Good morning, everybody. Welcome to day two of the Citizens Life Science Conference. We are pleased to have Aura Biosciences here and CEO Eli de los Pinos.
Yes, correct.
Joining us for a fireside chat. Aura is a name we've been covering for a few years now, and I think one of the more interesting stories when we think about kind of fundamental science and then commercial opportunity. Eli, maybe to start, can you talk a little bit about kind of your technology and what you guys are working on, and then we can jump into some details?
Yes, absolutely. We have a novel technology. We're working with virus-like drug conjugates. They have a unique mechanism of action, a dual mechanism of action by which we can have directed cytotoxicity and a very robust immune activation. We are strategically positioning our technology for the frontline treatment of cancer, mainly local early-stage disease, where we can have a radical impact in the life of patients with a very good safety profile.
Your lead indication, primary uveal melanoma, something that people may not be as familiar with. Can you talk a little bit about how many patients there are, how it's diagnosed, clinical consequence, all those details?
Yeah. So our drug, bel-sar, can have a dramatic impact in the field of ocular oncology, which is actually not just ocular melanoma, but it's a group of rare cancers that collectively are 66,000 patients with no drugs approved and mainly treated with surgical intervention or radiotherapy. That is the field. Primary uveal melanoma has an incidence of 11,000 patients. It's a life-threatening disease. It's diagnosed really early, pre-metastatic, and we basically treat patients with radiotherapy and blind them. We have a unique opportunity to really transform that field with a therapy that has shown dramatic efficacy with a very good safety profile. Again, that frontline opportunity in a space where there's no competition, we can really have a unique positioning in a very successful market launch.
I think what helps me thinking about that is anchoring to what's out there, because I don't think people appreciate the opportunity when we talk about kind of a white space where there's no drugs approved, but we have a drug approved, KIMMTRAK, for a subset of metastatic uveal melanoma. Can you talk a little bit about kind of the difference about how that's been treating and that that drug does fairly well? What does that mean for bel-sar and your opportunity?
Correct. You have to think about the disease in kind of like three stages. They are mainly diagnosed pre-metastatic. When you go to the ophthalmologist and you have a nevus, that's not a cancer, but 4% of Caucasians have nevus. That's hundreds of thousands of patients. A lot of those actually start with malignant signs of transformation, and those are diagnosed really early. Those patients already have a melanoma, small melanoma in their eye, and they are either observed or treated with radiotherapy and blinded them. That's the difficult part of that early-stage treatment intervention, which is we want to treat you, but we don't want to blind you. That is the whole bulk of patients that we are positioned. There are the patients that are diagnosed a little later with a medium to large tumor, and there are the metastatic.
In either of the larger metastatic, we play. We play in the earlier ones, and we hope that everyone that's diagnosed early would be treated frontline, because why would you choose to wait? Why would you choose to wait or be treated with radiotherapy and blinded when there is a therapy that works just as well and preserves vision in 90%+ of the patients? That is why it's very different than metastatic disease or even late-stage disease where you have like a very large tumor and you're trying to preserve the eyeball.
Do you think there's going to be any inertia to treat from physicians or patients just being like, hey, I want to have a watchful waiting approach and wait till something happens or is going to happen? Do we know kind of consistency of growth or consistency of metastasis? Like what are the consequences of not treating early?
It is very well known that waiting is not the right thing. It is known that, first of all, the mutations are present very early. It is known that there is possibility for micrometastasis. Waiting is just the choice now because they do not want to blind patients. Across the globe, we have the study in more than 18 countries. The unmet need is the same, and the willingness to treat is there. We have seen that, especially with an extremely favorable safety profile with a local approach where you have no systemic toxicities, everyone would choose to treat first. We actually think that this could just go and be much bigger than we think today because, you know, this is a therapy that could be treated by any retina specialist.
Maybe those early melanomas are really not going to be referred anymore and just treated, which would make the market really significantly bigger.
I think that's an interesting point. Can you talk about how bel-sar is actually administered? It's not chemotherapy. It's not something you have to go in for an infusion every month or every week. Can you talk a little bit about the administration?
Yeah. So bel-sar is extremely simple to administer. It's local. It's in the office. You don't even need the operating room. It's given with a supracoroidal administration, a supracoroidal injection, which is even safer than an intravitreal, right? You don't even get into the vitreous. It's a light activation that takes less than 20 minutes. It can be done all in one day. The patient doesn't need to stay in the hospital. It doesn't need any light precaution, no systemic toxicities. That's given for nine treatments. It's an acute treatment, and we've seen remarkably good durability of response. The patient receives for the first three months, nine treatments, nine days, and that's it.
Literally, for the majority of patients, we think it's going to be a local, durable cure that prevents them from losing vision, from having to go to radiotherapy, from having the comorbidities of not just blindness, but dry eye, a lot of surgeries that go associated with the treatment of radiation. It is a safety profile and a target product profile that is just so beneficial for a patient that has that life-threatening disease, is still pre-metastatic, and doesn't want to wait for something that's going to blind them later.
Where are you guys in clinical development?
We are in phase III with a SPA agreement. It's an exciting time for the company, especially for me that I've seen this drug from literally the bench. We now are very close to seeing that B of the BLA. It's an exciting time. The fact that we have the SPA is very important because it's a first in class and a first of its kind that it's going to be approved for this disease. There's a lot of excitement globally because, again, there's been a lot of need to treat early. It's also interesting because in some of these rare diseases, sometimes you have to find the patients. Here, the patients are already identified.
The fact that we have so many, even in our phase III pre-screening, we have like close to twice the size of the study of patients that are just waiting to get into the study. That's just the unmet need that there is, right? Rarely you find a rare disease where you have so many patients waiting to get in.
Can you talk a little bit about that, that you're enriching the population in phase III? What did you learn in your prior trial to make sure that you're getting the right patients in?
Yeah. Look, the drug is extremely efficacious. We have 80% efficacy. The key to show clinical benefit in a study that's actually a red carpet, which is versus sham, is to show that we stop the growth of these lesions and that the sham keeps growing and needs a standard of care. In order to do that, we are enriching for patients that have actively growing lesions so that the sham can fail very quickly. We have an extremely high-power study with just 100 patients. That's the design, which is perfect. The caveat is that the patients need to be at the same kind of like documented growth stage so that the two arms differentiate quickly. That is what we've been doing.
That's why we have this kind of like registry or pre-screening to make sure that the patients that all match the inclusion criteria of the study, they are just waiting to get that growth to be able to get in. That's one of the key things that we're saying, that when the drug is approved, that's not going to be necessary. All of these patients, they're just showing you the high demand that there will be. That's all of those that already match the inclusion criteria. A very exciting kind of like pre-market launch or awareness that we're creating, the demand of the drug before it's approved.
You mentioned about 100 patients in the trial. Have you said how many are in this pre-screening period and how many have been enrolled so far or timing for completing enrollment?
We're not providing enrollment updates, but we've been very clear that there's good momentum in Europe. Last year, we actually took a little longer to open European sites because of the EU CTR process. Now Europe is fully open. We're seeing a great uptake. In the coming months, we'll be updating exactly when we think the enrollment will be finished, but we're very excited to see the progress.
Cancer worries me as an analyst because I've been burned before with small phase II trials without controls that look great, and then we get a phase III trial and it doesn't work. Why is that not going to be the case with bel-sar?
It's not going to be the case because we're compared to sham, right? And because of the enrichment strategy, we know that these lesions, when they grow, they continue to grow. We've done the study with the exact same patients in phase II. The data in phase II that we showed with those response that we saw was with the exact same reading center type of inclusion criteria, documented growth, most of the same sites. We feel strongly that we're not changing anything and we're comparing to sham. If we were comparing to radiotherapy and we had to look for vision loss two years from now, that would be a different story. For us, it's just a matter to make sure that we have the same patients at the same growth. We think that the study is highly powered for success.
When is the primary endpoint measured?
The primary endpoint is time to tumor progression. The FDA wanted a minimum follow-up for all patients of 15 months. It will be when the last patient enrolled meets 15 months, at the end of enrollment + 15 months.
Okay. No interim look or adjustments, sample size?
We did not. It's a small study with 100 patients. We wanted it to have high power. Right now, there is not an interim analysis.
When you guys tell us last patient's in, we set the calendar, circle the date, and we can know when date is coming.
That is correct. Lots of other clinical milestones in between.
I don't want to talk about those now because the other interesting thing is the data you guys have generated in bladder cancer. This is an area that I think people are getting more excited about. There's a lot of commotion in the field. You guys are doing something very different. Talk a little bit about bel-sar's opportunity in bladder cancer and how it's different than what other people are doing.
Absolutely. Remember the same that I was telling that in ocular, there are like these three phases and we're going first because we're highly efficacious and safe. That same value proposition applies for bladder. What do we have in bladder? We have very high incidence, but a disease that is pre-metastatic and local, very similar to the eye. We have shown that with just a tiny injection of our drug with an ocular volume, we have four out of five complete responses. Now we're going to multiple doses. A very highly efficacious drug that has no systemic toxicities, no intravesical administration, so not even like bladder toxicities, extremely well tolerated. That is the perfect positioning to go first, not only for the safety and efficacy, but because of the profile or mechanism of action of this drug.
If you think about the unmet need in bladder cancer in this early stage, it's recurrence. We treat with surgery. The surgery is not clean enough. Patients recur and recur. We try to alleviate this like not really good surgery with adjuvant treatments. The adjuvant treatments, some of them claim to be pro-immunogenic. That is a good approach. What you want is not just a pro-inflammatory response in the bladder. You want an anti-tumoral response to the tumor because you have to educate the immune system to react towards the tumor. That is impossible with an adjuvant treatment because the adjuvant treatment by default is right after surgery. If you've removed the tumor, how can you have your drug act in the tumor? You're basically just having a pro-inflammatory response.
That is why you see all of these great complete response rates at three months and all kind of decaying at 12 months at 40%-50% response rates. That is by default to have an adjuvant treatment and the current mechanism of actions of like reformulated chemotherapy. If you think about our mechanism, it's highly pro-immunogenic. We have in less than eight days a strong CD8 T-cell response and CRs with a single dose. That is what you want. You need to treat the tumor first to educate the immune system. In most cases, we think that's all you need. In some cases, you may do it neoadjuvant. The key is that you want to do it frontline, the same as in the eye.
You want to do this treatment that it's safe, that it has no systemic toxicities, that it's not going to damage even the urothelia with something that really primes the immune system because that's what's going to give the durability of response. Guess what? You can do it simple. You don't need anesthesia. You can do it in the office. Any urologist can do it. In fact, they're all excited because like, I see the lesion, I see the papillary, I can just treat it and I'm done. This is great. That is the kind of like paradigm shift. Of course, we're early. It was a phase one for visibility and we already got 80% complete responses in intermediate risk.
It was great to see and just gives us a great incentive to accelerate the program, do a fast dose escalation, and start looking at that durability of response.
I think what's interesting about what you guys did, and I think you probably had to do this from an ethics perspective or IRB, is you gave bel-sar, but then you were not waiting to see what happened. You were monitoring response when they had resection of the tumor. It was kind of like, all right, we are going to do this and just see what happens. Then you got the stellar results you did get. Can you talk about, because we get in a spreadsheet and we talk lining up complete responses and what happens, but what you did is different than what we are seeing from other trials in small numbers, but it is a different way of looking at things.
Exactly. Yes. It is, if you resect the tumor and then give a drug, of course, you're going to have a CR because that's basically the CR created by your surgery. You're kind of having that consolidation. In our case, ahead of the surgery, we were having the CRs. The physician went there to do a surgery. They removed what was a little bit of an edema. The pathology came that there's no cancer cell. It's all full of lymphocytes and CD4 and CD8. It was a remarkable result that, again, we didn't expect with such a small dose with the ocular volumes that we gave. Now imagine we're going to a much higher dose escalation with two cycles to really boost that immune response, which we think that's what's going to give us that great durability.
With something that has no systemic exposure and no urothelial toxicity, we do not even have to give any pre-wash. The physician does not need a hood. There is no replicating virus, but it acts like a virus. It acts like chemotherapy and it acts like a virus without being chemotherapy and without being a virus. That is the beauty of this treatment.
Pushback we've heard, and I think this is a tough one because we're guessing about changing behavior, but urologists, they're surgeons, and they like to do surgery, and they get paid to do surgery, and the hospitals make money doing surgery. Why would they introduce something novel with some more risk that could make them less money and does something different than what they've been trained to do?
Yeah. First of all, the majority of urologists actually make less money doing a TURBT than they would do by giving a very good therapy in the office, right? Because they can treat 20 patients in the office with something as novel as bel-sar, where they can do two TURBTs, and then anesthesiologists probably make more money than them. The economics actually play nicely towards the office versus the OR just to start. We think that regardless of economics, if we do a patient-centric approach, it is true that for some patients, you may not need the surgery. For others, you may really want to do the surgery because the patient is more high risk, and you want to confirm that all the tumor is gone. Our treatment, it does not matter.
As long as you do our therapy first, you will have the optionality of like some patients may be immune ablative. You do not need the surgery, and others you do. It is not that we are replacing the surgery. We are adding something that really will give that durability of response with an immune-mediated response towards the tumor that you have to do first because you have to treat the tumor. If you remove the tumor, nothing is going to respond, right? The immune system is going to have very little antigenic material to respond to. You have to do it first.
Where are you guys in development in bladder cancer?
We've just started a phase II, and it's an exciting development because in this phase II, we're going to look at, as I said, because with a single dose, we had such high efficacy. We don't have to dose escalate dramatically. What we're trying is to see whether we can have this two-cycle approach with some time in between so that we can really try to prime the immune system to have as much CD8 T-cell response as possible. We're going to treat intermediate risk and high risk in different cohorts, and then we're going to look at both modalities, immune ablative and neoadjuvant. With that, in a very, very capital-efficient approach in phase II, we're going to be able to have that unequivocal proof of concept to move into phase III.
That could be in intermediate risk and high risk in separate studies or one and then the other.
How do you think about disclosures to the street? Is this going to be an open label where you'll be monitoring and letting us know updates intermittently, or are we going to get, we'll have an update sometime next year and you guys will tell us what to look for?
Yes. Look, in the space, there's actually a good FDA endpoint, which is the three months complete response rate, right? That's something that we couldn't have before in the window of opportunity study, and now we have this opportunity. I think that three months and 12 months is the obvious one. Whether we'll give six to nine months, that's to be determined. The three months complete response rate across these different modalities and risk profiles is for sure something that we're planning to do.
Are there benchmarks we should think about for what you want to see in terms of response rates, or is it we're treating early, anything we can do here is beneficial? How should we think about the efficacy bar here?
Right. If we look at intermediate risk, you should benchmark what's the efficacy with TURBT alone, right? The efficacy with TURBT alone is described between 60%-70%, meaning that 30% of the patients actually have not a clean TURBT, and at three months, they have a recurrence or a tumor present. That's the benchmark in intermediate risk. Now, if you do it as immune ablative or neoadjuvant in either of those modalities, you should be at least better than 60%-70%.
Okay. That's very helpful. And so bel-sar, primary uveal melanoma, non-muscle-invasive bladder cancer, but then also choroidal metastasis, cancers of the ocular surface.
Right.
Those are kind of moving along as well. Can you talk a little about those opportunities?
Yes. We're very excited because look, ocular oncology, as I said, is a group of rare diseases that collectively are 66,000 patients seen by 50 specialists in the U.S. and 50 in Europe. There are no drugs approved. They're basically all of these different types of rare cancers are treated with surgery. They're treated with radiotherapy, but they're desperate for better treatment options. Our technology, our therapy is tumor agnostic, meaning that we can treat a breast cancer in the eye as well as a melanoma in the eye. That is the opportunity of metastasis to the choroid, that with a very small study, we can show the value of our drug across probably five different etiologic or histology types. That is, again, the power of a platform within a product, right?
Because in a very small study, if you're seeing breast cancer shrink in the eye, you have something extremely potent that probably can treat early-stage breast cancer. If you have prostate cancer in the eye, having a response, then you can nicely correlate. Again, not just doubles the market opportunity from an ocular oncology perspective, but highly address the platform view of something that can now work in distinct cancer types as rare melanomas, urothelial carcinomas. Potentially, you could think about esophageal, head and neck cancer. Again, with data in a very, very capital-efficient way, we'll be able to demonstrate that value.
We kind of glossed over this, but I think it's an important point. When you're just listing off all the things bel-sar can do, why can it treat all these? Why is it tumor agnostic?
Because the way these virus-like particles of the virus where the technology is derived is binding is a biomarker that is expressed across many, many solid tumors from early-stage malignant transformation all the way through metastasis. That was the key of the uniqueness of this technology. It's not like an antibody that will target a growth factor receptor. We bind these modified glycans that are very important for the survival of the cancer cell. In fact, if you deplete them, the cancer cell goes back to epithelial. You get the opposite. You get to normal cells. We know that these are signals that are preserved. The way we're killing the cancer is ablative, right? We don't depend on a genetic mutation. We don't depend on a molecular pathway.
Both from the targeting and the ablative mechanism of action, you have something that should translate extremely well across many types of solid tumors. If you think about the future of cancer, we're diagnosing earlier and earlier. If I ask how many of your friends and family were diagnosed in stage one, you'll probably all raise your hands. We always treat with surgery and radiotherapy. Here we have the molecular surgery where you can be as efficient as surgery without removing your eye, removing your bladder, or maybe cutting half of the esophagus.
In my mind, given the data that we've seen in uveal melanoma, this just becomes a question of finding the right dose for the right application. Do you think that's fair?
It is fair. Obviously, the bladder cancer opened a remarkable opportunity for us, right? Initially, just with ocular oncology with 66,000 patients, that's a multi-billion dollar approach where there's no competition. We can get the market. The translation into these broader oncology indications in early-stage local frontline approach, where also we don't compete with metastatic disease, it's so unique and so big. We think that, again, the bladder cancer just unlocked that option. For us, it's obviously we need to remain focused and bring in value up to the finish line. That just shows you the potential power of the technology moving forward.
In the last minute, can you remind us of your cash position and then maybe what to look forward to the next 12 to 18 months in terms of updates from the pipeline?
Yes. As we've been showing in our earnings release, we have cash into the second half of 2026. We are fully funded across all our clinical programs, and there are key data milestones that we're going to show within not just 12, but six months. The bladder data with three months durability should come within six months. The metastasis data showing, again, the power in the eye and across the board and across other solid tumors is coming within six months. Obviously, CoMpass and the phase III study.
It's a very exciting time. It's a very exciting technology. I think people are just starting to realize the potential. Good morning, everybody. Welcome to day two of the Citizens Life Science Conference. We're pleased to have Aura Biosciences here and CEO Eli de los Pinos.
Yes, correct.
Joining us for a fireside chat. Aura is a name we've been covering for a few years now, and I think one of the more interesting stories when we think about kind of fundamental science and then commercial opportunity. So Eli, maybe to start, can you talk a little bit about kind of your technology and what you guys are working on, and then we can jump into some details?
Yes, absolutely. We have a novel technology. We're working with virus-like drug conjugates. They have a unique mechanism of action, a dual mechanism of action by which we can have directed cytotoxicity and a very robust immune activation. We are strategically positioning our technology for the frontline treatment of cancer, mainly local early-stage disease where we can have a radical impact in the life of patients with a very good safety profile.
Your lead indication, primary uveal melanoma, something that people may not be as familiar with. Can you talk a little bit about how many patients there are, how it's diagnosed, clinical consequence, all those?
Yeah. So our drug, bel-sar, can have a dramatic impact in the field of ocular oncology, which is actually not just ocular melanoma, but it's a group of rare cancers that collectively are 66,000 patients with no drugs approved and mainly treated with surgical intervention or radiotherapy. That is the field. Primary uveal melanoma has an incidence of 11,000 patients. It's a life-threatening disease. It's diagnosed really early, pre-metastatic, and we basically treat patients with radiotherapy and blind them. We have a unique opportunity to really transform that field with a therapy that has shown dramatic efficacy with a very good safety profile. Again, that frontline opportunity in a space where there's no competition, we can really have a unique positioning in a very successful market launch.
I think what helps me thinking about that is anchoring to what's out there because I don't think people appreciate the opportunity when we talk about kind of a white space where there's no drugs approved, but we have a drug-approved KIMMTRAK for a subset of metastatic uveal melanoma. Can you talk a little bit about kind of the difference about how that's been treating and that that drug does fairly well? What does that mean for bel-sar and your opportunity?
Correct. You have to think about the disease in kind of like three stages. They are mainly diagnosed pre-metastatic. When you go to the ophthalmologist and you have a nevus, that's not a cancer, but 4% of Caucasians have nevus. That's hundreds of thousands of patients. A lot of those actually start with malignant signs of transformation, and those are diagnosed really early. Those patients already have a melanoma, small melanoma in their eye, and they are either observed or treated with radiotherapy and blinded them. That's the difficult part of that early-stage treatment intervention, which is we want to treat you, but we do not want to blind you. That is the whole bulk of patients that we are positioned. There are the patients that are diagnosed a little later with a medium to large tumor, and there are the metastatic.
In either of the larger metastatic, we play. We play in the earlier ones, and we hope that everyone that's diagnosed early would be treated frontline because why would you choose to wait or be treated with radiotherapy and blinded when there is a therapy that works just as well and preserves vision in 90%+ of the patients? That is why it's very different than metastatic disease or even late-stage disease where you have like a very large tumor and you're trying to preserve the eyeball.
Do you think there's going to be any inertia to treat from physicians or patients just being like, "Hey, I want to have a watchful waiting approach and wait till something happens or is going to happen"? Do we know kind of consistency of growth or consistency of metastasis? Like what are the consequences of not treating early?
It is very well known that waiting is not the right thing. It is known that, first of all, the mutations are present very early. It is known that there is possibility for micro-metastasis. Waiting is just the choice now because they do not want to blind patients. Across the globe, we have the study in more than 18 countries. The unmet need is the same, and the willingness to treat is there. We have seen that, especially with an extremely favorable safety profile with a local approach where you have no systemic toxicities, everyone would choose to treat first. We actually think that this could just go and be much bigger than we think today because this is a therapy that could be treated by any retina specialist.
Maybe those early melanomas are really not going to be referred anymore and just treated, which would make the market really significantly bigger.
I think that's an interesting point. Can you talk about how bel-sar is actually administered? It's not chemotherapy. It's not something you have to go in for an infusion every month or every week. Can you talk a little bit about the administration?
Yeah. So bel-sar is extremely simple to administer. It's local. It's in the office. You don't even need the operating room. It's given with a supracoroidal administration, a supracoroidal injection, which is even safer than an intravitreal, right? You don't even get into the vitreous. It's a light activation that takes less than 20 minutes. It can be done all in one day. The patient doesn't need to stay in the hospital. It doesn't need any light precaution, no systemic toxicities. That's given for nine treatments. It's an acute treatment, and we've seen remarkably good durability of response. The patient receives for the first three months, nine treatments, nine days, and that's it.
Literally, for the majority of patients, we think it's going to be a local durable cure that prevents them from losing vision, from having to go to radiotherapy, from having the comorbidities of not just blindness, but dry eye, a lot of surgeries that go associated with the treatment of radiation. It is a safety profile and a target product profile that is just so beneficial for a patient that has that life-threatening disease, is still pre-metastatic, and doesn't want to wait for something that's going to blind them later.
Where are you guys in clinical development?
We are in phase III with a SPA agreement. It's an exciting time for the company, especially for me that I've seen this drug from literally the bench. We now are very close to seeing that B of the BLA. It's an exciting time. The fact that we have the SPA is very important because it's a first in class and a first of its kind that it's going to be approved for this disease. There's a lot of excitement globally because, again, there's been a lot of need to treat early. It's also interesting because in some of these rare diseases, sometimes you have to find the patients. Here, the patients are already identified.
The fact that we have so many, even in our phase III and pre-screening, we have like close to twice the size of the study of patients that are just waiting to get into the study. That's just the unmet need that there is, right? Rarely you find a rare disease where you have so many patients waiting to get in.
Can you talk a little bit about that? You're enriching the population in phase III. What did you learn in your prior trial to make sure that you're getting the right patients in?
Yeah. Look, the drug is extremely efficacious. We have 80% efficacy. The key to show clinical benefit in a study that's actually a red carpet, which is versus sham, is to show that we stop the growth of these lesions and that the sham keeps growing and meets the standard of care. In order to do that, we are enriching for patients that have actively growing lesions so that the sham can fail very quickly. We have an extremely high-power study with just 100 patients. That's a design which is perfect. The caveat is that the patients need to be at the same kind of like documented growth stage so that the two arms differentiate quickly. That is what we've been doing.
That's why we have this kind of like registry or pre-screening to make sure that the patients that all match the inclusion criteria of the study, they are just waiting to get that growth to be able to get in. That's one of the key things that we're saying. Like when the drug is approved, that's not going to be necessary. All of these patients, they're just showing you the high demand that there will be. That's all of those that already match the inclusion criteria. A very exciting kind of like pre-market launch or awareness that we're creating, the demand of the drug before it's approved.
You mentioned about 100 patients in the trial. Have you said how many are in this pre-screening period and how many have been enrolled so far or timing for completing enrollment?
We're not providing enrollment updates, but we've been very clear that there's good momentum in Europe. Last year, we actually took a little longer to open European sites because of the EU CTR process. Now Europe is fully open. We're seeing a great uptake. In the coming months, we'll be updating exactly when we think the enrollment will be finished, but we're very excited to see the progress.
Cancer worries me as an analyst because I've been burned before with small phase II trials without controls that look great, and then we get a phase III trial and it doesn't work. Why is that not going to be the case with bel-sar?
It's not going to be the case because we're compared to sham, right? And because of the enrichment strategy, we know that these lesions, when they grow, they continue to grow. We've done the study with the exact same patients in phase II. The data in phase II that we showed with those responses that we saw was with the exact same reading center type of inclusion criteria, documented growth, most of the same sites. We feel strongly that we're not changing anything and we're comparing to sham. If we were comparing to radiotherapy and we had to look for vision loss two years from now, that would be a different story. For us, it's just a matter to make sure that we have the same patients at the same growth. We think that the study is highly powered for success.
When is the primary endpoint measured?
The primary endpoint is time to tumor progression. The FDA wanted a minimum follow-up for all patients of 15 months. It will be when the last patient enrolled meets 15 months, at the end of enrollment + 15 months.
Okay. No interim look or adjustments, sample size?
We did not. It's a small study with 100 patients. We wanted it to have high power. So right now, there is not an interim analysis.
When you guys tell us last patient's in, we set the calendar, circle the date, and we can know when date is coming.
That is correct. Lots of other clinical milestones in between.
I want to talk about those now because the other interesting thing is the data you guys have generated in bladder cancer. This is an area that I think people are getting more excited about. There's a lot of commotion in the field. You guys are doing something very different. Talk a little bit about bel-sar's opportunity in bladder cancer and how it's different than what other people are doing.
Absolutely. Remember the same that I was telling that in ocular, there are like these three phases and we're going first because we're highly efficacious and safe. That same value proposition applies for bladder. What do we have in bladder? We have very high incidence, but a disease that it's pre-metastatic and local, very similar to the eye. We have shown that with just a tiny injection of our drug with an ocular volume, we have four out of five complete responses. Now we're going to multiple doses. A very highly efficacious drug that has no systemic toxicities, no intravesical administration, so no even like bladder toxicities, extremely well tolerated. That is the perfect positioning to go first, not only for the safety and efficacy, but because of the profile or mechanism of action of this drug.
If you think about the unmet need in bladder cancer in this early stage, it's recurrence. We treat with surgery. The surgery is not clean enough. Patients recur and recur. We try to alleviate this like not really good surgery with adjuvant treatments. The adjuvant treatments, some of them claim to be pro-immunogenic. That is a good approach. What you want is not just a pro-inflammatory response in the bladder. You want an anti-tumoral response to the tumor because you have to educate the immune system to react towards the tumor. That is impossible with an adjuvant treatment because the adjuvant treatment by default is right after surgery. If you've removed the tumor, how can you have your drug act in the tumor? You're basically just having a pro-inflammatory response.
That is why you see all of these great complete response rates at three months and all kind of decaying at 12 months at 40%-50% response rates. That is by default to have an adjuvant treatment and the current mechanism of actions of like reformulated chemotherapy. If you think about our mechanism, it is highly pro-immunogenic. We have in less than eight days a strong CD8 T-cell response and CRs with a single dose. That is what you want. You need to treat the tumor first to educate the immune system. In most cases, we think that is all you need. In some cases, you may do it neoadjuvant. The key is that you want to do it frontline, the same as in the eye.
You want to do this treatment that it's safe, that it has no systemic toxicities, that it's not going to damage even the urothelia with something that really primes the immune system because that's what's going to give the durability of response. Guess what? You can do it simple. You don't need anesthesia. You can do it in the office. Any urologist can do it. In fact, they're all excited because like, I see the lesion, I see the papillary, I can just treat it and I'm done. This is great. That is the kind of like paradigm shift. Of course, we're early. It was a phase one for visibility and we already got 80% complete responses in intermediate risk.
It was great to see and just gives us a great incentive to accelerate the program, do a fast dose escalation, and start looking at that durability of response.
I think what's interesting about what you guys did, and I think you probably had to do this from an ethics perspective or IRB, is you gave bel-sar, but then you weren't waiting to see what happened. You were monitoring response when they had resection of the tumor. It was kind of like, all right, we're going to do this and just see what happens. Then you got the stellar results you did get. If you talk about, because we get in a spreadsheet and we talk lining up complete responses and what happens, what you did is different than what we're seeing from other trials. Small numbers, but it's a different way of looking at things.
Exactly. Yes. It is, you know, if you resect the tumor and then give a drug, of course, you're going to have a CR because that's basically the CR created by your surgery. Then you're kind of having that consolidation. In our case, ahead of the surgery, we were having the CRs. The physician went there to do a surgery. They removed what was a little bit of an edema. Then the pathology came that there's no cancer cell. It's all full of lymphocytes and CD4 and CD8. It was a remarkable result that, again, we didn't expect with such a small dose with the ocular volumes that we gave. Now imagine we're going to a much higher dose escalation with two cycles to really boost that immune response, which we think that's what's going to give us that great durability.
With something that has no systemic exposure and no urothelial toxicity, we do not even have to give any pre-wash. The physician does not need a hood. There is no replicating virus, but it acts like a virus. It acts like chemotherapy and it acts like a virus without being chemotherapy and without being a virus. That is the beauty of this treatment.
Pushback we've heard, and I think this is a tough one because we're guessing about changing behavior, but urologists are surgeons and they like to do surgery and they get paid to do surgery and the hospitals make money doing surgery. Why would they introduce something novel with some more risk that could make them less money and does something different than what they've been trained to do?
Yeah. First of all, the majority of urologists actually make less money doing a TURBT than they would do by giving a very good therapy in the office, right? Because they can treat 20 patients in the office with something as novel as bel-sar, where they can do two TURBTs and the anesthesiologist probably makes more money than them. The economics actually play nicely towards the office versus the OR just to start. We think that regardless of economics, if we do a patient-centric approach, it is true that for some patients, you may not need the surgery. For others, you may really want to do the surgery because the patient is more high risk and you want to confirm that all the tumor is gone. Our treatment, it doesn't matter.
As long as you do our therapy first, you will have the optionality of like some patients may be immune ablative. You do not need the surgery and others you do. It is not that we are replacing the surgery. We are adding something that really will give that durability of response with an immune-mediated response towards the tumor that you have to do first because you have to treat the tumor. If you remove the tumor, nothing is going to respond, right? The immune system is going to have very little antigenic material to respond to. You have to do it first.
Where are you guys in development in bladder cancer?
We've just started a phase II. It's an exciting development because in this phase II, we're going to look at, as I said, because with a single dose, we had such high efficacy. We don't have to dose escalate dramatically. What we're trying is to see whether we can have this two-cycle approach with some time in between so that we can really try to prime the immune system to have as much CD8 T-cell response as possible. We're going to treat intermediate risk and high risk in different cohorts. We're going to look at both modalities, immune ablative and neoadjuvant. With that, in a very, very capital-efficient approach in phase II, we're going to be able to have that unequivocal proof of concept to move into phase III.
That could be in intermediate risk and high risk in separate studies or one and then the other.
How do you think about disclosures to the street? Is this going to be an open label where you'll be monitoring and letting us know updates intermittently, or are we going to get, we'll have an update sometime next year and you guys will tell us what to look for?
Yes. Look, in the space, there's actually a good FDA endpoint, which is the three months complete response rate, right? That is something that we could not have before in the window of opportunity study. Now we have this opportunity. I think that three months and 12 months is the obvious one, whether we will give six to nine months, that is to be determined. The three months complete response rate across these different modalities and risk profiles is for sure something that we are planning to do.
Are there benchmarks we should think about for what you want to see in terms of response rates, or is it we're treating early, anything we can do here is beneficial? How should we think about the efficacy bar here?
Right. If we look at intermediate risk, you should benchmark what's the efficacy with TURBT alone, right? The efficacy with TURBT alone is described between 60%-70%, meaning that 30% of the patients actually have not a clean TURBT, and at three months, they have a recurrence or a tumor present. That's the benchmark in intermediate risk. Now, if you do it as immune ablative or neoadjuvant in either of those modalities, you should be at least better than 60%-70%.
Okay. That's very helpful. And so bel-sar, primary uveal melanoma, non-muscle-invasive bladder cancer, but then also choroidal metastasis, cancers of the ocular surface.
Right.
Those are kind of moving along as well. Can you talk a little about those opportunities?
Yes. We're very excited because look, ocular oncology, as I said, is a group of rare diseases that collectively are 66,000 patients seen by 50 specialists in the U.S. and 50 in Europe. There are no drugs approved. They're basically all of these different types of rare cancers are treated with surgery. They're treated with radiotherapy, but they're desperate for better treatment options. Our technology, our therapy is tumor agnostic, meaning that we can treat a breast cancer in the eye as well as a melanoma in the eye. That is the opportunity of metastasis to the choroid, that with a very small study, we can show the value of our drug across probably five different etiology or histology types. That is, again, the power of a platform within a product, right?
Because in a very small study, if you're seeing breast cancer shrink in the eye, you have something extremely potent that probably can treat early- stage breast cancer. If you have prostate cancer in the eye, having a response, then you can nicely correlate. Again, not just doubles the market opportunity from an ocular oncology perspective, but highly address the platform view of something that can now work in distinct cancer types as rare melanomas, urothelial carcinomas. Potentially, you could think about esophageal, head and neck cancer. Again, with data in a very, very capital-efficient way, we'll be able to demonstrate that value.
We kind of glossed over this, but I think it's an important point. When you're just listing off all the things bel-sar can do, why can't it treat all these? Why is it tumor agnostic?
Because the way these virus-like particles of the virus where the technology is derived is binding is a biomarker that is expressed across many, many solid tumors from early- stage malignant transformation all the way through metastasis. That was the key of the uniqueness of this technology. It's not like an antibody that will target a growth factor receptor. We bind these modified glycans that are very important for the survival of the cancer cell. In fact, if you deplete them, the cancer cell goes back to epithelial. You get the opposite. You get to normal cells. We know that these are signals that are preserved. The way we're killing the cancer is ablative, right? We don't depend on a genetic mutation. We don't depend on a molecular pathway.
Both from the targeting and the ablative mechanism of action, you have something that should translate extremely well across many types of solid tumors. If you think about the future of cancer, we're diagnosing earlier and earlier. If I ask how many of your friends and family were diagnosed in stage one, you'll probably all raise your hands. We always treat with surgery and radiotherapy. Here, we have the molecular surgery where you can be as efficient as surgery without removing your eye, removing your bladder, or maybe cutting half of the esophagus.
In my mind, given the data that we've seen in uveal melanoma, this just becomes a question of finding the right dose for the right application. Do you think that's fair?
It is fair. Obviously, the bladder cancer opened a remarkable opportunity for us, right? Initially, just with ocular oncology with 66,000 patients, that's a multi-billion dollar approach where there's no competition. We can get the market. The translation into these broader oncology indications in early stage local frontline approach, where also we don't compete with metastatic disease, it's so unique and so big. We think that, again, the bladder cancer just unlocked that option. For us, it's obviously we need to remain focused and bring in value up to the finish line. That just shows you the potential power of the technology moving forward.
In the last minute, can you remind us of your cash position and then maybe what to look forward to the next 12 to 18 months in terms of updates from the pipeline?
Yes. As we've been showing in our earnings release, we have cash into the second half of 2026. We are fully funded across all our clinical programs. There are key data milestones that we're going to show within, not just 12, but six months. The bladder data with three months durability should come within six months. The metastasis data showing, again, the power in the eye and across the board and across other solid tumors is coming within six months. Obviously, CoMpass and the phase III study.
It's a very exciting time. It's a very exciting technology. I think people are just starting to realize the potential. I'm very excited to be tracking the progress. Eli, thanks so much for giving us the overview today.
Yes. Thank you for inviting us to be here.