Aura Biosciences Offers Hope for Ocular Melanoma

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Elisabet “Eli” de los Pinos was enjoying her job at Eli Lilly’s Oncology Business Unit where she was part of the leadership team responsible for Alimta’s market launch in Europe, a new drug for the treatment of Lung Cancer. But she took the leap, leaving corporate comfort to build Aura Biosciences from the ground up around viral-like synthetic nanoparticles that are closely related to wild type viruses in structure and behavior but lack any viral DNA. These empty protein shells resemble viruses but do not have the capability to replicate or integrate. Aura is leverage the technology to create AU-011, which can deliver potent cell-killing laser-activated molecule right to the point of ocular cancer. Aura says the molecule is activated by a standard ophthalmologic laser and treatment will be administered in an outpatient visit.

Podcast Guest

Podcast Transcript
Tom Salemi: Hi, Ellie, welcome to the Podcast.

Elisabet de los Pinos: Hello, good morning, Tom.

TS: Thanks for joining us. You know, you and I have actually something in common. I also am a winner of a World Economic Forum Technology Pioneer Award. I don’t think I mentioned that when we talked earlier. But – actually, I’m just joking.

EP: Oh, congratulations. No, you did not mention it.

TS: No, I think I was a runner up or maybe I came in third. I got a participation medal, but I don’t think I got the actual award. But you did in 2011, correct?

EP: Yes, that’s correct.

TS: Now when did you start Aura? What’s the origin of the company?

EP: Aura started in late 2009 and it was basically because I wanted to start a company and develop a new class of drugs for cancer. And that has been in my mind probably for a lot of years. Usually, entrepreneurs have something and they persevere. And I identified a technology that I thought would be the base for that idea, and it was a technology that had been discovered by John Schiller of the National Cancer Institute. And I partnered with John, and we licensed the technology and started the company in Boston. And it was a phenomenal partnership. Sometimes the academic partnerships are not good, but in this case, John Schiller had already developed a vaccine for the human papilloma virus. He knew very well what drug development was about, and was a great alliance with his lab, and he put all his team to work and help us develop this new class of drugs.

TS: So what was your situation at the time? You were in pharma, right? You had a stable job at a company, and you did what a lot of entrepreneurs do. You sort of find – take that leap of faith. What was your current situation and what was it about this particular opportunity that told you that was the time to try?

EP: Yes. I had worked at Eli Lilly, the pharmaceutical company, in the oncology business unit. And I had been very lucky, actually. I had a phenomenal job and we were launching a drug for lung cancer in Europe. And I had all the exposure of what is a commercial launch. But have always been an entrepreneur, and I always wanted to do more innovation rather than be at the end stage of just launching a compound, but rather a new class of drugs. And I think you’re just born entrepreneur, so yes, I did take the leap of faith, and I did start a company with very little capital and a lot of passion. And I think that that’s what it takes. You know, if you persevere and you have an idea, and you really commit to it, then you end up finding the capital, the team and things come along really nicely.

TS: What was it about this technology that you thought was so promising? Can you maybe describe the technology and what your approach is?

EP: Yes, absolutely. So this is a novel class of therapies. And we usually talk about targeted therapies, and those are therapies that act on individual cell signaling pathways. And for some cancers, that has worked really well. But what I thought is if we have the possibility to approach cancer and then deliver, the thing is extremely toxic, so not try to repair a molecular path, but really try to identify something differential on the surface of the cell that can then obliterate or ablate that cell very effectively, that would be a much better way to approach cancer. Of course, the universal targeting like this, it’s not accepted but what John Schiller had identified was a virus that had this universal targeting property. And there had been some background at that moment, obviously the oncology drugs had not been approved yet. But there was the idea that instead of using a virus, we could use a viral shell or a viral-like particle that would retain this property of universal targeting, and would allow us to deliver drugs really efficiently. And so that was the basis. The fact that he had identified this way to target tumors in such a different way with a very simple protein that could be applied broadly, I thought, would be extremely differential of any other thing that was being developed for cancer research, that would ultimately impact the clinic in ten years from that moment. So that was the idea. And it has worked really nicely. At the beginning, obviously you build on the data, and when you start working with an academic, you basically validate that data to make sure that it’s robust, and you do it in different labs. And it was very robust. It was a very nice way to uniquely target tumors. And that allowed us to say, well, if it’s so universal, we could go from very common tumors like lung cancer, breast cancer, and we had all the data about that. But we could also go to very rare tumors, where no one had really ever approached any type of therapy. And by doing so, we would not only create a lot of value for patients, but we would also validate the technology in a unique way, probably much cost efficiently than we would do it in a bigger indication. So that’s the basis for how a technology that’s so broad and a platform that can go in so many directions ultimately is focused on a very specific and rare indication.

TS: Was cancer always your focus, your primary passion?

EP: We’re the only company, as far as we know, that is working on ocular oncology. So we are trying to treat ocular cancers, and in particular ocular melanoma. That’s our first indication.

TS: And was it always – was cancer always the disease you most wanted to go after?

EP: Yes. Absolutely. That was – this technology is uniquely suited for cancer targeting. And doing so in a rare cancer where no one has ever developed any drug before and patients have no treatment options is an incredible value for our team, for patients, for the entire community. So that’s our driver.

TS: I know you’ll be presenting at OIS and telling the story of AU – is it AU011? How do you say it? It’s spelled out AU-

EP: It’s AU-011.

TS: All right, fantastic. I’ve got the lingo down.

EP: You’ve got it right.

TS: You’ll be telling the story about the compound there. Give us a little detail today. Where is that therapeutic at in development?

EP: It is probably the most exciting moment in drug development because we are very, very close to starting our phase 1-2 clinical trial. We’re going to start the trial in early Q1 2016. We’re just about to file an IND by the end of the year. And we have ten sites qualified to start and enroll patients. So we will be a clinical stage company very, very soon, and that’s sort of a great step for all of us.

TS: How is AU-011 administered? And how does it work? What does it deliver?

EP: AU-011 is administered by intravitreal injection. And that’s something that we’re very grateful that now in the ophthalmology field is something that’s so well accepted. Intravitreal injections allow us to bring this drug to where the tumors are located. The drug distributes really well and gets through the tumor. And the viral particles bind the tumor selectively, so it doesn’t bind the retina, it doesn’t bind the sclera, it doesn’t bind the ciliary body or anything else but the tumor. And then this viral particle carrying a huge amount of drug that’s pro drug. So it’s activated by laser. So once you administer the drug, four hours later, a period from four to six hours later, you can administer an ophthalmic laser, shine the light on top of the tumor, and that selectively activates the cytotoxic drug, which completely kills the tumor cells selectively. And it’s a very, very effective drug because the cells in the eye that we have are in the picomolar range. So we have, as I usually say it, it’s probably the most elegant way of targeting. And in the eye, you have to do so because you want to spare the retina and you want to kill tumors selectively. So by the 2 layers of targeting, one is by the viral particle, binding the tumor selectively. And the other one is by just activating the drug at the moment that you want it, and in the location that you want it, you have this beautiful way of eliminating what we call nearly molecular surgery. Because usually, we are – what happens in ocular melanoma is that we have tumors in a very small cavity, and very tiny tumors. We diagnose these tumors when they’re probably 1 or 2 millimeters. Can you imagine if you were able to do that in lung cancer or breast cancer?

TS: Wow. Yes.

EP: Well, in ocular melanoma, we can do that. Skin melanoma, all of these lesions are so small, they have a 90.9% survival rate. Of course if you have a mole in the skin, you’re going to go to the dermatologist and remove it. In the eye, we cannot do that. We cannot do surgeries in the eye as we do on the skin. And radioactivity leaves you blind. So there you have this incredible opportunity to have a tumor that has not yet spread, that’s very local, very small, and yet you don’t have any tools to remove it from the eye. So that’s where we come on board, where the early intervention for this disease can radically shape the outcome and the future life of these patients, because we’re not at the moment we’re just going to improving one-month survival. We’re going to be impacting their entire life where they can get rid of their tumor and preserve vision and have a normal life. So it’s a beautiful opportunity. I don’t think that as entrepreneurs we have this kind of opportunity so often, where you are presented with a disease that has been so poorly treated, and suddenly you have a unique molecular tool to approach it so well. So it’s very, very exciting. And I think the impact for patients and what we’ve seen both from patients, their communities, the KOLs that take care of them, and the FDA is that everyone is absolutely aligned to treat this disease early, which makes it very, very exciting.

TS: What are the current treatments? There are some available. They don’t sound very pleasant. What can be done today?

EP: Unfortunately, there are treatments, and the surgery, as you would imagine, is enucleation, which means it’s the removal of the eye. For years, this was the only option for these patients. Obviously, no one wants to lose the eye, especially if you’re a 45-year-old normal person, and you have a small mole, and the option is, well, we’re just going to take the eye out. The next step for patients or the next treatment option is radioactivity. Radioactivity in any other cancer, you would not worry so much. But in the eye, radioactivity leaves you blind. And not only this, the radioactivity that you would imagine is so easy to do, you want to focus the beam only – or the radioactivity energy only to the tumor. So in order to do that, patients have to through 2 surgeries because these tumors are in the back of the eye. The eye has to be removed. And so what they do is what’s called plaque brachytherapy, which is a metal plaque that the fill in with iodine seeds. It’s radioactive iodine. They attach it to the back of the eye. They insert the eye back. For seven days you have that plaque irradiating your tumor in the eye, as well as all of the other eye. And then another surgery to remove the plaque. Can you imagine the comorbidities –

TS: Yeah, I know, it’s –

EP: – that a treatment like that has for the patient? Of course it achieves what’s called tumor control. So the tumor stops growing, but it doesn’t prevent metastases and it doesn’t – and the problem is that then we have retinopathy, cataracts, glaucoma, dry eye. It is a really a horrible treatment with so many comorbidities that patients just are reluctant to go through it if the tumor is not really growing. And it’s a kind of one of these things that puts the clinician at stake because they identify a tumor very early. Sometimes they call them small melanocytic lesions. And if the tumor – it’s not yet fully transformed or growing, patients and clinicians don’t want to offer these very harsh treatments. So there is a pool of patients in the very early stage that are just without any treatment options. In the wait and see situation where if you’re unlucky, the tumor is going to grow and it’s going to be treated with this radioactivity therapy. And otherwise, you’re just waiting. And if it metastasizes, it’s a killer. So ocular melanoma, the problem that it has is that once it gets out of the eye, it usually goes to the liver. And that has a terrible outcome. It is less than 9-months survival. And so these patients are in this kind of like situation where do I choose to be blind or do I choose to wait and maybe if I want longer I’ll have metastases and in three years I’ll die. So –

TS: It’s literally a ticking time bomb, really.

EP: it’s really bad. Yeah. I think that what we have in our hands is the opportunity to help patients so early because we – most of – not most, all of the patients that are diagnosed with ocular melanoma, they are not metastatic. It’s when their tumor is tiny and in the eye, so that’s where we should be treating them as early as possible, as we do in skin cancer. And our hope – of course, we cannot say that we’re going to cure it. I think that in a few years we can say that we are the first company that’s ever developed a cure and not a therapy. But if you treat early in cancer therapy, in any cancer, the odds of survival are just great. And so we have the opportunity; we should be able to do it. And we’ll see next year. It’s very exciting.

TS: And what is the population like? I know you’ve recently attended, just this week or last week, there’s a patient retreat at the Cleveland Clinic, the I Am Not Alone retreat. I think you had kicked that off, actually. How large of a patient population is it? And how active are they in pursuing new treatments? Because they obviously need some better options.

EP: Yes. So it’s a really great community of patients and they help each other very much. I did participate at the OMF retreat and talked to the patients. With any rare disease, the numbers are always difficult. What we know is that approximately, we would say there are around 10,000 patients globally. Perhaps if we look at the number of patients that are treated in the early stage disease, this number – or they are not treated yet, this number may be bigger. Conservatively, we think that it’s about 10,000 worldwide.

TS: Fascinating. Is this your – is AU-011 your lead compound? And whether it is or not, what other cancers are you looking at?

EP: AU-011 is certainly our lead compound, and it can treat not only ocular melanoma, but all other ocular cancers. And that’s where we feel excited because once we have the safety data, we can definitely start treating all of these other rare cancers in the eye that have very poor treatment options and become really the flagship for ocular oncology. Of course, I told you that this is a universal targeting, and the NCI and us have developed a lot of data to demonstrate efficacy in many other cancers, especially solid tumors. We are very excited with the data in head and neck cancer and in bladder cancer. Those are 2 cancers that are also very local and have terrible treatment options, where a treatment like this could make a beautiful impact. So certainly, those are systemic indications outside of the eye that we will be developing.

TS: And how much capital have you raised so far? I think my research, my very preliminary research suggested $36 million. Is that accurate?

EP: Yes, yes, that’s accurate. We raised our latest series B round early in the year, and we have the capital to get through clinical development next year. So we’re very happy we have a very good group of investors. Henry Tamir is certainly a key investor for us. Also my mentor to help me build the company.

TS: That’s a great name to have assigned to the company. And finally, what are your future plans? Do you see a partnership, more capital needed in the short term? What sort of arrangements might you put – let me start that question again. This is where I’ll do some editing. And finally, what are your future plans? Do you see yourself partnering with pharma or raising more capital on your own to pursue this as an independent company?

EP: Well, the future is difficult to tell.

TS: Sure.

EP: But at this moment, if the data is positive, we will definitely try to raise more capital to go after the pivotal trial. The nice thing of this indication, and why it makes a lot of sense for us, that we’ve already had 2 pre-IND meetings with the FDA, and we’ve validated the clinical development strategy where we will have the phase 1-2 next year, and if that data is good, we’ll directly go into a pivotal trial. And that certainly is a very exciting path to development, where it doesn’t take an enormous amount of capital or resources where we could not do it on our own. And certainly, that’s something that it’s currently our plan.

TS: Excellent. Well, no doubt you’ll make many contacts at OIS@AAO in a couple of weeks. We’re so glad to have you out there.

EP: Yes, I’m very happy that they invited me to speak, and I look forward to participating.

TS: Excellent. And thank you for your time today and for your work. It’s a great story and we look forward to following it.

EP: Thank you so much. Look forward to updating and to provide good news for patients and the entire community.

TS: That’s sounds great.