Great. I'd like to welcome everybody back to our afternoon session of the H.C. Wainwright BioConnect Investor Conference at NASDAQ. My name is Andreas Maldonado. I'm a covering analyst here at the firm, and I'd like to welcome our next presenters, Aura Biosciences. Today we're joined by Jill Hopkins, Chief Medical Officer, President of R&D as well, and Tony Gibney, Chief Financial and Business Officer. Welcome on behalf of H.C. Wainwright and myself. Glad to have you guys here. Let's start from the top down. Just for investors getting to know Aura, can you walk us briefly through your VDC platform and why you believe bel-sar is uniquely positioned to transform early-stage cancer treatment?
Thank you. Yeah. The viral drug conjugate platform is a really interesting platform where we've taken an empty viral capsid and we've attached conjugated light activatable dye to that. We can see that we can offer dual selectivity. We inject locally in and around the tumor. The viral capsid then binds to these HSPGs on the surface of the tumor. We have very selective uptake only where the tumor cells sit. We then activate that with an infrared laser light very selectively only where we apply the laser. We are very excited by that dual selectivity from a benefit-risk perspective. I think that's a key piece of the question you ask of why in early-stage cancer. If we can look at treating early tumors with a very positive benefit-risk profile, we can look at changing the trajectory and the paradigm for multiple solid tumors.
We have a dual mechanism of action where we have the necrosis of the tumor cell at the time we activate it with the light. That is very important from a tumor-agnostic perspective. We treat these early tumors as they're just at that malignant transformation phase. We have necrosis of the tumor cells that then release into that tumor microenvironment neoantigens specific to the tumor. We then have our secondary mechanism of action, which is an immune activation where CD8, CD4, adaptive and innate immunity come in and work as an ongoing immune scavenger offering durable immune effect. We showed that in over 100 different cell lines, 20 different tumor models at the NIH, where our founding science comes from. We now have clinical data coming in ocular programs and in bladder cancer that confirm that mechanism.
Great note. Thank you for the context. You know, it's very refreshing to see, to look at Aura's strategy as a whole, you know, going where the field of oncology hasn't yet touched, specifically localized early-stage tumors. Why is it important to build a franchise starting in ocular oncology and how has that shaped the broader clinical expansion?
First of all, thank you for having us here at the conference. You know, I joined very recently, just in the last week I was announced. This is really one of the hallmark reasons why I joined the company. If you think about ocular oncology, upwards of 65,000 patients across three of the main indications we're looking to go into over time have never seen a therapeutic intervention. When we have a tumor-type agnostic platform, being able to really have that real estate, if you will, helps to be able to transform patients' lives in a significant way. We're looking at really halting the progression of cancer and also staving patients from going blind. The average patient in the choroidal melanoma comes in at 58 years old. The prognosis of them being able to have life without blindness for 20 plus years is very significant.
The company certainly could have chosen a variety of other solid tumor applications, but really the nucleus of the company when it was founded was in the ocular area. I actually come from the ocular area, as an Iveric most recently. When you see the side effect sparing of this with blindness, it's a profound change for patients and a hugely motivating opportunity set. I looked at the opportunity in choroidal melanoma alone, no competition, 11,000 patients. The next indication of metastases to the choroid, 20,000 patients, never seen a therapeutic intervention. The next one after that, coming very much in very close proximity would be cancers of the ocular surface, 35,000 patients. If you think about in AML, there's probably 80 clinical studies ongoing for 40,000 patients. There's nothing even in preclinical behind us in our indications.
Please.
Just add to that. I think from an ocular oncology community, there are 50 ocular oncologists in the United States, 50 in EU5. Ninety of them are in our phase three Compass program for choroidal melanoma. In terms of the ability to develop meaningful therapies across all of the indications that Tony mentioned with that same community, same treating physicians, same platform and mechanism, we are really excited by how quickly and expeditiously we can bring that to patients.
Great. Very helpful. As we look at primary uveal melanoma, radiotherapy remains standard of care and it is correlated to high rates of long-term vision loss. Can you expand on how bel-sar's delivery system and safety profile thus far could shift the paradigm toward earlier vision preserving intervention?
We know now with choroidal melanoma, particularly the small early lesions, patients often have the difficult conversation with their treating physician around, do I treat with radiation now and start on this pathway to blindness? As you outlined, 87% of patients five years after radiation are legally blind in that treated eye. This watch and wait paradigm exists where small lesions are monitored. The concern over time is that those may grow and metastasize and then require radiation. In bel-sar, in our phase 3 program, we're comparing bel-sar treatment to sham. That was based on the strength of the phase 2 data, where we saw that in the phase 2 trial, patients who were treated with the phase 3 regimen compared to those in a subtherapeutic regimen. It was a fairly rapid dose escalation.
Those early 10 patients got very low doses compared to the therapeutic doses that were received in the other group. We saw when we compared those two groups, 80% of patients that were treated upfront over the three months at 12 months had complete cessation of growth of their tumor and 90% of patients had preserved vision, even in eyes where the tumors were very close to vision sensitive structures like the optic nerve or the fovea. We were really encouraged by that with very positive safety profile as well. Just a handful of grade one AEs that were some mild anterior segment inflammation that was either self-limited or treated with topical steroids over six days.
A very healthy benefit-risk profile showing tumor control and vision preservation, which really changes the conversation that those same patients can have with their physicians about treating upfront early at a stage before they're concerned about growth or metastatic spread.
Great. In that same context, you know, with the phase two data in mind, where over 90% of patients maintain the visual acuity, how should we be thinking about, you know, what success looks like in the phase three? Internally, have you, do you want to beat what you saw in phase two? Do you have to beat what you did in phase two? If you can give us some context, that would be very helpful.
Sure. Our phase three program is now enrolling around the world. We're in 18 countries and we have a SPA agreement with the FDA, also agreement with the EMA on our endpoint. Our primary endpoint is time to tumor progression. That's important because that really is where you see the cessation of growth. In ocular oncology for melanomas, unlike other oncology indications, a local cure is defined as cessation of that growth, whether it's radiotherapy or whatever you would put in place. That primary endpoint is that time to tumor progression where we hope compared to sham, we will see really good tumor control in the bel-sar group. 80% would be lovely. I mean, I think our phase two results were tremendous. Again, tumor control ultimately the goal.
For vision preservation, our key secondary endpoint is a composite endpoint that is either tumor progression or visual acuity loss. That is important for us as well because we, you know, against sham, we do not actually anticipate that sham will have a lot of vision loss in the course of our treatment. What is very important is showing that ongoing vision preservation in bel-sar treated eyes that we could then label and speak to. We are, again, phase two data, our phase two criteria, our reading center, everything is exactly the same in phase three, very highly powered in phase three at 99%, 80 microgram to sham. We are confident that we have a good probability of success in that program.
Great. Very helpful. Can you just comment quickly before we move on to your bladder cancer program? In terms of how do you envision bel-sar fitting into the referral and treatment workflow for retinal specialists and just, you know, ophthalmologists as a whole, you know, and how should investors be thinking about anticipated uptake post-approval?
It's a great question. As mentioned, I think in the ocular oncology community, uptake will be swift in that they're involved in our trials. They're ready to go. What's really interesting though, and when we think about the potential not only to treat lesions earlier, so that funnel of actual lesions that may be amenable to treatment, we also see the potential for the funnel of treating physicians to expand. I'm a retinal specialist myself, spent 20 years in practice. I would follow these lesions until I was concerned with then send them to my ocular oncology colleague 'cause I didn't want to radiate them. Had I had a treatment like bel-sar where I could inject and laser in the course of my routine clinical day, absolutely I would've done that.
We see that the funnel of treating physicians expanding as well potentially over time, which I think is very exciting. To your point, the flow, you do not have to go to the operating room. You are not putting a radioactive plaque in place. You can do the injection in the morning, run your clinic, do the laser in the afternoon. A lot of ease in the clinical workflow, which I think again is very important with changing paradigms of care and healthcare expenditures. That is a benefit as well.
Great. Very exciting. In the interest of time, I want to ask you a few questions about label expansion of bel-sar now concerning with non-muscle invasive bladder cancer. For context, muscle invasive bladder cancer, as we all know, is one of the most hot topics within oncology with a host of modalities showing robust data. If you can walk us through some of the highlights of your phase I data where you saw CRs and robust immune responses, that would be great.
Thanks. Yeah, the phase one program, we ran what we call a window of opportunity study, meaning that we kind of stepped into the normal standard of care flow. These were patients who were scheduled to have a TURBT regardless. We were able ahead of that TURBT to go in and treat. Local in-office cystoscope in the urologist's office, injection to the tumor, cystoscope and laser application in the bladder in our phase one program. Then everyone went on to get their TURBT as scheduled, which actually was a very elegant design as it turns out because it gave us very strong data in human histopathologic tissue of our proof of mechanism. We used again, ocular doses here.
We took our ocular dose, our ocular volume, and we did one treatment at seven days when the physicians went to do the TURBT in our intermediate risk group, four out of five of those treated lesions had complete responses. They were not visible there. The physicians still took histopathology, so we were able to see the necrosis and immune infiltration. They also took some samples from non-treated lesions where we also saw complete response and immune activation. So that, you know, the early mechanism I was describing, the necrosis seen, immune infiltration, both innate and adaptive immunity within that seven-day window. Very compelling in terms of the proof of mechanism in human tissue.
Great. Thank you for that context. You know, from where I stand, what's really interesting and what we want to highlight next is, you know, you propose two novel treatment paradigms, immune ablation, immune ablative monotherapy and neoadjuvant prior to TURBT. Help investors in the audience understand how unique this strategy is when most of the NMIBC players are pretty much stacked on top of each other in a different, so you are competing, but you're not actually competing directly.
Exactly. I think, you know, important to remember when you think about our mechanism, we need the tumor to be there, right? It's gotta be there for us to go in, inject, get the neoantigens, and have that immune response that's gonna be important. We anticipate over time for durability, disease-free time points, and durability, which is key in this highly recurrent disease. We're thinking about that in two different ways. We treat upfront regardless, right? A lot of the space is in adjuvant. They go in, they remove the tumor, they apply a variety of things to hopefully decrease the burden for patients. That's not us. We want to treat everyone frontline. We have had discussions with the FDA on the basis of our data. We have a rapid dose escalation plan going now. We have started that. We're gonna increase the dose.
We're also gonna increase the cycle. So we're looking, can we prime boost that immune system even further? And we're gonna look in intermediate risk where we're saying, could we be truly immune ablative? So I go in, I treat upfront. I may never need a TURBT in that patient. So that's the immune ablative approach. When we look at more high-risk patients, that's where the neoadjuvant may come in, right? You can treat, and that's the design of our phase two, treat upfront, do the TURBT as scheduled, but then watch for that durability and that durable immune response. We'll have endpoints at three months and 12 months, the standard regulatory approvals. We do have, you know, alignment with the FDA that we can enroll those cohorts in parallel.
We would anticipate having that enrolled in 2025, within 2026, the three and 12-month durability data, which will be very important in this space.
Maybe circling back to, you know, what makes bel-sar so unique? Could you comment on, you know, relative to the standard of care BCGs or upcoming gene therapies, viral or non-viral, you know, can you, can we dig a little deeper on, you know, the uniqueness of the mechanisms of action here? And if you can comment how it differs in immune response compared to BCG, some non-viral vectors, viral vectors, or even traditional, maybe double chemotherapies.
Yeah. I think again, you know, sort of go to our paradigm shifting approach here, right? So much of this space has been adjuvant. You remove the tumor, you then apply whatever that may be, the mitomycin gels, the oncogenic, but you're really with the tumor out of there, you're not able to derive the tumor-specific antigenic response, which is what we really see as the key of our mechanism, that, you know, you're getting tumor-specific immediate release with necrosis in the tumor microenvironment that the immune system can then immediately react to, which we think differentiates us significantly. We also like the fact that we are a virus-like particle, but we're not an active virus. You don't need a special hood. You don't need a lot of pretreatment of the bladder, for example, to have the uptake, all in the workflow of a cystoscopy in clinic.
I do not know, Tony, if you wanna add, 'cause I know some of that was what led you to join us.
It's in some ways, it's a fairly simple proposition, which is you try bel-sar first. This is clearly gonna be the most convenient from a patient and a physician perspective. This works well into their practices. If they elect, patient or doctor, to want to do a TURBT, 'cause they see that being as something that's gonna be important for maybe just the history of how they've gotten to the disease, the request, if it just makes sense, we can be a part of, you know, you hit up the patient first, you TURBT, and then hopefully recurrence is gonna be deferred or delayed for a very long period of time. These are patients who have TURBT sometimes 10 times over the course of 10 years. Every single time is debilitating not only them, but their families. It's a very high morbidity process that they go through.
Just being able to defer that is a huge win for the patients. It is really the same idea with ocular oncology, which is based on the mechanism, based on the fact that we are tumor agnostic, try it first. Down the road, if there are faster growing tumors, like you could imagine being able to do repeat dosing for bel-sar, certainly not gonna be the gateway for approval, but for the faster growing tumors or even the more advanced ones, you know, it is a very benign treatment. It feels like all the incentives would be there to do that.
Great. Very helpful. Just a point of clarification, bel-sar can be administered, does not have to be administered by a physician, or does it have, can a nurse practitioner, PA administer it in the urology clinics?
It's done by a physician. Yeah.
Okay.
Yeah.
You know, as we look at the novel tumor agnostic mechanism of action here, you know, what are some of the tumor types that interest you the most down the road? You know, obviously runway is an issue, but curious mechanistically, you know, what fits the criteria as the next most attractive frontier for you guys?
Yeah. I think unmet need always drives a lot of what we think about. Also though, you know, when you look at areas of medicine, subspecialties, gastrointestinal would be one that comes to my mind always wearing my President of R&D hat, and that you have a group of physicians who scope and laser and snip and biopsy all day, every day from the top of the GI tract to the bottom and back again, would seem such a sort of perfect place to explore this.
You know, what I've really liked about our bladder approach and what we'll, you know, consider also with ocular surface cancers, these window of opportunity studies where you can, from a capital efficient perspective, get into clinics, tumors, a range of things, and then get histopath that really tells you very quickly how does this look in terms of response. I think, you know, again, I think Tony and I both feel the sky's the limit on that. It will require funding going forward.
Yeah. It's gonna be a question of what we do on our own versus what we do with partners. I think we're gonna have a unique lens coming from the metastases to the choroid. That's a study that we're gonna be seeing some readouts as early as toward the end of this year. We're amending the protocol to be able to look at really be more of a metastases-agnostic therapy. We could be looking at head and neck, breast, lung, prostate. We'll actually have a window as it metastasizes. If we see that there's tumor engagement, it does read back on the solid tumor. If the location of the primary tumor is accessible, we can shine light on it, we may have a fighting chance of making an impact.
Our focus from a strategic perspective is gonna be taking the ocular oncology opportunity, particularly in the U.S., forward on our own. We can, you know, certainly since we now have a formulation with bel-sar that is outside of the ocular therapeutic areas, it is gonna be distinct. We can partner that over time, meaning other solid tumors, while we really maintain a very rigorous focus on the ultra-orphan market that we're gonna be in.
Great. I think we're over time, but one last quick question. Would you like to highlight, you know, for investors, what can we expect over the next six to 12 months, you know, for Aura, maybe some commentary on potentially NDA filing and commercial readiness for your ocular oncology program and beyond that?
Sure. We raised $75 million last week. Great market to raise money in, but you know, we were able to extend our runway well into the first half of 2027 with that. We had launched a smaller deal. We were able to upsize it into demand. Very fortunately, I think we have a handful of new investors, including one anchor and a lot of support from ourselves. We take that capital that we have in this market very seriously. You're not gonna see us opening up a lot of new other opportunities. We're gonna be laser-focused on the four deliverables of data. We're gonna have all four of our indications, three being ocular, one being bladder cancer, and we're gonna be peppering, you know, the investor base with that and growing and learning more about the drug along the way.
We're very focused on potentially partner down the road, but we wanna be able to really de-risk the program before we probably look to do some of that activity.
Great. That is all our time for now. I would like to send an extended thank you for joining us from myself and the entire Aura Biosciences family. We look forward to future updates.
Thanks so much.
Understand.