Good morning. My name is [indiscernible] and I will be your conference operator today. At this time, I would like to welcome everyone to the EyePoint Pharmaceuticals Second Quarter 2023 Financial Results and Recent Corporate Development Conference Call. There will be a question and answer session to follow at the completion of the prepared remarks.
Please be advised that this call is being recorded at the Company's request. I would now like to turn the call over to George Elston, Chief Financial Officer of EyePoint Pharmaceuticals..
Thank you, and thank you all for joining us on today's conference call to discuss EyePoint Pharmaceuticals' second quarter 2023 financial results and recent corporate developments. With me today is Dr. Jay Duker, President and Chief Executive Officer.
Jay will begin with a review of recent corporate updates and discuss Phase II clinical trials for EYP-1901, I will close with commentary on our second quarter 2023 financial results and we will then open the call for your questions. Earlier this morning, we issued a press release detailing our financial results and recent operational developments.
A copy of the release can be found in the Investor Relations tab on the corporate website, www.eyepointpharma.com. Before we begin our formal comments, I'll remind you that various remarks we will make today constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995.
These include statements about our future expectations, clinical developments and regulatory matters and time lines, the potential success of our products and product candidates, financial projections, and our plans and prospects.
Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our most recent annual report on Form 10-K, which is on file with the SEC and in other filings that we may make with the SEC in the future.
Any forward-looking statements represent our views as of today only. While we may elect to update those forward-looking statements at some point in the future, we specifically disclaim any obligation to do so even if our views change.
Therefore, you should not rely on these forward-looking statements as representing our views as of any date subsequent to today. I'll now turn the call over to Dr. Jay Duker, President, and Chief Executive Officer of EyePoint Pharmaceuticals..
Thank you, George. Good morning, everyone, and thank you for joining us to discuss our continued success as we advance first-in-class therapeutics and delivery technologies to provide a brighter future for those at risk of losing their site.
First of all, I'd like to say that I'm honored with the name EyePoint CEO and I would like to thank the EyePoint's Board of Directors for their confidence in me. I would also like to thank Nancy and the entire executive team for their partnership, collaboration, and leadership during my tenure at EyePoint.
As a physician dedicated to improving outcomes in retinal disease, I'm incredibly passionate about EyePoint's mission of bringing innovative therapies to patients at risk of losing their sight.
For the past seven years, I've had the opportunity to work closely with the exceptional team of talented professionals at EyePoint to advance our exciting pipeline of products with the aim of transforming treatment paradigms for patients. I'm committed to continued execution towards this goal.
With the recent sale of YUTIQ, we at EyePoint, have completed our transformation to a pure play development stage biopharmaceutical company, and I'm incredibly excited to be stepping into the CEO role at this important juncture.
With our compelling clinical pipeline representing multi-billion-dollar product opportunities, our best-in-class sustained ocular delivery systems, along with a strong balance sheet, we're well-positioned to grow as a leader in ocular drug delivery and to bring impactful therapies to patients.
With that, I'll now review our recent progress and give an overview of upcoming milestones. Turning to our lead program, EYP-1901 a potentially paradigm shifting maintenance treatment for patients suffering from serious eye diseases. We are now fully enrolled in two oversubscribed Phase II clinical trials.
The DAVIO 2 trial for wet age-related macular degeneration or wet AMD and the PAVIA trial for non-proliferative diabetic retinopathy or NPDR. As a reminder, EYP-1901 is an investigational sustained release therapy that consists of Durasert E, the bio erodible formulation of our Durasert technology.
With vorolanib, a highly selective small molecule tyrosin kinase inhibitor with unique properties. EYP-1901 brings a new mechanistic approach to the treatment of VEGF mediated chronic serious posterior sigma diseases, such as wet AMD, NPDR, and diabetic macular edema. By acting as a pan-VEGF receptor blocker blocking all VEGF isoforms.
Compared to other TKIs, vorolanib features reduced off-target binding and does not inhibit the Tie2 receptor at clinically relevant doses leading to a potentially improved safety and efficacy profile for this differentiated molecule.
Additionally, another potential treatment benefit of EYP-1901's mechanism of action is the possibility for neuroprotection and antifibrotic effects. EYP-1901 delivers vorolanib consistently and reliably with steady zero order kinetic dosing for approximately nine months in the eye through the Durasert E technology.
At the ARVO annual meeting in April, we presented preclinical data highlighting the potential neuroprotective effect of vorolanib the active drug in EYP-1901 against photoreceptor degeneration in a validated retinal detachment model.
The preclinical data highlighted vorolanib's potential new mechanism of action for treating retinal diseases and its potential unique benefits that may set it apart from existing ligand binding biologics.
These preclinical data demonstrated that vorolanib significantly reduced the severity of change in baseline visual acuity and improved contrast thresholds in mice treated with vorolanib compared with placebo. Suggesting a neuroprotective effect against photoreceptor degeneration.
Should this be reflected in clinical data, it would provide an important new mechanism of action for the treatment of these chronic blinding retinal diseases such as wet AMD, NPDR, DME, and retinal vein occlusion. We are very pleased with the progress of our two key Phase II trials of EYP-1901.
In the DAVIO 2 trial, EYP-1901 is being investigated in 160 subjects with previously treated wet AMD with a goal to sustain the treatment effect for the majority of wet AMD patients up to six months or longer following a single injection of EYP-1901.
This could represent a significant improvement compared to current standard of care anti-VEGFs, which are dosed on average every two months in the United States. This lifetime of frequent treatment represents a tremendous burden for patients who are at risk for losing sight from wet AMD.
By using EYP-1901 is a maintenance therapy following induction treatment with large molecule anti-VEGFs, we aim to provide a sustained delivery of vorolanib, so that patients and practitioners can potentially have the flexibility to reduce the number of visits to their retina specialists without sacrificing visual outcomes.
All patients in the DAVIO 2 trial were previously treated with a standard of care anti-VEGF therapy, and were randomly assigned to one of two doses of EYP-1901 approximately two milligrams or approximately three milligrams versus an on-label Aflibercept control.
EYP-1901 delivered with a single intravitreal injection in the physician's office similar to current FDA-approved anti-VEGF treatments. Recently, we provided updates at several medical meetings for the Phase I DAVIO and Phase II DAVIO 2 trials.
At the OIS Retina Innovation Summit in July, we presented interim, mask, safety and baseline patient demographics from the DAVIO 2 clinical trial in wet AMD.
As of July 1, 2023, a mask safety summary found that there were no reported drug related serious ocular adverse events or SAEs or drug related systemic SAEs in the 160 enrolled patients in the DAVIO 2 trial.
Additionally, an analysis of the reported baseline patient demographics suggests that the Phase II DAVIO 2 patients have on average, better starting visual acuity and less central subfield thickness than the Phase I DAVIO cohort. Mean BCVA at baseline was 74 letters for patients in DAVIO 2 versus 69 letters for patients in the DAVIO 1 trial.
While on OCT evaluation, the mean central subfield thickness was 265 microns for patients in DAVIO 2 versus 299 microns in the Phase I DAVIO trial.
Additionally, at this year's American Society of Retina Specialists annual meeting in July, we presented 12-month ocular pharmacokinetic results from a study evaluating EYP-1901's drug delivery through the Durasert platform.
We also presented an encore subgroup analysis of the EYP-1901 final 12-month Phase I DAVIO results, which showed that of the nine Phase I DAVIO patients that had no excess fluid at screening, 67% did not require a supplemental anti-VEGF injection for up to six months, and over 50% did not require any additional therapy for up to one year.
In June, we presented an encore presentation of 12-month results at the European Society of Ophthalmology Congress 2023 in Prague for the Phase I DAVIO clinical trial evaluating EYP-1901 and previously treated wet AMD.
The presentation is significant, because it marks the first time that we presented EYP-1901 clinical trial results outside of the United States. We are very excited by the trial's progress, and we look forward to reading out top-line results for the DAVIO 2 trial in December of this year. Now, let me turn to our second indication, NPDR.
In June, we were pleased to report that we completed enrollment in the Phase II PAVIA clinical trial. This is a randomized controlled phase II trial evaluating EYP-1901 as a potential nine-month treatment for moderate to severe NPDR.
Similar to DAVIO 2 trial, our PAVIA trial saw significant investigator and patient interest during enrollment and the trial enrolled 77 patients succeeding the 60-patient target.
Patients were randomly assigned to one of two doses of EYP-1901 approximately two milligrams or approximately three milligrams, or to the control group that received a sham injection. As in the wet AMD trials EYP-1901 is delivered with a single intravitreal injection in the physician's office for NPDR.
As a reminder, NPDR is a very common eye disease that affects almost one third of diabetic adults over the age of 40 and is projected to impact over 14 million Americans by 2050.
In NPDR, blood vessels are weakened, potentially leading to swelling in the macula, which is called diabetic macular edema, or DME, and eventually abnormal blood vessel growth, which is called proliferative diabetic retinopathy, or PDR. Both of these complications can ultimately result in severe visual loss.
It's important to note that there remains a great unmet need for a safe, efficacious, and convenient treatment option for NPDR that proactively maintains a patient's vision over a long period of time with fewer intravitreal injections than the currently available therapeutic options.
Approximately 90% of patients with NPDR received no course of treatment apart from observation by their eye doctor until their disease progresses to a site threatening complication. Due to the burdensome nature of the currently approved short-acting treatments.
EYP-1901 and our phase II PAVIA trial could potentially safeguard patient's vision for a much longer period of time between treatments. Top-line data remains on track for the second quarter of 2024. Looking ahead, we also plan to initiate a phase II trial evaluating EYP-1901 and DME in the first quarter of 2024.
Importantly in May, we sold YUTIQ to Alimera Sciences for $82.5 million in addition to future royalties. This value creating transaction allowed us to retire all of our outstanding bank debt, reduced our projected SG&A, and extend our cash runway into 2025 as we prepare for potential phase III trials.
The sale also completed EyePoint's transformation into a pure play drug development company with sharpened focus on advancing and expanding our pipeline of sustained delivery treatments for serious eye diseases. I would like to thank the entire EyePoint team for an incredibly productive quarter.
I will now turn the call back over to George to review the financials.
George?.
Thank you, Jay. As the financial results for the three months ended June 30, 2023 were included in the press release issued this morning, my comments today will focus on a high-level review for the quarter. As Jay mentioned in May, we sold the YUTIQ franchise to Alimera Sciences for $82.5 million in addition to future royalties.
EyePoint received a $75 million upfront cash payment at closing and we'll receive an additional $7.5 million and equal quarterly installments in 2024. Importantly, we were able to pay off all existing bank debt from the upfront proceeds of this transaction, significantly improving our balance sheet.
In addition, commencing in 2025, we will receive a low to mid-double-digit royalty on Alimera's related U.S. net sales above defined thresholds for the calendar years 2025 through 2028.
Under the terms of the agreement, Alimera received global rights to YUTIQ outside of China, Hong Kong, Taiwan, Macau, and Southeast Asia, where YUTIQ is exclusively licensed to Ocumension Therapeutics and EyePoint will continue to receive royalties from Ocumension for its YUTIQ sales.
For the second quarter ended June 30, 2023, total net revenue was $9.1 million, compared to $11.6 million for the quarter ended June 30, 2022. Net product revenue for the second quarter was $5.3 million, compared to net product revenues for the second quarter ended June 30, 2022 of $11.3 million. Consistent with our exit from the commercial business.
The decline in revenue resulted from the sale of the YUTIQ franchise to Alimera in May, along with the discontinuation of marketing activity for the DEXYCU franchise. Earlier this year due to the loss of pass through reimbursement by CMS effective on January 1, 2023.
Net revenue from royalties and collaborations for the second quarter ended June 30, 2023 totaled $3.8 million, compared to $0.3 million in the corresponding period in 2022. The increase was primarily due to recognition of deferred revenue from the sale of YUTIQ, which will be recognized over a two-year period.
Operating expenses for the second quarter ended June 30, 2023, totaled $31.9 million versus $30.8 million in the prior year period. This increase was primarily driven by higher R&D spending on EYP-1901 clinical trials partially offset by lower sales and marketing expense.
Non-operating expense net totaled $0.2 million and net loss was $22.9 million or $0.61 per share compared to a net loss of $19.4 million or $0.52 per share for the prior year period. Cash in investments at June 30, 2023 totaled $142.5 million compared to $144.6 million at December 31, 2022.
We expect the cash, cash equivalences, and investments on hand at June 30, 2023, will enable us to fund our current and planned operations into 2025. In conclusion, we are pleased with EyePoint's progress in the second quarter and year-to-date, and our well capitalized to advance our product pipeline to key value inflection points.
I'll now turn the call back over to Jay for closing remarks..
Thank you, George. As you can see 2023 has been an excellent year for EyePoint thus far as we continue to execute on multiple clinical catalysts. Moving forward, we are well positioned to achieve a number of potentially value creating milestones, including top-line data from our Phase II DAVIO 2 clinical trial in December.
Dosing of the first patient in the Phase II clinical trial of EYP-1901 and DME in the first quarter of next year, reading out top-line data from our Phase II PAVIA clinical trial in the second quarter of 2024, and advancing our discovery stage pipeline that includes both wholly-owned products and partnered programs.
We believe EYP-1901 is a potentially game-changing treatment for patients suffering from serious eye diseases, providing unique benefits including delivery of the active drug vorolanib consistently over approximately nine months with a majority of patients not requiring any supplemental therapy up to six months after a single treatment.
A new mechanism of action to treating retinal disease beyond anti-VEGF ligand blockers, potential for neuroprotection and anti-fibrotic benefits to the retina, and a proven delivery technology with a positive safety profile.
This remains an incredibly exciting time to be part of the EyePoint story as we are well positioned to execute on our upcoming milestones and continue to transform the treatment landscape with innovative long-term solutions to improve both the vision and the lives of patients with serious eye diseases.
Thank you all very much for listening this morning. I will now turn it over to the operator for questions.
[Operator Instructions]. Our first question comes from the line of Tyler Van Buren of TD Cowen. Your line is open..
Hey guys, good morning. Congrats on all the progress. There's a lot to look forward to over the next year. I've got a couple questions for you. So, the first one is you mentioned the starting visual acuity in central subfield thickness for the DAVIO 2 patients that were enrolled in, presented on over the weekend, of course.
But can you discuss how that compares to the subgroup of patients in the DAVIO 1 trial that had no excess fluid at baseline and what the readthrough for those, what readthrough that has for the results coming in Q4? And then, the second question is, given the safety issues experienced by safe harbor early in the launch, what can you guys do during clinical trials to ensure that 1901 does not have the same issues pop-up upon potential market introduction?.
Well, thanks Tyler. Appreciate the questions. I'll take the first one on visual acuity and CST from DAVIO 2 trial. Again, just to remind people. In DAVIO 1, we had a pretty heavily treated group of patients. On average, they had received 8.6 injections in the year prior.
DAVIO 2, we believe, represents more of a cross section of wet AMD population out there. And so, the visual acuities in DAVIO 2 were about aligned better than in DAVIO 1. And the CSTs were drier 299 versus 265. Now, if you go back and look at the subgroup analysis in DAVIO 1, by definition, that subgroup had no excess fluid.
Remember, in DAVIO 2, we allowed some fluid, and the CST cutoff was three 50 microns, which allows some fluid. So, the CSTs in the no excess fluid group was about 244 microns. So naturally less than the entire DAVIO 1 cohort or even DAVIO 2.
Visual acuities, however, were worse in the subgroup analysis, again, reflecting the severity of the disease in DAVIO 1.
As for read through, again, I like to say, DAVIO 1 was the end of '17 and so it's dangerous to make broad statements about read through, but I think it's safe to say that the DAVIO 2 population was under better control with their wet AMD than the DAVIO 1 population.
The second question was around safety and of course that is on everybody's mind, in the retina community has been for a while. The good news is, there really has never been any significant safety signal that we are aware of in the Durasert platform. Remember, the Durasert platform has been in four FDA approved products over the last few decades.
We estimate over 80,000 people have received it. And again, has a very clean safety record. The Durasert E or erodible form the Durasert that we're using EYP-1901 has actually fewer excipients. So, we believe the safety profile should be similar.
Turning to vorolanib, vorolanib was tested as an oral agent in wet AMD in two trials, approximately 150 patients in total received it. And while it did have systemic toxicity as an oral agent at it had no ocular toxicity. And so far in the DAVIO 1, and DAVIO 2 trials, we have seen no evidence or had no reports of any drug related ocular SAEs.
Turning to preclinical, we have preclinical data on rabbits that show that the equivalent dose in a human of 10 times what we could ever put into a human, it was safe in a rabbit. So, we've not found the maximally tolerated dose of vorolanib in a rabbit at this point. Looking at inserts, we've injected up to six inserts into a rabbit eye.
The rabbit eye is about a quarter of the size of a human eye and no toxicity was reported. So, we're very comfortable with the preclinical talks and so far, the clinical talks with EYP-1901.
Of course, if you're talking about events that could occur 1,000 in 5,000 or 1,000 in 10,000, you got to do a lot of patients before something like that would come out..
Our next question comes from the line of Yatin Suneja of Guggenheim. Your line is open..
Thank you. Maybe just following up on Tyler question.
Can you maybe just tell us like in terms of these patients, the baseline that you provided, like what was the average injections for them coming into the study? So that's first and then can you maybe talk about the re-treatment plan in Phase III, what the goal would be? How would you get retreatment on the label, once you moved into the pivotal? Would you have to show that in the pivotal study?.
Thanks, Yatin. The first question about the number of injections for the Phase II patients leading into the trial. That data has been collected, but it hasn't been collated yet. That's the type of data that we will hold off from talking about or showing publicly until we're ready to show the top-line.
So, at this point, we as a company haven't seen that data and won't be talking about it until we're confirmed that the data is accurate. With respect to retreatment, we've been very consistent from the start of the EYP-1901 program. That we want to get a label for every six months retreatment. That's been our goal.
Why every six months? Well, the answer is first of all, that's what most retina specialists want when you poll them and ask them. Number two, you can ask, well, why, you have a insert that could last about nine months in a human, why would you go for six months? And the answer is flexibility. Every patient's different.
And that's been shown really, if you really drill down to the data in all these anti-VEGF programs that the number one determinant of when a patient needs a re-treatment is the patient, it isn't the drug. So as a result, we had patients in our Phase I, a third of them went out a full year without a re-treatment.
But we would like the doctors to have the flexibility to retreat as early as every six months on the label and that's been the plan. This was discussed with the FDA in our type C meeting last year. And the tox studies to show that re-injection is safe and animals have been completed.
And so, we are optimistic that when we have our end of Phase II meeting to plan the pivotal trials, the FDA will be agreeable to our plan to do YUTIQ 6 dosing throughout the pivotal trials..
Okay. Thank you..
Our next question comes from the line of Jennifer Kim of Cantor. Your line is open..
Thanks for taking my questions, and congrats on another great quarter of execution. Jay, again, congrats on your new role. The first is just following up on the last question about the baseline average injections of patients coming into DAVIO 2.
Could we get that data prior to the December readout? And then my second question is on the December readout, just any thoughts on the planned granularity of data in terms of the patient's reasoning for rescues, etc.? What should we expect in terms of what we'll get in December? Thanks. .
Thank you, Jennifer. First, baseline injections, again, that data has been collected, but this is historical from charts of the investigators. It isn't controlled within a study, and it's not something that necessarily you want to state publicly until you're confident that the numbers are correct.
So, I don't believe there's any value or advantage for us to talk about interim data around the injection numbers. Suffice it to say, we would expect it to be less than the 8.6 that we saw on DAVIO 1, but we really don't know at this point. However, when you really talk about that, what you're really getting at is the reduction in treatment burden.
And I actually believe that the vorolanib important denominator here to look at is not the retrospective injections leading into the study, but it's the prospective injections that the Eylea arm will receive.
So, drilling down into that, after month two when all the patients received their last Eylea load, and then they got either 1901 or a sham, for the six months following that visit, the Eylea arm should, on average, get at least three injections. And in fact, they may get more because they could also get supplemented.
That's really the best comparator because that is under the control of the study and six injections a year. Multiple studies have shown us that's kind of the average that patients get in the real world.
So, when we talk about treatment burden reduction at the top line, the first treatment reduction burden will be prospective against that Eylea arm, but we will also talk about retrospectively. One last point, which again, drilling down a little bit. Three injections in the Eylea arm and DAVIO 2 goes to six injections per year.
That's a smaller number than the 8.6 that the DAVIO 1 trial showed. So even if we do just as well in DAVIO 2 with supplements or lack thereof in the treatment arms, the percentages will be different, will be lower because the denominator against that will be lower. So, just a note there. Finally, granularity of the data.
I'd say once again, we're working through exactly what we will be able to show and be confident in, in early December, because the data will not be locked at that point. That takes another month or two.
But we will certainly show by group the visual acuity change in visual acuity, OCT data, we expect to show supplement free rate for all the arms and percentages of patients who were supplementary up to month six, which, I'm sorry, up to month eight in this study.
And also, safety, of course, we showed some safety data already and we should have the reported safety data pretty complete by the time we do top-line.
Jennifer, anything else?.
No, that’s great. Actually, maybe one question beyond DAVIO 2. The NPDR data is also right around the corner, so I'm wondering when you're thinking about that opportunity, we hear a lot of talks at these retina conferences about Home OCT and increased prevalence rates in DR than previous estimates.
Does that all factor into how you're viewing that opportunity? Thanks..
Well, that's part of it. We view the opportunity basically as large because physicians and patients report that the reason that they're really not opting for the large molecule ligand blockers in this disease is the treatment frequency is too great.
If the treatment frequency were much less, say every nine months or once a year, and the treatment was safe, effective, and tolerable, we believe a lot of patients and doctors would opt for it. Home OCT is an early warning system.
Again, under the clinical trials, when you've got patients who are motivated and are coming in every month or two in a clinical trial, you don't necessarily need Home OCT, you're picking up any problems. But in the real world, that's not what happens. We know 50% of diabetics don't even go in for eye exams.
So, Home OCT I think for the diabetic population in general, if you could get them to do it at home, would be very helpful to catch the disease earlier. And again, probably be an early warning for all of these retinal vascular diseases that the patient should be treated..
Our next question comes from the line of Colleen Kusy of Baird. Your line is open..
Great. Good morning. Congrats on the progress and thanks for taking a question. Jay, you spoke a little bit to the variability of response of patients with wet AMD to current therapies.
Do we have a sense of what's driving the variable response to current therapy and is there a way to control for that in your enrollment?.
Colleen that’s a great question. So, I would say the simple answer of what's driving it is how fast VEGF levels come up in an eye after an injection. Most eyes in wet AMD respond to anti-VEGFs respond anatomically, meaning the fluid gets better and 50% of the time goes away.
Remember, 50% of the wet AMD population, approximately, you never get all the fluid to go away, but we all have seen patients who, despite monthly injections, continue to have persistent fluid or worsening fluid.
The good news is there's not many of them, but the point again is I don't think you can take a patient who requires a monthly injection with one drug, and every time you try to treat and extend that patient to five weeks or six weeks, they get fluid.
You can't expect to switch that patient to another drug and get them to go out three months or four months, because they're just got high-VEGF levels. Now, to turn it back to EYP-1901, we really don't know yet how that's going to really pan out, because this is a different mechanism of action.
We're blocking intracellularly at the receptor level, all isoforms of VEGF. So, there may be a similar type of knowledge where there are good responders and bad responders. We expect that with any drug.
And just going back to the data that we have the end of '17 from our Phase I trial, it did appear that eyes that were failing standard of care, meaning despite monthly or every six-week injections of a standard of care in VEGF, these eyes had worsening fluid. It didn't appear that EYP-1901 had much to offer those eyes.
But we do believe that the bulk of the rest of the way AMD population could benefit from our drug if the safety, efficacy, and tolerability that we saw in phase I hold throughout the rest of the studies. .
And then can you just speak to how you approached the rescue criteria for the phase II, in light of balancing visual acuity fluid and getting patients rescue free?.
Sure. So, rescue criteria is interesting because as I know, you know, and I think a lot of people who in the field know that there's no standard for this. And again, there's also two categories really.
There's rescue criteria which means the day of that visit, the patient gets a non-mandated injection, non-mandated by the protocol, and then there's disease activity. Disease activity means that the eye shows disease activity, they're in that day anyway for a mandated injection. So, they're not quote-unquote being rescued.
They're just being shifted to a different interval of visit based on that. So, there are two different definitions, and within those definitions, every study has kind of different parameters. As far as I'm aware, the FDA has never actually given direction to companies on what the rescue criteria should be.
And you see companies change the rescue criteria from Phase I to Phase II to Phase III. So, that's just general statements for us, recall that the primary endpoint that we would like to achieve and are striving to achieve in the pivotal trial is a non-inferiority change in visual acuity against the Eylea control arm.
So, we elected in the Phase II to lower the standard for supplement in visual acuity to five letters. It was 10 letters in the Phase I. And that's again, in an effort to try to bracket, the visual acuity to try to keep it intact, which ultimately that's really what patients care about.
Yes, you can show a patient a picture of their OCT and say, oh look, there's fluid, or there's not fluid, but ultimately what they care about, what the retina specialist cares about is how are they seeing. So, OCT and fluid are a biomarker, but not a perfect biomarker for visual acuity.
So, ultimately that's the goal that we need to achieve non-inferiority change in visual acuity. .
Great that makes sense.
And then the last one from us, can you just remind us what your current thinking is for the plan of Phase III design? Would you go non-inferiority and just what your thoughts are on funding that program?.
Well, the first part's easy, the second part is a broad question, but, I'll go with the first part first. So, our Phase II was designed to look very similar to the plan Phase III. Remember we did have a type C meeting with the FDA to go over this and the FDA gave us excellent guidance at the time as to what was the expectations.
So, if you look at our Phase II protocol, the DAVIO 2 protocol, there are going to be two, I think, obvious changes in the pivotal trial. And one of them we talked about already, which is re-injection. We plan on doing a re-injection of EYP-1901 every six months in the two-year pivotal trial. The second difference is the efficacy readout.
The efficacy readout in DAVIO 2 was at eight months, 32 weeks. The efficacy readout for the pivotal trials will be at approximately one year.
Now, things like dosing, end of the study, inclusion-exclusion criteria, that's all undecided until we see the results of DAVIO 2, and the science from DAVIO 2 will inform us on those other things, but ultimately the structure of DAVIO 2 and Phase III will look very similar.
Now, from a funding perspective, I've just say we're very well-funded right now. Our balance sheet looks great. The sale of boutique really helped us. We've got cash into 2025, so, we can fund all our Phase II trials. There are multiple options we have and are discussing to fund the pivotals.
And maybe I'll ask George to kind of give a little more color on that..
Hi, Collen good morning. I think we've talked about this publicly. We're, as we look at Phase II and the ultimate cost of the Phase III, it really is going to be defined. We've talked openly that we do have some strategic interest, and while you never know what those transactions are, pardon me [ph].
We are evaluating a range of mechanisms to ultimately fund the Phase IIIs, which includes bringing in a partner, potential equity raises in other structures that may make sense. But I think we're going to be guided by the data.
The Phase II data is really going to give us a lot more clarity on what the total cost for the Phase III will be and the price, but I think for us sitting here today, we're on a good position and trajectory to date in December..
Great thank you for taking our question, thank you again..
Thank you..
Thank you. Our next question comes from the line of Daniel Catalin of Chardan. Your line is open..
Thank you for taking a question. Congrats on your progress. Just wanted to ask, what is your strategy for showing that EYP-1901 could also provide a benefit in patients with other approved anti-VEGFs other than PAVIA? Thank you..
Thank you for question. At the present time, the FDA guidance, at least for wet AMD has been in a pivotal trial. The control group can either be on-label LUCENTIS or on-label EYLEA. So, we're limited by the choices for wet AMD pivotal.
It's certainly possible then when we start our DME pivotals, that guidance for DME may be different and the standard of care for treating DME at that point may be different, in which case the control arm may be different. But currently, our wet AMD plan is to use EYLEA on the label in patients who have previously treated wet AMD as the control arm..
Thank you..
Thank you. One moment, please. Our next question comes from the line of Sean Kim of Jones Trading. Again, Sean Kim your line is open..
Hi, thank you for taking my question.
I guess the first question is, could you remind us whether the Phase II DAVIO 2 trial is a statistically powered for noninferiority to aflibercept, and also relating to the statistics, can you comment on the variability in visual acuity changes following treatment with 1901 as observed in Phase I DAVIO 2 trial, and looking ahead for the Phase II DAVIO 2, and what your expectations are regarding the variability.
Maybe specifically the standard deviation for both 1901 and oplibercept control. Thank you. .
Thanks, Sean. Great questions. First of all, with respect to the Phase II, the statistics are descriptive only. The study is not powered to show a, well certainly confidence interval, that would be necessarily non-inferior. It could do that, but the end of the study is probably too small to have that absolute confidence.
The variability of visual acuity in the Phase II, again, there's no statistics around that. There was variability, but remember this was four different doses of EYP-1901, and I'm not sure that there's much read through to variability in DAVIO 1 to DAVIO 2.
And finally, expectations for standard deviation, all we can do is go, by what's out there for previous studies. And if you look at the standard deviation for treatment naive wet AMD trials, it's usually around 12 letters. It's pretty variable.
The only study that we are aware of that looked at a perhaps similar population of maintenance patients was the port delivery system Phase III trial, which had a standard deviation of 7.1 letters, but that study limited enrollment to patients who were diagnosed with wet AMD for nine months or less.
Our study allowed, essentially any time of diagnosis of wet AMD and if I were guessing, I would guess that our standard deviation would be closer to the 7.1 than the 12. I think that would make sense. However, we don't know. That's one of the many reasons that we chose to do what I would refer to as kind of a classic Phase II trial.
Did that answer your questions?.
Yes, very helpful. Thank you very much. And if I could squeeze in on another question, it's a separate question.
So, I guess relating to the new proprietary injector that you're developing, could you confirm it's 1901 will be packaged as a drug-device combination for potential approval, or would you may allow an option for clinicians to use the standard intravitreal needle and apparatus? Thank you..
No, I can confirm that this will be a drug-device combination. We've been aware of that from the start of the development of the program since the EMA requires that. And while we were into the program, the FDA changed its guidance around that. So, we've been preparing for this to be a drug-device combo.
And no, we wouldn't intend to have doctors load the inserts into any kind of their own hypodermic. These injectors and it's true of the current syringe injector that we're currently using in the Phase II trials. They are preloaded, sterilized, and prepackaged.
The physician just opens up the sterile package, takes a tab or a wire out, and then goes ahead and injects. So, there would be no plan to deviate from that.
This is going to be something that's going to be completely preloaded, pre-sterilized, and self-contained for the doctors to make it really easy for them to safely and sterily deliver the inserts. .
Okay, thank you very much..
Thank you, one moment, please. Our next question comes from the line of I-Eh Jen of Laidlaw & Company. Your line is open..
Good morning and thanks for taking a question. Jay, the first question is that, in terms of the label seeking, potential label seeking of the pivotal study. You mentioned earlier you seek for six months. But just curious, in case of very few patients that potentially need to be rescued or need to be treated, re-treated in five months, for example.
Would that also be a label that you are seeking? So, the patient, you can cover all the patients being treated?.
So, I-Eh at the present time, we're planning on every six months in the pivotal trials. If we see positive results there, I could see a post-approval study pushing that to shorter timeframe. And part of that really depends on the results.
If we're not getting a lot of supplements in our pivotal trials at month five or month seven, it would be after 1901 goes in, then there may not be value in that. I think it's something will clearly be looking at. But at this point, I don't believe that we'll be testing it shorter than six months.
Part of this again is our whole view here about the treat to maintain, where in the Phase I trial over 50% of the patients could go up to six months with stable vision and stable OCT and didn't require any other supplement.
There was another approximately third of the patients in the Phase I who did get a supplement prior to month six, but the majority of those only got one, and many of those patients have been treated every four weeks or six weeks going into the study.
So, you've now shifted a patient from being treated every four to six weeks to being treated every three months. Albeit it could be alternating a, a, an approved ligand blocker with 1901.
And there's a lot of reasons why doctors might consider doing that, even as they push patients out further and further and treat and extend, remember with the ligand blockers, the drug's gone by certainly by three or four months.
And if that patient misses a visit or gets sick, I think doctors would appreciate a safe, effective, and tolerable sustained release insert that they know is working in the background for up to eight or nine months in that patient if they miss visits.
So again, back to the original question, right now, not planning on pushing it the label sooner than six months, but it's something we will certainly consider based on the data and based on what the retina community wants..
Okay great that's very helpful. And maybe just one housekeeping question for George. I believe you mentioned that your YUTIQ sales revenue incomes will be amortized over two years period.
I'm just curious, what might be the reasoning behind that given that the sale is already completed?.
Yes. Thank you, a lot, for your question. It's really accounting-driven, and because of the nature of the agreement and the ultimate sale and license to Alimera. There's really two components. One is the sale of the asset and license of the IP and that's the 82.5 million upfront.
Part of that, we also have a supply agreement with Alimera will continue to supply YUTIQ to them. And based upon the interpretation of the accounting rules, those are tied together. And so that total of $82.5 million will be recognized over a two-year period, based on predicted volume.
So, if you think about it from your modeling perspective, it would be roughly even quarterly over those two years. Again, it's non-cash [ph]. We've already got $75 million upfront. It's just the accounting treatment of the revenue, and that will never show up. As you see in the financials today, that shows up as a collaboration and royalty line.
It's not a product savings. .
And look like that, and more something enhances product sales?.
For sales to both Alimera and our partner in China, occur mentioned, but it's a very, very different line on our P&L now. No, it's not true commercial sales, but we're following the accounting from the treatment. .
Okay, great. Its very helpful. Maybe just squeeze one more question here for Jay. In terms of NPDR, it is known that more than 90% of patients not receiving treatment at the moment. So, in terms of 1901, if the data, turned out to be robust.
The question is that besides the infrequent dosing, is there other factors that can encourage physician and patient to use the drug against the current backdrop of the sort of treatment paradigm?.
Yes, true.
Again, it's a great way to think about this, but I go back to the first principle, what is the efficacy and safety? And so, if the safety continues to look really good as it has so far, and the efficacy because of the zero-order kinetics of the vorolanib release, if you imagine that is advantageous against the staccato injection of a large molecule ligand blocker, it's possible that our efficacy could be even better than what was seen with the currently approved therapies.
I think those two things coupled would really drive the market in our direction, but flipping it around and saying, well, what if you're safe but your efficacy is less? Well given that essentially physicians and patients are not opting to any large degree for the current ligand blockers, even if our efficacy is less than they have, if we're safe and tolerable, I still think we'll get a significant part of that market and we'll grow that market.
.
Okay, great. That’s very helpful, and again thanks, and congrats a looking forward in December's positive data..
Thank you..
Our next question comes from the line of Chaitanya Gollakota of H.C. Wainwright. Your line is open. .
This is Chait on behalf of [indiscernible]. You've answered most of my questions, so I'll just leave you with one quick one. Any major developments in the competitive landscape that you've noticed specifically for the maintenance treatment of wet AMD? Thank you. .
Well, thank you for that question and then I would say it recently, no, I don't think there are any developments.
I think, when you talk about true sustained release, true sustained release is what we are doing with EYP-1901, meaning that you've got a device or a method that continues to release drug, and that would be the sustained release inserts like EYP-1901 or gene therapy. I'd put that in the same category.
Against that as what I would refer to as extended duration. The extended duration means you've got first-order kinetics, but you're putting in a more of the drug in order to have it last longer. And obviously, that might refer to forizumab or high-dose EYLEA. Those two have been around for a while now. Obviously, high-dose EYLEA hasn't launched yet.
But again, we don't consider those to be really competitors, because we're looking at a maintenance population and we can be used in conjunction with them if the patient needs it or the doctor desires it.
So, unlike the previous iterations of anti-VEGFs where when the new one came out, the promise was, we're better than the last one, we last longer, you don't need them anymore. That's not our value.
Our value is we can do something they can't, which is take, we believe if the data holds at least half the wet AMD population out six months or longer with a single injection, and possibly provide neuroprotection and possibly provide anti-fibrosis, which may result in better visual acuity.
So back to the question, the simple answer to your question is I don't think there's been any significant changes in the competitive landscape in the last quarter..
And I'm showing no further questions in the queue at this time. Ladies and gentlemen, thank you for participating in today's conference. This does conclude your program. You may now disconnect. Everyone have a great day..
Thanks, everybody..