Thanks for joining us, Ellie. This is our. We saved the best for last.
Thank you so much. It's very exciting.
Last fireside chat of the day. We've got Aura, and Aura Biosciences is working on something that I think is gonna provide tremendous value to patients who have choroidal melanoma. This is something I didn't think could happen, but you can get melanoma in your eye, and the treatment options are pretty nasty, actually, and so I think this is a very welcome new approach. And then there's opportunity to expand into other diseases like bladder and stuff like that. So let me get all into that. I don't want to take the spotlight away from you too much, Elisabet, but tell us about the kind of the origin of Aura and how you got to the company to where it is today.
Yes, thank you. It's a pleasure to be here. So Aura spun out of the NIH, and the technology is based on virus-like particles that can be conjugated to multiple types of drugs. And so the class of drugs that we're developing are called virus-like drug conjugates, which is similar to the concept of an antibody drug conjugate, but instead of just an antibody delivering a drug, we have a virus-like particle that has a dual mechanism. One is the targeted cytotoxicity, and the other is the immune activation, and so it's a very new opportunity for the treatment of cancer, and of course, we can talk about the different indications that we're going after.
Okay, great. So we talked about the VDC platform. Give us an overview of kind of your development strategy for bel-sar at a high level.
Yeah. So bel-sar, initially, we thought this new class of drugs, we would go for early-stage local cancers where there was a high unmet medical need, and it would be a niche approach, but at a big opportunity for patients and a way to show the proof of concept that this novel class of drugs work. So that's the reason why we initially decided to initiate clinical development in ocular oncology. And it happens that ocular oncology is a huge unmet medical need, especially choroidal melanoma, where, as you said, there is cancer in the eye, it's diagnosed early, and we can make a big difference by treating with a better-targeted option that preserves vision. So that's the initial positioning. That doesn't mean that this class of drugs can only work in eye cancers.
As you said at the beginning, we think that this has a great opportunity to be early-stage local disease treatment for many other types of cancers, starting with melanoma in the eye, but moving into early-stage bladder cancer, potentially early-stage head and neck cancer or other esophageal. All cancers that are treated or diagnosed early with poor treatment options, that's where we could probably play a big role.
Great. So tell us a little bit more about choroidal melanoma. I feel like it's an area that really kind of needs a little bit more attention, and there haven't been a lot of drug targets there, so people haven't really focused on it. But I think it's a very important area. So tell us, like, who gets it, how many people, who treats it?
Yes.
What are the standards of care today?
Yeah. So first of all, the anatomy. What is the choroid? The choroid is 90% of the uvea, so a lot of people may have heard of metastatic uveal melanoma. Uveal melanoma is a cancer that starts in the eye, and the choroid is 90% of the uvea. So most of the uveal melanoma is choroidal melanoma when it starts in the eye. And this is a disease that it's diagnosed early, which means that 80% of the diagnosis is when the disease is not yet metastatic. So what an opportunity to treat early stage a disease that is diagnosed so early? Unfortunately, today, there's nothing that can be given to these patients. There are no drugs approved for the early-stage treatment, and we treat patients with radiotherapy. And what happens when you put radiotherapy in the eye is that you blind patients.
Not only that, but you create dry eye for the rest of your life.
Oh.
You have glaucoma, you have a number of radiation-related morbidities. So it's a really tough treatment. What happens is that patients actually delay treatment or say like: Well, maybe... Or it's a dilemma between the patient and the physician. So that's where the unmet need is. That's an enormous opportunity for a drug like us to capture all that early-stage disease. Patients will end up today metastasizing 10 years later and outside of the eye, then metastatic uveal melanoma is what we're now have Keytruda and other drugs that are trying to make an impact in the disease, but it's a very opposite end of the spectrum. The early-stage disease is many more patients. We're currently blinding patients. There are no drugs approved, and that's where we could make a big difference.
How many patients are there with early-stage choroidal melanoma?
Currently, there are 11,000 patients diagnosed every year in the U.S. and Europe, and 80% of these 11,000 are, like, early stage, would fit into the target population that we would want to treat.
How many-
We're talking about 8,000-9,000 patients.
Who treats these patients?
So the other opportunity is exactly that. Only 100 ocular oncologists between the U.S. and Europe. In the United States, there are only 50. So imagine all of these patients that are diagnosed early, that are treated locally with physicians that like to keep their patient, they don't treat the metastatic disease. There are only 50, and most of them are already working with us or familiar with our drug. We're hoping now that we're launching the phase 3 to involve as many as we can so that they are part of the development of the potential first drug that's ever gonna be approved in this, in this front, frontline treatment.
So you have a pretty good sense already that bel-sar works. I know you're in a phase 3, and it's fairly de-risked. Walk us through the phase 2 data.
Yeah.
What did it show?
Yeah. So we have run a study that just actually presented at the American Academy. And so we, with the same exact patients that we're gonna be dosing in phase III, with the exact route of administration, which, as you know, is suprachoroidal, and then with the same treatment regimen, we saw that in terms of the two endpoints that are critical for approval of the drug, and now, as you know, we have an SPA, so I can say that in writing, we have that is tumor control and visual acuity preservation. So in terms of tumor control, what we saw is that in the phase III eligible patient, what we're gonna be using in the study, we have 80% tumor control.
So out of 10 patients, only 2 failed, and they failed very late. If we look at the subtherapeutic regimen patients, those that would look like the sham treatment or, you know, equivalent to natural history, the majority failed, so only 20% stayed stable for, like, 12 months. So there's a big differences in those response between the subtherapeutic and the therapeutic that now is clearly demonstrated, and it's durable. That it's paired with the visual acuity, because we don't have any visual acuity or rarely any visual acuity loss compared to radiotherapy. As I said, radiotherapy blinds patients. We have only 1 patient with VA loss, and that patient lost only 18 letters, compared to an average of 40, 50, 60 letters. That's the definition of blindness.
So again, an incredible good efficacy in terms of controlling or stopping the growth of the tumor, like radiotherapy, like the standard of care, but on the other hand, an incredible safety with visual acuity preservation that the standard of care doesn't do. So obviously, why choose radiotherapy first if you have something that works just as well that preserves vision? And that's our value proposition.
The two patients that didn't have a response, tell us a little bit more about those?
Yeah, so those, we actually think that they responded, but, their progression was significantly delayed. They do progress very close to the 12-month endpoint. If you look at the subtherapeutic patients, they mostly all progress within 6-9 months. For phase 3, you know, it's a time to tumor progression, so it's not only the number of patients that fail, but the time of those patients to fail. So we've done an analysis of the phase 2 data in terms of phase 3, and we've seen that that actually plays a big role into the p-value that we're getting because, again, the sham should fail very quickly, whereas maybe we have 2 that failed. If they fail, they fail late. That actually helps with giving a very, very statistical significance.
So what does the long-term data look like, Ellie? So 'cause you wanna make sure if you're gonna kind of do all of this, a year later, you're not doing radiotherapy anyway. So what, what does the long-term data tell you about these patients who have an initial response?
Right. I mean, we don't have yet very long-term data, right? This is something that, as part of the FDA requirement, we don't need it for approval, but we need a registry data, where we're gonna be looking at these patients long term. What we can see is that the behavior of these patients, the curves are so flat that it looks like it's very, very unlikely that suddenly they all will start growing again. So we have to wait and see to have a little bit more follow-up data on the registry, but so far, everything indicates that if the response is so consistent and so flat, that they will continue to behave like that.
What is your follow-up so far?
The follow-up is 12 months.
Okay, okay.
Yes.
You mentioned that. Okay.
Yes.
So let's focus on your Phase III program now. Tell us about the design of that and how is it going so far?
Yeah, so the Phase III is a three-arm randomized and masked study. The key advantage is versus sham, right? And why can we run a study versus sham in oncology? The reason is that we're treating early-stage patients that currently the standard of care is observation. So the FDA now in writing agrees that we can run a study versus sham, which is really exciting for everyone, of course-
Right
... because the opportunity to show a difference between the treatment arm and the sham that is just in observation is, you know, highly the risk. The other thing that we have as a component of the study is an enrichment strategy. What does it mean? It means that we're enrolling patients that are actively growing, that have a little bit of documented growth. And why do we do that? We do that because then the probability of those, if they are in the sham arm, to fail quickly is very high. And that, as I said, it's the time to tumor progression and the number of events, so that will contribute into differentiating the arms very quickly. And that's exactly the same patients that we did in phase II.
So in phase II, we saw that you know, the subtherapeutic failed, the treated don't fail. That's exactly. That enrichment strategy will help differentiate the arms the same as we've seen in phase II. So those are the key elements. The endpoint, time to tumor progression as a primary, it's a big win, because again, if you have actively growing lesions, and the only thing that you're looking is that the progression between a treatment arm and a sham arm that's in observation, and our data shows that 80% respond, we think that it's highly likely that it will behave the same as in phase II.
Great. And just back to the phase II data, when will you have longer follow-up from those patients?
The study in phase II is 12 months.
The only follow-up that we will have is the registry.
Okay.
The registry obviously has its caveat. The registry is mainly there to look for metastatic outcome, right? The FDA wanted to make sure that we have a long follow-up of four years, so if there's a patient that, you know, has metastatic disease, we capture that information, because the idea is that we will have less metastatic disease, but from an FDA and safety perspective, we cannot have more.
This is a registry of your Phase II patients?
Yes.
Okay. Okay.
It's just that all the patients will go into this long-term follow-up, and it will be part of the BLA submission, but just as information on how they behave long-term, especially from a safety perspective. Now, we do have the possibility in some patients; it's not an obligation, but in some patients that opt to get into the registry to look at that long term, and we hope to have some information that we can say, "Look, of those that opted to get into the registry, look how well they, you know, the vision and the tumor control stays long term." But we cannot do like apples to apples because it was not all of the patients-
I see.
will go into the registry.
Okay.
But we will have some information that we will be, you know, obviously adding into the value proposition for the BLA.
Okay, I understand. Okay, good. So tell us about your bladder cancer. Actually, before we go there, walk us through the patient journey. So they, they get diagnosed with choroidal melanoma. They kind of go through the patient options, decide they're going to use bel-sar. Then, then what, what is the protocol? How does it work? What is the patient experience?
Yes. So, bel-sar is a drug that will be given in the office. It doesn't require an operating room, just little drops of topical anesthesia. You receive an injection, which is literally 2 minutes, and right now, it requires approximately 3 hours to allow the drug to distribute well into the tumor, and then less than 20 minutes of a procedure, that's the light activation. So that's it for one day, and that's for a treatment cycle, it's given in a month, 3 days, and then the study has 3 months. So it's basically during 90 days, you go 9 times to receive bel-sar. But that's it.
Without barely any pain, barely any side effects, with an in-office procedure that the ocular oncologists actually are driven to deliver, and it's supposed to be a curative treatment. It is possible that, you know, after approval, we could get a retreatment schedule, if possible, like a consolidation. But the reality is that for the majority of patients, we hope that this will replace the need for radiotherapy, the need for v- that replace that, that anxiety of having to watch for weight, and it would be the first line of treatment of choice-
Okay
... for early stage disease.
You have, I think, a little bit of bladder cancer data-
Yes.
-because that's the next indication going forward. So tell us about that.
Yes, the bladder cancer data is very exciting because, as I said, bel-sar is a drug that we think has the opportunity to provide value in early-stage local disease, where the cancer is diagnosed early, not yet metastatic. And usually, the current treatment options are either surgery or radiotherapy that are very, you know, damaging to the organ itself. So bladder is one of those cases. Like the eye, it's diagnosed really early, it's not yet metastatic, it's diagnosed by urologists, they see, you know, patient has blood in the urine, it goes to the urologist, and the first line of treatment for these patients is surgery. The problem is that this surgery is not very efficient. It's a local surgery, and patients recur, and they end up ten years recurring and recurring.
So imagine if, like in the eye, you can have a frontline treatment that, you know, you could give in this kind of like procedure way that urologists already love to do, like in the eye, injections in the eye, these injections in the bladder are something that they are keen on doing, but that it would prevent those 10 years of recurrences and need for additional therapies, and ultimately, the patient losing the entire bladder. So that's what we're trying to go frontline. Very similar positioning than in the eye, just that the market is much larger here because, unfortunately, there are many more patients. But we have the, you know, the safety is extraordinary, which is something that you never know with a new class of drugs, so very well tolerated.
Now the first patient in the light activation cohort, just with a single dose, we have a complete response. That is something also very exciting because we've never been able to see it in the eye. We have the exact same result in the eye, but we can't take the eye out, cut it in the middle, and show that it's all necrotic and dead. But here, we can. That's the opportunity in the bladder. We give the drug, then we do the surgery, and actually, there was no cancer. It was completely all that necrotic and a massive immune infiltrate, which is what we expect to see, right? This is a highly proimmunogenic type of cell death.
So it's a very exciting, very, very early data because it's a single dose, but, it fits fantastic into the treatment pipeline for these early-stage bladder cancer patients and in the urology practice. So if we can do that and consistently show this, then, you know, we're talking an overall different aura at that time.
Okay, great. So just in the time that's remaining, give us a snapshot of 2024 for, for-
Yes.
I know it's a year of execution, Julie and I were talking about.
It is a year of execution, but we, we're excited. Look, we have a phase III asset with an SPA agreement that's fully endorsed, that's now in the year of execution, right? That's with very good phase II data that the risk, the assumptions that we're taking. So that's obviously a study that will be running in the background, but we will be fully focused on enrolling. But there are two very exciting things in terms of new clinical data that we'll be able to talk, and it's related to our pipeline. One is the bladder cancer. We have now six patients, five for safety, one for the efficacy. Exciting. We need to have a few more. Mid-year, our goal is that we will have the full, you know, study enrolled, and it's a very quick readout.
So we will be able to, you know, have a nice package of data around this positioning and the path to approval for bladder. And then the other one that's very exciting, that both works on the oncology aspect that we were saying, but also ocular oncology from a commercial perspective, is choroidal metastasis, because patients with breast and lung cancer actually have metastasis that go to the eye. And these patients are treated for their metastatic disease by medical oncologists, but in the eye, by the same ocular oncologists that we are already working with. And so our drug is tumor agnostic. Our drug can work in melanoma. We've shown that it works in bladder. We actually think that it will work in breast cancer, and it will work in lung cancer.
So if we can show it in this kind of a small study in the choroid, we're gonna be able to say, "Now we have two indications in the eye." So the market for just the ocular oncology franchise, it's really robust. But then we can also say, "Look, now we have a drug that has shown efficacy in melanoma, in breast, in lung, and in bladder." That's a different oncology company again. So those are the two milestones that we're very excited while we're, like, laser-focused on the execution of phase 3.
Great. Well, thank you.
Very good. Thank you for the questions.