Kodiak Sciences Inc. Q4 FY2023 Earnings Call

Good day, and thank you for standing by. Welcome to the Kodiak Sciences Business Update webcast and conference call. At this time, all participants are in listen-only mode. After the speakers' presentation, there will be a question and answer session. Please be advised that today's conference is being recorded. I'd now like to hand the conference over to your first speaker today. John Borgeson, Chief Financial Officer. Please go ahead.

Thank you for joining our conference call and webcast to discuss recent business updates at Kodiak. I'm John Borgeson, Kodiak's Chief Financial Officer. Joining me today are Victor Perlroth, Chairman and CEO; and Pablo Velasquez Martin, Senior Vice President of Clinical Research and Development. After our prepared remarks, we will open the call for Q&A. The webcast portion of this call contains a slide presentation that we will refer to during the call. Those following along on the phone who wish to access the slide portion of this presentation may do so on the investors and media section of our website. An archive of this webcast will be available shortly after the event on our website. We'd also like to remind you that remarks made on this call today include forward-looking statements about Kodiak that are subject to risks and uncertainties and which are outlined on this slide. A more complete description of these and other material risks can be found in Kodiak's filings with the Securities and Exchange Commission, including its 10-K for the year ended December 31st, 2023, which has been filed with the SEC, and we encourage you to read those carefully. I will note that Kodiak does not undertake any obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise. Now I'm pleased to turn the call over to Victor Perlroth, Kodiak’s CEO. Victor?

Thank you, John. Good afternoon, everyone. Thanks for joining us. I trust many of you have read Kodiak’s press release from this morning announcing our recent business updates together with our financial snapshot. The goal for today's discussion is to provide additional context and color around some of our most recent activities and our going forward plan, and we will welcome your questions at the end. We're a retina-focused company. Retina is a challenging area for innovation, but there should be an increasing return to focus in time and dedication. At Kodiak, we have a top 10 plus years of fine-tuning of our ABC platform in our company. Also, being able to listen and to have the courage to make the important course corrections needed to get us to the finish line with medicines that are meaningful for patients and therefore valuable. The sector is concentrated with only Roche and Regeneron as dominant players. There's room for another major player, and that remains our aspiration. We look forward today to providing you with the broad view. Today, we are at a point of departure, and we are in motion. We have a portfolio of three clinical programs. Two programs are ABC platform derived with its core science of durability, and one program is platform independent. We think this pipeline represents a healthy diversification, both in terms of opportunity and risk. For some of you listening today, you may say, 'I'm not smart enough to know whether Kodiak's ABC platform represents a disruptive innovation that can deliver for patients and frankly, for investors, or not.' For you, let us show you. But in the meantime, you don't have to believe in the ABC platform to recognize that KSI-101 represents itself a potential important new branded molecule for retina. Highly potent on two powerful mechanisms, for patients with inflammation and some residual fluid. We call it a greenfield market opportunity. In the program, building as it does already from the base of bioactivity efficacy and safety seen in the KSI-501 program, sharing as it does the same protein. Kodiak can be a tremendously successful company and investment opportunity on the basis of KSI-101 alone. But for ourselves, we are big believers also in our ABC platform. Why? Durability remains a key unmet need and you want durability for all patients, as an inception regimen, as a maintenance for treatment-naive patients and experienced patients. And you want the durability without sacrificing immediacy, potency, or safety. They say the real test is whether you give the drug to your mother or grandmother. At this stage, not being marketed, we provide our investigational medicines in the context of our clinical trials. But our design, we're proud of the ABC platform, our novel proteins, our bioconjugates, our underlying science and design for durability. Now, the important adjustments we've made to the tarcocimab product improve the manufacturability in a prefilled syringe and we believe may also enhance the utility of the product, which we have also already flowed into the KSI-501 manufactured material as well. We believe now is the time to implement these changes given the additional clinical studies we plan to conduct. The FDA has agreed that these additional clinical studies are sufficient to bridge the former material to the go-to-market material, which we'd like to commercialize going forward. Tarcocimab and KSI-501 represent state-of-the-art molecules. Based on our view of our data and these design enhancements, I believe they meet the grandmother test. When we look commercially, given the rapid pace now of our planned development for tarcocimab and KSI-501, there is commercial complexity, but we are the innovator here, and we believe there can be a strong demand for our medicines in their unique design, science and unique performance in the retina marketplace. Taking it back to the top level, across these three, what I call, late-phase programs, there’s also a significant amount of operational synergy in moving these three programs forward together. Where useful, we can even run them in the same study or studies with low incremental costs per group. So where are we today? Let's start with an overview; from a cash position, we have an attractive cash position today as of Q4. When we look at Kodiak, we see three late-phase programs, and our intention is to bring these three programs to meaningful inflections within our cash runway. For tarcocimab, we have three positive Phase 3 studies that have been completed in diabetic retinopathy, retinal vein occlusion, and wet AMD. We have a strong and consistent six-month durability signal and favorable safety seen across the pivotal program. We have regulatory alignment now that's been achieved on a bridging strategy for our go-to-market formulation. The Phase 3 study GLOW2 in diabetic retinopathy is now actively recruiting patients, and we've added as an additional arm tarcocimab into DAYBREAK to validate the durability in wet AMD to strengthen tarcocimab’s competitive position and to bolster our ex-US regulatory dossier. For 501, the Phase 1 study in DME met our objectives. We're developing it towards high-prevalence retinal vascular diseases to bring durability and the extra mechanisms to bear. We've created the enhanced formulation informed from tarcocimab’s commercial manufacturing scale-up with many potential benefits. We're in the process of gaining or finalizing FDA alignment on the design of the Phase 3 DAYBREAK study in wet AMD and targeting enrollment to start mid-year. For our diversified KSI-101 program, we're developing it in a new area, macular edema associated with inflammation. We see it as a greenfield opportunity outside the established anti-VEGF class and with risks and opportunities uncoupled from our ABC platform and from our other two molecules. A Phase 1b study is planned for the second quarter to identify two dose levels, which we will then rapidly progress into pivotal studies. We're currently in the process of gaining FDA alignment on the design of dual Phase 2b/3 pivotal studies, which are also planned for initiation this year. Turning to Slide 6. Tarcocimab is our most advanced program, and we're one successful trial away from filing for registration in a success scenario. In the trial GLOW2, it will be conducted in a patient population diabetic retinopathy where tarcocimab already showed a clear win in our GLOW1 study. GLOW2 is actively recruiting patients. At the same time, we plan to advance KSI-501 and KSI-101 rapidly into pivotal studies this year. The Phase 1 study of KSI-501 demonstrated positive signals in terms of efficacy and safety to support further development. We're in discussion with the FDA on the study design of the Phase 3 daybreak study in wet AMD and plan to initiate it as soon as regulatory alignment is achieved, targeting mid-2024. We also intend to advance KSI-101 into a Phase 1b dose-finding study in the second quarter this year to identify the two dose levels we want to use in our dual pivotals. Our goal is to have four pivotal studies ongoing later this year across the three programs. Two serve as a broad and powerful BLA for tarcocimab, two serve as a new and powerful BLA for KSI-101, and one is half of what's needed for a KSI-501 BLA. Turning to Slide 7. Now let's turn to our most advanced clinical program, tarcocimab. Tarcocimab is an anti-VEGF antibody biopolymer conjugate or ABC medicine built on the ABC platform to provide extended durability. It's been studied in six pivotal studies, three of which met their primary endpoints across the indications, diabetic retinopathy, retinal vein occlusion, and wet AMD. My view is tarcocimab can bring six-month durability to the majority of patients across these diseases, and we can achieve this as an initiating therapy, not a maintenance therapy, without leaving any patients behind irrespective of disease severity. That's the future as we see it. In our GLOW1 study in diabetic retinopathy, tarcocimab demonstrated for the first time among anti-VEGFs that six-month dosing can successfully treat DR patients by improving disease severity scores and reducing the risk of vision-threatening complications by about 90%. In our BEACON study in retinal vein occlusion, tarcocimab demonstrated we could bring all RVO patients to once every two-month dosing versus the current standard of care, which is monthly dosing. Importantly, in the second six months of the study, tarcocimab was studied head-to-head against aflibercept on the same individualized dosing regimen. Approximately half of tarcocimab treated patients were injection-free in the second six months compared to about a third of aflibercept treated patients. Over the entire one-year treatment, tarcocimab treated patients achieved comparable vision and anatomic outcomes with meaningfully fewer injections compared to aflibercept treated patients, five versus seven. Lastly, in our DAYLIGHT study in wet AMD, tarcocimab met its primary endpoints and demonstrated that intensive monthly dosing of tarcocimab was safe and well-tolerated. These are important studies in large indications. Nonetheless, in our tarcocimab program, they represent a point of departure, and the value comes when you finish things. To that end, as I mentioned, we have also made adjustments to the tarcocimab product that improve manufacturability and may also enhance the product's utility. The FDA feedback indicated that one additional successful pivotal study using the go-to-market material is sufficient to bridge the clinical scale material to the go-to-market material, not just to bridge our go-to-market formulation. As of today, we have three positive Phase 3 studies of tarcocimab in three different diseases and we will need one more successful pivotal study in one of these indications to file for approval. We plan to evaluate, turning to Slide 8, tarcocimab in two new Phase 3 studies, the GLOW2 study in diabetic retinopathy and the DAYBREAK study in wet AMD. We've obtained FDA feedback on the study design of GLOW2, and it is already actively enrolling patients. The idea behind GLOW2 was to create a very high probability of success study. Therefore, the study designed for GLOW2 builds from GLOW1, which I see as having a high real and perceived probability of success. Thus, from an investor standpoint, I don't think you need to wait around to see the results to have some early confidence. Additionally, after much consideration, we also intend to study tarcocimab as a second investigational arm in our wet AMD DAYBREAK study with three purposes. First, to demonstrate conclusively tarcocimab's durability in wet AMD. Second, to strengthen tarcocimab's competitive position, given the importance of wet AMD in the anti-VEGF market. Lastly, to bolster tarcocimab’s ex-US regulatory dossier. We're in the process of obtaining FDA feedback on the study design of DAYBREAK and hope to initiate recruitment by mid-2024. Turning to Slide 9. The GLOW2 study design builds from the successful GLOW1 study with the benefits of a third monthly loading dose at week four as highlighted on the slide. We believe that the three monthly loading dose regimen provides greater flexibility to patients and is a nice addition to our BLA package. The primary endpoint is the proportion of eyes with a two-step or greater improvement on DRSS at week 48, the same as GLOW1. Now let's turn to KSI-501, our second investigational medicine. KSI-501 is a first-in-class bispecific antibody biopolymer conjugate or APC that inhibits both IL-6 and VEGF. IL-6 is a pro-inflammatory cytokine and growth vector implicated in retinal vascular diseases. It is known to stimulate defective angiogenesis, both by upregulating VEGF and by VEGF independent pathways. It is associated with anti-VEGF treatment resistance as well as disease progression in AMD, DR, and RVO. KSI-501 is designed with three tiers of innovation. First, a two-target mechanism potently inhibiting both the dominant VEGF pathway and the IL-6 inflammation pathway. Second, the potential for six-month durability based on Kodiak's ABC platform. Third, an enhanced KSI-501 formulation informed from tarcocimab's commercial manufacturing scale. We believe these three tiers of innovation position KSI-501 well to address the unmet needs in high-prevalence retinal vascular diseases, such as the need to target disease mechanisms beyond VEGF and the need for extended durability. The KSI-501 program is the result of fine-tuning our ABC platform and company over the past 10 plus years. The program itself represents a fast forward in design, manufacturing, clinical planning, and operational expertise. Turning to Slide 11. This slide is a reminder of the substantial variability in response to today's anti-VEGF standard of care agents. Therefore, there is a need to bring additional disease mechanisms beyond VEGF into our therapies. As you can see from this data generated in our own pivotal wet AMD study, there is substantial interpatient variability in their response to anti-VEGF monotherapy, both in terms of visual acuity outcomes and fluid reduction. The significant proportion of patients underperforming in terms of vision and/or anatomical improvement compared to the mean highlights the necessity for additional mechanisms of action. We believe KSI-501 can play an important role here. Turning to Slide 12. The anti-IL-6 VEGF trap bispecific protein in KSI-501 has a unique design that enables it to potently inhibit one or more VEGF dimers and two IL-6 molecules simultaneously. The VEGF trap portion mimics the native receptor and binds multiple targets, including VEGF-A, VEGF-B, and placental growth factor. The anti-IL-6 antibody binds IL-6, thereby inhibiting both IL-6-trans and cis signaling by its binding to soluble and membrane-bound IL-6 receptors respectively. Inhibition of IL-6 blocks IL-6 mediated inflammation and immune activation and normalizes blood retinal barriers. Turning to Slide 13. We conducted a Phase 1a/1b type study in DME patients that is now complete. The study was a multiple ascending dose study in DME patients, both treatment-naive and pretreated patients. Four dose levels were studied in the Phase 1 trial. Each subject received three monthly doses and was followed for 24 weeks, which allowed us to evaluate the safety, tolerability, and bioactivity signals of KSI-501. We are pleased with the Phase 1 study results, where KSI-501 demonstrated strong visual acuity gains in both treatment-naive and pretreated DME patients, and these effects were sustained over the 24-week study period. It also demonstrated meaningful CST reductions in patients. Though this was a small patient sample size, we should be cautious not to over-interpret the results but rather focus on the essential signals that suggest this could be a molecule with meaningful therapeutic effects. The Phase 1 study also demonstrated that repeated monthly dosing of KSI-501 was safe and well tolerated. Overall, we think the Phase 1 study results support further clinical development of the KSI-501 program. We’re planning to advance KSI-501 into a Phase 3 study in wet AMD, called DAYBREAK later this year. Preclinical and clinical evidence supports the role of IL-6 in choroidal neovascularization, both in terms of driving disease pathogenesis and mediating treatment response to anti-VEGF agents and disease reactivations. We believe the three-tiered innovation designed into KSI-501, as mentioned before, namely the bispecific mechanism of action, the potential for six months durability based on the ABC platform, and the enhanced formulation, position the molecule well to address the unmet needs in wet AMD. The DAYBREAK study is intended to be a non-inferiority study that evaluates the efficacy, durability, and safety of KSI-501 and tarcocimab in wet AMD against aflibercept 2 mg. Both KSI-501 and tarcocimab will be dosed on an extended regimen of every four to 24 weeks, while aflibercept 2 mg will be dosed per label. The study will use the go-to-market formulations for both KSI-501 and tarcocimab that improve manufacturability in a prefilled syringe and may also enhance the utility of the products. We are currently in conversation with the FDA to obtain feedback on the study design for DAYBREAK and intend to initiate enrollment as soon as alignment is achieved, targeting mid-2024. Turning to Slide 16. Now we'll turn our attention to our third investigational medicine, KSI-101. This is the unconjugated protein portion of KSI-501, with the same anti-IL-6 and VEGF trap design and its unique features as we mentioned previously. This is a greenfield development opportunity for us, as it focuses on a market outside the established anti-VEGF market. KSI-101 is also independent from the ABC platform, with opportunities and risks uncoupled from the platform, which presents a healthy diversification. With its bispecific anti-inflammatory mechanism of action, high potency on both targets, and high formulation strength at 100 mg per ml, this is a powerful medicine, and we are exploring it in difficult conditions, what we call the uveitic complex of diseases that have macular edema as a hallmark, which consists of retinal edema and inflammation, and for which no intravitreal biologic therapies exist today. Current treatments for patients with macular edema associated with retinal inflammation show limited efficacy and may have many undesirable and potentially serious side effects. Treatment is generally non-specific, such as steroids and immunomodulators. There is only one approved biologic therapy, adalimumab, which is an anti-TNF alpha agent that is administered systemically, but it is also associated with limited treatment efficacy and serious side effects. There are no approved intravitreal biologic therapies today that target the underlying disease mechanisms. We believe this disease area is primed for a powerful, safe, and effective branded intravitreal biologic therapy to change the treatment paradigm. We plan to advance KSI-101 into a dose-finding Phase 1b study in the second quarter of this year to identify the two dose levels to progress into our pivotals. We are currently in the process of obtaining FDA feedback on the design of the pivotal program here for KSI-101 and hope to initiate two Phase 2b/3 pivotal studies later in 2024. Turning to Slide 19 and summarizing. In summary, we're excited to be on plan to advance our three clinical programs into Phase 3 studies in 2024, with GLOW2 for tarcocimab already enrolling, DAYBREAK up next, and bringing forward two of our molecules, KSI-501 as well as tarcocimab, along with dual pivotals for KSI-101 in planning. We are at a point of departure, and we are in motion. We have our eyes focused on delivering meaningful Phase 3 BLA-facing value inflection points within our current cash runway. Now we will open the floor to analysts for questions.

Our first question will come from Michael Yee from Jefferies.

This is Xiao Jin Wei on the line for Michael Yee. I have two questions regarding the KSI-501 bispecific pivotal study. I noticed that there are multiple arms for tarcocimab and KSI-501 in that study. I wonder if those patients would be randomized to each of the arms at the beginning or they would be treated as needed and given more flexibility with the dosing, and what's your estimate of the sample size? My second question is, can you clarify if you plan to include data from the DAYBREAK, the pivotal study for KSI-501 as well, in the same BLA filing of tarcocimab?

To clarify the question, it's about the DAYBREAK study, which is planned to include aflibercept as the comparator and then to include arms for tarcocimab as well as KSI-501. The first objective of including an experimental arm with tarcocimab in the study is that it's economically and operationally efficient for us. Additionally, yes, the data from the study will be included in the BLA filing for tarcocimab. Our objective for the timing of the DAYBREAK study and the GLOW2 study is for those studies to finish at approximately the same time and to contribute to the same BLA. That’s an important element. On the study design for DAYBREAK, we are still in discussions with FDA to ensure that we arrive at a study that meets our needs. Our objective is to include durability for both tarcocimab and KSI-501, and to transition from monthly dosing all the way through to six-month dosing to showcase the power of our ABC platform medicines regarding immediacy and powerful durability.

Does that mean that you would have multiple arms of tarcocimab as well as KSI-501, and that essentially requires a big study for you to run?

We haven't disclosed the precise design of the study yet. Within ophthalmology, the regulatory landscape is evolving. One of our core objectives for the DAYBREAK study is that it be cost-effective. Kodiak has substantial experience running many of these studies in large diseases in retina. Obviously, we'll aim not to have more groups than we need to achieve our objectives. So let’s stay tuned and see where we come out on the study design.

Our next question comes from the line of Michael DiFiore from Evercore ISI.

A few questions from me. Number one, regarding the upcoming Phase 3 DAYBREAK trial. I know the design is currently being finalized, but could you provide any color on what dose will be used? A follow-up question to that is how is the enhanced KSI-501 formulation different from the formulation used in the recent prior Phase 1 DMA study?

For the DAYBREAK study, the plan is to use a similar 100 microliter volume. Therefore, it will be driven by the formulation strength of the formulations themselves. Both the tarcocimab and the KSI-501 formulations are 50 mg/mL strength. For this pivotal at 100 microliters, there will be 5 milligrams each. Each of those molecules will be in their go-to-market formulation or commercial scale up formulation, which includes adjustments from what was tested previously with tarcocimab in our pivotal program and also what was used in the Phase 1 program for KSI-501. So we are at an important point of departure as we step into these new studies with these adjusted and enhanced formulations, and we're excited to showcase what these molecules can do in these next set of pivotals.

My follow-up question is to clarify why exactly tarcocimab is being added as an active comparator in the DAYBREAK trial. Is it correct to assume that the FDA is not requiring this and that Kodiak is proactively doing this to have dosing flexibility on the label?

We struggled somewhat with what to do to finalize the tarcocimab program, and it took several months to determine our plan. On one hand, we wanted to lean into additional work in wet AMD, as that represents a large market segment for anti-VEGFs. On the other hand, we didn’t want to run a study where different stakeholders or investors would be concerned about the probability of success due to excessive dependencies on the outcome. Ultimately, we decided to run the GLOW2 study as our core study for approval for tarcocimab, which is designed for a high probability of success, given its similar framework to GLOW1, which was successfully executed. Additionally, we decided to incorporate an experimental group into the pivotal study we wanted to run for KSI-501. Economically, this is a cash-efficient approach. Having opted to run that extra wet AMD study, we will end up with the DAYLIGHT study as a successful study, and we hope the DAYBREAK study will achieve success for tarcocimab. Our overall package should include five successful pivotal studies for tarcocimab while also checking a box for KSI-501, marking the first of its two pivotal studies necessary for approval. This approach reflects Kodiak's broader strategy of advancing three late-phase molecules through pivotal studies starting imminently.

And our next question will come from the line of Anupam Rama from J.P. Morgan.

This is actually Malcolm on for Anupam. So just one from us. What is being assumed in terms of milestones between now and your cash runway into 2026?

Certainly, the completion of the two tarcocimab pivotals as well as the completion of the 501 pivotal. We're currently discussing with the FDA about the design of the Phase 2b/3 studies for KSI-101, and depending a bit on those designs and how they influence enrollment, we're hopeful to get those studies out within that timeframe as well.

Our next question comes from the line of Andrea Tan from Goldman Sachs.

Two for us please. As a follow-up to a prior comment, recognizing that the potency remains the same between the two formulations that you have. Can you share what data you’ve seen that supports durability of the original formulation will carry over as you transition from the biopolymer conjugate to now a mix of the conjugate plus free antibody?

We believe that disease variability in patients drives durability more strongly than the amount of conjugate that we have. For example, in our Phase 1b study, we tested 2.5 mg versus 5 mg of fully conjugated material with very little distinction on the durability results we observed for both doses. As we slightly reduce the conjugate amount to allow for a broader level of free protein, we anticipate bringing the benefits of both worlds into the tarcocimab and KSI-501 formulations without impacting durability and thereby creating a powerful medicine for patients.

My second question is to ask for more details regarding the Phase 1 data that you have seen in DME for the 16 patients from the Phase 1. Could you share what gives you the confidence to move directly from that in the 16 patients to a Phase 3 trial now in wet AMD?

The important point about the Phase 1 study with KSI-501 was to gauge safety and bioactivity in terms of vision and OCT. Given the overlap across retinal vascular diseases and existing agents, we started in DME due to predictable responses in bioactivity and safety, using that as a foundation to guide development into various diseases. Four main factors inspire confidence for moving directly into Phase 3 for wet AMD based on our KSI-501 Phase 1: First, the durability profile of the platform; second, the dual mechanism of action targeting both VEGF and IL-6, the latter being a known culprit in suboptimal responses and disease reactivation in wet AMD; third, our enhanced formulation; and fourth, the decade of design, manufacturing, clinical, and operational experience we have, which includes three INDs, three clinical molecules in different phases, two first-in-human studies, and eight clinical trials, seven of which are pivotal. We're not starting from scratch, and we're also considering exploring KSI-501 for DME and RVO in the future.

Our next question will come from the line of Gena Wang from Barclays.

Victor, based on current data, do you believe 501 is better than tarcocimab? Also, for DAYBREAK, aside from being cost-effective to avoid conducting an independent Phase 3 study for tarcocimab, will you design the study to demonstrate any clinical benefit differences between 501 versus tarcocimab?

I don't think it’s critical whether tarcocimab or 501 is definitively better than the other. There's clearly an opportunity for a twice-yearly anti-VEGF agent, and tarcocimab just needs to be pushed over the finish line; we will gauge physician interest. By running GLOW2 and including that tuck-in group in the DAYBREAK study for wet AMD, we’ll collect useful data for physicians regarding tarcocimab. Our objective is not to directly show a distinction between tarcocimab and 501 in the DAYBREAK study. If 501 even shows some favorable trends against aflibercept or tarcocimab, we see that as very positive because we would outperform those agents with our own. The KSI-501 program will indeed require a second pivotal study. At what point should we initiate it to ensure the molecule has a path to market? If both molecules perform favorably as we hope, with tarcocimab and 501 demonstrating differentiated durability, it's a problem we’d be pleased to have.

Our next question comes from the line of Ellie Merle from UBS.

It’s Sam on for Ellie. We just have two questions. First, where do you think about how IL-6 inflammation is relevant in this space?

We believe that IL-6 is broadly relevant within both high-prevalence diseases that make up the anti-VEGF market, and it holds significance outside of that, into what we term the greenfield area for macular edema and inflammation. This distinction is why we have two different molecules engineered for both contexts. KSI-101 allows us to leverage highly potent dual mechanisms for a direct and effective biological intervention. We are excited about targeting IL-6 since it plays a critical role in driving macular edema and inflammation. Within retinal vascular diseases, inflammation is clearly a significant contributing factor. I think the primary concern in drug development is how pivotal programs must demonstrate efficacy, and we do not need to deliberate on this for several years in Phase 2 trials while dissecting the subsets that exhibit significant inflammation. Instead, our plan is to execute non-inferiority pivotals to gain approval based on our clinical expertise, then conduct later studies to tie patients with high inflammation to improved efficacy outcomes, thus avoiding delays.

As a quick follow-up for DAYBREAK, you mentioned dosing KSI-501 every four to 24 weeks and dosing aflibercept according to the label. What is your perspective on the recent FDA draft guidance regarding the use of a comparable dosing regimen in terms of dosing frequency with the active comparator?

That’s a good question. We’ve been in constant communication with the agency for all three clinical programs and we will confirm the study design once we have all the necessary information. Kodiak has historically driven innovation with study designs through the FDA, and other companies have often followed our approach. At this stage, we're in discussion and will determine where we end up.

Our next question comes from Daniil Gataulin from Chardan.

I have one on KSI-501 in wet AMD specifically for the second pivotal study. Are you guiding for timelines on when you plan on starting that trial, and will that also include tarcocimab or do you plan to wait and generate tarcocimab data from DAYBREAK first before initiating the second study?

We haven’t disclosed nor do we have a complete plan for the second study in wet AMD. We know that we need one for KSI-501 to obtain approval in that indication. However, we haven't thought through whether it will be sequenced or will overlap with the two studies.

What do you think are the potential consequences if tarcocimab does not succeed in the DAYBREAK study?

We believe that tarcocimab can be an important medicine for patients with wet AMD. Rather than solely relying on the results of the DAYLIGHT study with monthly dosing, we found it makes sense to demonstrate it by incorporating a full group in DAYBREAK. If the DAYBREAK study did not meet its endpoint, physicians might hesitate to utilize it in wet AMD, and the possibility of not gaining approval could arise depending on outcomes from two unsuccessful studies in wet AMD. Thus, it represents a calculated bet, but one made confidently based on our comprehensive data review, the adjustments to our go-to-market material, and our experience from six prior pivotal studies. We’re excited to run tarcocimab in DAYBREAK, anticipate the data, and hope to share that with the community where it proves powerful.

Thank you. I’m not showing any further questions at this time. I would now like to turn it back to our CEO, Victor Perlroth, for any closing remarks.

I think we're done. Thanks very much. We look forward to people digesting all of this new information about Kodiak and our plans. We look forward to the next sets of information, especially on the new study designs as we finalize them. Thanks.

Thank you for your participation in today's conference. This concludes the program. You may now disconnect. Everyone, have a great day.