This is the JMP Life Sciences Conference in 2024. Kicking off our day in conference this morning is Aura Biosciences. My name is Jon Wolleben. I've been covering the story for 2, 2.5 years now, and we're pleased to have CEO Ellie de los Pinos, founder and CEO, joining us today to talk a little bit about the story and what to look forward to, through the next, you know, let's call it 12-18 months, because there's a lot going on. But Ellie, maybe to start, can you tell us a little bit about your lead platform, bel-sar, how it works and what you're going after at a high level, and then we can dig into some details? Yes, thank you. We are developing a novel class of drugs that are called virus-like drug conjugates. And the key is they have two mechanisms of action. The first one is a direct cell kill. Basically, we're delivering a powerful cytotoxic that kills the cell by necrosis. And then the second mechanism is an immune activation, because there is a virus delivering the cytotoxic payload. There is a natural adjuvant to the immune system, and the way we're killing the cancer cell is highly proimmunogenic. So it's a very differentiated type of drugs, and it's showing very good efficacy in phase 2, as we'll talk about. Your lead indication, choroidal melanoma, can you tell us a little bit about the background of that condition, who gets it, the prevalence, and how it's treated today? Yeah, so choroidal melanoma is it is a cancer that starts in the eye. So we call it primary choroidal melanoma because 90% of the patients are diagnosed early without evidence of metastatic disease. You basically the patient journey is that you go to the ophthalmologist with, you know, signs of visual symptoms and, or you have a nevus in your eye, so a black pigment in the back of the eye. And in some cases, these normal nevus transform. And they start showing signs of malignant transformation, like a little bit of growth or orange pigment and fluid, and that's a life-threatening disease. And unfortunately, for a disease that is diagnosed so early, the only alternative treatment today, or the only treatment, is radiotherapy. And as you can imagine, giving radiotherapy to the eye blinds patients. So patients have this early-stage, watchful wait that's very unsettling both for the patient and for the physician, because if you wait, you may increase your risk for metastatic disease. But if you're treated, you're blinded. So the opportunity for these patients is to have something better, targeted, that preserves vision and that prevents all the downstream problems of having, you know, your eye removed even, or metastatic disease. So it's a beautiful opportunity to make a difference for these patients, and unfortunately, there are no drugs approved. Can you tell us a little bit about the logistics of the operation, because I think that's also another important? Absolutely. So we're not talking about a regular, you know, treatment with radiotherapy in and out. The treatment of radiotherapy in the eye involves actually two surgeries. So it's called plaque brachytherapy. So you have this small lesion in the eye, and basically the treatment is to attach a metal plaque filled in with iodine seeds, radioactive seeds, for an entire week. You're radioactive for an entire week, irradiating your eye, your retina, part of your brain, and then another surgery to remove it. So as you can understand, such a very cumbersome treatment that removes the patient from the office, moves it to the operating room, involves the radiation oncologist, and has so many comorbidities for the patients, you know, it's not an easy thing to do. When you have such an early-stage disease, you're basically a healthy person, that suddenly has something in the eye that needs to be treated. And then how is bel-sar administered? bel-sar has a number of advantages. First of all, it's administered in the office. It doesn't require anesthesia. It doesn't require radiation. And it's something that can be done by the ocular oncologist who, at the end, are retina specialists. It's given in the morning with a supracoroidal injection, again, with a little bit of topical anesthesia, and then there is light activation, which means that with a standard laser that's available at all of, not all of, these ocular oncology offices, you activate it with five minutes light irradiation. So that is one dose of bel-sar. We usually have three cycles in three months, and that's it. It's supposed to be intended to be an acute treatment that cures the disease and prevents patients from having to require further radiation and, hopefully, prevents patients from further metastasizing, both because what I just said, the mechanism is not just a direct cell kill but also the immune-mediated CD8 T-cell activation that could prevent, actually, this metastatic disease. So again, an ideal target product profile for the early-stage intervention. Mm-hmm. of these patients that we were just saying have no drugs approved and just face the comorbidities of a very, you know, tough radioactive treatment today. You guys have produced some pretty compelling phase 2 data. Can you give us kind of the highlights of what you learned so far? Yes, the phase 2 data is really exciting. As I said, we presented an average of 12-month data for 90% of the patients. So the data is coming. The full data is going to be later this year. But what we learned was, first of all, that supracoroidal administration is the absolute right route for this drug and for this treatment. We administered it, and literally has very few, if any, side effects. Adverse events are grade 1, a little bit of anterior chamber inflammation that can be treated with topical drops. So that's very important because, as we said, we're treating early, early-stage patients, and we want to treat them in the office. So safety and the target product profile ideal. Secondly, efficacy. We are in the 80% efficacy comparable to radiotherapy. Radiotherapy has an efficacy range between 80%-90%, so we're right there to the standard of care. And the third, which is very important, is radiotherapy blinds patients. Well, we have 90% visual acuity preservation. And at the highest dose, with 3 cycles of therapy, even when patients have tumors right there at the fovea or the optic nerve. So, an impeccable safety really, really high visual acuity preservation, which is what differentiates us and will trigger the treatment early. Mm-hmm. Will, hopefully, as we said, prevent the use of radiotherapy for these patients for the future. So, you know, we identify one of these nevi or early choroidal melanomas, and the option today is, all right, wait and see if it keeps growing, and then you run the risk of it spreading, or we give you the plaque brachytherapy, and you persistently progressively will go blind over the course of, you know, most people are blind over. Mm-hmm. 4-5 years. bel-sar could come in, treat as effectively as the standard of care without that risk, or without, actually. Correct. Vision loss. Yes. Okay. And then tell us a little bit about your phase 3 trial, what you're measuring, where you are, and when we could get data? Yes, the study is enrolling is very exciting because it's a study that will support registration. We have an SPA agreement with the FDA, and it's a 3-arm study, randomized masked, sham control. So what we're looking is at two different doses, same regimen, 3 cycles, as we looked in phase 2, but two different doses, high dose and low dose, versus sham. And what are we going to look? First of all, we're looking at the efficacy measurement of tumor control. And it's very important that we are enriching the patient population in this early-stage disease for all patients that are a little bit growing so that we can see a difference of the sham patients continuing to grow and requiring the radioactive treatment within 6 months and the bel-sar patients not needing radioactive treatment. So it's a time-to-event in terms of tumor control or, or lack of progression thereof as a primary endpoint. The secondary endpoint includes not just tumor control but visual acuity, because that's, again, how we really win versus radiotherapy. And although it's a sham-controlled study, it's a great advantage for us to show that our therapy doesn't blind patients. So that's what we're going to be looking at: 100 patients. It's sufficient from this perspective of a safety database, and together with the phase 2 data, we think it's a strong package for approval. You're enrolling patients now, correct? Mm-hmm, we are. Tell us a little bit how that's going, timelines? Yeah, so we have a strong momentum, obviously, as mostly everyone else starts launching in the US. And we're on track with the number of sites and very, very active. I think we jumped over this before, but can you tell us a little bit about patient numbers opportunity for primary choroidal melanoma? Like, what's kind of the spread if these get identified? Where what your target? Absolutely. It's an incredible market opportunity, one of those that we rarely see these days. There are 11,000 patients diagnosed with this early-stage, you know, disease. 80% of 11,000 patients are diagnosed with early-stage disease. So we're talking about 8,000 between the US and Europe, but again, no drugs approved, radiotherapy is the standard of care, and the opportunity to treat with something that really preserves vision and has literally no side effects. So we think we have a, you know, a great opportunity to capture most of this market. And patients rarely would opt for radiotherapy ahead of bel-sar. But ocular oncology is not just that indication. And we think it's the opportunity is just much bigger than just the first one. The first one is already a billion-dollar drug. I'm happy to talk to you about choroidal metastasis and cancers of the ocular surface that, again, build up into this ocular oncology group of rare cancers that are seen by the same specialist and where we, starting as a first path to market with choroidal melanoma, we can get, you know, the first drug approved and really continue to add indications thereafter. One more on primary before we jump. Can you explain a little bit because there are two other companies playing in somewhat of the same sandbox, and I think there's some confusion. Immunocore has a drug-approved KIMMTRAK for metastatic uveal melanoma. Ideaya has got a program for neoadjuvant. It's a systemic chemotherapy. But can you talk a little bit about that differentiation you have versus those others and, you know, how these fit in? Yes, thank you for the question. It's a really important, because the reality is that early-stage disease is treated by ocular oncologists, and then metastatic disease is treated by medical oncologists. Very different disciplines. So when a patient arrives and it's like, as we were saying, the patient journey has most of the time early-stage disease, the lesions are really, really small. We're talking about mostly indeterminate lesions with some risk factors. Those patients are treated with the ocular oncologist, and that's where bel-sar plays. It's a in-office procedure, doesn't have side effects, can treat early on, and it's treated with procedures that the ocular oncologist wants to do and retain the patient. For some patients, less than 5%, they are diagnosed with later-stage disease. And, at the primary setting, they have a tumor that actually cannot even be treated with radiotherapy. It needs enucleation. So Ideaya is trying to do a neoadjuvant study. What does it mean? That those later-stage patients that have a very large tumor that is going for enucleation, they're going trying to treat it with a systemic treatment by medical oncologists, trying to avoid that enucleation. Again, a very small number of patients, but important for those patients because they likely, at that stage, when the tumor is so big in the eye, they may have some micrometastasis that warrant systemic chemotherapy. And obviously, if you, unfortunately, have metastatic disease, that's where both of those companies really play a role, either KIMMTRAK or, you know, darovasertib in combination with crizotinib. So very different opportunities, very different the types of patient, the stage of the disease is dramatically driven and different, and also the ocular oncologist versus the medical oncologist. It's a very different discipline. So again, we don't think that one cannibalizes the other, and we're all hoping to avoid radiotherapy and surgery. We're all hoping to preserve the organ, preserve the vision, and avoid those horrible interventions for a disease that's diagnosed so early. So those two programs are going for later-stage disease, more advanced, but, you know, smaller opportunity than what you guys could target because you're going to have the new incident population each year. And if your bel-sar is successful, that would actually limit the opportunity for those downstream. Potentially. Our hope is that by treating everyone early-stage, there's going to be less metastatic disease, and hopefully no one comes to the ocular oncologist with a 7- or 8-millimeter lesion. We're treating 1- to 2-millimeter lesions, the tiny, tiny ones. That's 90% of the patients, you know. So we really want to avoid patients losing their eye and metastasizing. And look, it's not rocket science. If you treat early, the outcomes are better. Mm-hmm. We wish we would be able to treat every single cancer in stage 0, 1. And then I wanted to jump to bladder cancer, which, you know, you guys have some data coming midyear. So can you tell us a little bit about the opportunity there, what you're studying? And then there seems to be a lot of investor interest in this space, particularly and you guys have been here for many years, so it's not, you know, all of a sudden you're jumping on board. But tell us a little bit about bel-sar's opportunity and what you'll be showing us around midyear. Yes, so in bladder cancer, it's actually really interesting, the parallel, because it is a disease that is also diagnosed locally. And the same as I was explaining, early on it's treated by urologists. Like, we treat the ocular cancers by ocular oncologists, not by medical oncologists. When it metastasizes, it's a different disease. So the early-stage bladder cancer has gotten a lot of attention because there are many more patients. The same as in the eye, early diseases have this funnel of patients that usually are treated with just surgery, and that's the case with bladder cancer. You know, you have an early-stage bladder cancer. It's diagnosed by blood in urine, and the first, you know, path for a urologist is to do what's called a TURBT, which is a surgery. The unmet need in that early stage of the disease is that surgery is usually not clean enough, and it recurs. Usually, patients will be even up to 10 years in this recurrent cycle. Ultimately, patients end up receiving BCG and adjuvant treatment and trying to prevent the loss of the bladder with cystectomy, very similar to the concept of the eye, right, trying to prevent the eye loss. In our case, the same as in the eye, we have the opportunity to treat very early with something that not only can have a direct cell kill but can have that CD8 T-cell response and prevent that recurrence. Not only that, we can in the case of the eye, we're preventing radiotherapy. We think that here we can prevent the surgery. The surgery, in the case of bladder cancer, is done in the operating room. If you think about the average age of these patients being 60 years old with quite a number of comorbidities, to go into the OR for just a tiny surgery to remove an early-stage lesion, shouldn't be the standard of care. So we are trying to position and again, hopefully the data will support it, but we think that we can position the drug early on, like we're doing in the eye, where most patients we're calculating 80,000 patients come with these papillary lesions that are recurrent and that actually, instead of sending them to the OR, the urologist now would be able to treat them in the office with something that has no biohazard risk, that is very easy to basically, you just need gloves to. Mm-hmm. To administer our drug, but has the same potency in terms of immune activation as a replicating virus while not being a virus. Mm-hmm. A beautiful target product profile for this early intervention where imagine the number of patients, and the opportunity is huge in this case. We're very excited. There's a lot of investor interest, obviously. The KOLs are really interested in this novel modality, first of all. Secondly, the opportunity, yes, to treat in the office. Yeah, I think the continuity of care from a patient-physician perspective is important, where the urologist can keep track of the patient, what's going on. And then also there is probably some downstream economics for them of doing the in-office procedure as well, which, you know, is not something to ignore down the road. So you have data coming. Can you tell us, you know, how many patients, what do you want to see, what makes you excited, as far as what, you know, data we'll get? Yes, so we have the study is approximately 20 patients, and the majority will be non-muscle invasive bladder cancer. We didn't want to exclude muscle invasive bladder cancer because we think the drug can play a role there, but the majority of the data will be in the NMIBC space. You know, in this study, it's a window of opportunity study. What does it mean? That we're treating and then removing the lesion. So in this case, even though we, as we said in the first patient, there would not be a need for surgery because we had a complete response with 1 single dose. So in that case, we would have obviated the need for surgery. But the study is designed that every single patient receives the drug and then, regardless, gets the surgery because that's a great way for us to see with histology that the drug works as we believe it, it does. And so it's a very powerful study because it will allow us, first of all, to evaluate, yes, safety and feasibility, but also tumor response. And what do we mean? Not like a phase 2 or a phase 3 with durability of response or even three months, but with very accurate assessment of what happens after treatment. Does the tumor shrink? Does the tumor, you know, are there, you know, immune cells there? Can we do a, a panel of types of immune cells that, that we can absolutely say, "Yes, we have a CD8 T-cell response against the tumor"? It will be a really, really good step forward, because it's a novel type of treatment. For this disease to be able to have that, it will inform then where do we position the drug, what's the design of the phase 2, and how do we get it approved. So that data's midyear. And then we're in the last kind of minute or two, can you just touch on, you know, you have more, more coming through, choroidal metastasis, so tumors that spread to the eye from other organs, and then also ocular surface cancers, which you just had some preclinical data at ARVO the other week. Can you tell us a little bit maybe about where those are in development and then those potential opportunities in terms of maybe patient numbers? Yes, our ocular oncology therapeutic area is just really, really exciting. So we have 3 indications and collectively 66,000 patients. Where there are no drugs approved, they're treated by 50 ocular oncologists in the US and 50 in Europe. Imagine the opportunity there where we're in phase 3 already for choroidal melanoma. So the other 2 indications we have much higher incidence than choroidal melanoma. We're in phase 2, so we're going to have an open IND, and we're going to be dosing patients this year, as we said we were going to do, in choroidal metastasis. That's mainly breast cancer patients whose metastasis go to the eye quite early, and unfortunately there are no treatments, and we blind these patients. Quality of life and vision, while yes, they have metastatic disease, and we are not trying to treat their metastatic disease, we're trying to treat the local disease much better while they preserve vision. So it's a it's a big unmet need and something that I'll we believe will allow us to go very rapidly into a, a registration or trial because, again, we have so much experience with the drug. It's the same physicians, the same route of administration, and actually the same drug. So that's choroidal metastasis. In cancers of the ocular surface, it's just a third. With again, it's the ocular oncologist telling us, "Well, we're seeing that the drug works. Please develop it in these additional indications," because we see these patients, and we see a lot of these patients. Mm-hmm. And last question, just given the audience, can you remind us of your cash position you just reported recently and kind of the runway that provides in terms of timing and then the data readouts you'll have? Yes, we have a very strong balance sheet. So we raised capital, as you know, last year, and we have cash to the second half of 2026. So all of these milestones for all our programs, are within that cash runway. The most immediate one, phase 2 full data readout of the choroidal melanoma this year, early data from the choroidal metastasis this year, and the phase 1 data from the bladder cancer this year. So within the year, we have three already. Very busy. I appreciate you taking some time to come see us today.