given us on our model in the ophthalmology space.
Dr. Theodore Leng: Thank you so much for having me. And I hope to talk to you again soon.
Andrew Brackin: We’ll see you next time.
