Good morning, welcome once again to TD Cowen's 46th Annual Healthcare Conference. I'm Philip Nadeau, one of the biotech analysts here at Cowen, and it's my pleasure to moderate a fireside chat with Aura. This morning, we have with us Eli de los Pinos, the founder and CEO. Eli, I'll hand it to you to begin. Can you give us a state of the company? What are the biggest strengths, biggest challenges, and what does Aura need to do to create shareholder value over the next year or two?
Yes, it's a pleasure to be here. Thank you, Phil. We're very excited. We're obviously leading in ocular oncology across three indications, a group of rare diseases where there are no drugs approved, and our phase III is enrolling very well. We're reassuring guidance, and I think that that's a key catalyst and milestone that a lot of investors are paying attention to. That will put top-line data in Q4 of 2027, with a high probability of success. As you've all seen, our phase II data is very strong. I think that that's our strength.
As we look at obviously where we can create value and where are the things that are weaknesses, I think that our bladder data, while it's very, very strong as a phase I, it's still a small sample size. Obviously it, we're not alone there because in ocular, we can say across three indications, 66,000 patients, we're the only ones here. Obviously, there are more companies. What I think the investors are missing is that we are uniquely positioned in the neoadjuvant setting where there's really no one in neoadjuvant development. Everyone else is in the adjuvant treatment.
Once we can correlate that there's enormous clinical benefit and opportunity for safety and ease of administration for a neoadjuvant approach, I think that then that will start putting us in the landscape for bladder cancer. That's our weakness, and I think that we're well positioned to provide that three-month first time that will show durability to investors mid-year.
Maybe to dive into bladder cancer in a bit more detail, updated data were presented last March, about a year ago, and bel-sar produced compelling signs of activity. Can you highlight the biomarker data and T-cell responses you saw in the study?
Yes. That's clearly where we differentiate. What we saw in that study, and remember, that was only a single dose of bel-sar, was really a true feasibility study. We were able to take biopsies before and just after complete responses to see what was the delta, what was happening, why did we have those CRs, and why did we see an abscopal effect. What we saw is with immune profiling, where you can see all of these different types of cell populations, we saw an influx of T-cells that was remarkable, not just in innate immunity, but true signs of adaptive, the formation of these tertiary lymphoid structures that only happen when adaptive immunity and anti-tumorality cell response is taking place.
That quantified showed a 40x increase in NK cell population, a 7x increase in cytolytic CD4 T-cells, and that obviously is the reason why we saw abscopal effect, right? When you have that kind of like influx of adaptive immunity, you see it without adding any kind of like comorbidity or safety to the patient. That's the key. That was with single dose. Now we're running a study with kind of a prime boost mechanism to really leverage that immune mechanism. Again, think of it. You can only have that if the tumor is there. If you have it as an adjuvant treatment and the tumor is gone, you remove not just the immune cells that are gonna react, but the tumor itself. Basically, if you try to have an immune activation as an adjuvant treatment, you're weakening your value proposition. You should give an immune treatment upfront.
Can you talk about the side effect profile that we saw last year? Were there any notable toxicities, and how does the side effect profile compare to other drugs for bladder cancer?
That's where we win, right? There's literally no adverse events. There were grade 1 toxicities. Not a single grade 2, grade 3s. We're not giving this systemic. You can combine it with anything. As you can think of the more you go into the spectrum of the disease, even in muscle invasive, you can envision it combining even with a checkpoint inhibitor and not adding 70% grade 3 adverse events, right? We're so well-tolerated, and it's so easy to do that that really gives us, just on feasibility and safety, a huge competitive advantage.
You referenced the ongoing phase I, II. Can you talk a little bit more about the design of the study?
Yeah. Remember, we started with a phase I. It was just feasibility. We didn't have durability of response embedded into that study. We went to the FDA and said, like, "Look, we're having CRs, and we're having this abscopal effect." We went into a very quick dose escalation. We're now treating multiple lesions and multiple cycles, meaning day one and day seven with an interval between the treatments to really boost that immune response. It's quick. It's done either as a single agent or in combination with surgery 'cause that neoadjuvant approach is so amenable to the clinical practice for these urologists. They already do the TURBTs. It takes a couple of weeks to schedule the TURBT anyway.
You do the two treatments before, and then you have the surgery anyways, either to confirm that it's a CR or to confirm that you've done something positive to the patients with a T-cell response. It's just a perfect study design. The FDA was very supportive. It will give us that kind of data to really show that we have a unique treatment paradigm approach.
Are data still on track for mid-year?
Yes.
Can you discuss the extent of the data release? Like how many patients, what measures will you be able to disclose?
Yeah. We have three key cohorts in parallel. Our study was a dose escalation, Cohort 4d, if you look at our slides, is 200 micrograms per lesion, and then we're going to 400 micrograms per lesion in two cycles. Both as an immunoablative or neoadjuvant, so plus/minus surgery to really see the effect of both. intermediate risk and high risk. Collectively, we're talking about 15-20 patients worth of data. That's a nice number of patients. It's no longer three or four patients, right? I think that will be something that will allow us to say, "Look, the drug works. This is the right positioning. This is commercially how it would look like. Physicians are supportive," and then how do we bring this forward into registrational studies.
Can you discuss what you would consider proof of concept and also how you'll figure out the phase II dose?
Yeah. Obviously, with what we saw in the phase I, a single dose working so well, we don't think we have to escalate too much, and it's so well-tolerated that the dose ranging is kind of short. We do wanna look at the effect plus/minus surgery because, again, we think that we have to take into account the willingness to do surgeries on these physician and type of practice. A good proof of concept would be a 15-20 patients at 12 months where you really see an impact in recurrence-free survival. That is not that difficult to beat because every single of these patients, either intermediate risk or high risk, at 12 months, they have a decay if you look at RFS.
If we can show an improvement with just this kind of, like, upfront neoadjuvant treatment where you can do plus surgery, and in the case of high risk, you can even do adjuvant treatment. You can choose seven adjuvant treatments, actually, but there's only one neoadjuvant upfront. If we show that benefit, that delta, I think that then we'll have many opportunities to partner and then develop it not just in non-muscle invasive, but in muscle invasive in a combination with a checkpoint inhibitor. There are, like, four checkpoint inhibitors in that setting that don't differentiate much. There's a ton of opportunity with 12-month durability data.
When could this trial complete, and what would be the next steps?
We're on track on the enrollment. I think that the next steps will be three months is a regulatory endpoint, right? Everyone shows the data at three months and then 12 months. Those are the key ones. The three months will, you know, do we have a drug or not? Is it competitive? It's safe? Are we seeing a clinical benefit? 12 months, do you really differentiate by providing a neoadjuvant treatment in this patient population?
Can you give an overview of the current treatment paradigm for this patient population?
In intermediate risk, basically, patients, either are newly diagnosed or are recurring. In our studies, many have been recurring even for 10 years. They've received five, six, seven TURBTs. They have multiple treatments with mitomycin, gemcitabine. So that's a kind of patient that the standard of care would be changed, meaning that it would come with a recurrent lesion. Instead of doing another surgery and adjuvant therapy, you would do neoadjuvant and then surgery, and that'd be it. Then for a high-risk patient that usually, again, it has a much higher risk of progression, and you're doing multiple adjuvant treatments, you do neoadjuvant surgery and, you know, maybe a reduced adjuvant therapy. You would spare the need for BCG for sure.
Can you remind me of the size of the market? How many patients per year?
Yeah. Actually, intermediate risk patients is 80,000 patients, right? If you look especially at all the recurrent patient population, these are not newly diagnosed. If you were thinking, "Well, we only need the new," no. I mean, all of the recurrent patients that are coming into our study have been there for 10 years. There's a huge population that cannot tolerate a lot of comorbidities with multiple adjuvant treatments. If for this patient population, you can streamline it, make it safe, make it feasible, something that you can do in the office, it has a huge opportunity. Obviously, everyone knows the numbers for high risk, and the funnel starts being smaller and much smaller for CIS. We're talking about 4,000 patients there. The more you go to the left, the bigger the pool. The same in ocular. The more you go to the early stage, the bigger the pool. How you win? With safety and a clear differentiated mechanism.
Turning to ocular, can you remind us of the highlights of the data from the phase II of suprachoroidal, bel-sar in choroidal melanoma?
Yeah. We're very excited with that data set. Look, in those patients, actually, those patients had received nothing before, right? Those are patients that have a melanoma in their eye, that they are basically in observation because they don't wanna be treated with radiotherapy because the radiotherapy blinds, and it's not rocket science. You put radiotherapy in the retina, it's gonna blind because it's gonna kill the blood vessels in the retina. In those patients that were actively growing, actually were clear melanomas, they were actively growing, we had data to document the growth, 80% of those, when they were treated with a therapeutic regimen of bel-sar, had a complete cessation of tumor growth. That means, like, obviously, when you have more long-term data, you could call it a cure, but you could say it's a local cure of the disease, right?
If you've treated for three months, then you look at them progressively up to 12 months and nothing grows, you feel pretty confident that that is a very good response. On the opposite, those patients in the phase II that received very subtherapeutic, meaning subtherapeutic because this was a very quick dose escalation. Those patients received one or two injections compared to full three cycles, where we're talking about nine injections. A clear delta in treatment and clear delta in response because in those, only two, like, 80% progressed, like the opposite. Not 20% were growth arrested. It, 80% progressed. It's a 20-80 delta, a 60% delta in response in phase II.
That is a, you know, with literally grade 1 adverse events. Obviously, if you look at that translated in phase III, same patients, actively growing lesions, same reading center, same treating physicians. The only difference is that instead of being treated with one or two injections, they're basically treated with sham. It's observation. That was a great way for the FDA to say, "Yes, not only we want vision-preserving treatments, but we acknowledge that there's nothing in early stage as such. Sham is a good comparator arm." If they did not acknowledge that, we would have to have comparator radiotherapy. Because we're early, the FDA agreed, physicians agreed, we have a such a highly de-risked phase III. Clearly once we complete the enrollment, it's just the time to read the data.
You have a SPA with the FDA for the phase III. Can you discuss what's in that agreement?
Yes. The SPA was critical because look, these are new endpoints. The key for us was to make sure that the study that we were running would support registration. When you're using endpoints that are very clearly understood by ocular oncologists, but not by any regulatory body because you're innovating, having those endpoints confirmed was very important. We agreed on time to tumor progression. Clean oncology endpoint. Basically the difference between having events of progression in the treatment arm versus the sham arm. If you have actively growing lesions, a lot of events in the sham, very few events in the treatment arm. Time to event actually helps because if we have any event, it should be a delayed one. Very clean.
If you look at the data in terms of that endpoint, we, with phase II data obviously, have a p-value of 0.0005, right? Now imagine the power if you have 40 patients per arm. We have a third arm, the middle arm, that if you look at our slides is like, "Why do you have a third arm?" That's also part of the SPA. We had to agree on having the most masked study. All purposes of masking are optimized in this study, and that's why the FDA, because vision is an effort-driven endpoint, wanted us to an arm where the physician really doesn't know, the treating physician doesn't know if you're treating with high-dose bel-sar or low-dose bel-sar. Not part of the statistical analysis. Those are the key aspects of the SPA. Endpoint, time to tumor progression, three arms, fully masked study versus sham, highly powered for success.
Can you give an update on enrollment? on the year Q3 call, I think you said 400 patients had been screened, 280 were eligible. Where does that number stand today, and when do you expect to complete enrollment?
Yeah. We have a high degree of confidence that we're gonna meet that guidance. Last year, look, it's a rare disease, we had so much interest. Like 400 patients in a rare disease, we could have enrolled the study 4x . It's very important, and we all understand that if versus sham, patients need to have events of progression. We wanted to have all the patients with actively growing lesions, similar as phase II, so that we could have a highly powered study. In last year, we were seeing like a lot of interest to get into the study, but we had to be very selective to get those patients in. Now, in the fall, we started seeing a consistent number of patients coming in. That's when we said, "Okay, now we can provide very clear guidance that we're absolutely gonna meet enrollment in 2026, having top-line data in Q4 of 2027." If you go a 15-month endpoint on the last patient in, that gives you the timing this year. That's going very well. We are reassuring the guidance.
Great. You briefly mentioned the primary endpoint of the study. Can you go into a little bit more detail in terms of exactly how that, the trial is powered for that endpoint?
Yes. If you look at the phase II data, right, 80% tumor control versus 20%, that's a delta of 60%. If you take that into phase III for the power, that gives you a power of 99.9 for the primary endpoint. One would say, "Well, you're very optimistic," right? Because that was a very good study. What if? We actually took a very conservative approach. We have still a high power of 95+, but with a smaller delta. When we powered the study, we did not think that it would be 60%. We thought, "What if it's 40%?" Right? 40% still gives us a power of 95% for the primary endpoint. Highly powered, also for the key secondary.
Even if we had events of visual acuity loss, which we have 90% visual acuity preservation, but even if we had some events of vision loss in the treatment arm that were not in the same patient. Either vision loss or tumor progression. They cannot be counted twice. Even with that, we have 90%, 95% power with our current assumptions for the key secondary.
How important is that secondary endpoint for regulatory approval and adoption?
The key is the primary. The reality is that we were very lucky because where we differentiate is in safety and visual acuity preservation. Physicians will want to use this drug because they don't have to compromise vision. Having vision, the value of vision was very important, and we wanted to have it in a claim. The study's versus sham, it's almost impossible if you don't do anything that you're gonna beat on vision. In the sham, patients are gonna lose vision after radiotherapy, they're gonna meet the event of tumor progression first, you can't really count it there.
The way for us to have that composite endpoint and to be able to say, "Even with 80% tumor control, we don't have to compromise vision," that was a key, you know, kind of like gift from the FDA to allow us to put that as the number 1 secondary. Is it required for approval? We think we're gonna meet it. It's almost identical to the primary, right? With 90% visual acuity preservation, you have a very tiny penalty on that key secondary. But again, the approval is driven by the key primary. The number one is time to tumor progression.
The trial seems to be well-designed, supported by the phase II data. What would be the key risks? Well, if it were to fail, why would that be?
Right now, with the high probability of success of phase II, any phase III study has a risk, right? That's why we run them. We've minimized those risks by having the same reading center, same treating physicians, very high power. As I said, we can go to a delta of even 20% and still be 90% powered. Like, we'd never think that we'll go there, but those are the key risks. Your assumptions in phase II are based on a small sample size, as such, you know, you wanted to make minimum changes in the patient population between phase II and phase III to make sure that you meet it. I think we've overcome the risk of enrollment because as a phase III with an inclusion criteria that's very strict, having sites that have not had clinical trials run globally, that was a risk. Now we're on the other side.
Can you discuss the market, in particular, how many patients are there, what's the incidence and prevalence, and where are these patients treated?
Yes. This is a key. It's one of those that I hope investors really see the value of this market opportunity because you don't really see this very often. Usually, these patients are identified by an ophthalmologist or an optometrist even. You have a nevus in the back of the eye, and if you ask around, I'm sure that you'll find three or four of your friends that have a nevus. Those are not melanomas, that's a clear risk for a melanoma. You know, these are imaging diagnosis. You have a lesion that's black, that changes color, that starts to grow, that it has fluid. You can see that. You don't have to stick a needle or put the patient under general anesthesia.
It's an easy identifiable patient population that right now has no treatment option. The current treatment paradigm is ophthalmologist to ocular oncologist, and the ocular oncologist does the surgery and radiotherapy, which blinds patients. There is a big lack of time between, "This patient has a melanoma. It's an early choroidal melanoma. Maybe I call it an indeterminate lesion because I don't wanna treat it, and then I'm gonna treat it once I have no choice but to treat." That's gonna shift dramatically when bel-sar is approved because then you have a vision-preserving therapy. There's an understanding that early choroidal melanoma is much, a much broader definition than what currently is treated by the ocular oncologist, and that's endorsed by all the ocular oncologists.
Then obviously, the patient population is gonna be much larger than what we already think today. Right now, if you ask anyone, there are like 2,000 ocular melanomas. Those are the treated ones. If you look at most of the large clinical practices, they'll say like, "3x of those are the ones that I observe versus 1/3 I treat." That's, that's the kind of like a patient population with ultra-rare disease pricing that then you can just move from ocular oncology into retina with something that is safe. You don't need a surgery. You can do in the office. You have premium pricing. This is like one of those that it's so easy to see that it will grow into a much broader early stage, type of treatment paradigm.
You have a drug that is not just for melanoma. For these ocular oncologists, you can say this is a drug that can work for any cancer in the eye 'cause we're tumor agnostic. We will show this year that we will have data in mets to the choroid and cancers of the ocular surface. Those are not melanomas. Those are squamous cell carcinomas. Those are breast carcinomas in the eye. Once we start showing that the drug works across and you have something that's approved and safe, you know, again, we're really underestimating the market opportunity, I think, even from the analyst projections, which I hope to beat.
We are aware of a couple other drugs in development for similar indications. Can you talk a bit about how the Aura development program differs from that of IDEAYA?
Yes. It's very clean differentiation. Look, our value proposition is to avoid the use of radiotherapy, not to reduce the amount of radiotherapy. If you want to avoid the need of radiotherapy, you need to position these for patients that are early stage, that with bel-sar alone, you're basically having a local cure. That's not the value proposition for a systemic treatment that has grade 3 adverse events. IDEAYA is positioning as neoadjuvant to radiotherapy, right? For meta tumors or, you know, avoiding the need for enucleation, so organ sparing. That's for even a much more acute type of or larger type of tumor. Neoadjuvant, look, if you can shrink the tumors and reduce the need of radiotherapy, is that valuable?
Well, you know, I think for some patients, there would be some value of having a prevention of met or something systemic. Clearly, to show a delta of visual acuity with a smaller amount of radiotherapy is a tough one. It's a very different story if you say like, "If you do this, you don't need radiotherapy." If you treat with bel-sar, you're gonna be able to treat earlier. Probably by treating earlier with an immune mechanism, you're preventing metastasis, but you're preserving the vision, and you don't need... Even if for 20% that you may need to retreat. You still can retreat and not give radiotherapy later. It's a very distinct value proposition. This is pre-metastatic. Obviously, Immunocore has, like, a great drug and has shown great value for patients. That is in the metastatic disease setting. They are not going early into the local setting. Medical oncologist versus ocular oncologist, different. Neoadjuvant versus replacing radiotherapy is also very different.
You, you discussed the analyst models and the market opportunity. What is the pricing assumption that we should make in our model? What? [crosstalk].
Yes.
Strategies do you have for that?
I think that across all analysts, more or less, they have a consensus on the, you know, ultra-orphan pricing corridor, which we strongly believe. If you look at Immunocore launched at $1.5 million per patient on a value proposition, a smaller patient population, metastatic disease. That's kind of like the bookend. You can nicely price ultra-orphan, not at that kind of, like, bookmark, and have a really, really competitive and multi-billion dollar market, especially if you're growing from melanoma to mets to ocular surface with the same drug, same pricing corridor. That's where a drug starts having the commodity of all ocular oncologists.
Maybe moving on to some of the other ocular indications, can you discuss choroidal metastases, maybe first an overview of the condition and the patient population?
Yeah. It's actually a really exciting opportunity to make a difference for these patients because look, imagine a breast cancer patient, metastatic breast cancer, is responding nicely to the systemic meds, it has a metastasis in the eye. What do these women do? They have to go to the ocular oncologist. Regardless of any systemic therapy, they are treated with radiotherapy. They are treated with radiotherapy for a month. They have to receive external beam radiation into that eye for a month. Obviously, they become blinded. Sometimes it's not like melanoma. Sometimes it's multiple lesions in both eyes. Now you're, like, removing quality of, like vision. Even, like, we all complain that we have to get LASIK to re-improve vision.
Like, complete blindness in these women that are mainly 55-year-olds is traumatic. If we can treat preserved vision with something that can be done in the office and spare just radiotherapy, just the need to go to the hospital, it would be huge. The number of patients is, like, higher and higher, thankfully, because metastatic breast cancer is actually working really well, and the drugs are very effective. That was an unmet need. Can we treat these local lesions in the eye instead of, same value proposition, remove the need for radiotherapy? We have a study that's not just breast cancer patients, any metastatic lesion that is in the choroid, because the choroid is what we treat. Same suprachoroidal administration, all the ocular oncologists the same type of treatment paradigm.
The only difference here is that we're obviously doing a dose escalation to see whether we need three cycles here or, like, we can treat with one cycle or maximum two cycles. Here, the advantage for investors is that these are actively growing lesions. They grow fast. We should see reduction in tumor size. One of the key things in our melanoma is like, "You're not seeing reduction in tumor size." Well, those are tiny lesions, and they have a melanoma and an tumor microenvironment that doesn't allow you to see much shrinkage. In mets to the choroid, we're gonna see shrinkage. In those patients, if you have an equivocal shrinkage, that goes with visual acuity preservation and even an improvement in vision.
To have a patient population like that as proof of concept, that shows that the drug works, that's what we're gonna be able to show to investors and to regulators. By the way, we're gonna have that data at the same time that we have the data for melanoma when we present the BLA. Our strategy is like, can we actually support a supplemental BLA, a very quick second indication, so that we can really get that broad market opportunity with ultra-orphan pricing. It's a very attractive for patients always first, but for physicians and for investors, this is a one of those that you rarely see that a drug can nicely have that additional number of indications within a field that's so tied into the ocular oncology community.
Are results on track for this year, and can you talk a little bit more about what would be proof of concept?
For metastasis, you know, a handful of patients showing that the tumor was growing and then it's shrinking, in these, we don't need to show complete responses, right? Just to show a delta that you can see like a modified RECIST criteria, if you would, for the eye and visual acuity. Show that we're not blinding, and show that the lesions are shrinking. We can show that in a handful of patients, and it's like two breast, three lung, or three prostate, one breast, that is like unequivocal, right? Then for cancers of the ocular surface, that's single dose, but that's a study that these lesions are actually accessible. Those are gonna be intralesional, similar as what we're doing in bladder because we don't need to give them suprachoroidal.
It's much direct access. In that study, proof of concept will be before and after, similar to bladder, and we'll be able to see did the tumor respond, did we see immune infiltrate. That's perfect because for the ocular oncologist to have proof of concept of mechanism of action in a tumor in the eye, we don't have that. I will always tell them like, "Look at the bladder." It's like, "Yeah, but that's not the eye." Now we'll be able with the ocular surface to just kind of like have it all kind of like in a really good story for the drug to have a good adoption.
That's perfect. With that, I think we're out of time. Thank you for coming by the conference.
Yeah. Thank you so much.