Kodiak Sciences Inc

NASDAQ:KOD

Earnings Call Transcript 2020-Q1

[Operator]

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. [Operator Instructions] At this time, I would like to turn the conference over to Mr. John Borgeson, CFO of Kodiak. Sir, please begin.

[John Borgeson, Chief Financial Officer]

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 in 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 on our current operating plans into 2022, including through 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.

[Victor Perlroth, Chairman and Chief Executive Officer]

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 team continues to deliver on our mission of helping patients with very serious retinal diseases. So to date, we’re seeing minimal disruption from COVID-19.

Our labs are operational. And from a manufacturing and a 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 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, in particular, 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 a 2 Phase 3 studies in DME, Diabetic Macular Edema, and 1 study in wet AMD, our ongoing DAZZLE study; and 1 study in RVO. 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 clin-ops component of the DME studies to be faster, simpler and more predictable.

And 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. And we look forward to providing 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; in other words, either in person at the meeting, or if that goes virtual, either through one of our partnered clinicians, right, or through a Webex similar to this.

Operationally, we’ve taken steps in line with guidance from 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?

[Jason Ehrlich]

Well, thanks, Victor, and good afternoon to everyone. Thanks for joining us. Yeah, so 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.

So 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. So some of the specific actions that we’ve taken include the use of remote study monitoring, if temporarily increased 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.

And 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. So we’ve been actively monitoring the ongoing trial participation. And 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.

And 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 to do so.

Maybe just some additional color on efforts that retina specialists and their staff are making to try to continue and 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. So 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. So meaning that the retina specialists were prioritizing patients who need anti-VEGF therapy and they continue to do so.

So I think this really highlights the importance of KSI-301, a safe and long-acting therapy can help keep patients on therapy for in between less frequent office visits, and potentially improve real world outcomes over time, particularly in the setting where it may become more difficult to readily access the clinic such as this pandemic.

So then back to DAZZLE then, 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. So currently, we do not intend to pause screening or enrollment into DAZZLE in the U.S., but 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 issued guidance encouraging 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.

And then as of late April, the number of weekly new patient screenings and enrollment at DAZZLE sites in the U.S. is increasing. And I note that we also see that in the Western EHR data that was published last week showing that retina clinic volume is starting to turn around in the U.S.

On the European side, in the first quarter of 2020, we have actually activated DAZZLE study sites in Europe. But then due to the pandemic, we defer the start of patient screening. But we do now expect to begin patient recruitment activities at certain sites in Europe in the second quarter of 2020, again, as guided by the local COVID-19 situation.

And then finally, with respect to DAZZLE, I’m pleased that the independent data monitoring committee met in early May and recommended that DAZZLE continue without modification. As you know, the IDMC is the group responsible for safeguarding interests of DAZZLE study participants, assessing safety during the trial and monitoring overall study conduct. And we’re grateful for their support and as well as their recommendation.

So then turning to the rest of the pivotal program. In the interest of monitoring the progress and impact of the COVID-19 pandemic, as Victor mentioned, we delay 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 without DME study on the same timeframe, we’re expecting the potential for a one to two quarter delay – additional delay in the NPDR study start, due to the pandemic resulting in deferral of diagnosis and follow-up in the NPDR patients. As you know, those patients have a lower overall disease severity than patients with wet AMD, DME and RVO. So more on this in a few minutes.

Additionally, I’d like to note that our supply chain and manufacturing activities remain intact. And we don’t currently anticipate disruptions to our supply of KSI-301 due to the pandemic.

Moving away from COVID-19 then, let me turn the call back to John to go through some additional recent business highlights. John?

[John Borgeson, Chief Financial Officer]

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 in Chief Financial Officer at BMS and brings a wealth of pharmaceutical, commercial and financial experience. The combined experience of Taiyin and Charlie supplement an already deep in a 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. Jason?

[Jason Ehrlich]

Thanks, John. So with respect to the Phase 1b study, we presented updated safety, efficacy and durability data from ongoing Phase 1b trial of KSI-301 at the Angiogenesis meeting back in February. And we believe that the data continue to support the highly differentiated anti-VEGF Generation 2.0 profile of KSI-301. Now 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.

So as Victor mentioned, we’re pleased with the data that continue to be generated in Phase 1b. And 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 is a virtual R&D webinar in a similar timeframe, and 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 of the durability if you will. So we look forward to sharing those upcoming data with you over the course of the year, starting with the presentation in July.

And then furthermore on the Phase 1b, again based on positive feedback from investigators, and a desire to continue to generate long-term safety and efficacy outcomes data with KSI-301, we 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. And I note also that in the Phase 1b study alone, 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.

So then moving on to talk about the KSI-301 pivotal program, following our communications with FDA at the time of the end of Phase 2 meeting as well as subsequently, we further upgraded the pivotal study program. And as Victor mentioned, we now intend to conduct 2 Phase 3 studies in diabetic macular edema to provide the mutually-confirmatory studies required by FDA for initial demonstration of safety and efficacy, and then 1 pivotal study in wet AMD with ongoing DAZZLE study, one in retinal vein occlusion and one in non-proliferative DR without DME.

So 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’s required for successful enrollment of the entire pivotal program. So 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 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, I think we’ll have better overall oversight of operational execution essentially all of the sites that were running our studies and can concurrently enroll naïve patients in wet AMD, DME or RVO. I 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, and then it’s a marginal if any increase in overall trial execution costs are given the similar timeframes for 2 DME studies versus 2 RVOs.

And then, 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. And 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 there, as compared to RVO. Now, we’ve been asked if we’re going to make a change to the pivotal program plan, why make it 2 DME studies as opposed to 2 wet AMD studies.

And we think 2 DME studies’ makes more sense for a couple of important reasons. First is, from a statistical perspective, the standard deviations are narrower in DME, and a non-inferiority margin is 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 now would be a fairly substantial cost difference. Cost is not, of course, really the only driving factor or a driving factor.

When we look at what’s happening in the community with so many people who are unemployed due to COVID, and potentially losing access to their healthcare, working age people the opportunity to participate in a clinical trial, where they can have access to high quality care to a retina specialist, so the 2-year deletion of the study, I think that’s also important, and that should – so we believe that the 2 DME studies should recruit relatively quickly, especially in this environment.

And also wet AMD patients, given that they are quite elderly or really almost at the highest risk of COVID-related complications. So to the extent that those people are less willing to go to the physician, again, we think focusing the 2 studies on DME makes a lot of sense.

So then, finally before I hand the call back to Victor, one other quick note on the acceleration of our bispecific conjugate the KSI-501 program. As you may remember, KSI-501 inhibits both IL-6, interleukin 6 as well as VEGF. And 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.

So OG2072, which is the bispecific fusion protein that we used to build our ophthalmology product candidate KSI-501 binds with high affinity to both of its targets simultaneously, both IL-6 and VEGF. And it shows some quite synergistic inhibition of those mechanisms in vitro. So we’re advancing by 6 months, the GMP manufacturing for the OG2072 protein, which may enable an assessment of systemically administered OG2072 in patients with worsening COVID-19 disease.

And ancillary benefits of acceleration include the use of GMP material for the KSI-501 toxicology program and 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.

So now I’ll back to Victor to wrap up our remarks and before we get into Q&A.

[Victor Perlroth, Chairman and Chief Executive Officer]

Thanks, Jason. Yeah, I think it would be helpful if we reviewed our upgraded KSI-301 clinical plan in portfolio quickly, as illustrated on Slide 5. And this refined slide kind of brings together the upgraded program. And as we work to finalize the study protocols across the program, and including the number of subjects with each study of being powered really to 90%-plus.

So the Slide 5 shows our current view of the clinical studies, their timelines for first patient in and last patient in, the overall treatment duration, and a rough view into top-line data availability. And this program and strategy, obviously, feeds – are in parallel 2022 BLA filing plan. So it’s nice to see this refinement of our clinical plan, which the 1b ongoing, the DAZZLE study continuing to enroll, and our plans to initiate the paired DME and the RVO pivotals in September, hopefully, and then the NPDR study, we’d like to bring it on board as much 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. Okay.

So moving into Slide 6, what we call sort of the 4 pillars of retinal vascular disease. As we continue to finalize the pivotal study designs in the program, we’re of course guided by the Phase 1b study design, and the data, which directly educate our Phase 3 pivotal study designs. So in addition to informing the design of the pivotal studies, the Phase 1b data we’re generating is lending, we believe, 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.

So these pivotal programs, each study alone and even more powerful together can support a very highly differentiated target product profile, what we increasingly call sort of the Generation 2.0 profile, are real and obvious shifting of that treatment interval within each one of these diseases, right, further to the right, with a clear whitespace between us and our comparator, EYLEA.

So we’re also thinking through the marketplace that we’ll be entering in 2023. Given a highly differentiated profile, we’re actively assessing also the manufacturing capacity desired to supply the first years of launch. This assessment includes the branded agents, but also assesses the upside opportunity for KSI-301 of capturing monthly Avastin patients and injections as well.

So this Slide 6 is a bit of an important summary that lets us look at each of these 4 indications for KSI. Take a look at some of the data that’s been generated from the 1b. That data helps us design and lock-in on the protocols in our pivotal program. And lets us think a little bit 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.

And then, that core differentiation on durability, which is meaningful within each one of these indications. And we believe lends a very high overall probability of success to the medicine in each one of the pivotals come together into a very powerful profile, as we think about the complexity of the market that we’re dropping into.

Moving into Slide 7, really the pieces of our efforts across our pipeline are captured well, by this 2022 Vision slide. The breadth of the indications we’re evaluating in parallel, for KSI-301, really reaches a crux or an apex in 2022, with our plans for a single BLA to be filed for wet AMD, DME and RVO, and if we can get the NPDR studies going with the right level of enthusiasm and momentum potentially DR throughout.

So for KSI-501, we hope to benefit from this manufacturing acceleration that Jason mentioned, which also increases our confidence to achieve an IND and first patient in, in 2021. And we’re thinking about a combined sort of Phase 1a/1b type study for KSI-501, because that’s worked quite well, obviously, for the KSI-301 in terms of evaluation of safety, but also utility of the molecules.

And lastly, we’re seeing very interesting progress internally with our new triplet inhibitors, in this case, KSI-601, which we’re bringing together initially for dry AMD. And we’re also looking forward towards submitting an IND for that program in 2022.

Moving on to Slide 8, we’ve achieved quite a lot in 2019. So looking to 2020, we’ll be excited to present additional data as we mentioned from our Phase 1b, that details the durability of the durability of KSI-301, and we expect to present data at the ASRS virtually or through, as we mentioned, to Kodiak hosted virtual event. So we’re looking forward to July for that new data update.

We will continue to execute on our DAZZLE study in wet AMD patients and move that execution also into Europe and ex-U.S. And 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.

Furthermore, we’ll seek to advance KSI-501 into the clinic. 2022 obviously is a massive year for the company, as we detailed in the prior slide. Our vision is to report multiple pivotal study top-line readouts in 2022 and submit that single BLA in the big indications. In 2023 then, we’re planning for regulatory approvals and commercialization of KSI-301 in key geographies.

So in summary, we’re very pleased with the business highlights for the first quarter – in 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. Operator?

[Operator]

Yes, sir. [Operator Instructions] And our first question will come from Anupam Rama with J.P. Morgan.

[Matthew Bannon, JPMorgan Chase & Co.]

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, so good job there.

I guess, one thing we’ve been trying to think about is little more forward-looking and relates to competition from additional biosimilars across indication, and what these retinal markets might look like when 301 potentially launches. So if you could just comment on how you expect market dynamics to play out, that would be really helpful. Thanks.

[Victor Perlroth, Chairman and Chief Executive Officer]

Sure. Well, Anupam, I think, 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, both are educated from the Phase 1b, so we can have a very high probability of success in those studies, which we think we will. And also, that the endpoints and the durability that we’ll be able to show are really going to be meaningful.

And I think what I mentioned is we like to think of it as this generation 2.0 profile, which is 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 one of these indications versus, say, EYLEA. And I think what’s really special about the data that we’re showing, and I think predicated on the underlying design of the molecule, right, is really having a lot of whitespace between us and EYLEA.

So we think that’s really important to be really differentiated and not coming out as incremental. If we can do that, we believe we’ll, first of all, be in a very strong position, right? What’s the complexity of the market, like in the 2023, 2024, 2025 timeframe? We believe, as we’ve mentioned, that biosimilars will be important for the branded agents. So Lucentis biosimilars will be Lucentis’ share.

And EYLEA biosimilars, whenever they come out exactly, for example, in the U.S. market, will likely eat EYLEA share to some degree. We’re getting smarter, I would say, on some of this I believe, in a way the retina marketplace is like a spec pharma, with high concentration. We believe that KSI as a branded molecule, there are a lot of incentives that will drive the physicians for sure, but maybe even payers to support KSI, ASP plus 6%, for example.

And we don’t see a lot of incentives for, say, leading players like Regeneron to really compete, say, with biosimilars on price. And, of course, biosimilars in retina are going to have to be more cautious and take things to a higher level of excellence in terms of manufacturing consistency. So those are a lot of words. I think the key 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 this important target product profile benefit and differentiation.

And then, vis-à-vis Lucentis and EYLEA, we think there will be an incentive to go with an attractively priced KSI-301 molecule for retina docs, who can bring a better molecule for their patients and perhaps make more money with our branded molecule. So we think we’re going to get smarter, as we continue to build this kind of pre-commercial kind of capability and knowledge and investment for Kodiak. But we think for right now, we’re making all of the 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 and fall into the market, that we’re doing it in a very thoughtful manner that we can compete and access branded share.

And a key component of all of this is well, what percent of the branded market do we think we should plan to capture from a manufacturing standpoint, in years 1, 2, and 3. And I think we hope that’s going to be a big number. And so, we’re working from the manufacturing standpoint, to be able to service that.

[Matthew Bannon, JPMorgan Chase & Co.]

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

[Operator]

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

[Michael Yee, Jefferies Financial Group, Inc.]

Hey, guys. Thanks for the update. Thanks, Victor. Two questions. One is you commented on enrollment in the press release. And 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? And what gives you that confidence to talk about these timelines? That would be helpful. And then, second question is contingent on those timelines that you’ve laid out. I think we’re all very excited for the data for AMD in 2021, potentially.

But is there any chance given all the things that have gone on or shifted that there is a chance 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? Is that something that’s still technically possible? Thanks so much.

[Victor Perlroth, Chairman and Chief Executive Officer]

Right. Yeah. Hey, thanks. 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 by and large activated globally, right, for a total of, say, 100 sites across the program.

We even through, let’s say, end of March and April, enrollments were, say, 25-plus patients a month. And 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. I think if you look at what we’ve put is we kind of put potential, and the reason isn’t that we could not – we could actually jam the enrollment through I believe with – done in a thoughtful and safe manner. It’s just we also want to be thoughtful about what percent of patients in our pivotal program, do we want ex-U.S., because in wet AMD and DME we could rapidly enroll those studies completely in the United States.

But we don’t want to do that. And we have to make a determination, is it going to be 15%, 20% or 25% of these patients in these studies that we want to have from the ex-U.S. site. And so, given slightly more complex dynamics in Europe, we’re going to be monitoring that fairly carefully. And so, in the end, we may hold the studies open in terms of last patient in, a little bit longer to bring up the ex-U.S. component.

So that could drive top-line data for, say, DAZZLE further into, I guess, that would be like early 2022. And then, that sort of means that this whole pivotal program would sort of be converging in terms of top-line data coming out of multiple studies with very quick succession. We don’t see that really as a negative. So, okay, how does that impact our view of looking at an interim kind of data analysis?

I think with the current – we were surprised pleasantly I think that physicians continued – wanted to continue to enroll patients in our studies, let’s say, in March and April, and that we were able to successfully do so. So – and we see things opening up a little bit. And with enrollment shifting up and our desire to begin enrolling and recruiting, randomizing patients in Europe, starting almost immediately, I think.

So things look up. I mean, if things were to take a very nasty tumble in terms of COVID-19, right, and enrollments went to even worse than they were in March and April, then I think we could revisit the idea of some of sort of interim, because we’re close to 250 patients enrolled, so at a one-to-one randomization of like 125 patients per group, that begins to be sort of interesting.

But I think we don’t see that today that things are getting worse. We think, overall, it’s opening up a bit for us that we should see enrollment rates, go north, certainly north of where we are today at 25 to 30. And as we activate ex-U.S., I don’t know exactly what monthly number we’ll get to.

So I think as long as things continue to have a reasonably upward trajectory, right, the concept of like we’re very well capitalized now, we don’t need the interim as a financing catalyst. And rather, we’re really focused on running these studies in parallel and driving towards that top-line data. And we think that will be really powerful and I think we want people to focus on.

Look, what do people think is the probability of success of our molecule based on the Phase 1b data, right, that’s hitting the endpoints in terms of non-inferiority of efficacy of Vision, right, and with a fundamentally differentiated durability. What do people think that PTRS is for our molecule in these studies? And how do people think about the receptivity, right, of clinicians and the marketplace to our molecule?

And I think the answer, hopefully, is that we have a very high PTRS, unless we get hit by a bus. And if that’s the case, I think, maybe you want to get in early as a shareholder, because there’s not a lot of free float available. We’re tightly held to a large degree, and we’re very pleased with the ownership that’s really concentrated with a lot of long-only funds as well as early owners.

So if you’re excited about Kodiak and our profile, you want to be excited early, because otherwise you’re going to pay up later, if we’re lucky.

[Michael Yee, Jefferies Financial Group, Inc.]

Thanks. I appreciate the perspective.

[Operator]

All right, thank you. Our next question will come from Matthew Harrison with Morgan Stanley.

[Maxwell Skor, Morgan Stanley]

Hi, thank you. This is Max Skor on for Matthew Harrison. Could you comment all about the –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 POS? Thank you very much.

[Victor Perlroth, Chairman and Chief Executive Officer]

Sure. Jason, you want to handle that maybe across the portfolio of studies?

[Jason Ehrlich]

Yeah, sure. Thanks. So call it for DAZZLE, we tightened up the criteria a little bit between the Phase 1b and DAZZLE. And again, thinking about what’s the different purposes of those studies, right, the Phase 1b is an exploratory study to help us understand how the medicine is performing in the clinic in these different diseases.

And, of course, the pivotal study at the end of the day is a non-inferiority study against active comparator, right. So – and in DAZZLE, whereas in the Phase 1b the criteria are for determining when somebody should be retreated in DAZZLE and in – if I get to in DME, say, the criteria are more for regrouping, right, for in DAZZLE it’s the patient on 12, 16 or 20 week dosing on a going forward basis, right, not whether or not they get retreated.

So the purpose of the criteria is also a little bit different. Now, that being said, right, as we presented at Angiogenesis, if you overlay, the DAZZLE criteria on top of the wet AMD patients in the Phase 1b actually, it looks quite favorable, right, with the time to first meeting of those DAZZLE regrouping criteria was – at that time in that cohort like 12.5% of them would have met those criteria at about 12 weeks, 12.5% at 16 weeks, and everybody else like 75% of the patients like at 5 months or 20 weeks.

So that was – that’s quite exciting and reassuring. So, as we look then to the DME study, we haven’t disclosed the specific criteria yet. But I think the idea is – the study design fundamentally is similar to DAZZLE, where EYLEA is on a fixed regimen and the KSI regimen will be able to float in this case between 2 to 6 months, right.

So we will tighten, keep those criteria a little bit tighter, most likely, right? Again, for the same reason that you need to have the right balance of durability versus making sure that you meet your non-inferiority comparison in Vision. So – and we think that the DME data are very supportive of the regrouping criteria that we’ll be using.

And then in RVO, right, in the first six months, which is, for the primary endpoint, EYLEA’s monthly and the KSI could be one of the every 8 weeks fixed interval dosing after the couple of loading doses. So there is not really the same criteria in that first 6 months.

[Operator]

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

[John McNeil, Goldman Sachs & Co. LLC]

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 maybe evolve over the course of the year?

[Victor Perlroth, Chairman and Chief Executive Officer]

Yeah, I think the rationale for sort of mentioning that I think was more like, well, if COVID were to get substantially worse and things moved more into like a hibernation phase, what’s attractive about Kodiak is with the 1b study in DAZZLE, and in broader efforts in the labs and stuff like that, where we don’t have a very high like organic kind of burn rate. So we can hibernate running our existing studies for a very long time.

As we – but the pandemic and its impact, we’re seeing – we’re going to continue to have the ability to grow and accelerate an increase in momentum, right, with our plan, the 2022 Vision, as we kind of mentioned. So I mean that burn rate will grow substantially, right, as we initiate the new set of pivotal, the gearing up, the ramping up over the summer, and then the initiation of those studies targeting September, so it will ramp up substantially. And then, of course, in the background, we have – our manufacturing related efforts, which as I mentioned. There are a number of choices there as we think about, well, what level of – how many millions of dosage forms, do we think we want to be able to service to provide the market, right in 2023, 2024 and 2025, and as we do the validation work right at scale for our BLA.

So when John talks about, what how far is our existing, say, $430 million going to go. I think, we provide guidance definitively into 2022. How far into 2022 really depends on the rate of enrollment, which I think as we articulate on that one clinical timelines slide. We do expect fairly aggressive and appropriate, I think, enrollment, and that drives a lot of costs. And then as I said in the background, a lot of the BLA related manufacturing components. I think, at this stage right our pipeline which is – we are definitely focusing on as part of the broader remit as a retina high science company, KSI-501 will begin to have increased costs and then in the background eventually our triplets.

But as you know, the majority of our burn rate is going to be driven by – the – say, 2,000 plus patients in our pivotal program for KSI-301, and then in the proper manufacturing scale up and validation activities for that manufacturing component of the BLA. So that’s sort of more of a backward looking thing. And the burn rate will increase substantially, but that will be in context of appropriate execution. It’s just not like we’re sitting on top of a massive burn rate, and it’s all going to be driven by moving towards the objective of the 2022 Vision.

[John McNeil, Goldman Sachs & Co. LLC]

Okay. Thank you. 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 think at all about looking to recruit treatment experienced patients, and maybe kind of related to that, how do you think about how going to market potentially only data and treatment naïve patients might impact sort of initial uptake?

[Victor Perlroth, Chairman and Chief Executive Officer]

Right. I think, we feel really comfortable with going – following the framework of the anti-VEGF biologics of by and large going into treatment naïve patients. We like the predictability, right, of being able to extrapolate from the Phase 1b situation into our pivotal designs. I think, we feel very comfortable that we can get enough treatment naïve wet AMD patients and we feel very comfortable that we can get enough treatment naïve DME patients. We’re – I think a premier anti-VEGF biologic, as a branded agent, such that, we find them anyway the community of retina specialists is excited to participate in our studies, we believe, and to help bring those treatment naïve patients into our studies.

For RVO, it’s not as, though, clinicians are less excited about our agent in RVO, it’s just that the overall prevalence of RVO is lower. And so we were thinking, we were going to have to go to more countries. But I think by shifting the plan or upgrading it, as we say to 1 RVO study, and perhaps, BRVO, is higher prevalence than overall CRVO? So we think the new design has a number of like predictability and efficiency. So we think we’re going to get there with the treatment naïve patients. I think, do we think it may be useful to run, generate some data, right, in a quote unquote pivotal context using a treatment experienced patients. I think the answer is that we have had some discussions along that line. I mean, Jason, you may want to provide a little bit of commentary. I don’t think it would hurt, from a commercial standpoint, if we did not have that.

Having said that, it could make sense to the extent that we might want to have a fuller label, right, because to the extent that say, for example, in DME were going beyond 6 months in patients in terms of requiring retreatment in the 1b. Having said that, we’ve taken our pivotal study and we’re actually allowing some patients that they need to drop to 8 weeks. That’s not because, we think, that’s fundamentally required from the standpoint of the medicine, but we want to have a broader label so that physicians can get reimbursement and can use KSI across all patients.

And in wet AMD, where we have the q12 as the minimum, we do believe it could make sense to have some treatment experience, let’s say, q4 weeks and q8 weeks, and not to wait till after the BLA or after approval to run those studies, and doing those credibly in treatment experienced patients could be a way to generate some of that data to get that broader label.

And you may remember that in your 2 of DAZZLE, right, in the wet AMD pivotal, we’re actually re-randomizing the EYLEA patients one to one, so half of those people will go on q8 week KSI such that we can begin to generate. And in a way that is sort of a defined treatment experienced population. So we’re doing it in a variety of different ways that I think are thoughtful and that we’ll – or keeping our kind of our eye on what we need from a label, and a market, and a commercial standpoint. Jason, did you have any quick comment on that? A good question.

[Jason Ehrlich]

Yeah, Victor, I think you covered it really nicely. I guess, the only thing I would say, additionally is – yeah, I think that there’s data on like what happens when you switch a patient from one therapy to another. We’re useful at the time of the EYLEA launch, but then I think people also realize that those data in and of themselves, at least the way that a lot of those studies were done to be hard to interpret, right, which is why we kind of like the part of our DAZZLE study, where we take naïve patients, treat them for a year with EYLEA, and then switch half of them, and see, what happens when we switch half of them and continue the rest on EYLEA. That’s a better experimental design for getting an answer to your question.

I think for market access, I don’t think, it’s critical or probably actually even important, fundamentally to have data on treatment experienced patients, because from a commercial market access perspective, that’s not typically something that’s required. I think that, people may switch patients, when they start using a new therapy, they may start with switching patients rather than new patients until they get comfortable, but a lot of our retina physicians were already have comfort with KSI-301 from participating in clinical trials.

But – to Victor’s point, ultimately, those data can and will be generated. It’s always a question of, what’s the best timing and way to do it in a way that is – gives you credible clinical answers to important clinical questions.

[John McNeil, Goldman Sachs & Co. LLC]

Okay. Thank you.

[Operator]

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

[Robyn Karnauskas, SunTrust Robinson Humphrey, Inc.]

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 2 daughters are going to make an appearance on this call, a guarantee, I promise you. But thinking about like the fears that people talk about both on the investment side and maybe or concerns in this [pivotal community] [ph] about inflammation. How in your – when you are thinking about developing your clinical trial plan? Did you think about maybe alleviating those concerns in a clinical trial setting versus having people saying, well, I’m kind of nervous in the real world, if I see some more events. And did that – how you’ve factored that in? Or what kind of trials would you do to help people do that? Do you think it’s even needed? And then 3 questions, am I clear that your bispecific drug, it sounds like it could be in the – when could it really go into patients? And are you hitting as much – I absorbing as much IL-6 as like an average IL-6 drug alone? Do you have a sense of that?

And third is probably a really stupid question. So it sounds like you could actually apply it in your BLA. Would you do all 3 of these indications so RVO, DME and AMD all at the same time in a BLA? Is that possible? Thank you.

[Victor Perlroth, Chairman and Chief Executive Officer]

Hi, Robyn. So I think your first question is a little bit around, well, is there a new safety environment for new anti-VEGF, because of what’s happened to Beovu. I think an important consideration there is, whether what happened with Beovu is like a surprise, right. And that only when it went into like a large commercial population, right, did people begin to see some tail event, okay, which I don’t think is really accurate? I think, if you look back, right, the report of this kind of retinal artery occlusion, right, or inflammatory blindness really goes back to the beginning of the molecule, right. You can look back at some of those FDA databases, back to 2015 under Alcon, right, and under the shortlist of a couple different severe adverse events, you’ll find reports of retinal artery occlusion.

So I think it was always present – at a useful yet, low percentage, right, maybe you could argue or quibble, right, with Novartis, is it 0.1%, but more seemingly in the label is closer to 1% et cetera. So I think – given that and then you begin to say, well, is it manufacturing, right? Or is it the actual molecule? And I think even recently, right, some of the new Novartis announcement suggests that they’ve looked at manufacturing and they don’t think that’s the cause. They haven’t found any correlation with manufacturing. I think, you begin to look more at the molecule itself, right.

And then you begin to look at more – some complexities around the biology of that molecule, right, very high pre-existing ADA, very high treatment-emergent ADA, lower visual acuity benefits for patients that have ADA, all of these things are unusual for anti-VEGF biologics. It turns out as the European regulators put it, right, as we’ve discussed, Robyn, in their assessment that this type of biology, right, high pre-existing ADA, high treatment-emergent has also been seen for other sort of quote unquote, non-natural antibody fragment platforms, right, like diabodies and [camelids] [ph]. So maybe there’s some whether it’s innate immune or I don’t really know, right. I don’t think anybody understands to date, but a complex biology that accidentally happens to be here with this Beovu format.

So we don’t have that, obviously, with KSI-301 were fully antibody, we haven’t had any pre-existing ADA, in terms of what we’ve measured to date and appear to have very low or what we may call spurious at treatment-emergent ADA with our molecule. And with the current clinical experience that we have, which is, north of 100 patient years now, across the 1 billion DAZZLE, haven’t seen any signs of like a similar problem that people see with Beovu.

Now, of course, people will worry, and the question is, well, when do you feel that enough data has been generated? So we have some confidence that there’s not a tail safety event. And I think, there’s not really an easy answer to that, right. I mean, we do monthly or more assessments across all of our pivotals. Don’t forget we’re running the pivotal program with all of the indications in parallel, right, rather than running one indication in series, right, and then the next and then the next.

So we’re trying to generate as much of this data both from a safety, efficacy and durability standpoint, as quickly as possible, and we’re trying to be as transparent, as we can with running this 1b study and presenting the data as we can. So I don’t think, there’s any special secret, but I think fundamentally, we’re not suffering a lot of the same baggage in terms of design and complexity of underlying biology. And we have a good amount of clinical data available, and we’re not seeing this complex pattern that they had. So that’s kind of a comment around Beovu.

In terms of the IL-6 VEGF, we call that our OG2072 protein, right, it’s the protein component of our bioconjugate, so it could be evaluated systemically. And as a systemic agent, which would be given in acute manner, right, say and COVID-19 patients, you can give whatever dose level you want. I think, if you look at the Regeneron, or you look at the Actemra, the Roche molecule, they have different dose levels in terms of mgs per kg. But from a systemic standpoint, you can get quite large doses. So we think, we can get very strong anti IL-6, in this case as a ligand. And also very strong anti-VEGF, whatever dose level is required. And also, as I think we mentioned, intriguingly we’ve seen some very interesting synergy across both of those biologies. And so, perhaps the molecule could be important, and so, we want to make the molecule available.

And at the same time, we get those ancillary benefits of some real manufacturing acceleration of the program, because the core critical path for the IND and First in Human really was GMP manufacturing of the antibody. So that’s a core feature of the KSI-501 acceleration. And then in terms of putting all 3 of the big indications into a single BLA, Jason, maybe you could talk a little bit about that regulatory strategy.

[Jason Ehrlich]

Yeah, sure. Thanks, Victor, and thanks, Robyn. Yeah, so – yeah, I think that that’s a – I think, quite a reasonable approach particularly at least in the United States, right. The more – of course, from the agency’s perspective, the more information that you have, the better on your medicine and you need to submit the safety data, all the safety data that you have right at the time, even if it’s across multiple indications. So I think the idea of submitting it in one package where they can really understand the total safety database as well as the efficacy across the different indications. I think that’s a quite nice strategy.

[Victor Perlroth, Chairman and Chief Executive Officer]

I mean, even beyond that, I mean, Jason, I would say we have in writing from FDA that there – we would look forward basically to receiving, I mean, certainly like the wet AMD and the DME, they expect us to submit those together. So submitting all 3 of them together is something that they – I think they appreciate, because it allows them to make higher quality decisions, I guess.

[Robyn Karnauskas, SunTrust Robinson Humphrey, Inc.]

Well, thanks for the color. And thank you.

[Victor Perlroth, Chairman and Chief Executive Officer]

Thanks, Robyn.

[Operator]

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

[Gena Wang, Barclays Plc]

Thank you for taking my questions. I have 3 questions. The first one also follow the single BLA filing, I understand that you talked with FDA. Just wondering, with that 1 wet AMD trial, 2 DME trials and 1 RVO trial was that agreed upon with FDA. And what is the EMA feedback?

And my second question with regarding the RVO study, what will be your thoughts on the patient they’ve done between BRVO and the CRVO? My third question is regarding the 5% – less than 5% and missed visits. Just wondering how do you collect the data afterwards? And how do you analyze the data and how would that impact the clinical endpoint data?

[Victor Perlroth, Chairman and Chief Executive Officer]

Right. Okay, just to summarize the questions, and Jason, maybe you want to hit them? I think the first is well, what we have from FDA specifically, in terms of our kind of what we call the upgraded KSI-301 pivotal plan, right. So where are we in terms of the FDA on that? The second being the expected breakdown within this single RVO pivotal for BRVO and CRVO. And third, when we do have missed visits, how important is that to the integrity of the study, and what are we basically doing to prevent them and if they happen; is it important or material to the study? Yeah.

[Jason Ehrlich]

Right. Yeah. So I think with regards to the FDA question, Gena. Yeah, I think, we’re quite comfortable with where we are, in terms of the regulatory feedback of what’s in the written feedback, as well as subsequent conversations. The RVO, in the context of a single study, we would stratify the randomization between the 2 different RVO sort of subtypes the branch vein and the central vein. And, this branch vein is more common, we probably have a minimum sort of cap, if you will on the number of CRVO patients to make sure that that category of patients is adequately represented. I mean, in the community, it’s probably, like branch vein is maybe like 3.5 to 4.5 times more common than central vein so that depending on where you are. So probably like a 20%-ish minimum on the central vein patients make sense to make sure that they’re well represented in the study.

In terms of the missed visits, and how does that impact the data? I’d say, I mean, at a high level, provided that that’s really one missed visit, say, for a patient or scattershot over time as opposed to like a series of missed visits in a row or many missed visits in a row. Then, I think those data are just handled by the statistical methods as they routinely are, right? I mean, there’s always missing data in every study. And the study is also adequately powered for assuming a certain rate of discontinuation from the study, and our rate of discontinuation as opposed to missing data is also very low.

So, I mean, most of the modern statistical methods will – basically have different – there’s different methods for imputing missing data in a study. So it’s really then a question of, if a patient where to miss, like, multiple visits in a row. How do you handle those particular data, and the protocol also specifies, considerations for whether a patient should continue if they’ve missed a certain number of visits. But fundamentally with missed visits at the rate that they are, I think the study will absorb those without any meaningful impact and they’re distributed, fundamentally they should be distributed equally across both groups. But I think, that should really be an important source of bias.

[Victor Perlroth, Chairman and Chief Executive Officer]

Right. I think even when we look in more detail, right at the design of the DAZZLE pivotal and as we think about educating ourselves as we finalize, right on the margin the designs for the new pivotals. I think, we believe we can withstand a substantially higher missed visit rate. I don’t know what number we would give, but is it 20% or more than that, or whatever, and still have very good studies that would get us to the right outcomes.

[Gena Wang, Barclays Plc]

Okay. Very helpful. Just wanted to follow-up, regarding the [bureau file] [ph] or the pivotal study program design, what is the EMA feedback on that?

[Victor Perlroth, Chairman and Chief Executive Officer]

Right. Well, that’s a good question. Jason?

[Jason Ehrlich]

Yeah, I’d say, EMA, in terms of like – how many indications you can file at once? I think they were ultimately have to be some more conversations with them, somewhere it depends on sort of national opinions versus EMA scientific advice. So I think that those are topics like how many of these indications can you get in the initial license versus subsequent variation. We’ll need some more discussion with EMA ultimately.

[Victor Perlroth, Chairman and Chief Executive Officer]

Right. I mean, one thing I think that’s interesting, Gena, is looking at, well, what’s been the response in say, the United Kingdom, in context of COVID-19 for retina, whereas in the United States, although visits have gone down, as Jason mentioned, from the best from data, right, the proportion of visits where there been the anti-VEGF injections has increased. And physicians, of course, are still seeing new treatment naïve patients. But in the UK, the guidance has been for treatment naïve patients, right, basically it’s not to see the patient. It’s basically to – I think, Jason wasn’t the feedback or the new guidance has specifically – basically come back in 4 months. So there’s an important alignment of the target product profile or the differentiation of KSI-301 for Europe.

And I think one of the things to do is, I mean, of course, we’re going to be running our pivotal studies in Europe, but also – to maybe look for like unique opportunities right where this new profile for our medicine is a nice fit, for example, in the UK, because it’s just not reasonable to leave patients with these diseases for 4 months without therapy.

[Gena Wang, Barclays Plc]

Thank you.

[Operator]

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

[Matthew Luchini, BMO Capital Markets]

Hi, good afternoon, and thanks for taking the question. So a couple from me, I guess, first with regard to the revised DME, RVO study timeline, beyond sort of 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?

And then, secondly, just you touched on it, I think in the last question, but I just wanted 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.

And then, lastly, I wanted to just come back to manufacturing. And so, it’s come up a couple of times. And if you could just remind us a little bit about where you are today, and versus what you think you need for the revised pivotal program, and then, ultimately, 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.

[Victor Perlroth, Chairman and Chief Executive Officer]

Right. I mean, I think, based on the information that we have today and the decisions that we’re making, and I think, as you mentioned independent of COVID-19, I mean, I think we’re feeling very comfortable about a September/October first in human for the new program. So that’s really what we’re targeting. And it’s going to be nice, because we’re able to follow the DAZZLE framework that we’ve put in, right, say, for example, in the United States into the same sites.

And a lot of the pieces of these studies, for example, as Jason mentioned, the DME study has a very similar design to the DAZZLE study. So a lot of the pieces of these new paired DME studies is going to come directly from DAZZLE into the same sites. And we’re going to drop RVO into the same site as well. And then, we’re ahead in terms of site activation, right, for DAZZLE in Europe, and then we’re going to flow these other studies directly into the same sites.

So there is – we have CTAs approved in many countries in Europe, and we’re basically ready to go there. So we feel good there. And those are really just based on conservatism, right, in terms of, well, what’s happening with COVID. And do we want to – should we cross the transom of activating all these additional studies in June, that didn’t seem wise, but targeting September seems quite good.

In terms of RVO, we believe that, as Jason mentioned, we’ll have both coverage for BRVO and CRVO in the pivotal. And we believe we’re in good shape there. I think on the manufacturing, there’s obviously a lot of retention on clinical from the standpoint of these types of discussions, right? If you don’t have your manufactured material, when you hit the market, you’re not going to be in good shape.

We don’t want to be in a situation of generating really exciting pivotal data, and then asking all of you to wait many years before we’re really able to service the market. So we’re spending a good amount of time. I think the fact that we’ve had such a wonderful safety profile to date, is a testament to the quality and attention that we put into manufacturing and have for a number of years.

If you remember, with Lucentis, when it entered to the market, right, it had as much as 15% inflammation, and then they were able to clean up that formulation, from their lyophilized into their liquid and now into their prefilled syringe, and really brought that down. We’re trying and want to launch in a prefilled syringe. And so, we’re working hard to make that a possibility. We’re at – currently we’re at 1,000 liter [Joe] [ph] scale, and we’re shifting that into the 6,000 to 10,000 liter range for launch.

So there is some process development and tech-transfer work that’s in process, but fundamentally, it’s the same master cell bank and the overall methods will be very similar as we scale to where we want to be commercially. And the conjugation that we do to make our bioconjugate, uses industry-standard ADC-type conjugation methods. And so, we don’t anticipate any technical, core technical challenges there, rather again, it’s more scale up into, say, larger facilities.

So there’s a lot of work there. That’s a great question. I think part of it is we can ask you and the community, well, what percent of the branded market do you think, in years 1, 2, and 3 post-launch Kodiak should be investing? What percent of that branded market in terms of millions of doses? For example, I think last year, there were, say, 25 million intravitreal injections that were given globally.

And if half of those were Avastin, right, that’s 12.5 million, and let’s say, it’s growing at say 6% to 10% a year, right? So, well, what percent of that market right, in year 1, 2 and 3 can KSI-301 credibly grab? And that helps to drive our view of manufacturing scale up. So it’s quite an interesting conversation. And we’re trying to do it in the context of prefilled syringe as well.

So a lot of activities and maybe that will become more important over the next couple of years. We have a tremendous amount of drug substance of bioconjugate that we manufacture and we did a very successful resupply over the last 12 months. So we’re very good in terms of bioconjugate drug supply to service the pivotal program. So really our attention is towards the scale up and the validation towards the BLA activities.

[Matthew Luchini, BMO Capital Markets]

Great. Thank you for all the color.

[Operator]

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

[Zegbeth Jallah, Roth Capital Partners]

I just have a quick question with regards to 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? And any learnings in that, that you could apply to your pivotal? And then, just another follow-up question just out of curiosity here, how did you come up with the idea for OG2072 for COVID-related diseases? And then, can you elaborate on any of the synergism between that program and KSI-501?

[Victor Perlroth, Chairman and Chief Executive Officer]

Could you repeat the first question again?

[Zegbeth Jallah, Roth Capital Partners]

Yeah, so just wondering in terms of expectations for the amended Phase 1b study, the longer-term data?

[Victor Perlroth, Chairman and Chief Executive Officer]

All right, well, I think our core focus this year is on what we call kind of the durability of the durability, right. So the early Phase 1b was sort of through the loading phase, and then coming out of the loading phase, it was a bit that time to that first retreatment across the 3 diseases. And now, we’re sort of looking at the durability of that durability, and when people, who got retreated at, say, 4 months, do they get retreated at 4, 6 or 2 months kind of thing. And how that looks across the population of patients?

So we think right now, that’s a really interesting focus. And that’s where we should be exploring. We’re, of course, extending the study, as you realize, out to, say, 3 years. And why are we doing that? Well, first of all, we think it’s really a nice way to follow and see the individual patient detail, of the patients and the medicine over time. And also, of course, it helps to extend like kind of the safety database that we want to have and a little bit of that safety experience.

So that’s really the rationale and then to be following them in the background. And hopefully, publishing on that and learning more and providing quite a lot of transparency in terms of how this medicine and anti-VEGF biologics work in a population that we track very carefully. And, of course, we’re trying to encourage as many of the patients to stay in the study through the 3-year period to maximize the utility of the data generated.

[Zegbeth Jallah, Roth Capital Partners]

Thank you. I think that’s really helpful, I suppose in terms of physicians’ comfort with the level of safety to want to continue to treat these patients even longer term.

[Victor Perlroth, Chairman and Chief Executive Officer]

Yeah, yeah. And then, in terms of like the OG2072, the bispecific protein, like I mentioned, there’s a lot of ancillary benefits to the overall KSI-501 program. But I’d say, the context of the synergy of some of this kind of activity of these two mechanisms is maybe a little bit surprising, the anti-IL-6 and the anti-VEGF; certainly, anti-IL-6, right, in COVID-19 for like the cytokine release syndrome component.

But I think maybe what we see from some of the more recent Regeneron data is that, there are other mechanisms of actions or like pathology that’s kind of happening maybe in parallel, right? And I think some of these ideas that the vascular permeability, that’s either caused directly by the virus in the tissues or is related to like the cytokine release, you get this vascular permeability in the tissues and you get that edema.

Well, don’t forget that anti-VEGF. It’s really maybe not an anti-angiogenic agent in terms of how it works in the eye, right? It’s an anti-permeability agent, and it really functions on vascular permeability. So if that’s important in this disease, you can kind of get the anti-IL-6 piece in this anti permeability piece with a molecule that’s showing synergy. And that’s quite potent.

And so we’re going to do a drug product run of our antibody, as a release drug substance, which is how we manufacture it anyway. And look to try and make that available in some of these basket clinical studies while we, of course, continue on our core mission in retina and ophthalmology.

[Zegbeth Jallah, Roth Capital Partners]

Thanks, Victor.

[Victor Perlroth, Chairman and Chief Executive Officer]

Sure.

[Operator]

All right, thank you. [Operator Instructions] All right, speakers, and at this time there are no further questions in the queue. I’d like to turn it back over for closing remarks.

[Victor Perlroth, Chairman and Chief Executive Officer]

Well, thanks, everybody, for participating. And, hopefully, it gives you a very up-to-date view of Kodiak and the activities for the remainder of this year. Thanks so much. Bye.

[Operator]

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.