Our global healthcare conference. The next 12 months are going to be eventful for Outlook, with ONS-5010 reading out, the NORSE EIGHT trial, and hopefully launching in the U.S. and Europe. So with that, I'll turn it over to Russ to tell us the Outlook story. Thank you, and welcome.
And thanks again, so much for having us. This has been an exciting year so far, and we do expect a strong finish as well. And the big idea for us is that we believe we've got an opportunity to enhance the standard of care for bevacizumab for treating retina diseases. Next slide, please. And this is our disclaimer. We will be making forward-looking statements. Next, please. So what do we mean by enhancing the standard of care? Let's first think about what is the current standard of care in treating retina diseases, those retina diseases being comprised largely of wet AMD, which is the largest category, followed by DME and BRVO.
And when we think about the most frequently injected molecule, today, it is bevacizumab, although it's off-label, and we're gonna talk about what the ramifications are, of that. We have already this year become the first company ever to receive European Union and U.K. marketing authorization for bevacizumab in the retina anti-VEGF space. Our original studies were all in wet AMD, and that leaves us an opportunity to continue on with future clinical trials associated with diabetic macular edema and branch retinal vein occlusion, which we do plan on commencing in the coming years. This is at least a $16 billion space, and it seems to be getting larger in both injection volume as well as with some of the new entrants coming in with even higher pricing than before.
This category will continue to grow. In Europe, in the second quarter, we did get great news from the European Union. We were able to show them both our clinical data in wet AMD, as well as our CMC data, and we got a positive opinion that was followed by approval for marketing or authorization in the EU. We then took those same data and applied to the U.K. MHRA, and we were able to receive marketing authorization from them in July of 2024. What we're doing in Europe right now is we're doing the important market access work that needs to be accomplished that will help establish pricing on a market-by-market basis, that does need to be negotiated in advance.
Our initial two markets are gonna be that we're targeting are the U.K. and in Germany. But we're also talking to potential partners in Europe. There are folks, companies that are out there that have European infrastructure, something we don't currently have. We've got to build that ourselves. Where we find a partner, if we should find a partner or partners that we believe can do as good a job or better for less money than what we can do it, than the launch costs that we would have to engage in, then we will entertain possibility of signing one of those companies as a partner. That's what we're doing in Europe right now. In the United States, we're still in clinical trials.
We have one more ongoing trial, this, our so-called NORSE EIGHT trial. We'd initiated that trial this year, and we'll give you some additional information later in this presentation about that. And then we will take those clinical data, along with answers to some CMC questions that FDA had, and resubmit our BLA, hopefully in the first quarter of next year. Next slide, Amanda. So as I said, this is a big space. It's $8billion-$9 billion in the United States, about $3billion-$4 billion in Europe. But one of the things that we've established years ago was there gonna be physician interest in an approved form of bevacizumab?
It was an open question because doctors have been using off-label bevacizumab, which was originally designed to be delivered through a drip IV to treat oncology, and that's indeed how it's used today for oncology. Those specifications for an oncologic version of bevacizumab are a bit different than ours. The standards that they have to live to are a bit different from ours, but the doctors were using it. They were using it about half the time. In fact, even you know patients were typically started on this product. We did some deep market research years ago to establish whether there was indeed physician interest in this category, and we found out that, yes, there was.
85% of the doctors in the United States were interested or highly interested in an approved version, in an ophthalmic-approved version of bevacizumab, as well as 82% of the doctors in the EU and U.K. Next slide, please. So what we find today, this oncologic drug is very popular. It just in terms of starting patients. It's reported that, you know, the U.S. physicians report that about 2/3 of the doctors start about 2/3 of their patients on this oncologic version of bevacizumab because it's cheap, it's available, it doesn't require insurance coverage, but there's been a demonstrated lack of potency that's been shown in peer-reviewed studies, significant safety issues, and quality and supply issues.
So our response to this was to apply for an 8.3 application, a mixed application in Europe, which we've already been successful with. We've already received approval. That will grant us 10 years of market exclusivity for this product, and likewise, or similarly, I should say, we've submitted as a 351(a) BLA submission as an original molecule in the United States, because this is an original molecule in ophthalmology. If we're successful achieving that FDA approval, that will grant us 12 years of regulatory exclusivity in the United States. Next slide. So there's a real and not imagined difference between what you're required to do to get an approval in ophthalmology versus oncology.
If you look at osmolarity specifications, if you look at pH levels that the eye likes to have, that the rest of your body doesn't really care about, if you look at the stability data and shelf life that we have to prove with every batch, you look at the approved packaging we've gotta have, a lack of bacterial endotoxin levels, these are all differences in ophthalmology in terms of specifications compared to oncology, and in addition to that, if you look at one of the other requirements around particulates or lack of particulates, for an oncologic version of bevacizumab, you can have up to 6,000 particulates that are 10 microns or larger per milliliter for an oncologic version of bevacizumab. That's the requirement.
We can't even have 50, and in fact, our manufacturing processes deliver a number that's closer to zero particulates than it is to 50 particulates. So these differences are real and not imagined in terms of what you have to prove in ophthalmology versus oncology. And then, in addition to that, drug protein concentration is probably the most important thing. Next slide. And when we're talking about drug, drug protein concentration, there have been studies that have been performed in the United States, where a group of doctors took off-label bevacizumab that was repackaged to be used in ophthalmology and compared it to just the oncologic version of bevacizumab. And what they found was that in 81% of the samples they looked at, there was less drug in the repackaged form of bevacizumab than there was in the original container of bevacizumab for oncology.
So there's something happening during the repackaging process that shears that molecule, and when it reaggregates on the other side of this refiltering, repackaging process, you end up with less drug protein. So that, I think, is part and parcel as to why there's so much switching that goes on. We find that 40% or more of the patients that start on oncologic bevacizumab are switched to ophthalmic brands. Next slide, please. So what we're doing to support this product in Europe is we're doing all of the market access work that needs to be done in order to get this product launch. We're engaging with leading retina KOLs. We've had some great recent meetings with KOLs in Germany. We're working with Cencora, a Fortune 10 company.
Many of you might know them as AmerisourceBergen, but they are a company that can well support a launch like ours. They've got services in regulatory pharmacovigilance, GPO contracting, payer connectivity. They helped us going through the HTA process, which must be done, and they've turned out to be a great partner. We're using them in both Europe as well as in the United States. Europe, in the condition where we launch it ourselves, or if we do end up signing up with a partner, AmerisourceBergen or Cencora is ready, able, and willing to help those partners if we end up signing an agreement with them. Next slide, please. So the roadmap to FDA approval is the following. Next slide, please.
We've already performed three studies in the United States, three human clinical studies in the United States, NORSE ONE, NORSE TWO, and NORSE THREE. NORSE ONE was a clinical experience trial, NORSE THREE was an open label safety trial, and NORSE TWO was our pivotal trial, where we had amazing data that I'll talk about in a slide or two. The one study that we still have yet to do is NORSE EIGHT. Next slide, please. The construct of NORSE EIGHT is that it will be a 400-patient trial, all treatment naive. They've never been treated before. This is for wet AMD, and the primary endpoint for this study is best-corrected visual acuity at eight weeks, and we want to show a non-inferiority margin of three and a half letters.
Remember that number, 'cause it'll mean something in a slide or two. The dosing is either gonna be randomized between our ONS-5010, which is our bevacizumab candidate, or Lucentis. They will be dosed at day zero, day 30, and day 60, and the patient's best-corrected visual acuity will be measured at day 60. Next slide, please. So the construct of NORSE EIGHT is exactly the same as the first three doses of our NORSE TWO trial that FDA has already opined on and said we'd met our, all of our, endpoints.
Again, it was dosing at day zero, 30, or 60 of either Lucentis or our product, and what we found was, at day 60, if you looked at that non-inferiority margin, there was about a letter difference in best-corrected visual acuity, well within the three-and-a-half letter non-inferiority margin that we're looking for. It happened to be in our favor in this particular study. In other words, our patients were seeing about a letter better than the Lucentis patients, but statistically it's the same number. It shows non-inferiority. So because we've already demonstrated this in NORSE TWO, we expect to see the same result in NORSE EIGHT. Next slide, please.
The NORSE TWO data, our primary endpoint in that one was the percentage of patients that gained 15 letters or three lines of vision, and we had almost 42% of our patients hit that endpoint, and that compared to 23% of the Lucentis patients. This was a superiority trial where we did more frequent dosing with the ONS-5010 patients than Lucentis. But that p-value demonstrates that this was a statistically significant superiority result. It was 0.0052 p-value. The FDA is only looking for 0.05, so we got an extra digit out of that one. This was a highly statistically significant result, and just exactly what we wanted to show. Next slide, please. What we've been able to achieve this year has been fantastic. In the first quarter, we went to FDA to get a SPA agreement on NORSE EIGHT.
We got it. We wanted to commence that NORSE EIGHT study in the first quarter. We did. In the second quarter, we were hoping for a positive CHMP opinion, followed by EU marketing authorization. We got it. We also wanted to submit in the U.K. We did it. In Q2 and Q3 in the United States, we said we were gonna conduct Type C and Type D meetings to run through with the FDA our CMC data. We accomplished that. We also in the first half of this year wanted to achieve U.K. marketing authorization. We did. We are continuing partnering discussions in Europe, and then we expect to be able to commence inventory availability to support the launch in Germany and the U.K. in the first half of 2025.
While meantime, we complete NORSE EIGHT enrollment in Q3 in the United States, announce our top-line data in Q4, resubmit our BLA in Q1 2025, and then hope for a positive FDA decision in the second half of 2025. Because we've hit all of our goals this year so far, we expect to see continued success next year. Next slide, please. From a financial standpoint, we showed cash and cash equivalents of $32 million when we reported our results for the June 30 quarter. We do have outstanding debt. It's a convertible note that's about $32 million. We did, in the first quarter, close a private placement that had gross proceeds of up to $172 million.
65 million was the first tranche, and that was from issuance and sale of shares of common stock, and then we've got the potential to receive another over $100 million upon the full exercise of warrants that were part of the deal, and we had top-tier institutional healthcare investors in this investment for the first time in Outlook's history. Next slide, please. This is a pivotal year for us. We have achieved the first approvals for bevacizumab in ophthalmology in Europe. We are engaging with potential licensing partners for commercial launch in the EU and U.K. early next year. We do expect top-line data from NORSE EIGHT in the fourth quarter of this year, and we are focused on getting our BLA resubmitted to FDA in the first quarter of next year.
We think we've got an opportunity to really be potentially transformational company in this space and really bring the possibility of a pristine level of safety and efficacy for bevacizumab patients for the first time in history. Next slide. I'd just like to say thank you to H.C. Wainwright for inviting us again. You've always put on a great conference, and we appreciate being a part of it. Thank you.
Thank you so much, Russ, for that comprehensive update. Lots of exciting milestones coming up, so we're excited to hear more about that as they come up. I just have one quick question, if I can ask, and you probably get this all the time anyway, but according to, keeping in mind the extensive market research you've done, would you just quickly comment on the pricing strategy? And do you think it's in a sweet spot enough to help the switchover from the off-label to 5010? Just a quick comment on that.
Yeah. I think what's important to understand about the landscape right now is the cheapest form of bevacizumab right now, the off-label repackaged version, right now can be obtained for a little under $100 per injection. The brand's wholesale acquisition cost range from $1,850 to over $2,500 per injection, being mindful that, you know, usually in the first year, five to seven injections are required for these wet AMD patients. Even the biosimilars have come in with wholesale acquisition costs of $1,100, about $1,130-$1,340. So there's a big difference. There's a large gap between the cheap off-label bevacizumab and the biosimilars and the brands that are much, you know, much more expensive.
What we've been able to demonstrate to payers is that when you start a patient on off-label bevacizumab, and you switch them 40%-50% of the time or more, your average cost per injection, including the cost of what you switched to, is closer to $1,000 per injection than it is $100 per injection.
In being able to socialize that with both the doctors as well as the payers, basically the request that came back from the payers was, "If you can price this less than the average of what I'm paying now," again, with that average being the combined cost of both the off-label as well as the branded versions that they're switching to, "then we would consider that a first-line treatment opportunity for us." Because if patients come and start on your biologic and stay at the same rate that they stay on the other approved brands, which would be the expectation, because we expect to show non-inferiority in the next clinical trial, then that would save the payer system money.
So we don't want to give a specific number on that until we're able to take or, you know, get an approval, take orders, and be able to defend that. But I think it's worth noting for all potential investors, we've had these conversations with the payers, and we've asked for their input. We have not gone into the payers and said, "This is our price, and here's our defense." We've gone into the payers and said, "What do you want us to charge for it?" And so our expectation, our belief, is that we'll be the first company to ever launch in this wet AMD space with a price that was suggested by the customer.
All right. Thank you so much, Russ. It was nice to meet you.
Nice meeting you, and thank you again for having us.