Kodiak Sciences Inc. Q1 FY2020 Earnings Call

Good afternoon and welcome to Kodiak Sciences First Quarter 2020 Business Highlights Conference Call and Webcast. My name is Chelsea, and I will facilitate the audio portion of today’s interactive broadcast. At this time, I would like to turn the conference over to Mr. John Borgeson, CFO of Kodiak. Sir, please begin.

Thank you for joining Kodiak Sciences’ business highlights conference call. I’m John Borgeson, Kodiak’s Chief Financial Officer. Joining me today are Victor Perlroth, Chairman and CEO, and Jason Ehrlich, Chief Medical Officer and Chief Development Officer. After our prepared remarks, reviewing updates to our business, we will open the call up for analyst 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 Events and Presentations section of our website. An archive of this webcast will be available on our website soon after the conclusion of this call. I would like to remind you that remarks made on this call today include forward-looking statements regarding our business, financial guidance, the initiation, enrollment, conduct, and results of clinical trials, our regulatory strategies, our research and development activities, risks related to our business, and certain other business matters. A more complete description of these and other material risks can be found in Kodiak’s filings with the Securities and Exchange Commission, including Form 10-Q for the quarterly period ended March 31, 2020, which was filed with the SEC yesterday. Kodiak does not undertake any obligation to update publicly any forward-looking statements, whether as a result of new information, future events, or otherwise. During the call today, we will review the impact of COVID-19 on our ongoing operations, provide corporate and clinical updates, describe our upgraded KSI-301 pivotal program, and discuss how we will execute on that program to meet our 2022 Vision. While this call is intended to focus on reviewing operational highlights and not so much to discuss financials, I would like to take a few moments to discuss the strength of our financial position, as was detailed in our 10-Q published yesterday. On the heels of our successful fundraising efforts in December 2019, we ended the first quarter of 2020 with over $430 million in cash, cash equivalents, and marketable securities. During the first quarter, we posted a net loss of $24.4 million, which includes non-cash expenses of about $6 million. Based on our current projections, we estimate that our cash runway will be sufficient to execute our current operating plans into 2022, including through the top-line readout of the DAZZLE study. How far our cash extends into 2022 is dependent on a number of factors, including how aggressively we choose to invest in pre-commercial preparedness. As we move forward with our 2022 Vision of a single BLA application covering the key retinal indications, we also expect to have access to the second tranche of $125 million from our royalty transaction. I will now turn it over to Victor, who will review business highlights from this past quarter.

Thanks, John. Good afternoon, everybody. Thanks for joining us for this first quarter 2020 business highlights webcast. We wanted to hold the call to discuss the recent business highlights including progress with the development of our pipeline, and to be clear in terms of how we’re managing through COVID-19 and its impact. I’m proud of the dedication of our team, the Kodiak employees, and our Kodiak community more broadly as we all navigate the challenges of the COVID-19 pandemic, and which the team continues to deliver on our mission of helping patients with very serious retinal diseases. To date, we’re seeing minimal disruption from COVID-19. Our labs are operational. From a manufacturing and clinical standpoint, we’re proceeding and proceeding well. In DAZZLE, as we’ll discuss in more detail, patient missed visit rates are less than 5%, and clinical trial sites continue to enroll new patients. This is a testament to the serious diseases that we’re attempting to treat here at Kodiak and it’s a vote of confidence from the patients, physicians, and study sites who are partnering with us to advance KSI-301 towards the market. As John mentioned, removing non-cash charges, our monthly burn-rate this past quarter was only $6 million per month. So with over $430 million in cash and equivalents at quarter-end, we remain on a very strong financial footing. Now, as of today, we did delay the initiation of our next set of KSI-301 pivotal studies by 1 quarter. We were planning first in human in the June/July timeframe, and we’ve now shifted that planned first-in-human for the additional pivotals for KSI-301 to the September/October timeframe of this year. Now, we’re using this time wisely, not just to assess with physicians and our business partners how best to minimize the impact of COVID-19 on clinical trial conduct, but, 1, to optimize our pivotal study designs; 2, to engage with regulators on upgrades to the pivotal program; and 3, working with our partner companies, particularly on manufacturing and clinical, in terms of execution, and the structure of our relationships there, to put them in the best possible structure for this next stage or phase of escalation and acceleration of Kodiak’s growth. Importantly, our 2022 Vision towards a BLA filing in the key retinal disease indications remains intact. And as I mentioned, we have taken good advantage of the additional quarter, this additional time, to upgrade our pivotal study plan for KSI-301, and Jason will discuss that in more detail. In summary though, we now intend to conduct 2 Phase 3 studies in diabetic macular edema, and 1 study in wet AMD, our ongoing DAZZLE study; and 1 study in retinal vein occlusion. And 1 study in non-proliferative diabetic retinopathy. There are multiple reasons for this shift into 2 DME studies and 1 RVO, from our earlier plan, where we had proposed 2 RVO studies and 1 DME study. On the operational front, with this new plan, we expect a more predictable execution of the studies, and of the pipeline and the plan. In other words, we expect the clinical operations component of the DME studies to be faster, simpler, and more predictable. We also believe we’ll be able to run studies in fewer countries, and fewer research sites, which is an important simplification. This returns predictability to the program and it’s particularly important in light of COVID-19, especially in the ex-U.S. geographies. Further, we prefer to shift resources on the margin into the higher prevalence, higher unmet need disease of DME, rather than RVO. DME remains the leading cause of blindness in working-age adults in the U.S. and the EU. Importantly, the data that continues to emerge in our Phase 1b study remains very consistent with observations that we shared in February. We look forward to providing the next R&D update on the Phase 1b data in July of this year. That will either be virtually at the American Society of Retina Specialists meeting; either in person at the meeting, or if that goes virtual, either through one of our partnered clinicians, or through a Webex similar to this. Operationally, we’ve taken steps in line with guidance from the CDC and the State of California, to protect the health and safety of our employees in the community. And Kodiak, as a company, we’ve implemented remote work arrangements for non-essential employees since March 17. Notably though, as I mentioned, we continue to be operational in our laboratories. I’d like to pause here and hand the call over to Jason. Jason, could you talk about how we’re managing ongoing clinical trials through COVID-19, and also introduce the new KSI-301 pivotal study program?

Well, thanks, Victor, and good afternoon to everyone. Thanks for joining us. Over the last few months, the Kodiak team has been focused on ensuring both patient safety and data integrity in our ongoing KSI-301 clinical trials. The Phase 1b study, which is in patients with DME, RVO, and wet AMD; and then DAZZLE, our pivotal study in wet AMD that compares KSI-301 to standard of care aflibercept. We’ve made numerous enhancements into the ongoing study execution and planning, really to help ensure the safety of patients, physicians, study site staff, and Kodiak operations team members as much as possible. Some of the specific actions that we’ve taken include the use of remote study monitoring, temporarily increasing study site budget overhead rates, to help with additional time that’s required for the studies and to procure the appropriate PPE and so on, providing additional transportation service options for patients to make sure that they can safely and comfortably attend the study visits. We’ve also been focusing new patient enrollment only at the study sites that have appropriate backup resource plans in place, and importantly, where the local COVID-19 situation allows. We’ve been actively monitoring the ongoing trial participation. We’re really being as proactive as we can, both with the study sites, our corporate partners, such as our CRO and logistics vendors, as well as regulatory authorities to safeguard study integrity and promptly respond to potential disruptions. In light of the efforts undertaken by our investigators and their teams as well as our team and the high risk of permanent vision loss that’s presented by the retinal diseases that we’re trying to treat with KSI-301, I’m happy to say that existing patients continue to participate with very few missed visits to date, less than 5% missed visits in overall March and April, and new patients continue to be enrolled in the ongoing DAZZLE study in the U.S., again, where it makes sense based on the local-COVID situation. Maybe just some additional color on efforts that retina specialists and their staff are making to continue to see patients who need anti-VEGF therapy, as well as the seriousness of those diseases. The pattern that we see in our studies is also reinforced by EMR data that’s collected by Western Health and others that’s been published recently. You may have seen that overall ophthalmology outpatient visits in the U.S. were down by some 80% in March and April, and retina specialty clinics themselves saw declines of over 45% in patient visits in March and early April. But the proportion of those visits that were for anti-VEGF administration was up substantially. Meaning that the retina specialists were prioritizing patients who need anti-VEGF therapy and they continue to do so. This highlights the importance of KSI-301, a safe and long-acting therapy that can help keep patients on therapy for in between less frequent office visits, and potentially improve real-world outcomes over time, particularly in settings where it may become more difficult to readily access the clinic such as this pandemic. As of May 8, 2020, 245 patients have been enrolled into DAZZLE, and through most of the first quarter recruitment into the study was very robust. The reflection I think on the enthusiasm for KSI-301 on the part of investigators and patients as well as underscoring the unmet need for long-acting therapy. Currently, we do not intend to pause screening or enrollment into DAZZLE in the U.S.; we are seeing slower patient enrollment compared to the 50-plus patients per month that we saw in February and March. As part of the COVID measures that I discussed earlier, we encouraged study sites to prioritize participation of currently enrolled patients over enrolling new ones if necessary, for example, due to staffing limitations or site closures during the pandemic. As of late April, the number of weekly new patient screenings and enrollment at DAZZLE sites in the U.S. is increasing. We also see that in the Western EHR data published last week showing that retina clinic volume is starting to turn around in the U.S. In the first quarter of 2020, we have actually activated DAZZLE study sites in Europe. But due to the pandemic, we deferred the start of patient screening. We now expect to begin patient recruitment activities at certain sites in Europe in the second quarter of 2020, again, guided by the local COVID-19 situation. So with respect to DAZZLE, I’m pleased that the independent data monitoring committee met in early May and recommended that DAZZLE continue without modification. The IDMC is the group responsible for safeguarding the interests of DAZZLE study participants, assessing safety during the trial and monitoring overall study conduct. We’re grateful for their support and recommendation. Then regarding the rest of the pivotal program, we’re monitoring both the progress and impact of COVID-19, as Victor mentioned, we delayed the initiation of our next set of KSI-301 pivotal studies for DME and RVO into September and October of this year versus the previously planned June or July timeframe. We’re still evaluating whether we can initiate the NPDR study on the same time frame, we’re expecting the potential for a one to two quarter additional delay in the NPDR study start, due to the pandemic resulting in the deferral of diagnosis and follow-up in NPDR patients. Those patients have a lower overall disease severity than patients with wet AMD, DME, and RVO. Additionally, I’d like to note that our supply chain and manufacturing activities remain intact. We don’t currently anticipate disruptions to our supply of KSI-301 due to the pandemic. Moving away from COVID-19, let me turn the call back to John to go through some additional recent business highlights.

Thank you, Jason. As many of you may remember, we announced an agreement for the sale of future royalties of KSI-301 for $225 million on December 1, 2019. During the first quarter of 2020, we closed on the first payment under the agreement, receiving $100 million on February 4, 2020. I’d also like to say a few words about our Board of Directors. In the last several months, we’ve made 2 strong additions to our board with the addition of Dr. Taiyin Yang, and most recently, Charlie Bancroft. Taiyin currently serves as Executive Vice President of Pharmaceutical Development and Manufacturing at Gilead and brings deep experience and leadership with commercial manufacturing and quality operations. Charlie was formerly the Chief Financial Officer at BMS and brings a wealth of pharmaceutical, commercial, and financial experience. The combined experience of Taiyin and Charlie supplements an already deep and well-rounded board with knowledge that will be instrumental as we accelerate our planning towards BLA and commercial launch. Lastly, I would like to quickly comment on the continued progress with our IP portfolio. Most recently, we received full registration of our trademarks Kodiak and Kodiak Sciences with the U.S. Patent and Trademark Office for our exclusive use, further establishing our name recognition as a leader in research and development of medicines to treat and prevent retinal diseases. With that, let me turn back to Jason to further elaborate on more clinical highlights.

Thanks, John. With respect to the Phase 1b study, we presented updated safety, efficacy, and durability data from the ongoing Phase 1b trial of KSI-301 at the Angiogenesis meeting back in February. We believe that the data continues to support the highly differentiated anti-VEGF Generation 2.0 profile of KSI-301. We plan to continue presenting data updates from the Phase 1b study throughout this year, and if meetings or congresses are canceled due to COVID, or become virtual, we would anticipate one or more virtual R&D webinars where new data will be presented. We’re pleased with the data that continue to be generated in Phase 1b. We look forward to providing the next important R&D update in July, either at the ASRS meeting, depending on whether and how that meeting occurs, or else in a virtual R&D webinar in a similar timeframe, as we collect additional follow-up data on patients in the Phase 1b up to 9 months, 12 months, and beyond. The focus of those presentations will start to turn towards long-term outcomes and the durability. We look forward to sharing those upcoming data with you over the course of the year, starting with the presentation in July. We’ve further amended the Phase 1b program to include an additional 18 months of treatment and follow-up per patient for a total of up to 36 months. We’re now approaching 100 patient years of exposure with KSI-301 and continue to be very pleased with the safety profile that we’re seeing. Moving on to talk about the KSI-301 pivotal program, following our communications with the FDA at the time of the end of Phase 2 meeting as well as subsequently, we further upgraded the pivotal study program. We now intend to conduct 2 Phase 3 studies in diabetic macular edema to provide the mutually-confirmatory studies required by the FDA for initial demonstration of safety and efficacy, and then 1 pivotal study in wet AMD with the ongoing DAZZLE study, one in retinal vein occlusion, and one in non-proliferative DR without DME. By conducting the paired studies in DME, we’re able to generate additional data on the safety, efficacy, and durability of KSI-301 in this area of high unmet need and commercial opportunity while also narrowing the number of sites and countries that are required for successful enrollment of the entire pivotal program. We expect the majority of research sites to be located in the U.S. with contributions from certain countries in Europe, China, and potentially Israel. Given that we’re currently seeing continued new patient enrollment and low missed visit rates in DAZZLE in the U.S. through the pandemic, we believe that refocusing the KSI-301 program and narrowing our focus in terms of number of sites and countries will really help us minimize uncertainty with respect to trial conduct during and through the pandemic towards our 2022 vision. A few additional specific reasons for running the paired DME pivotals, and one RVO as opposed to be the other way around, include fewer countries and sites needed for 2 DME studies versus 2 RVO studies, which will help with both the cost and logistical burdens of opening and supporting trial sites that might only be needed to participate in the RVO studies. Next, we’ll have better overall oversight of operational execution since all of the sites that are running our studies can concurrently enroll naïve patients in wet AMD, DME, or RVO. We think we’ll have a lower probability of COVID-related disruptions over time since the scope of countries and sites is more focused. As Victor mentioned, there’s a higher unmet need in DME compared to RVO. There’s a marginal if any increase in overall trial execution costs, given the similar timeframes for 2 DME studies versus 2 RVO studies. On top of those really operational considerations, we remain quite pleased with the DME clinical data that we’re seeing in the Phase 1b study. We want to align the area of greater clinical data generation in DME, given the large number of diabetic patients and the higher unmet need compared to RVO. We’ve been asked if we’re going to make a change to the pivotal program plan, why make it 2 DME studies instead of 2 wet AMD studies. From a statistical perspective, the standard deviations are narrower in DME, which has a non-inferiority margin of 4.5 letters in DME for a comparison to aflibercept whereas it’s 4 letters, a little bit narrower in wet AMD. So when you add those things up, an additional wet AMD study would require at least 100 more patients than the DME study, which would be a fairly substantial cost difference. Cost is not the only driving factor, of course. When we look at what’s happening in the community with many people unemployed due to COVID, and potentially losing access to their healthcare, working-age people have the opportunity to participate in a clinical trial, where they can have access to high-quality care from a retina specialist. So the 2-year deletion of the study, I think that’s also important, and we believe that 2 DME studies should recruit relatively quickly, especially in this environment. Patients with wet AMD, given that they are quite elderly, are at the highest risk of COVID-related complications. Ultimately, I want to highlight the acceleration of our bispecific conjugate the KSI-501 program. KSI-501 inhibits both IL-6, interleukin 6, as well as VEGF. IL-6 blockade is being explored as a novel therapeutic strategy in patients with severe and critical COVID-19 disease. VEGF is also a potent inducer of vascular permeability and edema, which may play a pathological role in COVID-19 driven lung dysfunction. We’re advancing the GMP manufacturing for the OG2072 protein, which may enable an assessment of systemically administered OG2072 in patients with worsening COVID-19 disease. Notably, we’ll also be able to use GMP material for the KSI-501 toxicology program and have a more predictable IND submission and First in Human timeline for the bioconjugate KSI-501 in 2021 in patients with retinal vascular disease featuring an inflammatory component. I’ll hand the call back to Victor to wrap up our remarks and before we get into Q&A.

Thanks, Jason. I think it would be helpful if we reviewed our upgraded KSI-301 clinical plan and portfolio quickly. This refined plan illustrates the upgraded program. We’re working to finalize the study protocols across the program, including the number of subjects with each study being powered really to 90%-plus. This program feeds into our 2022 BLA filing plan. It’s nice to see this refinement of our clinical plan, which provides the 1b ongoing, the DAZZLE study continuing to enroll, and our plans to initiate the paired DME and RVO pivotals in September, hopefully, and then the NPDR study, which we’d like to bring on board in parallel. But as Jason mentioned, it will depend a little bit on the clinical community’s guidance in terms of whether we’re credibly going to be able to bring those patients in during the pandemic and/or what’s happening with the pandemic come Q4, into Q1 of next year. Moving into the next slide, we’re continuing to finalize the pivotal study designs in the program, which is guided by the Phase 1b study design and the data, which directly educate our Phase 3 pivotal study designs. The data helps us design and lock-in the protocols in our pivotal program. We believe we’ll see a very high degree of confidence in being able to hit the primary endpoints in these studies and to clearly differentiate KSI-301 on durability. We think these pivotal programs, each study alone and even more powerful together can support a very highly differentiated target product profile, what we increasingly call the Generation 2.0 profile, as we shift that treatment interval within each one of these diseases. We believe we’ll also be entering a marketplace in 2023, given this differentiation. We’re actively assessing the manufacturing capacity desired to supply the first years of launch, including the branded agents but also the opportunity for KSI-301 of capturing monthly Avastin patients and injections as well. This summary allows us look at each of these 4 indications for KSI. It also helps us think about the target product profile that we may end up with in terms of non-inferiority of vision in the core pivotals as a primary endpoint. We believe this lends a high overall probability of success to the medicine in each one of the pivotals as we think about the complexity of the market that we’re entering. Looking ahead, we’ve achieved quite a lot in 2019 and are excited to present additional data this year from our Phase 1b, detailing the durability of KSI-301. We expect to present data at the ASRS virtually or through a Kodiak-hosted virtual event in July. Additionally, we’ll continue to execute on our DAZZLE study in wet AMD patients and move that execution into Europe and ex-U.S. We’ll activate the full KSI-301 pivotal program in the additional indications. In 2021, we’ll continue to report data from our Phase 1b study and execute on our clinical operations with the potential DAZZLE pivotal study readout. 2022 is a massive year for the company, as we detailed. Our vision is to report multiple pivotal study top-line readouts in 2022 and submit that single BLA in the big indications. In 2023, we’re planning for regulatory approvals and commercialization of KSI-301 in key geographies. In summary, we’re very pleased with the business highlights for the first quarter and the first part of the second quarter of 2020. We believe we are well positioned and we’re looking forward to accomplishing our goals for the remainder of the calendar year 2020. We’ll now open the floor to analysts for questions.

Yes, sir. Our first question will come from Anupam Rama with J.P. Morgan.

Hey, guys. Thanks for taking the questions. This is Matt on for Anupam. So first off, well done with being so agile around 301 development to be efficient and keep timelines for Vision intact as much as possible; great job there. I guess, one thing we’ve been trying to think about is a little more forward-looking and relates to competition from additional biosimilars across indications, and what these retinal markets might look like when 301 potentially launches. If you could just comment on how you expect market dynamics to play out, that would be really helpful. Thanks.

Sure. Well, Anupam, we are focused right now on the acceleration in the clinical execution, and making sure that we have the right pivotal study program, right, that the designs of those pivotal studies are educated from the Phase 1b so we can have a very high probability of success in those studies, which we think we will. The endpoints and the durability that we’ll be able to show are really going to be meaningful. What we like to think of it as this generation 2.0 profile is that we’re going to be shifting that distribution with non-inferior efficacy and safety but shifting the dosing interval, that distribution substantially to the right in each of these indications versus EYLEA. What’s special about the data we’re showing, and predicated on the underlying design of the molecule, is having a lot of whitespace between us and EYLEA. We think that that’s really important to be differentiated and not coming out as incremental. If we can do that, we’ll be in a very strong position. Regarding the complexity of the market in 2023, 2024, 2025, we believe there will be important biosimilars for the branded agents. Lucentis biosimilars will uptake Lucentis’ share, and EYLEA biosimilars, whenever they come out for example in the U.S. market, will likely eat EYLEA share. We’re getting smarter on some of this and believe that KSI as a branded molecule has a lot of incentives that will drive physicians and payers to support KSI, ASP plus 6%, for example. We don’t see many incentives for leading players like Regeneron to compete with biosimilars on price. It’s important to note biosimilars in retina will need to be wary and excel in manufacturing consistency. The key takeaway is that we even believe there’s the possibility for us to be able to eat Avastin’s share, if we really bring a molecule like KSI with the important target product profile benefits and differentiation. We think we’re making right decisions in terms of our pivotal study protocols and designs, such that when we come through this program with all of these indications in parallel, we’ll be executing in a very thoughtful manner to compete for branded share. Additionally, we’ll have to assess together the percent of the branded market we should plan to capture from a manufacturing standpoint over the first 3 years so we can effectively address the projected demand.

Great. Thank you very much, guys. Thanks for taking the question.

Thank you. Our next question will come from Michael Yee with Jefferies.

Hey, guys. Thanks for the update. Thanks, Victor. Two questions. One is you commented on enrollment in the press release. I thought this was pretty important, given it’s kind of a gating factor to getting data. Can you just comment about what gives you confidence in the timing for completion of enrollment this year in AMD? What are you seeing in April and May, the shape of the curve? What gives you that confidence to talk about these timelines? That would be helpful. The second question is contingent on those timelines that you’ve laid out. I think we’re all very excited for the data on AMD in 2021, potentially. But is there any chance given all the things that have gone on or shifted that you look back at that potential interim analysis that’s built into it and say, hey, what are the factors that we could look at this and don’t have to wait till the end of 2021? Maybe just talk about that and whether that’s totally off the table? Thanks so much.

Right. Thanks, Michael. I think on the wet AMD timeline, we were enrolling 50 to 60 patients a month in February and March. We have close to 50 sites activated in the United States. Our objective is to have another 50 sites activated globally, for a total of about 100 sites across the program. Even through the end of March and April, enrollments were 25-plus patients a month. We expect that to increase certainly through the end of this year. We’re not going to fall on the sword over finalizing enrollment in DAZZLE this year. In fact, we put potential timelines in our communications. The reason isn’t that we cannot ramp the enrollment through, but we also want to be thoughtful about the percent of patients in our pivotal program that we want ex-U.S. Given dynamics in wet AMD and DME, we could rapidly enroll those studies completely in the United States, but we don’t want to do that. We must determine what percent of these patients should come from outside the U.S. Given slightly more complex dynamics in Europe. Hence, we’ll be monitoring fairly carefully. Last patient in’s could be a little longer in the high-level but versatile enrollment. So could this also drive top-line data further into the early 2022? I don’t see that as a negative. We think it’s important to focus on the ongoing trajectory of enrollment, and how many patients we need to enroll; and with these 250 patients enrolled, that begins to be interesting.

Great. Thank you very much, guys. Thanks for taking the question.

Thank you. Our next question comes from Maxwell Skor with Morgan Stanley.

Hi, thank you. This is Max Skor on for Matthew Harrison. Could you comment all about regarding the re-dosing criteria for the Phase 3 trials? Will it be different in the Phase 1b trial? And in any way could it alter the probability of success? Thank you very much.

Sure. Jason, would you want to handle that across the portfolio?

Yeah, sure. For DAZZLE, we tightened up the criteria a bit between the Phase 1b and DAZZLE. The different purposes of these studies reflect this. The Phase 1b is exploratory to help us understand the medicine's performance in the clinic across these diseases. The pivotal study is a non-inferiority study against an active comparator. The criteria in DAZZLE for determining when someone should be retreated focuses on patients on 12, 16, or 20-week dosing going forward. While in Phase 1b, we focus on just regroups. Now, that being said, if you overlay the DAZZLE criteria on top of the wet AMD patients in Phase 1b, it looks very favorable. For instance, at around weeks 12, 16, or essentially at 20 weeks, a good number of those patients achieved relatively favorable outcomes. So as we look towards the DME study, we haven’t disclosed the specific criteria yet, but the overall design I think will be similar to DAZZLE, where EYLEA is on a fixed regimen while the KSI regimen will allow flexible dosing between 2 and 6 months. So we’ll tighten those criteria a little bit, most likely, to balance durability versus non-inferiority comparison. We believe the DME data are favorably supportive of the regrouping criteria we’ll be deploying.

Thank you. Our next question will come from John McNeil with Goldman Sachs.

Hi, guys. I’m actually dialing in on behalf of Graig Suvannavejh. Just a quick one from us. How sustainable do you think that $6 million monthly burn rate is? And how could that evolve over the course of the year?

The rationale for mentioning that burn rate was to emphasize that even if COVID were to get worse, Kodiak has the ability to hibernate our operations for an extended period without compromising our existing studies. However, we expect that burn rate to grow substantially as we initiate new pivotal studies, ramping up over the summer targeting the September start. We anticipate major expenses associated with the BLA-related manufacturing activities as we prepare for market. As we assess how far our existing cash of approximately $430 million will go, we can provide guidance into 2022. The extent of our runway into 2022 depends on our enrollment rate, which will subsequently drive costs. Manufacturing scale-up for the pivotal program will influence our cash needs as well.

And if I could maybe get one more. How do you think about – I know you talked enrollment a lot, but if enrollment rates did sort of surprise even further to the downside? Would you consider looking to recruit treatment-experienced patients? How do you feel about how going to market potentially on data only from treatment-naive patients might impact initial uptake?

We feel comfortable going into treatment-naive patients. The predictability allows us to extrapolate the Phase 1b situation into our pivotal designs. We believe that we’ll recruit enough treatment-naive wet AMD patients, and DME patients, as a premier anti-VEGF biologic. The community of retina specialists is excited about participating in our studies. For RVO, interest in our agent is present, but the overall prevalence is lower, so we were thinking that we may have to go to more countries. But we believe our new plan has delivered on a number of logistical efficiencies. We’ll ensure we can recruit effectively without looking to treatment-experienced patients at this time unless we need to broaden our label to better address reimbursement concerns.

Thank you. Our next question comes from Robyn with SunTrust.

Hi, guys. Thanks for taking my question. I guess, everyone is asking about biosimilars all the time. But I was just thinking, given Beovu, and by the way, my two daughters are going to make an appearance on this call; I promise you. But thinking about the fears that people talk about both on the investment side and maybe concerns in this pivotal community about inflammation. How in your thinking about developing your clinical trial plan did you think about maybe alleviating those concerns in a clinical trial setting versus having people say, well, I’m kind of nervous in the real world, if I see some more events? Did that impact how you think about your trial design or how you plan to address it? Do you think it’s even needed? And then I have a couple of follow-up questions about the bispecific drug. It sounds like it could be in the clinic. When could it really go into patients, and are you hitting as much – absorbing as much IL-6 as like an average IL-6 drug alone? Do you have a sense of that? And third, probably a really stupid question; so it sounds like you could actually apply it in your BLA. Would you do all three indications, RVO, DME, and AMD all at the same time in a BLA? Is that possible? Thank you.

Hi, Robyn. Your first question revolves around whether there’s a new safety environment for new anti-VEGF because of what happened with Beovu. It’s worth considering that the safety events were previously observed. If you look back at some of those FDA databases from as early as 2015, you’d find reports of retinal artery occlusions at low percentages with existing agents. So we’re trying to show that we are not suffering from the same baggage in terms of the design and complexity of underlying biology. At the same time, we're gathering further confidence through ongoing studies, and we’ll want to continue to present the clinical data transparently without delay while we assess how our agents perform in a clinical context.

Yeah. I think Victor covered that well, Robyn. Regarding OG2072, I see that as a unique opportunity for our development program moving into COVID-19, particularly regarding inflammation and cytokine release syndrome, working closely with IL-6 and VEGF inhibition. Notably, it’s important to inspect what happens with vascular permeability caused directly by the virus or cytokine release. If we can establish a strong production process through GMP, our planned studies could potentially yield meaningful results. We aim for the bioconjugate to support key hypotheses about efficacy as it relates to retinal vascular complications. As for the BLA, I believe submitting all three indications at once is feasible. FDA has indicated they appreciate getting all the safety data at the time of review. Thus, we will begin conversations with EMA to align expectations. It’s vital to get it in writing for an ideal timeline.

I completely agree with Jason. Our alignment with both FDA and EMA will be key as we develop a beneficial and safe clinical profile for the anticipated market entry.

Thank you. Our next question comes from Gena Wang with Barclays.

Thank you for taking my questions. I have three questions. The first one also follows up on a single BLA filing. I understand you talked with the FDA. With that 1 wet AMD trial, 2 DME trials, and 1 RVO trial was that agreed upon with the FDA? And what is the EMA feedback? My second question regarding the RVO study is what will your thoughts be on the patient sample between BRVO and CRVO? My third question is regarding the 5% less than missed visits. Just wondering how you collect the data afterwards? How do you analyze the data, and how would that impact the clinical endpoint performance?

Right. Jason, can you take that?

Sure. Regarding the FDA, we’re quite comfortable with where we are. We have received clear feedback supporting our pivotal plan. The RVO study will stratify randomization between the two different types; BRVO and CRVO. BRVO is more common, whereas we plan to ensure a minimum cap on the number of CRVO patients is adequately represented. For missed visits, if that’s really one visit, that’s scattershot over time, then those data can be analyzed statistically. Ideally, the study should be adequately powered to withstand reasonable rates of missing data as well. Most modern statistical methods handle this routinely, allowing us to adjust without materially affecting study results.

Moreover, when we analyze our ongoing studies, we believe we can withstand a higher missed visit rate as well.

Thank you. Our next question will come from Matthew Luchini with BMO Capital Markets.

Hi, good afternoon, and thanks for taking the question. So a couple from me, I guess, first with regards to the revised DME and RVO study timeline, beyond the broader COVID environment, are there any other factors that could impact the start of those trials from the new September/October timeframe that you’re putting forward? Secondly, just to make it explicit, with a single RVO study, the plan is to still get a broad RVO label as opposed to something indication-specific to either BRVO or CRVO. Lastly, I wanted to just revisit manufacturing. If you could just remind us where you are today versus what you think you need for the revised pivotal program and where you hope to be over the next, let’s say, 12 to 18 months as these studies are starting to read out. Thank you.

Based on the information we have today and the decisions we’re making, we feel good about targeting a September/October first in human for the new program. We believe we can leverage DAZZLE framework to the same sites for smoother rollout of the additional studies. Since we have CTAs approved in many regions of Europe, we’re ready to proceed smoothly. Regarding RVO, we’re keen to have both BRVO and CRVO in our pivotal study; we’re in good shape there. On the manufacturing side, the process has to address clinical demands. Our aim is to scale production without complications. Our current scale is 1,000 liters, and we’re looking to transition to 6,000 to 10,000 liters for the eventual commercial market. We’re focused on conducting scale-up validation processes.

Great. Thank you for all the color.

Thank you. Our next question will come from Zegbeth Jallah with Roth Capital.

I just have a quick question regarding the expectations in terms of the longer-term data from the amended Phase 1b study. What are you hoping to see from that data or what are you hoping that investors would focus on in that next set of data? Any learnings in that that you could apply to your pivotal? I’m curious to know how you came up with the idea for OG2072 for COVID-related diseases. Can you elaborate on any of the synergism between that program and KSI-501?

We're keen on focusing this year on what we call the durability of the durability. The early Phase 1b study looked at overall safety, and how patients responded during the loading phase. Now, we want to see how those patients operate beyond that, observing when they get retreated and tracking if they require retreatment sooner or later. Furthermore, we want to see how different patient diseases ultimately perform with KSI-301. This long-term data will assist in understanding how the medicine behaves over time and we'll plan to share that information transparently. Regarding OG2072, it should be noted that it was designed in response to some of the increased focus on certain inflammatory pathways, including cytokines driven by COVID-19. We’re observing serum data to better inform our assessments on patient responses in this aspect.

The synergy we’re seeing with KSI-501 relates to the potential interaction existing from co-targeting IL-6 and VEGF in terms of inflammation and vascular permeability. This is particularly relevant in the context of COVID-19. It’s still early on, but as we continue our comprehensive data collection, we may uncover additional mechanistic insights alongside our primary goals.

Thank you. Speaker, at this time there are no further questions in the queue. I’d like to turn it back over for closing remarks.

Thanks, everybody, for participating. I hope this provides you with an up-to-date view of Kodiak and the activities for the remainder of this year. Thanks so much. Bye.

Thank you, ladies and gentlemen. This concludes today’s teleconference. You may now disconnect. Thank you for your participation and please enjoy the rest of your day.