Lyra Therapeutics, Inc. (LYRA) Earnings Call Transcript & Summary

Welcome to the Lyra KOL Event. I'd like to turn over to our first speaker, Maria Palasis, President and CEO of Lyra Therapeutics.

Thank you, Priscilla. Good afternoon, everybody, and thank you for joining our KOL event today on chronic rhinosinusitis. We will be making forward-looking statements today. I encourage you to look at our risk summaries in our SEC filings. Lyra's development over the years has been guided by KOLs and experts in the field, and we're thrilled today to have 3 of those experts. We have Dr. Robert Kern, who is our Chief Medical Officer and also the Chairman of Otolaryngology at Northwestern. We also have Dr. Amber Luong, who is Professor and Vice Chair for Research in Otorhinolaryngology at University of Texas; and Dr. Brent Senior, who is Professor and Vice Chair of Otolaryngology at the University of North Carolina. I'll start with a brief overview for those who are new to the story, and we'll describe our XTreo platform. And then I'll turn it over to Dr. Kern, who will then provide an overview of our 2 product candidates. And then he'll moderate a panel with Dr. Luong and Dr. Senior. And then we'll go into a question-and-answer session. Lyra Therapeutics has focused on developing technology that allows us to target drugs directly to the site of disease over a sustained period of time and, in doing this, able to treat chronic diseases. So many of us have taken drugs systemically. And for many diseases, systemic drugs actually don't work. They don't work very well. They result in systemic side effects, and patients benefit more so by a localized therapy. And one of those diseases is chronic rhinosinusitis. It's a great example of a disease where steroids are really the foundation of care, but the issue is how do you get the steroid directly to the site of disease. For chronic rhinosinusitis, 8 million patients get treated each year. But we know that roughly 50% of them failed medical management each year. 400,000 patients each year get surgery. So there is an enormous unmet need of patients who are failing medical therapy and are being undertreated. So we have applied the XTreo platform and now have conducted 3 clinical studies to date and have seen safety and efficacy in each of these studies. We have the only implant that's been developed to treat this broad patient population, and we're in a position to address this unmet need in the CRS space. So what's required to be able to chronically treat a disease in a targeted way is having a technology that has a high surface area, that allows for very good contact with the mucosa, that allows a large dose of drug to be loaded and then being able to meter that drug over time. And for CRS, we deliver it over 6 months in a very consistent way. The attributes of the XTreo platform are specifically months of local drug delivery and then consistent metering of that drug over many months. And also, the other very important aspect is shape memory properties. So it's important that the implant can adapt to the surrounding so that it can stay in place as tissue remodels. And then finally, being straightforward to administer and comfortable for the patient. And we can do this with the XTreo with -- in a single in-office administration. So the panelists understand the technology, and they certainly understand the impact that it can have for their patients. I'm going to turn it over now to Dr. Robert Kern, who will take us through the 2 product candidates and share some of our data with you.

Thank you. Thank you, Maria. Before we get started, I want to state that neither Drs. Luong or Senior are employees of Lyra, but they have been compensated for their time in relation to this event. And all opinions expressed during this discussion belong to them and do not necessarily reflect the opinions of their affiliated institutions. So Maria talked a little bit about chronic rhinosinusitis, and it's been called an unrecognized epidemic because it's really extremely common. A conservative estimate would say that about 14 million people in the United States suffer from chronic rhinosinusitis. Only about 8 million of them actually seek care. Of those that seek care, they receive medical therapy. It's primarily steroids, some antibiotics, a few other things. But about 4 million of them fail standard medical therapy. And this results in about 400,000-or-so surgeries annually. Now chronic rhinosinusitis is -- it's a syndrome, not really a true disease. And it's characterized by the 4 cardinal symptoms you see listed there: Obstruction, pressure and pain, smell loss and nasal discharge. Now those together with confirmation by either a scan or an examination in the office gives you chronic rhinosinusitis. Now you have to have those symptoms, at least 2 of them, for 3 months, and then you're in the, what we would call, the CRS syndrome. Next slide, please. So laying this out, 4 million who fail therapy, about -- you can see 60% of them there, and these are the patients we're targeting with LYR-210. They have never had surgery. Those are people that are suffering. They've never really gone the full -- they're struggling with medical therapies. They're getting incomplete relief, but they haven't had surgery. And of the 4 million, 40% of them, 1.6 million, have had surgery. But again, they're still not -- they're still requiring ongoing medical therapy, and they still are symptomatic. So those are the candidates for LYR-220. So the Lyra philosophy here is to provide therapy for the full range of CRS patients, all 4 million that fail standard medical therapy. Now there are niche patients that might benefit from some of the other products out there, and we'll talk a little bit about that in a minute. But chronic rhinosinusitis, the syndrome, they are really -- it's broken down into 2 groups. There's patients with and without nasal polyps. Now the -- if you see there what we have, the shaded areas, those are patients with polyps. There are some who have never had surgery and a larger group that have had surgery. And those are potential -- the niche for the antibodies and for other treatments that are currently out there really touch only a very, very tiny percentage of patients, less than maybe 20% at most of the entire circle there. Next slide. So let's focus on LYR-210 for a minute. The -- this has many positives. First of all, it's a local drug. It doesn't have systemic effects. Secondly, there's 6 months of treatment with one application. And it's for the full range of patients, the with and without polyps. Now this is a device that's designed to fit into the sinus anatomy that's not been operated. And now we'll talk a little bit about the 220. But after surgery, the space is much larger, so you need a little bit different implant. But the drug dose and the kinetics are the same. This requires -- most importantly, requires no patient compliance. The problem with saline rinses, with nasal steroids is that patients have to cooperate. And patients don't like using nasal sprays. The taste, the irritation, nose bleeds, et cetera, et cetera. So the beauty of this product is you put it in, and the patient doesn't really have to think about it anymore. It's essentially like inserting one of those small canisters of nasal sprays into your nose and a miniaturized one and just forgetting about it. Now this demonstrates the anatomy and the insertion device here. It fits right under -- in a little niche there right underneath the middle turbinate. Mometasone is locally delivered. This is the -- Nasonex would be the nasal spray that supplies this. But it gives -- this drug is extremely safe. Very, very little is absorbed in the system, but it works right where the action is, at the epicenter of the sinusitis. And because of the kinetics of the release, it provides continuous treatment over the course of 6 months. And essentially, since these patients have all -- they are candidates who have all failed surgery, the 4 million -- I'm sorry, have failed medical therapy, the 4 million that have failed it, this is really an alternative to surgery. It's applied easily and simply with this applicator device. Local topical anesthesia can be slipped in easily. The product is not noticed by patients. They don't realize it's there. And it's designed to -- it can be replaced -- well, the kinetics indicate that it could be replaced every 6 months to provide continuous care, if more is needed after that 6-month with the initial treatment. And this is the only product out there that can provide that 6 months of treatment. Other products out there can provide some treatment but not to that duration, and that is a particularly important point to take home. 6 months is an excellent treatment window. Now some of you may be aware of these, but the Phase II results have been presented and aren't nearly impressed. They have been accepted, but they're not quite yet impressed. The -- I talked about the 4 cardinal symptoms, but this shows the data from 3 cardinal symptoms. Four cardinal symptoms were fine, too. But for the Phase III trials going forward, we're going to use 3 cardinal symptoms. And there's an aggregate score here. And the change, which is a drop, means that they have less symptoms. And you look that very rapidly, we noticed improvement with the LYR -- the 75-microgram dose. And by 12 weeks, there's a dramatic separation. And by 24 weeks, which is -- again is a 6-month window, there's a tremendous difference between the control patient and the treated patient. This is really quite an amazing response. And this works in both the polyp patients and the non-polyp patients. So the full range of nonoperated patients can benefit potentially from this. And this is, again, 6 months of treatment from one office insertion. Next slide. Now the 3 cardinal symptoms is -- were useful for the FDA trial, but the patients and doctors both think in terms of standard quality of life instruments like what's -- a typical one is a SNOT-22. Now that's someone's idea of a little bit of a joke, but it's basically 22 questions, and the patients rank it 0 to 5. And the higher the score, the more severe the disease burden. And you can see here the 2 doses, 2,500 and 7,500, and the control there. With the 7,500, again, rapidly separates and by 24 weeks is fairly dramatically different. The SNOT-22, a difference of about 9, 8.9, the patients will -- the overwhelming majority of patients will notice. 19-point difference is a massive change in the SNOT-22. This is similar to the kind of change you would see at surgery at 6 months or with these fancy new biologics, which, again, can only treat a small percentage of patients. But that's a $38,000 a year drop. And at 6 months, this product is essentially changing the SNOT-22 at a similar level. So that's a pretty dramatic change. It's twice the MCID or the clinically significant difference. And even as early as week 4, 70% of the patients have attained that 8.9 change, and 100% of them have achieved it by 24 weeks. But the aggregate difference between ours and the controls, our device and the controls or our drug and the controls, is twice the MCID. So again, this is an enormous difference, particularly when you consider this as 6 months with -- of local treatment with one office visit. So to switch gears and talk to LYR-220. It's essentially a very similar product. It's just it can expand to take -- to, how should I say, to address or fill the enlarged anatomy postsurgery. When you have sinus surgery, some of the air cells are removed there. So there's a wide space. And if you tried to slip LYR-210 in there, it would probably fall out, at least a significant percentage of the time. So this is a larger product, the same drug, same kinetics, the same materials. But it fits in there in a way that won't fall out. And there should be significant regulatory pathway advantages with the success of LYR-210. Now again, looking at the 40% of patients here that have failed surgery, this is what 220 is we're working on. Now there's a small number of those patients that would be candidates for the dupilumab or mepolizumab or omalizumab, the approved biologics. But they would not be at all indicated for -- at least not at this point, for patients without polyps, which -- so failures without polyps, the large dark green area there, they would not be useful for. So LYR-220 can really reach the entire group. Now there are other products out there for that small segment that essentially compete with the biologics for the small segment there. Again, it has responded, in the dark green part, to the antibodies and steroids, now -- and steroid implants. Now some of you may be familiar with SINUVA, which is a product produced by Intersect. Those would also be a potential use in that treatment segment. But again, it's much smaller than what we are offering. We have a much wider range of use, much larger market potential. Next slide. So the 2 trials that are upcoming should begin in late December. First one is the Phase III program, the ENLIGHTEN, which will be 350-or-so patients, 2 staggered studies, one shortly -- starting shortly after the other. Very similar structure and inclusion criteria as was done for the Phase II trial. The primary end point will be the 3 cardinal symptoms at 24 weeks, as mentioned, that's 6 months. And the other end points will be studied. The SNOT-22, the CRS PRO, rescue treatments, sinus CT scans, et cetera. So there will be other things tracked. And it's a 2:1 randomization. So twice as many patients will get the drug as controls. Now the BEACON study, the LYR-220, is for the larger implant for patients who had already -- who were failing but had already tried surgery. The -- this is a Phase II study. It's going to be in the U.S. and Australia. Primary end point will be -- this is just a safety and feasibility study, but we will track outcomes as well. And this is a 1:1:1 randomization. And the reason we have -- the dose is the same, the product is the same. It's just one has a little different mesh. And the reason for that is that we're trying to test the retention capabilities, which sort of seems to fit in there. It could be inserted easier and stays in better. That trial, again, has a similar time point. Next slide, please. So now I'd like to turn the question -- or the presentation over to our KOLs and -- Dr. Luong and Dr. Senior. And it would probably be best if you can just tell us a little bit about your practice setting, what kind of patients you see, what your role is at your institutions. And Amber, if you would go first, please?

Sure. Good afternoon, and I'm Amber Luong. I am a rhinologist but also a physician scientist at an academic facility at -- in Houston. And so my interest clinically has been primarily to treat these inflammatory diseases, specifically chronic rhinosinusitis, both with and without nasal polyps, as Dr. Kern had talked to you about. My basic science research, I also run a lab, has been focused on understanding the pathophysiology of chronic rhinosinusitis, so a lot of the immunologic or immune profiling of these patients. As Rob talked about, this is a big group of patients that we treat, so CRS with and without nasal polyps. I think that -- I get a lot of patients that were referred to me from primary care physicians or -- I mean, I should say, the general ENTs. And so we see a lot of patients who've already undergone several different treatment options, medical therapy as well as surgery. So I think I get the chance to kind of see the whole spectrum of patients who come in for their primary symptoms and getting diagnosed with chronic rhinosinusitis. And a bulk of my patients are those who have undergone multiple other treatment options and are looking for other therapies.

Thank you.

Brent?

Brent?

Yes. My name is Brent Senior, and I'm a Professor and Vice Chair here at University of North Carolina in Chapel Hill, where it's a balmy 90 degrees out right now. I care for all types of sinusitis in my clinical practice. I deal with also tumors of the skull base, but about 80% of my practice is inflammatory sinusitis. And the vast majority of that is patients who have had surgery and have not done well after surgery. So I would argue, I would say probably about 80% of my practice is sort of that difficult challenging patient who has had all sorts of treatment -- up until now, sort of standard treatments, and they're not getting better. So now they show up at my office and looking for other options. Yes, so I think that's really about it.

Terrific. Thank you both. I'm just going to throw this basic out there. What -- Amber, why don't you go first? What -- if it's an entry patient with chronic rhinosinusitis, how do you see the treatment paradigm? What's your standard protocol? How do you approach it therapeutically?

So are you talking about the person who's just showing up, has never been really seen or worked up for chronic rhinosinusitis? Is that the patient population?

Yes. Or -- yes, yes, essentially. Start from what the basics are.

Yes. So it's interesting. A lot of patients will come in and say they have sinusitis and -- or they'll say, "I have the sinus." And so as a physician, you sort of have to go through the history, and Rob had alluded to this. But once you have the history of these symptoms for longer than 3 months, then we need some objective finding. And once you have all of that in place and you figured out that they have chronic rhinosinusitis, then the paradigm does change a little bit by doing that nasal endoscopy and we see with or without nasal polyps. And so from there, even though you have these 2 different subgroups with the ones with polyp being more responsive to steroids, frankly, both of them undergo an initial treatment of failing irrigation and a topical steroid, even prior to surgery. And the challenge there, I think we'll go into a little bit more in depth, is just being able to penetrate the sinus cavity with those topical medications that are currently on the market. But those are probably the first-line therapy, saline irrigations and a nasal steroid spray of some sorts. And then if those then fail and they have chronic rhinosinusitis, you either offer them another round of medical therapy or proceed on to sinus surgery.

Okay. Brent, anything...

Yes. Rob, I think it's an interesting thing because when you think about medical management of chronic rhinosinusitis -- chronic rhinosinusitis, it's really been quite an amazing moving target in the last 10, 15 years or so. I know when I was starting in practice 20 years ago, we always viewed chronic rhinosinusitis as a disease that required antibiotics, right? Antibiotics were really the key to treatment. And what we came to know is that it's more than that. It's not just simply a bacterial disease, and it's a disease of inflammation. And so now we recognize that something that manages inflammation, in other words, steroids, is really a key to helping control this disease. And it's not just simply polyps. It's actually also chronic rhinosinusitis without polyps. So it's all forms of chronic rhinosinusitis really requiring management of inflammation. And so steroids become much more important for us for all of those patients. And we're always -- we do find that oral steroids are very effective, right? They can really be quite helpful in management of these patients, but there are so many side effects potentially with taking frequent courses of oral steroids. And patients will oftentimes respond to a course of oral steroids. But then just within a few weeks, they'll be right back where they were. And so we're always thinking about ways of administering steroids in a safe way, and that's where topicals come into play. And applying steroids topically, we do feel, is a much safer alternative and oftentimes a much more efficacious method for managing all these different forms of sinusitis.

Can I add something also to that? I think that at least for a lot of my patients, they think that there is a cure because -- and just to reiterate what Brent was saying, this is an inflammatory -- chronic inflammatory process. And I like to equate it to almost like arthritis of the joint. And sometimes people don't understand that the treatment, in order to keep their inflammation under control, then they are going to be on these chronic anti-inflammatory medications. And in our situation, it's going to be steroids. And so exactly, as Brent was saying and to reiterate the point, the topical delivery option is going to be much more -- much safer for the long run because we know these patients are going to need this on -- for a long-term basis and systemic steroids not only for other reasons, which we could talk about from the patient's perspective. But it's not a good health perspective -- on a health perspective, option being on it for long term.

Yes. I mean, both of you touched on something that when -- I'm a little bit older than Brent, but antibiotics were sort of the mainstay of treatment. Steroids were okay for polyps, but antibiotics were the mainstay of treatment. And it's only recently have we admitted that they really don't work very well. And mostly, they just make patients sick. And steroids are the standard, more effective than anything else we really have that's readily available anyway. And you pointed out the oral prednisone just has way too many side effects. So topical steroids really are the best thing we have out there, but I don't know how -- what your guys' experience is. But the patients don't like using those sprays. And most of it goes down the back of their throat. And there -- this new product, XHANCE, what's your experience with that? And how do you see that fitting in?

So XHANCE is an interesting product. It is a fluticasone product that is administered into the nose. So it's a country cousin to Flonase, what's out there right now. But a big difference in the way -- or the big difference in XHANCE is that it's a fairly significantly higher dose of fluticasone of the steroid than you get with Flonase. And it's actually administered by blowing into a device, and it sort of blows the medicine up into the nasal cavity. It is effective. It seems to help out patients. My personal experience is that it's not a huge difference from what I see with other topical nasal steroids like Flonase, though I would say it is definitely causing a better appearance to the cavity overall. But I have to be honest, I've been a little concerned about the dosage of the fluticasone in these patients and the potential for systemic absorption, the way that it kind of gets into the back of the nose and potentially gets swallowed over time. So I don't use it a lot in my practice. I also find it's frankly extremely challenging to get it paid for, and it is quite expensive for our patients. We struggled quite a bit with that as well. So I think it's an interesting option for patients, but it's not been a panacea.

Amber, any thoughts?

Yes. I think -- I mean, Brent brings up a great point about these currently available steroid applicators, right, whether it's through XHANCE or a nasal steroid spray. There is a significant amount that gets swallowed that people don't necessarily consider or think about because they are available over the counter. That being said, so what I normally will try is the steroid in my -- in the patient's saline irrigation. Now that's an option that is kind of a little -- maybe easier to get ahold of sometimes than XHANCE, although not all the time because it's considered off-label. But putting -- having patients put budesonide is -- that is used in nebulizers for like asthma treatment and putting that in the saline irrigation. But then again, the distribution up into the frontal sinus is better than nasal steroid sprays, the ones that you have over the counter, but not the best. And so back to your question, Rob, when do I use XHANCE? It's kind of, to me, is an escalation method for me. So if they can't -- if the nasal -- the budesonide irrigation don't seem to be controlling the inflammation primarily in the frontal recess area, the ones above your eyes, then I will give them a trial of the XHANCE because it does seem to go up into those more difficult areas in the sinus cavity better than maybe your steroid irrigation.

Yes. I would agree, Rob. I would just say that XHANCE for me is kind of second-tier therapy. I will, most commonly, as a first tier for my patients, utilize some sort of a compounded steroid solution so that they're irrigating their nose with a little bit of steroid in the solution before I would actually utilize the XHANCE product.

Again, that's -- also, the steroid irrigation addresses another thing, which is compliance, right? Because we're wanting our patients to do the saline irrigations as well. And that's a huge problem in keeping patients under control. Because we know it's a chronic disease, they have to stick with their treatment regimen, whatever that happens to be. And saline irrigation is always a cornerstone. And so when you are able to sort of put those 2 together, that's always helpful. But sometimes it just doesn't work, right? So then we're going to saline irrigations and something else. So anything that can help with compliance with treatment is going to be very advantageous for our patient population.

Yes. I mean, to me, I think it's an upgrade over Flonase or Nasonex. The problem is that the patients still have to remember to use it. And the second problem is unless they've had surgery, it just doesn't access the action. So those are 2 kind of limitations, although I think it is a step above -- costs notwithstanding, it's a step above Flonase or Nasonex. So that gets to the next question is, what about delivering -- I mean, this is rhinosinusitis, there's a problem in the nose and the sinuses. And then we think the problem when it gets in the sinus is it creates more symptoms. So how can you deliver the steroid to the sinuses more effectively? What do you think about SINUVA, which it's a little bit of a niche product because it's only for polyps, but how do you use that?

Yes. I think -- go ahead.

So go ahead, Brent.

Well, I was just going to say, I think -- yes, I think it has a role. I think it's another way of topically applying steroids for our patients with polyps. And so thereby getting the benefit of steroid, again, in a safer way for our patients. It does require placement. It is an actual device. It's another stent-like device that's placed into this previously operated sinus cavity with polyps in it, and it's done in the clinic setting. And it gives a fair benefit, I would argue, for patients acutely. Within a few days, patients will oftentimes be feeling a little bit of an improvement with it. It doesn't last very long. I don't remember exactly what the time frame is on SINUVA, but it is not a real long-acting product. And so it does have to be replaced and redone potentially on a frequent basis. So that would be one downside. It is fairly expensive as well. And just as with the XHANCE product, I've had some issues honestly with the cost for my patients. It is pretty pricey and a little bit difficult, a little bit out of reach for some patients as well.

Amber?

Yes. So I have to admit that I was extremely enthusiastic about the SINUVA product when it first came out. Having that ability to deliver relatively higher concentrations of steroids into the inflamed -- to that inflamed tissue where the disease is, right, within the ethmoid cavity, and if you have recurrence, this may prevent patients from going back to the operating room. It seemed to make a lot of sense. And then I did. I used it quite on a few patients when it first came out. The problem that I saw is exactly what Brent alluded to is that -- so the device is marketed for 3-month delivery. But the problem is that it turns out that their profile of distribution, their kinetic profile of releasing the mometasone, much of it comes out in the first 30 days. And then a significant portion, I think, if I remember correctly, about 80%, is completely removed within -- or gone off of the stent within 60 days. But then you're supposed to keep that device in for 90 days. So trying to get -- so what my patients would tell me is that they had great responses, and it would last around 60 days. And all of a sudden, the effect was starting to wear off. But if I -- but it was supposed to last for 3 months. And so from an insurance perspective, it was hard to get it in sooner. And also, you really didn't want that option. You wanted it to last longer, right? The whole purpose was for this to be something that the -- we could put into a patient, not think about it and let's say, back then, 3 months, and just forget about it and then have them come back and change it. But that wasn't the case. And so that was a very frustrating experience. The other experience was that at least when I was initially starting with the SINUVA product, I would try in some of my more challenging patients, but frankly, the ones that would have recurrent nasal polyps, which is a group of patients called aspirin-exacerbated respiratory disease. And so I have placed the SINUVA product into a couple of those. And it basically -- it would just disappear within the polyp. And my gut feeling is that just the amount of steroids that was necessary for that disease population just wasn't sufficient. And so it would have very minimal effect. And so because of those 2, along with the difficulty in reimbursement, it sort of waned and kind of fell out of favor in my practice. So I don't use it very often these days.

Yes. I would just echo what Amber was saying about the enthusiasm. I was pretty excited about it as well when it first came out. But exactly as she's saying that you got that sort of initial burst of improvement with patients, but it just didn't seem to last. And so that was kind of frustrating from that standpoint.

Yes. I think we were all really excited about the idea of being able to deliver steroids directly to sinus cavities. And I mean, there were some problems with the rollout. That didn't help, of course. That took a while to get straightened out. But the limitations really, in my mind, are: One, the person has to have had surgery before; and secondly, it's only for the polyp failures. That's all they're FDA approved for. So it's narrow. And then the last one, probably the biggest -- well, not the biggest, but one of them is the fact that the duration of the response is relatively brief, which creates reimbursement issues. So -- but the idea, the concept in my mind is delivering the steroids to sinus cavities because that, at least theoretically, should be able to really make a difference. What about biologics? Where are you using them now? And how do you see them fitting in this?

Yes. So the biologics are just super expensive, right? So from my perspective, they become kind of a third-tier-type option for patients. I'm going to want to make sure that my patients have had a very, very good surgery. I'm going to consider some of these other methods of local steroid deposition. So whether -- at the very least, they'll be on steroid irrigations. I'll consider products like XHANCE, consider problems like -- products like SINUVA. And if patients aren't improving with those types of treatments, and again, this is for polyp patients we're talking, not the non-polyp patients, but for polyp patients, then I'll start considering the biologics. Biologics are somewhere around $36,000, $37,000 a year here in North Carolina. They're a challenge to administer in that they're administered as an injection, self-administered as an injection with dupilumab. We give it every 2 weeks. And really, the challenge also is that we don't really know what the end point is with these drugs. So potentially, once you start using this drug, the biologic, you may be committing the patient to having to use it for an indefinite period of time, which is a lot to consider. If a patient comes in, they're 35 years old and they've been suffering from polyps for the last 10 years of their life and -- or 5 or 10 years and realize that they're going to go the next 35 or 40 years taking some sort of a biologic, that's a big commitment because we do know when patients stop the biologic, they seem to go right back where they were. So I'm -- they clearly work. They give tremendous benefits to our patients, but it's really a third-tier option and one that I have a long discussion with my patients about before I start administering it.

Yes. And I would reiterate what you sort of started out the whole conversation with, Rob. It's the fact that it is a really small group of patients that we're considering this because even in that patient -- I guess, I would say it's a very small group of patients who have polyps who also recur because of their disease process, meaning that they would be candidates for biologics or something, and I agree with Brent that it's a third-tier treatment. Otherwise, sometimes patients recur, and it also recurs several years later because they just fell off the bandwagon for their medical therapy, right? And in that situation, repeat surgery or some of these other -- we have to restart the algorithm again in terms of the treatment and don't necessarily need to go on to biologics because of all those concerns that Brent brought up with the biologics. Now for the patient population that it does, it seems to be a good option for us. So that patient population I alluded to, aspirin-exacerbated respiratory disease, these are the patients who may have had 3 to 7 surgeries in the past, those are great options. But if you're talking about your garden-variety CRS with nasal polyp patients who may have recurred 5-or-so years after their initial surgery, that is not the patient population.

Yes. I think these drugs are wonderful, but the cost is enormous. And again, it's only a small window of the 4 million people that fail standard therapy. It's a small number. It's -- SINUVA is, again, a small number. And XHANCE, it's a nice idea but, again, requires patient compliance. And it doesn't really get access. Unless the patients had prior surgery, it doesn't really get access very much to the sinus cavities. So despite the noise, we're still not that -- the ball hasn't moved that far down field. So in light of that, what is each of your reactions to the LANTERN data that -- the Phase II that I briefly went over there, that you both have seen presented a couple of times already?

Yes. So I think it's very enthusiastic, the results that are coming out of these trials. So as you sort of mentioned -- so chronic rhinosinusitis is a quality-of-life disease, right? So it's how it's affecting the patient's disease, I mean, luckily, only in a very rare population where there can be complications from their sinus disease. This is not life-threatening. So the symptoms are the key, I think, for how well these treatments and how effective or how successful these treatments are. And the fact that you're getting a SNOT-22 drop that is similar to what we can see in the range of sinus surgery and with oral steroids, that's excellent. So I'm excited about that.

So I'll take it even a step further, Rob. I was -- I'm not going to say dumbfounded, but I was very impressed. The one thing that really caught my eye with the LANTERN data was how good the LYR-210 product performed compared to the biologics. Now admittedly, it's apples and oranges, right? We don't have a one-to-one comparison here. But when you look at the biologic trials like the Dupixent SINUS-24 trial, and you see the amount of benefit with the SNOT-22 with Dupixent over control. And then you compare it to how the LYR-210 did over control, I mean, they're very similar, really remarkably similar. And for me, knowing how well my patients -- those selected isolated patients that I used biologics on have done, that's really encouraging to me. That's a big message to me that this is an impressive product, and it has a potential for really doing a lot of good for our patients.

So how do you think patients will -- do you think the 6 months -- do you think -- you've both seen it inserted. How do you think the patients will respond to this? Do you think this is something they would like, the -- both the timing? And you've seen it inserted and it gave you an idea of how difficult it is. Would you comment on that?

So I think over the last, I don't know, about 3 to 5 years, there's been kind of an insurgence of in-office procedures for sinonasal issues. So I think as rhinologists, general ENTs, we're getting a lot more experience offering and doing in-office procedures such as the ClariFix procedure, which sort of targets that same idea. This is a cryotherapy delivery into the back of the middle meatus. And so -- and my patients have -- are very enthusiastic about an option that is short of going to the operating room. I've done many, I don't know how many, but over 50 of these procedures just over the last couple of years for postnasal drainage. And I can tell you that the in-office -- the patients are able to tolerate these procedures with our local anesthesia methodologies. And so I don't think that, that is going to be an issue putting this device in even in a patient who hasn't been operated on before.

Yes. I agree 100%. We do lots and lots of procedures in the nose with local anesthesia, and patients are remarkably tolerant of it. It's actually -- it's a wonderful thing that we actually have the ability to anesthetize the nose with local anesthesia as well as we can. And we can do quite a bit, and patients do very, very well. And let me just tell the folks that are listening, this is not like a COVID test because we do give anesthesia before we put things into the nose. So it is a more comfortable experience, potentially more comfortable experience than what many of you may have experienced with the swabs up inside the nose for COVID.

I agree. I think patients were warm to this, the insertion, and as well as the fact that you get 6 months and you don't have to think about your nasal sprays anymore. And in the surgical failures, the 220 would be another option. It gives you a lot more punch and a lot broader range than what's currently out there with SINUVA. And with -- compliance with regard to budesonide can be very tiresome to do. So I think the patients will like it. But what about the physicians? What about the ENT physicians? Do you think this will slow them down? Do you think this will -- they'll feel like they're losing surgery or income or what?

No. So I think that this is going to be received very well by the general ENTs. I think we have to remember, going back to one of your initial slides, Rob, in your presentation, what, 4 million people about go and seek medical therapy for chronic rhinosinusitis, but yet only a very small percentage, 10% actually, proceed on to sinus surgery. And I suspect that a big portion of these patients who have failed medical therapy do not proceed on to sinus surgery because of whatever -- numerous reasons why they don't want to do it. They heard horror stories about surgery and so forth. So I think there's a large group of patients that our general ENTs or rhinologists are not treating and would welcome an option, a treatment option that they can give to their patients short of surgery or, again, another step. And then if that doesn't work out, then maybe you have to proceed with sinus surgery. But it just provides options. So I don't think that's going to be a deterrent to it. And just by seeing the success that we're seeing with some of these other in-office procedures, and there's a number of them now that are on the market for these various different -- nasal remodeling, rhinitis, and they're well received. So I don't think that, that's going to be an issue.

So I think it will absolutely decrease the number of surgical cases that would be -- if the pie were fixed, that would be within that pie. But what Amber is saying, I believe, is 100% true. I believe that if the word gets out there, the patients that are just afraid to come into the ENTs because they've heard the horror stories of sinus surgery will now start coming in to see us. And so I think we'll make up that difference quite well with the additional patients who will show up. I think -- the truth is, is that traditionally, nasal sinus surgery has a bit of a bad reputation. And there's been lots of horror stories about it for patients. And so I do think that patients are just afraid to see the ENT doctor. And this will be a reason for them to see the ENT doctor, knowing that there are nonsurgical approaches that can be very beneficial for their sinus disease.

But as a surgeon, I would like to reiterate that things have changed a lot, right, Brent, in the last several years, which makes these stories definitely less common. So all of those things that they heard about, I think that many of the patients who do undergo surgery don't be -- don't experience those. But those stories exist on the Internet through -- between family members over Thanksgiving dinner. They tell these stories. And so...

No. I don't want to be at your Thanksgiving, if that's what you're talking about.

I know, right?

I mean, realistically, we have 4 million people fail medical therapy. And a majority of them -- only 400,000 are having surgery. So the majority of them are a little leery of surgery. So they're large volume. And then you talk about there's, according to the studies we've done, at least 6 million people that aren't getting treated at all because they either -- they're using nasal sprays on their own and don't particularly like that or they're just wandering out there. So the ENTs are always afraid that the next thing will change their life, but I think this is unlikely to make a substantial decrease. It will open up new horizons. And so lastly, just last question before we go to the participants, where do you see this fitting into your treatment paradigm, the 210 and 220?

Yes. I kind of see 210 as being somewhat of a whole change to my paradigm, honestly. I think it will be something that I'll offer my patients before I consider surgery for them and really giving them a chance to avoid surgery. I think it's an exciting thing because it could be a big paradigm shift.

Amber?

Yes. I would agree. There's -- when I'm in front of a patient, I can kind of already see -- as I'm laying out the treatment options to patients, I kind of can feel what they're up for, what they're not up for. So I'm excited to consider that there will be more treatment options, knowing that many patients either cancel or can't follow through with it or just are very leery of it. So I like that option. And then going -- thinking forward, having a device that we can put into a patient who has recurrent nasal polyps and can keep them at bay for 6 months, and I really like the delivery mechanism. I think that, again, we were talking about the -- how excited we were for devices such as SINUVA, where they were releasing -- delivering steroids directly to the mucosa. Having something that can deliver it evenly across the entire duration that it's supposed to be in there, I think, is a huge advantage and something that I'm looking forward to.

Yes. And at much higher dosing than SINUVA. And yes, it's -- I see this product changing -- driving out oral prednisone. I mean, why would you -- we give oral prednisone because those nasal sprays aren't getting enough steroid to the tissue. Well, this is the answer, the way to do it without the side effects. I mean, we've all dealt with the side effects. People, they can't sleep, they're nervous. So then there's -- so I think that's what's really going to make a change and something we really haven't talked about.

Really. It's a great point, Rob. And if we can get rid of oral prednisone, it will be such a blessing for our patients, a really, really great thing.

Agreed.

Well, it's time to turn it over -- turn it back to Maria for the questions from the -- from our participants and open that back -- open up to the audience.

And we can just go ahead and open up the line for questions with our first caller.

[Operator Instructions] And we will take our first question from Bert Hazlett with BTIG.

Thank you to all the physicians for the -- and obviously, the company management for conducting this. It's very enlightening. I really appreciate all your time and your insights today. I've got a couple actually. First, Dr. Luong, I think you described it, and Dr. Senior as well, the kind of the treatment course of a patient and initially had failed saline and topical steroids. And thinking about the product of -- or the profile of LYR-210, is there a chance then that if it does perform in pivotal studies as it did in the Phase II studies, is there a chance that you may actually suggest this option, a LYR-210 option, to patients earlier rather than kind of driving them through 3 or 4 courses of topical steroids? Or just your sense of when you might consider something like LYR-210 in the treatment algorithm would be helpful. And then I've got 1 or 2 more.

That's a great thought, and I completely agree with you. If the data, as it looks like it's showing, has the effectiveness that we are seeing, I can see it serving -- because right now, it's really just -- the idea is that you want to get steroids and saline irrigations. Right now, the reason why these are considered first-line therapy is the effectiveness and I guess the delivery route for everything. Now it will also depend, I guess, ultimately on, I guess, how easy it is to get for the physician and for the patient as to where that will lie in terms of treatment options. But I can definitely see that being an option and maybe moving on to first-line therapy even before nasal steroid sprays. Now because of the fact that nasal steroid sprays are over the counter, you still will get that as an advantage over the topical sprays. Brent, anything else to add to that?

No. That was what I was getting at with when I said that I can envision a paradigm shift with this type of a product. I can tell you, if I were a patient, I would love to have something placed in my nose and forget about it for 6 months rather than having to irrigate my nose twice daily with a big saline bottle and then administer Flonase in my nose, as an example, twice daily. So I think that it really does potentially change the way that we think about the treatments. I agree with Amber. Intranasal steroids, fluticasone, Flonase, Nasacort, all of those are over the counter. So those aren't going to go away and certainly not going to go away in the treatment paradigm for a while, but I do envision this potentially coming on much earlier in the paradigm than what we might otherwise think.

It sounds like patients will have some -- hopefully have some important options in the not-too-distant future. And with regard to the data and SNOT-22, and I just want to -- you mentioned the SNOT-22 and the strength of the data further out relative to biologics. How important then is the CRS end point? I know it's a regulatory requirement at this point. But how do you think about the CRS end point vis-à-vis the SNOT-22 score as you view data?

You mean the cardinal symptom score?

Excuse me, yes, the 3 cardinal symptom scores, excuse me.

Yes. The 3 CS versus the SNOT-22.

Forgive me. The CS end point, forgive me.

I think they're both very important. You're almost speaking to different audiences in a way when you look at the data and those 2 components. The SNOT-22 is what we as rhinologists look at and we think about a lot because we deal with that scientifically all the time. We use -- utilize this type of data. The cardinal symptom score is really just getting it from the patient, right? It's just hearing about their congestion, their drainage, their pain. And that's the advantage of the cardinal symptom score. So I think both have a place -- a significant place for us as we evaluate this data.

So what I would say and add to that is that the SNOT-22 kind of takes into mind all the other effects that these symptoms within the sinus and the nose can have on other areas of their life. So if you look at the SNOT-22 score, the questionnaire talks about fatigue. It talks about how do you feel. It talks about headaches and sleep quality. And so all of these symptoms that are specific to the nose, nasal congestion, drainage, pressure and pain, they do have impact on these other domains. And so the SNOT-22 sort of takes a little bit a bigger global picture of the patient. The cardinal symptom scores are exactly what they're -- they say. It's the specific symptoms for the nose and the sinuses. So one is a little bit more specific, and then SNOT-22 is more global is how I would look at it.

But the other issue is that SNOT-22 has a number that you can compare from study to study because it's a standardized questionnaire. Now cardinal symptoms you'd think would be, but the questions are asked slightly differently in this study, in that study. So you can't really compare -- they use different 0 to 5 score, 0 to 10 score. So you can't really compare the results of one trial and the other. But the SNOT-22, you can. So it becomes like an international currency that you can say, "Okay, well, the biologic moved 20 points. We move to 20 points. So there's some similarity." So it allows the physicians to communicate with each other better. The other thing is really, the FDA doesn't like those kind of aggregate instruments as primary end points.

That's helpful. Of course, a 3 CSS score is what I was referring to. And then just one other question with regard to polyp and non-polyp patients. I don't think we've gone into the data tremendously here today, but I'd just be interested in the physicians' commentary with regard to polyp patients, in particular. If we get good data in the pivotal work with 210, would you expect the treatment algorithm to absolutely go through LYR-210 prior to biologics or other topical approaches in polyp patients?

I think what you're asking is, will it be as effective in patients with polyps as they are in patients without polyp, I think, and that they would fit into the other treatment options for chronic rhinosinusitis with nasal polyps, even though the study is not directed at polyp patients? So going back and looking at the data, what it shows is that both patients with and without nasal polyps at 6 months had the same degree of response to the LYR-210 in both patient population.

Yes. There doesn't appear to be a different -- difference in the response, at least in the Phase II. I mean, if you're comparing it to other products out there, they're really not geared for the non-polyp group anyway. So we would be -- we're not going to have competition beyond nasal steroids for CRS without polyps. So there isn't any treatment you can -- I guess you could use things off-label if you try, but it's not particularly easy to get it paid for. Any more questions?

We will move next to Chris Howerton with Jefferies.

Thank you also for holding this event. I guess maybe just a couple of questions for me. One is staying on the topic of polyps, I guess, maybe I'd like to just take it slightly higher level and also a clarification of Bert's question. First of all, I think the observation that we can make from the investment community side is that most drug developers have gone after polyp patients. And I think that there's been some uncertainty with respect to that, whether those are more severe patients or perhaps they're more homogeneous, or perhaps it's easier to show a drug effect. So my specific question to you, Dr. Kern and the rest of the KOLs, are what do you guys think about that? Is there something to be said about drug development in polyp patients specifically as opposed to the broader CRS population, is the specific question there? Then with respect to the follow-up to Bert, I think the question there that I'm interested in and maybe what he was asking, which was that if you're in a situation where you have something like a biologic or other therapies approved for polyps, what would be the advantages of choosing 210 relative to the other features? And how are your expectations of things like payer management in those types of situations going to occur? And then if you'll indulge me, I do have a final third question, which would be, obviously, it's a little bit more of a niche product. But would you be able to compare your experiences with Intersect ENT's PROPEL products to what you've seen so far with 210? And certainly, what your expectations would be in the postsurgical patients for 220?

Amber?

Okay. Let's see here. The first question was -- I can only remember the third question because the first one was addressed to you, Rob.

The first question -- yes, no problem. Let's do it again. So the first question is polyp patients and the thought of drug development in that space specifically. So is there anything unique about them that lends it more credence to drug development? Or is that a conspiracy theory that investors thought so?

Yes. Thank you. No, no. Yes, yes. No, thank you. Thank you for the reminder. So I think the reason why nasal polyp was targeted first for some of the therapeutics was because, number one, it was easy to clinically phenotype, right? If you see significant polyps, that's a clear cohort of patients to study. The other one is that this was a market that the rhinologists, the ENTs had difficulty with, right? So when you have recurrent nasal polyps coming back and what do you do? So there was a definite need other than giving them oral steroids or having surgery. So there was a clear need. But I think what this study has highlighted is the fact that you can do studies in CRS without nasal polyps, and it addresses a -- the gap that has been relatively ignored by ENTs, which is that group of patients who have seeked medical therapy may have responded but then lost the response or did not respond at all and needed surgery and that they -- then you just lost to polyps. So we, as ENTs, if they don't come to our office, we don't see it as a problem, as a gap, right, versus we see patients with polyps and when they come back, then it's an obvious gap. So I think it was just the fact that we just haven't recognized this as a need, but it clearly is a need based on the numbers. And now that we've sort of tackled that easy thing of, okay, this is an issue that frustrates us, what else can we do in the space?

Brent, do you have anything to add?

No. No, no. I was just trying to -- I have to admit, I missed question 2 as well.

I got it. So I can do it again. Yes, question 2 was a follow-up to Bert's, which was as we're thinking about a scenario where there's multiple drugs approved for presurgery CRS in the case of dupilumab, obviously, it's just for polyp patients, talk to us about that decision. Is it really just about access and pricing? Or are there clinical features that would make you choose one or the other in that situation?

So I think pricing is a big component, truthfully. There is -- that is the reality of the world that we live in. So that will be a big component. I think that the advantage of this product in that environment is, again, the idea that it just gets put in and then you leave it and you're done, as opposed to having a chronic daily therapy regimen for the patient. So that's where I think that it could potentially be an advantage in that particular patient.

Chris, to amplify the answer to your first question, too, the polyps are more considered by investigators, by -- were considered a more homogenous group. Non-polyp patients were considered a ragtag. And also, the polyp patients have a tighter linkage to asthma. So they were seen as a higher value target, let's say. And also, the surgery didn't work as well because the recurrence rate after surgery is higher in a polyp -- that cohort. But -- and we didn't have a good surgical treatment. Before endoscopic sinus surgery was created or invented, we didn't have a good surgical treatment for nonpolypoid sinusitis. So the answer to your question is really quite complex, but the need is enormous in nonpolypoid sinusitis. And fortunately, the FDA appears to be reasonable in terms of how to set up a study. And we've worked with them, and I think we have -- we're teed up in this Phase III trial to really be able to have something to offer to non-polyp patients.

Yes. I would almost say -- it's almost heresy to say this, but I almost believe now it's the non-polyp patients that are the more challenging population for me to manage than the polyp patients because we have so many options out there for the polyp patients. And I do think our surgeries have also improved. And now all of a sudden, I'm sort of realizing that my non-polyp patients are a more difficult population. So again, making me a little more excited about this product because it can be used in the non-polyp situation.

Yes. The data were very encouraging. And it speaks to the idea that this is an inflammatory disorder, broad -- that's the one thing that links it. Sure, it's heterogeneous. But the one thing that -- the final common pathway where the drain all drains into is inflammation, and steroids are broadly anti-inflammatory. And you had one more question, though.

I did have one more question. It sounds like you will indulge me. So it was the comparison, if you have any, in terms of clinical experience with the PROPEL series of products and how you expect that to compare to 220, certainly. And if you could, any comparison you'd like to make to 210.

Amber?

So I've used and continue to use the PROPEL family. So the one big difference is the amount of steroids that are in these different devices. So the SINUVA has the highest concentration in that sort of family of devices there at 1,350 micrograms. Keep in mind, so the LYR family has 7,500 micrograms. So it's significantly higher. And I'm trying to think. So the other ones, the PROPELs are 750. Is that correct, Rob?

Yes.

Okay. So it's like a magnitude difference in terms of how much steroids can be delivered. Without having it in my hands, I don't know if it's going to be -- if the LYR are going to be something that we can deliver at the time of surgery. That's a very exciting prospect and something that if you knew upfront that you would have a patient with polyps, that because of their disease entity, so that cohort I keep alluding to, aspirin-exacerbated respiratory disease, we know that, that's a very challenging group. Let's say you happen to be that physician's first surgeon and you know that they've got this diagnosis, after you do the sinus surgery and having the option of putting something in like the 220 after surgery and knowing that, that would be their postsurgical regimen, I think, is a very attractive option that can be utilized because right now, the PROPEL stents are used in the -- after surgery. But we know that most of the drug, which is, as you can see, significantly less than what the 210 or the 220 can deliver, really is dissipated by about 2 weeks. And so the effect is not long term. So this would be different in the fact that you can consider it as a long-term regimen rather than just kind of getting it over the hump of the inflammation that we incite just from having surgery, which is kind of how I see the PROPEL family. What it serves for me at the time of surgery is just to help the patient get through that postsurgical phase where I'd look things up just by operating.

Yes. I would echo that. I was honestly believing that the PROPEL family would be better for me that way. I kind of thought it would give the effect that we're talking about with the LYR product here in that it would be a long, linear release of the steroid. And the way I view it now in my practice is I kind of see it as the alternative to a sort of rapid taper of steroid basically because it is clear that there's sort of a rapid release. It's a relatively big hit initially that seems to rapidly taper off. That's sort of my clinical impression with regard to how those particular products seem to work.

Yes. The weakness of PROPEL is that you can't -- it breaks down very quickly, and you have to remove it fast. It causes trouble if you leave it in. You can't just sort of let it go away. So that's the kind of the limitation. The -- and that's really approved only in immediate perioperative situation. I mean, people have tried to use it in the office, it didn't work very well. And that's when they developed SINUVA, which was designed for the office and not for the OR. But in either case, they're really only to treat the -- I think they would compete very poorly in both settings with 220 head-to-head, to be perfectly frank, because the amount of steroid and the way -- and the kinetics...

The PK.

And -- yes. So -- are there any more questions? Are we in overtime?

There are -- we will actually move next to Tim Lugo with William Blair.

I'd also like to add, thank you for hosting this. It's been very insightful. I believe one of the KOLs mentioned potentially driving out oral prednisone with 210. Could you maybe dig into that a little bit? Because there's obviously managed care that we all live with these days. And I think that there was also an allusion to some managed care pushback with SINUVA. And prednisone is obviously a cheap generic. There's also OTC options. But I'd just love to hear more about kind of the managed care landscape right now.

Well, I mean, the managed care landscape varies all over the country. So I don't know if any of the 3 of us can give kind of an aggregate response because you're correct, there will be pushback. I was the one that said it would drive out oral prednisone, but I meant it in terms of the -- purely the -- what we would like to do. We don't like to give for oral prednisone for a local disease that's focused in the nose. And please the other -- please chime in, Brent or Amber. But depending on the pushback and things, you're right. But it -- theoretically, it could absolutely kind of a huge dent into the amount of oral prednisone we use.

I mean, the reality is...

Yes. Go ahead, Brent.

The reality is, is that these patients oftentimes are relying on oral prednisone for keeping themselves at a reasonable level of function, so they can live a fairly normal life in society. I mean, it's not unusual for our patients to require 3, 4 courses of oral steroids a year. And over a lifetime now, you're talking about a very, very significant amount of steroid exposure, which you're exactly right, you alluded to the fact that it is pretty much cheap as water. And there's no doubt that, that's true, and that's going to be hard to convince our payers to consider other alternatives. But from a clinical standpoint and from a safety and efficacy standpoint, there's no doubt that a product like this is going to be far superior to take than the oral steroids.

Yes. I would support everything that's been said. The other thing is that one of the biggest concerns about oral steroids is the potential influence on blood sugar, weight gain, and with that comes potential complications. So I don't know -- to try to reason with payers is a -- it's a challenge. But if they could understand that if we can avoid also oral steroids and some of the complications associated with it, there may be advantages from even their perspective of trying to minimize the utilization of oral steroids for this treatment. But again, it's very difficult to sometimes reason, especially with long-term effects, with our payers. So -- but yes, I agree with Rob that from a physician perspective, we would like to avoid oral steroids, if at all possible, because of these complications.

Cost analyses have looked at this to a degree. I mean, it's difficult to model out the population at large. But if you need more than 2 courses of steroids, oral steroids a year for sinusitis, you're probably out of balance with regard to the overall costs because of what that drives, not just the cardiovascular, but you're guaranteeing cataracts. You're guaranteeing glaucoma. Guaranteeing is a strong word, but you're greatly increasing that. So one could easily imagine a study that would -- could expand on that to make it, let's say, sellable to Kaiser, the all-you-can-eat, sort of all-in plans that are out there.

Okay. That's incredibly helpful. And can you just maybe broadly -- I guess on the other end, everyone mentioned and we all kind of understand how expensive the biologic options are. Can you -- it sounds like those are relatively a niche product. Is that kind of safe to say? And then with LYR-210 probably coming in much under the biologics world several years away, do you see it as just kind of the obvious product to use before biologics? Is that safe to say?

I would say that, that's a fairly good possibility. The biologics clearly work. They have great, great data, and our patients do well with them. But if we had an alternative that was providing a fairly similar clinical response that was much less expensive and didn't require every-other-week injections, I think that, that would be pretty well accepted.

I would agree.

Just to put some numbers behind that, we showed you a wheel there of 4 million patients. Personally, I think that, that's a conservative wheel. But the biologics -- so Sanofi has their target of about 90,000 patients. So that's their published target. Well, it's published, but it's out there. I don't know if they published -- where they published, but it's out there in their slide deck. And so that will give you an idea of the scale we're talking about. Now $38,000 a patient, 90,000 patients, that's a lot of dough, but it's a small niche.

And we will take our next question from Jason Gerberry with Bank of America.

I guess most of my questions have been asked. But the payer theme, specifically with novel therapies, does come up a lot with this space, maybe just because it's a large market. And so what I'm wondering is, is this really a function of -- does Lyra really need to solve for the reimbursement challenge? Do you think it's more a function of doctors fighting through the prior authorizations more vigorously because of the value proposition of the therapeutic implant combination? Just kind of trying to get a feel a little bit more if you were advising the company from the KOL perspective, maybe what the more recent novel introductions maybe have done wrong and how they can overcome that access issue?

Brent?

I think that you have hit on a very important issue. And I think the -- throwing this at the physicians to be doing the prior auths and what have you is not going to be very well accepted. We sit and do those -- multiple of those every day anyway, and to kind of put us into a position where we have to be doing that yet once again is not going to be very well received. So that does throw the ball into the company's court to some degree to try to figure that out for us. And definitely, that's part of the -- I think that's part of the business development here that has to happen to make sure that, that's being addressed.

Amber?

I would agree. I think -- yes, I would agree with that. The -- whatever that can be done to streamline the process, we know that that's probably going to have to happen as with -- even with surgeries, we're having to do more peer-to-peer, more prior authorizations. So even in things that we have been doing on a regular basis, we're having to do that more often in this climate. Whatever new device, frankly, any new device really needs to have that as a key component of their rollout was to understand how are they going to help the physician and the physician's office get this reimbursed because there may be a lot of enthusiasm for the drug or for the device or whatnot, but without some sort of clear streamlined mechanism, it's going to face a challenge in terms of getting adopted.

And I would argue that's been a significant issue for some of the other companies out there that have come out with some of these products that we've been talking about today.

Intersect did struggle with that, for sure. I was there in real time. That happened. And -- but they did plow a lot of ground. And they sort of didn't really anticipate a lot of things. But it is important for the local reps to partner with people. And we see that -- Sanofi did it beautifully. So it can be done. It's just a question of you have to have the expertise.

And I am showing that we have no further questions at this time. I will turn the call back for any additional or closing remarks today.

Well, I would like to thank everyone for joining us and for a very interesting discussion. I'd especially like to thank Dr. Luong and Dr. Senior for their involvement: Dr. Luong, her upcoming role as Coordinating PI in one of the Phase III trials for LYR-210; and Dr. Senior's work as Chair for Data Monitoring for LANTERN's Phase II. So now I'd like to turn it back to Maria for her final comments.

Thank you, Rob. And thank you, Amber and Brent, for providing your valuable insights today. It was very helpful to hear your perspectives on how the current therapies are limited, what their limitations are. I've -- my notes, I have here 5 limitations of which our platform is able to address everyone. So we do think that we will have a paradigm change here, that our products can be a new standard of care and really providing meaningful difference to your patients. So thank you for your participation, and I hope everybody enjoys the rest of their afternoon. And people can disconnect now. Thank you.