STIFEL 2026 HEALTHCARE CONFERENCE - AURA BIOSCIENCES INC

All right, thanks everyone for continuing to join us here at Stiefel's 2026 Healthcare Conference. My name is Dara Azar, senior biotech analyst here. It is my pleasure to welcome Natalie Hollis, president and CEO of Aura Biosciences. Natalie, great to have you here. Thank you so much for having us, it's been a great day. Yeah, maybe it would be great to start with an intro to Aura, maybe overview recent milestones and upcoming milestones. And walk us through the rationale for focusing on ocular oncology. Yeah. So I've been with the company for six months, just about. It's been a really fantastic time of really excellent execution on the part of the team. We are developing our product candidate, Belsar, for the treatment of early choroidal melanoma. And And we completed enrollment in our pivotal study in May of this year, and we're on track for top-line efficacy data in the second half of 2027. It's a very exciting time for the company. The platform technology that is the basis for the product candidate shows really excellent promise against really any solid tumor. Some of the foundational work from John Schiller's lab at the NIH shows that across 140 different cell lines of different solid tumor types, BELSAR has excellent potency and selectivity. So if you're a big visionary, like the founder of the company, Elizabeth De Los Pintos, you see the potential for using this in a range of solid tumors. And so a few years ago, the decision was made to move into the NMIBC, the bladder cancer space, in parallel with the work that the company was already doing in ocular oncology. When I came into the company, my history and background is primarily in late stage and commercial phase rare disease companies. And so I looked at the opportunity, as we'll talk about, in early choroidal melanoma and saw an incredible potential for delivering really transformative value for patients who have a very poor set of choices when they're given this diagnosis and consequently create a lot of value for shareholders. And in my experience, the more things you're trying to do at the same time, the more execution suffers a little bit. If you want to be the best in the world, you kind of have to go all in on it. So we announced preliminary data from the NMIBC program in the summer. It actually looked quite encouraging, which provides a nice read-through into the ocular oncology space. But we decided to put that program, finish the study but deprioritize it, and go all-in on building the world's preeminent ocular oncology company around BELSAR with the initial indication in early choroidal melanoma, but also we have earlier stage programs in metastases to the quarry from other solid tumors and ocular surface cancers, which, you know, if they go forward, have the opportunity to really be a first-in-class frontline therapy for a really devastating set of diseases. We typically see in oncology that companies go for a late line label behind the competition and then they work their way up to earlier line settings. It sounds like Aura is doing things a little bit differently. It would be great to frame the opportunity and competitive positioning here. Yeah, so first it's important to understand that when we're talking about choroidal melanoma, it is more or less synonymous with uveal melanoma. So 95% of uvea tumors appear in the choroid. Most, actually all of the drug development that has been done in the uveo melanomas to date, to space to date follows the model that you, that you suggested. So there has been a fair bit of drug innovation in the metastatic setting, a little bit of innovation in the large to medium-sized tumors, but in early choroidal melanoma, where the vast majority of these patients sit, these tumors are generally caught early. There's been no meaningful innovation. The profile of BELSAR is such it's local therapy that is delivered directly to the choroid. The mechanism of action of Belsar is exquisitely selective for tumor cells. the cytotoxic activity only occurs with light activation, we have a profile that really lends itself to treating early, which all the data in the field shows leads to the best outcomes. And so when we think about the competitive landscape of uveal melanoma, there is no competition in the early choroidal melanoma space. We are the only program to our knowledge that is exploring treatment of the early stages of the disease, and hopefully these patients never get to later stage disease if we're successful. How significant is the unmet need, and what kind of options do diagnosed patients have today? Yeah, so the unnet need is significant. This is a really devastating diagnosis to get. The current treatment options are you have a melanoma growing in your eye. Number one, we can leave it alone and roll the dice. And all the data show that the bigger these tumors get, the larger the risk of metastatic disease. Number two, we can treat with radiotherapy, either plaque radiotherapy or proton radiotherapy. It will stop the tumor from growing further, which is considered a complete local cure. But you put the majority of patients on an irreversible path to blindness in the treated eye. And the third choice is we can take the eyeball out altogether. We can do a nucleation. So it's a really difficult decision to make. Do I trade increased risk of advancing disease for preserving my vision? Or do I treat the tumor early, but know that I'm going to blind this patient? So the unmet need, I think, is unarguable. And the value proposition with BELSAR is, as we saw in the Phase II study, we see excellent tumor control. 80% of patients who were treated at the therapeutic dose in the phase II study achieved tumor control, 90% of those patients preserved their vision. So if now there's an option to treat this disease early, stop the tumor from growing, but preserve vision, it really opens up the treatment paradigm to have a lot more patients treated earlier in the disease course. Before we get into your already available data from Phase 2, it would be a good idea to briefly touch on Phase 3. What sort of design elements would you point to in your Phase 3 design, and what's the current status of that trial? Yeah, so the Phase 3 COMPASS study is fully enrolled. We completed enrollment on 108 subjects at the end of May of this year. And the primary efficacy analysis is at 15 months from the last two enrolled patients' enrollment date. We look at percentage of patients who have tumor control who have progressed versus the ceased tumor growth. And then there's the 24-month study, so we'll continue to follow these patients and look at durability of tumor control as well as vision preservation and overall safety. One of the important elements for enriching for a higher probability of success is, and this is something that was negotiated with the Ophthalmology Division of the FDA on our special protocol agreement, is that patients on the way in needed to have documented growth. So the tumors needed to be actively growing in order for these patients to be enrolled. What that does is it enriches for a separation of the curves within a 15-month time period. So it was a design element that was intended to increase the probability of seeing a signal within a reasonable time frame. It made the enrollment a bit of a pain to get through, to be frank. But importantly, there are precedent examples with this division of employing these enrichment strategies that set up very stringent inclusion exclusion criteria, again, to sort of enrich for success in the trial design, that don't translate into a narrow label. And so when we look at the overall addressable patient population, we certainly do not expect to be limited to active growth, because as I said earlier, the data show the earlier you treat, the better that these patients do in the long run. But it was an important thing to do to give us the high probability of success that we have on the primary endpoint. We are over 99% powered at 100 subjects to detect a difference in line with the phase two results with the study enrolled as it is. And how comparable are the populations and progression assessment criteria between phase two and phase three? Yeah, so by design, we wanted to keep everything as consistent as possible going from the phase two to the phase three. So inclusion-exclusion criteria are more or less identical. And the assessments, the only change in the primary efficacy assessment is that rather than a 12-month look, it's a 15-month looks, which, if anything, should sort of increase the separation of the curves even more from an additional quarter of treatment. But otherwise, we've maintained excellent consistency in the design and the study population from the phase two to the phase three. Okay. From your experience, how variable would you say the disease natural history is with patients who are set to receive sham, and what kind of design considerations have you built into the trial to control against subjectivity and variability? Yeah, it's a great question. So there's actually a fair degree of variability in the clinical presentation of these early choroidal melanomas. And it's one of the reasons that we agreed with the FDA on the documented growth criterion. And what we know about these small choroidal melanomas is once they start growing, they generally don't stop. And so we enriched the study population to make sure that we had a reasonably consistent set of patients who were randomized to treatment versus control and that we can expect to see reasonable concordance with the event rates that we saw in Phase 2 as we head into Phase 3. And how well would you say your Phase 2 data and overall experience with BELSAR has been with the proposed mechanism and your translational team's expectations headed into data? Yeah, so I loved this question because it made me realize we haven't thought about translational questions in a long time. We've got a fair body of clinical evidence at this point around BELSAR. We started with intravitreal administration in the early choroidal melanoma studies before we moved into superchoroidal injection. We also have the data from our bladder cancer study that we showed. So we have a really solid body of human evidence showing that this is an active drug with an excellent safety profile and with respect to the eye, excellent tumor preservation. I talked about the preclinical data from John Schiller's lab looking at the potency and selectivity for tumor cells preclinkly. We have our tox data. Aren't great animal models for early cradle melanoma, but I would say that the clinical profile that we are seeing is very consistent with the selectivity of the mechanism of action of BELSAR. Okay. And speaking of selectivity, and you touched on safety a little bit too, when you look at the body of evidence on safety and intolerability, how appropriate would you see this treatment for patients with an early disease? Yeah, that is the entire value proposition card thing, and what differentiates BELSAR from the systemic therapies that are used in more advanced forms of uveal melanoma. So in the phase two study, we saw a really promising safety profile. The vast majority of the AEs were grade one. There were no treatment-related SAEs, no discontinuations, so very clean safety profile. And importantly, we saw that 90% of patients in the phase two study had their vision preserved, which is, as we know, a very different outcome than is expected with radiotherapy. So I think the selectivity translates into a really promising safety profile. The local administration is also important. These are otherwise healthy patients. And so to be able to limit the treatment to just the specific part of the eye anatomy where the tumor is growing via the suprachoroidal injection, and then only to get the cytotoxic activity when it is activated via an ophthalmic laser, really makes it kind of purpose-bred, if you will, for treating early disease. And should we be expecting more updates from that Phase 2 study? And are patients being followed up with in that cohort? Yeah, so we don't have, and those patients weren't rolled over to a long-term follow-up study. So we don'T have data beyond the 12-month data that were presented a couple of years ago. The manuscript is in submission from that phase 2 study, So we'll have a peer-reviewed paper out, you know, hopefully sometime in 2027. But the focus for us right now is getting to top-line data and compass and, you know, answering the big question of do we have a drug or not here and then moving towards registration. Okay. Maybe switching gears to the commercial opportunity, how would you characterize the commercial opportunity and what patients would be the most natural group initially to receive Belsar, in your opinion? I would characterize the commercial opportunity as underappreciated. It was the thing that got me most excited about joining the company earlier this year. And I also think this is an area where there's the most confusion, if you will, within the investment community. I think the natural interpretation of a study that was slow to enroll is that, well, there aren't that many of these patients out there. If it took this long to enroll, this is, you know, a vanishingly small patient population. And for the reasons we talked about, we don't believe that the enrollment timelines are a read-through to the patient population? One of the things that's been an interesting evolution in the ocular oncology field over the last few years, which I think has been driven at least in part by the community's experience with BELSAR in our clinical development program, is that this historical delineation between what was called indeterminate lesions versus small choroidal melanomas is kind of going by the wayside. There's this recognition that all of these early tumors, they're all the same disease. There is a, I would say, a spectrum of clinical presentations of these various clinical features of concern is what they're called. But really, the delineation between indeterminate lesions and small cradle melanomas was largely driven by the decision of whether or not to treat with radiotherapy. If I'm not going to treat, I'm going to call it an indeterminate lesion. If I am going to treat, it's a small croidal melanoma. Now that there's a treatment coming that enables tumor control without sacrificing vision, the field is moving towards these are all early croidal melanomas. So we view that entire population as the eligible population for BELSAR. And I think, again, because the evidence is clear that treating earlier is better, I think it can be misleading to look at, you know, ICD-9 codes on plaque radiotherapy and say this is a really small patient population because for many physicians who manage these patients, they want to wait as long as possible. They recognize that losing vision is one of the single biggest hits to quality of life there is, and so I'm going to wait as long als possible. And they say if this treatment becomes available, of course I'm going to treat earlier. And on the other side of the spectrum, there are physicians in the field who treat very aggressively early. The belief being I would rather blind 10 patients than lose one patient to choroidal melanoma. They also say I would use Belsar. And so it's hard to, I think it's impossible to make a blanket statement that I believe it will be sort of larger tumors within the small choroidal melanoma spectrum, if you will, that would get it because that's where radiotherapy is used. I think it will ultimately be used across the population as early as possible. Okay. And you talked about your clinical network a little bit too. I'm curious, what level of overlap do you see from phase two to phase three to the sites that you ultimately or initially target for a commercial launch yeah so phase two was a small study only 10 subjects of therapeutic dose we have we've expanded the network of trial sites to support compass to the point where about 90 percent of the ocular oncologists in the us and europe are involved in our program in some way so that the overlap between the develop our um our colleagues that are supporting us in development and who will ultimately become our customers is very high which is great. It's a very focused community. They all know each other. We have one of them that works for us, actually. And they've gained a lot of familiarity both with Belsar and with Aura as a company. And so I have no illusions that launch is easy. Drug launches are never easy. I've been involved in a couple of them. They're always harder than you expect them to be. But I think given the dynamics and the size and the focus of this community and the profile of Belsar and the promise that it offers to these patients, I think we're in a good place to have a really successful launch. And what could a typical treatment day with Belshar look like in the clinic and what type of practices would be participate in phase three and ultimately in a commercial launch in your opinion? Yeah. So one of the things that we hear that excites ocular oncologists the most about Belsar is that this is an in-office administration. When they're doing radiotherapy, it's a surgical procedure. They're out of clinic, they're in the OR to do the implantation, they'RE back a week later to take it out. So it interrupts the flow of their clinic. With BELSAR, it's two injections on either side of the eye, 30 minutes apart. So a patient will come in in the morning, get their injections, and then they'll leave for a few hours, go get a coffee, go to lunch. The physician can see other patients in clinic, and the they come back four to six hours later, go the laser suite, get the laser, and they're out for the day. So it fits really seamlessly within these practices, these ocular oncology practices. They're used to doing suprachroidal injections. They're use to doing the lasers. And so one of the advantages of BELSAR is that they're not going to have to make big changes to the way that they organize their practices in order to make this treatment available to their patients. And what kind of potential and path do you see for Belsar beyond early choroidal melanoma and other indications, and what kind work to date supports that potential? Yeah, so I would say, I'll answer that question too. First, from a clinical proof-of-concept perspective, I think the bladder data are really compelling. So this was direct intratumoral delivery into the bladder where we saw really excellent response rates and importantly really interesting really promising durability out three out of three patients who made it out to 12 months have maintained their complete responses two out of two at nine months so i think that we have we already have evidence that this drug can be used for more than early chroidal melanoma and back to your translational question the preclinical data certainly support that within ocular oncology we have two earlier stage clinical studies ongoing The first is in choroidal metastases of other solid tumors, the two most common being breast and lung. And the second indication in tumors of the ocular surface, where like in bladder, we're doing direct intertumoral injection into these tumors at the front of the eye. So what we've committed is that in the first quarter of 2027, we will come back to the street with a more fulsome update on what are these disease states, what's the unmet need, what is the study design, what are the data you can expect and when can you expect it. So more to come on that. But the vision is, as I said at the top, to build a really valuable ocular oncology company around Belsar that starts with early choroidal melanoma but has the potential to expand to these other solid tumors over time. Right. And I saw that you have an event coming in December. Could you please preview that, what to expect there? What are we going to learn? Yeah, certainly. So as I said a few minutes ago, I think one of the important open questions for the investment community is what is the addressable market in early choroidal melanoma? It has been eight years since the company has done epidemiology, so far before my time. And the field has changed a lot in the last eight years, due in large part to the advent of the Belsar Development Program. So what we'll be doing on the December 8th event is providing, sort of showing our work, if you will, on an updated view of the epidemiology of early choroidal melanoma. We'll also have a key opinion leader with us, Dr. Arun Singh from the Cleveland Clinic, who will talk about this evolution in the field that I mentioned a few minutes ago of moving away from indeterminate lesions and small choroidal melanomas to this sort of combined grouping of these are all early choroidal melanomas. So we'll have our own ocular oncologist, Dr. Anthony Daniels, in conversation with Dr. Singh. We will have our head of commercial present the really detailed work that we've done, both primary and secondary market research, to support the epidemiology. So the goal being that we really explain why we think the market is what it is as we head into a really important year next year for us. Okay. And what kind of questions do you think the COMPASS trial can answer for the opportunity to be on early choroidal melanoma? Yeah, well, I think a couple of things. So number one, just showing tumor control in ocular tumors. I think that is the most direct read-through into other ocular tumor types. The suprachoroidal injection method of administration that we're using in early chroidal melanoma is what we are also using in metastases of the choroid. So I think there's a close read through there. And then even with the ocular surface tumors, it's a different mode of administration, different primary tumor types. These are squamous cell or melanocytic tumors on the front of the eye. But again, if we can show that this exquisitely selective and potent mechanism of action is working in early choroidal melanoma, I think it's a pretty clear read-through to the other indications. Okay. And are there any commercial precedents that you'd consider appropriate or inappropriate for thinking about Belsar's opportunity in early choroidal and broadly in ocular oncology? Yeah, I love this question, and I've been thinking about it a lot. And the short answer is there are no great direct comps for what we're doing. We are building a market, which is exciting, but it also means you can't point to comps and say, look at this launch or look at that launch. That's exactly how this is going to go. I think that within the field of ophthalmology, you can look at thyroid eye disease or geographic atrophy, where there have been agents that have come to market that have grown the diagnosis, grown the treatment in a way that we anticipate seeing an early coital melanoma. But I think those are different disease states with different value propositions. Here, we're talking about tumors that can metastasize and prove fatal. And we're looking at treatment options, which, you know, again, very tough decision to make. Do I treat my tumor or do I keep my vision? So I think the value proposition and the unmet need is singular in early choroidal melanoma. So I look and the focused call point means that we can do this ourselves. I would love to launch another drug. It's one of the things that got me really excited about coming to Ora. So, I could I could point to different elements of other other drug launches as being directionally informative for what we expect from Belsar but I think we we have something really special here looking forward to growing the market ourselves any questions from the audience you'd like to ask okay maybe a last one from us what does the balance sheet look like right now and what kind of milestones can it cover yeah so we just announced our key three earnings yesterday and We're just shy of $300 million, and it's $297 million on the balance sheet. That funds the company into 2029, so well through top-line data from Compass in the back half of 2027. We have the 24-month readout from the Compass study in 2028, and we don't have guidance around when to expect data from the earlier stage programs. We'll provide that in Q1. But that runway assumes continued full funding of those programs. Okay. Very good. Thanks so much. Thank you so much! Appreciate it. Thank you.