Study Update

Aug 3, 2021

Press release

Hello, welcome to the Outlook Therapeutics NORSE TWO Top Line Results conference call and webcast. At this time, I'd like to remind our listeners that remarks made during this webcast may state management's intentions, beliefs, expectations, or future projections. These are forward-looking statements and involve risk and uncertainty. Forward-looking statements on this call 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 Securities and Exchange Commission's website. We encourage you to review these documents carefully. Joining us on the call today from the Outlook Therapeutics senior leadership team are Russell Trenary, President and Chief Executive Officer; Terry Dagnon, Chief Operating Officer; Lawrence Kenyon, Chief Financial Officer; and Jeff Evanson, Chief Commercial Officer. I would now like to turn the call over to Mr. Trenary, President and Chief Executive Officer of Outlook Therapeutics. Please proceed. Good morning, everybody. Thanks so much for joining us. Wow, is this an incredible day for us at OTLK. Hopefully, you're looking at our agenda slide. Today, we'll be talking about the NORSE-2 study design and demographics, followed by the amazing top-line efficacy and safety results. We'll touch a little bit about the wet AMD market overview. I'm sure many of you are already familiar with that. Then a few comments about our commercial strategy and next steps now that we have these data before us that you will see. Next slide, please. The star of the show is right in the middle of this page. The NORSE-2 pivotal trial, which was our second registration trial, and Terry Dagnon will be going through the details of that, but the top-line data that came out of that were data that we just could not have been more pleased with. As a reminder, you probably all remember or might know that in advance of this study, NORSE-1 was conducted. It was a clinical experience trial. Had dozens of patients associated with that treated in Australia. That was actually our first registration trial. Had really good results coming out of that. In addition to that, NORSE-3 was an open-label safety study that has been completed in the past and did provide the kind of data that the company was looking for to support the BLA requirements. Today, the star of the show is NORSE-2. Next slide, please. The NORSE TWO pivotal trial, which again, was our second registration trial, was a randomized, mask-controlled trial, and it featured ONS-5010 in one of the arms, our bevacizumab-vikg versus Lucentis ranibizumab. There were 228 patients that were enrolled. The trial was conducted entirely in the U.S. In the trial arms, these patients were essentially treatment naive. Over 95% of the patients had not received any kind of treatment previously. The safety and efficacy data that came out of this support our planned U.S. BLA submission. We're aiming for calendar 1 2022. Now to give you some of the remarkable highlights from this front, Terry Dagnon, Chief Operating Officer. Terry? Thank you, Russ. On slide 7, our NORSE TWO innovative pivotal trial design. As Russ said, it was a randomized, mass-controlled trial. We enrolled 228 subjects. It was ONS-5010 or bevacizumab-vikg administered monthly versus Lucentis dosed via the PIER dosing regimen, which is 3 initial monthly injections followed by quarterly dosing, which many forget is also 1 of the approved alternate dosing regimens in the Lucentis labeling. The primary endpoint was a different in proportion of subjects gaining at least 15 letters of best-corrected visual acuity at day 330 or also known as month 11. Next slide, please. Study disposition, we are very quite pleased with. We ran this study, obviously, during the COVID epidemic. 378 subjects were screened. The randomized in the ONS-5010 were 113 randomized to Lucentis 115. The ONS-5010 arm and 96 complete the Lucentis treatment arm. The ITT population was 113 ONS-5010, 115 Lucentis for protocol 85 and 78 respectively. The safety population was, of course, the same as the ITT population. Next slide. On slide 8, you can see our top-line results. We believe that the results were unprecedented as seen in registration trials, 41% with ONS-5010 were 3-line gainers. We were very excited to see that. We saw in our intent to treat population, the primary endpoint subjects who gained at least 15 letters, 41% ONS-5010, 23% Lucentis with a highly significant P value of 0.0052. This was also confirmed in the secondary per protocol data set with almost exactly the same numbers, 41% and 24% respectively, with a P value of 0.04. Our key secondary endpoint, mean change in visual acuity, through month 11 from baseline change. Intent to treat 11.2 letters for ONS-5010, 5.8 letters for Lucentis, again with a highly significant P value of 0.0043. This was also confirmed in the secondary per protocol data set, 11.1 letters and 7 letters with a P value of 0.05. Next slide, please. The safety results that we saw reported in NORSE TWO are consistent with our previously reported safety results from NORSE ONE and NORSE THREE trials. There was only 1 subject in all 3 trials at this point who had ocular inflammation, which we've been tracking very closely because some of the other potential therapies coming to market have had a problem in that area. In NORSE TWO, we also only had 1 serious adverse event that was reported in the bevacizumab-vikg treatment arm, which was resolved and no sequela. There were no unanticipated safety signals that were detected. The most common ocular adverse event was conjunctival hemorrhage, which is associated with the injection procedure that is that thin layer on top of the eye, and just hemorrhaged blood vessels due to the needle penetration. We're very excited about this safety database and the combination of the safety population from NORSE-1, 2, and 3 supporting our trial, and that we've seen it very similar to what's been previously published for bevacizumab in trials such as the CATT trial and other trials. We're very excited about our NORSE-2 safety results and moving forward with filing. Russ, that's all I have. Turning back over to you. Thank you, Terry. Hopefully the slide that's in front of you now is the summary of the NORSE-2 results. Again, we just could not be more pleased with what came out of that. It demonstrated statistical significance across the primary and key secondary endpoints. In this trial, ONS-5010 was demonstrated to be safe and well-tolerated. This is the final step we needed in order to have what we need to prepare and move forward with our U.S. FDA BLA preparation, which again, is targeted for calendar Q1 2022. This next slide. You all have seen these market size slides before, be on the edge of your seat for these next two, because it really does begin to spell out the opportunity that's in front of us. We're sitting on top of a $13 billion marketplace currently. As you can see from the slide, the vast majority of this marketplace is, A, in the U.S., with $9 billion of it, and B, it's wet AMD, which is the condition that we were studying in this trial. That marketplace is estimated to be growing at a compounded annual growth rate of over 4%. By 2030, this will be approximately a $20 billion space with, again, a huge chunk of it in the U.S., and most of it, the vast majority, still being wet AMD. Next slide, please. Take a look at this. 50% of the treatments that occur in the U.S. are with a product that's not approved by the FDA for ophthalmology use for the treatment of wet AMD. That's the space that we're stepping into. what does it mean for a doctor and patients when we come out with an FDA approval for something that charges into this space? Well, it means a couple of things. I'd ask you to consider why is it 50% now? Is that the top end? Can that number go up? Can that share for this bevacizumab molecule go up? Well, think about this. If you survey doctors and you ask them, why do you not write for off-label Avastin. A lot of them will say, "Look, I want to take the best care of my patients that I possibly can, and I rely on FDA-approved products to do that." Why do they rely upon that? Part of it is because there are vast requirements associated with, first of all, getting an FDA approval, and secondly, keeping it. There are vast requirements and specifications associated with getting products out of a GMP-approved facility. When you have products that come out of such a factory, what you are assuring the doctor, the payer, and the patient is that you're living to the standards that will ensure that the identity, the strength, the quality, and the purity of that product, which has been studied and manufactured for this condition, which is FDA-approved, that those requirements have been met. It's a big deal to bring an FDA-approved product to this space. In addition to that, we all know that there are some malpractice insurance entities that are happy to or willing to cover the first eye of a patient who receives an off-label product, but not necessarily the second eye. Again, that's a market segment expanding opportunity for us because we are going to have an FDA-approved product for this space. Next slide, please. As we look at the commercial planning activities that are underway, there's been a lot of work done with physicians. Patient outreach, a lot of work will be done there. There's been work, but there will be an expanded effort aligning with key opinion leaders. The company's done some really excellent work reaching out to the payer community to understand what their needs are. We believe that our bevacizumab, VIKG, when FDA-approved with a cost-effective profile, will be potentially widely adopted by payers and clinicians worldwide as a potential first-line drug of choice, especially for payer-mandated step edit in the United States. One of the things that holds this notion back is the fact that there has not been a cost-effective FDA opportunity in this segment, in this space. By winning on this big idea of getting an FDA approval here, we believe that that's going to have market-moving capability. Next slide, please. We're not going it alone. We have partners on the manufacturing side and on the product development side that the company's been dealing with and working with and will continue to do so. Fujifilm Diosynth and Ajinomoto Bio-Pharma Services are both excellent partners that the company's been working with on a manufacturing standpoint and will continue to do so. In addition to that, the company has product line research and development depth associated with new delivery systems. This is a device that ends up being put in the hands of retinal surgeons. Yet, for the segment that we're stepping into, the syringes and needles were not specifically designed and tested and FDA-approved for use and treatment of wet macular degeneration in the retinal space. We will step in with a product ultimately that does include a prefill syringe with materials, needles, et cetera, that are all specified and designed specifically for these treatments. Again, it's not just the FDA approval, but we are also bringing high-quality partners and a product development effort that we believe will enhance the quality of care, has the potential to enhance the quality of care in this space. Next slide, please. The next steps for us simply, again, to get this U.S. FDA BLA submission into FDA in the first quarter, at least in the first quarter of 2022. To continue to accelerate the pre-commercial planning and activities, now toward execution in the United States, especially for manufacturing, distribution, sales force planning, a continuation of the great work that's been done by Jeff Evenson in working with the physician and payer advisory boards. Now a real live ability to have some meaningful conversations with key opinion leaders. Before, the company had a good story. It had some big dreams. Now we have data. We have facts. These facts will lend themselves, I think, to some very fruitful conversations with key opinion leaders in the space. Next slide, please. People, got a lot of friends who ask me, "Why Outlook? We didn't see this coming for you. When I look back in the first 40 years that I've spent in the ophthalmic space, the most fruitful moments and the most rewarding moments have been opportunities that I've had to participate in being able to change or enhance the standard of care. We have that opportunity to do this with this product, this indication in this retinal space. I could not be more happy to be here. We've got a wonderful team that's engaged in some excellent planning. We've got some great execution opportunities in front of us now and really looking forward to moving this forward and creating great opportunities for patients, doctors, and payers alike, as well as our shareholders. With that, we'll open it up to questions. Thank you. Ladies and gentlemen, at this time, we'll conduct our question and answer session. If you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate that your line is in the question queue. You may press the star key followed by the number two if you would 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 key. Once again, to ask a question, press star one on your telephone keypad. We'll pause for a moment to poll for questions. Our first question comes from Douglas Tsao with H.C. Wainwright & Co. Please state your question. Hi. Good morning. Thanks for taking the questions, and congratulations on the data. Just to help clarify, if you could provide some background on the sort of differences between the ITT and the per-protocol group. Also, Russ, you mentioned the pre-filled syringe. Just curious what you need to accomplish to get that to market and how quickly after just the vial presentation will come to market do you expect it to be commercializing the pre-filled syringe? Thank you. Yeah. Great. Thank you, Doug. I'm going to pass the first question to Dr. Data to talk through the differences between our ITT and our per-protocol group. Jeff, we'll hand it over to you on the work that's been going on the pre-filled. I know you're proud of the work that's been accomplished and that which is to come. Terry, you're up. Yeah. This is Terry. Doug, the difference in the ITT and per-protocol populations, the number of patients that were in the ITT population were people that were consented, enrolled, and got at least one dose. The per-protocol were patients that obviously had completed the study and completed it as absolutely as per-protocol. The ITT for superiority study designs is always the primary dataset for registration. That's why in the slides we called the ITT the primary and secondary. The good news is we saw there's always a difference in number of subjects between those databases, but we saw remarkably similar results in both the ITT and per-protocol, and all for both the primary and the secondary were significant. In the case of the ITT dataset, in both cases, highly significant. Jeff, I know that anytime there are products under development, there are timelines that are goals and timelines that are reality. I think there's been a tremendous work that's been done in this area. If you could address that next question, please. Yes. Thank you, Russ, and Doug, thanks for your question. We are very excited, as we have shared previously, about our pre-filled syringe and the development plans there. Our plans are to, of course, get to market as soon as possible with the work that we're doing. At this point, we've talked about this being a follow-on post-approval supplement. Those timelines we are finalizing in the coming months about when exactly that'll occur. It would be very near term from a vial presentation. I think on that point, what we feel is critical is to first get the FDA-approved bevacizumab, our product, ONS-5010 on the market, whether it's a vial or a pre-filled syringe. We are, though, very excited about the work of the cyclodextrin polymer syringe and the advantages it brings, not only against compounding options, which are non-ophthalmic syringes, as Russ referred to earlier, of insulin and tuberculin syringes, who have still had a tremendous number of issues in the market. Even against in-line approved FDA options of glass syringes. We're a non-glass syringe, we're working hard. The team is fully integrated and a lot of that under Terry's leadership, just couldn't be more excited about that. It'll be as soon as we can get there, Doug, is really the answer, I think we'll be sharing dates as we get through probably later this year about the timing more specifically. Okay, great. Thank you so much. Yep. Thank you. Just a reminder, to ask a question, press star 1 on your telephone keypad. Our next question comes from Kumar Raja with Brookline Capital Markets. Please state your question. Congratulations on the positive data, and thanks for taking my questions. First, with regard to baseline visual acuity, what can you tell us with regard to both arms? Then with regard to plans for filing in Europe, what needs to be done there before you can file, and what kind of interactions have you had with the European authorities? Maybe you can talk a little bit about plans in RVO and DME. Thanks. Well, that sounds like three pitches right at you, Terry. Yes, absolutely. Good questions. The first one on best-corrected visual acuity, obviously that was a key secondary endpoint. The intent to treat, we saw the 11.2 and 5.8 letter difference, highly significant. The secondary per-protocol data set, again, with p value of 0.05. Obviously, on clinicaltrials.gov, we've posted the inclusion/exclusion criteria, so baseline visual acuity was between 20/50 and 23/20. In regards to the second question, our rapporteur and co-rapporteur have been assigned in the European Union. We're working with the small business office and directly with the CHMP project manager. We're in the process of scheduling a pre-submission meeting at this time. We're super excited to be able to go into that meeting with these results and the other things that we've done and coordinate the actual submission date and what's going to be in the filing for the MAA in Europe. Hopefully, that answers your three questions. Yeah, I had a question on plans for DME and RVO. Yes. How are you guys planning that? Yeah. That's on track. As we've previously stated that we have FDA-approved SPAs for what we call NORSE FOUR, FIVE, and SIX. Assuming wet AMD's already approved, we only need to do one further study in BRVO and two studies in DME, that's NORSE FOUR, FIVE, and SIX. We plan on enrolling patients at the end of first quarter next year for those. That's what we've said. Nothing's changed on that. That's what we've said previously publicly. Okay, great. Thanks so much. Thanks, Kumar. Our next question comes from Douglas Tsao with H.C. Wainwright & Co. Please go ahead with your question. Douglas Tsao, your line is open. Please go ahead. You may have yourself on mute. Oh, sorry, I put myself on mute. Thanks for taking the follow-ups. Just given the strengths of the results, does this change how you're thinking about the opportunity in terms from a business development standpoint? Thank you. Doug, I think the company has always been optimistic that the results would be good. I think the p values that came out of this study give us tremendous confidence that in going through regulatory bodies, any potential for hesitation from them due to the data should or could have been erased now. As it pertains to business development opportunities, I guess if there were people that were on the outside looking in at what the company was attempting to do, maybe they would've thought it would be successful, maybe not, but I got to think that this is going to wake up a lot of people. It really doesn't change how we think about things, though. We've always planned on, well, at least since I've been here, and it's almost been a month, we've always planned on going direct in the U.S. I've been involved in four very large launches during my career, some of them with sales in excess of $50 million in the first year of sales. I think obviously, no hesitation, we're full speed ahead, all hands on deck to be in a position to go and execute in the U.S. As we engage in partnering activities, that engagement's been going on for a little bit of time, I guess if anybody was wondering, can the company and this bevacizumab-vikg pull off compelling results? They need not wonder any longer. We don't think about it any differently, maybe others might be a little bit more encouraged to want to be able to do something with us if we're willing to do so. Great. Thank you so much. Again, congrats on the data. Thank you. Thank you. There are no further questions at this time. I'll turn it back to Russ Trenary for closing remarks. Again, thank you everybody. This is, again, it's a great day to be at OTLK. The data were the stars of the show today. We believe that our desire to be able to be a potential player in enhancing the standard of care is now even clearer. We now have facts instead of just a story. We look forward to meeting you all down the road as we execute on our plan. Thank you all for coming. Thank you. This concludes today's conference. All parties may disconnect. Have a great day.