I'd like to welcome everybody back to our H.C. Wainwright Connect Conference. My name is Andres Maldonado. I'm a Biotech Analyst here at the firm, and it's my pleasure to welcome you to our afternoon session. Our next session is with Aura Biosciences, and it's my pleasure to welcome Tony Gibney, Chief Financial Officer and Chief Business Officer, and Anthony Daniels, Vice President, Therapeutic Area Head Ocular Oncology. Welcome, guys.
Thank you very much.
I guess as a good primer for Aura Biosciences, it would be great to just kick it off with a brief overview of the pipeline and some of the company's current strategies as you're moving your lead asset, bel-sar, forward across ocular oncology and beyond.
First of all, thank you very much for the invitation. You've been wonderful partners for us at HCW, thank you. From an overall orientation, our pipeline's founded on bel-sar, which is a novel compound which has utility across a broad array of solid tumors. We have chosen ocular oncology as our beachhead for proprietary development in choroidal melanoma initially, also then extending into two other very important ocular oncology indications, which is metastases to the choroid, which is cancers that originate otherwise and metastasize into the choroid.
A variety of tumors can make up that grouping of, of tumor types, as well as cancers of the ocular surface, which is a much larger indication, and Anthony will walk you through a number of the, the nuances of the different indications. Separately from that, we have an ongoing phase I-B/II in non-muscle invasive bladder cancer with a readout for the initial three months, mid-year this year, so coming up quite soon. And that is both looking at a an immune ablative opportunity as well as a neoadjuvant approach to bladder cancer.
Great, v ery helpful. A lot to unpack here with VDC platform. I guess one of the first questions we have is can you give us a brief understanding of the core mechanistic rationale for really combining, you know, targeted tumor cell killing with immune inhibition, and why that's so well-suited to pursue early-stage localized cancers?
Sure. happy to speak to that in the eye. When we think about melanomas at the back of the eye, ultimately these patients go on to die from metastatic disease where it spreads to the liver. There's a long latency between treating the eye, and with the current paradigm, we're probably treating too late with radiation, and the development of metastases. We know that there's a role for immune surveillance to reduce that. Having a treatment that's targeted to the tumor in the eye, and we know both from the clinical work and also from the bladder work, that it generates a tumor-specific immune memory that would certainly have the ability to reduce the risk of metastases down the road as well.
As we think about other ocular indications, including cancers of the ocular surface, a lot of these are squamous cell carcinoma. That's a very immune sensitive type of cancer as well. Lots of opportunities to leverage all of that.
Great. No, that's super helpful. You know, in early choroidal melanoma, you know, the current dilemma is, you know, watching a potentially life-threatening tumor versus treating with radiotherapy and all the caveats that come with the risk of vision loss. I guess, how do you see bel-sar changing that paradigm, you know, given that high bifurcation thought to beat there?
I think in two ways. You know, the first is that this isn't theoretical. I actually still see patients, and I have this conversation with patients every single day that I'm in clinic, which is on the one hand, yes, your tumor's growing. The longer it grows, the greater the chances of you developing metastases down the road, which are basically uniformly fatal. On the other hand, as soon as we treat you, we are putting you on the path to going blind, and the amount of vision loss that patients get with radiation is not minor. 87% of patients end up losing so much vision that they're less than 20/200 legal blindness. They can't see the big E.
The certainty of the extremely high likelihood of vision loss with radiotherapy is the one thing versus, you know, the risk of dying from developing metastases. As a consequence of this, we delay therapy as long as we can to try to avoid vision loss, and we know that under that current paradigm, at the time that we're currently intervening, patients are already at high risk for developing metastases. I think bel-sar can have two main changes to this paradigm. The first is you can have your cake and eat it too. You can do what you do in every other type of cancer, which is diagnose early and treat early. We'll shift to patients being treated earlier and without having to sacrifice vision to cure their cancer.
Great. For the CoMpass study, the phase III trial, you know, it would be helpful if you could walk us through some of the key design features, speak about the primary endpoint, the ongoing, you know, FDA SPA, or any kind of, you know, lesser under-the-radar elements that give you conviction in CoMpass.
Yeah. The CoMpass study is a randomized masked study. The patients either get the regimen of 80 micrograms of bel-sar for three cycles, the exact same regimen that we used in our phase II study on which the CoMpass phase III study is built, and it's randomized that versus sham. The tumors all have to be actively growing and to have documentation that they're growing prior to getting into the study, which is helpful because that way we know that the patients who are randomized to sham are likely to progress, right? They're actively growing. They continue to do so when they get sham. Then the primary endpoint is time to tumor progression. You know, in the patients who receive bel-sar versus sham.
The first key secondary endpoint is a composite of either tumor progression or vision loss, whichever comes first, which allows us to show that not only are the patients not progressing with bel-sar, but their vision is being preserved in these patients as well.
Given that CoMpass is a highly powered study, can you just give us a kind of historical lesson on what the phase II data encompassed, what it showed, and where the highest points of correlation can be for the phase III data?
Sure
In your view?
Yeah. The phase II study was a dose escalation and expansion. There wasn't a sham arm, but there are the early cohorts that got very sub-sub-therapeutic amounts of drug, one or just a couple injections at low doses, and then the later cohorts got the full therapeutic regimen at the high dose. We can compare those to get an idea of what bel-sar versus sham would look like. Expect sham to be worse than low dose, you can compare those two. The patients who received the therapeutic regimen had 80% tumor control.
When we looked at growth rates, that was complete total tumor control, meaning not only did the tumor stop growing, but you stop bel-sar, you give it up front, then you follow the patients for one- year afterwards, and there is still zero growth even off of treatment for one- year. That was in the therapeutic arm. In the sub-therapeutic or sham-like arm, there were only 20% of patients didn't hit the progression threshold. We had 80% versus 20%, and it was maintained even off of drug out to one- year. That was combined with excellent vision preservation. If you think about, you know, vision loss, the definition of vision loss in the field is usually 15 letters of loss. Had only one patient that lost vision, and it actually wasn't from drug.
It was from tumor-related factors. There was some subretinal fluid, as there often is, and it progressed in vision loss. That's one patient. The average patient lost three letters of vision. To put that in perspective, that's half of one line. Meaning if you came into the study seeing 20/20, a year later, tumor's controlled, and you're still seeing 20/20, but you missed a couple letters on that last line. For comparison, the average patient getting radiation loses 30 letters of vision, six lines of vision. That's almost the entire chart. Excellent tumor control combined with excellent vision preservation.
When we think about how that maybe predicts what we might expect to see in the CoMpass study, I'll just point out that the tumors that are being enrolled are exactly the same regimen, the route of administration, the dose, the criteria for progression, even the independent reading center. Everything is exactly the same to recapitulate the phase II, except we're going up against true sham.
Maybe to follow up on a little bit more granularity to the vision preservation narrative being central to bel-sar, help us understand, you know, how those outcomes differ between what matters most for physicians, patients, and regulators?
Yeah, I think those are actually excellent questions. You know, patients really care a lot about losing vision. I mean, You just see their face drop when you tell them, "I can treat your tumor." They would say, "Oh, great, then my vision will get better," right? Say, "No, we're actually gonna make it worse." It's, it's very, very meaningful to patients and leads them to choose to avoid treating their tumor as long as possible. Also to doctors, right? Nobody went into ophthalmology to blind patients, right? You're actually doing a treatment that you know is gonna put them on the path, on the path to blindness in the short term. I think there's actually a lot of alignment in that way.
The nice thing is that you don't have to pick now between the two. You can have both. From a regulator point of view, we actually have alignment on the endpoints between Europe and the FDA, which is great that they both agreed on the primary endpoint being tumor time to tumor progression. We do, and it was actually a suggestion by them to incorporate this composite endpoint as a first-key secondary, because that allows us to then make claims around vision preservation as well.
From the payer side of things and from the regulators, if you're halting the progression of the disease in its tracks, that is a functional cure. A functional cure with also the prospect of not having the eye going blind, we think that there's a tremendous value add of curing cancer effectively, as well as keeping those patients on average when they enter, they're in the high 50s, low 60s in the study. Therefore, you're saving them two decades on average, based on life expectancy of that eye going blind. We think it's an extremely significant value add for an orphan disease.
Great. I think where the CoMpass study is today, I think it would be helpful for our audience to, you know, get some color from the team on some of the commercial opportunities in the early, you know, choroidal melanoma space, particularly if you can speak to, you know, how patients may be coded or managed as either high risk intermediate lesions rather than treated just as melanoma. What are some of the puts and takes of this initial launch from both perspectives there?
Yeah, I think that's a great question. You know, when we think about who's coded as melanoma right now, we don't code patients as having melanoma until we've made that decision that we have to bite the bullet and treat them with radiation. That's because you don't want to code something as cancer and then say, "I'm not gonna treat it," right? On the other hand, at the time that you're gonna treat, you code it as cancer, as melanoma to support radiation, et cetera, metastatic surveillance. Right now, what's coded as melanoma isn't all the patients that we think need treatment right now, but just those where we have no choice but to go on to radiation despite the consequences of it.
There's the much larger population of patients who we're having the discussion every time, like I just described, you know, patients who need treatment. We know they need treatment, but we're trying to delay as long as possible. When we think of the, all the patients who the doctors would want to treat who need treatment, it's about 8,000 patients, 4,000 in the U.S., 4,000 in Europe.
Incidence.
Yeah, sorry. That's incidence.
Great. Moving on to outside of choroidal melanoma, the company's also pursuing metastasis to the choroid and ocular surface cancers. There are a lot to unpack there, but where should we start on the basis of the scientific rationale translating to the clinical rationale and the overlap between those type of lesions versus what CoMpass is looking at?
Yeah, I think that they're both very exciting opportunities. If we talk first about metastases to the choroid, these are cancers from elsewhere in the body that spread to the eye, metastatic lesions tend to grow quickly. These are tumors that grow quickly, expand, leak fluid under the retina, patients actually lose vision. It can happen in actually both eyes. It turns out that the back of the eye, the choroid, is a very fertile ground for seeding metastases. These are largely breast and lung cancers, then basically every other type of cancer in a smaller percent . The way that the drug is being delivered is exactly the same as we're doing for melanoma. Same suprachoroidal injection, same laser activation.
The sort of exciting opportunities with this are that number one, in this one study, we can demonstrate that bel-sar works against a whole host of primary tumor types. We have the preclinical data to support that it works just as well for all those other cancer types as well. The endpoints are very short because these tumors grow very quickly, and when you treat them, they actually shrink as opposed to just stopping growing because the whole mass itself are these malignant cells. Short endpoints, no need to document growth to prove it's growing because nobody's born with a lung tumor in their eye, right? We can demonstrate across a large swath of tumors that this works. On the ocular surface, this is exciting for, I think, three reasons.
The first is that there are a lot of patients who could potentially benefit from this. Actually, if you look at these three indications, each one is bigger than the one before it. Ocular surface is the largest of the three in terms of number of patients with either melanomas on the surface of the eye or squamous cell carcinoma or the precursor lesions that all need treatment, on the surface of these patients. We have the opportunity to inject directly into the tumor because it's right there in front, and it's easily accessible. We know from bladder just how well direct intratumoral injection works. You can imagine a patient saying that you can just inject directly into the tumor, activate with a laser, and melt the tumors away.
Kind of circling back to one of the first comments you made about just de-risking bel-sar into a broader scope of ocular cancers. Does either metastases to the choroid or ocular surface cancers represent maybe a lower hanging fruit to generate data that de-risks it across all kind of eye geography?
I mean, I think the metastases to the choroid program is a little bit further along than the ocular surface program. I don't think it's really an either/or. I think, you know, a big hit on either one would be fantastic, and obviously you're hopeful that it'll happen in both.
Great. No, this is very helpful.
With the capital raise we just did two weeks ago, for the first time, we can take these early pilot studies. We see the right results go directly into more advanced, aggressive. You know, we're gonna try to push the next stage of development as aggressively as possible. We're not gonna have to do watchful waiting for documenting growth. A lot of the pain and suffering a lot of people went through, including the company to have, you know, have recruitment finally be at the doorstep of conclusion. That whole paradigm that we sort of had to go through, the learning curve we've gone through into CM and having that study done, it's just not gonna be a part of the next two studies.
We think we can catch them up to closer proximity than you might typically think for numbers two and three to do an sBLA.
Sure. It's also the same doctors that treat all of these tumors. As we go to doctors and sites to be in the other studies, they're already very bel-sar savvy. They know how to do this. They're old hat at it from CoMpass.
Completely.
Great. In the time we have left, I want to turn the page to the NMIBC program, which is very exciting. I want to give you a few minutes to describe the positioning of the NMIBC program and how different where you guys are developing it is compared to a lot of the noise that's been made in the NMIBC space there. I guess you could start by talking about the differentiated strategy by focusing on the neoadjuvant approach before TURBT, rather than just an intravesical adjuvant approach.
First of all, from the broader picture, you know, if you look at the ocular indications, we see no competition, even in preclinical development, any of these. In our positioning as a company is we wanna own the ocular oncology space for the long duration. We see the opportunity space in bladder as being extremely interesting and we think we have a significant impact. It's also a larger and more crowded area. You know, the field is certainly showing some tremendous results in certainly the adjuvant side, where you're looking at CIS patients, you're looking at BCG unresponsive patients, where a lot of that is being done. The initial three months looks very compelling. Durability tends to trail off into the 50% range at 12 months.
Still there's been just a broadening of the opportunity set. Those therapies are reasonably effective, but certainly there's room to improve, but they're highly morbid for the patient. They have tremendous side effects. We think we have an opportunity to really change that whole paradigm by going earlier in the treatment area. There's one other competitor, UroGen, who did a very nice job in the intermediate space, which is sort of the smaller tumors or less aggressive tumors, being able to show that being able to avoid going into a TURBT has benefit. We're actually exploring that in our clinical work right now.
We call that immune, you know, sort of immune ablative as opposed to chemoablative, is really creating a tumor-specific immune response that we've shown data, which shows a very robust response within 9 - 12 days of showing that, and we're gonna continue to see that happen. We're looking at that patient population as well as looking at the neoadjuvant population. These are patients who will have a TURBT. We're, we're treating the patients, two weeks later, they have the TURBT, and then we're following up to see if we can actually enhance that durability at three months and ultimately to 12 months and be able to avoid having to go to that next much more, morbid and complex procedures of the adjuvant therapies. It's, it's a shifting mindset.
It works to the bel-sar mechanism exceptionally well. We feel like we're frankly reasonably proximate to the durability data. At 12 months, we're gonna have a huge winner on our hands. Now we have been speaking publicly that from the capital we're raising, we're looking to take the ocular indications as far down the road as we can. We'd be looking for the, in the bladder arena, likely doing the next phase of development with partners, where they could look at NMIBC, looking at other areas within urology, even outside of urology. We're gonna be learning a lot about the immune activation part of the mechanism, how that translates to durability, and see, you know, see where we wanna take bel-sar out of the eye, likely through partners.
Great. In the couple of minutes we have left, it would be great to just get a 12 month overview of what to expect in the back half of the year looking into 2027.
Sure. We have the three month data returning mid-year. If you roll the calendar forward for the three month data in bladder, that'll be into the early second half of 2027 for the 12 month data. We are guiding in 2026 for the next of the core data, the initial phase I work, as well as the initial proof of concept work in ocular surface also in 2026. We have a lot of data flow coming in the next, you know, six plus months.
Great, and I think we're out of time, but I wanna thank Tony Gibney for being here, and Anthony Daniels, thank you so much for the great talk, and we look forward to future updates.
Andres, thank you so much. Take care.