Good afternoon, and welcome once again to TD Cowen's 44th Annual Healthcare Conference. I'm Phil Nadeau, one of Cowen's biotech analysts, and it's my pleasure to do a fireside chat now with Aura Biosciences. We have Eli de los Pinos with us here today. She is the co-founder, or sorry, founder and CEO of Aura. Eli, maybe I'll hand it to you to start. Can you give us a brief state of the company overview, what are Aura's strengths, its challenges, and what do you need to do to create shareholder value over the next year?
Yes, absolutely. It's a pleasure to be here. Thank you. So yeah, it's an exciting year. First of all, Aura has a drug that works, that has a very robust data in phase II, and we're actively enrolling in a phase III global study with an SPA that supports registration, right? That is a very exciting thing for us. The second is that initially in our ocular oncology market, there are 60,000 patients. That's ocular oncology. Our just initial path to market is primary choroidal melanoma, and that's 11,000 patients. So it's an enormous market with multi-billion dollar potential, where our frontline positioning, where the majority of the patients are, there's no competition. So that's the other exciting thing, just in ocular oncology. And then if we add urologic oncology, listen, we're early, right?
We only have one patient, but that patient happens to be a CR. While early, it allows us to really unlock that promise that this is a drug that could work across many different types of solid tumors. So exciting year for Aura.
Maybe taking a step back on the technology platform, what is the technology platform that underlines bel-sar, and how does bel-sar itself work?
Yeah. So, the technology platform we call virus-like drug conjugates. And in concept, this is very similar to an antibody drug conjugate. Instead of an antibody, we have a virus-like particle that's uniquely targeted to what we call heparan sulfate proteoglycans, are highly sulfated by cancer cells themselves. This is the glycobiology of cancer development, and as such, it's not downregulated. So usually, when these signals are present, they are constantly present. So that's what the virus binds to and creates this cell activity, that allows us to really call it a platform, because then these virus-like particles that we now have at scale, and we're in phase 3 commercial manufacturing, can be used for a rare cancer like a choroidal melanoma in the eye, to a much more prevalent cancer like urothelial carcinoma without changing it.
So again, a great opportunity to develop a new type of biologics that are highly targeted and very versatile.
You mentioned that bel-sar works, which we know 'cause we've seen the data. What were the data that were presented at AAO for SC, bel-sar?
Yeah, it's very exciting data. We presented 12 months for the majority of patients. 90% of the patients were at 12 months, and we had two key endpoints. Again, for early-stage disease in ocular melanoma or primary choroidal melanoma, you're looking at tumor control, which is the surrogate or very similar to a complete response. Basically, you're hoping that by treating that tumor, the tumor will stop growing, and it will be the equivalent of a local cure, but with the advantage of visual acuity preservation, so that our goal is really to replace radiotherapy. So that the majority of these early-stage patients don't have to endure the really harsh side effects and blindness of radiotherapy. So what did we see? On that 90% of the patients, we achieved 80% tumor control.
So 8 out of 10 had what's the equivalent of a complete local cure, and 90% visual acuity preservation. So not only did we have that high level of efficacy, but it was paired with unprecedented safety because we're treating even tumors that were under the fovea, and we were preserving vision. So that is what excites us. That's why we say we have a drug that works, because right now, for those early-stage patients, there's nothing. There's basically radiotherapy, and many of them actually delay treatment because of that. So we can get that big, big market without really a trade-off on safety.
Within the development of bel-sar itself, you transitioned from an intravitreal delivery to suprachoroidal. How did that change the adverse event profile?
That was a fantastic move for us. These are choroidal lesions, so as you can understand, suprachoroidal administration is the ideal route, and we happen to have the microinjector for it. So we saw what was anticipated. When you give intravitreal, you have a little bit more posterior inflammation, and when we get suprachoroidal, that disappears. And so we have the targeted treatment with the efficacy and the immunogenic cell death just happening in these tiny lesions in the choroid, without the problems of having the drug in the vitreous for a long period of time. So it was an ideal approach. It showed actually in the data, the data in both routes showed that the drug works, but obviously, the side effects, as you said, were much better.
It was much better tolerated with suprachoroidal administration, and that's what we're moving to phase III.
You mentioned the Phase III. What is the design of that trial?
Yeah. So, now it's with the SPA, I'm so proud that we have it. It's a three-arm randomized masked study, where we're going to look at three cycles of bel-sar versus sham. And there is a middle arm, and the middle arm is not part of the statistical analysis. It's just there in terms of, like, optimizing the masking of the study. It's a requirement, a requirement by the FDA. But it really is, for us, a red carpet, which... Why? Because to have a drug that works with such high efficacy and safety compared to sham, it, it, we have a very high probability of success, and also to position the drug where we want it to be launched, right?
We want this drug to be for the early-stage treatment for these patients that, you know, right now are really deferring treatment, and they shouldn't with a life-threatening disease.
What specifically was addressed in the SPA? What design elements do you have agreement on with the FDA?
So the key were the endpoints, right? We're looking at, as I just said, local tumor control may look familiar to a lot of investors, and this is the absolute endpoint that ocular oncologists use for this early-stage disease. To have the stamp that that's actually an endpoint for approval was really important, not just in the U.S., but also in Europe. And also visual acuity. So to have those endpoints kind of like in written that support approval was very important. To have the safety database, like, as you know, when you're talking now in the big league of approval studies in rare diseases, that becomes very important. So 100 patients now in writing is what's sufficient to support that safety database, and, and then, you know, what is the time for the primary endpoint? As you know, it's 15 months.
We discussed whether it would be 12-15, and at the end, the FDA recommended that we did the primary endpoint readout at 15. So those three aspects were very important, and now we know that we're in good grounds. Now it's an execution game.
You've disclosed that the trial's 90% powered to detect an 85% rate of tumor progression in the sham arm versus 35% in high-dose bel-sar arm. What gives you confidence that those are the right, right assumptions? It seems like, in particular, sham has not been well characterized.
Yeah. So there's always this question around: How much risk are we taking with the sham? Do we have data with the sham? So one of the key things, if you look at our public presentation, what we did with phase II data was look at all of those cohorts of patients that received very low dose. At one or two injections, it's very similar to sham because our therapeutic regimen is nine injections. So we compared those patients that are basically very similar... those two groups are very similar, as if it was the sham, right? Our own data, not data that's historical, not data from any side, our own data, and we plotted it. And as you can see, and we have that in our deck, the events or tumor progression that happens in those subtherapeutic groups is very high, right?
So we anticipate that if you don't treat them at all, it's gonna be even worse, and that's important because we have a very high level of tumor control. What we want is the sham to fail, and as such, you know, if we use that internal data, it seems that it will. In addition, we're doing, as you know, the enrichment strategy, which means that all patients in our study will come with a little bit of growth. And in cancer, if you start growing, you don't stop growing by itself. So that will also help into that sham and the assumptions that the sham should 80%-80% fail within the first year. So we feel with those two risk mitigations, that our own data and the enrichment strategy, the trial is highly de-r isked to achieve success.
The key secondary endpoint is time to visual acuity failure. How important is that for regulatory approval and uptake?
Yeah, so look, we have 90% visual acuity preservation. As I said, that's unprecedented. Really, only one patient lost 18 letters. The threshold is 15, but with radiotherapy, we're looking at 30, 40 letters. So we have a beautiful way to say you should receive bel-sar because it really preserves vision. But if we didn't include it in the endpoint, you can't talk about it, right? You cannot make the claim. So for us to be able to put it there as a secondary endpoint was really important. We think that, again, based on our current data and the intravitreal data too, we should absolutely meet that endpoint, and, you know, it will be a good thing for the launch of the drug to be able to say not just, you know, we think we preserve vision, but we actually do.
You've been very clear about your confidence in the trial's success. If you had to think of what risks still are out there for to the trial's success, what would those be?
Right. So look, this is a global study in a rare disease, and there is no precedent, right? So we never underestimate the execution. I usually laugh and say, "Now you only have to execute well," if it was that easy. So we have to make sure that the study is run properly. We are opening 90 sites for 100 patients, so a big you know, de-risking there, but still complex logistics. And we're, you know, hoping to be able to do that in 18 months. So that is what, you know, is what we're all in, and it's about education and execution, and we have a full team. I have, you know, a lot of expectations for people to make it happen.
So when should we expect data from the study? Based on the timelines, you said it's kinda early 2026, mostly.
Right. Yes, our first patient was, you know, late December last year. And we have given guidance that it's gonna be 18 months enrollment, with a 15-month primary endpoint. So we're looking at the first half of 2026 for the, you know, the full de-risking and the full value generation for this company. In the meantime, don't forget, we have a phase II in choroidal metastases and phase I in the exciting field of non-muscle invasive bladder cancer these days. So it's not that we don't have any other readout, but yeah, the big one is early 2026.
There is another study that you're conducting, the retrospective case-match study. What's the purpose of that trial? Or not trial, but what's the purpose of that study and the current status?
Yes. Again, was kind of like, to build on the value of visual acuity preservation, because sometimes we forget, right? The... And, and or it gets a little bit confusing is, is the tumor that's creating the vision loss? In these cases, our own intervention, our medical tool, which is this radioactive plaque, blinds patients. So we wanted to retrospectively compare, to say even with intravitreal data, we're so much better than radiotherapy, and to show in a much case control that, look, unfortunately, the only thing available really blinds patients. It's not if it blinds, it, it really does. So that was the reason we did it with 1 and 2 years. We showed it, obviously, you know, the more years that go by, the worse outcome with radiotherapy. So we already have shown that.
Now we're evaluating whether we run the exact same study with suprachoroidal, which the data we already know it's so much better, just to build on the value of vision, right? These are not studies that are gonna support approval. They are complementary, but they are important for us to be able to have something to, to really show it and say, "No, it's, it's not someone else's publication, but ours.
You briefly touched on the market size in your opening remarks. What is the number of patients who have choroidal melanoma each year, the current treatment paradigm, and where could bel-sar fit in?
Yeah. So as I said, 60,000 is ocular oncology. 11,000 is just our initial path to market, that's choroidal melanoma we're talking about. And that 11,000, mainly in the US and Europe, is usually detected very early. So when we talk about our early-stage market, it's 80% of these 11,000, which is 9,000 split 50/50 between the US and Europe. It's not a tiny disease, right? We've shown that out, actually, the metastatic fraction of that market, which is much smaller, we're talking about 1,000 patients there, actually has a very successful market performance. So, so if you translate that to 10 times larger, we think that once we're there, we're gonna show that unfortunately for patients, there is an unmet need, but we can tackle that effectively.
It is hard when there is no precedent, especially commercially, to say what that market is. That happens with rare diseases, but, we will hopefully show it very soon.
In terms of the current standard of care, what happens after brachytherapy, radiotherapy? What is the vision lost for the patients?
Look, with radiotherapy, and this is not rocket science, if you put radiotherapy in the retina, it's very difficult to retain vision. Now, these patients usually gradually lose vision because radiation retinopathy damages the blood vessels in the retina. So it's not just a spot, it's the entire retina, and it's a, you know, irreversible, and it will take approximately 18-24 months, depending on the publication and depending on the location. Unfortunately, for these patients, there's no, you know, go back. We actually for Rare Disease Days, we had the patients telling us about their experience, and it's devastating to lose vision. It's one of these key functions of human beings that you never want to lose.
In the 11,000 patient number that you noted, is that choroidal melanoma, specifically? How do indeterminate lesions fit into that number?
Yes. Look, the definition of indeterminate lesion to a small melanoma is highly controversial even in the ocular oncology community. And why? Because a lot of them don't want to treat. And so because they don't want to treat and blind patients, they don't want to call it a melanoma. And so depending on who you are, it would be an indeterminate lesion; it's just indeterminate because I don't want to blind you. What we believe is that, you know, ultimately, the early-stage disease, indeterminate lesion, small melanoma, is a continuum, a spectrum of the disease, and we want to treat them all. So what we did was, okay, if the ocular oncologist don't agree, we're not gonna create it, so let's include both in the study. And the FDA agreed, the ocular oncologist agreed, and so that's the opportunity that the label will include it.
We hope that every single patient with an indeterminate lesion will be treated. It doesn't matter if it's two or three risk factors. If it's no longer healthy, you should be treated.
A couple more questions on choroidal melanoma before moving to choroidal metastases. In terms of the market, what is your thought on pricing for bel-sar?
Right. Look, it's hard to talk about pricing, as you know, before getting the drug approved. I always talk about the value for patients and how valuable it is to have something, an intervention early that prevents your function, that prevents your organ, and that potentially prevents metastatic disease, right? So we usually look at comparables of rare oncology, where, you know, just with those comparables, we would have a multi-billion dollar market. So I think that there is plenty of room for pricing, but especially what we're focused on is delivering value for patients.
What about redosing? Does that fit into your treatment paradigm or market model at all? If a patient were to get dosed once and then years later there'd be progression, would redosing be possible?
Absolutely. Right now, that's what we can do, right? You can't put a plaque twice. Actually, we have patients that after a plaque, just because of the side effects of plaque, have had to go through enucleation. So with our therapy, the hope is that we'll get it approved, and approved is just, you know, three cycles, year one, easy, let's get it approved. And then we can run a retreatment study and offer that opportunity. I cannot believe that that will not be, you know, adopted, because again, what's, there's nothing to lose and a lot to win.
Maybe moving to choroidal metastases, can you give us an overview of that market and the current treatment paradigm?
... Yeah, choroidal metastasis is a real indication. Like, one of the surprises things for us was the tremendous pull from the KOLs when we were, you know, in choroidal melanoma, looking at the ocular oncology space as a whole. We initially were not thinking about it, and yes, it was the KOLs themselves that said, "We want this for metastasis." And there are many more patients, so we're looking at 20,000 patients. Again, as I look at 60,000 patients of ocular oncology, 11 for melanoma, 20,000 for metastasis, we absolutely have an obligation with a drug that works. And I usually look at this disease as, okay, you're a breast cancer patient that has endured your metastatic disease. You're a survivor.
We have so many of those beautiful survivals, but by the way, and now you have metastasis in your eye, and you have to be blinded? I can't, I can't tolerate that with a drug that preserves vision. So I think that we're very committed. We actually have sites that are in, in waiting list. "Can we get in the metastasis study?" And we usually say, "Well, yeah, let's get CoMpass on." So yes, it's a, it's an exciting indication, and it's good to have a, a drug that... Look, we're not a drug for a particular type of mutation. Genetic mutations, great, but we're a drug that is tumor agnostic, right? We can treat in the eye regardless if it's a melanoma that's early, or it's a metastasis from breast cancer that's late, or it's a, a cancer of the ocular surface.
What we want is to preserve the function and preserve the organ, right? With something that is so targeted and that works. So that's the opportunity, and hopefully, you know, investors will realize that that's a large market opportunity.
You got it to starting a phase two trial this year. What will be the design of that study?
That study is a dose escalation, obviously. It's the first time that we're going to metastasis. The same location, same physicians, but we have to start conservatively. That's something that I've learned in drug development. You start conservative. You then can go really fast, but you start conservative. So we'll start with a cycle of the drug, something that we've shown in melanoma that it works and it's safe, and potentially we can, you know, scale that in many different ways.
What will the patient population look like? I guess in particular, are there certain types of metastases that are more likely to respond to bel-sar, and conversely, are there some that are less likely?
Look, the majority of these patients come with either breast or lung lesions. The average size of the lesion, to our advantage, is very similar to the melanomas, right? We're talking 2-3 millimeters, and the majority actually are also single lesions. So it's, in concept, not that different from the melanoma. In composition, biologically, very different because they're all metastatic, and they're actively growing, and they're not pigmented. So in animals, in our preclinical models, our drug works phenomenal in those. But, you know, again, from the kind of like how it looks like, it would look very similar to the melanoma.
When could data be available? When you see data, what will be the bar to progressing towards a registrational study?
Yeah. So, we have guided towards data before year-end, and we're excited that we can provide that. What we believe is going to happen in this indication is that we may see a little bit more of a regression of the lesions versus the melanoma, whereas I just said, you know, we stop the growth because that's what you see with radiotherapy in this kind of nevus situation. But in metastasis, they're all growing, and we think that our drug is going to be more effectively across the entire lesion, not just the melanoma cells, but entire lesion, and it should shrink. So that would give us two advantages, right? Shorter time to read out. In melanoma, we have to wait quite a bit.
In this metastasis, we could see it earlier, and we could also see it in distinct types of tumors, which would show that the technology works across, this is really tumor agnostic. So both on the speed and the, you know, validation of the platform is an exciting early data readout, for us as a company.
Turning to bladder cancer, can you remind us of the design of the proof of concept study in bladder cancer?
Yes, bladder cancer is an early study called Window of Opportunity Study. In bladder cancer, as you know, there is the local disease is divided into non-muscle invasive and muscle invasive. Initially, again, our drug potentially in, in our preclinical works across the stages of the disease. So we didn't want to limit to just testing a particular subset of these NMIBC or MIBC. So we did this Window of Opportunity where the FDA allowed us to treat any potential patient that has a papillary lesion that we can inject, and as such, we're going to see patients potentially that are BCG refractory, BCG naive, that they have CIS plus, minus papillary, and they are muscle invasive.
So, Aura, we have 20 patients, and that's important for us because we will be able to show mechanistically that the drug is very consistent, and it should work across this disease stage-agnostic kind of approach. And then once we have the data, we'll be able to determine, okay, where are we going to go first, and what's the design of the study? And there's a lot of opportunity. Obviously, there's a little bit more competition in the space, but we're in a position where we can really create what we call immune ablation, right? We can treat selectively and have this strong immune response early on. We think patients would highly benefit. Still a promise. We have a CR. It's early days. We have a CR with a single dose. It's exciting for a company, nonetheless.
... what about the safety profile among the first five patients dosed, mentioned one CR. Any notable adverse events or DLTs?
So no, the reasoning is that we're very focal. Look, mostly everyone else in this space is giving treatments, instillation into the bladder, right? And they either put a gel in the entire bladder, or they have to give a pre-treatment so that the virus go, crosses the urothelium. We're not doing that. We're just going because we want the drug to work where the tumor is, very focally, and get that immune response toward the lesion. That goes with safety. You treat just the lesion, you don't have anything in the entire bladder, and that will differentiate us.
If we can do something that potentially requires less administrations, is very safe, can be done in the office by the urologist that like procedures, and actually protects patients from recurrence, and ultimately getting 14 cycles of a potential oncolytic virus, we think that that could be highly beneficial, but we have to show. It's still early.
When do you expect to release data from the trial? And what will be the extent of the disclosure in terms of patient numbers, follow-up?
Yeah. So as I said, 20 patients is a very fast readout, because we remove the lesion or whatever is remaining and look histopathologically, so we don't have to wait a long time. So we've guided towards midyear to have the entire data set, and that would be, again, across the spectrum of the disease, not just NMIBC or intermediate-risk muscle, all comers with a histopathologic evaluation. What we want to see is the consistency of the mechanism of action. If we can show the local effect with necrosis immune activation, that would be incredibly important, and then, obviously, we'll guide the industry on what's next and what to expect from our next study.
Is that, is that the bar to moving forward, or do you have a response rate bar that you want to see?
So there's not a response rate bar in this particular study because it was so broad, right? So the only thing, it's a safety study. We want to also see that it's feasible to administer it this way. We're the only ones doing it this way. Can urologists really do it? Is it gonna be adapted? It's easy. And then do we have consistently the mechanism of action that we want to see? If that has shown, then I think it's very easy for us to say, "Okay, so we're gonna go in this particular set or two, and this is, you know, the path to approval.
There's been a fair amount of excitement about bladder cancer on Wall Street. Where would you see bel-sar fitting into the treatment paradigm?
Look, it's hard for us to say this is exactly where we are. I can tell you that I am very eager to position our drug as early as possible. At the beginning, in ocular oncology, they told us, "No way, you have to demonstrate survival." Look, we don't, right? If you have something that's very safe and there's clear value for the patient, the regulatory agencies are very open to that. And so we are frontline in ocular oncology, and we should be here as well. Ideally, with something that is so targeted with such a strong immune mechanism, if we can have an immune ablation for patients that have, you know, intermediate risk, that would be fantastic. We're talking about 80,000 patients, right? It's a lot of patients that come with papillary lesions.
And so that would be something that it would be fantastic if we can, but MIBC, the opposite, right? It's still local, but it's invaded the muscle. If we have that immune activation there, a lot of patients are not fit to receive neoadjuvant chemotherapy at that stage. Could we provide value that way? So there are many avenues that I'm excited, but you'll hear me always that early, early is always better. Not rocket science.
We discussed bel-sar's three programs. What other indications could VLPs contribute to the standard of care? Any other places that you're thinking of progressing?
Yes, absolutely. Look, actually, the value of the bladder cancer data and choroidal metastasis open the possibility, can we do more? There's a natural path to prostate, right? If we're in urologic oncology, if we can successfully treat bladder cancer, could we treat prostate? That's the number one killer in the world. So we would be very excited to be there. But we could also envision other indications like cutaneous melanoma, potentially esophageal, where... You know, I see these as early interventions where we can preserve the function, and we can preserve the organ. That's where we're lucky that we diagnose early, and we're still kind of Middle Ages with our tools of surgical intervention. Can we do immune ablation in those cases and have a much better outcome for patients preserving their function and their organ?
So that's how we're envisioning it, and there's so much opportunity, so much. So, we're excited.
Last question on the balance sheet. Can you remind us of your balance sheet? What's your cash balance and anticipated cash run rate?
Right. As you know, we were one of the lucky ones to do a good financing last year, not many. So we're funded through 2026, and that's, as you know, when we expect to see the big readout of the phase 3. So it was important for us to not depend on the market to run our CoMpass study.