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The Bioverge Podcast: Curing Blindness with Cell Therapy

On this episode, Arnaud Lacoste, chief scientific officer of Aurion Biotech, sits down with Neil Littman to discuss the company’s experimental cell therapy to restore vision in patients with corneal endothelial disease.

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On this episode, Arnaud Lacoste, chief scientific officer of Aurion Biotech, sits down with Neil Littman to discuss the company’s experimental cell therapy to restore vision in patients with corneal endothelial disease.

Available on SoundCloud, here.

Available on iTunes, here.

Full Transcript


Danny Levine (Producer)
Yeah, we've got Arno Lacoste today. who is Arno?


Neil Littman (Host)
I am thrilled to welcome Arno to the podcast today. Arno is the chief scientific officer at Aurion biotech. They are developing a novel cell therapy for the treatment of a debilitating eye disease. He comes from a great experience throughout his career in the cell and gene therapy space. He led a number of programs at Novartis, which as many of our listeners know was the first company to actually develop a car T cell therapy to, and the first company to get FDA approval. And he was there during that time. I'm really excited to talk to him about that. He did some academic research involving induced pluripotent stem cells. I think we'll have a lot to talk about today.


Danny Levine (Producer)
What exactly is Aurion trying to do?


Neil Littman (Host)
Yeah. So Aurion is developing a cell therapy for a debilitating eye disease. It's a, it's a basically corneal endothelial disease is the name of the disease and it's disease that results in blindness. It results from a damage of a single layer of cells in the cornea. Their thesis is that if they can actually replace the damaged cells with a new functioning cells, that they can actually restore vision and I'm excited to talk to or know about this, but, they've, I think been in over a hundred patients to date and they've seen some really wonderful and encouraging early clinical results about patients restoring some vision. I think there's a lot of proof of concept here. I'm excited to talk to our know about,


Danny Levine (Producer)
It would seem like an ideal application of regenerative medicine, particularly given the limitations of corneal transplants. What do you see the potential here?


Neil Littman (Host)
I think a huge potential here, number one, I think this is, the, I being immune privileged, at least at the side of the cornea is an ideal application for cell therapies to begin with, oriented approach is an allogeneic approach, right? I think there's a lot of potential there in terms of to control cost of goods, to make sure that this is not only a safe and efficacious, product, but one that could be, relatively cost-effective and scaled as well since it's not a autologous based therapy. I think, that from a business model perspective, I think is also really exciting. As you mentioned, I think there's a lot of limitations in terms of, availability of transplants and what patients that are suffering from this disease in terms of their current treatment options. I think there's a lot here to dive into with our know, and I'm really excited about some of their early clinical results.


Neil Littman (Host)
I'm excited to jump into the discussion.


Danny Levine (Producer)
I think of a company like Aurion now, delivering on the types of therapies were thinking would be possible with regenerative medicine outside of cancer and really restoring function. Does it feel like we're moving into a new phase of regenerative medicine to,


Neil Littman (Host)
I, I certainly think so. I mean, I think there, there's no question, I think that the field of gene therapy has really led the way in terms of regenerative medicine, right? There's a number of approved gene therapy products, right? Spark has an approval for gene therapy targeting a debilitating eye disease based on a genetic defect. I think companies like Aurion and what are know are pursuing is this sort of next wave of cell therapies, which I think are still relatively early, but, you know, as they amass more, you know, proof of concept in the clinic, safety and efficacy, I think there's enormous potential for these types of therapies to treat, you know, unmet medical needs, you know, things that are not only in the eye, but throughout the body. I think the eye is a great place to start. I think we'll, we'll see some, some really exciting developments here over the next 3, 5, 10 years.


Danny Levine (Producer)
Well, if you're ready,


Neil Littman (Host)
Let's do it. Arnaud, thank you so much for joining me on the show today. I'm, I'm really thrilled to have you with us.


Arnaud Lacoste (Guest)
Thank you for having me.


Neil Littman (Host)
My pleasure. So today I am very excited. We're going to talk about stem cells, regenerative medicine, and specifically cell and gene therapies and your efforts to develop a regenerative therapy to restore vision at Oregon biotech. Before we dive into what you're doing today, though, I want to spend a little time on how the field has progressed over the last decade. You have, I think a really great vantage point. You previously directed cell and gene therapy at Novartis for 12 years. You were involved in the development of treatments for spinal muscular atrophy car T based therapies, cell therapies for the treatment of retinol and, and other debilitating eye diseases. Love to start with about your background at Novartis. Can you talk about the programs that you led there and what you learned over that time?


Arnaud Lacoste (Guest)
Sure. Yeah. My time in a month has been amazing experience managing amazing part of my career. I joined Novartis in 2009. I'll explain in a minute why that is actually relevant. I was hired there to build the company's first stem cell platform. I had directed a stem cell facility that was creating human embryonic stem cells and the so-called Ikea cells. We can maybe get into the detail of what that is a relator before joining of artists. This had been also an amazing experience. There was so much going on with not only around the science, but around the social aspects and ethics that was involved with running some an IPS cells that doing that at that time was fantastic. One question that really kept bothering me was how can I maximize the chances of, in my, within the time that I have in my career have a significant impact on people's lives, patient's life lives and an opportunity to solve big problems in medicine.


Arnaud Lacoste (Guest)
Novartis really provided that opportunity for me for at least three reasons. The first one was technology. At the time when I joined the tech, the company was building these very advanced platforms for what is called high throughput biology and high throughput genomics. All these platforms that are driven by robots that essentially work DNI and creates thousands, if not millions of data points every day. The second amazing thing about this was the quality of the science. What was really incredibly rewarding about this was the quality of the scientists there and read that constant desire to dive deep into biological mechanisms, molecular pathways, developmental pathways. The goal was really never to just publish papers there, but read to push until at some point a door would open and our understanding of biology and these mechanisms made it possible to really create something that would be life-changing for someone it's essentially a therapeutic idea.


Arnaud Lacoste (Guest)
The third thing that was really important at Novartis for me and I use that everyday now is that there was a culture of not just a culture of innovation. A lot of companies say they have a culture of innovation. There was a culture of constant reinvention, self reinvention at Novartis, so that the scientists there, they clearly wanted to create the medicine of tomorrow. Again, a lot of companies say that, but the big difference there was that these scientists were not afraid to question everything they knew about therapeutic design and consider new paradigms such as cell therapies and gene therapies. This is why I came in and consider these. I mentioned earlier, I joined in 2009 to create an ITSs platform or platform at Novartis. Remember that the first human IPS paper was published right at the end of 2000 2007, beginning of 2008 and right away, Novartis decides, okay, let's make this part of our platform.


Arnaud Lacoste (Guest)
A lot of companies time for those who remember that period, we're talking about the potential of IPS cells for drug discovery and drug design Novartis. Their approach was right away to say, okay, let's go hire that French guy from Rockefeller university and test this IPS team. I got to create that proven stem cell platform. They're connected to connect it with the company's high-throughput biology capabilities, and very quickly, this led us to understand much better how some diseases could be treated. For example, to your question about what programs I worked on, this led us to a new treatment for a disease called spinal muscular atrophy. Very importantly, this culture of Novartis and this interest in cell therapies, cell-based models or advanced cell based models, and originally medicine created momentum for additional innovation there. For example, we realized very quickly that if were going to use cells as therapies, we had to be able to engineer the cells.


Arnaud Lacoste (Guest)
That led us to create gene editing platforms. They are studying losing fingers, talent, and need to CRISPR to use, Archana acronyms, maybe. And, and so these creative in terms of internal familiarity with cell engineering, gene engineering, and this created that momentum within Novartis that led to Novartis leading the cart he wave, and also the wave of new gene therapies for the treatment of Binus and other diseases. Very exciting part of my career, I, I got to use and develop amazing technologies and amazing therapeutics work with some of the best scientists I've ever met there, and also learn how to manage innovation inside a complex organization. I use that everyday as a, as a startup exec, a huge, huge value for me, not just from the point of view of getting to be involved in these new types of therapeutics, but also in terms of now creating a company from the ground up.


Neil Littman (Host)
Or no, there's a lot to dive into there. I, you and I clearly share a passion for regenerative medicine. The development of cell therapies as our listeners. No doubt. Now I lead business development at the California Institute for regenerative medicine for a number of years. I want to, I do want to dive into the IPS cells and the platform that you were building in a minute, but I want to take our listeners back. Cause I think you bring up a really good point. I want to take our listeners back in time because the, and I distinctly remember the partnership that Novartis struck with the university of Pennsylvania around the car T program, I think was a major inflection point in the field. That type of thing had never been done. Right. I think that really ushered in this new wave of cell and later gene therapies and really put the field on the map, so to speak.


Neil Littman (Host)
Of course, Novartis was the first company to actually develop and commercialize and get FDA approval for car T. I think, your time there seeing all of that, must've just been incredible.


Arnaud Lacoste (Guest)
Yeah. The story is there, the stories that we had internally within the scientists, but not just within sciences within the, the people who are in charge of business development in charge of regulatory, instead of manufacturing were amazing, just very unique to be there at the time. Of course, the stories from the patients, some of these patients, pediatric patients, just to put some, some context, the first car T programs are now commercializing the brand named Kymriah by Novartis targets, form of leukemia that affects children and adults. Has a lot of the patients who we treated were at a stage where everything has had been tried. That was, they were at the end of what could be done to save the lives. That the parents, the pediatric patients, parents enter them in the trials that were running there. You talk to the clinicians who worked with us at Novartis about this, and they will tell you, some of these patients were on their deathbed, especially one little girl.


Arnaud Lacoste (Guest)
I remember that story. To me, my condition on a deathbed in June, back in school, in September. So, these amazing stories, again, just talking to how much, how much cell and gene therapies will have any impact, essentially the are already having an impact today, but they will have so much more of an impact.


Neil Littman (Host)
Yeah. And I couldn't agree more. Those stories, I, I don't remember exactly what the clinical results were from those early trials, but they were something like 80 to 90%, I think, complete response rates for children that were refractory to all other forms of treatment. These were really not only groundbreaking, but were really a, as you said, it was a last ditch effort to save a lot of these children's lives. They had no that had failed all over all other forms of therapy. So really amazing therapies that were developed. I do want to transition back and just talk about induced pluripotent stem cells and your work at Rockefeller university, and then what you were doing at Novartis, as you mentioned, IPS came on the scene, I guess, kind of the 2007, 2010 ish timeframe, obviously Shinya Yamanaka was the recipient of a Nobel prize for you're creating Yamanaka factors and creating induced.


Neil Littman (Host)
Being one of the people to create induced pluripotent stem cells. I think that was in 2012, that he was the recipient. Could you talk maybe just for our listeners, could you talk about what a IPS C is and then your work building th that type of platform at Novartis, and even before that at Rockefeller university?


Arnaud Lacoste (Guest)
Yeah. IPS says IPS means in prohibiting stem cells. What does that mean? That means that these are cells that have the ability to differentiate in to virtually any of the cell types that constitute the human body. That's the definition of Floyd proteins and induce comes from the fact that they are created in a lab by reprogramming readily accessible cells. For example, skin cells, as a reason for a seed, from a simple skin biopsy or blood cells reprogramming them using what you mentioned just a second ago, the Yamanaka factors into a new cell type that now has properties and are called IPS cells. When this technology was first created, it really created a lot of hope that we could create healthy cells and tissues in the lab, and then use them to repair the effective organs in our body. This discovery was made and, and published the feed of medicine started talking about taking skin cells, for example, from a patient with Parkinson's disease, reprogramming the skin cells into, again, these IPS cells, and then differentiating these into the type of neurons that are dying in the Parkinson's disease patients, and then inventing them to that person, same concept with diabetes or Alzheimer's and other diseases.


Arnaud Lacoste (Guest)
That was over a decade later, here we are today. And, if you look at the evolution of that field, it has gone through so much learning. We cannot say today that, the type of therapies that we hoped we would have pretty quickly in 2008 exists today. Don't nothing has been approved yet, but the concept is still here. We have learned a lot about what it takes to engineer reprogram differentiate, and importantly, manufacturing the cells at the same relevant scale, and at the level of quality that can provide the FDA with the incentive to prove these drugs. Now several clinical trials are ongoing and some of them are starting to show amazing results. For example, just last week, a company called SEMA therapeutics reported that at least one of their patients in the trial, that they are running to cure diabetes. One of the patients essentially saw their symptoms reverted back to normal.


Arnaud Lacoste (Guest)
So an amazing development. We see, how these trials, these trials are successful. If they are, if the semi-trailer are successful, we may be looking at a second high impactful cell therapy. The first heightened bad cell therapy in many ways is what we just mentioned. The car T cell therapies. This could be the second one with just something that completely changes how we manage or even treat diabetes. Of course, we at Dorian, from what we see in our patients believe that our lead cell therapy candidates will have an impact that is probably similar in scale. We take patients who are blind and then restore vision.


Neil Littman (Host)
Yeah. I want to dive into that in just a second. And I think you're right. I mean, the SEMO trial is extremely exciting. That's what I've been following for a while. I mean, that technology was out of Doug Melton's lab at Harvard. I think someone was acquired by vertex a couple of years ago. Really exciting to see that's finally now in the clinic and that's being used to treat patients. I do want to now transition to what you're doing at Oran and talk about the program you mentioned going after, debilitating eye diseases. Could you talk about your lead program and the scientific rationale behind it?


Arnaud Lacoste (Guest)
Yeah. Our lead program targets a type of blindness that is caused by a layer of cells dying in the cornea. In one word it's called corneal disease. It causes blindness in about 16 million patients in the us, Europe and Japan. It's again, it's called caused by the fact that a single layer of cells degenerate called the corneal endothelium. If you have this disease today, first, you will go blind and your options are worldwide. Very limited in the, in the us, in the west in general, you get a corneal transplant, we'll discuss in a minute why that is actually also limited, but in the rest of the world, there's just not enough supply of Cornell's donated corneas to cure you. There's, in fact, there's a gap of one to 70, there's only one Cornell available worldwide for 70 needed. In general, a lot of patients have no treatment options.


Arnaud Lacoste (Guest)
The second issue in digital supply is that where Cornel transplant is possible, this kind of surgery actually is quite complex, and there are not enough surgeons who know how to do it well. There are about 20,000 of technologists in the U S for example, and about 1500 Cornell specialists. About 300 at the most of these Cano of specialists are actually actively performing corneal transplant. And, and most of them, most of them are actually on the learning curve of trying to essentially better the techniques. In general, there's a lack of surgical skills in the west, and there was no surgical skills, essentially in the rest of the world. The, the procedure of corneal transplant is also inconvenient for the patients. You receive a canula transplant, you essentially have to rely on your back for several days. It's very uncomfortable. A lot of patients complain about this, and then there's a lot of what we call regraph rates.


Arnaud Lacoste (Guest)
These Conor transplants tend to fail in up to 25% of the patients. What we are doing is saying, well, conceptually, these could all be solved by eventing the cell therapy since the disease is called by caused by the fighters, only one cell type in one cell layer, degenerate let's amplify the says, manufacturer them in vitriol, and then simply position them on the post-sale side of the cornea, where they normally reside have the patients. Let's the cell and graphs that says and graphs, which takes on you about two to three hours, and then they can go home. From what we see now, patients, this has showed amazing results. We have patients who come to us blind and recover vision enough vision to drive, and some of them recover 2020 vision. So, so an amazing chance, really, exactly. What's the promise of cell therapy was, taking patients who had dying tissue causing in this case, blindness and reverting the situation to essentially normal, healthy states.


Arnaud Lacoste (Guest)
A lot of over on these, a lot of quantum specialists and Trini excited about this, we get pretty much every day, we get contacted by an ophthalmologist asking us when is this going to be available?


Neil Littman (Host)
Clearly, some amazing progress in some really incredible early results that you're seeing, w what is the starting cell type that you're using.


Arnaud Lacoste (Guest)
So we are studying with donated corneas. We take the cells that are needed in the patients from these donated corneas, and then they expand them in the lab or in manufacturing facility at a scale that essentially closes that gap. I mentioned earlier that there's a gap of one corner need for 70 patients by taking con by taking the cells from one cornea and expanding them in our manufacturing process. We essentially, from one cornea, I able to provide hundreds. In the near future, we probably be able to provide thousands of doses from that one, one studying tissue. Essentially right there, we just completely changed the supply situation, and completely solve the problem of lack of supply.


Neil Littman (Host)
Our know that there's one actually a critical point. I want to dive into here. So, so you're pursuing a allogeneic approach as opposed to an autologous based approach. Could you talk about the difference between those two and why the eye is maybe an ideal candidate to go after, because it is immune privileged and what that means for a allergenic based approach?


Arnaud Lacoste (Guest)
Yeah. Great. One of the big advantage of this particular cell therapy is we know clinically that these cells are not rejected. All the patients need is a simple topical application of steroid eyedrops to essentially maintain allogenic tissue. We know that because Connell transplants with these topical third treatment are not rejected. Our cell therapy is not rejected either because it comes from the same tissue and these biologically. That is pretty amazing is due to the fact that what maintains the even privilege of the front part that is of the eye is precisely the cells that we transplant, they themselves, a secret the factors that instruct the recipient's immune system to stay away. This allows us to create what you just mentioned is an allogeneic cell therapy, meaning a cell therapy that can be manufactured from one donor tissue, and then delivered to any patients regardless of their actually type.


Arnaud Lacoste (Guest)
This is important because what, so the, the alternative would be an autologous, personalized, essentially cell therapy, meaning that we would have the case for Kathy, for example, we would have to manufacture a new set here before each patient's cost associated with that would be very high in this case because we can scale production and treat more than one patient with each batch. We make, we bring the complexity of this, and also the costs down to shoot extent.


Neil Littman (Host)
I, and I think that's a critical point for our listeners to understand is, the, the first wave of car T's were all, autologous based. And, those therapies cost several hundred thousand dollars. I think what you're doing, because you're doing an allogeneic approach, there's the potential to significantly reduce your cost of goods, to have a lower price point for therapy itself, right. That becomes, more and more critical as you're going after larger and larger patient populations. I, and I think, I'd love your perspective on this are no, but I think for us to really see the next wave of cell therapies being more widely adopted, I think we will probably need to get, price under control before we see this next, next wave of cell therapies, really hitting the market and really being adopted more mainstream than they are today. But I'd love your perspective on that.


Arnaud Lacoste (Guest)
Yeah, correct. At this point in time, the one of the main problems with even the cell therapies that are, for example, that show amazing efficacy, the problem is price. The cost of policing. These cell therapies is so high that it's almost impossible as of now to reduce the price to the payers and to the patients. A very significant fee. The only way that one of the main ways to do this is to transform or to transition from an autologous paradigm to an allergenic paradigm. Essentially make these car T cell therapies or cell therapies in general, render them able to evade the recipient's immune system. These, as we mentioned earlier, enables us then to treat more than one patient for each batch of cell therapy produced, meaning that we can now start to make economies of scale and drive the price of these therapies down. I think that this is going to be, this is a major hurdle in the field of cell therapy right now.


Arnaud Lacoste (Guest)
When we manage to move beyond this problem, th the impact on patient populations, the impact on the practice of medicine in general, it's going to be really very significant.


Neil Littman (Host)
I couldn't agree with you more. Okay. I'd like to talk about where you are in terms of clinical development. So w where are you today? What do you know? I mean, you talked about the safety, the efficacy from, the patients that have been treated so far, what is the path forward for the therapy and just ballpark? What are the timelines look like?


Arnaud Lacoste (Guest)
Yeah, so we have treated over a hundred patients in Japan and other patients outside of the U S very successfully in Japan. We think that we are going to be able to apply for conversation probably in the next two, three years, hopefully earlier, we'll see, in the U S we have to go through the FDA process, which of course is distant from the Japanese regulatory process. This is going to take longer, but again, we are in a unique position where we enter these FDA related process with a drug, which we know works. We know it actually has efficacy, very good safety profile. We have a flow of data, five at least years of data innovations that we've fostered, that were frustrating in Japan saying we have something that really looks like a cure, something that restores vision very long term in patients.


Neil Littman (Host)
Our know, could you talk about the decision to pursue initial trials and approval in Japan versus the U S is that simply an artifact of that's where the technology originated or was it a business decision, or I'd love to understand that thought process a little more?


Arnaud Lacoste (Guest)
No, so yeah, it was decided it was not a business decision. It was related to how essentially this technology came to be the first really research group that started turning this idea of using corneal endothelial cells as cells therapeutics was a group in Japan, led by in CURO. They really push the concept very far. They treated patients through the last number of patients for the, for the Japanese system. They really followed these patients for years after delivering the cell therapy. Essentially proved clinically very convincingly that the concept works leads to really, again, amazing efficacy and also has a very favorable safety profile. That led us to create, and we created that in the us from that self-therapy asset, essentially, that was already clinically validated.


Neil Littman (Host)
Do you see that there's potential to expand to other indications? I get, I guess, where my, where I'm going with this question is how broad a set of conditions do you think this approach might be able to address?


Arnaud Lacoste (Guest)
Yeah, so this particular cell, is specific to comment on the through disease just by definition, but the technologies that we use to manufacture the cells, deliver the cells are reusable for other cell types in the eye, and probably outside of the eye in the rest of the body. We are working on these, creating a portfolio of cell therapies using what we are, the manufacturing process and the technological platforms that we are using for these lead cell therapy programs to create other cells, other types of cell therapies, which we think will have a similar impact, at least on how we treat blind patients.


Neil Littman (Host)
I, I meant to ask this before, but I think this is a really important question, and that's a mechanism of action of the cells. Do you, it sounds like the MOA for these is that they actually in graph and then help reconstitute the function of the damaged or diseased cells or the, the other potential is that they don't actually in graph what they help recruit indogenous factors and work by the power can effect. How do you think these cells are actually working.


Arnaud Lacoste (Guest)
Well? One of the advantages of the eye and especially working on the cornea is that you can email the cells and you can see the cells that you deliver noninvasively envision. You can apply a microscope to the surface of the cornea and see each individual cells. We know for a fact that the cells that we deliver actually, and graft and reconstitute the tissue that is missing these patients. That's one of the situation where the debates between whether the cell therapy actually regenerates the tissue or whether the cell therapy provides trophic factors that help the recipient's body regenerates the missing tissue. That's where the debates actually, solves. We know that in this case, we are truly original in the tissue. It's, it's a big difference or significant difference with other types, cell therapies, IP therapies, for example, that are currently being tried in clinical trials for the retinol where cells are delivering the retina.


Arnaud Lacoste (Guest)
We don't know for sure that the cells reconstitutes the, the dying part of the retina, or whether the provides trophic factors that enable whatever tissue is remains in these patients to close the lesions, that altarpiece patient's vision.


Neil Littman (Host)
Yeah. I think that's a really critical point. The other point that you brought up, which I want to just spend a couple of minutes on is manufacturing. I've talked about this on the podcast before, but the manufacturing is, is absolutely critical clearly in the, particularly in the cell therapy space, it sounds like you're doing manufacturing in-house. Could you talk about the manufacturing process, your decision, if you are doing it in-house to keep it in-house versus to manufacturer externally via a contract manufacturing organization?


Arnaud Lacoste (Guest)
Yeah. As of now, we are not doing it, in-house, there's a number of reasons for this. The simplest one is we need to progress as fast as we could. We really want to bring this to patients as fast as we could. We didn't want to delay the program by just spending time creating a manufacturing suite inside of the company. For now we are using Excel manufacturing contractors, in this case, the manufacturing process is very well controlled. Again, there's a lot of clinical validation for the cell therapy. We have a lot of knowledge about how to expand the cells, how to qualify the product. So, we, it makes it really easy for us to transfer technology, train and work with external organizations who already have cell manufacturing suites. For us, we are in a situation where we are now in a position to move really fast towards clinical studies.


Neil Littman (Host)
I mean, it's very exciting place to be. I want to, I want to take a step back and get your 30,000 foot point of view on where you see the field of cell therapy progressing over, let's say the next five or 10 years.


Arnaud Lacoste (Guest)
Yeah. I, I, I tend to say, I think that we are two points in this field where we are in a new way is essentially is forming a new wave of cell therapies. If you look at the history of cell therapies, in many ways, you can say it started in the 16 with the invention of blood transfusion. First practicing in dog's first attempted in 16, 28. If I remember correctly, of course it failed for decades until it succeeded in around 16 65, 67, that was before we knew of actually types and blood types. That was essentially the first time that this concept was tested successfully. This concept that, we can replace a missing tissue or defective tissue with a new tissue. What is amazing is when you look at the cell therapies that we develop today, such as car T, and again, very successful, they still use many of the same concepts that are used for blood transfusion.


Arnaud Lacoste (Guest)
In fact, Gotti is largely based on transfusion technologies. And, and so, for all these cell therapies that do not require that we reconstitute the precise tissue architecture, this first wave of technology is okay, but we have to realize that, the, the promise of cell therapies will only come through if we become able to rebuild complex biological structures. For this, we have to start something new and that's for a number of years, weren't in a position to where we didn't really know how this was going to happen. I think that there's at least three scientific and technological advances that are now giving these new waves, some good momentum. The first one is new detection capabilities. More and more, we have non-invasive ways to detect disease early. This is very important because it means that our ability to intervene before tissues get to damage is increasing. This in terms means that the severity and scale of the damage that we're trying to treat with cell therapies are decreasing.


Arnaud Lacoste (Guest)
More and more, we are going to catch a problem at a point where it's easier to solve the first there's this, the second technological advance and send if to advanced, that is really helping form that new wave is around material sciences and the creation of new biomaterials. We've seen it in the past few years, that really a lot of effort has gone towards making these new bio matrices, these new bio materials that we can use to control the environment or the cell therapies that we deliver in the body. That helps us, of course, direct tissue, regeneration, but also form much more complex architectures. The third advanced of course, it's is advances in software and hardware, specifically high precision robotics and machine learning. This is really also critical because in many organs, the eye is a great example. A human motor capabilities will not be precise enough to enable us to deliver cells and recreate fully functional tissue architecture.


Arnaud Lacoste (Guest)
In the eye, if you want to recreate the tissue, a few microns, a mistake of a few microns makes a huge difference in terms of efficacy in terms of patient's quality of life, essentially. We wanted the next wave of cell therapies to actually be, if we want the next wave to be safe and efficacious. We also need to think about how we are going to augment our surgeons, motor capabilities, how we are going to enable. Now the human hand, the surgeons hands to create tissue architectures using the cells that we manufacturer that are precise at a certain micron, sometimes a scale. We need more precise robotics, and we need probably the surgeons to be helped by this new AI and machine learning concepts. We are trying to see startups create various combinations of these three basic concepts or new detection, new material, especially biomaterials and use of hardware and software.


Arnaud Lacoste (Guest)
And this is a full part of what we are building current yet Aurionted. I think that this is really the next wave in cell therapies is a much more comprehensive, essentially a type of cell based therapeutics.


Neil Littman (Host)
I think there's no question we're at a very exciting time in the field. Well, our, no, I think we could probably talk for the next two or three days straight about some of these topics, but I do want to be cognizant of your time and wrap up here and say a big, thank you for joining me on the show today. I really appreciate your time and a wonderful discussion.


Arnaud Lacoste (Guest)
Thank you for having me.


Danny Levine (Producer)
Well, what did you think?


Neil Littman (Host)
I think those are a great wide ranging discussion. I really appreciate, I really appreciated our nose background, from his time at Rockefeller university and working at the stem cell facility there, where he was really focused on induced pluripotent stem cells to building that type of platform within Novartis. Then, his role at Novartis over, I think it was about 12 years where he had a vantage point of some of the car T's that they were developing there. You heard him talk about a program for spinal muscular atrophy. I think Arno really has a great perspective on the industry as a whole. And then of course, what they're doing at Aurion, I think is really exciting. I think in many ways will hopefully lead to this next wave of cell therapies that we're going to be seeing come to fruition. And, the next five or 10 years.


Danny Levine (Producer)
RN is addressing a large unmet need, but in some ways it seems like it's exploding in a unique opportunity with the eye. Do you think this points to a broadening of regenerative therapies or is this just going after some low-hanging fruit?


Neil Littman (Host)
I'm not sure there's any necessarily low-hanging fruit when it comes to developing novel cell and gene therapies. I mean, it's all extremely challenging work. I think, you heard our know, talk about this idea of the cornea being immune privileged. I think there are certainly a lot of advantages there. I think there are advantages as well because the cornea can be imaged relatively easily and noninvasively, so they can actually see that the cell, what the cells are doing. You heard them talk about, they can actually see that the cells aren't grafting, right? With a lot of cell based therapies, w in different locations within the body, you don't really know if they're in Grafton, if they're not in grafting, what the duration looks like if they're working with, by the trophic effects and recruiting indogenous factors, it sounds like Arno and his team have a very clear idea of how these cells are functioning.


Neil Littman (Host)
So I think that's a huge advantage. So, I think it makes a lot of sense to start with the eye in this situation. We also talked about, allogeneic force autologous, again, makes sense to go after the I here. I don't view it as low-hanging fruit, but I, it seems to make a ton of sense that, develop a cell based therapy that is targeting, debilitating eye disease.


Danny Levine (Producer)
One of the most interesting parts of the discussion for me was towards the end when artists started talking about the precision involved in all this, and I think, tend to take a somewhat simplistic view that you grow the cells, you stick them in the eye and it takes care of itself, but what role does precision plan all this and how much technology is going to be needed to develop around these types of therapies to really get them to work well?


Neil Littman (Host)
Yeah, I think that's a really good point. I think our know, brought up the, I think you mentioned that if the cells off by a few microns, that makes a huge difference. And, I hadn't necessarily thought about that before, but clearly, placement of the cells when it comes to the coordinator or elsewheres is critical. I think developing additional technologies that can help surgeons make sure that they're placing the cells in the exact right place is going to be critical, not only for their, immediate and longer-term safety, but for the efficacy of those cells to, and then the durability of their cells over a, a long timeframe. It's not just that the development of the cell therapy itself, there's a lot of other enabling types of tools and technologies that need to be developed in conjunction with the cell therapies to actually deliver them effectively. I think that's a really critical point.


Danny Levine (Producer)
How big a limitation do you think price for these therapies are and does Aurion's approach give you hope that they can address that issue?


Neil Littman (Host)
It, it does. I mean, there's a lot of, debate in the field, right? I mean, the autologous based approaches are much more expensive, right? If you look at the car, T's, there are several hundred thousand dollars per course of treatment. Those are going after relatively limited markets might tell a limited number of patients, right? When you talk about much larger patient populations, the cost is going to become prohibitive, right? There's a lot of different cell and gene therapies that are targeting sickle cell disease, for example, is a much larger patient population, right? We need to bring costs down in order to deliver these therapies effectively to larger patient populations across the globe. So, the allogeneic based approach, particularly in the, I think our notice had there was about 16 million people worldwide suffering from this disease. I think this represents a nice proof of concept that these types of therapies can be developed in an allogeneic fashion.


Neil Littman (Host)
We can keep costs under control and then deliver them to the patients. Obviously they have a long way to go, but, early clinical results are looking very promising.


Danny Levine (Producer)
Do you think Aurion's work says anything about the future direction of regenerative medicine?


Neil Littman (Host)
I certainly hope so. Yeah. I mean, I think they're, they have some really novel groundbreaking work that they're pursuing here. The proof is it will be in, well-controlled larger clinical trials. You, you heard that they're going after approval in Japan first makes a lot of sense for them. That's where the technology originated and that's where the initial patients were treated. I think, having, larger clinical studies is going to be critical, them getting approval, hopefully in Japan, at some point in the relatively near future will be critical. Of course bringing the, the drug, the cell therapy to the U S for clinical trials and approval will be critical. Yeah, I mean, I think in many ways you heard our notes talk about this idea of this next wave of cell therapies. I think what he and the team at Aurion biotech are doing is exactly that, right.


Neil Littman (Host)
They're pursuing this next wave of cell therapies. I think it represents a tremendous potential.


Danny Levine (Producer)
Well until next time,


Neil Littman (Host)
Thanks, Danny.