Good morning and welcome once again to TD Cowen's 6th Annual Oncology Innovation Summit, Insights for ASCO and EHA. I'm Phil Nadeau, one of the biotech analysts here at Cowen, and it's my pleasure to moderate a fireside chat with Ellie de los Pinos, the founder and CEO of Aura Biosciences. Ellie, maybe first I'll kick it over to you. Could you give a brief state of the company overview, biggest strengths, biggest challenges, and what does Aura need to do to create shareholder value over the next year or two?
Yes, thank you, Phil, and good morning, everyone. It is an exciting time for Aura. As you know, we have a late-stage asset in phase III clinical development for ocular melanoma, and that is our key value driver. In general, we are in late stage in our pipeline for ocular oncology. One of the key opportunities is that we have, you know, a number of clinical data readouts in that ocular oncology therapeutic area. First of all, we have obviously the CoMpass study. It should complete enrollment this year and have that top-line data potentially early 2027, if not late 2026. We also have two additional indications in ocular oncology. By the time that we read CoMpass, we have phase II data in metastasis to the choroid, which doubles the market opportunity. We are initiating clinical development in cancers of the ocular surface.
If you think about it, it's a late-stage asset with a potential market of 66,000 patients in phase III late stage with three indications that are highly synergistic: opportunity for orphan pricing and rare disease. That is our, you know, biggest opportunity, and we're very excited about that. The other program, as we'll talk a lot, is our bladder cancer program. That study is a phase II study that has just started. We have a new formulation that's going to differentiate the two areas, so ocular and bladder, very distinct products from now on. That's exciting. That's early, and we'll talk a lot about that, but that's our fourth program in clinical development. A lot going on.
Maybe we'll start with bladder cancer. Can you describe the design of the phase I trial? In particular, what's a window of opportunity study mean? Then secondly, data were released in March. Could you provide a brief overview of that data?
Yeah, so the opportunity and the design of that study was that very quickly, from literally taking an ocular dose and ocular volume, we were able to get into this complete new indication by giving the drug just once before standard of care, which is in this space, as you know, is surgery called TURBT. So that's the opportunity. Very quick, you get the possibility of seeing if it's feasible and some early readout on efficacy and safety. The negative is that by design, it's a study that does not have durability of response, right? It's a short study, quick. It allows you to have a signal, and then it allows you to move quickly to phase II. That's a design, and it's important because a lot of people ask as well, the data is great. What about durability?
The study was not designed for that, but the data was extraordinary. Usually, for those kind of studies, you just really look for signals of visibility, safety, and some biology. We had, you know, in the intermediate risk population, especially with literally one dose suboptimal volume ocular dosing, we got four out of five CRs. That is remarkable. Obviously, it is very exciting because it means that definitely we have a drug that warrants further investigation in phase II to find what is the right dose and treatment and durability to play a role in that disease. That is, again, that is the snapshot of what we had: a very strong signal, both intermediate risk and also in high risk, and now a phase II that has just started.
Maybe diving into the efficacy a bit further, some of the biomarker data were particularly impressive to us from the study. Can you describe the biomarker measures and what was shown?
Yes, we have, as you know, a unique mechanism of action where our drug works when the tumor is present. It's very highly cytotoxic, but very highly pro-immunogenic, meaning that we have a strong immune activation. That is meaningful because that immune component is what should, especially if you use the drug first, front line, should give us that durability of response. We are able to measure that, as you say, with a biomarker assessment because the design of the study was such that we get tissue out of treatment and we can do immunohistological staining to show, okay, what are the immune signals that we see there? What was incredible was that in just seven days, obviously with those kind of robust CRs, we saw that it was a very strong immune activation, both CD4 and CD8 T cells showing signs of adaptive immunity.
As you know, the key that everyone dreams is, can you treat safely, early, local, and generate that long-term adaptive immunity so that the tumor does not come back? With our biomarker data, we know that that was happening just with a little single dose. It is very exciting to see the full potential of full multi-dose dosing on what that could mean for the key and med need in this disease, which is durability, which no one has yet been able to tackle.
What about on the adverse event or toxicity side? Anything notable? Anything concerning?
That's another advantage of our highly targeted and safe approach. We literally only have grade ones in, you know, one or two patients. We don't have a single grade two or grade three adverse events. If you put the risk benefit for a front line treatment, that's what you want, right? There's no trade-off. You give it first. Why wouldn't you give it first if there's not any kind of trade-off from a safety perspective? It's so well tolerated. It can be done fast in the office. Doesn't need general anesthesia. You do it first. You have that immune response that should translate into durability. Later on, you want to do surgery. You want to do multiple adjuvant treatments. Sure, but you should do us first.
You referenced the ongoing phase I/II trial or the phase Ib/II trial. Can you describe the design of the study and how it differs from the phase I?
Yeah, so this is a key study to look at durability of response, right? This is no longer a window of opportunity. This is a more classic design, like seen by others, where they say, what is the complete response rate at three months, at six months, at 12 months? We will be able to generate that data so that then you can compare us to other treatment modalities. We are in a unique modality here because really, as you think about upfront treatment, there is really no one else that is done before the surgery. Mostly everyone, by concept, is adjuvant treatment, and adjuvant treatments are after the surgery.
Our study design is before surgical intervention, either as a standalone treatment, which would be immune ablative, meaning that the data is robust enough that you do not need to go to a surgery, or as a neoadjuvant, meaning that you give our drug first, then you do surgery. It is very important because our drug is not going to work if the tumor is removed, right? It is not an adjuvant treatment, and we do not compete with any adjuvant treatment. The study is designed to evaluate these two modalities, immune ablative or neoadjuvant, and to look at the durability of response. It will have two cohorts, the high risk cohort and the intermediate risk. You will have two groups where you are going to see the results.
That's, again, important for us because early on, we saw very strong signal in intermediate risk, but we also saw with very low dose, good signal in high risk. There is no reason why we should discard high risk from phase II dose exploration. That's why the study is looking at both intermediate, high risk, and these two modalities, immune ablative and neoadjuvant.
When does our estimate initial data could be disclosed?
Yeah, so we're guiding that our initial data at three months, right? That's a quick readout, is an endpoint that's very well established in this field by the FDA. We could get some signs of three months durability before year-end, but the majority of the data of our study is going to be in 2026. The most important is the 12-month durability, right? That's where we should clearly differentiate, and that will be at the end of 2026. We expect to have the study fully enrolled this year. Twelve months from then puts us at the back end of 2026 for some good solid 12-month data.
How will you determine the recommended phase II dose? Will that be mostly on the 12-month durability data, or are there other key metrics?
I think that we will know earlier because the study will give us that, you know, the three, six, nine months, it should already tell us what is the right dosing regimen and whether we need to further escalate. You know, with the data that we currently have, which was such a low volume and low dose, we do not think that we will need to escalate dramatically, right? That is the advantage that we have. That is why it is an expedited kind of dose escalation. What is important for us is to really look at two cycles so that we can truly optimize the immune response. That is the key differentiation. We are not a chemotherapy where our drug really will differentiate and work well in this patient population if we can get that immune response as high as possible.
That is the key for us, that kind of prime boost and two cycles to see if that can get us, with the biomarker assessment, the right immune profile.
What would be the next steps in bladder cancer? Do you think you could move right to a pivotal study or would a phase II be necessary?
No, the idea is that this study is robust enough that it should give us information on how to design a phase III study, either for intermediate risk or high risk, and enough data to go back to the FDA and discuss with them. This is a complete new approach, right? No one else is doing neoadjuvant treatment in intermediate risk or high risk. It will be very exciting to have the data and be able to agree with the agency on what's the best path to approval.
You've referenced this briefly in your opening remarks, but how would you size the market for bel-sar in bladder cancer, particularly in the neoadjuvant or front line setting?
As you know, the earlier you go in a front line position, the bigger the market, right? Just in the U.S., we're talking about 80,000 patients in intermediate risk. And those kind of patients would favor dramatically from a safe drug that doesn't have any grade two or three risks that can be done in the office, that doesn't require getting into the anesthesia. That is a huge market opportunity. We also see the opportunity of being neoadjuvant or front line in high risk because, unfortunately, what we're seeing is the durability of response remains the unmet need. It's not that the other drugs that are providing successful data in phase III are solving that. We see the Kaplan-Meier's going down significantly at 12 and 24 months.
There is the opportunity, especially if you're not adding toxicities and if you're doing something at a different treatment paradigm, which is front line, that you could potentially play a big role in those other stages of the disease. Again, the market could be very, very big, and we don't think we compete because, again, we're not an adjuvant treatment.
Great. Maybe turning to choroidal melanoma, bel-sar's phase II most recently produced data at the Retinal Society meeting. For those less familiar with the program, can you briefly summarize the phase II that supports bel-sar's pivotal development?
Yeah, it was a very robust phase II data set. What we had was, in terms of efficacy, 80% tumor control, meaning 80% response that was durable for 12 months. Again, it's important to look at that because we give our treatment in the eye also front line only for the first few months. We don't treat again, and these responses are durable at 12 months. 80% efficacy, very, very strong. From a safety, which includes also visual acuity, in this disease, visual acuity is actually an efficacy endpoint. We had 90% visual acuity preservation.
This is important because what we're trying to do in front line approach in any of the indications that we're going is to do something as good as the surgical or radioactive interventions, but really so safe that preserves the organ function so that you would choose that first before removing the bladder, removing the eye, or radiating the eye and leaving you blind with blindness. That was a very important data set, 80% tumor control, 90% visual acuity at 12 months.
You referenced the pivotal trial in your opening remarks. Could you briefly discuss the design of the trial? What arms are being tested and how many patients are being enrolled?
Yes. As you know, we have a SPA agreement with the FDA, and that is an advantage because by default, what we are doing is a different positioning. It's front line, it's early stage. It's not metastatic disease, it's not late stage. We wanted to make sure that there was an agreement with the FDA in terms of the endpoints and the design of the study. We are randomizing treatment to sham. What does that mean and why sham? If you are thinking about treating early stage in this disease, there's no real treatment option. There's no competition because what we do with these patients is watchful wait. The intervention that's available is radiation and that leaves you with blindness, and patients and physicians don't want to blind their patients. By default, by going early, we can compare to sham.
That was agreed with the FDA. It is a study that is randomized, masked, meets all of those regulations from the agency to support approval. It is really a red carpet from a development perspective because if you have a drug that works 80% with 90% visual acuity preservation and you compare it to sham, you know, our primary endpoint is 99% powered. It is a very robust study to support approval and that has the SPA endorsement to align with the agency on those endpoints that will support it.
What is the primary endpoint and how will the data from that endpoint resonate with physicians?
Yeah, so the primary endpoint is a time to tumor progression. It's a pure oncology endpoint, which is important because that's aligned with the FDA and EMA. What does that mean? It means that you have patients that have small melanomas and they're actively growing. If you're a patient in the sham arm, the treatment obviously is sham so that patient will continue to grow and meet the threshold for progression. In the treatment arm, patients will not grow, right? The tumors will be completely arrested because we have 80% efficacy. The time to tumor progression is not just a landmark analysis of how many failed at 12 months, it's the time to failure. It's a very beneficial endpoint for us because what we've seen is that we have 80% tumor control, right? Very few patients fail, but even those that fail, fail very late.
The Kaplan-Meier, as we've plotted the phase II data, gives us a p-value of 0.0001. Very, very good p-value. That's what we expect to see as a time to primary analysis in the phase III study.
A key secondary endpoint is a composite of time to tumor progression and time to visual acuity failure. How important is that secondary endpoint for regulatory approval and commercial adoption?
It's important, especially for us to be able to include vision in the label, right? We have an extremely good drug that preserves vision. That's the value, right? It's not that it just works and leaves you blind. It works and preserves vision. Having visual acuity as part of that composite endpoint is a big win. The reality is that they're nearly overlapping. The time to progression or the time to tumor progression is the big driver of the differentiation between the two arms. We have a few events of vision loss potentially in the treatment arm, and maybe we'll have one or two events of vision loss in the sham arm. The reality is that it's just mainly driven by the time to tumor progression, and it allows us to be able to say we have a drug that works and preserves vision.
As you know, the phase II data were really strong. I guess one debate among investors is, what are the risks to the pivotal study? There's none that seemed obvious to most people. How would you characterize the risks to the trial in your mind?
Of course, we've discussed all the factors that they're risked, right? The fact that it's versus sham, the fact that it's a very robust phase II data, it's very safe. The key is more on us having the right patients enrolled because we want the patients in sham to fail quickly so that the two arms separate quickly. As such, we have to have this enrichment strategy for actively growing lesions, and those have to be at the very same moment of kind of growth rate so that, you know, again, the two arms will separate. It's more of an enrollment strategy that is important not to deviate from that and have the right patient and have the number of sites and all the right things so that the study is protected.
I think that once we complete enrollment, that risk will be off the table, and I think that that is a very highly powered study for success.
Can you remind us of the timelines again? When do you think you'll complete enrollment in the study? What does that imply about the timing of the top line data release?
Yes, at our latest earnings, we reported that as early as the end of 2025, we anticipate completing enrollment. As you know, it's a 15-month endpoint, so that puts us at the beginning of 2027 for top line data.
Perfect. Can you describe the global incidence and prevalence for choroidal melanoma, how are patients typically diagnosed, and what is the treatment paradigm today?
Yes. We've done a lot of work to identify the incidence of this rare disease, and it's 11,000 patients, mostly in the U.S. and Europe. This is a Caucasian population disease that are diagnosed. The opportunity, though, is that 80% of these patients are diagnosed in what we consider the early stages of the disease, which means that are pre-metastatic. That's the opportunity to treat early, treat front line, avoid the need for systemic approaches, and really try locally with something that is safe and can completely cure locally that disease. If we talk about that positioning, it's really we're talking about 8,000-9,000 patients and truly no competition because for those early stage disease where the disease is, you don't have risk of metastasis or you don't have risk of the disease really being so big that you have to remove the eye.
The safety, the local approach, the ocular oncologist to be able to treat as early as possible is what will define the commercial success. We think that our target product profile is ideal for that front line approach. Really, again, you have the opportunity for rare disease pricing without truly competition and being the first ones to get hopefully the drug approved will nicely get us that commercial anchor that then we're not just an ocular melanoma company. Remember, as I said at the beginning, our drug, which is tumor agnostic, could have an indication in melanoma, cancers of the ocular surface, metastasis to the choroid, all of those cancers that happen to be in the eye that are treated by that small of ocular oncologists, that's the opportunity for this drug. That is unparalleled. None of them have competition.
All of them, or the majority of them, are rare. So we're very excited that that is what's going to put this company in a very unique value proposition for investors.
Could you go into a bit more detail about your thoughts on pricing? You mentioned orphan disease pricing. There's a relatively wide range within the orphan space. What are some proxies or some parameters you're examining as you think about pricing?
Yeah, as you know, you know pricing is not for the faint of heart these days. What I would say is like, look, we're lucky because a recent proxy of a very successful company that we admire very much is at Immunocore, which has a successful drug for metastatic disease. As you know, that's not our market or we plan to go to metastatic disease, but they have priced and successfully launched the drug for these patients at a very high ultra rare pricing, right? If you calculate, it's approximately $1.2 million per patient per year. We think that that's probably the bookend of ultra rare pricing. We don't have to be at that very extreme to be a very successful multi-billion dollar franchise, again, because it is for us a value proposition. These patients are pretty young, 55, 60 years old. They have a lot of years.
Blindness is something that has a very high pricing associated with it, and we can prevent blindness for not just one or two years, but maybe for a decade. Very exciting value driver with the target product profile. With that anchor of benchmark of pricing, we feel comfortable to say ultra orphan corridor should apply for our pricing discussions with payers.
Maybe last topic, choroidal metastases. You noted a phase II going on now with initial data, perhaps by the end of the year. Can you describe the design of that study and what you'll be looking forward, what we'd be looking forward to advance bel-sar and choroidal metastasis?
Yeah, choroidal metastasis is unique for two reasons. One is and always is the main driver for our company. Is there an unmet need? Do patients need better treatments? As you know, patients with metastasis in the eye are treated by their primary tumor, which let's put, for example, is breast cancer. Unfortunately, for these patients, even though they have systemic medications, they all unequivocally get treated for their local eye metastasis, and the only treatment is radiotherapy. Again, is there an unmet need? Absolutely, yes. We don't want to blind these women or any patient that has now endured metastatic disease and has five, six very good years of quality of life, and they shouldn't be blinded because of the local treatment. The unmet need is high. The number of patients is high. It is the same ocular oncologist. What do we need to show?
Our phase II study right now initially was just breast and lung cancer patients because we thought, well, those are the majority. We're going to dose escalate and find the right dose. Let's do more of a tight inclusion. We've seen actually as we were launching the study that there are many other patients with other primary tumors, prostate, kidney, and why discard those which would support a broader label. Now is the time to try it. We decided to broaden the inclusion criteria. That's the key thing that we announced, and hopefully that will give us some early readout again where those escalating, finding the right dose. It's important for us not to exclude those other patients. By the end of the year, this study should give us proof of concept data.
Here it's the advantage that we have with this study is it's a quicker readout. Remember, in melanoma, because it's primary, there's that nevus, and we have to look at cessation of growth. It's more of a durability endpoint. Here, on the opposite, these are fast-growing metastases, and they grow, and by just the growth themselves, they kind of affect vision. If we can shrink these tumors, we will see potentially a benefit in vision, but also a very quick readout of tumor regression, which we couldn't see in the primary melanomas. We're excited. I think that, again, fast readout, broad opportunity to also see the translation of this technology across many other tumors because we're not launching a breast cancer study or a prostate cancer study, but by default, these are breast cancer and prostate cancer patients.
If we see those metastases in the eye responding, it shows you that you have a drug that's much bigger than just a drug for ocular oncology or non-muscle invasive bladder cancer. Potentially, that data will allow us to translate into the true value of the drug that we're working with.
Great. With that, I think we're out of time. I'd like to thank you for a very interesting discussion and best of luck with everything in the second half.
As always, it's a pleasure to talk to you, Phil. Thank you.