Yatin Suneja : Thank you so much.
Operator: Thank you so much. Your next question comes from the line of Jennifer Kim of Cantor Fitzgerald. Your line is now open.
Jennifer Kim : Thank you for taking my questions. As to, the first is just touching on the BCVA question. Jay, I think in your prepared remarks, you said a BCVA letter change differences, three letters are better would be good. And I think investors are generally aligned with that. The most pushback I’ve gotten is on the minus three to minus four letter scenario. So I was curious to see if you have any thoughts on that scenario. Is a base case or the hope that it would be better than that? And similar to that, in this scenario, where you get a minus three letter difference. With stat they have to assume a standard deviation better than what we’ve seen with say PDL.
Jay Duker: Sure. Great questions, Jennifer. Thanks. So the best corrected visual acuity of three or less difference, really would be I think kind of a clear pathway in everybody’s mind, if we can replicate that in the pivotal trials. Minus three to minus four is it kind of at theoretical range where one could argue that with a minus, let’s say three and a half letter difference in a large enough n and a small enough standard deviation, that that could be statistically non-inferior. But then you’re getting into a point here, where would it be commercially successful. So while it would meet that first bar of FDA approval, it may not meet the second bar of what the KOLs want, and perhaps, as you say, what the investment community might want to see as a result.
So I would say, again, centering on the three letters are better, I think that meets everybody’s test for success here. I’d remind everyone that, we were minus 2.5 letters in the Phase 2 at six months after the 1901 was injected and one would expect and of course, we don’t know this yet, but one would expect the EYLEA control arm to be relatively stable after the load between weeks, eight, and week 32. And if it is, and we can replicate minus 2.5 again, I think that that would be really an upstanding result. So the words again, is base case. And it’s again, I think a lot of this depends on what the view of what we need to do to advance the drug into, Pivotal trials. And one could see with a very tight standard deviation that even minus three letters would be statistically significant.
So you mentioned the PDS standard deviations. And again, if you go back and look at the pivotal trials, and wet AMD, I think basically, every one since EYLEA was approved was done on a non-inferiority basis, and treatment naïve patients and generally had standard deviation to the change in visual acuity of around 12 letters. That’s because their treatment naive, some eyes respond some eyes don’t. The PDS Phase 3 enrolled previously treated patients, like we did, but they limited the length of time to diagnosis to nine months prior. So some of those eyes were still relatively early in their treatment and still perhaps being treated extended. They weren’t at a stable kind of pace of their — treat of their disease, yet. They had 7.1 letter standard deviation.
So we have reasons to believe that because of our enrollment of eyes that had the disease longer than nine months, are suggesting they’d be more stable that our standard deviation could be lower than that. That ends the questions?
Jennifer Kim : Yeah, it does. If I could one more?
Jay Duker: Sure.
Jennifer Kim : Your competitor received — or announced that they received an agreement under their superiority trial design this morning. Net net, this seems like good news for the overall space given the post draft guidance world we’re in. But I’m wondering if you have any takes on that?
Jay Duker: Well, yeah. And again, that was just announced this morning, with no details. But at a high level, this is great news. It’s great news for all of the TKI companies, because it shows that the FDA is willing to work with us to advance this new paradigm into the clinic. And as we know, it’s great for the space. When investors see that there’s a clear pathway to approval, then things are derisk. From our perspective, we’re very comfortable with our Phase 2 design. And if we get good to great results. At this point, I think our Phase 3 design, which the FDA has already seen and commented on and through our Type C meeting, I think that still would represent the fastest, least risky way to get approval for our drug. Again, last comment about this, though, is once we are able to see the details of the spa [ph] that Oculus received.
We will like any company should do is, take a look at our program and see if there’s any learnings from what they’re doing. But I have to again, state we’re very comfortable with our approach to the pivotal trials in pathway to approval.
Jennifer Kim : Okay, that’s helpful. Thanks for taking my question.
Jay Duker: Thank you.
Operator: Thank you so much. Your next question comes from the line of Colleen Kusy of Baird. Your line is now open. Colleen, your line is now open. You may ask your question.
Jay Duker: Maybe we could go back Colleen after the next one.
Operator: All right. Your next question comes from the line of Daniel Catalin of Chardan. Please go ahead.
Daniel Catalin : I couldn’t hear that was my name that was called. Yeah. Thank you for taking the question. I have a quick one on 2301. Wanted to ask for the rationale for this product, and specifically, how does it fit with 1901 strategy given that there could be some overlapping indications? Thank you.
Jay Duker: Thanks, Daniel. That’s a great question. 2301 is based around a molecule that’s been studied into Phase 2, by a company called Aerpio, we acquired their assets, and their lead product AKB-9778, was delivered subcutaneously for diabetic macular edema, and for a diabetic retinopathy. And it showed really promising anatomic results. Although the visual results did not enable the company to really go forward into pivotal trials. This drug activates TIE-2, and by activating TIE-2, you stabilize blood vessels, and you down regulate angiopoietin or Ang2. Now, you may be aware that Obiosmo [ph] is bispecific that blocks VEGF and Ang2 so that pathway of Ang2 blockage is a validated. And we believe that AKB-9778 now EYP-2301 may be a better way to block that pathway by activating TIE-2.
Secondly, we can now deliver it sustained release. So these bispecific molecules still require relatively frequent injections. And we believe we can deliver at therapeutic levels for over six months with sync injection of 2301. So how does it fit in? Well, that remains to be seen. I think that we could develop it and tested in a non-inferiority fashion to get a label against the standard of care for either wet AMD or DME or both or we can choose to go for a superiority trial using it in conjunction with an anti-VEGF, that, of course, would be perhaps riskier because the anti-VEGF are so effective, it sets a really high ceiling. On the other hand, if one is successful with that approach, you would likely have a multibillion dollar product because doctors would relish the opportunity to do even better than anti-VEGF alone.
