How would it fit into a EYP-1901? You can highly speculative, because we’ve got a long pathway to go with 2301 shorter pathway with 1901, but you could envision a day when both have approval as standalone and as combo and one could do it one of each in a single injection. Obviously, that there’s a long pathway to that and a lot of permutations that we’re going to look at. But in a nutshell, what we believe we can do with 2301 is activate the TIE-2 pathway secondarily inactivating Ang2 and to do — to do it in a sustained release fashion with a derisked molecule.
Daniel Catalin : All right, got it. Thank you.
Operator: So much. Your next question comes from the line of Sean Kim of Jones Trading. Please go ahead.
Sean Kim : Thank you for taking my questions. Just a couple quick ones. So I guess for the wet AMD program, following the DAVIO 2 readout, would you be requesting on end of Phase 2 trial with FDA to further guide to Phase 3 trial design?
Jay Duker: That’s our plan. In fact, we would plan currently on having both a clinical end to Phase 2 and a CMC into Phase 2 to gain alignment in both those areas.
Sean Kim : Okay, got you. And the potential timing of that meeting?
Jay Duker: I would say late in the first quarter of next year, may lead into early second quarter of next year, depending again, how soon we can get all the clinical tables DAVIO 2 in a format that we can submit.
Sean Kim : Okay, great. Thank you.
Jay Duker: And the [multiple speakers] winning step here.
Sean Kim : Okay, got you. And what rally by your complement inhibitor collaboration? What updates should it — should we be expecting from that program in 2024?
Jay Duker: Thanks for that question. Sean, that’s a good question. And the answer is, as we’ve kind of said before, we’re really excited about the collaboration, we’re really excited about the molecule. Getting complement inhibitors, to last several months at therapeutic levels in the eyes of challenge. If it wasn’t a challenge, you’d see them already. However, we’ve made great progress. And we remain optimistic that we will be able to sustain release a complement inhibitor. But until we have really, are confident in our formulation and our ability to do this consistently, we’re not going to make any public statements around that. So I would say that, again, we’re still working on it. We have made great progress. We have some really great scientists working on this. But it’s not an easy task to accomplish.
George Elston: Yeah, Sean. Maybe I can add to that, because if you look at how we — our cadence on disclosure, we just disclosed 2301 this past quarter, because we’ve gotten that to a point where it formulates and we’re in a position to move it into those preclinical programs. And I think you should think the same for the compliment space as well. Once we get that formulation that we know works and has the right window, we’ll start talking about it a little more publicly on what that pathway looks like.
Sean Kim : Okay, I got you. Thank you. And last one from me, is that about the cash runway into 2025. The study includes potential pivotal three, Phase 3 trials in wet AMD as well, now that you’re looking to start in second half.
George Elston: Yeah, thanks for that question, Sean. So our phase — I’m sorry, our cash guidance into 2025 includes the ongoing Phase 2s. The planned phase in DME, which is the VERONA trial, which will we expect to start in Q1 along with a significant amount of Phase 3 prep, to start to be in a position to start the trials, sometimes second half of next year. It does not include the actual clinical trial costs for the pivotals. And, as we’ve talked previously, that’s something that we’re going to look to a range of options to fund, which includes potential equity weight arrays, we’ve got strong strategic partner interest and some other levers that we can pull. And we’ll be talking about that, over the coming months on our plans to fund that really after Phase 2 results.
Sean Kim : Okay, thank you again, for taking my questions.
Jay Duker: Good question. Thank you.
Operator: Thank you so much. The next question comes from the line of Yale Jen from Laidlaw & Company. Your line is now open.
Yale Jen: Questions to end, my question probably will be focusing on the potential future Phase 3 study. The first one is that in the one of your latest presentations, you have laid out four scenarios in terms of Phase 3 of different BCVA outcomes. I’m just curious, based on those assumptions, what might be your thoughts in terms under each scenario, what the Phase 3 study sites might be, then I have a follow up.
George Elston: Yeah, you’re talking about on the BCVA measures? Is that what you’re refercing?
Yale Jen: Right from 1.0 all the way to minus 4?
Jay Duker: Yeah. Yale, if I may, that those are actually we’re — our interpretation of the Phase 2 outcomes of where they might land and what they might mean for those outcomes. Without knowing the standard deviation of the change in visual acuity, we can’t predict the size of the trials. But you can run it into a statistics package and we’ve certainly done that. If we’re minus one letter worse than the EYLEA control and the standard deviation is seven or less, we could do pivotal trials that might involve as few as 250 to 300 patients. So it’s fluid because we don’t know those results yet. But there’s a second consideration. I think for most of these trials, that when you’re doing treatment naive patients when the standard deviation is larger companies ended up doing 500-600-700 patient trials.
But that’s because not only the standard deviation, because the FDA requires a certain number of patients for safety. So the FDA requires that you submit and you’re able to submit with one year efficacy data of your second trial, you don’t needed to your safety to submit. But at the one year, you need to have 300 patients treated with your go-to-market dose or higher. Ultimately, you need approximately 400 patients treated with your go-to-market dose or higher for safety. So that’s another consideration for the end of the trial. And that might, suggest that we would maybe not do a one-to-one-to-one randomization in the pivotals and have more patients in the higher dose to reach those safety measures, knowing that the statistics would allow a smaller number.
As I’ve said already, our view is to do this as quickly as safely as de-risked it as less expensive as possible. And that’s how we’re going to view all the options and the pivotal trials.
Yale Jen: Okay, great. That’s very, very helpful. And you mentioned earlier that the Phase 3 also incorporate the retreatment options or costs. Could you elaborate a little bit more in terms of at least what you propose the retreatment, any details on that?
Jay Duker: Sure. Yeah, thanks. And we’ve been — I think we’ve been very consistent from the start. Even though we have in-vivo and in-vitro evidence that these EYP-1901 inserts will release the therapeutic levels for approximately nine months, we’ve done enough tox studies to show that even if we reinject earlier than that, we’re in a very safe area for toxicity of vorolanib in number of inserts. In fact, we have not found the maximum tolerated level of a vorolanib within [Indiscernible]. So from a safety perspective, it’s not a problem. Why did we choose six months? I think it’s simple. That’s what retina specialists want. They want flexibility to dose drugs when they want to dose them. And while it’s clear that some eyes can go longer than six months, remember, in our pivotal — in our Phase 1 trial rather, we had a third of the eyes made it a year without supplement.
We’re going for the label of every six months, because we want to give the doctors flexibility to dose that often should they choose to.
