We asked the FDA if we could take the protocol violators and the dropouts and consider them in an ITT analysis that would have them all put into the 15 letter loser category. The FDA understood the question, told us that it would be a review issue clearly for patients that are dropping out or going outside of treatment protocol for efficacy reasons. That appeared to be a reasonable approach and that as part of the review, we would look at all of the data in its totality. That was a hugely reassuring bit of information from us, because as you know, on an ITT analysis, those dropouts and protocol violations generally need to go in one of the two categories. And we wanted to be sure that they would not be placed arbitrarily in the non-15 letter loser cohort.
And that was confirmed by the FDA. I don’t know, Rabia, is there any more you can add on this?
Rabia Ozden: No, I mean, you described it really well, Anthony. The only thing that I would add is that we are really, like happy to receive the guidance from FDA, how we should collect the information on those patients. They’re clear, like direction on the information FDA wants us to collect on whether they drop out because of the safety, efficacy or some other reason. That — as Anthony mentioned, is very encouraging.
Unidentified Analyst: Okay. Thanks. That’s very helpful. All right, thanks again for taking my question.
Antony Mattessich: Thank you.
Operator: Thank you. One moment, please. Our next question comes from the line of Colleen Kusy with Baird. Your line is now open.
Unidentified Analyst: Hi, this is Abbvie, on for Colleen. Congrats on the SPA and all the progress. I had a question regarding the patients at baseline. Previously you said, you were planning on enrolling patients that were closer to 2020 vision or who got to 2020 vision after induction with ILEA. Is that still the plan? And can you comment on how you think this entry criteria will impact your rate of enrollment?
Antony Mattessich: Yeah, that’s what’s in our SPA. Our SPA is for patients that after two doses of ILEA induction improve to 2020, that they are enrollable in the trial. Now, the great thing about having the SPA is that it’s really allowed us to have a concrete response from the FDA and allowed us to have a tremendous number of conversations with sites and with the opinion leaders. And we’ve had a lot of feedback from those sites. Now that they’re used to the concept of what we’re doing with this trial, and now that we have the endorsement from the FDA that this is a legitimate trial for registration, a lot of ideas about other broadening that definition and allowing more patients into the trial. Now, clearly to make any changes to that protocol, we need to go through a process with the FDA to ensure that the SPA reflects that.
But even as is, we’re able to start enrolling patients immediately. And we do think that that patient population that can get to 2020 is reasonably sizable, especially given the earlier diagnoses of wet AMD with the nearly ubiquitous use of OCTs in yearly ophthalmic exams. So we think we’re going to have enough patients with the protocol as is, but there are opportunities to broaden that entry criteria as well.
Unidentified Analyst: Wonderful. And then I was wondering if you could talk through what your expectations are in the earlier control group as to what proportion of those patients you’d expect to lose 15 letters.
Antony Mattessich: The working assumption is between 30% to 50% of those patients would progress to a 15-letter loss if allowed to do so.
Unidentified Analyst: Wonderful. Thank you so much.
Antony Mattessich: Thank you.
Operator: Thank you. One moment for our next question. The next question comes from Kelly Shi with Jeffries. Your line is now open.
Unidentified Analyst : Hi. This is Clara [ph] for Kelly. Thanks for taking our question and congrats on the process. Just wondering what degree study design was activated to be applicable to the second wet AMD trial as well? And also for diabetic retinopathy, what kind of data do you need to see to move forward to the Phase 3 pivotal trial? And what might be the expected cause associated with that trial?
Antony Mattessich: Sure. Rabia, you want to field that?
Rabia Ozden: Yes. The first question, whether the second pivotal would be the same. Yes, it would be the same design as, like the design that we are going to run with the first trial. And can you please repeat your question on the second question, Kelly? Clara, sorry.
Unidentified Analyst : Yes, sure. So I was asking in terms of diabetic retinopathy, what kind of data in Q4 do you need to see in order to move forward to Phase 3 pivotal trial? And what might be the expected cause associated with the pivotal trial? And how do you plan to fund the trial?
Rabia Ozden: Okay. I’ll just take the first part of that question. I’ll leave the funding to Anthony. For the DR trial, our expectation, as you know, this is a small trial. The number of the subjects, we enrolled 22 subjects in the trial. And they are like two to one in expats versus the sham. Our expectation is to see a trend in the improvement in the DRSS score. We are really not looking for any non-inferiority. Our sample size would not, is not enough for that. That’s why we are looking for a trend in the DRSS score improvement. Anthony, would you like to take the rest of the question?
Antony Mattessich: Sure. I mean, obviously, we’re not committed to a particular form of funding at the moment. I mean, we’re very fortunate that we have cash at the moment and we have a runway into 2025. There are opportunities in a number of different both dilutive and non-dilutive opportunities to be able to help fund that second trial. Clearly, the SPA gives clarity that we did not have before and that creates an investment opportunity that, or a partnership opportunity that’s a bit more clear than what existed in the past. So, I think this SPA actually opens up more avenues than we had before, but we haven’t committed to a particular source of funding. Clearly, once we get traction on this first pivotal, the desire to set up another pivotal in order to get to market in a reasonably short period of time is overwhelming, given that the destination, the value of two positive pivotals in a wet AMD with a nine to 12 month product is a multi-billion dollar opportunity.
And we’d like to get there as fast as we possibly can.
Unidentified Analyst : Terrific. Thank you.
Antony Mattessich: Thank you.
Operator: Thank you. One moment for our last question. This question comes to the line of Yi Chen from H.C. Wainwright. Your line is now open.
Yi Chen : Thank you for taking my question. I recall you previously reported that 73% of patients were rescue free and months 10 with 600 micrograms. Now, you are using 450 micrograms. So, what percentage of patients do you expect to be rescue free at the end of nine months?
Antony Mattessich: Well, we would expect that number to be the same or higher. I mean, this new formulation will deliver just like the older formulation or the pre-optimized formulation. It’ll deliver drug continuously for nine to 12 months. And as we mentioned, for the first nine months, it will deliver drug at a slightly faster rate than the 600 microgram dose. So, up until nine months, you’re actually going to get more drug to the target tissues than you would have with the previous 600 microgram formulation. So, up through that nine month timeframe, we’re very confident that we’ll do at least or better than that. Certainly, in terms of the drug delivery, we will. We believe we’ll still have enough drug in the target tissues and in the vitreous post-dose to be able to extend the effective concentrations in the RP and the choroid up into month 12.
Yi Chen : And will you use the 450 microgram formulation for MPPI as well in the future?
