All right. Good morning, everybody. Thank you for joining me. We've got Elisabet from Aura here with me this morning. So glad to have you at our conference. Welcome down to Miami.
Yes, thank you. It's a pleasure to be here.
Great. Let's jump right in. Can you give me a brief overview of Aura and the Bel-sar product right now, where you are in development, and then we'll get into some specifics on those major indications?
Yes, absolutely. We are developing a novel class of drugs that we call Virus-like Drug Conjugates. It has a unique mode of action where we can drive direct cytotoxicity, like an ADC, but with a very robust immune activation. We have seen that in our late-stage programs. We have a phase III ongoing in ocular oncology in the field of early-stage choroidal melanoma. That is a very exciting key value driver for us. We are also seeing some data early, and we will talk a lot about bladder cancer, where that mechanism of action fully recapitulates what we have seen preclinically. We are very excited with those two therapeutic areas and with a year ahead with a lot of near-term catalysts. We have our phase III and the phase II programs reading. Hopefully, good news soon.
Hopefully, good news soon. Let's start with the ocular program. The primary indication here, as you say, choroidal melanoma, it's a subset of uveal melanoma, currently in phase III. The late stage in this indication is dominated by KIMMTRAK in the metastatic setting, but we've also seen other recent data sets in some other portions of early-stage disease. Can you talk a little bit more about how you're positioning relative to others in this rare indication that I think most folks are not as familiar with?
Yes, absolutely. It's important because we're basically across all our indications, we are pre-metastatic, meaning that we're treating early-stage disease locally with the idea that with our technology, you would have both the preservation of the organ, most importantly, and the prevention of recurrence and metastasis. We really treat frontline ahead of metastatic disease. That's the key differentiation to KIMMTRAK. In the earlier stage, as we think about early choroidal melanoma, this is a disease that starts in the eye. Most of the time, it's early diagnosis, meaning that patients really don't even have treatment available. Radiotherapy is usually when the tumor has grown a little bit. In those early stages where you have a life-threatening disease, the patient has a big decision to make. Do I keep waiting and potentially risk metastasis, or do I treat and risk blindness?
It is a very difficult decision at that early stage of the disease. That is where our positioning is very clear and the value proposition of having a life vision-preserving and something that actually we think can prevent metastatic disease. It is very appealing for the patient with a safety profile that has basically no Grade 2 adverse events. It is really Grade 1 locally. They can be treated with a little bit of topical steroids. That frontline position for that early choroidal melanoma market is really our unique opportunity where literally we have no competition. We can own that market for more than 10 years. We can price it in the rare disease ultra-orphan space. From there, we can expand.
Excellent. Let's talk about the population in the phase III. CoMpass, obviously, ongoing. You gave enrollment guidance for the first time recently. What does the natural history show in patients in this indication from the perspective of progression, obviously, which is the primary endpoint here?
Yes. These patients that we're targeting will be diagnosed early when the disease is either growing a little bit or the tumor is growing a little bit or not yet growing. The majority will end up requiring treatment within one or two years. Right now, the field is evolving.
When you say require treatment, you mean primarily radiotherapy, plaque brachytherapy?
That is the treatment that's available. Correct. Yes. Local radiotherapy that basically is the insertion of a plaque. It's called plaque brachytherapy, and that leads to all of the comorbidities of blindness. That's within one or two years. All of these early choroidal melanoma patients, either if they are growing or not growing, if they have risk factors, the field is evolving into earlier intervention. The dilemma is vision preservation versus early intervention. That kind of group of patients, some call them indeterminate lesions, some early choroidal melanoma, the whole field is evolving into that's all early choroidal melanoma. They all kind of share similar characteristics. They will need treatment within one or two years. Those are the ones that we are enrolling. Now, we are enriching in the phase III, as you said, like what is your patient population in the phase III?
We're enriching for those that are already growing so that we can have a very definitive population that will show a differentiation in the sham versus treatment arc.
Now, this has been a bottleneck for enrollment. You've got a lot of folks that are in the early identification stage, but then you're waiting to see or waiting to confirm growth, I suppose I should say, before the patients are officially enrolled.
It certainly is. We have 400 patients in a rare disease like this that actually are deferring to be treated with radiotherapy and just wait to be able to get into our study. Comments like the patients are disappointed if the tumor is not growing because they want to get into our study. That is something that you would never expect in an oncology study. It is so threatening to have this kind of radioactive treatment and really be blinded that an alternative is so much needed. Yes, you are right. It has been a bottleneck. It is important because the fact that we have this kind of enrichment strategy allows us to have a study that is so highly powered. It has a very high probability of success. It is highly powered.
It is important because if we do not have these type of patients that are already growing, the sham needs to have events of progression in order to show that we have such an efficacious drug. Yes, it has been a bottleneck, but now we have been confident with our guidance. We have waited. We wanted to see consistent enrollment to be able to project enrollment and then be able to meet that guidance. That has happened. We are very confident now at earnings. We said this is a study that will complete enrollment in 2026. We will have the top-line data in Q4 of 2027 because we have been seeing that consistency, that conversion of patients that have been waiting for 6, 9, 12 months, and now they are all coming into the study.
Now, one of the things you just said there I wanted to get a little deeper on, and that was the probability of success, the high powering of the study. The phase II that you ran didn't have a true sham, but it did have a subtherapeutic set of dose arms that are acting sort of like a sham there. And the efficacy appears to be very high. When we look at the phase III design, just taking typical assumptions about phase II efficacy and driving powering off of those, it would seem that the phase III is wildly overpowered. You're enrolling way more patients than you need, perhaps delaying the trial way longer than you need to show efficacy. Can you talk a little bit about how you arrived at the powering decision that you made and what was driving that need for that many patients?
Yes. The discussion about the sample size and the assumptions that supported the powering were all through the SPA negotiations. Initially, we had our full intravitreal study data. When we were discussing with the FDA for the SPA, we had already seen the suprachoroidal data was significantly superior. We still wanted to take very conservative assumptions. We said, although based on the phase II data from suprachoroidal, our power would be 99.9%, let's assume that we take a conservative approach. What if the data is a little bit less? Can we power the study at 95% even with the intravitreal data set? That kind of conservative assumption played a big role in us setting expectations that even if it did not play out as incredible as the phase II data that we saw, we would still have a successful study. That was number one.
Even with that, we have a sample size that's way too big. We can run a study. It doesn't need to be 95% power. It could be 90% power. The discussions with the FDA, we wanted this study to fulfill the safety database. That was kind of like a compromise of 100 patients. This is something that, again, we have additional patients being dosed in the bladder study. We have additional patients in metastases, in cancers of the ocular surface. All collectively will be part of the safety database. That was a little bit at that point in time what was a compromise from the FDA perspective.
Safety so far has been very well tolerated.
That is our big win. Safety, which aligns with visual acuity preservation. We have something that has such high efficacy, but with literally Grade I local adverse events. In the eye, it's probably the most delicate organ. We are seeing also minimal side effects in the bladder. If you don't see them in the eye, you're probably pretty sure that every other organ is going to tolerate the drug really well. There's no systemic exposure. This is something that for frontline positioning for a patient that's basically healthy, safe, safety and tolerability are critical. Because then why wouldn't you choose this first? You have the advantage of priming the immune system, treating locally, not adding any kind of toxicity with the opportunity of that long-term durability.
I want to return to the enrollment funnel at this point because we have to wait for patients to progress to get in. You say you're following 400 people, which is more than you need in the study. The study is already larger than you need from an efficacy stats perspective, at least based on the phase II data. What's going to happen to all of those patients who are on the top of that funnel once the study is once enrollment is formally complete?
Right. So unfortunately for patients, that's actually one thing that we're saying to the sites. All of these patients that are so excited to get in, now you have the opportunity. We can't force the tumor to grow, but the interest from the patients is definitely there. Unfortunately, once the study, the enrollment is complete, then it's a 15-month follow-up. Those patients will not have access to the drug. It will help us show to the FDA the enormous interest, the unmet need. As you know, patients play a big role in the approval of drugs. We feel very excited that we have that interest. Hopefully, that will trigger our fast approval.
All right. Another important feature of the phase III is the secondary endpoint, which is a composite that includes some visual acuity endpoints. One of the things that jumps out at me when I look at the phase II data where you show a version of progression and a version of the would-be composite for phase III is that the curves look very, very similar, perhaps not surprisingly. Can you talk about how that composite endpoint is designed, why it's being included, the way it's being included? If vision deterioration typically only happens after tumor progression and treatment with radio, how is the progression element—isn't the progression element the bulk of the composite anyway?
Yes. It's such a good question. We did that actually because from advice from the FDA, from Dr. Wiley Chambers, because we were seeing the value proposition of our drug is visual acuity preservation. In the patient population that we're going after, comparing to plaque didn't make sense because plaque comes a little later. How can we show the value of our drug if we're comparing versus sham? Wiley said, look, you can actually show that in a composite endpoint. Your visual acuity is 90%. You maybe have one or two events of vision loss in the treatment arm, but you're still going to show that you have a superiority in that endpoint. You can then use it in the claim that you have a drug that has a visual acuity preservation, which is a really important thing.
That actually, I have to give credit to the FDA for kind of giving us that idea, which still is a very highly powered secondary endpoint because it's, as you said, it's almost identical to the primary.
All right. I want to make sure we have time for bladder cancer here. Before we get there, there are two other ocular indications you mentioned earlier, metastatic and ocular surface cancers. How are these similar and how are they different from the uveal melanoma indication, from the choroidal melanoma indication? Where are the current data sets?
Yes. Look, ocular oncology is not just early choroidal melanoma or uveal melanoma. Ocular oncology is a specialty that treats every cancer that happens locally in the eye. These physicians, which are like a very small group of physicians, see all of these cancers. When they were seeing the efficacy and tolerability of the drug, they were the ones to say, we can use it here and we can use it here. Those two other studies are really set to be proof of concept. They will represent the confirmation that the drug works in distinct types of tumors. Because in metastasis, those are mainly breast cancer patients that will have small mets in the eye. In cancers of the ocular surface, squamous cell carcinomas, very different from the melanoma.
We can show as proof of concept that we have good responses in those tumors, while different from an etiology perspective, that shows the breadth and opportunity of the drug. For us, it's really reassuring. Whether that is done and then we have the phase III readout, those programs will probably then be part of a discussion with the FDA for a supplemental BLA and where we can accelerate and with minimal data.
Minimal additional data.
Minimal additional data, we would be able to get the approval. It is very exciting for us. Those are going to happen this year. Now patients need to be selected properly, especially metastasis, because those patients are a little bit, as you can imagine, metastatic patients. With such impeccable safety, we want to make sure that those patients are selected properly. That is a little bit of the bottleneck in metastasis. Both are really important proof of concept studies for 2026.
Great. Let's talk about bladder.
Bladder.
You showed some early data here already from phase I. There is a mix of different patient types included, a mix of different risk factor stratifications. Your focus here, as well as in the ocular indications, is in neoadjuvant just on very early stage tumors. Obviously, this is a market that is being encroached upon, shall I say, by would-be competitors that started in the adjuvant setting, in the later stage setting, in the high-risk setting. Can you talk to me a little bit about the market position here, where you're sitting, and how different that is from folks who are currently running trials in BCG unresponsive and more advanced NMIBC?
Yes. We really position this, as you said, frontline neoadjuvant. There is a reason for us. Mechanistically, our drug works if the tumor is there. If you have removed surgically the tumor and then you're trying to do an adjuvant treatment, then our drug is not going to work because you need tumor to be able to have a cytotoxicity and, most importantly, to have a T cell activation against the tumor neoantigen. By default, we have a frontline advantage. That's a first advantage because the patients come with the tumor. If we have a technology and approach where we can treat them locally with something that is extremely high tolerated and it shows that by doing that, you have better RFS, better durability, less recurrence, everyone should do that frontline. Now, is there anyone else doing that in the neoadjuvant setting? Really, there is not.
There is a clear neoadjuvant approach in muscle invasive disease where actually they are showing great pathological complete responses and the probability of that field moving into preserving bladders and not doing surgeries anymore. That positioning in neoadjuvant where we can also play in the muscle invasive space has not happened in the NMIBC. Everyone else is adjuvant, whereas you can have something that's just so appropriate to be done neoadjuvantly, both in intermediate risk and high risk, that contributes to the efficacy of TURBT, doesn't replace TURBT. In some cases, if the tumor is gone, you don't have to do TURBT because there's nothing to do it on. In the majority of cases, you can do it as a confirmatory surgery but really have the advantage of improving that long-term RFS. The endpoint is exactly the same as the adjuvant therapies.
You can use an RFS endpoint, which is highly validated. It's very used by everyone. If you look at the intermediate risk study designs by J&J and CG Oncology, they're all using RFS. We're going to use the same endpoint. We're clearly going to show that by doing that frontline in a way that doesn't create any burden to the patient, that can be done by the urologist in a formulation that is absolutely optimized for the urologist's office, that actually translates into better outcomes.
OK. Let's dive in there. I want to be very specific, right?
Yes.
Because as you say, there are other folks who are playing in the adjuvant space. RFS, it makes sense as an endpoint there, both adjuvant and for neoadjuvant treatment. I would have expected that from an efficacy perspective, at least, people would compare you to the adjuvant treatments on an RFS basis and feel confident that when a patient walks into the doctor's office and has a choice, neoadjuvant, adjuvant, what they care about is RFS, what the doctor is going to care about is RFS. Based on what you just said, it seems like you think there's an additional impetus to go for a neoadjuvant-based therapy over an adjuvant therapy, maybe even all of the things being equal.
You could consider that by doing a neoadjuvant treatment, you can actually reduce a little bit of the adjuvant treatment, not necessarily replace it. You could actually have a neoadjuvant approach with a drug that's specifically driven to ignite an immune response and a durable response by a T cell activation, the surgery, and then some kind of concomitant or consolidation with adjuvant.
Yes, and.
Right. You do not compete. You do not replace. You are adding. For certain patients, you may add it, absolutely high risk. For example, in the intermediate risk, it may be some patients yes, some patients no. The key is who comes first. The neoadjuvant always comes first.
All right. In the last couple of seconds here, let's talk about catalysts. We mentioned obliquely a couple of things coming next year. Can you just lay out for us what the catalyst path is in 2026?
Yeah. We are obviously excited. There is one key catalyst in our ocular study, which is the end of enrollment. That is for sure our number one key driver of focus, which will drive that top line data in 2027. We have the two proof of concept studies in ocular that will also read in 2026. For bladder, we have three months data. That is the number one. It is a regulatory endpoint. Everyone.
Completely sponsored by.
Yes, exactly. How does the drug do in the absence or with TURBT? We have different cohorts to explore the efficacy as a single agent even without the surgery. That is going to be important. We have four cohorts with three-month data that we hope to provide data. Again, we do not want to be dropping data of one or two patients, but really give a comprehensive because this is such a new approach, a new positioning. We want to make sure that once we present the data, it is really comprehensive. There is 12-month data. You have in our company that it is in late stage with a phase III and a SPA with a clear risk and high probability of success, and then three very good phase II readouts in the meantime to show the breadth of the opportunity in two therapeutic areas.
It is an exciting time for the company.
Excellent. We'll look forward to seeing all that data next year.
Yes, absolutely. Thanks for inviting me. This was a great conference.
Thanks for coming.