Study Update

Aug 3, 2021

Press Release

Hello, and welcome to the Outlook Therapeutics NORS II Top Line Results Conference Call and Webcast. As a brief reminder, all participants are currently in a listen only mode. Following the presentation, there will be a question and answer session with analysts and qualified investors. Note that this webcast is being recorded at the company's request and a replay will be made available on the website following the end of the event. At this time, I'd like to remind our listeners that remarks made during this webcast may state management's beliefs, expectations or future projections. These are forward looking statements and involve risks and uncertainties. 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 Bagnon, Chief Operating Officer Lawrence Kenyon, Chief Financial Officer and Jeff Evenson, Chief Commercial Officer. I would now like to turn the call over to Mr. Chenery, President and Chief Executive Officer of Outlook Therapeutics. Please proceed. Good morning, everybody, and thanks so much for joining us. Wow, Is this an incredible day for us at LTK? Hopefully, you're looking at our agenda slide today. We'll be Talking about the NORS II 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. And 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. So the star of the show is right in the middle of this page, the NORS II pivotal trial, Which was our 2nd 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, NORS1 was conducted. It was a clinical experience trial, We had dozens of patients associated with that treated in Australia. It was actually our first registration trial, had really, really good results coming out of that. And in addition to that, NORS III 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. But today, the star of the show Is NORS II. Next slide please. The NORS II pivotal trial, which Again, was our 2nd registration trial, was a randomized mass controlled trial and It featured ONS-five thousand and ten 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 United States. And in 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. And now to give you some of the remarkable highlights from this front, Gary Dagnon, Chief Operating Officer. Gary? Thank you, Russ. So on Slide 7, our NORSCH 2 innovative pivotal trial design, As Russ said, we randomized it was a randomized mass controlled trial. We enrolled 228 subjects. It was ONS-five thousand and ten or bevacizumab VIKG administered monthly versus Lucentis Dosed via the peer dosing regimen, which is 3 initial monthly injections followed by quarterly dosing, which many forget is also one 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-five thousand and ten were 100 and randomized to LUCENTIS 1 100 and 15. We had 103 complete the ONS-five thousand and ten arm and 96 complete the Lucentis treatment arm. The ICT population was team ONS-five thousand and ten-one hundred and fifteen LUCENTIS for protocol 8578, 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-five The 10 were 3 line gainers. We were very excited to see that. We saw in our intended treat population, the primary endpoint Subjects who gained at least 15 letters, 41 percent ONS-five thousand and ten, 23% Lucentis, with a highly significant p value of P052. This was also confirmed in the secondary For protocol data set, it's almost exactly the same numbers, 41% 24% respectively, with a P value of 0.04. Our key secondary endpoint mean change in visual acuity Through month 11 from baseline change, intend to treat 11.2 letters for ONS-five thousand and ten, 5.8 letters For Lucentis, again with a highly significant p value of 0.0043, This was also confirmed in the secondary per protocol dataset, 11.1 letters and 7 letters with a p value of 0.05. Next slide please. The safety results that we saw reported in NORS II are consistent with our previously reported safety results from NORS I and NORS III trials. There was only one subject in all three 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 NORS2, we also Only had one serious adverse event that was reported in the bevacizumab VIKG Treatment error, 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 hemorrhage blood vessels due to the needle penetration. So we're very excited about the safety database And the combination of the safety population from NORS I, II and III supporting our trial and That we've seen is similar, very similar to what's been previously published for bevacizumab in trials such as the CAT trial and other trials. So we're very excited about our Norse II safety results and moving forward with filing. Russ, that's all I have. Turning back over to you. Thank you, Terry. So hopefully the slide that's in front of you now is Summary of the Norse 2 results. And 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. And in this trial, ONF-five thousand and ten was demonstrated to be safe and well tolerated. This is the final step we needed, in order to prepare 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, but be on the edge of your seat for these next two because it really does begin to Really spell out the opportunity that's in front of us. We're sitting on top of a $13,000,000,000 marketplace Currently, and as you can see from this slide, the vast majority of this marketplace is A, In the United States, it's $9,000,000,000 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%, which means by 2,030 So, be approximately a $20,000,000,000 space with again, most of it a huge chunk of it in the United States and most The vast majority still being wet AMD. Next slide please. So take a look at this. 50% of the treatments that occur in the United States 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. And so what does it mean for a doctor when we come out with a And TEGR's and patients when we come out with an FDA approval for something that charges into this space. I'll need a couple of things. And 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. And why do they rely upon it? Part of it is because there are vast requirements associated with, 1st of all, getting an FDA approval and secondly, keeping it. And 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, the patient is that you're living with 2 of 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. So 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. So Again, that's a market expanding, 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 will a lot of work will be done there. There's been work, but there will be an expanded effort aligning Key opinion leaders and the company has 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 widely 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. Again, 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. So 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 has been dealing with and working with and will continue to do so. Fujifilm Diosyn and Aji BioPharma are both excellent Partners that the company has been working with on a manufacturing standpoint and will continue to do so. And 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 this is a device that ends up being put in the hands of retinal surgeons And 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 pre fill syringe with materials, needles, etcetera, that are all specified and designed specifically for these treatments. So, 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. So the next steps for us simply, Again, to get this U. S. FDA BLA submission into FDA In the Q1, at least in the Q1 of 2022 and then to continue to accelerate the pre commercial planning and activities and now 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 and working with the physician and payer advisory boards, and 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. And these facts will lend themselves, I think, to Some very fruitful conversations with key opinion leaders in the space. Next slide, please. So people got a lot of friends who asked me why outlook. We didn't see this coming for you. And when I look back in the 1st 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. So 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. And with that, we'll open it up to questions. Thank you. And ladies and gentlemen, at this time, we'll conduct our question and answer session. From the queue. Our first question comes from Douglas Tsao with H. C. Wainwright. 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 prefilled 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, you expect it to be commercializing the prefilled syringe? Thank you. Yes, great. Thank you, Doug. I'm going to pass the first question to Doctor. Data to talk through the differences between our ITT and our Per protocol group and then Jeff will 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, do you have a Yes, this is Terry. So Doug, the difference in the ICT and Pure Protocol populations, the number of patients that were in The ICT 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 data set for registration. So 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 But we saw remarkably similar results in both the ITP and per protocol and All for both the primary and the secondary were significant. And in the case of The ICT dataset in both cases highly significant. And then Jeff, I know that anytime there's their products under development, there are always There are timelines that are goals and timelines that are reality. I think there's been tremendous work that's been done in this area. So if you could address that next question, please. Yes. Thank you, Russ. And Doug, thanks for your question. So we are very excited as we have shared previously about our prefilled 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, but at this point, we've talked about this being a follow on post approval supplement, and that those timelines we are finalizing in the months about when exactly that will occur, but it would be very near term from a vial presentation. But I think on that point, what we feel is Critical is to first get the FDA approved bevacizim, our product ONS-five thousand and ten on the market, Whether it's a vial or a prefilled syringe, we are though very excited about the work of this type of polymers syringe and the advantages Not only against compounding options, which are non ophthalmic syringes, as Russ referred to earlier of insulin and tuberculin syringes, We have still had a tremendous number of issues in the market, but even against in line approved FDA options of glass syringes, we're a non glass syringe and so We're working hard. The team is fully integrated and under a lot of that under Terry's leadership And just couldn't be more excited about that. But it will be as soon as we can get there, Doug, is really the answer. And 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. 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 activity equity, what can you tell us with regard to both arms? And then with regard to plans for filing in Europe, what needs to be done there before you can Fine. And what kind of interactions have you had with the European authorities? And maybe you can talk a little bit about Plans in RVO and DME. Thanks. Well, it sounds like Three pitches right at you, Terry. Yes, absolutely. So, good questions. The first one on Best corrected visual acuity, obviously, that was a key secondary endpoint And the intent to treat, we saw the 11.2 and 5.8 letter deference, highly significant. And The secondary per protocol data set again with p value of 0.05. Obviously, on clintrials.gov, we've posted The inclusion, exclusion criteria, so baseline visual acuity was between 2,050 and 2,320. In regards to the second question, we've 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. Yes, I had a question on plans for DME and RVU Like how are you guys planning there? Yes. So that's on track as we previously stated that We have FDA approved spas for what we call NORS IV, V and VI. We only need to do assuming what AMD is already approved, We only need to do one study, one further study in BRVO and 2 studies in DME, that's NORS IV, V and VI, And we plan on starting enrolling patients at the end of Q1 next year for those and that's what we've said. Nothing has changed on that. That's what we have said previously publicly. Okay, great. Thanks so much. Thanks, Kumar. Our next question comes from Douglas Tsao with H. C. Wainwright. Please go ahead with your question. Douglas Tsao, your line is open. Please go ahead. You may have yourself on mute. Sorry, I put myself on mute. Just thanks for taking the follow ups. Just given the strength of the results, does this change how you're thinking about the opportunity in terms from a business development standpoint? Thank you. So Doug, I think the company has always been optimistic that the results would be Good. I think the P values that have been 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 have 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 United States. I've been involved in Four very large launches during my career, some of them with sales in excess of $50,000,000 in the 1st year of sales. And I think the obviously no hesitation, we're full speed ahead, all hands on deck to Be in a position to go and execute in the United States. As we engage in partnering activities That engagement has been going on for a little bit of time, but I guess if anybody was wondering, can the company And this bevacizumab, BIKG pull off compelling results, they need not wonder any longer. So We don't think about it any differently, but maybe others are might be a little bit more encouraged So want to be able to do something with this, if we're willing to do so. Great. Thank you so much. And 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. Well, again, thank you, everybody. This is, again, it's a great day to be at OTLK. Okay. And 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 and 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.