Clearside Biomedical, Inc. (NASDAQ:CLSD) Suprachoroidal Space Drug Delivery Call July 24, 2024 8:00 AM ET
Company Participants
Jenny Kobin - Investor Relations
George Lasezkay - President and Chief Executive Officer
Glenn Yiu - Scientific Advisory Board
Victor Chong - Chief Medical Officer
David Brown - Director of Research, Retina Consultants Houston
Conference Call Participants
Annabel Samimy - Stifel
Andreas Argyrides - Oppenheimer & Co.
Serge Belanger - Needham & Company
Yi Chen - H.C. Wainwright
Operator
Greetings, and welcome to the Clearside Biomedical KOL Webinar. As a reminder, this event is being recorded.
I would now like to introduce your host, Jenny Kobin, Clearside Investor Relations. Please go ahead.
Jenny Kobin
Good morning, everyone, and thank you for joining us today. Before we begin, I would like to remind you that during today's events, we will be making certain forward-looking statements that represent our views as of today. Various remarks that we make about the company, its future expectations, plans and prospects constitute forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors including those discussed in our SEC filings available on our website.
Today's agenda is provided on Slide 3. Dr. George Lasezkay, Clearside's President and CEO, will highlight the versatility of suprachoroidal delivery. Dr. Glenn Yiu, Professor of Ophthalmology at the University of California, Davis, will cover the real-world use of suprachoroidal delivery. Dr. Victor Chong, Clearside's Chief Medical Officer, will discuss pipeline opportunities; and Dr. David Brown, Director of Research with Retina Consultants Houston, will provide the large practice view of suprachoroidal delivery. After the formal presentations, we will conduct a question-and-answer session that will also include Clearside's CFO, Charlie Deignan.
With that, I'm now pleased to turn the program over to George.
George Lasezkay
Thanks, Jenny. Next slide. At Clearside, our singular focus is delivering on the potential of suprachoroidal drug administration. We are the proven leader in the suprachoroidal space. Our proprietary SCS Microinjector has been used in thousands of clinical injections to date. Our injection platform has been validated in several ways. We've developed the first and only product to receive FDA approval for suprachoroidal administration. We've established multiple strategic collaborations with companies that have technologies or expertise that we don't possess internally.
And thirdly, we've created a comprehensive intellectual property portfolio around the design, manufacture and use of the suprachoroidal microinjector platform with many different drug categories in various retinal disease states. Finally, internally, we've developed a suprachoroidal delivered tyrosine kinase inhibitor, axitinib, for wet AMD that's just completing Phase IIb trial in the United States. The data from this trial is expected late third quarter of this year.
Next slide. At Clearside, we not only have an SCS Microinjector platform, but we have extensive formulation experience with small molecules for suprachoroidal delivery. We have an ISO certified commercial scale manufacturing capability for our microinjector. We have extensive experience in drug device combination regulatory pathway, as evidenced by our track record of obtaining the first and only SCS administered product, XIPERE, the approval from the FDA. And finally, we received a permanent CPT code for SCS injections to aid physician reimbursement for the use of suprachoroidal products.
Next slide. This pipeline chart demonstrates the diversity and versatility of our injection platform as well as our internal corporate strategy that has two prongs. One, developing internal products on our own; and two, partnering strategically our suprachoroidal microinjector with third parties. As you note at the top, in light blue, CLS-AX, which is our Phase IIb wet AMD product is internally developed and is just finishing Phase IIb, more will be discussed by Dr. Chong about CLS-AX later in this presentation.
XIPERE, which was the first product approved for suprachoroidal administration is currently being commercialized in the U.S. by Bausch & Lomb and they are currently seeking Canadian approval for the product. That same product known as ARCATUS in the Asia Pacific region is being developed by our Asia Pacific partner, Arctic Vision, which recently completed its confirmatory Phase III trial in China, and Arctic Vision is seeking approval in the People's Republic of China as well as Australia at the present time.
Our SCS Microinjector collaborations, there is three important ones. First one was Aura using their viral like drug conjugate for the treatment of choroidal melanoma. They are exclusively using our SCS Microinjector in an ongoing global Phase III trial for the treatment of choroidal melanoma.
REGENXBIO and AbbVie have recently completed two Phase II studies in diabetic retinopathy as well as wet AMD using our microinjector administering their gene-based therapy RGX-314 for both those indications. And finally, our most recent collaborations with BioCryst for the formulation of their small molecule, a plasma kallikrein inhibitor, which they would like to administer suprachoroidally. Formulation work cooperatively is going on at the present time. And BioCryst hopes to be in the clinic by late next year with that product.
At this point in time, I'd like to turn over the presentation to Dr. Yiu for him to share his thoughts on the uses of suprachoroidal delivery. Dr. Yiu?
Glenn Yiu
Thank you, George. Thank you for that introduction. We can move on to the next slide. So I want to talk today a little bit about the real-world use of suprachoroidal delivery. I've been interested in suprachoroidal delivery and studying it actually since I was a fellow more than a decade ago. And even back then, Clearside has always been one of the main innovators in this space.
Accessing the suprachoroidal space involves – so the suprachoroidal space is a potential space that's between the wall of the either sclera and the choroidal vasculature, which is underneath that, which separates it from the retina tissue that we are trying to treat. Unlike traditional intravitreal or subretinal injections, intravitreal injections work fine, it's easy to perform, but the drugs don't easily necessarily get to the space that you want. It actually also affects the anterior segment of the eye, like the iris, et cetera.
Sub-rental injections, which is often used for things like gene therapy, requires complex vitreoretinal surgery. But the suprachoroidal space can be accessed either with microneedles such as the product from Clearside or with microcatheterization, which is also a surgical procedure where you extend the cannula through the wall of the eye.
Next slide. Now several years ago, we've already demonstrated that actually when you do a suprachoroidal injection, you can visualize that drug entering that space. First, with work from Charlie Wykoff showing from anterior segment OCT. So this is imaging that shows a cross-section front of the eye, you can see that little gap on the right side where the drug went in. But more interestingly, when we looked at the OCT images from the TANZANITE study, and I don't think that the plot is shown here, but essentially, we show that you can detect a measurable expansion of that suprachoroidal space in the back of the eye after these suprachoroidal injections.
Next slide. Now suprachoroidal triamcinolone acetonide has been tested across a variety of retinal conditions. But it's really the Phase III PEACHTREE study, which randomized 160 patients with uveitic CME to either suprachoroidal triamcinolone versus the sham control, which really demonstrated functional efficacy where you can see patients who received the treatment gained vision compared to sham and also with low rates of rescue out to past six months in the clinical trial.
Next slide. So one of the questions that we've always been interested in is that, that's only in the clinical trial setting in the pivotal trial, how does XIPERE, which is a suprachoroidal triamcinolone that we're talking about, how does it perform in real-world settings? So for this study, actually the team at Bausch & Lomb conducted a study using the IRIS Registry.
This is a national registry of many, many clinical practices aggregating real-world data. And they essentially included all patients who are over the age of 18 with a history of diagnosed with uveitic macular edema and had received the suprachoroidal triamcinolone acetonide. And they looked at patients from January 2022 to 2023, and that's roughly around those first-year or so after the product was approved and had a J code. The index date was the first time they got the injection. And essentially, they measured the second time any steroid, including more XIPERE or other steroids were given out to at least six months.
Next slide. And the study demographics on the left was generally what we expect from patients who have uveitic macular edema, but two things of interest. First on the upper right, you can see that 41% of the patients have some glaucoma or ocular hypertension to begin with. And that's a good sign that physicians, in general, in the real world, are comfortable with the concept that this drug can be given in patients with a history of glaucoma.
We know that in general, we try to avoid intravitreal steroids in patients with the history of glaucoma with the concept that intravitreal steroids can lead to a steroid IOP response, whereas here, it seems like at least close to half the patients already have existing glaucoma. We also know that roughly a third to half of patients have had previous corticosteroid use prior to them receiving this. So many of these patients are not treatment-naive that they are possibly resistant to treatment before they were given XIPERE.
Next slide. So this is what's interesting. This is a Kaplan-Meier curve showing the real world plotted against the PEACHTREE trial. So the real-world data from the IRIS Registry and the PEACHTREE trial being the pivotal trial. And what we found was that actually, 86.5% of the patients in PEACHTREE did not require rescue out to six months. But even in the real-world data, which is the blue line above, you can see that actually very few patients actually needed a rescue in that real-world setting. And please note in mind that in PEACHTREE, actually, everybody has to receive a second injection at week 12. So they actually got two different XIPERE injections at weeks 12 and 24.
Next slide. When we look at the patient, the type of rescue steroids that were received by patients, we can see that roughly half of them were another XIPERE, another quarter or so were intravitreal and some were receiving intravitreal dexamethasone implants, et cetera.
Next slide. Now you included any steroids that includes topical. So the last slide was about injectable. When you include the topicals that number does go down a little bit, but it's still quite good that largely three quarters of the eyes did not require any steroids by week 24.
Next slide. So what are considerations when giving a suprachoroidal injection in the real-world setting? First of all, patient selection is important. We try to be more mindful of patients who have high myopia or may have evidence of the scleral thinning. We will try to maybe err on the side of using the shorter needle. Things like a history of glaucoma, ocular surgery, particularly if they've had a shunt or a tube in the area where you're injecting, you might want to be mindful of that.
I think setting expectations are the most important, at least in my experience. I think patients who've had a history of an intravitreal injection can't assume this will be a bang, two second thing and run out the door like an intravitreal injection. I usually will explain to them, it's going to take a longer period of time. We have to set you up, and we might have to even consider switching needles and there will be a lot of pressure when the injection is given. So I usually tell them that they'll have the sensation of like a pressure wave. It's not really like a sharp pain, but it's kind of like, some people call it like maybe like an ice cream headache sometimes.
The procedure takes longer, as I mentioned. And then when I do it, I usually have the patients lie back, make sure they have good head support, so they're not kind of free floating. We usually give the typical topical anesthetic or subconjunctival in some cases, although we can talk more about that, but I generally prefer topical for suprachoroidal injections. We use the same antiseptic and we generally recommend using a lid speculum because of the longer duration of the procedure.
Next slide. The product comes in two needle lengths. It's a 900-micron and 1100-micron. We generally prefer the superotemporal to inferotemporal because it's easier from an ergonomic standpoint, coming from the patient side. And this is pretty much the same as what we would do for an intravitreal injection. In both the clinical trials and in most previous studies, a majority of injections can be successful with just a short needle from the superotemporal location where the sclera is a little bit thinner, a majority of the time.
Next slide. And both us and a group of colleagues, including Dr. Brown on the call, have published on what we consider to be like a consensus expert guidance on what are the best practices for doing these injections. Critically, because this is a very short needle, so the more perpendicular you are, the more likely you will access the space more readily and use the full length of the needles of holding the injector perpendicular to the surface is important.
Dimpling and maintaining firm contact during the injection to maintain that access to the space, and slowly injecting it. That's one of the key criteria, I think, to minimize discomfort because usually, any reports of pain or discomfort is because the provider is injecting it a little too quickly. And it's that first, first of the fluid entering the space. I think applying it slowly and steadily, many of my patients have been very comfortable with that.
Next slide. So I always think of suprachoroidal delivery as a platform technology. It's not just for delivering steroids. It can be used to delivering many different kinds of stuff. And I think that, that's the information or the message that we try to convey to providers. There's been the question about uptake. Right now, uveitic macular edema is a relatively limited indication. And if there are more indications for that product, then it's important for providers to be able to know how to perform these injections. And one of the most exciting upcoming developments is gene therapy for geographic atrophy.
So currently, all the intravitreal biologics have failed for the treatment of geographic atrophy. The only ones that are currently approved are small molecule or aptamers, RNA aptamers for blocking complements. But theoretically, GA is one of those diseases where I think patients are not really interested in repeated treatments oftentimes, whereas for wet AMD, you are doing an injection, you do an OCT, you look at the product, the treatment response and you can make a decision to inject or non-inject based on them, whereas with dry AMD and geographic atrophy, you are pretty much just injecting on a regular basis with the hope that it would give you some treatment effect in the long run, and you don't really get that individual personal feedback for every patient.
And because of that, for GA, it almost makes more sense for a gene therapy where it's a one-time treatment. You kind of set it and forget it. Many of these patients are older than your typical wet AMD patients. So they don't want to come in for frequent injections. So theoretically, a biofactory approach that generates a product that can be helpful for GA will be very important.
However, intravitreal injections, as we know, generally cause more ocular inflammation, and that has been a major limitation for the development of intravitreal gene therapies currently. Sub-rental injections, even for wet AMD has been difficult for patients to accept, it's still a surgery. It requires vitrectomy. If you're a [faceache], you can't get it at least without knowing that you will worsen your cataracts. So perhaps suprachoroidal delivery maybe the preferred way to go. And I think Victor will talk a little bit more about that later.
Next slide. So the key takeaway is that the suprachoroidal microinjector enables targeted in-office delivery to the suprachoroidal space is the only FDA-approved product, the XIPERE, which is used for treatment of uveitic macular edema. The durability of this suprachoroidally injected triamcinolone in the real world from the IRIS Registry seems comparable to Phase III trial results with only about 12% of people who need a subsequent steroid injection over the six months. And so suprachoroidal delivery represents a new and innovative technique with many potential applications potentially including angiogenesis inhibitors and gene therapies.
So with that, I'd like to turn this over to Victor, who I think will tell you more about those opportunities.
Victor Chong
Thank you, Glenn. So Dr. Yiu has shared with you our early suprachoroidal journey in the real world with our first FDA-approved product, and also gave you a glimpse of our promising future in gene therapy. But let me share with you our plans for the next few years.
Next slide, sorry, yes. Now as a reminder, suprachoroidal injection are potentially safer than intravitreal injection, and we believe it has close to no risk of endophthalmitis, an uncommon but serious infection of the eye after intravitreal injection. To [retinal physicians], endophthalmitis is one of the most feared complication as patients can lose the vision completely and may even lose their eye. And suprachoroidal space is protected by the immune system. So any bugs and contamination get into the space will be killed by the immune cell in the choroid. And now that we have over 10,000 injection of suprachoroidal and have no case of endophthalmitis have ever been reported.
The drug is injected into the coat of the eye and hence flow behind the retina with a reduced risk of floaters, now the drug would be able to get into the anterior chamber causing problem, which we do see some time in patients who have intravitreal implant. Importantly, that we can redose as easy and simple just like a standard anti-VEGF biologics. The injection procedure is similar to intravitreal about 10 second longer like what Glenn had mentioned earlier.
Now this is actually reflected in the reimbursement rate of the CPT code and reimbursement of suprachoroidal injection is about 10% more the intravitreal. So in money terms, that's about $10 more. I think that's a pretty good deal for the surgeon $1 per second for the surgeon's time.
Next slide, please. So when we talk about intravitreal injection, we normally think about using a 30-gauge needle. For Clearside suprachoroidal injection, we are also using a 30-gauge needle although it's a little bit shorter. However, to inject the intravitreal implant, 25-gauge and 22-gauge are needed, which are trice or four-times as great, respectively. A bigger wound increased the risk of infection and also other potential complication such as retinal tears.
Next slide, please. Let me focus the next couple of minutes on our CLS-AX wet AMD program before talking about future pipeline.
Next slide. Axitinib is the TKI that we use, and it is one of the most potent TKIs. The IC50 for blocking VEGF all three VEGF receptor are often over 100x lower than many other TKI. What does that mean? In other words, the concentration of Axitinib can be 100x lower to achieving the same blockage effect, allowing longer duration for the drug with the same PK profile. Our proprietary suspension formulation is FDA approved as part of XIPERE.
Dr. Yiu has already showed you that in real-world setting, more than 85% of patients did not require rescue therapy over six months, serving the possibility of longer duration. Similarly, CLS-AX is using the identical Clearside SCS Microinjector. And we believe our experience in navigating through the more complex combination product approval with identical microinjector and similar suspension formulation with obviously with a different API, we can potentially save time and allow us to overtake other TKI competitors to the time of approval.
Next slide, please. So when we think about our TPP, it is really based on our understanding of patient with wet AMD and also the current wet AMD market.
Next section. In the next few years, we think that when CLS-AX is approved in a few years' time, VABYSMO and EYLEA high dose are likely to be the market leader, at least in terms of revenue. And we do believe wet AMD patients have individual needs and after the initial loading dose, CLS-AX can potentially be used as a maintenance therapy two to three times a year in almost all the patients as comparing to three to four times a year in patients with VABYSMO or EYLEA high dose, and in terms of the number, you might not sound very much, but we were encouraged by the uptick of VABYSMO, showing only a small duration benefit of EYLEA can be very rewarded.
Next. As I mentioned already, we can highlight that we do mention in one more time to reinforce the message. The injector used in our TKI competitors are differed from the approved product. And our SCS Microinjector device is identical to the one in FDA approved product. We are also gaining additional experience with our pilot program in oncology and gene therapy using identical devices, as George mentioned earlier.
Next. Due to the limitation of the redosing frequency of our TKI competitors, they cannot really redose until the first implant is dissolved. They need to use anti-VEGF biologic to rest to the patient between the treatment. Now in the clinical trial that you see the patient every four weeks, so you can identify who and when to rescue. But in the real world, if we need to see patients every four weeks, you would actually increase the treatment burden rather than reducing it. And as a treating physician, I know that my patient do not like visits as even more than they don't like injections.
Next. So as I mentioned, that CLS-AX has flexibility similar to biologic. So we are now planning to develop a Phase III study, which will allow retina specialists to use CLS-AX as a replacement of VABYSMO or EYLEA High Dose in the real-world setting. And just why VABYSMO is replacing EYLEA over the past year, bringing [Roche] over $4 billion of revenue.
Adding to the potential advantage of no risk or very low risk of endophthalmitis as well as CLS-AX is a small molecule and you have a much lower risk of [indiscernible]. And furthermore, it does not even need to be put in the fridge, David Brown and I talk about in Stockholm, that thing about the hurricane and power cut that might actually occur with our changing world.
Next slide. So our Phase IIb design is called ODYSSEY. 60 patients was randomized in a two-to-one ratio for comparing CLS-AX to on label Aflibercept as shown in this diagram. And both groups are started with three monthly Aflibercept. CLS-AX was entered with the second Aflibercept. And CLS-AX can be used again earlier from week 12, if needed, based on selectivity assessment. However, if there were no disease activities assessed that was detected by week 24, every patient in the CLS-AX group will be redosed at week 24 and our primary endpoint is at week 36. And we believe that is very important.
Next slide, please. As compared to our other TKI competitor, every patient in the CLS-AX group will be [redosed] at least once. As wet AMD is a current condition, we feel it is critical to understand the effect of redosing. And it is risky to move to Phase III without any redosing data in Phase II. And we will be the only company using TKI for wet AMD to have that data at Phase II. And we will have those data based on this year.
And second, our primary endpoint is 36 weeks, which is similar to what FDA recommended for Phase III wet AMD study. And if our Phase II is positive, this will further derisking our Phase III study. As mentioned, we can potentially use our CLS-AX just like biologic, allowing much straightforward implementation in the clinical practice once CLS-AX is approved. I think Dr. Brown will discuss that a little bit later this morning.
Next slide. So let me give you an update on what we see so far, and it is completely on track. As some of you know, some of you remember that we finished recruitment back in December last year. Every patient now has completed six months of treatment. So patients in the CLS-AX group, all of them have received at least two doses of CLS-AX. In earlier this month, Safety Review Committee meeting, the SRC recommended the trial to be continued without any changes. There were no drug-related SAE in particularly no endophthalmitis and no retinal vasculitis. So we are on track to reach our topline data in late September, the end of the Q3 this year.
Next slide. So what would success look like? Well, we would expect no drug-related SAE for safety. And for efficacy, the majority of patients in the CLS-AX group should be able to reach week 24 without retreatment. And we believe that BCVA and CST should be similar in most visits to the Aflibercept control arm, in particular, at week 24 and week 36.
Next slide, please. Now may I take the next few minutes to share with you our plans beyond CLS-AX. As most of you know that I have a lot of experience in Phase III clinical development, but I have even more experience in translational medicine moving preclinical molecule to the clinic. And this is really just logical for Clearside to expand our pipeline into geographic atrophy.
Next slide. Well, geographic atrophy is actually more common than wet AMD. So we believe the market size can be larger than wet AMD. It is exciting to have two FDA-approved products, but their efficacy can be improved. And even if we cannot improve the efficacy, extending the duration would be helpful. And third more, attacking another pathway beyond complement may also bring synergy and enhancing efficacy.
What is a misconception, at least in my book, that geographic atrophy is a primary RPE disease, retinal pigment epithelium. As RPE loss is used as approval endpoint, and indeed, more scientists, including myself, think that RPE loss is secondary to a choroidal disease that compromising the photoreceptor in RPE cell leading to the demises.
Next slide, please. Now we believe that geographic atrophy in the primary choroidal disease and our colleagues in our world have demonstrated very nicely that endothelial cell in the choroid are damaged even before any significant RPE changes. The vascular density is significantly lower in geographic donor eye supporting geographic atrophy is a choroidal disease. And furthermore, which have level increases with lower vascular density, supporting the choroidal hypoxia theory as a key AMD pathophysiology in general. So treating the choroid is important potentially for GA as well as wet AMD.
Next slide, please. So we know that complement activation are present in both RPE and choroid despite that we think that the choroid is the primary area of disease. The RPE suffer and complement get activated. And as we know that intravitreal drug could be able to penetrate the retina to the RPE, but large molecules, such a biologic or even the current approved, PEGylated peptide, might not be able to get to the choroid. And in particular, the Bruch's membrane separating the RPE and the choroid is even thicker with aging and also in AMD patients. So it was even more difficult for a large molecule to penetrate. But for a small molecule, we can penetrate and hence can treat complement activation in both the RPE and the choroid.
Next slide, please. So Glenn has already mentioned a little bit about the potential benefit of suprachoroidal in gene therapy. However, they always argue that suprachoroidal will be the preferred route of delivery, a small molecule suspension can trip both side and to improve the efficacy and give a long duration.
Next slide, please. So from top to bottom, we think that there's a lot of advantage of suprachoroidal delivery in geographic atrophy, and we believe suprachoroidal delivery can reach the choroid first, providing the highest drug level and as geographic atrophy is a primary choroidal disease and that might improve efficacy. And furthermore, small molecule can treat RPE and retina because small molecule can readily diffuse through the Bruch's membrane.
Suprachoroidal sterile suspension have already demonstrated duration of six months, and we have seen low risk of inflammation and some of our efficacy have already seen in our partner in gene therapy delivery anti-VEGF. And furthermore, we have seen the level of inflammation with suprachoroidal gene therapy are also significantly lower than intravitreal. And Glenn has already mentioned, that suprachoroidal is a simple procedure as compared with the retinal surgery.
We believe with the optimized capsid, the way that the virus that is delivering and transfecting cells, we might be able to improve the efficacy even further. The procedure can be easily learned and performed in the office, and I think Dr. Brown will talk a little bit more about it as Glenn has already talked about it already.
Furthermore, we believe that the complementization of suprachoroidal injection give a high drug level in the retina, RPE and the choroid, in particularly the choroid, but a very low level in the front of the eye, so reducing the risk of adverse events. And as mentioned, that there is possibly no risk of endophthalmitis.
Next slide, please. Let me finish by giving an overview of the potential target pathway of geographic atrophy. Over 10 years ago, [Frank Holz], a good of mine, and expert in geographic atrophy suggested some of the pathway that can be targeted. And some of this already fell over the last 10 years. And complement have two recent success, but after multiple previous failure. And HtrA1 is a very strong genetic risk, it is a controversial topic after the recent Roche failure of anti-HtrA1.
And I think we need better understanding on the part of theology of the role of this genetic target. And neuroprotection and lipid pathway are also challenging in drug development, and we have seen that in other AFRP areas such as in neurology. And Clearside looking into the changes in the choroid in particularly several groups have identified specific immune cells present around geographic atrophy lesion, mast cell, microglia cells and macrophages. So targeting damaged cells and to me, are low-hanging fruit.
And furthermore, improving the choroidal perfusion should be able to improve retinal function and might slow degeneration and small molecule can be used to target these two pathways, combining with Clearside device and suspension expertise, that will allow us to bring the generated geographic atrophy drugs to the market.
Well, let me stop here and pass to Dr. Brown to discuss how CLS-AX can be implemented into high-volume busy retinal pathways and what type of potential Phase III data that would help him and other retina specialists to achieve our goal to treat wet AMD patient will reduce the patient burden and maintain clinical trial efficacy in the real world. Dave?
David Brown
Thanks, Victor. Thanks for having me. I literally have two slides here because this is mainly going to be a question-and-answer with Victor and with the advisers. So next slide. We do a lot of intravitreal injections every day. I mean my record is over 100. And they don't take very long, but they take way less time than when we started. In other words, a retina surgeon is doing a procedure, whether it's in the operating theater or whether it's in the clinic, you learn how to make it quicker and quicker.
The suprachoroidal injection, the first time you do it, you do have some nuances. I did several hundred and it really doesn't take me much longer than an intravitreal injection. But from a patient experience, it's a very, very small part of the whole process. Like this is way more efficient than my clinic. This doesn't include the fact that my clinic doesn't work as efficiently as a Toyota production line. There's a lot of waiting.
Our average visits, we're happy if we can get them below an hour and a half. This implies that my visits are like 40 minutes. And even then, injection as a percentage of the whole time is a very small fraction of that. It's even smaller in real life. So if we have a procedure that allows patients to actually be treated three months, four months, five months, six months longer, it will take over the world. We don't have any drug out there despite ones among the primary author of where the majority of patients can go three months or four months between injections.
Next slide. One thing I like about the design that Victor has briefly announced and the details aren't there. But the problem with our previous drug trials, again, ones that I'm primary authors on is that the agency allowed more and more flexibility to try to get the sponsors push to make it look like their drugs work longer. The reason people have retreatment criteria of 25 microns, 50 microns, 100 microns, make you lose vision, make you cough up blood and become disabled to lose your driver's license before you rescue is they are just trying to make the drug look good.
If you really think your drug works, make it a real-world treatment criteria where in the clinic, if you have two microns of new fluid and I can definitively prove that on ImageTrack allover tracking, I shortened your interval. I don't allow you to get more and more disease. It'd be like your oncologist saying, we found a little recurrence of cancer, but we're not going to worry about it until it's big enough that it meets some criteria. It's ridiculous. Nobody in the real world treats that way.
A treatment criteria that's more real world is absolutely what you need to know if your drug works. In a trial, we're totally comfortable seeing patients more frequently and having tighter criteria because it's better care for the treatment. Again, we've got good drugs out there. Faricimab is a great drug, Aflibercept 8 milligrams is a good drug. But you have no idea really how many patients can go 12 weeks or even 8 weeks if you rely on patients having to have preset criteria that are nowhere near what we do in the clinic.
Victor, I know we talked about a bunch of stuff in Stockholm. Happy to have you go over whatever you think the analyst and Clearside want to have a candid answer on.
Victor Chong
Yes. Well, thank you, Dave. I think that you're like, what you and I have discussed about that physician do light idea of flexibility. And we are going short to aim a potentially a label of q.12, in other words, every 12 weeks to q. 24 every 24 weeks. And although that we think there might be very few patients would need redosing at week 12. But then going to that, some investors have concern that as a doubt, we don't believe our drug actually work. But I think that we'd like to hear your opinion and on why that kind of almost more flexible label can help you?
David Brown
Yes. Certainly, we've learned a lot from intravitreal injections. If you look at view the average patient can go by with 8-week dosing. However, in my clinic, 40% to 50% needed four or five-week dosing. Why is that? And I think I've made a pretty good case at Retina Society and then in the poster, I showed at ASRS, that the main reason with our clinicians is drug clearance.
In other words, if you look at the Faricimab filing data, 10% of the patients have a half-life less than five days, and 10% of the patients have a half-life over 11 days. And in the filing data, they do the work for you. It correlates with increased – if you clear the drug faster, that correlates with needing more frequent dosing 0.0001. So there's this big bell curve of variability.
And if you have easy patients with a long half-life, sure, they can go 8, 10 weeks with 2 milligram Aflibercept. However, if you're a 5-day half-life, you are barely going 28 days with either Faricimab or Aflibercept. 8-milligram would give you, by definition, two extra half lives for that patient with a 5-day half-life that's only 10 extra days.
To be honest, we don't know the clearance from suprachoroidal, it could be not the same. It could be that there's not this wide variability. It could be that there is. And those patients that need more frequent dosing are really hurt by labels that are limiting like the 8-week EYLEA 8-milligram label to challenge. And I know Regeneron is working on reducing that for a treatment-naive population, it's a small part of the population.
However, in my clinic, the easy ones go away, like if I'm only seeing every three months, that's 4x a year, if I'm seeing every month, you're there 4x more often. So I have 4x as many tough ones as easy ones. And so in a real-world clinic, a lot more of the patients need more frequent dosing with intravitreal than our clinical trials suggest, and I'm not sure that the analysts and the commercial world kind of gets that. They kind of get what we show with treatment-naive patients, which is that bell curve. And the first time you get a shot, you're in that bell curve.
However, by the time we figure out that you need a bunch of dosing, you're with a bunch of other patients that need a bunch of shots. And so I applaud Clearside and pushing for a more frequent label. We will know why don't we do this trial and run the horse race. If Clearside is correct, and we do have everybody going to 12 weeks, that will be a game changer. We have nothing like that in the market today.
Victor Chong
Thank you, Dave. So the second question is about that. I appreciate about what you already said about extension in Faricimab and EYLEA High Dose and our competitor on TKI, they are also trying to use in rescue criteria, I mean, it could be fair, even on our ODYSSEY, the criteria are not the same as you mentioned. But if we believe the future world that all these TKI get approved and including gene therapy to get approved, and how do you think that in your practice that you're using those in terms of how do you identify when to rescue the patient, no matter what rescue criteria you choose to use when they become approved. Because at the moment, as I mentioned that they are seeing the physician every four weeks, and obviously, then you can find out who to rescue.
David Brown
Yes. In the real world, if you come to me or you send your family member to me, I'm going to treat you the best that I know how. And we don't have any data to show that is acceptable to tolerate some level of disease activity. If you have intravitreal fluid or subretinal fluid and you give a great anti-VEGF and it does nothing sure, you don't need to keep treating it, right? It's non-VEGF responses. However, if you have great response to therapy, all the fluid goes around your OCT, you do your treatment extend and they start getting fluid, you know your drugs worn off.
And when your drugs worn off, whether it's an anti-hypertension or whether it's a cancer agent or whether it's an intravitreal agent for AMD, you need more frequent treating. The dirty secret of retina clinics is our visual acuities aren't very good. We don't refract. A lot of times grandma brings the wrong glasses, our neighbor from the nursing homes. She loses two lines of vision because you don't have the right glasses, but there's no fluid on OCT. I don't retreat. We basically live and die on the OCT. If a patient comes though and says, "I'm having more trouble driving." And they notice a visual acuity change, we really look hard to figure that out. Sometimes that's an intraretinal hemorrhage that we can't see on the OCT. But visual acuity is not near as important in the clinic for determining treatment criteria as OCT because the OCT is very accurate, it's reproducible. And in the real world, if this thing keeps people drive for whatever period of time, that's where we'll figure out the interval to treat.
Victor Chong
So do you think, so I mean can you imagine a way that how that you can incorporating, the other TKI that need to be given every six months and then try to find rescue in between. I mean how would you think that will be easy to implement?
David Brown
I don't. In the real world, people really don't use treatment criteria from any clinical trial. And so I know that some of the other TKI programs, which I, to be honest, help design some of those programs. You did with the agency with [indiscernible] right? As the agency was in transition, there's still a debate whether the agency wants sham injections, which I don't think any of us are comfortable with, not sham injections, but a true placebo injection.
I don't think that most internal review boards, especially academic institutions are going to allow a placebo injection of saline with the risk of endophthalmitis. If you have to go superiority, you often are pressed into something where you have to, and you have to have exactly the same dosing. That's why they have some rescue criteria that are really way higher than a lot of doctors will even accept for a clinical trial. We'll see how that pans out. I don't think anybody in the real world is going to use their rescue criteria for retreatment or they're going to lose a lot of vision. Long-term, you're going to lose vision if you allow patients to have large excursions on OCT or documented loss of visual acuity.
Victor Chong
Okay. But finally, for me that you already hinted on that, I mean, some of the investor concern about suprachoroidal injection is very difficult to learn because no one are doing it. I think you already hinted on it. Kind of how do you think that when CLS-AX is approved, do you think adaptation will be an issue from your perspective?
David Brown
Yes. From our perspective, if you can get these patients that are requiring every four weeks or five weeks Faricimab, and you can really get them to 12 weeks, they'll put up with whatever it takes. I mean, the procedure is easy. I would say 19x out of 20x, it's not much different than intravitreal procedure. You have some squirly patients that they don't want to look the way you want them to look and or they have very tight lids or they have very thick sclera and they have to change the needle, where it does take a little more. But I think if we're doing this 10x, 15x a day, it will become as routine as an intravitreal injection.
Victor Chong
Great. So I think that I'll stop there and then open up to other investors or other people on the line to ask them questions as well, so we’ve got opportunity that we are kind of right on time at the moment.
Question-and-Answer Session
Operator
[Operator Instructions] Our first question will be from Annabel Samimy.
Annabel Samimy
Hi, everyone. Thanks for taking the questions. I had a couple here. So maybe this is for Dr. Brown. In your opinion, what is the correct rescue criteria for these patients. If you're not looking at BCVA, you're looking at OCT, there's a little bit of variability in OCT from, what is exactly the right criteria for retreatment? And again, for BCVA, when you see some trials have rescue at loss of five letters versus rescue at loss of 10 letters, what is the right place to really rescue them?
David Brown
Yes. Let me preface this. In terms of the visual acuity, visual acuity, I'm okay with visual acuity rescue criteria in a clinical trial. Just in the clinic, we don't do a 30-minute refraction. And in the clinic, our visions are often very spurious because the patients don't bring their correct glasses or haven't been refracted or get the wrong glasses or what have you.
In the clinical trial, that each DRS is a very regimented way of doing a visual acuity change. That being said, especially in macular degeneration, there's a five-letter fluctuation routinely in patients, if a patient has a rough night and doesn't sleep well, if they have the best night of their life and eat their favorable porridge and do great on their vision. That's okay, but we don't have any agent that I know of that really addresses just pure vision.
In other words, the reason our anti-VEGF work is they get rid of disease activity. They get rid of fluid, intraretinal fluid, subrentinal fluids. So I think the best criteria is pure OCT. And if you have disease activity, subretinal fluid or intraretinal fluid that increases from your lowest, that means you would do better with more anti-VEGF.
Subretinal fluid and intraretinal fluid, has been defined with very weak OCTs years ago right after approval of LUCENTIS, carvedilol and I wrote an invited perspective in AJO that define those. Those exact pictures were used as the [CAT] criteria for retreatment. The CAT had great rescue criteria. If you add a new intraretinal fluid or subretinal fluid, you got retreated. That's what we do in the clinic. That's the tightest. Pharmaceutical companies don't want to do that because they want to make it look like their drug lasts twice as long as it really lasts.
And if you really want to go, if it's a mass trial and you're going head-to-head and your drug works better, no matter what your retreatment criteria, if you have tighter retreatment criteria, you will show that your drug is better. A lot of times, you may not show it if you have a retreatment criteria that relies on vision because there's so much variability. 10 letters is a lot of letters, but it's going to happen in diabetes or vein occlusion with new fluid, you lose vision pretty quick because that's how you function.
In AMD, it's variable. There's a delay as you gain vision when you lose fluid and there is a delay before you, it's a lagging indicator. In other words, you try off the retina with a retinal detachment repair, you can improve vision for up to a year. You improve somebody's edema from macular degeneration with the anti-VEGF patient, they can improve for several months. And so there's not a direct correlation with fluid and vision. I would encourage any sponsor to do as tight criteria as they can if they really believe their drug works.
Annabel Samimy
Okay. And then maybe is there a way, could you be a little bit more specific on the amount of fluid...
David Brown
Any fluid.
Annabel Samimy
Any fluid...
David Brown
It's like communism, it's like cancer. It's like fire ants, fluid in the nervous system is never good for you. Post-traumatic stress, I mean the reason boxers and football players become demented is they get edema in their brain over and over. The same thing happens in the retina. You lose neurons, you lose function. Like why would you allow a little bit of renal carcinoma to come back before you retreat it, right? It's the same. Fluids never good for you.
Annabel Samimy
Okay. And then one question for Victor. Are you going to be partnering with anyone for the gene therapy program? And further from that, is there a good understanding of how the endpoint should be measured for a gene therapy program. It's not necessarily like anti-VEGF where you see response and there's retreatment, you're just kind of monitoring progression. So do they have a good idea of gene therapy endpoints at this point?
Victor Chong
Yes. The first question is we're already partnering gene therapy with REGENXBIO right now. And again, obviously, that actually shows some promises with the current progression. But yes, I think that we would be considering gene therapy partnership, I just mentioned earlier that at the moment, as a small company, go for low-hanging fruit first, and then gene therapy is certainly not immediate, but it's much more longer term. But again, there is a lot of company out there who have a lot of gene therapy expertise but they might not have the right device. And so it might be a [indiscernible] that kind of things in the future.
Now in terms of end point, FDA is very clear. And in fact, I was one of the earlier people to suggesting that we really want to use lesion growth as an endpoint. And because that is much more easy to do to kind of that measurement and progression. So that has been accepted as a first to drug approval. And I think that was still, to me, is still a good endpoint. However, that we already see those drugs have problem with [indiscernible].
And so again, if you can demonstrate functional benefit, that would be helpful. And you probably don't have to demonstrate both and depending on what would be the preferred important, but at least for the FDA that they always saw about this 15 letter and that it's quite hard to see the 15-letter change in geographic atrophy. So it might be a compromise that we have discussed previously, if we can use a lesion size or FDA approval and a slightly different vision function endpoint for the rest of the world. So those is actually what we're looking at. I don't think Clearside being a small company, we're not necessarily leading it. But as you know, in my previous role that a lot of big pharma are working hard on that.
Annabel Samimy
Thank you.
Operator
Next question will be from Andreas Argyrides of Oppenheimer.
Andreas Argyrides
All right. Thanks for taking our questions and great presentation here. For Dr. Brown, and you've got this, I mean, we've kind of talked about this several times in this conversation, and you've got this discussion numerous times before as well. But what is really the ideal timeframe to go without an injection? Is it now every 12 weeks? And if that's the case, then what are you looking for from the upcoming results from CLS-AX that would differentiate it?
David Brown
Yes. I think there's two points there. One, you'll see from some papers I'm writing and from the stuff we've been presenting, that variability in bell curve is the big problem. In other words, why did EYLEA become a $8 billion drug or whatever it is. It became an $8 billion drug because for most patients, it was a week or two longer than ranibizumab, Lucentis, right? And that doesn't sound that much. I mean, you take somebody to go from four weeks to six weeks though, it's 13 doses a year to 9 doses, right? It's a considerable reduction in having to have their daughter take off work from school to drive them to my clinic. So all you really have to be is incrementally better than the best drug out there. And you can argue whether you think the best drug out there is Faricimab or Aflibercept 8 milligram, but there are still patients that need five or six-week dosing with that drug. If you got every patient to 8 weeks, you'd run the world, right?
And so that being said, you have patients that can go 9, 10 weeks with ranibizumab 0.5 milligram. That patient, you would hope that with this drug, you could go considerably longer. And so if they really can get every patient to 12 weeks, they'll take over all the drug market that we have now, right, or any of these TKIs, right? You have several different programs on shots on goal right now. Two programs, recruiting patients or at least getting close. And it just has to be better than what we have in the clinic.
Andreas Argyrides
Okay. Great. And actually its a segue to my next question here. So what are your thoughts on the safety advantage of suprachoroidal compared to, let's say, intravitreal injections and then the use of the biodegradable inserts as you alluded to?
David Brown
Yes. So TKIs, I've been doing work with TKI. I mean, I run the biggest clinical trial center from academic generation of the world. And we have had TKIs literally attempts shots on the goal for 12 years now. And they showed a biologic effect. I mean we had one [indiscernible] that was an eye drop that showed an effect, but it's staying the cornea red. The problem has always been just a pharmacologic delivery of these things. Inside the eye, they've migrated implants, you've had snow globes with TKI. The advantage of the suprachoroidal space is, you don't have to have a clear molecule. In other words, when you test some of these TKIs in monkeys, they're like swing flies, and it's the same thing. Patients don't see any floaters with our current agents.
They notice biodegradable implants. Some of them spin around like it at a time, like your advantage is you're not having to be in that optically clear space. Your other advantages is that there's less inflammatory processes that we know of in the suprachoroidal space, that exist within the eye to try to clear on anything. So yet to be proven if this TKI in the suprachoroidal space is going to do what Clearside hope it is. But if it really works, it has a lot of advantages of being outside the visual pathway.
George Lasezkay
Yes. I can also chime in a little bit in terms of the safety. One of the major advantages of the suprachoroidal space is that it's outside the blood retinal barrier. And that's actually quite critical because as Victor mentioned, first of all, when you're outside the blood retinal barrier, first of all, you don't get endophthalmitis. If there is a theoretical risk of infection, you would often likely get things like a little scleritis or something like that. But because you're outside the blood retinal barrier, there is actually inflammatory cells that are immune surveillance that will actually treat your infection. So that's why there's the risk of endophthalmitis is nearly zero. If the injection is done correctly and it actually enters the suprachoroidal space. So I think that that's why I think the safety is significantly better than intravitreal and certainly much better than subretinal.
Andreas Argyrides
All right. And then just one quick last one from me and I'll hop back in the queue, but we've got updates at ASRS and there were some updates on the intravitreal gene therapies and wet AMD. So I mean, I kind of probably know this answer, Dr. Brown, but your thoughts on the safety around intravitreal gene therapy. And then I mean, for it to really make sense, do you need to see durability out to like several years?
David Brown
Yes. I've done a lot of work on gene therapy, and I have a lot of hope that we would have perfected things by now. I'm not going to comment on any particular program, but everybody has had more late surprises than we expected. The inflammation or pigmentary changes or what have you that comes nine months to 12 months after you start a program is not related to the capsid. And that's the main thing we always kind of blamed. It almost has to be related to your gene product.
And for some reason, most of these programs are showing a reaction to gene products late in the experiment. One possible explanation for this is that whenever I make drug in a [indiscernible] line, it's a perfect cell line. But you still don't get perfect drug. You have to purify the drug because the gene constructs, you get some truncated proteins, you get some misfolded proteins. You purify that before you put it in a vial or syringe and ship it to my clinic.
When I created gene factory in [indiscernible], I can't clean up her production line. And so it's possible that some of these truncated proteins, misfolded proteins over time, create an immune response to that is being reacted against. I hope that's not the case because I don't have an answer for it. It would be pretty easy to figure that out. They could do AC taps and do gel electrophoresis and see what size of proteins you're making and how much percent exactly what you want to make and how much percent isn't. And maybe that doesn't exist, but I think we're going to have to look harder to try to figure out why those late reactions are happening. I still think we'll figure it out. I still have hope that gene therapy is going to be one and done, but it's sure been harder than I think a lot of us expected when we started this journey 10 years ago.
Andreas Argyrides
Thank you.
Operator
Our next question will be from Serge Belanger from Needham & Company.
Serge Belanger
Hi, good morning. And thanks for the Clearside team for hosting this event. I have a couple of questions for both Dr. Brown and Dr. Yiu. We've seen some high-profile approvals in this space over the last couple of years with VABYSMO and High Dose EYLEA and the we feel the implant is also back as of earlier this month. Just curious how you've incorporated these products in practice how exchange your practice and what you've been able to achieve in terms of retreatment rates? Maybe how many patients get to that 12-week retreatment? And then Dr. Brown, you talked about the ideal Phase 3 design for longer duration products, how would you incorporate these new products as an active control arm in these trials? Thanks.
David Brown
Glenn, you'll start?
Glenn Yiu
You go ahead. Why don't you start...
David Brown
All right. So let's see, the first thing is how we incorporate into the practice. Both drugs fortunately have not had the brolucizumab below eyeball experience. So that's good. There's a lot of patients that we are starting primarily on these drugs or switching. The majority of patients can go longer, but very few have dramatic changes. In other words, the four weekers can go five or maybe six weeks. The eight weekers can go nine, 10, 11, but it's about what you expect just for having more anti-VEGF, to be honest, I think that's the main benefit we're seeing with Faricimab as it's 2.4x the anti-VEGF of 2 milligram of Aflibercept and by definition, 8 milligram is 4x the anti-VEGF of 2 milligrams. So you're just getting extra half life and less clearance. We use it exactly the way we use our other drugs. We treat and extend. I typically don't reload.
If you're on 8-week of Aflibercept, then I move you to 2 milligram, from 8 milligram, I do one interval at 8, and then I go to 10 and then I try 12. And when you fail, I go back to 10. What percentage are going to 12 is, I don't know if it's that relevant because the ones they get out to 12 or longer were ones that were probably 7 or 8 on ranibizumab, right, 0.5 milligram. I mean it is better, they're happier, and it is an incrementally better drug. We have a lot of insurance plans, most of our insurance plans make us step through Avastin, many of us haven't stepped through Aflibercept, ranibizumab. And so by the time you step through two things, you have a tougher population. And not many of those can go 12 weeks, right, to be honest, after have failed Avastin and failed ranibizumab, which is a pretty good drug. Once we get into Aflibercept BioSim, if we ever do, I think then you're going to have to fail 2 milligram Aflibercept, which is a high bar, it's a great drug. So that was how we're incorporating. In terms of – what was the last question again, I'm sorry, the clinical trials.
Serge Belanger
Yes, how you would incorporate these new products as a active control…
David Brown
That's tough because in the clinical trials, they all had a dose regimen in criteria, right? And so before the agency didn't make you go head-to-head. So the reason people play these games is you would go against 2 milligram Aflibercept, which you gave every eight weeks. And then you would have some criteria that allowed you to go longer and longer with your drug to make it look good because you're comparing against the drug that didn't have the same criteria. If you use the same dosing, in other words, if you go PRN, which I don't really like in the clinic, but I'm okay with a tight PRN in a trial or if you have a rescue that's exactly the same in both arms, you could easily do a Faricimab or Aflibercept and have a pretty long dosing interval, make it 16 or whatever the highest is in their label.
But in every four weeks, have the same dosing criteria for both rescues, any fluids, subretinal fluid and intraretinal fluid. And if the Clearside molecule is really lasts the whole four months, and we know that very few patients are going to last the whole four months with tight criteria with either Faricimab or 8 milligram, you'll win. So I think you could do it.
The agency is going to make you give, it's a little challenging if you have to give it to six months, which is what Clearside thinks they can get because then you have to do both at six months. You could do it both at four months. That's probably the easiest because both have a 16-week label. You might be treating the Clearside interval more frequently than you need to. But to be honest, I kind of like that. Whenever you dose more than what you'll do in the clinic, you really test the safety aspect, right? In other words, if I get the drug too much. And I still am safe that's got to give the agency and clinicians comfort as opposed to not knowing that safety curve.
Glenn Yiu
I guess in terms of me, I actually completely agree with Dr. Brown, how exactly I would use incorporate these newer drugs in the real-world setting. I guess coming from a more academic perspective, I also only observed really incremental improvement with the newer Faricimab or High Dose EYLEA. I think we did actually an internal study of real-world outcomes. And most of our patients can extend maybe a week, maybe two weeks like it's a little bit more than one point something week on average, if you just continuously extend from their prior interval to and switch them to a new drug. And I think that, that's pretty much what most people in our community have experienced.
From an academic standpoint, we generally try to at least my practice is a lot of Medicare. And generally, there's not as many restrictions in terms of step therapy. So we actually typically have switched a majority of our patients to one of the newer agents. For me, it's primarily been VABYSMO mainly because of the more limited treatment interval options for EYLEA High Dose. So we've been using primarily a lot of Faricimab and switching over to that.
In terms of incorporating into a clinical trial setting, I again agree with Dr. Brown. I think that in my sense, I feel like the ideal interval would be close to four, maybe even six months. I actually don't think that there's need to go even longer mainly because I think most of us retina specialists feel uncomfortable with sending a patient that we'll see you in two years in terms of their next visit anyway. So we're probably going to be seeing them at least every six months. So I always feel that six months is kind of the ideal dosing interval and visit follow-up interval, if I can get to that point. So I think that the challenge, as Dr. Brown mentioned also, it's this whole FDA requirements of whether it be similar in terms of the retreatment criteria in interval. So I think that every four months, essentially every 16 weeks or every six months would be reasonable design.
Operator
Our next question will be from Yi Chen of H.C. Wainwright.
Yi Chen
Yes. Thank you for taking my question. My question for Dr. Brown and Dr. Yiu is, have you observed any difference between High Dose EYLEA and VABYSMO in terms of treatment efficacy or safety besides the treatment duration in your patients?
Glenn Yiu
I can start this one, at least personally, I have not used the High Dose EYLEA very often. So I don't think I have a good comparison of the two products. But there are some challenges to using the High Dose Aflibercept, mainly because it's a slightly larger volume. And also, I generally don't give it to people who are like a monthly or every six-week previous treatment on EYLEA, mainly because of the label that only allows us to give it every eight weeks. So at least for me, I haven't seen a significant difference between the two products. I'd love to hear what Dr. Brown thinks.
David Brown
Yes. They're both great drugs. I mean, Aflibercept 8 milligram is an easier sell because most of the patients are on Aflibercept 2-milligram and you go, we're going to, from Tylenol Extra Strength Tylenol, they kind of shake their head. And so I think there's just an innate comfort level of using a drug where there's been 80 million doses of a molecule given, right, especially with our disastrous brolucizumab and [indiscernible], that being said, VABYSMO has a great safety record, and I haven't had any problems with it.
I think they're both good high-end drugs. I think in the real world, what's going to happen, though, is that once we get an Aflibercept biosim, the insurers are really going to push us to use to have Aflibercept 2-milligram failures before we go, it's probably going to be a less than $1,000 drug pretty quickly. To go straight to a $2,300 drug for a healthcare system, I think you're going to have a pretty strong step to get there.
And then you've got basically your VABYSMO and your 8 milligram is going to be your cleanup, your Mariano Rivera, Ace in the hole, if you have trouble from your – if you can't win the game otherwise. And so we'll have to see how big that market actually is. You hope that innovation doesn't get stifled if those drugs go to $2 billion or $3 billion drugs instead of the $8 billion EYLEA is now, there'll be less people trying to make a better mousetrap and that's a shame for patients. But you never know. They're most great drugs.
Yi Chen
Yes. A quick follow-up. So do insurers always request you to use regular EYLEA before using either EYLEA HD or VABYSMO?
David Brown
They don't at all because it's an $1,800 drug, right? You're kind of going from $1,800, the big difference will be when we have a biosimilar. Like we're going to have a biosimilar, the biosimilar ranibizumab ASP is going to be less than $1,000 next year, right? And that's a big difference. If it's less than $1,000 versus $2,300, it doesn't take a finance major to figure out that the more you can push to the $1,000, the more you'll save healthier, right?
Yi Chen
Right. Got it. Thank you.
Operator
We will now take a question from the virtual audience. Jenny Kobin, please go ahead.
Jenny Kobin
Thank you. This question is for George. Will the patent protection for the SCS Microinjector be long enough to get a potential small molecule through the clinic?
George Lasezkay
The current patent protection we have on the Microinjector lasts until at least 2034. And it's way too early for us to put together a development timeline for a GA product. We're in very early stages of formulation and product action. But the Microinjector itself is covered at least until 2034. We have pending applications currently that might extend that into 2040. And as we continue to develop a GA product, I would anticipate the possibility of filing additional applications that would take protection into 2040 and beyond. So we currently feel very good about our IP protection for the injector and the injector platform.
George Lasezkay
I think that's our last question. So let me thank you all for joining us this morning. We appreciate your interest in suprachoroidal drug administration and in Clearside Biomedical. We're excited about our future opportunities, and we look forward to providing you updates on our progress. Operator, you may now disconnect. Thank you, all.
David Brown
Thank you, all.