Morning, and welcome once again to TD Cowen's Fifth Annual Oncology Innovation Summit. I'm Phil Nadeau, one of Cowen's biotech analysts, and it's my pleasure to moderate a fireside chat with Aura Biosciences. We have with us today, Elisabet de los Pinos, the founder and CEO of Aura. With that, Elisabet, maybe I'll hand it to you. Could you give us a brief state of the company overview, biggest strengths, biggest challenges, and what do you think Aura needs to achieve to drive outperformance over the next year or two?
Yes, thank you, everyone, thank you, Phil, for the invitation. So this year is our year of execution, and we're on track. Number one, we're well capitalized, and we have exciting clinical milestones coming up within the next six months. So obviously, there is a lot of investor interest on our time of presenting the phase I bladder data, which is coming up soon. But in addition, we have two other clinical milestones in our ocular program. The full phase II data readout of primary uveal melanoma in the fall, and then we also have the second indication in the eye, which is metastasis to the choroid, which is just about to start, and we expect some early data. So overall, you know, a great excitement across the programs.
I just want to point out that today, actually, this afternoon, we have a KOL event that's gonna talk about the overall opportunity in ocular oncology. It's at 2:00 P.M., and we're gonna have ocular oncologists from all over the world, talking about not just melanoma, but up to 4 different types of tumors. More than 60,000 patients without drugs approved, where we can make a difference. So that's exciting and just happening today. Now, you were asking about challenges and strengths, right? So I would say, the biggest challenge that we currently have is to navigate the clinical trial execution globally. That's not different than anyone else, especially when you're first in class, there has never been a drug approved in this indication.
But the strength on that end is that we have an incredibly active ocular oncology community that is so committed to bring innovation to these patients. You'll see it at the KOL event this afternoon, but the endorsement and just activity around the globe is really palpable. So we're excited with that, and hopefully, we can get to the Phase III readout very soon.
Before we dive into the individual programs, in particular, for those less familiar, could you provide a brief introduction to bel-sar, including its mechanism of action and the underlying technology platform?
Yeah, so bel-sar is in the field of precision therapies in oncology, and we have a dual mechanism of action. First of all, we have direct cell kill. That's very important, right? We kill... As long as the virus-like particle binds the tumor, it's gonna be consistently having a direct cell kill effect by necrosis, regardless of tumor genetics or, you know, different molecular pathways that may be altered in the cancer cell. And the second is a very robust immune activation, adaptive and innate immunity. And so it is these type of, you know, novel mechanisms that we think that can make a big difference, especially in the types of cancers that we're going after.
The next novel data event, release of new data will be from bladder cancer. We are getting a number of questions on that program from investors, so I thought we'd maybe start there. For those less familiar, could you describe bel-sar's, the design of bel-sar's trial in bladder?
Yes. So, this is a phase I study. We have fast tracked. We were very quickly moving from the eye into the urologic oncology space. And, what does it mean, a window of opportunity? It means that because these patients go through the standard of care, which is a surgery, we have the opportunity to give our drug first, and then with the surgery, which is the standard of care, get histopathological evidence of tumor response. So that is very exciting because it allows us to go really fast into patients that could be, you know, BCG refractory, BCG naive, even muscle invasive, and see across the spectrum of the disease if the drug consistently works. And it's an unequivocal evidence of response because you have the histopathological assessment, right?
And with that, we can just not see necrosis, as I was saying, direct cell, cell kill, but we can also see the immune activation, which in particular for bladder cancer, if we can show innate and adaptive immunity, it would be highly differentiated to anyone else in the space. So that's the, you know, the design of the study. It's 21 patients. 5, remember, we were just, for safety, we just treated them with bel-sar alone without activation. That is data that has already been presented. But then we have 10 in non-muscle invasive and 6 in muscle invasive, and we're eager to present that data, very soon.
In terms of the five patients that were treated alone, what did you see in those patients?
It was extremely safe, and most importantly, you know, we're going after a very novel approach, which is a focal administration of the treatment into the bladder, not intravesical, but really focal into the tumor. So that allowed us to say that the technique was feasible, there were no major, major problems to give it in the office, and it was something that could be done with the routine standard procedures that urologists do in the community urology. So no safety events, very easy to move forward into the second phase, where we're really looking at the, you know, at the mechanism of action and tumor response in the histopathological assessment.
... What do you hope to establish with the next data release? What, what would be considered proof of principle in, in your mind?
First of all, feasibility. As I said, we want this to be used routinely in urologists, in the community urologist office, and so the feasibility and safety is number one. The second is, if we show consistency of activity, both in terms of direct cell kill with necrosis and immune activation across the disease stage, that opens an enormous opportunity for development. We may decide one type of patient versus another, but initially, it's all comers, so that is a great opportunity for this type of study to then go to the FDA and say, "Look, we've established that the drug works consistently. Now, this is gonna be our focus for phase two.
I think you said, is it 16 patients that we'll get at midyear, or will you have somewhat, somewhat less than the midyear data release?
Yes. Look, we're still enrolling, so our expectation is that we'll have the majority of patients. You know, as I said, there are 10 in the nmIBC and 6 in miBC, so where we can see, you know, also the differences between those indications.
And when could we see a more fulsome release of the data?
Full- we expect to do it at a medical conference. As you know, that's where we hope to also foster the excitement of the urologic oncology community. So we haven't announced yet if it's, you know, if we're gonna release some data by a company event, and the full at a medical conference, we'll provide more guidance in the summer.
When could you provide the next steps following the current study? Would... is that also likely to come in the summer or after the full completion of the trial?
So look, usually you want to assess your full development plan once you have the full data. So we'll see. I think that likely after the medical conference presentation, we'll be able to provide, you know, the development path. We're still deciding when will that be.
It may be too early to understand this, but where do you think bel-sar could fit into the current treatment paradigm? You know, what's the standard of care, and that you think you could displace, and what are the limitations or unmet need in the indication that exists and could be best served by bel-sar?
Yeah, so we think that there's one very key unmet need, which is the problem of recurrence in the low-grade intermediate risk. And not only that is a big unmet medical need, but it affects the majority of patients. We looked at more than 80,000 patients a year just in the U.S., not to say in Asia and the rest of the world, with this type of, you know, low risk. It's not high risk, it's low, but so low grade, but with intermediate risk, like keeping recurring, recurring, and needing multiple surgeries. So what are the key benefits that bel-sar would have in this particular population if we were to choose this one?
First of all, it's the only focal therapy that has a strong immune activation against the tumor itself, because we're treating the tumor, and we're generating not just innate immunity, but adaptive immunity with CD8 T cells. The second is that this immune activation, that it's as good as a virus, comes without the biohazard risk because we don't have a virus, right? We don't have a replicating virus. All that potency comes with just a virus-like particle that's extremely safe. And the third is optimal for community urologists because now, instead of having to send all of these low-grade intermediate-risk patients to the OR and to receive a surgery called TURBT, we now can move all the management of these patients to the office, to the community urologist.
And it benefits not just the patient because it avoids anesthesia, but also the urologist because now they can manage it without having to send it and book the OR and having all that complexity. So for that population, which is, again, a very large unmet need and a very large number of patients, we think that the value drivers are, you know, optimal, and hopefully, we can provide those across the development pathway.
Maybe moving to the ocular indications, like you said, where you're gonna have a KOL event this afternoon. Maybe starting in choroidal melanoma, the most recent data were presented at AAO 2023 from the phase II trial. Can you remind us of the highlights of that data?
Yes, it was a very exciting time because, remember, we're launching the study, the phase 3 study, based on this data. We had 90% of the patients at 12 months at that time, and we showed that at the therapeutic regimen with suprachoroidal administration, we had 80% tumor control and 90% visual preservation. With an unprecedented safety profile, which positions this drug as an ideal frontline therapy for the early-stage treatment of the disease, right? Those patients that the disease is still local, it's not seen by a medical oncologist or an ocular oncologist, early-stage local approach, ideal target product profile. Clearly better than the intravitreal administration. We were able to reduce the posterior inflammation. We saw no SAEs, so again, a very clean profile to capture all that local upfront treatment of the early-stage disease.
So that's, you know, basically the phase II that launched the phase III. Obviously, as I said, this year, we have the full readout of the study. At that time, we had only 90% of the patients. We now have the full study completed, and we hope to present that in the early fall, and that, again, will be a reassurance that we're taking very conservative assumptions for the phase III.
... I think a key benefit of bel-sar is the side effect profile, the adverse events, and as you mentioned, the vision preservation. How does the data that you just described compare to standard of care?
Yeah, so we have very similar efficacy as the standard of care, which is radiotherapy, but we have extreme safety and visual acuity preservation compared to radiotherapy. So radiotherapy basically blinds patients, and it's a devastating upfront treatment because the patient is mainly healthy. He has these nevus with an indeterminate lesion in the eye, and you're offering something that not only blinds the patient, but then will give them dry eye for the rest of their life, glaucoma, radiation retinopathy, and, you know, even enucleation because the side effects of radiotherapy are so bad. So now compare these to something like bel-sar that can be given in the office, that has, you know, only one patient, and it just lost 18 letters. The radiotherapy, the vision loss is 40-50 letters.
So again, you know, with unprecedented visual acuity and safety, no one would choose radiotherapy first, right? So now all of those patients that are, like, in the early stage of the indeterminate lesion phase, where are in observation, they're not really treated today, now they will have an opportunity to be treated and not have that waiting for a disease that it's a life-threatening disease, ultimately. So it really is an, an ideal target product profile. We're very excited.
You referenced the pivotal trial. What arms are gonna be tested? How many patients will enroll? When will enrollment complete? What are the basic design features?
Yeah. So as you know, we have a SPA agreement with the FDA, and the key things that were negotiated and approved was, number one, number of patients, 100 patients to support the safety database, and that's very important. Number two, as a novel approach, a novel, treatment for a disease that has never had a drug approved, the key for us were the endpoints. So to have endpoints that are approved by a SPA are critical, and so the time to tumor progression as a primary, very clean, highly de-risked based on the phase II data. And then the statistical analysis plan, as you know, it's a time to event analysis with a log-rank test, which actually just, you know, helps us.
The phase II was a landmark analysis, but the phase III is a time to event, which not only the number of events, but the fact that they occur really late or, you know, not at all in the treatment of the patients with bel-sar, and they come, you know, pretty early if you have actively growing lesions in the sham. So those are the three key things.
What is the powering of the study? What benefit is assumed in the bel-sar arm versus the sham arm?
Yeah, so very conservative assumptions. Based on the phase II data, which as I said, is 80% tumor control and 90% visual acuity, we have 99% power. If we were to cut all the assumptions by half, what does that mean? If we were half as good in the treatment arm and the sham had half the number of progressions, we're powered at 95%. So that's how highly powered we are, and with, again, very, very conservative assumptions based on the success of the phase II. So we think that, again, the study is, you know, the risk, significantly the risk for a success.
There had been some questions about what would be necessary for an FDA filing. You recently clarified that through a Special Protocol Assessment. Can you discuss the terms of that agreement with the FDA?
Yeah, so the FDA, in the special protocol assessment, actually confirms in writing that the design of the study supports registration. It's a randomized, you know, three-arm study, where we're gonna be comparing the high dose of bel-sar in three cycles to sham. There is a second arm that has half the number of patients that's really there just for masking purposes, and as I said, the safety database of 100 patients, the endpoints being a time to event analysis of the primary endpoint and just events of tumor control, and then the full statistical analysis plan. So it's a very, you know, robust set of, like, agreements that allow us to to really now just focus on enrollment and make sure that we get the study completed.
A key secondary endpoint of the trials is the composite endpoint of time to tumor progression and time to visual acuity failure. How important is that endpoint for either regulatory approval or commercial adoption?
Look, we're going through the ophthalmology division of the FDA for approval, and vision is key for us and for them. And why do I say for us? Well, that is the key value driver of the adoption of bel-sar, right? That we don't have vision loss, and as such, to have it as an endpoint is something that will allow us to have it in the label, and we wanted that. The advantage of having it as a in the composite is that it still allows us to show superiority when comparing to sham. So it was a very creative approach to allow us to have still the vision there and still a sham-controlled study, which is obviously like a red carpet for approval.
What do you think the key risks to the trial's success are?
Yeah, so look, we have the same risk as everyone else moving from phase II to phase III, right? Is the, these great phase II data gonna reproduce in phase III? So what have we done to mitigate that risk? We've done two things. As I said, conservative assumptions. Even if we cut by half the response in the treatment arm and the sham assumptions were still 95% powered. So that's one, right? Mitigate the risk of consistency of phase II moving into phase III. And then the enrichment strategy, we make sure that every single patient that enters the study has the exact same growth phase, so that the sham will predictably fall and fail within this treatment period that we're looking at. So those two, from an efficacy or, you know, translation from phase II to phase III, are the key risk mitigations.
The second risk, everyone has it, too, is enrollment, right? And especially with a rare disease. So what have we done to mitigate that risk? We have gone through, like, a very large number of sites globally. We need to enroll 100 patients, and we're gonna open 80 sites. So that highly mitigates the risk. Really, every site needs to put one or two patients within the time, you know, that we have, which is 12-18 months. So those are, again, you know, very classic risks from phase II to phase III, and we think that we've done the best to risk mitigate them.
When do you think we could see the initial data from the trial?
Yeah, so we're planning to have data in 2026. As you know, we've guided, and we've been conservative, 18 months enrollment, 15 months to the data readout, and we're gonna be consistent with that guidance. So 2026 for a phase 3.
Turning to the market, could you discuss the global incidence and prevalence estimates for choroidal melanoma? How many patients are typically diagnosed, and what clinical features do they present with at the time of diagnosis?
Yes. I mean, look, it is one of the key cancers that start in the eye, and we have in our epidemiology research, it shows 11,000 patients diagnosed every year. If you look at the prevalence, especially in the indeterminate lesions, we can count as much as 50,000, because all those indeterminate lesions are a buffer of patients that not necessarily get treated every year. So a big unmet need in terms of early-stage disease, because that's the majority of patients. In this particular indication, of these 11,000 patients, 80% are early-stage disease. 80% are in the indeterminate lesions or small tumors that really have a low risk of metastasis. The disease is still 1 or 2 millimeter. They are seen by retina specialists, and sometimes they are not referred early enough to the ocular oncologist.
We're seeing now, Phil, it's incredible. We have 7% of Caucasians have nevus in their eyes, and actually, in the U.S. and in Europe, there are these nevus clinics where we know these patients. We know the patients that are at risk. You know, Caucasians, blue eyes, with the nevus in their eyes. So it's not difficult to think that, you know, those retina specialists are sitting on a number of indeterminate lesions that because there is no drug to treatment, and they're gonna be blinded by an ocular oncologist, they are not really sent until the disease really evolves and grows significantly. So we see an enormous opportunity on positioning the drug, very safe, easy to be given in the office, no need for anesthesia, no need for radiation.
Something that could easily move from the ocular oncologist office to the retina specialist office and really open that bandwidth of early-stage treatment. It would also... You know, how exciting would it be for the ophthalmology community to have something so innovative that can really, you know, not just treat vision or preserve vision, but save lives? So it is, again, the unmet need, particularly for this disease, is something that we see can be transformational. Because you're not just saving at the end of the spectrum when you have, unfortunately, metastatic disease, you're really treating very early and making a difference for the life of the patient.
Are there any good figures as to the proportion of patients that go through watchful waiting rather than being treated each year?
Yeah, so, you know, in our epidemiology assessment is, you know, 2/3 are watchful wait, 1/3 are really in that kind of, like, decision to treat. It depends on the type of physician. There are physicians that now, because it's so clear that indeterminate lesions are not healthy patients, they are starting to plaque earlier and earlier. So that balance of 2/3, 1/3 may be different depending on how aggressive to treat the physician is. But in general, that's what we see across the U.S., Europe, and rest of the world. That's about it.
Maybe last couple minutes, moving to choroidal metastases, where you plan to initiate a phase II trial in the second half of this year. Can you talk about the opportunity there? What makes you think bel-sar could work in choroidal metastases?
Yes, it's exciting to think about ocular oncology, not just melanoma, right? Because the reality is that there are up to four different types of cancers that go to the eye or start in the eye. And all of these are seen by the exact same ocular oncologist, like the 50 in the U.S. and 50 in Europe. So for us, it's just a natural path because our drug is tumor agnostic. So if we've shown that we can treat a melanoma or a urothelial carcinoma, we could expect that we could also treat a squamous cell carcinoma in the conjunctiva or a squamous cell carcinoma that comes from the breast into the eye. So again, the opportunity for us is really large. Metastasis to the choroid, that's how we're gonna start calling it, Phil, to differentiate from choroidal metastasis.
Metastasis to the choroid, meaning that breast and lung cancer going into the choroid, is a large unmet medical need, double the number of patients of melanoma, 20,000 a year. These patients, it's interesting because the whole treatment paradigm and the unmet need has changed. Why? Because now, thankfully, metastatic breast cancer, for example, has a much better prognosis. And these, women that now are surviving 10 years or more, now, currently, the unmet need is now you have, you know, metastasis of that breast into the eye, and we either have to blind you or remove the eye. That's... You know, I feel like that's the most unfair after surviving metastatic breast cancer. So we're so excited because we think, like, we've seen response, again, squamous cell carcinomas.
We work phenomenally well in those types of cancers, so why not giving the same suprachoroidal administration, the same ocular oncologist, the same sites that are now being trained to use the drug? And so this is a study that, again, it's a selective number of sites. It's starting in the U.S. because we wanna respect the enrollment for CoMpass, but, but we hope to give some early data before year-end, and this is one that I am particularly really passionate about. I really wanna make a difference for patients with breast cancer.
Great. With that, I think we're out of time. Thanks for a very interesting discussion, and we're looking forward to this afternoon's KOL even t.
Thank you so much, Phil. It's a pleasure, as always.