Opthea Limited (OPT) Earnings Call Transcript & Summary

What we are having this year, we're confident we're going to be able to provide value to you with over 550 companies presenting at this conference and multiple sector tracks to vertical life sciences, crypto currency, blockchain and Fintech, technology, media and telecommunications, clean tech and growth. H.C. Wainwright is a full-service investment bank dedicated to provide in corporate finance, strategic advisory and related services to public and private companies across multiple sectors and regions. We have a total of 24 publishing senior analysts in over 648 companies covered across all sectors. Please visit hcwco.com for more information. The in-person venue for the event is the Fountain Blue Hotel in Miami. Virtual participation will be staged simultaneously with over 550 company presentations scheduled as live feed and available on demand. Please join us for one-on-one meetings, corporate presentations and panels that will be available live and streaming on May 24 through the 26th. With that said, have a productive and enjoyable day, and I'd like to introduce our presenter, please welcome Megan Baldwin, the CEO of Opthea Limited.

Thanks very much, Trevor, and thanks, everyone, for tuning in and to hear an update on Ophtea Limited. We are developing a novel therapeutic for the treatment of retinal eye disease. This is the forward-looking statements causes. So at Opthea, we are developing OPT-302. This is a first-in-class better see VEGF-C, VEGF-D track inhibitor to be used in combination with the standard of care anti-VEGF-A treatments. This is the first and the only retina asset in development that's demonstrated strong clinical evidence of better visual acuity outcomes over and above the current standard of care anti-VEGF-A treatments that are currently available for age-rated macular degeneration. And we've demonstrated that with a well-tolerated safety profile. As you may be aware, the currently available treatment options and for those that are approved as well as for those that are in development, really are focused on reducing the burden of care, reducing the number of injections into the eye, whereas OPT-302 as a novel mechanism of action, a novel therapy is really designed to improve clinical outcomes for patients by improving clinical visual acuity in patients so that they can see better. So OPT-302 we expect it to be rapidly adopted by patients, physicians and payers globally because there is an existing and are very much a high unmet medical need despite the availability of drugs like Lucentis and EYLEA, which are all VEGF inhibitors. There is an established with wet AMD market in clinical practice and very much favorable physician and health system economics that will favor the rapid adoption of OPT-302 in the market. FDA has granted OPT-302 Opthea fast-track designation based on our superior Phase IIb results and a recognition of the existing unmet medical need for the treatment of age-related macular degeneration for patients. We have 2 concurrent Phase III clinical trials that are currently ongoing. We are on track for top line data in the middle of 2024 and a commercial launch of the product in 2025. OPT-302 represents a multibillion-dollar commercial opportunity because we are agnostic with respect to the standard of care treatment that we can add on to. We can tap into a multibillion-dollar existing market as a combination therapy. And there's long-term value opportunity given our intellectual property position that takes us out through 2024 and beyond given further patent term extension data and market exclusivity periods and the ability to also test our therapy in other retinal diseases such as diabetic macular edema and retinal vein occlusion, which represent large market opportunities in themselves. So the problem with the existing treatments with treatment of wet age-related macular degeneration of wet AMD is that many patients actually achieve an incomplete response to those therapies. Over 45% will not achieve any meaningful visual acuity gain and many will have persistent retinal fluid at the back of the eye, which will impair their ability to have improved vision. The majority of patients will not achieve a 20/40 visual acuity, which is required to drive a car, for example. The cause for this is that AMD is a multifactorial disease. It's not just been were on particular factors such as VEGF-A. And VEGF-C and D are other signals that have been shown to also signal through the same validated pathways that the standard of care treatments also target. We are also targeting a novel mechanism that actually is related to clinical resistance with the current standard of care treatments. So OPT-302 is a VEGF-C, D inhibitor, has the potential to be the next transformative step and to improve visual acuity outcomes in patients with this retinal eye disease. This is the pathway that we target with OPT-302 to track molecule. It's a significant blocker of VEGF-C and D's activity, completely shutting down its ability to activate through 2 receptors, VEGF receptor 2 and VEGF receptor 3. You can see the difference in the mechanism of action compared to the current available standard of care treatments, which include Lucentis, Avastin and EYLEA, all of which worked with VEGF-A, used in combination with any of these existing treatments, we can complete a much broader blockade of these pathways that drive the disease. And we can also shut down compensating up-regulation of these 2 parts of the pathway that can contribute to clinical refractoriness and suboptimal responses to any of the standard of care treatments. So we get a broader blockade and greater clinical efficacy by using our therapy in combination with any of the standard of care therapies. So when AMD is a leading cause of irreversible blindness left untreated. 80% of people will actually become legally blind because it is left untreated. It impacts 4.2 million patients in the United States, Europe and Japan. There are currently 1.6 million patients in the United States and 200,000 new patients diagnosed each year in the United States alone. 80% of those total patients are diagnosed. Despite that, the majority of patients will not achieve an optimal outcome despite receiving ongoing and regular treatment with the current standard of care therapies. There's a new need for innovative therapies that actually target new mechanisms that can actually see patients do better. Our opportunity here is to tap into the entire VEGF-A inhibitor market because we are agnostic with respect to what we can add on to. We can add on to Lucentis treatment, EYLEA treatment and actually tap into patients that actually receive off-label use of Avastin. This makes us a multibillion-dollar commercial opportunity for our therapy given our strategy to be used as a combination treatment. We are currently in Phase III clinical development and the Phase III clinical trials were informed by the outcomes in very large Phase IIb clinical trial, which was a multicenter randomized double-mass controlled study of intravitreal OPT-302 in combination with ranibizumab all the centers in patients with neovascular with wet AMD. This is the design of the clinical trial. And you can see that 366 patients were randomized to 1 of 3 treatment groups, either the control group, who received just ranibizumab all centers, or they received combination treatment of low-dose OPT-302 or a higher dose of 2 milligrams of OPT-302 in combination centers and all patients received injections into the eye on an every 4-week basis for up to 6 months. The majority of patients completed the studies. We have a very good rate of follow-up in this study, over 95% completed the study in the control and the 2-milligram group, as you can see here. The study demographics and baseline characteristics were well balanced between the treatment groups. Of note, we stratified our patient population to ensure that we had a balanced number of patients with different types of wet AMD lesions, which are generally classified as predominantly classic, minimal classic and cold lesions, and these were very well balanced across the treatment groups, as you can see here. We make the primary endpoint of the study demonstrating superiority in visual acuity over and above ranibizumab when OPT-302 is used in combination with Lucentis therapy, as you can see here. This is the blue curve. You can see the greater efficacy in the improvement of visual acuity was evident from 8 weeks and was extended out through the entire dosing period of the study over a 6-month treatment course, generating a significant superior gain in visual acuity of 3.4 letters over and above the control of Lucentis alone. This was highly statistically significant. And as I said, this was the primary endpoint of this clinical trial. The secondary endpoints that generally looked at further visual acuity outcomes or anatomical changes at the back of the eye further supported the visual acuity benefits that we saw in patients that received OPT-302 combination therapy. Importantly, more patients gain 5, 10 and 15 letters of visual acuity. This equates to 1 line, 2 lines and 3 lines of improved visual acuity over and above the standard of care. More patients actually achieved those thresholds and fewer patients actually lost vision when they received OPT-302 combination therapy. In addition, we saw greater reductions in retinal thickness, subretinal fluid, intra-retinal fluid, lesion side and neovascular area demonstrating our regression of the wet AMD lesion on OPT-302 was used in combination. We went into the Phase IIb study understanding that different wet AMD lesion types can actually demonstrate different clinical outcomes when they receive anti-VEGF-A treatment. We understand that the 3 main different wet AMD lesion types of occult newly classic and predominant classic lesions are differentially responsive to VEGF-A inhibitors or the standard of care treatments with occult and minimally classic patients representing the majority of patients with wet AMD and these representing the least and only moderately responsive patients to the current standard of care treatments. Indeed, this majority of patients with minimum classic and occult lesions were the patients have demonstrated the best clinical outcomes in our Phase IIb clinical study. Minimal and classic occult patients, which tend to respond less well to standard of care treatment actually did very well on OPT-302 combination therapy, achieving 16.1 letters as a visual acuity benefit after 24 weeks of treatment compared to 10 letters of gain with Lucentis alone. This equated to over an additional line gain of visual acuity of 5.7 letters in a highly statistically unadjusted P value of 0.0002. So this is a very compelling additional clinical benefit when OPT-302 was administered in combination with ranibizumab. And this also translated into an improved proportion of patients that actually gained 3 lines, 2 lines in 1 gain of visual acuity, a 42%, 30% and 20% relative increase open above what could be achieved with standard of care alone. There was a 42% relative increase in the proportion of patients that actually achieved 20/40 vision, and this is the threshold for being able to drive a car in the United States. We're meaningfully improving the proportion of patients that actually achieved that visual acuity benefit. In addition, we saw great efficacy in the difficult to treatment wet AMD lesion type, which has a very large unmet medical need because polypoidal choroidal vasculopathy, which is highly prevalent in Asian populations and often described as the most prevalent form of wet AMD typically displays less responsiveness to the standard of care treatment. However, in this subgroup of patients with polypoidal choroidal vasculopathy or PCV lesions, we almost doubled the outcome for patients demonstrating a 6.7 letter further gain in visual acuity compared to the control and a significant P value of 0.0253. So this is a very compelling vision acuity benefit once again in a lesion type of wet AMD that is highly prevalent, a very large commercial opportunity and which displays a sub response to the existing available standard of care treatment. So this is a very large opportunity for OPT-302, and it suggests that these are the type of lesions that are more sensitive to OPT-302 treatment. Our safety profile of OPT-302 individually injected was very, very well tolerated with a very low instance of ocular inflammation, which was comparable to standard of care treatment. Compared to some of the other therapies that have come through late-stage clinical development already been approved. Tolerability of OPT-302 continues to be very favorable, supporting OPT-302 use in the clinic. And this is a really important key factor of differentiation for our treatment in this landscape of agents that are coming through. So just to recap on our Phase IIb clinical trial before I talk about a Phase III pivotal studies that are all going. We met the primary endpoint of the clinical trial. We demonstrated and limit that OPT-302 works best in those patients where standard of care treatment is not as effective. We saw a 5.7 letter gain in the high responding group of patients with minimal plastic and occult lesions, which represent the majority of patients that we enrolled in our study in the majority of patients in the real world. And we've taken that forward. That will be the first patient population that we analyze in our Phase III clinical trial. We've also shown efficacy across the total patient population in a study that was designed for demonstrating clinical superiority. Moving now on to the Phase III pivotal trials. We are conducting 2 concurrent randomized controlled 3-arm Phase III studies called ShORe and COAST. So the ShORe clinical trial investigates OPT-302 when it's combined with Lucentis or ranibizumab. And we're asking the question when OPT-302 is added onto standard of care treatment with Lucentis, do we see improved clinical efficacy and improved visual acuity outcomes in these patients. The SHORE study will recruit 990 patients and will compare the combination of OPT-302 dose dominate with 4 and in every 8-week dosing regimen with ranibizumab that is dosed according to its approved label of every 4 weeks for the course of 52 weeks, which is a year of dosing. The COAST study on the other hand, will investigate or bit efficacy in combination with EYLEA or Fintech, and in this case, Fintech in the control arm is dosed every 4 weeks for the first 3 loading doses and then move to an every 8-week dosing regimen. OPT-302 combination will be dosed on an every 4 or an 8-week dosing regimen comparable to the standard of care treatment there. So we will get information of added clinical benefit of OPT-302 on 2 dosing regimens, a frequent dosing regimen every 4 weeks, but also on an extended dosing regimen of every 8 weeks. The primary endpoint of the study is anticipated to be read out in the middle of calendar year 2025. The primary efficacy endpoint after 12 months of treatment. And we have the intention to submit biologics license and marketing authorization applications with the FDA and the European Medicines Agency, respectively, following the completion of the primary efficacy phase of these 2 Phase III clinical trials, which are currently recruiting patients globally around the world right now. So the Phase III program is definitely informed by the Phase IIb. We've really kept a lot of consistencies in our Phase IIb for this Phase III clinical trial. We've optimized this for success based on how we intend to analyze the data arising under the Phase III trial. We are excluding RAP lesions from the clinical trial population, which will increase the additional mean BCVA gain in the total study population from 3.4 lives to 4.4 that is overall. And we are conducting a hierarchical primary analysis through a statistical means. First, looking at the efficacy in the high responding patients before we then ask the question, how does our patient population respond from the total group that will be recruited into clinical trial. We maximize the commercial opportunity by testing the therapy in combination with the 2 leading blockbuster agents than the standard of care treatments. And our strategy for Phase III design is aligned with the U.S. FDA and the EMA regulatory agencies, which have had input into the design of these trials and are fully aware of the statistical analysis that is proposed for these 2 studies. So as I said, OPT-302 has the potential to really revolutionize and improve outcomes for patients with wet AMD. This is a very large market, very large commercial opportunity, a $12 billion in excess to $12 billion market opportunity for OPT-302, where standard of care treatments actually are often associated with significant self responsiveness. And there is really further opportunity for visual liquidity gain with therapies that target novel mechanisms of action. In our Phase III clinical trial with this first-in-class VEGF-C track inhibitor, we've demonstrated an additional 5.7 letters of gain in the high responding patient population, which is the majority of patients. We've demonstrated efficacy across the total patient group. And we've also demonstrated efficacy in the polypoidal PCV group which is a high unmet medical need, particularly in Asian populations. We have fast track status for OPT-302. We're moving forward with our Phase III clinical program and anticipate top line data in the middle of 2024. We're well positioned now to launch the product in the U.S. in 2025 with the European, Japan and rest of the world markets to follow. We have compelling patient position and payer value propositions that will propel acceptance adoption and uptake, and we are the only VEGF-C, D inhibitor that's in development with no big threat in the competitive product line. This is a multibillion-dollar commercial opportunity for this therapy, and we look forward to taking it forward Phase II, but we have also further life cycle management and further expansion of the therapy into other retinal eye diseases that represent further blockbuster upside opportunity with a long patent life on the molecule. Thank you very much for your attention. Please don't hesitate to reach out should you have any questions. And thank you again to H.C. Wainwright for the opportunity to participate in today's conference.

Thank you, Megan. And I want to thank all of our presenters for taking part in what has been a very productive and informative series of presentations. We appreciate the time and effort that went into preparing them. We're very grateful for your flexibility and your presence at our conference this year. Thank you again from the H.C. Wainwright team.