Clinical Day 2021

May 20, 2021

It is now my pleasure to introduce your host, Jenene Thomas, Investor Relations. Thank you, Jenene. You may begin. Thank you, Jessie. Good morning, and thank you for joining us for Outlook Therapeutics' Virtual Clinical Day. Outlook Therapeutics is a late clinical-stage biopharmaceutical company working to develop ONS-5010 as the first FDA-approved ophthalmic formulation of bevacizumab for use in retinal indications, including wet AMD, DME, and BRVO. Outlook Therapeutics is publicly listed on NASDAQ and trades under the ticker symbol OTLK. At this time, I'd like to remind our listeners that remarks made during this event may state management's intentions, beliefs, expectations, or future projections. These are forward-looking statements and involve risks and uncertainties. Forward-looking statements during this event are made pursuant to the safe harbor provisions of the Federal Securities laws and are based on Outlook Therapeutics' current expectations, and actual results could differ materially. As a result, you should not place undue reliance on any forward-looking statements. Some of the factors that could cause actual results to differ materially from these contemplated by such forward-looking statements are discussed in the periodic reports Outlook Therapeutics files with the Securities and Exchange Commission. These documents are available in the Investors section of the company's website and on the SEC's website. We encourage you to review these documents carefully. Joining us for today's event is Larry Kenyon, President, CEO, and CFO. Terry Dagnon, Chief Operating Officer, Jeff Evanson, Chief Commercial Officer, and key opinion leaders, Dr. Mark Humayun, Medical Advisor to Outlook Therapeutics, and Dr. Firas Rahhal, Senior Partner at Retina-Vitreous Associates Medical Group in Los Angeles and Associate Clinical Professor of Ophthalmology at David Geffen School of Medicine at UCLA. Larry Kenyon will begin today's event with some opening remarks, followed by a regulatory strategy and clinical update from Terry Dagnon, an overview of the NORSE-2 pivotal phase III study from Dr. Mark Humayun, a discussion around patient safety and a practicing physician's perspective from Dr. Firas Rahhal, an overview of the market opportunity and commercialization strategy from Jeff Evanson, and closing remarks from Larry Kenyon. Following each segment of the discussion, there will be a Q&A session. I would now like to turn it over to Larry Kenyon, President, CEO, and CFO of Outlook Therapeutics. Thanks, Jenene. To begin today, I would like to personally thank both Mark and Firas for joining us. I know that you both are extremely busy, and we very much appreciate you spending this time with us. Terry, Jeff, and I are all very much looking forward to the conversation. As Jenene mentioned, Outlook Therapeutics is a late clinical-stage biopharmaceutical company working to develop ONS-510, LYTENAVA, as the first FDA-approved ophthalmic formulation of bevacizumab for use in retinal indications, including wet AMD, DME, and BRVO. If approved, we expect to commercialize ONS-510 as the first and only FDA-approved ophthalmic formulation of bevacizumab for use in treating retinal diseases in the U.S., Europe, and other markets. Currently, unapproved repackaged bevacizumab, also known as AVASTIN, is the most frequently used treatment for wet AMD in the U.S. If the results from our ongoing, fully enrolled pivotal trial of ONS-5010 are as successful as we expect this summer, we believe we are in great position to finally be able to provide patients and physicians with the responsibly priced approved bevacizumab that has been missing from the market. Because bevacizumab has not previously been approved for use in retinal diseases, we cannot use the biosimilar pathway and will instead seek approval as a new drug with the potential for 12 years of regulatory exclusivity. ONS-5010 has the potential to be a $1 billion drug in a $13 billion market that already understands the value proposition of treating patients with bevacizumab. Because of this, we expect that ONS-5010, if approved, will be readily accepted by the patients and doctors currently using and prescribing bevacizumab if priced appropriately. If approved, we are looking for ONS-5010 to provide the foundation for building a high-growth biopharma company positioned to maximize shareholder value. It goes without saying that the team at Outlook Therapeutics is very excited about ONS-5010 and what it represents for wet AMD patients. Today, for the first section of our program, Terry Dagnon, our Chief Operating Officer, will now walk us through the ONS-5010 regulatory strategy and provide a review of our clinical program to date. Terry? Thank you, Larry. The anti-VEGF market has been the standard of care since the launch of LUCENTIS and also the advent of the off-label use of, as you stated earlier, AVASTIN, that was demonstrated in the CATT trial published results in the New England Journal of Medicine. As Larry stated already, the predominant use of anti-VEGF remains the unapproved repackaged bevacizumab off-label. The CATT study is something that changed everything. That study, conducted by the NEI, over 1,200 subjects, showed a remarkable efficacy and safety similarity, sameness, equivalence in the CATT study. Also important today, as we talk about the study design of our NORSE ONE and NORSE TWO studies, is the LUCENTIS PIER study and what that monthly dosing looks like when compared to quarterly dosing with an anti-VEGF therapy. These two studies are cornerstone in the design of our phase III program. We are currently on our pathway and have a planned BLA filing for the first wet AMD indication. Our U.S. BLA filing target will be in Q1 of 2022. We've completed and shared the results from our NORSE ONE clinical experience trial that will be included in our BLA. Top-line data from our NORSE TWO pivotal phase III study is expected in Q3 of 2021, and we've also completed and reported the top-line data from our NORSE THREE safety study, an open label safety study. NORSE ONE provided a high level of confidence in the outcome of the ongoing, fully enrolled pivotal trial. This was our clinical proof of concept study and a clinical experience study. We demonstrated the anticipated safety and efficacy signals that we were expecting to see that were consistent with previously published results for ophthalmic bevacizumab. This provided us the successful proof of concept, and we absolutely continued the program. It was a randomized, mass-controlled trial, ONS-5010 versus LUCENTIS. 61 subjects were enrolled. The trial was conducted completely in Australia, and it's expected to support our planned BLA in first quarter of next year. ONS-5010 ophthalmic bevacizumab demonstrated the safety and efficacy. 30 treatment-naive or previously treated subjects were enrolled. Baseline visual acuity of 20/40 to 23/20. Subjects received either monthly ONS-5010 versus ranibizumab dose with initial 3 doses, followed by quarterly dosing. The PIER dosing regimen. As you can see from the graphic on the slide, at the primary endpoint, which was the different in the proportion of subjects that gained 3 lines of vision at month 11 monthly injections versus 5 at the primary endpoint, and the absolute trough effect after that fifth injection. We're very excited that we saw the proof of concept that we were expecting, validated our trial design, and very much look forward to our Phase III results from NORSE-2. NORSE-2 enrollment was completed. The top-line data is expected in Q3 of 2021. Again, a randomized, mass-controlled trial, ONS-5010 versus LUCENTIS. 228 subjects were enrolled. Trial was conducted completely in the U.S. Both trial arms include predominantly treatment-naive subjects with a baseline VA of less than 20/50 at the trial start. That is a difference from the other study. 20/40 was allowed in the first study. Safety efficacy data expected to support planned new BLA, as we said earlier, in Q1. The ongoing pivotal trial design was, as we said, informed by our clinical experience trial, and the study has a larger sample size. The same schematic, as you can see from the graphic, 11 monthly injections of ONS-5010 versus five, which the first three initial injections of LUCENTIS followed by quarterly dosing, and the difference in three line gainers, proportion of three line gainers at month 11 will be at the absolute trough effect after that fifth injection of LUCENTIS in the quarterly dosing arm. What's slightly different in this study is treatment-naive subjects, 20/40 versus 20/50 at baseline. We're very excited and look forward to presenting the full results this year. NORSE THREE was an open-label safety study. We needed to round up our patient population to meet the minimum number of safety exposures that we would need to file our BLA. We are very excited to report very positive safety profile in the press releases that we've done on this study. We will be presenting full results at an upcoming meeting later this year. No unexpected safety trends were seen. The safety profile is consistent with prior published data on the use of bevacizumab for the treatment of wet AMD. There were zero cases of ocular inflammation, something that has been highlighted by some of the recent wet AMD candidates and recently approved products. Our trial obviously was open-label safety study. We enrolled 197 subjects that were diagnosed with either wet age-related macular degeneration, diabetic macular edema, or branch retinal vein occlusion. The two other indications that we intend on pursuing and starting studies in later this year, early next year. Subjects received three doses of ONS-5010 over a three-month period. Again, this was conducted to make sure that we had the full safety population necessary for a successful BLA filing and approval. I'm going to stop there and open for questions. Great. Thank you. At this time, we will be conducting our question and answer session. If you would like to ask a question at this time, please press star one on your telephone keypad. The confirmation tone will indicate that your line is in the question queue. You may press star two if you'd like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Jesse, while we wait for people to submit questions, one of the things that I think would be great to talk about here is we've noted that we have two registration trials, Terry, in the program, but only one of those studies is pivotal. I know that the FDA guidance is clear that you can submit a BLA with one pivotal study and supporting clinical data. How does that work here? Maybe you can provide a little more color. Great question, Larry. As you know, it won't be just NORSE ONE, NORSE TWO, NORSE THREE. There's a significant body of literature. Clearly, the landmark CATT study will also be used in our application as additional ways of showing evidence of effectiveness for the product. What you just stated was consistent with what is in our end-of-phase II meeting minutes. We got agreement on a small study and one larger study, and then rounding up the safety population with an open label study. That's something that we met with FDA, we got in writing, and we're absolutely executing that strategy. We're pretty excited about that. It is, as you said, a well-known, well-documented in FDA guidance documents and in our end-of-phase II meeting minutes. Thanks, Terry. All right. We do have some questions coming in. Our first question is coming from the line of Kumaraguru Raja with Brookline Capital Markets. Please proceed with your question. Thanks for taking my questions and continuing the context of your comments right now. Obviously, there is a lot of data with regard to AVASTIN, which is available. With regard to the NORSE TWO study data, what role or how much importance would physicians give in terms of using that for prescribing ONS-5010 and also in terms of FDA, how much importance are they going to give to that? Given that you are using once every three months dosing of LUCENTIS, what is the expectation there, right? That's not the optimal dose. That's a great question, Kumar. Hey, Terry, why don't you start, and then I think Mark might have some insights as well. Absolutely. Everybody forgets that the PIER dosing regimen is actually in the approved labeling for LUCENTIS. A quarterly dosing regimen was part of the FDA approval of LUCENTIS, and we did get approval of that study design for FDA. I think it's important to note that our regulatory strategy and our registration studies that we're conducting aren't about answering new questions. It's actually about meeting the criteria to get FDA approval in the leanest, quickest way possible. We could have done a non-inferiority study, but that would have been hundreds more subjects and taken us a lot more time and a lot more money. What we did was have an innovative clinical trial design, a superiority design, which required less patients, could be enrolled quicker, and was cheaper. As I said earlier, it's based on the science that's already been proven in the CATT trial and the PIER study that was conducted by Genentech and is in the actual approved labeling as an alternate dosing regimen. Good question. Mark, do you want to pick up from there? Yeah. This is Mark Humayun. Kumar, great question. Terry just explained why from a regulatory standpoint, this is perfectly acceptable. From a clinician standpoint, we know how LUCENTIS behaves. In fact, in the real world, we don't dose it monthly. We do a treat and extend, meaning we do an injection, we try to extend the next injection, and often, it's eight, 10, 12 weeks. We know how LUCENTIS behaves. I think the importance of this trial is to show that ONS-5010 monthly behaves as AVASTIN. It previously has in the CATT trials and other trials. We'll be able to see that very clearly from a physician standpoint. In terms of the control arm, we know how LUCENTIS behaves. We use it very differently in the real world. There won't be any issues. Great question. Thank you, Kumar. Okay. Maybe a question on NORSE ONE. Obviously, there's a variability in terms of the inclusion criteria in NORSE ONE versus NORSE TWO. Maybe you can give your thoughts on what do you think of the efficacy data there. Larry, you want me to take that one? Yeah. Why don't you start, Terry? Another great question. Obviously a very small study, not powered to show a significant difference, but we wanted to validate the design, and we did need to enroll both previously treated and treatment-naive subjects, which do behave differently in a clinical outcome. We did see the same level of signal in three line gainers and changes in mean visual acuity as were previously reported, the percentages in the CATT trial, in the PIER trial, in our NORSE ONE data. We also saw the same safety profile, which was equally important for us. We validated, number 1, the primary endpoint. Number 2, our product ONS-5010 had a similar safety profile to which was reported in the CATT study, which was similar, the same, non-inferior to LUCENTIS. We were very excited about that. We knew we weren't going to have significant results, but we did want to see those signals, and we presented those numbers in our press releases, the specific percentages of each of the different criteria. We're pretty excited about that, validating our design, and look forward to the results from NORSE TWO. Mark? No, I agree, Terry. I think that although Kumar raises a really good question, the importance is that, again, looking at ONS-5010, it did behave like we expect AVASTIN to behave in terms of three-line gainers. If we didn't see that, if we didn't see any patient get the improvement, we'd be more concerned. We saw that clearly, a really good signal. Again, safety was excellent. Small study in that. Safety was, again, very, very good. We continue to be very excited about ONS-5010. Okay, thanks. Thank you. Our next question is coming from the line of Douglas Fowle with H.C. Wainwright. Please proceed with your question. Hi, good morning. Thanks for taking the questions. I was just wondering if you could just provide an update in terms of the development of a prefilled syringe for your. I think you got cut off there, we can talk briefly about that here for the moment, we will speak to that as we get to Jeff's portion of the presentation. Terry, did you want to kick off a little bit on where we are with the prefilled syringe? Absolutely. That development program is absolutely underway. We have some, as we've previously talked about, some world-class partners that have experience with injectables and with prefilled syringes. We do still anticipate that it will be a post-approval supplement after the approval of the original BLA. We're very excited about the syringe that we have, and we are going to go into detail about it, the ongoing development program, and the team of experts that we've brought into that project to make sure that that is something that's immediately available after approval with the post-approval supplement. Thank you. We'll move on to our next question, which is coming from the line of Ed Woo with Ascendiant Capital. Please proceed with your question. Yeah, thank you for taking my question. Was there any impact from the pandemic in terms of delays in the clinical trial? Do you anticipate any issues with the FDA approval process with the pandemic, even though it's winding down? That's a great question, Ed. We've been very fortunate, I will say, so far. Terry, why don't you walk us through the details? Absolutely. When COVID hit, we immediately got on the phone with the division director at FDA and asked for a statement that made it very clear that these were very necessary treatments that needed to continue during COVID because it's a sight-threatening condition. He was absolutely supportive, and we got that word out to our investigators. We had relatively no impact from COVID. There's very few missed visits and very few treatment visits that were missed. We're very excited the data is intact. In regards to the FDA review of the database, it's going to be very straightforward because of that. Very much thank you to all of our clinical investigators and the patients, because they continued to show up, they continued to be treated, and continued to be evaluated. We're pretty excited about that. We don't see that there was any impact to the trial from COVID. In regards to supply chain, it's as everybody else. There are peaks and valleys in regards to shortages. Obviously, Warp Speed does get to go to the front of the line on many things, and glass vials, for example, are at a premium. You have to plan way ahead, which we are doing. There has been some small impact on the timeline, but no major impact in regards to our planned filing early next year and the ability for FDA to review and approve our product. I'd just like to add to that, reiterate something you mentioned, Terry. A big shout-out to the sites and the patients. We all got surprised, obviously, understatement of the year, in March of last year. The sites that we were using quickly put protocols in place so that they could just keep operating, and if somebody went down with COVID, then they were able to pick up the slack. Made it very safe for the patients to come in and get their subsequent treatments and the follow-up visits. That ran very smoothly once we got past the initial wave. In fact, the only impact we saw a year ago was a little downtick in the enrollment while we were still enrolling patients. We never really saw any interruption to ongoing visits. Thank you. Thanks, Ed. Great question. I think with that, we're going to move on to the next section of the presentation today. We've already heard a little bit from Dr. Humayun, Mark will walk us through expectations for and the relevance of the ongoing pivotal NORSE-2 clinical trial. I just want to note one more time, Mark is a medical advisor to Outlook Therapeutics, and he also serves as the chairman of our recently formed Global Retina Advisory Council. Mark, I think we can move on to you now. Great. Thanks, Larry. Glad to be with everyone today. Terry laid out very clearly how NORSE-2 is a critical part of getting regulatory approval alongside with our extensive experience with AVASTIN in general and NORSE-1 and NORSE-3. This is very exciting. It's a previously validated molecule and target. Again, the study design is to not invent something but really provide a product that does not have to be compounded. Dr. Rahhal, who's going to speak to you after me, will describe some of the things that we experience as clinicians with a compounded product. Compounding pharmacies do the best they can, but they do fall short on some safety issues, some things with syringes that Dr. Rahhal will talk about, introducing silicone oil, tiny bubbles inadvertently. Also, just in terms of efficacy, sometimes the drug is not stored or shipped properly, or we may not even get as much volume. All that to say is, it's really exciting to be able to have a product that will be FDA-approved, that we can use and also use, as we just talked about, with a pre-filled syringe eventually. The clinically relevant primary endpoint is the difference in the proportion of participants who gain at least 15 letters at month 11. As Terry Dagnon pointed out, study is powered for statistical significance. We've had excellent enrollment. We haven't suffered from the COVID pandemic, which is very fortunate, but also because of proper planning on our part. The unmet need this meets ONS-5010 is to show that it behaves in the eye as AVASTIN does in previous trials, and I mentioned that and talked to that already, and provide an ophthalmic formulation that's cGMP and approved. Then, of course, importantly, do all this at a responsibly priced product. I'll stop there and take any questions. Great. Thank you so much. Ladies and gentlemen, once again, we will be conducting our question and answer session. If you would like to ask a question at this time, please press star one on your telephone keypad. We will pause for one moment while we poll for questions. While we're paused, Mark, I think one of the things that I'd like to have you talk to for a moment is the view from a practicing clinician on the fact that the data that we're going to generate from NORSE-2 is monthly for 5010 versus the PIER dosing regimen, definitely well-understood dosing regimen that seemed to be inferior to monthly dosing. Is that going to impact, do you think, your peers on the use of the drug and how they view ONS-5010 in the clinic? I think this is the same question Kumar asked, and it's a question that is a very good question and worth reiterating the answer, which is that we know how LUCENTIS behaves, so we don't need the control arm to be monthly. In fact, in the real world, we don't use LUCENTIS monthly. We use it in a treat and extend manner. Most of us do, which ends up being 6 to 12 weeks, depending on the patient needs. It isn't so much that we're focused on the control arm, but we are very focused on the treatment arm. We want the treatment arm to behave, look like in terms of safety and efficacy as AVASTIN has done in previous trials. That's really the focus. As retina doctors, and again, Dr. Rahhal will talk a little bit about this, we're very familiar with LUCENTIS. It's been around forever. We just want to make sure that the ONS-5010 product behaves like AVASTIN and how AVASTIN has done in many trials over many years. Thanks, Mark. Thank you. We do have some questions coming through the telephone line. Our first question is from the line of Kumaraguru Raja with Brookline Capital Markets. Please proceed. Yeah. Thank you. Maybe with regard to in terms of physician perspective, in terms of what do you think would be appropriate pricing? Maybe you can talk a little bit about how AVASTIN is being reimbursed and how that plays out in terms of the ASP plus reimbursement. Obviously, that's higher for LUCENTIS. I guess for AVASTIN, it's not material. Maybe your thought on that. Kumar, I think Jeff's going to speak to the commercial part of this later and probably provide more detail then. I think that is a good question here. Just maybe briefly, Mark, you can bring your perspective on how you see the physician perspective on reimbursement. Jeff, I'd also like to get your thoughts as well on how that rolls into what we would expect to do when we put, if approved, ONS-5010 into the normal supply channel that you would expect to see for LUCENTIS or EYLEA or any of the other approved drugs. Jeff, you want to go first? Sure. I think as it relates to pricing and the mechanism by which we go from here to getting the support of payers, I will reference in some of the information that follows. I would say as a general point, we've studied well the idea, pricing elasticity, testing at various levels. We've had payer advisory board engagement to really understand. Our goal, just corporately, I would say at the outset, is to find that perfect price where all of the stakeholders find value. Outlook, obviously, we need to find value in the price, but we really want to do it in conjunction with the retina community and really be thoughtful about that and the patients that they're treating. We are not in a position now, and later this year, we'll get closer to what a launch price would be. I would just say that I think we all agree there's a wide window between what is happening with off-label use in terms of not only the cost, but the reimbursed rate around $81 to the branded options at $1,850, $1,950 at list price. There's a pretty wide band there. Again, we use the word responsibly priced, and we mean that. We're going to really get specific later in this year and certainly next year as we get closer to launch. Okay. Maybe you can talk a little bit about the use of 5010 before you are able to get the prefilled syringe. How do you think that's going to go? I'll start and then Jeff, you want to talk a little bit about it. The plan is, as Terry mentioned, is that we would launch with the vial. That's what our approval will be in. Upon approval for the vial of ONS-5010, we would plan to file a supplemental BLA for the prefilled syringe. We would expect to, based on the PDUFA guidance, a response in four to six months following launch of the vial or following approval of the vial. It should be a pretty short window. I probably didn't leave enough for Jeff to add at this point. I would just say, I think, and we'll talk a little bit more about this, and Dr. Rahhal, I suspect will also address this as Mark has, as we're trying to solve important issues around safety and continuity and FDA-approved, GMP-sourced products, we eliminate the downside to bevacizumab while giving them something that they know works when provided safely. Having it in a vial with a companion syringe is definitely a step in the right direction, and as Larry mentioned, there's a short window we anticipate between that and ultimately getting the prefilled syringe. We studied this from a sheer preference, from a quantitative market research perspective, and I'll share a little bit of that output in the slide that follow. Okay, thanks. All right. I think that's the last question for this section. For the next topic, we'll give Firas a chance to talk. Dr. Rahhal is a founding member of our Global Retina Advisory Council. I'd like to note that, too. For his section, as Mark has alluded to, and I think all of us have at some point, we wanted to get a practicing physician's perspective. Not that Mark's not a practicing physician, he is absolutely as well. We wanted to get Firas' take on this and talk to things like patient safety that are an issue, even though we don't see it in headlines as frequently as one might expect. Firas. Thank you. Thanks, Larry. I want to just start by reiterating a couple of things that were excuse me, already said by Terry and others. I was an investigator in the CATT trial. It really was an outstanding multi-centered clinical trial that essentially the entire community accepted immediately as proof of the efficacy and safety of, at the time, off-label AVASTIN. I personally use off-label packaged AVASTIN, repackaged AVASTIN, 50% of my patients, not just for wet AMD, but also for vein occlusion and diabetic retinopathy. The CATT trial was specifically wet AMD, but the retina community is extremely comfortable using this drug repeatedly, frequently, often in all these diseases. The other point I'd like to add too was the great question regarding the clinical trial design. I agree with what Mark said in response, would like to add that the retina community, it's pretty small, and they're a fairly sophisticated group in understanding clinical trial and clinical trial design. My group is involved in a ton of clinical trials and helped design many. The retina community will understand that the trial design with the control group was more about regulatory standards, meeting standards for the FDA. Their comfort level with AVASTIN in terms of efficacy is already off the charts, as has been noted by Jeff and others. What % of patients are receiving this drug in the U.S. and around the world today is enormous. It's the overwhelming majority. I don't think they'll need a whole lot of, we want to prove it, but I don't think they'll need a whole lot of efficacy data. They might do this more on the safety side, which I'm going to address here in a couple of minutes, and recognize that the PIER data, although not necessarily standard of care in the industry, is a regulatory acceptable hurdle, and I think they'll be sophisticated enough to understand that and will adopt it. Let me go on to some of the things I've been asked to speak about with regard to the safety issues of the current compounded repackaged AVASTIN or bevacizumab. The potential advantages to an ophthalmic formulation are numerous and very important, and I'll start with the most common and move to some of the less common but perhaps more dangerous. Mark alluded to the most common already, and that's what I'd like to start with, which is the silicone oil bubbles. There's plenty of both anecdotal and paper literature now on the silicone oil bubbles that have emerged in the vitreous of patients receiving repeated injections of repackaged AVASTIN. I hardly can think of a retina doctor I've spoken to over the last five or more years who hasn't experienced it themselves. I've personally seen it many times. It's frustrating. We know where it comes from. It comes from the syringes. The interior of a tuberculin syringe or the like are often coated and lined with silicone oil, a very commonly used substance, to reduce viscosity, to reduce the stickiness of the syringe. Ultimately, after multiple uses, this started showing up in the vitreous of patients as these globule-like floaters. Unfortunately, they're quite symptomatic for the patient. They're very frustrated by it, and it's also likely to be permanent. They're not likely to disappear on their own. Some patients have had to undergo vitrectomy surgery to remove the vitreous and the symptomatic oil bubble floaters. That's probably the most common thing and really would be great to get rid of that. Already some changes have occurred at the compounding pharmacy levels to try to mitigate against this, but it hasn't been resolved. A pure ophthalmic formulation would resolve that, particularly if it's in a preloaded syringe, but also with the vials. When we were doing the vials of LUCENTIS and EYLEA, we didn't see this problem. It doesn't have to be the syringe alone to solve that problem, but it certainly makes it easier. There's the more serious potential complications of repackaged compounded products. Again, I'll reiterate what Mark said. The compounding pharmacies are doing the best they can. This is not trivial stuff that they're trying to do under hoods, prepare all these products sterilely. They do it not just for AVASTIN, but countless dozens of other drugs, several in the eye. There have been outbreaks. By inflammation and infection, I'm more fearful is infection, but we do see inflammation as well, sterile inflammation. Infection is fortunately rare, but when it occurs, it's devastating. It's called endophthalmitis. The eye can actually be lost. There have been some small outbreaks with lot numbers from particular pharmacies. There have been papers published on this. Again, you don't want to point the finger at any one compounding pharmacy, but there were a couple that were identified that had either fallen short and there was streptococcal organisms cultured out of these patients and then ultimately out of other prepared syringes that hadn't been released or used yet. A contaminant had clearly gotten in. That was devastating. Those patients did extremely poorly, and most of them lost their sight or even their eye. Infection, again, although rare, is a very serious problem. This led to a lot of debate in our community about how to deal with this. It resulted in greater scrutiny of the process, appropriately so. It resulted in some regulatory changes regarding compounding pharmacies. Several were shut down. The industry consolidated somewhat, but that remains always a risk. Any pharmacist who works at a compounding pharmacy or in the hospital even, where the conditions are optimized, will tell you that in the course of compounding drugs, sterility can be broken, or purity can be lost. There's the practical considerations, what is labeled here on this slide as syringe malfunctions, among other things. The syringes are highly variable, and as simple as it sounds, different lots and different compounding pharmacies use different syringes and are changing all the time based on cost and availability, especially through the pandemic. I'm sure there were some lines broken. The syringes can malfunction, and the most simple thing, the needle, is where I find personally, and I probably did 35 of these injections yesterday, so I'm very familiar with using the repackaged AVASTIN. The needle becomes a real problem at times, and it's highly variable how sharp and effective they are, how much dead space they have, which I'll talk about in a second. This can create more difficulty in actually performing the procedure for the surgeon and obviously for discomfort for the patient. If the needle's not an effective needle, and this comes up not rarely, it hurts more. It's harder to complete the procedure fastly. With regard to the dead space, we're going to talk about dosing in a second, but the dead space in a needle, what we're referring to is the syringe is loaded with drug, and then you have to push the drug to a specific level into the needle. These are such small quantities of liquid and drug that if the compounding pharmacy hasn't properly calculated the dead space of any particular needle, and each needle has its own different hub and different size of dead space, it can have critical effects on dosing. I think this is actually, for me, in my hands, and I can see it even when I'm doing it sometimes, that the drug is frequently underdosed based on poor calculation of volume relative to the dead space in the needle. We then will complain about it, and the pharmacy will try to do better for their next lot. That's a whole lot of perhaps hundreds of vials that we've received already on our shelves that might be underdosed. That, to me, is probably the most common efficacy side problem for this. With regard to dosing, there's other sort of more scientific questions that I don't have a lot of knowledge in, but in terms of the concentration of the actual drug in the fluid itself, there have been several papers out of very respectable university ophthalmology departments showing highly variable dosing in terms of the concentration of drug. I'm not sure how that comes about and what goes into compounding the drug biochemically to get the concentrations right. As you see on this slide here, 81% of samples had too low a protein concentration. When you combine that with what I just said about the practical volume considerations, that probably means a lot of patients are being underdosed, and clearly that's going to tremendously affect and reduce efficacy. Summarizing the compounding pharmacy part, again, they do the best they can. This is a skill, and it's challenging, but there's very few quality assurance parameters on-site at the compounding pharmacy and in our own offices once we receive these huge bags of prepackaged syringes. There's really not a lot of good data to tell us how long these products can sit refrigerated, how long these products can sit unrefrigerated once we take them out and put them on the desktop to use for the day. How many hours are they good for? This all creates potential risk to the patient, ultimately. I think that I've reviewed safety and efficacy. For me, both are equivalently likely to be resolved with a prepackaged formulation. If we could go to the next slide, I've summarized here, but if you could have an ophthalmic formulation, the purity will be essentially guaranteed, the sterility will be essentially guaranteed, most importantly, in my hands, the dosing will be guaranteed. Again, I've repeated that two or three times because I think that's probably less spoken about relative to the other safety issues, which are more obvious and have been published. I think dosing has become a consistent question for me when I'm using intravitreal AVASTIN. That's what I would like to close with, that if we could have a product that assures the safety but also assures the dosing, unequivocally, the patients will do better, the doctors will be happier. Thank you. I'll take questions anytime. Thank you. We will now begin our next question and answer session. We do have a question coming from the line of Douglas Tsao with H.C. Wainwright & Co. Please proceed with your question. Douglas, your line is live. You may proceed with your questions at this time. Oh, can you hear me? Yes, we can hear you now. Okay. Dr. Rahhal, just curious, how would the availability of a sort of approved bevacizumab affect your prescribing? I'm just curious. How would you think about it in the context of some of the newer products like BEOVU, which is out there as well? Where would it sort of fit into the sort of treatment paradigm relative to some of the newer products? That's a great question. If I'm in your seat, that's the question I would ask as well. I think I can answer it this way. I currently use, as I mentioned, approximately 50% of my intravitreal anti-VEGF injections are AVASTIN when you look at across all disease processes. Again, we're talking primarily from a regulatory standpoint today about the wet AMD, but in real life, we use AVASTIN for the other two diseases, just as commonly, if not more commonly, in diabetic retinopathy and macular edema. That 50% of patients are receiving it from me, and that's a similar number to the national numbers because we believe in the product. To answer your question, I don't see any reason why that 50% of the market in my hands and in the hands of the majority of retina doctors in clinical practice would be available to and optimized by using this more properly packaged pure product that's more predictable. In other words, with BEOVU, which has small market penetration because of the well-known now reports of inflammation, it's gaining a little traction. EYLEA and LUCENTIS have a large market share, but those are not likely to change much because the AVASTIN part, the 50%, that's the part of this market that I could see this product taking up a lot of, if not all of eventually, if a licensed approved FDA product is available, it's hard to not choose it over a prepackaged off-label product. Okay, thank you. We'll move on to our next question, which is coming from the line of Kumaraguru Raja with Brookline Capital Markets. Please proceed with your question. Yeah, thanks for talking about safety. Several years back when there was a significant increase in infection cases, people were using AVASTIN vials, just a single vial for a single patient. Are people still doing that? Also in that context, how does that impact your thoughts on pricing of 5010? Yeah. The way it's generally done now, there's only been some slight change in this since those outbreaks. You're right, there were some changes made at the compounding pharmacy level and at how we obtain. The way it's done now is we actually order the IV version to be delivered directly to our compounding pharmacy of choice, who then packages 60, 70, 55, whatever number they get out of one of those directly into tuberculin size 1 cc syringes and send it along to our office in a refrigerated package. We have them in the syringes right away by the time we get them. The single-use vial that you're referring to, that is the intravenous vial used for cancer, and that houses the volume of approximately 70 or so intravitreal doses. That's not generally what the doctor is handling, but there are exceptions to that. The doctor, myself, and my partners, and others around the country are handling that vial directly when there's a so-called formulary-type pharmacies. When the insurance company is contracted directly with a pharmacy, sometimes they'll send the whole vial for the patient, maybe not recognizing that they're wasting tremendous amounts of money to send a whole vial for a one-time use. In those instances, we do draw it up directly ourselves into the 1 cc syringe. That's a small minority of the cases. The overwhelming majority, that vial, the large one, goes directly to the compounding pharmacy. We never see it, and they prepackage for us and send us a bag full of syringes. Okay. You touched about it a little bit. Once 5010 is approved for AMD, I assume that probably you'll be more comfortable using 5010 for BRVO and DME compared to off-label AVASTIN? Yes, I would. I do think that to be fair to the patients, a lot of the patients who receive AVASTIN now, to be quite frank, are those who are "underinsured." They have large co-payments or the insurance company, of course, would prefer us to use the lower-cost drug, so would the patient in many instances. To be fair to those patients who are coming in trusting us to give them the best possible result, and we do, if there's an available pure form that reduces their risk of serious complications like endophthalmitis or less serious complications, but certainly symptomatic like bubbles and floaters in their vision, I think it's incumbent on me to order that product over the current existing product. Yes, the answer is I would use it for all the different categories of disease that I use AVASTIN for now, all three of those. In California, it's covered for a number of other things-Related to those diseases, we have codes for other conditions like neovascular glaucoma. These are less common things, idiopathic perifoveal telangiectasia, not something everybody comes across every day, but we will be using it, I think, in those settings as well. Thank you so much. Thank you. Thank you. Our next question is coming from Ed Wu with Ascendiant Capital Markets. Please proceed with your question. Yeah. Dr. Rahhal, since you are very familiar with off-label AVASTIN, how quickly do you think the uptake will be, assuming it gets approval right away? Do you think your fellow clinicians will be very familiar and will be able to switch right away? Do you think there's still going to be the normal lead time for people to get familiar with this new product? That's a great question. I've been at this a long time, and we've taken on new anti-VEGF drugs multiple times in the last 15 years in sort of this sequence. There is this, as you implied, kind of gradual acceptance, even though the data's there and so forth in the literature. Again, the retina community is pretty sophisticated. They read the literature, they go to the meetings, they know the data. Doctors, for the most part, tend to be conservative animals. That said, this is a little different because everyone has massive experience with this product and its efficacy results in their own hands. They don't have to be skeptical in any way about efficacy data from the clinical trial being perfected like so many trials do. The trials are set up to create success. There's no doubt about it. I helped to design some trials, and there's good reason for that. Clinicians sometimes are a little skeptical that transitioning the clinical trial data, the perfect data, into real-world clinical practice sometimes falls short, and we've seen that recently in a couple of products. In this instance, I don't see that at all. This is kind of the other way around. The clinicians are absolutely comfortable using tons of intravitreal AVASTIN. I think the rate-limiting factor, and I'll leave this part to Jeff and Terry and Larry, who know much more about this than I do, but the limiting factor, if any, is going to be how quickly, and this is true for the other stuff too, the other products we've taken, but particularly here, how quickly will the payers adopt this versus the compounded version, and how will those be managed on the financial and acquisition side? I think from an efficacy standpoint, the adoption will be large and immediate. Okay, thanks, Ed. That was a great question. Great response for us. Thank you very much. Since there aren't any other questions for us at the moment, what we want to do to address the final topic for today is to have Jeff Evanson, our Chief Commercial Officer, walk through the market opportunity for ONS-5010 and a bit on the commercialization strategy and spend some time also talking about our thinking around the prefilled syringe and what we're trying to do there. Jeff, take it away. Well, thank you, Larry. I think all of us in this discussion can see not only why Outlook is very excited and thrilled to advance this in the clinic and ultimately get approved. As you hear from Dr. Humayun and Dr. Rahhal, there's a really important problem to solve for, and as such, there's a great opportunity getting to the finish line, getting the approvals. As we've talked through and Terry outlined, with our target product profile with wet AMD, and we have plans for DME and BRVO, and as outlined, we offering this in a vial initially with a companion syringe and ultimately the prefilled ophthalmic syringe, which we'll share more details on. We're really excited about that, especially due to recent and ongoing concerns around not only off-label, but I think there's also a conversation with those that are on-label and prefilled syringes in terms of glass syringes. One thing that's worth noting, I think two things with efficacy safety in general that is probably not as well understood is that when the CATT study was performed, the reason there was a safe product provided is that it was done under an IND, and as such, it was as close as you could get to an FDA GMP-type product, and that's why the demonstration of not only efficacy, but safety was there. Since that time, as Dr. Rahhal rightfully outlined, the steps that occur with compounding, it's an age-old challenge, right? Again, nobody has bad intentions there, but if it can go wrong, it does go wrong at times. Setting up our target product profile is really about removing the things that are the downside of a product that they know to be a trusted standard of care in the market. As it relates to the prefilled syringe, we just yesterday had a technical summit of sorts that Terry referred to, one of the best technical teams I think I've had the chance to work with in all of my time in developing and launching products, really a collaborative effort of very smart people. The basis and the potential of this product, it's a cyclic olefin polymer. It's a non-glass syringe that essentially acts like glass as you need it to, but without the downsides of glass. It's not a breakable prefilled syringe, for example. As we talked about, this is a plasma applied siliconized layer, so it's silicon oil free. You eliminate the issues around injecting and having the concerns around silicon oil droplets, which is a major advance. No delamination, no leachables. The dosing accuracy that comes along with the tight tolerances provided with this ophthalmic design syringe, we feel is an important advance, again, not only with the off-label use, where it's not only tuberculin syringes, but insulin syringes are used, and that's where problems can occur. Also against the glass prefilled syringes that are available today in market. We really feel not only is this an important advance, but I think a real differentiator that ultimately when we go to market, one of the elements that we'll talk about is why this matters and why this is such an important step for us in providing not only bevacizumab in an approved version, but also in a prefilled syringe. That it's a real game changer. As both Dr. Humayun and Dr. Rahhal referred to, after all of this time, as you look at the market, and I think well familiar with everybody in this conversation, from a patient share point of view, off-label use remains to be the number one for bevacizumab, remains the number one patient share product in the market, followed by EYLEA and LUCENTIS in the U.S. There are a number of reasons for that. One of them is certainly a cost consideration for patients. You're starting to see some of the impact of clinical bulletins from major payers like Aetna and UnitedHealth, who are requiring that there is a step through off-label bevacizumab before authorizing use for other products. We see this as an opportunity, and I'll share a little bit more about some of the engagement we've had with payers already, where we are attempting and will position this product to earn the right to be a first-line option for not only the retina physicians, but the patients that they treat. Again, just very excited about some of the initial steps that we've taken with payers. One of the things that we focused on in the last 18 months or so was while we're excited, and as you hear about those that get close to the program from a physician point of view are very excited, we really wanted to get the answer about from the overall retina community, not only in the U.S. but in Europe, just what their interest is in a target product profile that we've outlined, that we've shared. We were very nicely surprised with the results of that share preference study. We both did quantitative and qualitative market research with both payers, in this case, the physician response. What you're seeing on this slide is essentially the interested, highly interested in a product that's approved in bevacizumab, and that was north of 80% between the two markets. For those of us that have done a lot of research in this area, you generally, if you get above 60% or 70% for the top two boxes we call it, you're in a great situation. For us to be at 84%, 85%, 82% in Europe, exceeded really all of our expectations, but it really validated what we're doing and why we're doing it. Part of what we are looking at, and we really see anti-VEGF, and in this case, ONS-5010, as being a cornerstone within the standard of care. It obviously, when LUCENTIS and off-label bevacizumab began to be an option for patients, it transformed the care overnight. Patients regained vision quickly and over time, with ongoing care, remained with vision. Within the blue area here, seeing ONS-5010, we clearly have the opportunity to be a first-line option given some of the discussions we've had with payers, with the caveat that we talk about responsibly price. While we're doing that, making sure that this is an option we add to the market, to the armamentarium first line. As Dr. Humayun was referencing, treat and extend, trying to stretch the patients out as far as we can between further injections. Certainly ONS-5010 could be an ongoing part of that care. If you look at the future markets and options that might come into the market, not only is there some discussion certainly around a longer-acting anti-VEGF like a PDS type system or other longer-acting where you may get six or 12 months of durability ultimately. We really feel that there is a really nice pairing with ONS-5010, not only for the initial treatment. We know that payers are saying that there would have to be some sort of a response to anti-VEGF, that ONS-5010 could be an important part to play there before any more advanced, quote-unquote, "future therapy." In the case where there's a breakthrough, I think that for patients that if you're on a zero order kinetic type device, you may need to bump a patient with an injection now and again. We think ONS-5010, given our pricing expectation, will be perfectly paired there. As well as with any adjuncts that come to market. If you have a VEGF kind of product that comes to market previously in development with a PDGF that needs an anti-VEGF, in that case, we really feel this is a great opportunity for ONS-5010. I think the payers really responded, as well as the physician, to that way of thinking. They really see this as a strong option within the standard of care clinical program. As I referenced, and as Larry has shared, we have a number of commercial planning activities underway. And patient outreach in terms of additional research, we have started not only the advisory board that Larry had referenced, but we will have an upcoming advisory board of retina leaders that will really help provide key insights to the way we're thinking about going to market, input, and certainly guidance on price and other factors. We've had deep discussions with, I would consider, best-in-class commercial support in terms of distribution and reimbursement services of known players, and those really codify the plans that we have going to launch and a real commitment to having an ideal customer experience so that going from manufacturing to the clinic and ultimately in the injection sites, we've done things in a perfect way. Last, and definitely not least within this, we've had the opportunity recently to engage into a managed care network discussion where we have an extensive reach into both national and regional plans in the U.S., where we share our program, what we're doing, and really with the aim to partner with the payer community. Often as people will appreciate, industry generally goes to market with a price that they will name, especially with J-code products, and hope and expect that the communities, both physician and payer, align around that. We're taking a different path. We really want to get the ideas and the good ideas from the payers about how to do this together from the beginning. We were really very nicely surprised there as well about the true collaboration. They see the off-label use, the associated problems that were referred to before. They know it occurs, and once they are aware of an on-label product at a responsible price, they have really shared their support in a number of ways. We're excited about that work, and that work will continue between now and ultimately launch. Just sort of wrapping this all up in together, with the potential value, I think we've all talked about just what this enables the retinal community to provide. Again, adding an important option to this market. One really important point is we have gone deeper with the societies, notably the American Academy of Ophthalmology, and ASRS, among others, is that a past president of the Academy was referring to OMIC, one of the key insurance providers, if you will, for the retina community about restricting bilateral injections for off-label bevacizumab. That's a really important point that we are solving for by the fact we have seeking FDA approval. As everyone knows, there is a good number of patients, roughly 35% wet AMD patients that require bilateral injection over time, and less so for DME, but it's appreciable amount, about 15%-20% of patients. We can solve for that, getting an on-label product in this case. I think there's also an element around because we'll have a unique J-code, and we will be similar in that way to EYLEA or LUCENTIS option, where we have the opportunity to provide a price that we consider a winning price for every one of the stakeholders. Then we can guard against the physicians. There has been a lot of discussion around the reimbursement rate, if you will, for off-label use of bevacizumab. We can really solve for that problem, having a consistent supply and the price around that. As talked about, synergistic with future innovation that we see. The last point on this slide, I think very much worth noting, is that because we're a branded option, we can provide, just as Eylea and Lucentis have done, commercial volume-based rebating. We can also support as per compliance the patient co-pay assistance programs. We will follow and be able to provide those to the physician community and the patients that they treat, which is different than off-label. Obviously, that's not opportunities that they have given the way that it is purchased and supplied. We are very excited about this program, and we're really getting very deep into a lot of our commercial planning activities. We're in that exciting window of time to launch, and glad to have shared a number of these updates with you all today. With that, I think we can turn it over to Q&A. Thank you. Once again, to ask a question at this time, please press star one on your telephone keypad. Please hold while we pull for questions. Thanks, Jesse. Hey, Jeff. I think one thing to expand on here at the end, you were mentioning how this gets reimbursed and rebates and J-codes. I think it might be helpful here to just speak a little bit to J-codes today for unapproved off-label bevacizumab versus what we'd expect for an approved ONS-5010. Yes, Larry. Right now, currently, there are roughly four codes that are used for off-label bevacizumab, and those codes vary by payer and physician preference. There is options out there, but they're all being used under either miscellaneous codes or actually for the oncology preparation. There isn't an appropriate code. As a new BLA, we have a clear path to seeking a unique J-code for this product. What we factor in is, because now they are issuing J-codes quarterly, it used to be an annual process, there is a very efficient means in seeking a J-code. We will do that upon approval. Beovu was a recent example where that permanent J-code was actually within the quarter they submitted their application was provided. We anticipate CMS in this regard to be very efficient, just like they were recently. As such, we'll continue from that point, it should be available quickly upon approval. Great. We do have some questions coming from the phone line. Our first question is from the line of Ed Woo with Ascendiant Capital. Please proceed. Yeah. Can you talk about your strategy for international commercialization? Yeah. Ed, I think our initial focus obviously is to launch here in the U.S. as quickly as possible. We are planning to file in Europe at or on the heels of the timing of our filing here in the U.S. Europe is a big part of the value for ONS-5010, and those conversations are underway as we speak. Jeff, Terry, I don't know if you have more to add to Ed's question. Other than the discussions are ongoing and consistent with what people would expect from the European Union. I think one thing to add in, Ed, is that as we move forward, we're considering all options. We're at this point putting the pieces in place to be able to launch ourselves because we don't want to let any time slip between getting an approval and starting to generate revenue. At the same time, we're considering a number of partnering options as well. I think Europe is a key area where we could potentially partner ONS-5010. It's what's done in the retina space. If you look at drugs like LUCENTIS and EYLEA, we see an opportunity here as well. Again, we're not going to let any of that just sit, and we'll be taking those steps necessary to be able to launch here in the U.S. If we needed to do more in Europe, that's definitely an option. For right now, we think finding a partner in Europe makes a lot of sense for us for a number of reasons. What about opportunities in Asia, particularly in Australia? Sure. As you know, our NORSE ONE trial was done in Australia, and I think for us, any place outside of the U.S. is a great option for a partner. As you may recall, we've already partnered the China rights. We've entered into a joint venture in China with a large investor here at Outlook Therapeutics, Syntone Technologies Group Co. Ltd. We look to that as a decent model that we can use going forward for other regions outside of Europe. Great. Thank you. Thank you. Our next question is from Kumaraguru Raja with Brookline Capital Markets. Please proceed with your question. Thank you. Once the ONS-5010 is approved, you can potentially try to block AVASTIN. How are you guys thinking about that, and what do the physicians feel about that? We've talked about this in the past. There's a number of options available to us. I think it's in our best interest and our shareholders' best interest to do what we can to make everyone aware that there is an approved bevacizumab. We would expect to take the appropriate steps upon approval with citizens' petitions and other avenues to protect our spot as the approved bevacizumab. Quite frankly, and we've been very clear about this, we don't expect that we will fully replace unapproved repackaged bevacizumab. We think that there probably will continue to be those patients and physicians that will need to use that type of product. We think that there's enough room in this very large $13 billion market to be able to have an approved bevacizumab as well as the other approved products. We think we're in a prime position with the approval to, in those cases where there is a step program in place, to be that drug as the first choice for being used in wet AMD and other retina diseases. Terry, I don't know if you have more to add on that. No. Quite simply, the regulation states once an approved product is available, compounding is no longer authorized. That's the regulation. That doesn't mean compounding is eliminated. It just goes back to the named patient basis. There'll still be patients that might be allergic to one of the excipients to where the product does need to be manipulated. Those are existing regulations that are actually enforced. To the other part of your point around the question is, I think Firas Rahhal did a great job earlier of speaking to this from the physician's point of view. The advantages of having an approved GMP formulation of bevacizumab is important to the physician community. Okay. Maybe you can talk a little bit about how you guys think about competition from biosimilars. I understand that they are down the road. How do you guys think about it, and how do you think you can position yourself strongly before biosimilars come on board? I'll start with this, and then I'll let Jeff chime in. I think we've talked about this earlier on in the presentation. There's a wide range, obviously, in pricing between where we could potentially price and where the current approved product's priced. We think biosimilars will use the standard model for discounting in retina, as we've seen in other places here in the U.S. With that, quite frankly, there still is a wide gap between where we would probably want to price versus where those biosimilars will price. I think responsible pricing for an approved bevacizumab is going to be key. I think in most of the scenarios that we look at, we still would be by far the lowest cost alternative. Jeff, did you have more to add to that? Maybe just to add, put a finer point on, if you look at Coherus or Biogen, who have ran aflibercept programs in other categories, as Larry referenced, the discounting has been pretty modest, to be honest, against the listed brand that they have entered into. We do anticipate a similar approach here with retina. As Larry mentioned, there is a very wide-open price space, if you will, a pricing corridor that we think we can really win. I think why we think there's such an important discussion to have around the pre-filled syringe is another really dimension that we feel we can win with. Having this ophthalmic-specific syringe will be a centerpiece of how we promote. I think the uptake and just the satisfaction from physicians will be tremendous when they get familiar with this product. That's one component. The other part of this is having the benefit of having previously worked for large companies who really commit themselves to the ideal customer experience, for us, goes beyond just providing a product in a great pre-filled syringe. We think of things around distribution. We think of elements around patient services. We think about contracting and being flexible and offering volume-based rebating. We fully intend to offer best-in-class services around that because at the end of the day, there will be smaller decisions made that may become bigger because there's options in the marketplace. We intend to win on all fronts and are committed to doing that once we get to market. Okay. You touched on it a little bit. Maybe you can provide more insight in terms of economics for physicians, in terms of 5010 ASP plus reimbursement versus the reimbursement they are getting for AVASTIN, how different that will be? To start off, I think that's a conversation for maybe a year from now when we actually have a price to talk about. I would put it this way, that this will be just like in terms of how the physicians get reimbursed. It's just like you would see with LUCENTIS and EYLEA, the normal type of rebating process for volume discounts, ASP, all of that comes into play here, and it's part of the formula we're looking at. For today's call, I think it's too early for us to really commit to that level of detail. I think we're not going to reinvent the wheel here. What physicians are used to seeing, what patients are used to seeing, what payers are used to seeing from companies or drugs such as LUCENTIS and EYLEA is what you would see here. My understanding is that probably they will come out better using 5010 compared to AVASTIN. Is that a fair understanding? I think that's right. Yeah. I would agree with that, Larry, Kumar. We've done some extensive math already, and as Larry said, we'll further research this. As you know, the way the mechanism works, price is a predicate to what economics the physicians do get with the ASP plus 6% now. We're going to refine that over time. It's an important consideration, and I agree with your conclusion that at the end of the day, we want to not only have consistency in the economics. That was one thing that's inconsistent now with the changes, with even the enhancements that compounders have had to undertake to improve the safety part of this, the costs have gone up. That's squeezed the margin, and even the societies have had a call to action about raising that reimbursement rate for off-label. It hasn't happened. We think that's an important consideration we're committing to solving for that and providing better economics at the end of the day, especially for those that are sensitive to that issue. Some of the physicians are less sensitive, but for those that are, there will be a path. Okay, great. Thank you so much. Thank you. Our next question is coming from Douglas Fowle with H.C. Wainwright. Please proceed with your question. Hi. Good afternoon. Thanks for taking our questions. Jeff, you touched on it a little bit before, but I'm just curious in terms of the support services that you expect to need to offer, just given the nature of this product, which ones do you think will be most important? Just in terms of the overall general detailing work that'll be needed, just given the familiarity and the already very high market share for compounded AVASTIN, what do you think the sales model will be, and how intensive do you think it will need to be, and maybe what messages do you think will be emphasized? Larry, do you want me to. Go right ahead, Jeff. Jump right in. Yeah. Great questions. This is the area where, for a commercial guy, I get very excited because we, as I referred to, and I think we will share more details in the coming months of who we're partnering with outside of the core services we intend to have in the U.S. I think it'll be a familiar partner that really is deep in retina in terms of distribution. The other services, I keep referring to patient services and making sure prior office support is, for example, initially especially. We've got a great team that we can partner with that know retina and anti-VEGF well, and so that'll be an important part of our go-to-market strategy. In terms of share of voice, the benefit we have, and Dr. Rahhal referred to this several times, is how small this community really is. If you look at field teams for other companies, whether in vitrets for surgical or even the anti-VEGF teams, they're pretty efficient. There's generally 30-40 people in the field, so to speak, and we think we can be very lean and efficient because we're not trying to commit somebody to new science. We don't have to share a new mechanism or go through that heavy burden of education and awareness. This is really about solving important problems, sharing about the pre-filled syringe. We're really going through the exercise of what we would do as Outlook and what we want to partner to really be as cost-effective, but also the best possible solution ultimately. Larry, is anything to add to. No, I think you hit it right on the head, Jeff. Great. It appears we do not have any additional questions at this time. All right. Well, in closing today, I'd like to just take a minute here to make it clear that the Outlook Therapeutics team strongly believes that a responsibly priced, FDA-approved bevacizumab will make an important difference to patients and physicians. Our innovative pivotal NORSE-2 clinical trial will read out in just a few months. We are optimistic that the results will prove that ONS-5010 can become the first and only approved bevacizumab for the treatment of wet AMD. Our previously completed NORSE-1 and NORSE-3 clinical trials provided both the proof of concept and the safety data that gives us great confidence in the outcome of the pivotal NORSE-2 trial. As a result of today's conversation, it should be clear how ONS-5010 fits into the broader treatment paradigm for wet AMD. It does fill a critical need for a GMP-produced, responsibly priced, FDA-approved anti-VEGF therapy for retina patients. If approved, ONS-5010 is expected to receive 12 years of regulatory exclusivity as the only approved ophthalmic bevacizumab. Perhaps the most exciting detail about Outlook Therapeutics for me is that ONS-5010 has the potential to be approved and available for use in less than two years. Market for us, once again, I would like to thank each of you for taking time out of your incredibly busy morning to join us on this call and provide your expert point of view. You provided us with some great insights. Thank you everyone online for participating today, and I hope that you found this event to be useful and informative. Take care and stay safe.