Mitie Group Q4 2023 Earnings Call Transcript

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March 28, 2024

There are 10 speakers on the call.

Operator

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

Operator

Please go ahead.

Speaker 1

Thank you for joining our conference call and webcast to discuss recent business updates at Kodiak. I'm John Borgeson, Kodiak's Chief Financial Officer. Joining me today are Victor Perlroff, Chairman and CEO and Pablo Velasquez Martin, Senior Vice President of Clinical Research and Development. After our prepared remarks, we will open the call for Q and A. The webcast portion of this call contains a slide presentation that we will refer to during the call.

Speaker 1

Those following along

Speaker 2

on the phone who wish

Speaker 1

to access the slide portion of this presentation may do so on the Investors and Media section of our website. An archive of this webcast will be available shortly after the event on our website. We'd also like to remind you that remarks made on this call today include forward looking statements about Kodiak that are subject to risks and uncertainties and which are outlined on this slide. A more complete description of these and other material risks can be found in Kodiak's filings with the Securities and Exchange Commission, including its 10 ks for the year ended December 31, 2023, which has been filed with the SEC. And we encourage you to read those carefully.

Speaker 1

I will note that Kodiak does not undertake any obligation to update publicly any forward looking statements whether as a result of new information, future events or otherwise. Now, I'm pleased to turn the call over to Victor Perlroft, Kodiak's CEO. Victor? Thank you, John. Good afternoon, everyone.

Speaker 1

Thanks for joining us. I trust many of you have read Kodiak's press release of this morning, announcing our recent business updates together with our financial snapshot. The goal for today's discussion is to provide additional context and color around some of our most recent activities in our going forward plan and we will welcome your questions at the end. We're a retina focused company. Retina is a challenging area for innovation, but there should be an increasing return to focus and time and dedication.

Speaker 1

At Kodiak, we sit atop 10 plus years of fine tuning of our ADC platform in our company. Also being able to listen and to have the courage to make the important course corrections needed to get us to the finish line with medicines that are meaningful for patients and therefore valuable. The sector is concentrated with only Roche and Regeneron as dominant players. There's room for another major player and that remains our aspiration.

Speaker 3

We look forward today to providing you the broad view. Today, we are at a

Speaker 1

point of departure and we are in motion. We have a portfolio of 3 clinical programs. 2 programs are ABC platform derived with its core science of durability. And one program is platform independent. We think this pipeline represents a healthy diversification both in terms of the opportunity and risk.

Speaker 1

For some of you listening today, you may say, I'm not smart enough to know whether COEAC's ABC platform represents a disruptive innovation that can deliver for patients and frankly for investors or not. For you, let us show you. But in the meantime, you don't have to believe in the APC platform to recognize that KSI-one hundred and one represents itself a potential important new branded molecule for retina, highly potent on 2 powerful mechanisms for patients with inflammation and some residual fluid. We call it a greenfield market opportunity. In the program building as it does already from the base of bioactivity, efficacy and safety

Speaker 3

seen in the KSI-five zero one program sharing as

Speaker 1

it does the same protein. Kodiak can be a tremendously successful company and investment opportunity on the basis of KSI-one hundred and one alone. But for ourselves, we are big believers also in our ABC platform. Why? Durability remains a key unmet need and want durability for all patients as an inception regimen, as a maintenance for treatment naive patients and treatment experience.

Speaker 1

And you want the durability without sacrificing immediacy, potency or safety. They say the real test is whether you give the drug to your mother or grandmother. At this stage, not being marketed, we provide our investigational medicines in context of our clinical trials. But our design, we're proud of the ABC platform, our novel proteins, our bio conjugates, our underlying science and design for durability. And now the important adjustments we've made to the tarkosumab product that improve the manufacturer ability in a prefilled syringe and we believe may also enhance the utility of the product and which we have also already flowed into the KSI Fiber Molecular Material as well.

Speaker 1

We believe now is the time to implement these changes given the additional clinical studies we plan to conduct. And the FDA has agreed that these additional clinical studies are sufficient to bridge the former material to the go to market material, which we'd like to commercialize going forward. Tarkosumab then and also KSI-five zero one, these represent state of the art molecules. And based on our view of our data in these design enhancements, I think these medicines need the grandmother test. And when we look commercially, given the rapid pace now of our planned development for tarcosumab and KSI-five zero one, while yes, there is a commercial complexity, we are the innovator here and we believe there can be a strong demand for our medicines in their unique design, science and their unique performance in the retina marketplace.

Speaker 1

Taking it back to the top level across these three what I call late phase programs, there's also a significant amount of operational synergy in moving these 3 programs forward together. And as we'll see very useful, we can even run them in the same study or studies with low incremental costs per group. So where are we today? Let's start with an overview of where we are. Number 1, from a cash position, we have an attractive cash position today as of Q4.

Speaker 1

Number 2, when we look at Kodiak, we see 3 late phase programs. And number 3, our intention is to bring these 3 programs to meaningful inflections within our cash runway. So for tarcosumab, we have 3 positive Phase 3 studies that have been completed in diabetic retinopathy, in retinal vein occlusion and in wet AMD. We have strong and consistent 6 month durability signal and favorable safety seen across the pivotal program. We have regulatory alignment now that's been achieved on a bridging strategy for our go to market formulation.

Speaker 1

The Phase 3 study GLOW-two in diabetic retinopathy is now actively recruiting patients. And we've added as an additional arm tercosumab into Daybreak to validate the durability in wet AMD to strengthen fercosumab's competitive position and to bolster our ex U. S. Regulatory

Speaker 3

dossier. For 501, the

Speaker 1

Phase 1 study in DME met our objectives, okay, we're developing it towards the high prevalence retinal vascular diseases, okay, to bring durability and the extra mechanisms to bear. We've created the enhanced formulation informed from turcosumab's commercial manufacturing scale up with many potential benefits and we're in the process of gaining or finalizing FDA alignment on the design of the Phase 3 Daybreak study in wet AMD and targeting an enrollment start mid year. And for our diversified, let's say KSI-one hundred and one program, We're developing it in a new area macular edema associated with inflammation. We see it as a greenfield opportunity outside of the established anti VEGF class and with risks and opportunities uncoupled from our ADC platform and from our other 2 molecules. A Phase 1b study is planned for the Q2 to identify 2 dose levels that we will then rapidly progress into pivotal studies.

Speaker 1

And we're in the process of gaining FDA alignment on the design of dual Phase 2bthree pivotal studies, which also are planned for initiation this year. Turning to Slide 6. Focostamab is our most advanced program and we're one successful trial away from filing for registration in a success scenario. In the trial, GLOW-two will be conducted in a patient population diabetic retinopathy where tarkosumab already showed a clear win in our GLOW-one study. GLOBE-two is actively recruiting patients.

Speaker 1

At the same time, we plan to advance KSI-five zero one and KSI-one hundred and one rapidly into pivotal studies this year. The Phase 1 study of KSI-five zero one demonstrated positive signals and efficacy and safety and support further development. We are in discussion with the FDA on the study design of the Phase 3 DAYBREAK study in wet AMD and plan to initiate it as soon as regulatory alignment is achieved targeting mid-twenty 24. We also intend to advance KSI-one hundred and one into a Phase 1b dose finding study in the Q2 of this year to identify the 2 dose levels we want to be using in our dual pivotal. We're in the process of gaining regulatory feedback on the pivotal program design and we hope to initiate 2 Phase 2b studies later this year.

Speaker 1

Our goal is to have 4 pivotal studies ongoing later this year across the 3 programs. 2, service a broad and powerful BLA for tarcosumab, 2 service a new and powerful BLA for KSI-one hundred and one and one is half of what's needed for a KSI-five zero one BLA. Turning to Slide 7. Now let's turn to our most advanced clinical program, tarcosumab. Tarcosumab is an anti VEGF antibody biopolymer conjugate or ABC medicine built on the ABC platform to provide extended durability.

Speaker 1

It's been studied in 6 pivotal studies, 3 of which met their primary endpoints across the indications diabetic retinopathy, retinaldin occlusion and wet AMD. My view is tarkosumab can bring 6 month durability to the majority of patients across the diseases and that we can get there as an initiating therapy, not a maintenance therapy and without leaving any patients behind irrespective of disease severity. That's the future as we see it. In our GLOW-one study in diabetic retinopathy, tarcosumab demonstrated for the first time among anti VEGFs that 6 month dosing can successfully treat Doctor patients by improving the disease severity scores and in reducing risk of vision threatening complications by about 90%. In our BEACON study in retinal vein occlusion, tarcosumab demonstrated we could bring all RVO patients to once every 2 month dosing versus the current standard of care, which is monthly dosing.

Speaker 1

And importantly, in the second 6 months of the study, tarcosumab was studied head to head against flibercept on the same individualized dosing regimen. Approximately half of tarkosumab treated patients were injection free in the 2nd 6 months compared to about a third of a bliparcept treated patients. Over the entire 1 year of treatment, tarkosumab treated patients achieved comparable vision and anatomic outcomes with meaningfully fewer injections compared to a flippercept treated patients, 5 versus 7. Lastly, in our daylight study in wet AMD, tarkostamab met its primary endpoints and demonstrated that intensive monthly dosing of tarkostamab was safe and well tolerated. These are important studies in big indications.

Speaker 1

Nonetheless, in our tarkostamab program, they are a point of departure and the value comes when you finish things. So to that end, we have also, as I mentioned, made adjustments to the tarkosimab product that improve the manufacturer ability and may also enhance the utility of the product. And we have received FDA feedback that one additional successful pivotal study using the go to market material is sufficient to bridge the clinical scale material to the go to market material, not just to bring our go to market formulation, not just to bridge our go to market formulation, but as of today we have 3 positive Phase 3 studies of tercosumab in 3 different diseases and we will need one more successful pivotal study in one of these indications to file for approval. We plan to evaluate, turning to Slide 8, tarkostamab in 2 new Phase 3 studies, the GLO-two study in diabetic retinopathy and the DAYBREAK study in wet AMD. We've obtained FDA feedback on the study design of GLO-two and it is already actively enrolling patients.

Speaker 1

The idea behind GLO2 was to have a very high probability of a success study. Therefore, the study design for GLO2 builds GLO1 and I see it as having a high real and perceived probability of success. So from an investor standpoint, I don't think you need to wait around to see the results to have some early confidence. In addition and after much consideration, we also intend to study tarkosumab as the 2nd investigational arm in our wet AMD Daybreak study with 3 purposes. First, to demonstrate conclusively tarcosumab's durability in wet AMD.

Speaker 1

2nd, to strengthen tarcosumab's competitive position, given the importance of wet AMD in the anti VEGF market and third, to bolster tarkosumab's ex U. S. Regulatory dossier. We're in the process of obtaining FDA feedback on the study design of Daybreak and hope to initiate recruitment mid-twenty 24. Turning to Slide 9.

Speaker 1

The GLOBE-two study design built from the successful GLOBE-one study with the benefit of a 3rd monthly loading dose at week 4 as highlighted on the slide. We believe that 3 monthly loading dose regimen provides greater flexibility to patients and is nice to have as part of our BLA package. The primary endpoint is the proportion of eyes with 2 steps of greater improvement on DRSS at week 48 the same as GLOBAL. Turning to Slide 10. Now let's turn to KSI-five zero one, our 2nd investigational medicine.

Speaker 1

501 is a 1st in class bispecific antibody biopolymer conjugate or ADC that inhibits both IL-six and VEGF. IL-six is a pro inflammatory cytokine and growth factor implicated in pathophysiology of retinal vascular diseases. It is known to stimulate defective angiogenesis both by up regulating VEGF and by a VEGF independent pathways. It is associated with anti VEGF treatment resistance as well as disease progression in AMD, Doctor and RVU. Firal 1 is designed with 3 tiers of innovation.

Speaker 1

1st, a 2 target mechanism potently inhibiting both the dominant VEGF pathway and the IL-six inflammation pathway. 2, the potential for 6 month durability based on Kodiak's ABC platform and 3, an enhanced KSI-five zero one formulation informed from tarcosumab's commercial manufacturing skill. We believe the 3 tiers of innovation position KSI-five zero one well to address the unmet needs in high prevalence retinal vascular diseases such as the need to target disease mechanisms beyond VEGF and the need for extended durability. As I mentioned above, the KSI-five zero one program is the result of the fine tuning of our ABC platform as a company over the past 10 plus years. And the program itself is a fast forward, the design, the manufacturing, the clinical planning and the operational expertise.

Speaker 1

Turning to Slide 11. This slide is a reminder of the substantial variability in response to today's anti VEGF standard of care agents And therefore, the need to bring additional disease mechanisms beyond VEGF into our therapies. As you can see from this data generated in our own pivotal wetting AMD study, there is substantial inter patient variability in their response to anti VEGF monotherapy, both in terms of visual acuity gains and fluid reduction. A substantial proportion of patients underperform in vision and or anatomical improvement compared to the mean responses, which highlights the need for additional mechanisms of action. And we believe KSA-five zero one can play an important role here.

Speaker 1

Turning to Slide 12. The anti IL-six VEGF trap bispecific protein in KSI-five zero one has a unique design that enables it to potently inhibit 1 or more VEGF dimers and 2 IL-six molecules simultaneously. The VEGF trap portion mimics the native receptor and binds multiple targets including VEGF 1, VEGF A, VEGF B and placental growth factor. The anti IL-six antibody binds IL-six, therefore inhibiting both IL-six trans and cis signaling by its binding to soluble and membrane bound IL-six receptors respectively. In addition of IL-six blocks IL-six mediated inflammation and immune activation

Speaker 3

and normalizes blood retinal barriers. Turning

Speaker 1

to Slide 13, we conducted a Phase 1a1b type study in DME patients that is now complete. The study was a multiple ascending dose study in DME patients, both treatment naive and pretreated patients. Four dose levels were studied in the Phase 1. Each subject received 3 monthly doses and was followed for 24 weeks, which allowed us to evaluate the safety, tolerability and bioactivity signals of KSI-five zero one. Turning to Slide 14.

Speaker 1

We are pleased with the Phase 1 study results where KSI-five zero one demonstrated strong visual acuity gains in both treatment naive and pretreated DME patients that were sustained over the 24 week study period. It also demonstrated meaningful CST reductions in patients. So this was a small patient sample size. So we should try not to over interpret the results, but rather we look for the essential signals that suggest this could be a molecule with meaningful therapeutic effect. The Phase 1 study also demonstrated that repeated monthly dosing of 501 was safe and well tolerated.

Speaker 1

Overall, we think the Phase 1 study results support further clinical development of the 501 program. Turning to Slide 15. We're planning to advance KSI-five zero one into a Phase 3 study in wet AMD called DAYBREAK later this year. There is abundant preclinical and clinical evidence for the role of IL-six in choroidal neovascularization, both in terms of driving disease pathogenesis and also in mediating treatment response to anti VEGF agents and disease reactivations. We believe 3 tiered innovation designed into KSI-five zero one as mentioned before, namely the bispecific mechanism of action, the potential for 6 month durability based on the ABC platform and the enhanced formulation position the molecule well to address the unmet needs in wet AMD.

Speaker 1

The DAYBREAK study is intended to be a non inferiority study to evaluate the efficacy, durability and safety of KSI-five zero one and tarcosumab in wet AMD against aflibercept to make both 501 and tarkosumab will be dosed on extended regimen from every 4 to 24 weeks, while the flippercept 2 make will be dosed per label. With this study, we'll use the go to market formulations for both 501 and tarcosumab that improve the manufacturer ability in a prefilled syringe and they also enhance the utility of the products. We are currently in conversation with the FDA to obtain feedback on the study design for DAYBREAK and intend to initiate enrollment as soon as alignment is achieved targeting mid-twenty 24. Turning to Slide 16. Now we'll turn our attention to our 3rd investigational medicine KSI-one hundred and one.

Speaker 1

This is the unconjugated protein portion of KSI-five zero one with the same anti IL-six and VEGF trap design and its unique features as we mentioned previously. This is a greenfield development opportunity for us as it focuses on a market outside of the established anti vegf market. KSI-one hundred and one also is independent from the ADC platform with opportunities and risks uncoupled on the platform, which presents a healthy diversification. With this bispecific anti inflammatory mechanism of action, high potency on both targets and high formulation strength at 100 milligrams per ml. This is a powerful medicine and we are exploring it in difficult conditions.

Speaker 1

What we call the uveitic complex of diseases that as hallmark have macular edema, that's retinal edema and inflammation and for which no intravitreal biologic therapies exist today. Turning to Slide 17. Current treatments for patients with macular edema associated with retinal inflammation show limited efficacy and many undesirable and potentially serious side effects. Treatment is generally non specific such as steroids and immunomodulators. There is only one approved biologic therapy adalimumab, which is an anti TNF alpha agent that is administered systemically, but it also is associated with limited treatment efficacy and serious side effects.

Speaker 1

There are no approved intravitreal biologic therapies today that target the underlying disease mechanism. We believe this disease area is prime for a powerful, safe and effective branded intravitreal biologic therapy to change the treatment paradigm. Turning to Slide 18. We plan to advance KSI-one hundred and one into a dose finding Phase 1b study in the Q2 of this year to identify the 2 dose levels to progress into our pivotal. We are currently in the process of obtaining FDA feedback on the design of the pivotal program here for KSI-one hundred and one and hope to initiate 2 Phase 2bthree pivotal studies later in 2024.

Speaker 1

Turning to Slide 19 and summarizing. In summary, we're excited to be on plan to advance our 3 clinical programs into Phase 3 studies in 2024 with GLO-two for tarkosumab already enrolling, with Daybreak up next and bringing forward 2 of our molecules, KSI-five zero one as well as tarkosum and then dual pivotals for KSI-one hundred and one in plan. We are at a point of departure and we're in motion and we have our eyes focused on delivering meaningful Phase 3 BLA facing value inflection points within our current cash runway. Now we will open the floor to analysts for questions. Operator?

Operator

Thank you. Our first question comes from the line of Michael Yee from Jefferies. Your line is open.

Speaker 4

Hi, good afternoon. This is Xiaojiu Wei on the line for Michael Yee. Thanks for taking my questions. I have two questions regarding the 501 bispecific pivotal study. I noticed that there are multiple arms for tarcosumab and KSI 501E in that study.

Speaker 4

I wonder if those patients would be randomized to each of the arms at the beginning or they would be treated as needed and given more flexibility of the dosing? And what's your estimate of the sample size? And second question is, can you clarify if you plan to include data from the daypart, the Phase the pivotal study for 501 as well in the same BLA filing of takosiban?

Speaker 1

Thanks. To try to make sure that we understood the question, It's around the DAYBREAK study. And that study is planned to include aflibercept as the comparator and then to include arms for tarcosumab as well as KSI-five zero one. So the first objective of including an experimental arm with tarcosumab in the study is it's very efficient economically for us and operationally. But also the data from the study will yes be included in the BLA filing for tarcosumab.

Speaker 1

So our objective on the timing of the DAYBREAK study and also the GLOW-two study are for those studies to finish at approximately the same time and to feed the same BLA. So that's an important element. Then on the study designed for DAYBREAK, we're still in discussions with FDA to make sure that we get to the study that meets our needs. Our objective is to include durability for both tarcosumab and KSI-five zero one and to be able to go from monthly dosing all the way through 6 month dose to be able to showcase the power of our ABC platform medicines from the standpoint of immediacy, but also their powerful durability.

Speaker 4

So does that mean that you would have multiple arms of taukocilumab as well as 501 and that essentially requires a big study

Speaker 1

for you to run? We haven't disclosed the precise design of the study yet. As you know, within ophthalmology, the regulatory landscape is evolving. One of our core objectives for the DAYBREAK study is that it'd be cost effective. Kodiak has a substantial amount of experience running many of these studies in the big diseases in retina.

Speaker 1

And so, obviously, we're going to try not to have more groups than we need to have to be able to like achieve our objectives. So let's stay tuned and see where we come out on the study design.

Speaker 4

Got it. Thank you.

Operator

One moment for our next question. And our next question will come from the line of Michael DeFior from Evercore ISI. Your line is open.

Speaker 5

Hi, guys. Thanks so much for doing the call and for taking my question. A few questions from me. Number 1, regarding the upcoming Phase 3 DAYBREAK trial, I know the design is currently being finalized, but if you could provide any color on what dose will be used? And a follow-up question to that is how is the enhanced KSI-five zero one formulation different from the formulation used in the recent prior Phase 1 DNA study?

Speaker 5

And I have a follow-up.

Speaker 1

For the DAYBREAK study, the plan is to use a similar 100 microliter volume. So therefore, it will be driven by the formulation strength of the formulations themselves. So both the tarkosumab and the KSI-five zero one formulations are 50 mg per ml strength for this pivotal at 100 microliters, so they'll be 5 milligrams each. And each one of those molecules will be in there what we call kind of go to market formulation or commercial scale up formulation, which as we've mentioned does include adjustments from what was tested previously with tarkosumab in our pivotal program and also what was used in the Phase 1 program for KSI-five zero one. So as I said, we're at an important point of departure as we step into these new studies with these adjusted and enhanced formulations And we're excited to be able to showcase what these molecules can do in these next set of pivots.

Speaker 1

Got it. That's helpful.

Speaker 5

And I guess my follow-up question is, just want to clarify why exactly ticosumab is being added as an active comparator in the DAYBREAK trial. Is it correct to assume that the FDA is not requiring this and that Kodiak is proactively doing this in order to have dosing flexibility on the label?

Speaker 1

We really struggled somewhat with what to do to finish the tarcosumab program. And I would say it took us some months to figure out what we wanted our plan to be. And on the one hand, we wanted to lean into additional work in wet AMD because that represents a large part of the market, right, for the anti medjabs. On the other hand, we didn't want to run the study where, let's say, different stakeholders or investors were worried about the probability of success because we'd have so much hanging on the outcome. So in the end, we decided to run the GLOW-two study as our core study for approval for tarkosumab, which we can which will have a very high probability of success given that it's essentially the same study as GLOW-one, which was a tremendously successful outcome.

Speaker 1

And then in addition, we decided that we would tuck in an additional group into the pivotal study we wanted to run for KSI-five zero So economically, it's very cash efficient to tuck that in. Having decided to run that additional wet AMD study, then we'll end up with the daylight study as a successful study and we hope the DAYBREAK study also has a successful study for tarkosumab and our overall package will then include 5 successful, we hope pivotal studies for tarkosumab. And at the same time, we're checking a box for KSI-five zero one and it will be the first of its 2 pivotal studies that we'll need to file a prebiolyde. So if you think about CoDx program with 3, what I call late phase molecules, right, with all of them being run through pivotal studies starting imminently. That's the philosophy that we're bringing to the next several years of Kodiak's development.

Speaker 5

Got it. Very helpful. Thanks so much.

Operator

Thank you. One moment for our next question. And our next question will come from the line of Anupam Rama from JPMorgan. Your line is open.

Speaker 1

Hi, thanks for taking the question. This is actually Malcolm on for Anupam. So just one from us. What is being assumed in terms of milestones between now and your the end of your cash runway into 2026? Well, certainly the completion of the 2 tarcosumab pivotal as well as the completion of the 501 pivotal.

Speaker 1

And we're in discussions with FDA currently on the design of the Phase IIbIII studies for 101. And depending a little bit on those designs and how they translate into enrollment, we were hopeful that we'll be able to get those studies out in that timeframe as well. Great. Thank you.

Operator

Thank you. One moment for our next question. Our next question comes from the line of Andrea Tan from Goldman Sachs. Your line is

Speaker 6

open. Thanks for taking the question. 2 for us, please. Maybe as a follow-up to a prior comment, recognizing that the potency remains the same between the two formulations that you have, can you share what may or maybe speak to what data you've seen that supports that durability of the original formulation will carry over as you transition from the biopolymer conjugate to now a mix of the conjugate plus free antibody?

Speaker 1

Thanks, Andrea. Well, that's a good question. We believe more broadly that disease variability in patients is what drives durability more strongly than the amount of conjugate that we have. So for example, in our Phase 1b study, we tested 2.5 mgs versus 5 mgs of fully conjugated material and there's very little distinction between the durability that we saw on the 2.5 milligram dose and the 5 milligram dose. So as we bring the level of conjugate down on the margin to allow a broader amount of free protein, we believe that we can bring the best of both worlds into both the takosumab and the KSI-five zero one formulations without impacting durability and creating a powerful medicine for patients.

Speaker 6

Got it. And then just maybe one quickly on the Phase 1 data that you have seen in DME for the 16 patients from the Phase 1. Could you just share or speak a little bit more about what gives you the confidence to move directly from that in the 16 patients to a Phase 3 trial now in wet AMD?

Speaker 1

Well, that's a good question. I think the important point about the Phase 1 study with KSI-five zero one was to gauge safety as well as to gauge bioactivity in terms of vision and OCT. And given the broad overlap across the retinal vascular diseases and with the existing agents, the idea of starting in DME where you can see predictable responses of bioactivity and safety and then using that kind of as a point of departure into any number of

Speaker 3

the different diseases. So, I

Speaker 1

mean, the four reasons that give us the platform 2, the dual mechanism of action right with best in class VEGF inhibition from the trap and where we also target IL-six, which is a known culprit of some optimal response and reactivation of disease in wet AMD. 3rd is our enhanced formulation. And 4, the 10 years of design, the manufacturing and the clinical and the operational experience that we have, the 3 INDs, the 3 molecules in clinical phase, the 2 first in human studies, the 8 clinical trials, 7 of them pivotal. So we're not starting from scratch here. And furthermore, in the future, we may be thinking of exploring KSI-five zero one in DME and RVO as well.

Speaker 6

Got it. Okay. Thanks so much.

Operator

Thank you. One moment for our next question. And our next question will come from the line of Gena Wang from Barclays. Your line is open.

Speaker 7

Thank you for taking my questions. Victor, based on current data, do you believe 501 is better than takosumab? And the related question is for DAYBREAK, other than being cost effective to avoid running an independent Phase 3 study for takosumab, will you try to design in a way to power to show the clinical benefit differences between 501 versus ticosumab?

Speaker 1

I don't think it's important whether ticosumab or 501 whether one is better than the other. There's clearly an opportunity for, let's say, a twice a year in the majority of patients. Anti VEGF agent and tarkosumab is just needs to get pushed over the finish line. And why don't we see how physicians like it and by running GLOW-two and having that tuck in group and the DAYBREAK study in wet AMD, we're going to be creating a useful amount of data for physicians for tarkosumab. It's not our objective to power a distinction between tarkosumab and 501 in Daybreak.

Speaker 1

I mean, if 501 showed maybe some trend that it was better than aflibercept or better than tarkosumab. We see that as very positive because we're also leading those agents with our own agent. And the question there for the 501 program is, it's going to need a second pivotal. And so at what point do we think it would be useful and important to start that such that it's a molecule that could be on a path to enter the market. I mean, if both molecules perform as we hope, right, tarcosumab and 501 showing a differentiated durability profile and they both meet the primary endpoint.

Speaker 1

It's a problem that we would be delighted to have.

Speaker 7

Okay. Thank you.

Operator

Thank you. One moment for our next question. Our next question comes from the line of Ellie Merle from UBS. Your line is open.

Speaker 8

Hi. It's Sam on for Ellie. We just had two questions. I guess first, where do you think about how IL-six inflammation is or like where do you think IL-six inflammation is particularly relevant in the context of this space? And then I'll ask my second after.

Speaker 1

Well, I think we believe that it's broadly relevant both within the high prevalence diseases that represent the anti VEGF market and we believe it's highly relevant outside of that into what we call sort of that greenfield area of macular edema and inflammation or the uveitis complex. And we believe those are 2 different opportunities and that's why we have 2 different molecules to be able to develop into both of them, right. So the KSI-one hundred and one allows us to have the protein alone, which is really a sledgehammer, highly potent on the 2 mechanisms at a very high formulation strength that should have a strong immediacy. So we're excited about that. And obviously IL-six plays a very important role in driving the macular edema in those patients and also in driving the inflammation.

Speaker 1

Within the retinal vascular diseases, inflammation clearly plays an important role. I think the question though, when you think about the drug development, what is necessary to show in a pivotal program? And do you want to play around for several years in Phase 2 studies trying to explore what large subgroups within say wet AMD, right, or what large subgroup within DME, right, where that inflammation is driving elements of the efficacy or the lack of efficacy in those patients. So rather than take that approach, what we're planning to do is to run the non inferiority to get the molecule approved in the different indications based on our expertise in running those studies and then work either in parallel or in smaller studies or investigator sponsored studies or post approval to be able to really tie patients with high inflammation to the drug to be able to show some improved level of efficacy. But we don't think we need to do that in a Phase 2 setting.

Speaker 1

We can drive these molecules for approval in the non inferiority setting and then work with physicians to showcase the special contribution of the mechanism.

Speaker 6

Okay, great. Makes a lot

Speaker 8

of sense. And then just a quick follow-up. For Daybreak, you mentioned dosing 501 every 4 to 24 weeks and then dosing a flip percent according to the label. What is your perspective on the recent FDA draft guidance regarding the use of a comparable dosing regimen in terms of like dosing frequency with the active comparator?

Speaker 1

Yes. Well, that's a good question. I think we've been in constant communication with the agency for all three clinical programs. And we'll confirm the study design once we have all the specifics. It's needless to say, but the final study design for all of our pivotals will be based on feedback from the FDA.

Speaker 1

I do think historically looking back, ODAC has driven innovation within study design with FDA successfully for ourselves and other companies followed our example. And at this stage, we're in discussion and we'll see kind of where we end up.

Speaker 8

Great. Thank you so much.

Operator

Thank you. And our next question comes from the line of Daniel Gadolin from Chardan. Your line is open.

Speaker 9

Hey, good afternoon and thank you for taking the question. I have one on 501 in wet AMD. Specifically for the 2nd pivotal study, are you guiding for with regards to any timelines when you plan on starting the trial and will that also include tarcosumab or do you plan to generate tarcosumab data from daybreak first before initiating the second study?

Speaker 2

We haven't disclosed and we don't have a complete plan for the second study of wet AMD. We know that we need one for approval for 501 in that case, but we haven't thought we haven't disclosed and fully have a plan of sequential or is it somewhat overlap between the two studies.

Speaker 9

Got it. And I have another quick question on what do you think are the potential consequences if dorkastimab does not succeed in the DAYBREAK study?

Speaker 3

Well, I guess

Speaker 1

we believe that taucosumab can be an important medicine for patients with wet AMD. But rather than just relying on the results of the daylight study where we dose monthly, we've decided that it makes sense to demonstrate

Speaker 3

that by having a full group in Daybreak. So if

Speaker 1

we didn't meet the endpoint in Daybreak and physicians would not feel excited to use it in wet AMD or presumably maybe based on having 2 unsuccessful studies in wet AMD, we might not be able to get approval in the indication. So it represents a bet that we're making. We're optimistic and we think it can drive substantial demand in wet AMD for tarcosumab and be really important. So in some way, introducing tarcosumab in the DAYBREAK study is a gamble, but it's one that's educated based on our detailed review of our data and also the adjustments that we've made to the go to market material and also our, I suppose, expertise or lessons learned from having run 6 pivotal so far. So we're excited to run tarkosumab in Daybreak and to see the data and hopefully to include that and to share that with community and we think it can be really powerful.

Speaker 1

Got it. Thank you very much.

Operator

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

Speaker 1

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

Operator

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

Speaker 6

Goodbye.

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Earnings Conference Call
Mitie Group Q4 2023
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