Advancing Inner Ear Therapeutics: Research, Innovation, and the Future of Hearing Loss Treatment

Hi everybody, and welcome to the Future of Hearing Health Care 2026. We have our next e-panel and our topic is Advancing Inner Ear Therapeutics. We’re going to talk about research and real-world implications. I’m your host today Brian Taylor, and I want to introduce our esteemed panel.

So As you can see, we have several well-known researchers from around the world, and I’d like each of them to introduce themselves and talk a little bit about their company. So maybe, Jonas, we can start with you first.

Sure.

Thank you, Brian. My name is Jonas Dürfjeld Johnsen. I’m the Chief Scientific and Chief Development Officer of Acousia Therapeutics. We are located in southern Germany, Tübingen, close to Stuttgart for those who travel a bit in Europe. And we are working on a specific target that is highly expressed in the outer hear cells, a potassium channel called Kv7.4. This is a channel that helps set the level of amplification, the level of frequency selectivity of the sensory cells in the cochlear. And incidentally, the same channel is also expressed in the mitochondria of these cells. So we have a target that can sort of in a dual fashion help to modulate activity of the sensory cells and protect them against damage. Right now we’re waiting to read out by end of Q2 our first Phase 2 clinical trial in testicular cancer patients where we are attempting to prevent their hearing loss induced by cisplatin chemotherapy, which is a significantly underestimated problem in adults. In our blinded data sets, we see more than 90% of the patients having suffered significant hearing loss. So it’s a really exciting time to see to which degree we’re able to do something about this. Thank you, Jonas.

Hugo, we’ll go with— go to you next.

Thank you, Brian. Thank you for hosting this panel today. I’m Hugo Peris, founder, CEO of Spiral Therapeutics. We’re based in South San Francisco, California. We’ve been in business for about 10 years working on inner ear disease. Focus of the company has been around drug delivery, thinking that it is important to get drugs to the inner ear efficiently and minimally invasively. And around that, we’re building a pipeline of different therapeutics. The first one is SPT-2101, which is a treatment for Meniere’s disease based on a steroid formulation that has long-acting capabilities. That same steroid formulation we are exploring for its use across other applications, including cochlear implantation. And we recently announced a collaboration with Advanced Bionics, which is a leading cochlear implant company in our field. And in addition to our steroid efforts and the interest in addressing inflammation and protecting those inner ear structures with that mechanism, we are advancing a pipeline of different strategies, including neuroprotection and also protection of chemotherapy-induced hearing loss, like Jonas described, that’s also an important unmet need. And yeah, so we are recently funded through our Series B and looking forward to advancing towards a Phase 2b/3 study in Meniere’s disease later in 2027, hoping to push our drug towards approval in the next few years. Great.

Jonathan.

Well, again, thanks for the opportunity, Brian. I’m Jonathan Kil, the co-founder and CEO of Sound Pharmaceuticals. We’re advancing a small molecule taken orally that interacts with a novel drug target called glutathione peroxidase 1. This is highly expressed in the cochlear. In fact, it’s highly expressed in the 3 critical structures involved in the majority of hearing loss and tinnitus. So we feel we picked the right drug target. We have Phase 2 success across 3 different indications and now Phase 3 success in Meniere’s disease. We were recently awarded breakthrough therapy designation from the FDA and have ongoing studies in Meniere’s, cochlear implantation. Our collaborators, MED-EL, a leading cochlear implant company. And ultimately, we want to use this drug for age-related hearing loss and chronic tinnitus. So we hope to have it approved next year for Meniere’s disease and expand that label to include multiple indications. Very good. Thanks. Celia.

Hello, everybody. So I’m Celia Belline. I’m co-founder and CEO of Cilcare. Cilcare, it’s a biotech company as well with a pipeline of drugs developed to address different diseases in hearing loss. Our lead compound is called CL001. It’s a single transtympanic administration in the format of a gel that diffuses into the cochlear to address cochlear synaptopathy, which is the difficulty of hearing in a noisy environment that is also considered as the early stage of age-related hearing loss. So we are entering Phase 2a with two studies, one in the US where we focus on the subpopulation of tinnitus patients to restore speech in noise in this population. And another study in Europe with about 5 countries and 20 centers where we focus on type 2 diabetes patients. Because on the top of the pipeline, we’re working a lot on the detection of hearing loss. So we are building tools and algorithms to be able to really precisely phenotype different subpopulations of patients and better diagnose patients with hearing loss.

Excellent.

Well, I want to thank all of you for taking time out of your busy schedule to be with us. We’re representing a number of time zones here, so it’s not easy to coordinate these things. So thanks for being here.

What I want to talk about first is sort of the state of the field. If you could describe, you know, maybe what’s changed in a meaningful way over the last couple of years. And where you’re seeing most of the momentum. Is it around gene therapy, delivery approaches, those kinds of things? So maybe we can start with, I don’t know, who wants to go first? I think, I think Celia has had a lot of exposure to a lot of things also by way of early research and seeing other applications for other drugs. Okay, so Celia, you’ve been volunteered to go first.

Thank you. But first, I think we can really congratulate Regeneron for the authorization and the approval of their gene therapy on the US markets. I want to point out that I’ve been in the pharma industry for the last 25 years now, and they did, not only Regeneron, I mean all the people who have worked on this, on this gene therapy, in less than 10 years, they brought those drugs to approval. So they brought it for free to approval, but that’s great for patients and that’s great for the field.

I think this will bring a very very high momentum to the field, including for, I would say, non-gene therapy application, which is what we are all developing right now, the 4 companies that you have here. So really, it’s fantastic news for the field, and I really want to congratulate them. So that’s the first thing. Second thing, there has been a lot of improvement, thanks to partly all the people that are here around the table, on how we design a clinical trial in hearing loss, including, you know, this definition of what we call primary endpoint, secondary endpoint in a clinical trial. So what do we want to see improve with a drug, and how do we measure, and in what time point can we measure that improvement with a drug, and which population we select. So what are the inclusion/exclusion criteria in this type of field? And I think I’ve been on the field for the last 10 years, 12 years now. This has also greatly improved with a lot of new thinking. We are really working on having central reading of the data in a clinical trial, which seems totally obvious for every therapeutic area except hearing. When I came to start working on the field, there was no central reading tool. The choice of the populations were large, the definition of the disease not enough precise. To be able to demonstrate the effect of a drug. So that has improved a lot as well with the help of all the players, audiologists as well, largely involved in this analysis. And then in terms of mechanism of action and type of drug that we can see now in development, so beyond gene therapy and cell therapy, so we also have cell therapy in the field, we see a lot of small molecule approaches with I would say inflammatory, neuroprotection, oxidation. So there’s an anti-apoptotic, which was also an approach of Spiral at some point in time. So this is really covering, I would say, all the main mechanisms. We even see some cocktail approach, so people trying to work on combination from the very start, which also might be a a great improvement as a, I would say, a second line of treatment that will maybe be brought in about 10 years to the market. Because we see that your hearing loss is complex with central approach, peripheral approach. So that has always been approached like this. But there’s also many mechanisms that can work at the same time, so together. So the best approach maybe, you know, at some point in time will be to have cocktail like we see in oncology, for instance. Who would like to go well, I think as Celia said, it’s it’s clearly garnering a lot of momentum and good attention for us to see this success of Regeneron and, and x decibel for that matter since there’s still a lot of that team involved there.

I think it’s also an opportunity to, to reflect on, on the requirements for having such a a relatively fast level of success and what kind of bar, what kind of expectations that set for the field in general, right? Because I think their disease type, their population, their approach has a lot of advantages in the sense that you have a relatively narrow set of patients. You have a a very good way of identifying them. They are fairly homogeneous. You have a large pharmacodynamic window to work with for your clinical pharmacology, for your actual clinical trials. Everybody starts from no hearing, so detecting a change is somewhat easier. You have a drug product, an active ingredient that’s developed from scratch. You have delivery straight into the cochlear. And I think almost everybody else is working with a lot more of inhomogeneity in their programs, whether that be patient populations, identification, different medical history of the patients. What don’t we know about what their hearing was subjected to before they came into our trial? How does that affect how things will turn out for the individual patient? Subpopulations of patients within your patient collective, repositioning of drugs, various challenges of delivery. So I think it’s also an opportunity for all of us to be extremely reflective or conscious about what are the known unknowns for the programs and how can we learn from the need to potentially get even tighter on those control parameters in the future for our programs to be able to follow this up, right? Because it sets a very high bar, but it’s not necessarily a type of trial, a type of therapy, and a type of population that is extremely reflective of the sort of broader hearing loss populations.

Yeah, those are topics we’ll get into in a few minutes. Jonathan or Hugo, do you have any other additional insights that you’d like to share about this? Current state of the field? Well, just to build on what Celia and Jonas already stated, we’ve been in this field for 24 years now, and it’s been humbling. We’ve seen a lot of companies come and go, and as many of us know, when Decibel was launched from Third Rock Ventures 11 years ago, they had a very different goal. And that goal was involving neurotrophins or growth factors to stimulate reinnervation of the inner hear cell to overcome cochlear synaptopathy, a drug, or I should say, a potential indication that Celia mentioned. Their second product was discontinued. It involved a local injection of sodium thiosulfate in ototoxicity. And so their third, if you will, indication or product pipeline, which is the one that received recent success with their accelerated approval for auditory neuropathy, or the otoferlin variant that gives rise to that, was successful. So I think in terms of successful drug development, you know, broadly, you need good biology, the right target, the right compound or drug. You need to test the drug in at least, I think, 2, maybe 3 different study populations. One of the best predictors of Phase 3 success are the number of Phase 2s that you’ve done. And finally, as Celia said, the protocol, the inclusion/exclusion criteria, the assessments, defining an endpoint that the regulators like the FDA will accept as being clinically relevant, meaningful to the patient. Is it disease-modifying? We all hope for that, as we’ve seen the early results from the OTOFURLAN trials. They appear to be disease-modifying. But as with any gene therapy trial, the patients need to be followed out for 5 years. And at that time, when the study’s completed, they may be able to receive a full approval if the result is durable in these first 20 patients. So it’s, it’s still a lot of work ahead of them.

I think we’re more optimistic now than ever. As one of the principal investigators of that trial was quoted in saying, he never thought in his lifetime that they would see this type of effect in genetic deafness or auditory neuropathy. So it is a wonderful accomplishment from bench to clinic, and it was done so in a relatively short time frame. Hopefully this will not be the only success in genetic deafness. It will be just one of many to come.

Excellent. Hugo.

Yeah, I don’t know that I can add much more to what has already been said. Maybe emphasize that, that yes, this field has been working on solutions for a very long time.

I think this panel represents people that are to have a long-term commitment to the field. We are not just people that are excited about pharmaceuticals or drug development. We’re committed to pathology and building solutions for these patient populations.

I think to the point about the gene therapies and how exciting they are, and no doubt that Regeneron deserves a lot of credit for what’s been done and all the people that came from Decibel before that, it’s also a response to what the markets want, right? Right? And in a way, I think what we see is companies that have had to pivot in their interest based on what they thought was going to be more likely to be funded. And I think that’s what we saw with gene therapies. To John’s point, hopefully we’ll see more success beyond adeferlin because that only addresses a very small patient population. There are gene therapy strategies that might take us beyond that.

I think it’s really exciting to see how Not only Regeneron, but also Lilly has made significant commitments to other strategies in hearing, thinking about other forms of advanced therapy. There’s also some place in cell therapy with Lineage, with Rinri that are pushing in that direction. So it’s very nice to see different modalities.

I think ultimately here we’re representing 4 companies focusing on small molecules. That’s the original spirit of pharmaceutical development and one that is very important. And maybe sometimes, you know, those advanced therapies are going to be exciting, but starting with the foundation of what, where medicine is, which is having small molecules that have worked in other fields or mechanisms that are very well established for other forms of disease in other organs that we can now translate into autology are going to be exciting and very impactful. But yeah, I think we’re in a moment of good momentum on the back of recent success.

I think that’s also translated in some of us being able to get our efforts funded. Which hasn’t been without a lot of effort and suffering, but we’re getting there. And of course, the hope is that in the next few years we see a lot more of that success on the back of all the thinking and all the good science that has been going on in the field from academia to other companies that tried and unfortunately didn’t succeed. But it is a very exciting time for us. Well, that’s all— that’s good to know.

I think I’d like to kind of build on, you know, given the current state of the field and some of the bottlenecks and challenges that you’ve all mentioned, and given that our— the primary audience for this panel are hearing care professionals, I guess I’d like to hear from all of you how you think where we are today with inner ear therapeutics, how that might begin to change the way they’re integrated into clinical practice? You know, maybe not today, but in a few years, how do you see these inner ear therapeutics being integrated into the clinic? Maybe Jonas, we’ll let you go first.

Well, I think we’re still at the point with what’s approved right now. And I think we shouldn’t also forget that that we actually also had an approval recently with Phenix Petmark. So there is a small molecule and a gene therapy approved. And to Hugo’s point, we still in general see somewhere between 50% and 60% of new approvals of therapeutics in general being small molecules. So I don’t think we are completely out of left field with 4 companies pursuing small molecules. It’s still sort of the majority of what goes on in therapeutics development.

I think it’ll be gradual.

I think we’re still seeing, at least for now, more narrow populations being addressed, right? So it’s not going to be perhaps something that revolutionizes the field from one day to the other, all the way out to the audiologist in primary contact with the majority of the patients who suffer hearing loss. If we’re dealing with with genetic hearing loss. And as Jonathan mentioned, potentially more types of genetic hearing loss, that’s still probably mostly going to be hospital-based. So is treatment of, or prevention of chemotherapy-induced hearing loss. Once we get to orals, something that can be generally prescribed, that’s when I think we’ll see the real flip. But in between, it’s not going to be a binary 0 to 1, as many people like to talk about in tech development. It’s going to be gradual. It’s going to be more and more of these specific populations and indications that will eventually get an opportunity as an alternative to simply getting a hearing aid that may or may not work for many people, especially if you’re principal losses in the extended high-frequency range, or in the prevention of hearing loss in indications where currently you can only wait and see what your problem is going to be down the road, which has generally been the problem. And I think also one of the problems with development is that for the vast majority of hearing loss types, if you call up a doctor and say, I’ve suffered a hearing loss, then say, well, give it a couple of weeks and come back and let’s see if you need a hearing aid, right? That’s even complicated the, the possibilities to recruit patients to clinical trials. So the more we get of these different smaller subgroups that become treatable or could get a benefit from a new therapy the more it could start some sort of flywheel effect where it’ll make it easier to recruit, they’ll get more attention to it, we’ll get more funding. But I think the real big breakthrough is going to come once we have some broader-acting orals that can be prescribed outside of the specialty clinics as well. Makes sense.

Yeah, I think I would build on that from what Jonas said. When we think generally in the US, if you have to operate on the cochlear, deliver drugs locally to the cochlear. This requires a very specialized surgeon, oftentimes times an otologist, neurotologist. In the case of children, a pediatric otolaryngologist. So there are probably about 1,000 of them in the US. So if they saw 100 patients a year, well, that would be about 100,000. To have truly broad impact, millions of patients, it will have to be something that’s systemically delivered that the patient can take themselves or could be potentially injected subcutaneously by themselves to have that, you know, multiple millions treated. We know that in the US, 50 million Americans have significant hearing loss and tinnitus. A lot of people don’t realize it’s the third leading chronic disorder. There are 5 million veterans that receive service-connected disability due to hearing loss and tinnitus every year. So how we treat them is going to have to be, you know, broadly applicable. It’s still unclear as a person ages, what are the appropriate drug targets? I mean, we’ve studied this in cancer. Immunology. As Celia was saying, there are first-line treatments. And then if you’re refractory to that, second-line treatments, and even third-line. And sometimes they change significantly. We don’t know yet in hearing loss and tinnitus. The biology is still being discovered. What was true in neonates, newborns, may not be true in older patients. And then the continuum in between. So hopefully we’ll have a lot more success in the next 10 years. I’d like to maybe take a counterpoint to what was just said.

I think if we look at the field of ophthalmology, I think that’s a good example for what might happen, or I expect that that’s the way that our field could evolve. And I think we’re a few years behind and maybe driven by the fact that the eye is a lot more exposed than the ear and it’s easier to get to. But if you think about ophthalmology, it’s not that there are a lot of oral treatments and maybe because you can just have topical stuff. But even for the back of the, for the back of the eye, which is maybe what’s more relatable to what we do in terms of inner ear treatments, local therapies are still most prevalent. And it is true that ophthalmology, especially retina, used to be a surgical field, and basically they did laser for everything, and it was a bucket indication or diagnosis where people were all treated mostly the same way. And over time, and, you know, with the first anti-VEGFs that were developed and approved, that opened up the idea that you could inject the eye And I understand that the first few months of that, those companies introducing that approach, there was the concern of, well, no patient is going to want to get a monthly intravitreal injection to treat their retinal degeneration. But eventually, that became a very large opportunity affecting a large number of patients. And I think if we translate that to— and maybe one more thing to say about ophthalmology is that also opened up the opportunity for better diagnosis to the point where what what everybody thought was just a single disease, it ended up breaking down into very specific diagnosis, understanding exactly what’s going on. And even things like retinitis pigmentosa now is just very different subsets of patients that are better understood with different strategies to— for treatment. So eventually, I would expect— and I don’t know how many years or decades it will take for us to get there— but I would expect that, that we could just get across that barrier of getting that first drug for maybe local delivery approved, that would open up the field, would establish an incentive for patients flowing through the clinic, those clinicians understanding how those patients can be treated, but also eventually learning how to reduce the invasiveness, make everybody more comfortable with the idea that it’s a minimally invasive procedure that can be done in the clinic. Under local anesthesia that they can be in and out. You can go back home and do, continue with your day, but you still can get exposed to effective treatments. And then that’d probably be the first step. But ultimately with drugs approved and patients understanding that there is a possibility to get improvement to their symptoms by way of receiving those treatments, that that would also open up slowly improving the diagnosis of what’s going on in the ear so that we can then start identifying better targets or better molecules to address different indications. And I think, for example, for John and I, we’re working on treating different stages of Meniere’s disease. We describe Meniere’s as an indication, right? But it is very well understood now that there are potentially different subsets of Meniere’s with patients that will develop their disease differently, will express their symptoms differently. So eventually what starts as we’re going to treat Meniere’s disease, in 10 years, 15 years, might be that we have 5 different strategies to treat 5 different forms of Meniere’s, but also what today we think is maybe a 600,000 patient population in the US could blow up into being many more patients that are actually suffering from it because we have better ways of diagnosing those patients because there’s better incentive for the providers to identify, okay, this patient has this. So because we have the right way to address their problems, we can now identify them, classify what the disease is, and then provide them with the right support and the right treatment. So that’s what I would expect for the field. Maybe it’s a dream. Maybe it’s just my strong desire, and I don’t know how long it will take us to get there. But ultimately, we have some examples of other fields of medicine that I think we could follow.

Thank you. Celia, we haven’t heard from you on this topic.

Yeah, and I think I will go a little bit further actually, because I see And it’s maybe because we have a foot in Japan with Shionogi and that we address hearing loss as a prevention, a risk factor of the evolution of different brain diseases. So with that angle, I would say that my perspective for the field is a little different. I don’t really care about the route of administration.

I think that the transtympanic local administration is really not a barrier to, to the market access for different reasons. First, if I benchmark with aesthetic surgery, I can tell you that anybody can get now injection in the face, and this was done by aesthetic doctors first, and now there’s many other types of doctors that can do this kind of injection. So that’s one thing, which I can also go a little bit further on this. There’s a lot of out-of-pocket in this market that will certainly see as well in hearing at some point in time, and depending on the country. So that’s number 2. So I don’t think the route of administration— I think we are really starting a revolution in terms of diagnostics and patient detection. And I see the major player of the tech, like Apple for instance, being able to actually screen patients and drive patients to the right doctors for the right treatment at some point in time. So there’s Today, the problem we have, and I take the example of CellCare, we have our first drug going to type 2 diabetes patients, so cochlear synaptopathy in type 2 diabetes patients. The type 2 diabetes patient in the US, the CDC has actually already required a hearing test to be performed every year since many years. This is not the standard practice. So even if you put patients into passway where they have to have all the things assessed with their chronic disease. It’s not necessarily the reality. But with all those tech companies that are now monitoring hearing with AirPods all the time, there’s a very high probability that we can detect things and they can detect things earlier. So the diagnostic is going to be totally revolutionized everywhere. Then I’m really seeing addressing hearing loss, and that’s the case also for sub-sub-subpopulation. I really see that addressing hearing loss as a risk factor of other chronic disease and especially brain disease, but maybe not only, is something that everybody should push right now because this is how tomorrow— this is how hypertension that is not a disease killing anybody, cholesterol, high cholesterol that is not killing anybody either. Obesity, even obesity or diabetes, have been developed thinking that those are risk factors of cardiovascular disease. If you start really seeing, hearing— which is, it’s not me saying that, it’s a reality— if you start seeing hearing loss as a first sign of hearing loss as possibly a risk factor of the evolution of very horrible brain disease, then you start treating it. The earlier you can, not only to hear better, but also for the overall health status of the patient. And this was fundamentally changed the market access and also how the pharmaceutical field and the medical field is seeing this otology. You know, otology, it’s still the little niche of doctors working on the ear and the anatomy of the ear. If you start saying that this is an important entry point to the overall health, then it’s not only the otologist, which is the expert, of course, to do the surgery of the cochlear and that kind of things. It’s not only the ENT doctor that will care about hearing. There’s going to be a lot of others that will actually address also this hearing loss as a comorbidity factor of other disease. So I’m really pushing for that because this is what is published, and it’s not me again. And I think this is the prism or the angle that can help also the field to grow faster with more players and with better market access. I’m curious from the rest of the panel if they had any additional insights they wanted to share based on what Celia just said.

Well, I think we are all not necessarily in disagreement, any of us. I’m certainly also not saying that local administration is a bad idea. We are pursuing both.

I think it’s just more applied to a more limited patient population, some that may need it because you need to get something delivered that you cannot deliver otherwise, or you need a lot of it very fast. But I think in general, taking the sort of broader or more meta perspective from Celia, it’s a matter of a lot of building blocks that have to come together to keep stacking together, whether it’s individual populations that get addressed in a potentially slightly more invasive way or not with a chronic applicability, in order to garner the interest to bring in all the players that look at it from the perspective of preventing brain disease, etc., etc., so that we get to this flywheel effect that availability to subpopulations create awareness, which creates investment, which creates engagement which eventually builds us to the really large numbers of, of billions of patients that we all know per the WHO is, is out there and, and currently not necessarily very happy with their, with their treatment availability right here and now, but also with their future perspectives.

Yeah, to build on what Celia said, I mean The link between hearing loss, acquired hearing loss, sensorineural hearing loss, and dementia risk, I think, is now accepted. Lancet Commission has been, for the last 10 years, tracking this. There have been many national studies that have quantified a 10-decibel loss above mild to moderate hearing loss results in an almost 10 to 15% increased risk for developing dementia. So as I recently told an investor panel, so after you’ve suffered 50, 55, 60 decibels of hearing loss across multiple speech frequencies, the Lancet Commission and national studies would say that your risk of developing dementia has gone up by 50%. That catches a lot of attention.

I think Celia is right in that the use of these circulating biomarkers and their correlation to disease, or in the case of hypertension, a simple blood pressure measurement was, you know, it took half a century of research to link hyperlipidemia, cholesterol, to increase coronary vascular disease. And interestingly, there are a lot of surgical approaches to unclogging coronary vessels led the way, and now there are thrombolytics.

I think what really, you know, impairs us is the inability to visualize the cochlear, and more specifically, the cells within the cochlear. You know, when I was in clinic, we could look into a patient’s eyes, and I could see evidence of vascular leaking, and hence wet AMD. I could see evidence of drusen, and hence dry AMD. Unfortunately, even with very good imaging, we can’t resolve The cellular phenotype, the cells that are involved, whether they’re hear cells, supporting cells, spiral ganglion neurons, stria vascularis within the cochlear, we know pathologically they’re all critically involved in 99% of all hearing loss and potentially tinnitus. I don’t know if we’re going to have that level of diagnostic certainty in the next 5 or even 10 years. And you know, the cochlear is 1/20th the volume of the eye. It’s bone encapsulated. Right. So a lot of people don’t realize that when we talk about doing these critical mouse experiments, well, why don’t you just inject the mouse cochlear? I have to explain to them that volume is 1 microliter. They’re going, what? 1/50th of an eyedropper volume. They’re like, well, how can you do that? I go, well, then there’s a big question. So you know, I think many of our otology, neurotology, pediatric otolaryngology brethren would love the ability to broadly inject patients. This is how ENT clinics make money. We have to keep that in mind as well. But much like cochlear implantation, it’s limited. Cost is also an issue. But when you think about it, last year across the 3 or 4 cochlear implant companies worldwide, I think there are only about 100,000 implants performed worldwide after 40 years of approval. So we have to, you know, think about costs. You know, again, it’d be lovely someday to use telehealth in a very rigorous way.

I think Celia is right, at least for screening, we’re already there. But for true diagnostics, I think you’re still going to need a clinical audiologist in an appropriate environment. I do think something like tinnitus where we have no objective measure. I can bring you into clinic. I will still rely on your patient report of your tinnitus. There’s no objective way of me measuring it.

I think an effective tinnitus drug could have broad utility and be prescribed to millions through telehealth.

I think that’s where we’re going in the next 5 years. It’s interesting. That’s not at all a complex area to work in either, right? So that’ll be easy in 5 years to get there. Well, if it’s patient-reported, and, you know, Jonas brings up an interesting comment, you’re going to have a massive placebo effect. We’ve seen this across many trials, especially in Ménière’s disease. If you give gait-on vertigo patient-reported vertigo, the placebo rate can be as high as 60%. In tinnitus trials, as high as 40%. So having still some sort of more objective measure other than a patient report may be helpful. But there are diseases that are well managed with pharmacology. Migraine, that’s patient report, although observers can see the patient suffering with migraine. It’ll be interesting to see us, you know, cross that threshold. My point was more on the mechanistic aspects and pathophysiology of developing a therapy than how to diagnose it.

Yeah, it’s still— it’s amazing, you know, the power of placebo. And I’ve talked to some people about this. The more you lay hands on a patient The higher the effect. We’ve seen this with chiropractory, the laying of hands, the spending time with the patient, the sounds, the feel. It’s amazing. I don’t know how much of it is real. It’s well documented here in Germany as well. We happen to be in the area where homeopatics were invented. They did a study some years ago, and basically the patient satisfaction as a measure of placebo correlated with the time spent with the practitioner, which for a homeopathic practitioner was about 45 minutes versus 15 minutes with a GP. So you’re absolutely right, comforting and placebo and that doesn’t mean that it has no benefit, but it’s it definitely seems to be a strong, a strong problem to deal with if you’re looking at more mechanistic effects. It’s amazing. In this country, they’ve done similar studies about patient satisfaction, and chiropractors have the highest. And it’s the willingness and ability to explain what they’re doing, the time spent. It’s them for that 50-minute session. 45 minutes is them, and laying on of hands sights and sounds, feelings. They can be beneficial to the patient, but there involves a lot of what we would call operator-dependent phenomena. As healthcare professionals, we, we like to hang our hat on something that’s a bit more objective. It may be more limited, but You know, I think for patients who are really suffering from tinnitus, intractable tinnitus, they have tried every modality under the sun. We, we get calls every day from tinnitus sufferers wanting to try our drug, and they go through a laundry list of everything they’ve tried. They are even thinking about transection of the nerve. To end their tinnitus, but they understand that that could, tinnitus could still remain after transecting the cochlear nerve. Interesting conversation. We’re kind of wrapping up here, the last 10 or 15 minutes of the hour.

I guess I’d, to kind of end things, I’d like to go around the room, the virtual room, and get your take on, maybe what you’re most optimistic about over the next few years, where you see meaningful progress happening. There’s a lot of things to be excited about, as you’ve mentioned. I’d love to hear your take on the near future. So maybe, Hugo, we could start with you.

Of course, my optimism will be driven by seeing more therapies be approved and more funding coming into these companies that are working in that direction. I do think that that’s likely to happen. We have lots of programs entering into Phase 2, later-stage studies. John was mentioning the opportunity to advance SPI-105 to the market.

I think that would be wonderful to see.

I think that the more there is and the more we can capture the imagination of the clinicians, the patients, the investors in the sense of improving quality of life for patients, that will drive attention to the field and even more innovation, and that is necessary.

I think things like what Salkia is doing in terms of trying to improve diagnosis and identify subsets of patient populations that could benefit from treatment are extremely exciting, and that’s probably also going to drive a lot of opportunity for innovation. So I think first, thanks to Celia and Salkia for driving that thinking, but also I think that that’s going to be something that we as a field need to think more of and try to keep driving. But yes, ultimately, I think success is what’s going to drive success, and getting the first step in, the foot in the door, is what’s going to start opening up the opportunity for this field to start growing. And unfortunately, we come from the last 10, 15 years, maybe even longer, of a few failures and challenge in getting drugs to show success and those outsized placebo effects. But things seem to be changing, and that gives us a lot of hope. So I think I would say we got to keep going, and it’s good that we have people like the four of us here that are committed to the field and will keep driving it. Exactly.

Celia? Yeah, so maybe the first thing I want to point out, I say that very often, it’s my benchmark with, you know, my experience in pharma and my experience in other therapeutic fields.

I think we still have a lot of margin in hearing because there has not been so many drugs in development and especially in clinical development. So it’s true that there has been some failure from companies that have not succeeded in clinic, but not so many. And there is a rule in pharma, there is a rule where you have to have a certain amount of drug developed and tried to be able to narrow it to the one that reached the market. So it’s better of course to be the company that brings the drug to the market, But I’m very optimistic because there’s still a lot to do in developing drugs, in clinical development, so that there is one that, and several then, that reach the market. But the second thing is also in the era of artificial intelligence, I’m sorry to put that name again on the table, but it’s very important to understand that what will help a lot is also our capability to generate a lot of data and good data in hearing. Because until very recently, the only cohort auditory data in patient cohort that we had access to are the one where you have some perception of the patient, whether they hear well or not. So what will matter, and this is, I think, a common work with the audiologist as well and with all the company developing hearing aids, cochlear implants. So how we can use more and more clean data so that at the end we can also develop objective measures for being able to assess treatment effect using other— it’s a correlation of data. So it will be audiology with electrophysiology with maybe blood biomarker imaging. So there’s going to be many things that we can consider to fine-tune the diagnostics of patients with hearing loss and then be able to give them the right drug for being treated. So the generation of mega data sets in hearing, and not only audiology, I insist, the audiogram is not enough, but a lot of meta— this is something that may help the field a lot because this is how we can really— we will diagnose hearing diseases that we did not know before. Because as Jonathan said today, it’s impossible to see the ear and the cells. So there’s certainly much more diseases than we know today that have different pathophysiogenesis and that we can certainly treat and address with biologics, pharmaceutical, gene, or whatever. So I think the data, the use of artificial intelligence to be able to go faster in the analysis of those data, correlate the data, is something that is very exciting, and that will bring together different players. Us, of course, but also the tech players, the major tech players I was talking about. So the one doing the screening and being able to do some detection. The audiologists will be there, the hearing aid players with the cochlear implant players. And so this is fantastic if we can have everybody together.

Jonathan.

Yeah, one thing that we’ve seen clearly evolve in clinical practice over the last 10 years is a focus on speech discrimination. So I agree with Celia, pure tone audiometry still is the gold standard for diagnosing hearing loss. But 90% of patients have mild to moderate And what often drives them to see a healthcare professional is, “I’m having a difficult time hearing in a noisy environment.” So using speech discrimination tests like Words in Noise test— last year, this was one of the single word tests recommended by our national institutes. And I think focusing on that could drive more patients to seek therapies versus saying, “Well, my grandfather or father had hearing aids and it didn’t work that well for them.” And I agree with Hugo’s comment. Once you have a therapy that has some broader applicability, that drives the market, if you will. It better defines the diagnoses. You’ll see some patients who will be a little refractory, But that’s also opportunity from a drug development standpoint. We’ve seen that in many fields, as Hugo brought up with the VEGF inhibitors that were injected locally for wet AMD. There’s been label expansion to diabetic retinopathy, macular edema. It actually has 3 indications, if you will, and it’s been modified at least 3 different times. Hopefully they’ll find other druggable targets other than VEGF. But, you know, the cochlear is still a very unique biology. And what I feel proud of, of us 4 companies, is we’ve all committed at least 10 years of our life to this. And I think it requires that kind of perseverance. I mean, again, it wasn’t Decibel’s first swing at the bat that got them success and approval. It was their third. So that’s a great point.

Jonas? Yeah, I certainly think that the additional development of diagnostics is good, but I wanted to point out one simple thing that also feeds into the point of Celia about better, broader, more robust datasets. Simply using the currently available diagnostic tools to their fullest in terms of doing a full audiogram and not stopping at 8 kHz already moves the needle a lot. I mean, we’ve seen now, after years of hearing that cisplatin-induced hearing loss is not a big issue for adults based on the literature, considered to be somewhere in the 30 to 40% range of cancer patients treated with cisplatin when they are adults that developed significant hearing loss. When you do an audiogram up to 16 kHz, then all of a sudden the number is between 90% and 95%, which then ties back to Jonathan’s point. Is it really the need for only for speech discrimination testing, or is it the need for a full audiogram that actually validates the patient experience, as opposed to being told, well, you don’t have a hearing loss, so we can’t do anything for you. They might still not like the message that you do have a hearing loss, but the hearing aid is not going to help you in that range. But at least you have two already existing measures that can correlate between an extended high-frequency loss and a speech discrimination problem. So even before we develop new tools, I think broadening and thorough use of the existing tools and really capturing those datasets without limitation could help feed whether it’s AI or deep learning or whatever we want to call it.

I think too many people hear AI and think chatbots. I don’t think that’s what we’re necessarily looking for. But as a person with a lot of modeling background, the old saying of garbage in, garbage out still holds, and that can also be sort of interpreted in the way of sparse data set in, garbage out. So deeper, broader, higher resolution data sets and covering the whole hearing range, I would definitely advocate for.

I think that the— to not drag us too much over time, I think the, the interesting point for me to see now, and what I’m optimistic about, that with, with Regeneron getting an approval, this is the first time that that an approval has now happened for somewhat major player. Maybe you don’t count them in, in the same level as as Lilly, Sanofi, Novartis, etc., but, but they’re close and they’re pretty high up in, in the rankings among multinational biotechs, as they call themselves, and not pharma companies. Lilly might potentially follow along since they have a similar program. Now we start seeing some of the, some of the major players perhaps getting into the market. Cellia has the collaboration with Shionogi. They are at least big in Japan, to cite an old German ’80s song. But I’m optimistic that that level of attention, that level of impact can drive a lot of momentum in the field. Hopefully the next thing that gets approved actually also can be profitable and not just given away. That might drive even more interest. But once the investment field starts seeing this kind of interest and this kind of potential, then I think we can see more funding flowing into the field, supporting more development programs, and hopefully even pushing the accelerator further.

Well, thanks for helping us connect all the dots. I see that our time is up, so very briefly, I’d like to go around the virtual room here, and if you could all maybe share a website or where our listeners or viewers could learn a little bit more about your respective company. So Jonas, we’ll start with you and just briefly go around the room here.

Very simple for us, it’s acousia.com.

Excellent.

Hugo, our website is spiraltx.com. Jonathan, Ours is soundpharma.com. And then Celia? It’s cilcare.com, so C-I-L-C-A-R-E. Right behind your right shoulder.

Well, I want to again thank all of you. I mean, it’s incredible to me, the dedication, the tenacity that all of your companies and all of your researchers, your your people bring to the table. So, you know, there’s millions of people out there that thank you for all your work, your dedication, and on behalf of Hearing Healthcare and Technology Matters, I want to thank all of you for your time today. I really appreciate it.