Okay, good afternoon, everyone. Welcome to the Jefferies Healthcare Conference. My name is Billy O'Neill, I'm with the Jefferies Investment Banking team. I have the pleasure of introducing Elisabet de los Pinos, Founder and CEO of Aura Biosciences, who's now here to present. Thank you.
Thank you. It's a pleasure to be here today. Let me introduce you to the company's highlights. As you know, we're developing a novel class of drugs called virus-like drug conjugates. The highlights are that we have now an SPA agreement with the FDA that really supports the regulatory submission for the bel-sar, who is our lead drug for the treatment of primary choroidal melanoma. We also presented at the American Academy of Ophthalmology just a few weeks ago, our phase II data that supports the assumptions for the phase III study, which is now powered at 95%, and the global study is in full launch. We expect to dose the first patient before year-end.
I'm also gonna present updates on our urologic oncology franchise, and we have the first patient that's been treated with just a single dose, showing a complete clinical response, and proof of mechanism with immune activation and necrosis seen by histopathology. Also, the FDA has allowed us to include not only non-muscle invasive bladder cancer, but muscle invasive bladder cancer in our study, and I will present some updates there. As you can see, our pipeline, we are in phase III for the early stage treatment of choroidal melanoma with a filing expected before year-end. We're also going to have our phase II study in choroidal metastasis, which is our second ocular oncology indication next year, and as I said, that we have an ongoing phase I study in bladder cancer.
So our novel class of drugs, virus-like drug conjugates, are similar to the concept of an ADC, but instead of an antibody, we have a virus-like particle that adds an innate immune activation of the immune system. We've also shown that it has a very specific targeting to cancer cells by binding to glycosaminoglycans that are highly sulfated by cancer cells themselves. And this targeting has been confirmed together with the NIH in a number of solid tumors. So we can really talk about a platform because we can treat rare cancers in the eye, we've shown and we will see the data in phase II for choroidal melanoma, as well as more prevalent cancers like urothelial carcinoma, without really changing the composition of the virus-like particle. So what is bel-sar, our first VDC in the clinic?
It was designed for the treatment of eye cancer. It is, as I said, a virus-like particle that's uniquely targeted to the cancer cell, and it's conjugated to a light activatable drug that's activated with infrared light. So the drug really is non-toxic. It can be safely administered. It binds selectively the melanoma on the membrane of the cancer cell. Once it's activated with light, it generates reactive oxygen species that break down the membrane of the cancer cell. The cell goes into necrosis, and it's a highly immunogenic mechanism of action with the liberation of damage-associated molecular patterns and the activation of CD4 and CD8 T cells. So what's the unmet need in early-stage choroidal melanoma?
This is a cancer that actually starts in the choroid, and the choroid is 90% of the uvea, which is the layer that it's constitutes the choroid, the ciliary body, and the iris. As I said, it's a primary tumor that it's diagnosed very early. It impacts 11,000 patients in the U.S. and Europe, and 80% of the patients are diagnosed early without any evidence of metastatic disease. Unfortunately, this is a life-threatening disease, and 50% of the patients will end up metastasizing in the liver. So this is the current treatment option. Despite the fact that early-stage choroidal melanoma is diagnosed without evidence of metastatic disease, the early-stage treatment is a very, very harsh radioactive plaque, that it requires multiple surgeries and leaves patients with a large, large number of morbidities. The most important one is blindness.
80% of the patients will be blinded with radiotherapy within the next five years after treatment, and it's irreversible. So what happens today, despite the fact that we said that most of the patients are diagnosed early without evidence of metastatic disease, patients defer treatment, and plaque brachytherapy is only given at the very, very end of this tail when the tumors really have no alternative or the patients have really no alternative. As you can see, there is a big demarcation between early-stage disease and the number of patients that are diagnosed early to those that metastasize. Patients metastasize 50% in 15 years, and there is a small number of patients that have metastatic disease. We now have systemic chemotherapy for those, but there's no treatment for the early-stage disease, and there is a very high unmet medical need.
That's exactly what we can do with our drug. We have shown that with suprachoroidal administration, it's an extremely safe route, allows us to give a very high dose of the drug. It's activated with a standard of care of ophthalmic laser, which is available in all of these ocular oncology services. The goals of treatment are the local tumor control equivalent to the radioactive treatment, with the opportunity to preserve vision, to avoid those radiation-related morbidities, and the opportunity, most importantly, to avoid metastatic disease and improve the quality of life for these patients. What does that mean from a commercial opportunity? Ocular oncology is a multi-billion-dollar addressable market that currently has no competition. We are the first ones who are ever positioned to have the drug approved for the first-line treatment option for primary choroidal melanoma.
As you can see, 11,000 patients a year, 80% of the patients non-metastatic... no drugs approved, just radiation. 100 ocular oncologists, basically 50 in the U.S., 50 in Europe, with a team of less than 20 MSLs, we can capture the entire value of the market. So where are we? We presented the data of the phase II clinical trial at the American Academy. The study is with suprachoroidal administration with the exact same patients that we're gonna include in the phase III study, that now has an SPA agreement. As you can see here, the clinical endpoints are the exact same as in phase III, that also have been agreed with FDA, and the study has two parts: a dose escalation and expansion.
The expansion, as you can see here with the dark blue boxes, is the exact same treatment regimen that we're gonna be running in phase III, and the dose escalation has subtherapeutic regimen that is equivalent, or we will use it throughout the presentation as if it was the sham, as the phase III is a study versus sham. So the primary endpoint that's agreed with FDA is the local tumor control. As you can see, there's a clear dose response between those patients that received subtherapeutic regimen versus those that received the therapeutic regimen of 3 cycles with suprachoroidal administration. Now, with 90% of the patients completed 12 months, this is a clear de-risking of the primary endpoint. What you can see here in the detailed analysis is, the subtherapeutic on the left-hand side in red versus the therapeutic on the right-hand side in blue.
There's a clear difference of—as you can see, what is expected to see in natural history is very much what you see in the subtherapeutic regimen, which patients continue to grow and meet the threshold for progression between six to nine months. On the opposite side, there is a very robust response to the treatment with the majority of the patients, 80% rep resulting in a complete arrest of growth and tumor reduction. 2 patients progressed and met the threshold much later than the natural history, close to the 12-month endpoint, giving an 80% tumor control rate. So this is paired with an extremely high level of safety, safety and visual acuity preservation. Across the study, we only had 1 patient that lost vision, and it's 18 letters lost, which is the threshold is 15 letters.
If you think about radiotherapy, patients treated with radiotherapy lose an average of 30-60 letters, which is the definition of blindness. So extremely high and unprecedented levels of visual acuity preservation, where the majority of the patients had tumors close to the fovea. And safety. In order to capture all that early-stage disease market, we have a level of safety for a cancer therapy in the eye that has never been seen before. We barely have any type of adverse events, grade one, that have no clinical sequela. They are treated with standard of care anti-inflammatory drops. In contrast, you can see what radiotherapy does. Patients that receive radiotherapy as a first-line treatment option have radiation retinopathy, glaucoma, dry eye for the rest of their lives, and vision loss blindness.
So obviously, there's a huge difference between a therapy that's so safe that you can treat without any trade-off, that preserves vision and has a similar efficacy as the standard of care. So what does that mean, and what has the FDA agreed that it will take to get the drug approved? As I said, we have an SPA agreement with the FDA that acknowledge there are no approved therapies so that we can have our drug randomized, our high dose of bel-sar randomized versus sham. We're gonna have an enrichment strategy, where we're gonna enrich for patients that have actively growing lesions, exactly the same as phase II.
As you remember, we had 80% tumor control in phase II and barely any tumor control in the subtherapeutic, which is anticipated to behave like the sham, which is a very, a very high power for 100 patients, which is the minimal safety database that's required. So if we look at the phase II data, in terms of the endpoint that's agreed for phase III, time to tumor progression, you can see that in the primary endpoint, we only have 2 events of tumor progression. If you remember, those happened very late at 12 months, versus the subtherapeutic regimen, which have most of the events of tumor progression between six and nine months. Only with 10 patients per arm, we have a P value of 0.0012. The key secondary endpoint is very similar.
It's just adding events, either of tumor progression or visual acuity failure, and as you can see, adding that additional event of visual acuity failure, we still have a very low P value to meet the key secondary endpoint based on the phase II data. So what's next? In our pipeline, the next very exciting program is in bladder cancer. And why do we think that bel-sar can play a role in bladder cancer? Because very similar to ocular oncology, in urologic oncology, we also diagnose these patients very early. We also diagnose them without evidence of metastatic disease, and they are also treated locally. Very similarly, ocular oncologists are very similar to urologic oncologists. They are, you know, procedure-driven, and they like to take care of the patients locally. They don't treat metastatic disease. The difference is the size of the market.
In urologic oncology, just in the U.S. for NMIBC, we're talking about 60,000 patients and 20,000 more if you add muscle-invasive bladder cancer. A huge unmet medical need, and if you look at the patient journey for these patients, for an NMIBC patient, the first thing is blood in urine, and patients are referred to the urologist. The urologist diagnoses the diagnosis of non-muscle invasive bladder cancer, and the first line of action is a surgery called TURBT. But this surgery is not a definitive treatment. This surgery recurs, and patients end up recurring for over 10 years. Patients will receive over 20-30 surgeries and end up receiving adjuvant chemotherapy with gemcitabine.
They receive BCG, which is now in scarcity and patients don't have access to, ultimately become BCG refractory, and then the only alternative is cystectomy, the loss of the bladder. So what can we do? How can we transform this disease? Very similar to the eye. In the eye, we're going frontline, early-stage disease, the same here, and we can give our drug, neoadjuvant to the treatment of surgery to prevent those recurrences and probably to avoid all of the, additional therapies that these patients have to go through. So what is the study that we agreed with the FDA? It's a first in men.
Obviously, we have a lot of safety and efficacy in the eye, so we had to do a small part one, which is just with bel-sar alone, without light activation, where we saw no treatment-related adverse events, no serious adverse events or those limiting toxicities in any patient, so extremely well tolerated. And we're very early in part two, but let me tell you the exciting data that we saw with just one patient, single dose. And I say this because it's single dose with the dose that we give in the eye, an extremely small amount compared to the size of these bladder lesions. So what is the design of the study? As I said, it's neoadjuvant. So a patient will come with a diagnosis of NMIBC. Day one, they will have a biopsy to confirm the diagnosis.
That same day, the patient receives the treatment with the exact same procedure that the urologists do for the biopsy, nothing additional. On day two, they will receive the light activation. That, again, is the exact same wavelength, the exact same laser that we've developed for the eye, nothing that needs to develop further for the bladder. It's given through a cystoscope. The study says that after seven to eight days, the patient can come back, and the study design was for the surgery to take place, for the physician to remove the lesion and then do histopathology, where we were hoping to see the signs of focal necrosis and immune activation. What happened was that when the physician went back to remove the tumor, there was no tumor. It was a complete clinical response.
There was still the surgery done on the surface of the bladder wall, just to make sure there was no carcinoma left behind. I'm gonna show you some images of the histopathology before and after. This is the histopathology before. You can see the image of the urothelial carcinoma. These are 1-2-centimeter lesions. They are not millimeter lesions like we do in the eye, but we treated with the dose in the eye, a tiny drop. And this is what we saw. There was no carcinoma left behind, not a single cell after 12 blocks of resection done, and there was massive necrosis and immune infiltrates. Is this surprising? Well, it is surprising because it's a single dose, but it's not surprising because we've seen this consistently in our animal models. This is how our drug works. It's an extremely potent drug.
It creates this proimmunogenic cell death, and the massive amount of immune infiltrate is a sign of a tumor or an anti-tumor response. So what we are excited about, this can really transform the treatment of bladder cancer. There was not a single adverse event in this patient. So you could see that this is a treatment that it's procedure driven, that can be given with safety, frontline, and in most cases, you can still do the surgery. The surgery is gonna be just confirmatory that there's no cells behind and there's a massive immune response. The trial is still enrolling, so we're planning to present data of this study mid-2024 while we're running the phase III for approval, with the expectation that if this data gets confirmed, although preliminary, we will have a discussion with a regulatory agency to design study for approval.
Thank you very much. If there are any questions, I'm happy to answer. Please.
Going back to the eye, could you maybe clarify the term? You're using tumor control in the eye. Does it shrink the tumor in the eye, or how should we think about that maybe?
Yes, there's a little bit of tumor reduction, but in the eye, why is tumor control? Because these lesions start with a melanocytic nevus, which is basically pigmented melanocytes that are normal, and there is a small part of melanoma within the nevus. So we effectively kill the melanoma, and we see a little bit of tumor reduction, especially in the first few months, and then it's, like, completely stopped, and there's no further growth. Because there is not such a RECIST criteria accepted in ocular oncology, we went with the definition of efficacy that's seen with radiotherapy, which is this definition of tumor control, because it was the standard of care in the ocular oncology community. So we went with that to the FDA, and they agreed.
They had a panel of experts, and that's what the local cure equivalent from an endpoint perspective is considered in that early-stage disease.
Will that be different for bladder cancer then?
It will be different for bladder cancer. That's very, very unique of melanomas in the eye because of the, the way they start. It's one or two millimeters from a nevus. Here, the squamous cell carcinoma papillary lesion is very different. It has a much more, like, active growth in the sense that you can see the regression. Again, this is not metastatic disease, so it's not seen by MRI, but it's a clinical pathological response seen by the urologist that can be measured. All right. Thank you very much.