Kodiak Sciences Inc. (KOD) Earnings Call Transcript & Summary

Yes. Okay. Good afternoon, everyone. Welcome to the 4:40 p.m. session on day 1 of the 42nd Annual Goldman Sachs Global Health Care Conference. My name is Graig Suvannavejh. I cover both U.S. and European biopharma names here at the firm. It's my pleasure to be hosting Kodiak Sciences today in a fireside chat. And with that, let me welcome Victor Perlroth, who's CEO of the company; and John Borgeson, who is CFO of the company, who is just slightly to the side of your screen.

But with that said, Victor, it's good to see you. Thank you again for your participation. And maybe if I can just start everyone at a very high level for those who are perhaps newer to the Kodiak Sciences story or perhaps revisiting it after some time, can you please just tell us a little bit more about the company and what you believe are either your core technologies or your core key areas of expertise?

Yes. Thanks, Graig. Thanks for having us at the conference. And I think it's nice. I think we have about 40 minutes. So that's a good amount of time where we can get to good back and forth and a good discussion that can be very informational and educational for all the listeners. So thanks a lot. Kodiak Sciences, we were founded back in 2009. So that gave us the opportunity to really focus on the core science, underlying what we now call our ABC platform. We make antibody biopolymer conjugates or just antibody conjugates. And we're focused on developing these biologics for retina. And in particular, for high prevalence diseases in retina. So that would be macular degeneration, diabetic retinopathy, predominantly, everything to do with the retina. So our first program KSI-301 is an antibody biopolymer conjugate that we're developing for macular degeneration, the wet form. And also for diabetic retinopathy, DME, diabetic macular edema and also earlier non-proliferative diabetic retinopathy, sort of as a preventive. And then also in another disease, retinal vein occlusion. And that's really exciting. Retina is a field with LUCENTIS, really was a miracle therapy back in like 2006. We had EYLEA, 2010, '11. Since then, not too much. And now I think with faricimab and KSI-301, really well positioned for some exciting new molecules to enter the space. I think with faricimab, we'll talk more about it. But the new science there was another bispecific antibody, in this case. Another mechanism of action and other biology is supposed to deliver superiority, in our case, but has shown to be an incremental agent. I would say, whereas KSI, we have strong science around the design of our ABC platform in the design of KSI-301, our conjugate. Really interesting biophysics around how we decided to build our science, our kind of core competence around design of these biologics, and then now the development of our biologics in retina. And we're really a retina franchise-focused company in terms of design, KSI-301. We have KSI-501. We have KSI-601, building on different aspects of our ABC platform. And we own our IP. We own our platform and our products on a global basis. We haven't partnered any of those. And so we have 100% focus on discovery, development and potentially commercialization of our medicines as a retina franchise company with a really strong mission preventing and treating blindness on a global basis. And just to remind people, I mean, retina is a wonderful area. It's very complex to develop drugs in retina. There have been a number of failures recently and over the last few years. And a lot of hard roads for different types of players. I think we're playing the long game. Going back to 2009, we've made very thoughtful, very careful choices in the design of our platform and of our medicines. And now we have, I would say, an aggressive, but also a very realistic operational plan around the development of KSI-301. And we're really focused now in a period of execution in the company. We're within 12 months of 2 top line data readouts from our 2 first Phase IIIs to read out. DAZZLE wet AMD study in Q1 of next year and our BEACON RVO study probably in the second quarter of next year as well. And then our DME studies and our new wet AMD DAYLIGHT study and so on. GLEAM, GLIMMER and DAYLIGHT reading out, certainly less patients, less visits is our objective for the end of 2022 for those 3 studies. So at a minimum, we hope 5 studies over a short period of time. It's going to be very exciting. And we think we're playing the long game for a medicine that's really highly differentiated and a lot of white space between where we can read out with our pivotals in our development plan versus all other agents available at that time. So it's an exciting time. We have good science. We have a good team, and we're focused in retina. All aspects of this in development and potentially commercialization on a global basis.

Appreciate that background is very thorough, and I think it lays a good groundwork for kind of the basis of discussion going forward. I would love to ask you about actually the polymer technology you have. And you are a retina-specific company. The idea to those who don't know the technology well is you've got this polymer that you're putting in the eye. So perhaps one of the initial things that I would think about or one could think about, nothing I think about it. But what is the safety of having your KSI-301 long-term in the eye in the context of this polymer technology that you have?

Well, it's really a philosophy of safety that goes back to the origin and inception of the company and the technology. So we built these antibody biopolymer conjugates and the biopolymer portion is built out of kind of how in our body the cell surface is the phospholipid bilayer, that's what you learn like in high school. You have the fatty part and you have this hydrophilic part. Well, the hydrophilic part is mostly phosphorylcholine. That's a really cool substance in the body. Actually, it's zwitterionic, which means it has kind of a balance that's in between a positive and negative charge. And it turns out -- it's not really an accident that we have that all over the body. I used to think like, oh, our body is mostly water. And I used to think, well, that water is like slushing around. That's not actually true. The water of the body is bound or what we call structured by the phosphorylcholine that's all around our body. Water is defining the interactions between the biological molecules in the body. When 2 proteins bind, you often have 2 hydrophilic amino acids zeroing in like space station and then the dragon capsule coming in precisely with the right stereochemistry kind of thing and getting that docking exactly right. And in the body, that's what happened to protein. I just you always have like a little molecule of water in between each of those amino acids. All of that is structured and driven by phosphorylcholine and by the zwitterionic kind of water structuring and water binding. And so what we did is we built these branched very well-characterized polymers of phosphorylcholine with a defined chemistry that we used to conjugate into the antibody to create this stable linkage, and so it's 3/4 polymer and basically 1/4 antibody. And this thing is super safe, the Polymer is essentially, we call it macromolecular water. It's essentially water in a special form that's very like biocompatible and very much like what the body likes and it has a lot of really cool properties. It drives really long half-life in the eye after you inject because that thing is large. Of course, it's mostly water, okay? The polymer is also like very lubricious in form sort of like what we call a water ball bearing kind of layer. So it's very slippery on the edge. So it can navigate into the retina in the core that are kind of the tissues of action for these retinal diseases, okay? At the same time, when it gets to where it needs to do its work, that special water structure drives that stereospecific interaction that docking with the target like the VEGF, okay? And then that thing is like always slowly leaving the eye. So there's no like accumulation of this thing in the eye. And then it's really cool. Once -- what you really want, you close your eyes and say, well, what's the best next-generation kind of platform for retina? But you wanted it to act big in the eye but you wanted to kind of get to where it needs to go. You want -- then you want it to be potent, right? You really want it to kind of bind with its target and activate it. And then once that thing gets out of the eye, because you don't want it to stay there, you want it to be cleared very quickly from the body. And so the way the polymer conjugates into the antibody, we perturb that FcRn binding site, which is the part of the antibody that drives long half-life in the body and recirculation of antibodies. And that's why they have a long circulation time, but ours is blocked and so it rapidly clears through the body mostly through it. So it's a very thoughtful design. And then, of course, we manufacture these things with a lot of attention and a lot of excellence as can be evidenced by really essentially almost 0 inflammation that we've seen in any patients. So it's a great design. The polymer aspect of it is really built with the philosophy of safety from the beginning of how the body builds a water structure environment that's natural, right, water is safe and specific fat hydrophobic particles suspension as opposed to aqueous solutions those are bad, aqueous clear solutions with biologics and water that's good and safe. And those were the philosophies that drove the design. And I think we're seeing the dividends of the many years of design and now the right capital allocation in some way the right pivotal study program and design. Bringing all of those indications, wet AMD, DME, RVO into 1 BLA filing is our objective. I think we hope to achieve that based on positive top line data out of those 5 studies to really get a broadest label inception. And then the broadest label of any of the medicines to get what we call a drug for all patients with retinal vascular disease, and that's our objective. And the safety that we've seen to date is tremendous. Obviously, that's something that you look at every day. I think we -- and when we do look at that, we remain almost -- we remain astounded by the safety that we're seeing. We're gratified by the philosophy of safety we've taken from the beginning in our design, also by the level of excellence of our manufacturing to continue to see safety and to continue to expand and to dose more and more patients. I think at this point, we've given over 2,500 injections in patients and are probably not quite there but approaching 1,000 patients dosed with KSI. So it's a great profile, built on design and philosophy, delivering safety for the patients.

Well, it's great to hear how extensively the safety profile of KSI-301 has been studied. Clearly as exciting of a space, the wet AMD competitive development landscape looks today, especially with multiple programs in development, spanning different modalities. Inflammation has come up as an outstanding key area of focus, and it has impacted, obviously, certain programs quite significantly. And we'll revisit that in a moment. But to date, in terms of the clinical data that you've generated on the efficacy side in the context of a very large clinical development program that you have with multiple studies ongoing. Could you just point us to kind of the key efficacy data? And what ideally does the product look like in terms of an aspirational profile as it relates to kind of treating wet AMD patients, given the treatment paradigm?

Well, the development plan for KSI is a non-inferiority development plan. So our objective in our studies is to go head-to-head against EYLEA as a standard of care agent and to show that we have the same gain in vision that were non-inferior in terms of vision versus EYLEA and then to give fewer doses. And the primary end point, therefore, is non-inferiority vision. So to date, the primary study to look at is our Phase Ia/Ib study, sort of a I/II study, where we enrolled 121 treatment-naive patients with wet AMD, DME and RDO. And then we looked at what the gain in vision was at 1 year. And we have very strong and appropriate gains in vision in all 3 of those treatment naive indications, looks very strong and very appropriate. And also very strong and appropriate improvements kind of in what's called retinal anatomy or the fluid in the eye that these patients get and that's why they're treated. So -- with many fewer doses. So for example, in the Ib study, 2/3 of the patients in all 3 of those diseases went for 6 months or longer in between injections of KSI-301 in that first year. So that's a very strong durability and very strong and appropriate efficacy. So that's very exciting. And then we designed our pivotal program, essentially based on the data to showcase what I'd call sort of the North Star for our ABC platform in KSI-301, which is long interval dosing, which is where the field needs to go. Because patients just are not able to get into the clinic often enough to be dosed with LUCENTIS or EYLEA because they essentially need to be given very frequently, say, which LUCENTIS essentially monthly, with EYLEA maybe half the patients monthly and half the patients every other month, for example, where some people say 1/3, 1/3, 1/3. 1/3 monthly or worse, 1/3 at 6 to 8 weeks and maybe 1/3 at 10 to 12 weeks. So that's really too frequent for these patients to make it into the clinic, whether they have wet AMD or whether they have DME. So the North Star in the field is long interval dosing with the same efficacy and the same safety. And that's how we designed our pivotal program.

Do you think that with the potential of, say, dosing once every 3 months, how incremental in your mind based on your interactions with either physicians and/or patients, how incremental of a step is once every 3 months? How much more incremental is once every 4 months? And is there a need or a strong desire knowing perhaps an element of practice economics, whether once every -- longer than that is ideal?

Well, I sort of like this concept of the goldilocks zone. So you want to go longer, but you don't want to go forever. You don't want to go too long because the physicians actually like to see the patients, right? They worry about the patients. They also like to see them. I mean, from a financial standpoint, and you want to keep your eye on the other eye. So you want to keep the relationship going. So the goldilocks period and the goldilocks medicine is, I think, an intravitreal biologic injected on an infrequent basis. And I think, say, for example, the DAZZLE interval or the GLEAM and GLIMMER interval. So DAZZLE is every 3, 4 or 5 months dosing. So it's 100% of patients on 3 months or better, 3, 4 or 5. And then in GLEAM and GLIMMER, we have every 2, 3, 4, 5 and 6 months. So our hope with dazzle is that will bring a majority of the patients to 20 weeks right to 5 months in between doses. And for GLEAM and GLIMMER and DME, I hope is to bring more than a majority of patients to 6 months in that program. But we'll also have some patients in DAZZLE at 3, 4 and 5 months. And I think GLEAM and GLIMMER will have some patients, say in every 12, 3 months, 4 months, 5 months and 6 months. But like I said, it's sort of a like North Star, like a 5- or 6-month predominant profile is really where we want to take the field. That's kind of the goldilocks kind of zone. You also want to be able to provide the medicine to be able to be used on patients that have very high needs. Say like every month or every 2 months, but we can talk about that a little bit later. The initial question, different patients have different needs for the amount of therapy and the amount of drug that they need. And the real home run opportunity, I would say, is even if you're incremental, but you're really incremental, right? So the concept is you have this histogram or a distribution of twice a month, once a month, right, every 2 months, 3, 4, 5, 6 months. Our objective is to meaningfully shift that curve to the right, hopefully, for every patient, but it may have a curve shape that has a slightly different shape depending on the need of the patient. And there's tremendous unmet need towards that North Star long interval dosing. I think we're well positioned to achieve that. And to do that in a way where, like I said, we have a lot of whitespace between where what we put together in terms of our data and the data that is generated by say faricimab or EYLEA before that.

Okay. You recently announced a new study called DAYLIGHT, which is going to evaluate a once-monthly dosing regimen. And so in the context of the argument or the case for extending duration, I think the once-monthly trial has caught some by surprise. And so I'd love to revisit kind of the strategy from a clinical development perspective and from an overall perhaps commercial perspective, the reasons why you felt starting a once-monthly as you are prosecuting perhaps longer duration versions made a lot of sense for you at this time?

Well, that's a good question. I think the DAYLIGHT program, which is a monthly program in wet AMD accomplishes a lot of important objectives for Kodiak. It's not a required study. And at this time, it makes a lot of sense for us to initiate daily. So we want to develop KSI-301 as a medicine for any patient with retinal vascular disease. We don't want to give up any patient. We don't want to say we're the drug only for those long interval dosing patients. We saw in our Phase Ia/Ib study, that there's about a single-digit percentage of patients in wet AMD, DME and RVO, who benefit from need, say, monthly dosing. And if you add on top of that to patients who need every 8-week dosing. Because in DAZZLE, we only have 12, 16 and 20 weeks. That could be somewhere in the range of, like, say, 10% or maybe 15% or maybe 10% to 20% of patients in the real-world that may benefit from 1 or 2-month dosing. We don't want to abandon those patients, okay? When -- our objective, as a retina franchise company, is to be committed to retina across our programs, but also with KSI-301 to be committed that the physician, we want them to use our drug in every patient. That's what they say -- they say, look, I'm using KSI in the clinical studies. I've seen great efficacy, great safety and great durability. And I want to be able -- you need to prosecute your development program and get this thing approved so that I can use it in my patients. And I want to use it in every patient. Because if you have efficacy, safety and durability, that's great, why wouldn't I ship all my EYLEA patients on the KSI-301? Well, that would be amazing. In order to do that, we can't just, for example, in wet AMD, have 3 loading doses and then they have to wait for 12 weeks before they can give the next dose. And that's really what happens in the real-world is, if you have a 12-week kind of label. In that intermittent period, it's a little bit of a dead zone, not only can't they give KSI-301, but they can't give Avastin, LUCENTIS or EYLEA, get reimbursed for the drug or for the procedure. Now this was a problem that EYLEA had in the first 5 years or so because it had a label that said every 8 weeks. By the way, it could also be used every 4 weeks, but there's no additional benefit for doing so. And so as a result, the physicians tend to sort of battle with the payers for a number of years to get reimbursed monthly until they went to FDA and Regeneron and said, let's fix this and then they fixed the label. Now basically says it can be used every 8 weeks, but some patients benefit from every 4 weeks. When launched, they didn't have a 4 week in the label. And that was a little bit of a headwind on the launch. I mean, of course, now they run into the vasculitis. And so that's really become the tail that wags the dog from that age. But out the gates, they didn't rebate that effectively, and they didn't have a monthly label. Now first, about, let's see what they do. I think our view is they don't really have the data and the safety database and the clinical design to get monthly in their label. But for us, we have the time and the money to do what I call a tuck-in study, and that's really what DAYLIGHT is. So we're going to start screening, I think, this month, maybe early next month in randomizing patients. So we now have treatment naive studies as pivotals for DME, that's GLEAM and GLIMMER; for RVO and BEACON study; and now we have -- and DAZZLE is already fully enrolled. So we're not enrolling any treatment naive wet AMD anymore, but now we will with DAYLIGHT. So we're going to have a pivotal study for any treatment naive patient who comes in with any of the major diseases. And operationally, we have clinical operations on a global basis now, and we've even put in the improvement. So we have, for example, an integrated supply chain, right? So that the clinical site can basically go to the same refrigerator and grab the box of EYLEA or Sham or KSI-301, it's all the same dose. Essentially right for all those 3 studies of KSI-301, it's the same EYLEA comparator, and it's the same sham. And we have all the operations needed to basically effect treatment naive, major disease indication between now and enrolling patients through like the end of this year. So it's an exciting opportunity that we step up into to be able to really have that very broad label at launch, all 3 major diseases. And we spoke with FDA, and they said, we asked them, if we were to run the study, with more frequent dosing, let's say, monthly, in wet AMD, could we then get monthly in RVO and DME? And the answer was yes. So that's also very powerful to be able to have this concept of extending the safety database. And so with DAZZLE fully enrolled, we expect last patient last visit in December of this year. BEACON is enrolling well. So DAZZLE will have top line data announcement in the first quarter of next year. And BEACON should also readout in, say, this late second quarter of next year, plus or minus. So we're inside of 12 months of top line data from 2 of those pivotals. Now DME in a pandemic was a bit slow on the enrollment. When somebody gets DME, it really means they're not controlling their systemic sugars that well. Those are the types of patients who didn't come into the clinics as much during the pandemic. So I'd say GLEAM and GLIMMER enrollment was a bit slower than we anticipated. However, that provides somewhat of an opportunity for us while GLEAM and GLIMMER completes enrollment, let's say, through the end of this year to really initiate enrollment for DAYLIGHT. And DAZZLE at the end of its enrollment period, we were enrolling between 80 and 100 patients a month. And I think we'll hope to be able to achieve a pretty strong clip in DAYLIGHT for treatment naive wet AMD enrollment in a similar set of global sites where we're already running studies for being it delivered. So I expect let's hope strong enrollment into DAYLIGHT, that could hopefully a bit matched together with GLEAM and GLIMMER. Now DAYLIGHT is only a 9-month endpoint, 40 weeks. So we expect -- I do anyway, we're working towards last patient, last visit, let's say, for that study, close to year-end, I think, in year-end 2022, maybe a little earlier if we can achieve that. So I don't see it building our time lines. Like I said, I call it a tuck-in. I think it will be powerful to get that label broadening. It's part of our strategy for KSI-301 to be a drug for every patient. The other thing to say is, as a physician, they don't know when a new patient comes in, whether this is going to be a 6-month patient, let's say, for KSI or a 1-month patient. You don't know because there's no pharmacodynamic marker. There's no surrogates, there's no AI. There's nothing that can tell the physician. All they can do is put the patient through the loading phase and then see what happens. And you don't want the physician to have like anxiety on the margin because they don't like to switch the patient from one drug to another. We want this to be a drug for all of their patients. And so when the patient comes in, you want them to naturally lean into putting the patient on KSI-301, this new patient. And then as they go through the loading phase and they see, that's 100% of the patients. It's not like you say, "Oh, well, only single-digit percent are going to need monthly dosing. So why are they running a study for a single-digit percent of patients." That's not actually how it works. You want them to think about KSI for 100% of the patients. And the way to do that is to have that broad label from the beginning, even if the North Star is that long interval dosing, you don't abandon those earlier patients because that's how you get to the long interval dosing for all of the patients.

And you've walked me be through if you've got a KSI-301, that in one study is supportive of an extended duration profile, let's just call it, once every 4 months, just to make the midpoint. And then you're developing a KSI-301 that may be more appropriate for once-monthly is not, in essence, introduce the idea like 2 separate products, 2 different formulations, 2 different brands, like how do we think about that?

Well, if you look historically, the other predicate molecules were approved in wet AMD first, and then a number of years later were approved in, say, DME or RVO and then earlier non-proliferative diabetic retina, whereas we have a different strategy, right? Our strategy is to run all the studies to read out at essentially the same time and to file them all into an initial BLA. So a tremendous amount of data, both safety data as well as efficacy and durability data will all be available at the same time when we file the BLA. And then at the time that we do a commercial launch. So we're going to have a tremendous amount of information. We're getting integrated like all of that information and think a little bit about median number of doses for example, and then use that to help us think about pricing, right? And then to think about that in the United States and on a global basis. I mean the good news is we're not in a rare disease. We're in very high prevalence disease. Populations are aging, and there's more and more diabetes. So the demographics are very favorable. This is a medicine that prevents and treats blindness. And it's differentiated, and I think it will show through its clinical data, the pivotals to be in a class of its own. Then the question is, well, where should pricing come out? And what fundamentally is going to be the tail that wags the dog kind of unlike pricing, right? And I don't think we know yet where our pricing should be. Certainly, we were interested to see the Biogen decision on their pricing. But I think we have a long time, and we'll also see what works for us, and choose to price. There's a lot of water under the bridge before we need to have those discussions. But I think we're going to have that very broad label. I don't think it's going to hurt us running DAYLIGHT. It's actually going to be just an additional piece of information. And I think health systems and payers are going to appreciate the philosophy that we brought, which is to bring a lot of information to the table when we engage in those initial discussions.

Okay. Fair enough. That insight is appreciated. I want to maybe spend the rest of our time talking about the competitive landscape because I think for investors who are trying to keep track of everything that's happening in the space. You mentioned faricimab. We've got a port delivery system. We've got a couple of gene therapy products. We've got some products that are TKI-based. Some have late-stage data, some don't. How do you, as a company, make a sense of kind of what's happening in the competitive landscape? And how would you characterize that competitive landscape changing over the past 6 to 12 months? And how could you see kind of depending on the data, how that evolves over the next 6, 12 months because it has been quite dynamic, to say the least?

Yes. Yes, I think it has been. Yes. Retina is a complex area. You really benefit from focus and attention, a high level of excellence in the work that you're doing, not just on those design decisions. I touched on it a little bit earlier. Design decisions are really, really critical as is manufacturing as is always true in biotech, you can't fix compromises that you made earlier. You can't fix those later. So you have to be real thoughtful. So I think it is a difficult area to work in. I think we really benefit from the focus and attention and the kind of the time horizon that we always brought to there in our decision-making. So we say that we make the long-term decision like every day. So there have -- so you talked about the port, faricimab, gene therapy, the TKIs, right, Beovu as well. A lot of sharks in the water. I think of it a little bit like -- we -- VIEW had the same problem really from the first 100 patients. And whether it's 1% or 2% or 3%, it didn't really improve, and they couldn't fix that. They kept pushing that can down the road, and they've gotten to a pretty bad place. The port system is a little bit like that in a way. It had 20-plus percent serious adverse events in their Phase III. I think a number of the physicians really like faricimab and sort of wonder in the context of faricimab really where is the place for the port. With our Phase Ib data, we brought 2/3 of the patients to 6 months. The port is bringing patients to 6 months but with indwelling device. So really, and mostly like previously treated patients that were shown to be responsive. So it's a little bit hard to know what is the perfect patient for the port. I think that TPD a little bit, faricimab is a nice product. I think the Phase III data cards that they turned were probably better than what people thought. If you talk to KOLs, what they say, about faricimab really as, well, it's a tiny bit better than EYLEA, but across every aspect. So it didn't achieve the superiority they hoped, right, through bringing another mechanism of action, right? They hope to show superiority in DME. They didn't do that. But in wet AMD, the vision is the same. Maybe it's a little more dry, okay, than EYLEA, could be. In DME, they tried to make a case for more durability and a little bit of long-interval dosing. It's a bit shallow, I think, is our view. They say a median number of doses of 8 in the first year and 10 for EYLEA. So it's pretty marginal on the durability actually. And their flutter and the CT is basically on the same interval as EYLEA. So it's really not a long-durability agent in DME. But incrementally, the physicians say it looks a little better. And I think it can be commercially like a strong product. And I think KSI will compete very effectively against faricimab is our view. And I think also effectively against EYLEA. So we're planning really with the big dogs in the space, LUCENTIS, EYLEA, faricimab, and that's really where the anti-VEGF biologics are. I think like I was trying to say and think a little bit earlier, is like, there's a lot of sharks out there, a lot of sharks in the water of retinal drug development. So gene therapy, I think the chickens come home to roost a little bit on that with some of that inflammation seen a long time ago, and eye doesn't like chronic inflammation. That's what we said. And I think that's why -- I think that's the conclusion. And I think for the TKI is, I guess, my view is, well, what problem are we solving actually? What is the patient set for the TKIs? Because if the concept is, they're a small molecule version of a biologic, we why do you need that, right, because the biologics work very well? Oh, well, maybe the rationale then for the TKIs as well, they have a broader mechanism because they are a little bit dirty in terms of the kinase inhibition. So they need a bit more receptors. So then they're for recalcitrant patients, right? They're for the patients that don't respond that well to anti-VEGF. Well, I mean, are they being explored in that population. Right now, what about the delivery challenges? And if you're worried about recalcitrant patients, well we have KSI-501, right, where we bring the anti-IL-6 and anti-VEGF. And the IL-6 inhibition isn't just about inflammation. IL-6 is a powerful cell mitogen. And so there's a lot of optimism that we have that maybe that 15% to 25% or 20% to 30% of patients who don't respond super well to anti-VEGF alone, like say, treatment naive wet AMD, maybe they'll respond really well to a dual inhibitor of IL-6 VEGF based on some of the surrogate marker data that's available coming out of some of the earlier predicate studies. So I think when you look at retina, it's a complicated area. It does require a lot of focus and attention, a lot of capital, don't make compromises. And ask the question of what's the philosophy of the design of your platform and your molecule, right? What are you trying to accomplish and what's your North Star? Do you have the capital to get there? And are you comfortable making the hard decisions that may be aren't popular, like, I guess, our DAYLIGHT study? Because we think in a medium-term time horizon, that's the right thing to do. And that's really the same thing as investing in manufacturing, which is what we're doing to be able to get millions of doses manufactured in a clean manner. And everything that you need to do to think about how do we build a company that can manufacture, design, develop, rebate, commercialize and retain our optionality up through some critical point, right? And then do you get acquired? Do we build commercial capability? Those are things that we don't have to address today because our current focus is really operational execution and focusing on the pivotal top line data readouts over the next 12 to 18 months.

Right. Thank you for that. We've got perhaps just a few more minutes left. And so with the bulk of my prepared questions being asked and very incredibly answered. Maybe just a few last housekeeping questions with regards to -- as you think about what your current cash balance is? And what you may have said about the current cash runway? Certainly, you've got a very broad development program that would require funding. And you've got a unique relationship with Baker Brothers or other affiliates. And so with that, can you talk about cash? And then just quickly, I know we've talked about it over the course of this fireside chat. But again, just pinpointing those next clinical development updates in terms of the trials that you're running?

Yes well, I think, John, our cash at the end of the last quarter is around $930 million?

Yes. We have about $900 million in cash currently.

Yes. So that's a lot of capital put to work to support the pivotal studies that we're running and to support the manufacturing scale as well as the pipeline. I think once you get into 2023, we think being post-BLA filing, we think about building -- beginning to build inventory actually from a commercial standpoint. So we have a lot of capital to do all of those things. And to run the right set of pivotal studies and to drive the pipeline to drive the right scale and manufacturing. So it's exciting to be, I think, in a good capital position at this stage of the company. From the standpoint of clinical data, I think, like I mentioned, DAZZLE first quarter of next year, Beacon tail end of Q2, hopefully, from RVO, GLEAM and GLIMMER and DAYLIGHT, let's say, in the fourth quarter of next year. Certainly, last patient, last visit. So bringing a lot of the manufacturing investments together at the same time as bringing those clinical investments together. Putting those into a complex but single BLA is our objective. So a lot of operational work, put our seatbelts on in the context of operational execution now through these pivotals and the manufacturing. And then next year, a tremendous year for top line data readout, really exciting. As a focused company in retina and ophthalmology, a tremendous potential to prevent and treat blindness. We're really excited to grow the company to continue to execute and to move through these next stages.

And maybe a last question that I've been asking the CEOs who have been part of my fireside chat. But as you see the company, say, in 5 years from now, if we're going to be doing this fireside chat in 2026, where do you see Kodiak? Obviously, you've got the visibility on potential filing time lines. But in 5 years from now, what do you hope to see from the company?

Yes. Wow. Well, I mean, I think my personal hope and I think our aspiration in a way is, why can't we be the Gilead of ophthalmology, to be honest? We don't, of course, need to have that level of success to deliver a tremendous mission for our patients and our clinicians. But I hope KSI-301 can be best-in-class and that we can be approved and broadly used across not just wet AMD, but change the game entirely for the treatment of diabetic retinopathy. DME and earlier NPDR, there's tremendous need there. There's an opportunity for more DME patients and more NPDR patients to come to the retina clinics. And our DME data is absolutely amazing and tremendous, and we're really optimistic about GLEAM and GLIMMER to bring a lot of patients to 6 months. That can't really change the game for patients. And then the earlier preventive work and earlier nonproliferative DR. Diabetes is still the leading cause of blindness in working-age people in the developed world, and KSI-301 can really change that. So that's really exciting to bring more DME patients and to think about commercializing and rebating and really think about how we can work with that clinical community and really be an ambassador as a retina franchise company, delivering more and more molecules, right, more and more science. So Kodiak should become hopefully more dominant in retina as a therapy area, whether we're alone or whether we're working with a partner, whether we're acquired, the goal is to have real impact for patients on a global basis. And we don't need to be all in on the ABC platform either because as we grow, become more valuable, right? And as we bring more science and more scientists, we have our eyes more broadly across other avenues, other vitalities. So eventually, gene therapy may be great and maybe will be the ones to develop that. Let's see. But for now, biologics are really where you want to be, and our ABC platform looks to be tremendously safe and having the impact across many diseases. And of course, our triplets, which is really an amazing new format, that merges small molecules and biologics. The bispecific antibodies or monospecific, right, like a 301 or KSI-501, probably bring novel small molecules that are mechanistic for inside the cell to bring other biologies and to really change the game in the other high-prevalence retinal diseases like dry AMD or the retinopathies or glaucoma. Single mechanism medicines for those diseases can have impact and are important for patients in the interim. But I think bringing these multi-mechanism modalities, nicely inside of that water structure of the polymer with very high loading like hundreds of copies of small molecule per antibody, hit it inside the water structure of that macromolecular water, is tremendously exciting. And I think we can have even more tremendous impact. So we have a wonderful platform, the first agent that can have a big impact on the 2 leading causes of blindness, right? Macular degeneration in old people and diabetes and working-age people. Then we have 501 that maybe can have a big impact in more refractory patients in wet AMD and DME. And then we have 601 in the triplets coming behind for, say, dry AMD and glaucoma. So it's a tremendous scientific potential with a good philosophy of design and development. So let's hope things turn out well. And like I said, where could we be in 2026? Well, let's pull that curve forward and let's try and build the Gilead of ophthalmology for the benefit of patients. So maybe in 5 years, we could be here with some of the same team. And we'll just focus on execution with the right strategy in mind.

Well, it's a very provocative and enticing vision of the future of the company. We wish you luck on that process and look forward to seeing progress as well. And thank you, Victor. Thank you, John, as well, for joining us. And I want to thank the audience for joining us as well. So with that, have a great rest of your day, and have a great rest of the conference. Thank you.

Thanks a lot.

Thank you.

Thanks.