Ladies and gentlemen, welcome to the 43rd Annual J.P. Morgan Healthcare Conference. My name is James Curtis, and I'm delighted to be introducing Nawal Ouzren from Sensorion, who will be speaking to us today. Over to you.
Thank you. Welcome to the Sensorion story. I'm very pleased to have the opportunity to share with you what we're doing at Sensorion. So, Sensorion is a clinical-stage biotech company that is specialized in the development of hearing loss therapeutics. So, we are publicly listed on the French Euronext Growth market, so all the information I'm going to share with you is actually public information. So, the ambition of Sensorion is to build the most comprehensive franchise to do three things: we would like to be able to treat hearing loss after it happens, we would like to be able to prevent hearing loss in situations where we know it may happen, and we would like to restore hearing for babies who are born deaf.
This gene therapy journey started in 2019 with a very important collaboration with the Institut Pasteur, which is one of the top academic institutions driving the science of hearing. I don't know if you knew, but they were the first ones who identified actually the genes causing deafness. Fast forward to 2019, we currently have two gene therapy programs in development with them: one in the clinic called SENS-501 that I will describe a little bit later, and the second one that I called internally the Holy Grail that is focused on the gene called GJB2, which is the biggest cause for congenital deafness due to genetic reasons. One thing that we are doing that is significantly de-risking the execution of our clinical studies is the investment in prospective natural histories.
Beyond our gene therapy pipeline, we also have a small molecule currently being investigated in two proof-of-concepts that I will describe a little bit later. 2025 is going to be a very busy year for Sensorion, with multiple clinical milestones that are going to be disclosed in our gene therapy pipeline as well as in our small molecule. From an organization standpoint, we are a little bit less than 70 people. We currently are listed on the Euronext growth market. We are very pleased actually from the support of blue-chip life science investors. Our last cash position that has been publicly disclosed is EUR 87 million that was disclosed last June, and this will fund the company until the end of this year. This is a visual illustration of our pipeline. If you focus in the dark blue here, this is actually the gene therapy.
The most advanced gene therapy is called SENS-501. This is focused on the replacement of a very important protein called otoferlin. It's actually important for the good functioning of hearing. It's currently being investigated in a Phase 1/2 . We just completed the enrollment of the first cohort, and we are going to complete the recruitment of the second cohort by mid-year. The second program, GJB2, holy grail, very interesting gene. As you can see, it's actually involved in the development of a three type of hearing loss, the biggest cause for congenital deafness, but it's also responsible for progressive hearing loss in the pediatric population as well as adults, and this insight about the adult onset is actually an insight coming from the Institut Pasteur, which was very interested in actually these young adults who start losing their hearing and who become completely deaf by the age of 50.
And when they genotype them and they compare them to the normal population, they found these monogenic forms of GJB2. As we speak, we are actually preparing the CTA and IND enabling studies, and we plan actually to file the clinical trial application by the end of this year. For the sake of today's conversation, I will actually focus on gene therapy, but we also have a very important molecule called SENS-401 currently being investigated in two clinical studies. The first one is actually in collaboration with the global market leader for cochlear implants. It's a company called Cochlear. We actually investigated SENS-401 to preserve residual hearing after cochlear implantation. We have disclosed the data at the end of last year, and we have met primary endpoints, and we're currently talking with Cochlear on the potential next steps.
The next indication currently actually being investigated with SENS-401 is the prevention of cisplatin-induced ototoxicity in adult patients. We are going to complete the recruitment imminently, and we will disclose the final data by the end of this year. I'd like to speak a little bit about the business model of Sensorion because we're really proud of that. So, I spoke about the Institut Pasteur, which is actually very important for Sensorion because it's feeding the pipeline. But we did not stop there. You know, what we are trying to do is actually really quite innovative, so we thought it was very important to engage the medical community even though we were still in preclinical.
It started actually with the effort of structuring prospective natural history to standardize the diagnosis pathway in Europe, and we leveraged first the relationship with Necker Hospital, which is the biggest pediatric hospital in Europe, but it's also the European Reference Center for Deafness, but now we have actually 10 centers all across Europe, in Australia, in Canada, and soon in the U.S., who are now systematically genotyping babies who are born deaf to identify actually these mutations, and this is really important for the de-risking of the execution of the gene therapy. Beyond that, we are also very proud of our industrial partnership, so I spoke about Cochlear, with whom we are working on clinical studies. They are a shareholder. We also have Sonova, which is a Swiss company.
They are the global market leader for hearing aids, and they are also a shareholder of Sensorion, and we're currently working with them on a natural history focus on adult patients. Obviously, we also have strong internal capabilities, and for the sake of today's conversation, I'd like to highlight the investment we made in CMC for gene therapy because, obviously, you know, the process is the product, so we have bioreactors internally, up to 50 liters. Our teams are developing the process. We also have the analytical development team to fully characterize the product. And then for the GMP activities, we work with Thermo Fisher, so now, for the sake of today's conversation, I will speak about the gene therapy pipeline, and I will share some of the proof-of-concept data that we have.
When we started our gene therapy journey, we actually selected otoferlin deficiency, which is a rare actually disorder, but it is the perfect proof-of-concept indication to evaluate the potential of gene therapy in the inner ear. Why is that? The babies are born bilaterally deaf. They are not suffering from any other type of syndrome. There is no evidence of degeneration of the sensory hair cells. We estimate that it impacts around 8% of congenital cases due to actually genetic reasons. Prevalence is being estimated around 20,000. US EU5 incidence is around 1,100. Based on the work we're currently conducting with our natural history, we think it's probably underestimated. Still, it is rare, which makes us eligible for all the incentive programs for rare disease. We have the orphan drug designation in the US and in Europe, and we will be eligible for the rare pediatric voucher.
One thing that happened actually quite late last year, which is very important, we received the agreement from the European authorities on the pediatric investigational plan, which is a key milestone for marketing authorization. Otoferlin, we think, is going to pave the way for GJB2-related hearing loss. I mentioned the three indications in my introductory comments. As you can see here, the prevalence is actually quite bigger compared to otoferlin. We estimate that there are around 100,000 adult patients with that specific GJB2 mutations, and we estimate that there are around 200,000 pediatric children suffering from that GJB2 mutations, 80% congenital, 20% progressive. The current standard of care actually for these patients, because they are suffering from profound deafness or severe deafness, is cochlear implantation. But we believe that there is a rationale for gene therapy to transform this standard of care.
Now let's switch gears and discuss more specifically about otoferlin deficiency. This is an executive summary or snapshot of the proof-of-concept data that we generated with the Institut Pasteur. Obviously, there are two things that matter in gene therapy. The first thing is like how long it is going to last. That's the key questions, you know, in all therapeutic areas for gene therapy, and how big is the effect. In the chart here on the left, this is actually the sustainability question. Let me orientate you. The way we measure actually the outcome in hearing is with an electrophysiological measure that we call auditory brainstem response. It's measured in decibels. The higher the level of decibels, the louder the sound. 120 decibels, if actually you have a threshold there, it means you're profoundly deaf.
And then, close to 40 decibels is probably actually the level of speech. So, Pasteur developed a knockout animal model, and as you can see here in red, this knockout mouse is profoundly deaf. Even when you apply a sound at 120 decibels, nothing happens. In green, this is actually the proof-of-concept once we injected using our candidate, the knockout mice. And as you can see, we've been successful in restoring levels close to normal, actually, hearing. We see improvements at four weeks after the injections and sustainable effect up to 52 weeks, which is quite late in a mouse life. Then, obviously, we considered, you know, the dose-finding study. So, the good news is that there is actually a dose-finding. The higher the dose, the better the effect. And what we also observed from a functional standpoint in this chart has been also demonstrated from a histological perspective.
Maybe let me show you the picture here, the histology picture that we have here. This is the mouse that has been injected. Otoferlin is being expressed in what we call the inner hair cells. What you can see here in white, this is the presence of otoferlin in the inner hair cells. What's very interesting is that our candidate is not expressing cells that are not usually actually expressing outer hair cells, so we're very specific. If you compare that to the non-injected here, if you look at the inner hair cell row, you see actually there is no presence of otoferlin. This data, obviously, with the CMC package convinced us to start a clinical study.
And when we reflected about the design of this clinical study, we really wanted to make sure that we would gather the maximum information from this actually very rare, precious patient population. So what we wanted to do was be able to demonstrate by itself the contribution of the gene therapy in the hearing restoration in the patient population that would benefit the most. The second thing we wanted to demonstrate, because that was feedback we got from the payers, was that it's good to have hearing restoration, but is this hearing restoration contributing to positive behavioral change and speech development? So we wanted to be able, with our clinical study, to demonstrate that. And the last piece, which was very important for the payers as well, is improvement in quality of life. So here's the bar that we have set for ourselves in the clinical study design.
The best patient population that would benefit from not only hearing restoration, but also speech development, this is toddlers and infants, and ideally below three years of age. We are not allowing in our clinical study concomitant cochlear implantations because, again, we want to demonstrate by itself what the gene therapy does. We are not enrolling patients who have already received a cochlear implant because they would have developed the brain plasticity and they would have developed language, and then that would be very difficult to demonstrate speech development, and the last piece is the global clinical network. It's a rare disorder, so we want to make sure that all doctors have the opportunity to actually practice with our gene therapy, so this is how it looks. Our phase one-two is going to enroll toddlers between the age of six months up to two years and a half.
They are naive of cochlear implants. We are going to assess, obviously, safety, tolerability, and efficacy of SENS501 after unilateral injection. We are going to start with a dose escalation, pretty standard. We have already enrolled the first cohort, so we have already injected our first three patients on the low dose. There will be a DMC. We expect that the DMC will give us actually the authorization to escalate the dose. Then we will enroll three patients that we will dose at the higher dose. And then there will be a DMC that will look again at the totality of the evidence, and they will make a recommendation on which dose needs to be investigated in this expansion part. And this expansion part, at least in Europe, contingent to the data, may be considered pivotal. The primary endpoint for the dose escalation is safety.
We will have a secondary and exploratory review of the efficacy. And we agreed with the current regulatory agencies that ABR may be an appropriate primary endpoint for the expansion part, where we will be enrolling at least six patients. So where do we stand? So we're very pleased to report that the first cohort has been completed. We're very pleased to see that the first three toddlers are doing really well after actually this unilateral injection. The surgery went fine. There was no dose-limiting actually toxicity. There was no serious adverse event. We looked at the function of the inner ear after the surgery, so the vestibular function has been maintained. The OAEs, which is a marker of the health of the outer hair cells, remain present, so the surgery went really fine. We're also observing preliminary behavioral improvement in the first two toddlers that we injected.
What are the next steps for us? As I said, we are going to enroll the next three patients in the second cohort. We plan to complete that by mid-year. We continue the natural history. We are already pre-identifying actually patients who could potentially be candidates for the second cohort. We are going to disclose the preliminary data during a KOL event that will be held in Q1. And we are engaging, so we are filing actually a pre-IND meeting to discuss with the FDA this preliminary data and open an IND, hopefully in the U.S., in the first half. Switching gears, now we're going to discuss the second program, GJB2 gene-related hearing loss. So, as I mentioned in my introductory comment, we think SENS501, the first gene therapy program, is going to significantly de-risk GJB2.
GJB2 is a very important program, but the bar in terms of development is actually way higher because the bar in terms of safety for GJB2 is higher. What we know is that if we start expressing the Connexin-26, which is the protein being regulated by GJB2 in cells that usually don't see it, that would be toxic. So that would be a non-starter. So the experience we use to develop our first gene therapy candidate for SENS501, obviously, we will leverage that for GJB2 because we have to be very specific. We have, obviously, to demonstrate a proof-of-concept and right level of transduction of the target cells. We have to demonstrate limited off-target biodistribution. And we are leveraging actually the surgery technique that we developed with our panel of independent ENT surgeons. First thing first, as I said, safety.
So here is a snapshot of actually the safety data we generated in non-human primates. So the first thing that was very important for us was to have a good understanding of which cells are actually expressing Connexin-26 and which cells should not express Connexin-26. So, as you can see here in blue, this is the cells that we should successfully transduce, and in gray, this is the cells that we should completely avoid: inner hair cells and outer hair cells. So, if you look at the histology picture here on the left, you can see in non-human primates, our gene therapy candidate is not expressing Connexin-26. It's completely black. It's the same for outer hair cells. And if you look at the pictures here in the middle, you can see actually a strong level of expression of Connexin-26 in the supporting cells that are supposedly needing to express Connexin-26.
Then, it was very important to develop the proof-of-concept of efficacy. And here, again, we're very pleased to work with the Institut Pasteur because they have such a deep understanding of the physiopathology of this disorder that they've been successful in developing a mouse model that can mimic the congenital form and the progressive form. So here on the left, this is actually the proof-of-concept data showing that our gene therapy candidate is able to actually maintain hearing in the progressive form. So in the non-injected ear, so at the beginning, actually, it was normal, but over time, it became severe to profound, actually. And in the injected ear, you can see that we've been successful in maintaining a good level of hearing, supported by histology data. I'm not going to go through the details, but in green, you can see expression of Connexin-26 where it's supposed to be.
Here on the chart on the right, this is the congenital form. In red, this is the mutant mice that are not being treated. As you can see here, they are actually suffering from severe to profound hearing loss. This is in blue, the control mice, and in green, these are actually the mutant mice that have been injected with our gene therapy candidates, and we've been successfully maintaining good hearing restoration. So where do we stand? We have disclosed actually quite in detail at the last ESGCT meeting the proof-of-concept data in terms of efficacy and safety. We are, as we speak, working on the IND/ CTA enabling studies, namely actually GMP manufacturing for the GLP tox. We will conduct the GLP tox study to support an IND/ CTA application by year end.
So with that, I'd like to conclude my presentation for Sensorion, and I would like to leave you with some key messages. I have to say we're very proud of the work we're currently doing at Sensorion. We think this therapeutic area, there is such a high unmet need for patients suffering from hearing loss, and we were really working tirelessly to bring a contribution, a positive contribution for these patients. We have a very strong business model with a strong partnership, industrial partnership, academic partnerships, medical partnerships, and we have a very strong team to execute our ambitions. 2025 will be a very busy year for Sensorion with multiple clinical outcomes that you can be expecting from us. And as a summary, for the first gene therapy program, we will complete the second cohort by mid-year.
For our small molecule, SENS401, currently investigating in the prevention of cisplatin induced ototoxicity, we will complete recruitment beginning of this year. We will disclose the full data by the end of this year. And for GJB2, we will file the clinical trial application by the end of this year. With that, I would like to thank you for your attention, and I'm happy to take any questions you may have. Thank you very much for that. We've got a few questions that have come in, but we'll start with the floor. If anyone has a question, please raise your hand. Feel free to do that as I continue. We'll start with one question, which is, could you please highlight the key differentiation elements from your peers that you have in the market? For the gene therapy pipeline? Yes.
Yeah, so during my presentation, I spoke about how we're raising the bar in terms of the design of the clinical study, so as I said, we are not allowing actually concomitant cochlear implantation. We are not enrolling patients who have already received a cochlear implant, and we're going for extremely young toddlers and infants, so if you look at the competition, so the first ones that actually disclose data, they have injected a pre-teenager. The ABR data were, I would say, quite positive, but the outcome in terms of speech development is actually really poor. This pre-teenager is not able to develop language, will never be able to develop language, so they won't be able, with that patient, to actually write the whole story of the contribution of gene therapy in speech development. The second patient that they have enrolled has already received a cochlear implantation.
This is an eight-year-old girl, and she has already acquired language. So again, they won't be able to tell the whole story. The other players, they have actually quite mixed bags of age with patients who have already a CI, allowing cochlear implants. So I think we will be probably in the best position to be able to respond to all the building blocks. Do you have hearing restoration? Yes, no. Do you see behavioral improvement? Yes, no. Is the child actually being back to speech development? Yes, no. With actually the best number of patients. Thank you. Another question that we have is, you mentioned the natural history studies that you're doing. It would be interesting to hear what benefits you're leveraging from those.
I have to say, I remember exactly a year ago, you know, when I was at this conference and I was meeting with investors, nobody believed we would be able to enroll patients at the speed we were saying, and we always spoke about actually this network of prospective natural history that would enable us to enroll patients, and I think we have been able to demonstrate that we successfully enrolled three patients in six months. The other players, within the first year after the approval, they could not identify a patient. We are already pre-identifying patients for the second cohort. For GJB2, the Holy Grail, we're not even in the clinic. We are already actually enrolling patients with the GJB2 mutations, looking at the different phenotypes to inform the clinical study designs, educating the parents.
So the doctors are educating the parents, and there are already some parents who are raising their hand to potentially participate contingent to the regulatory approval in our clinical study. So I think it's a key differentiator in the way we execute the studies. That's great to hear. Thank you. And another one that we have here, and excuse my French, but you mentioned the Institut Pasteur. Could you outline your relationship with them and how that's helped? It is a very important actually relationship. So we signed in 2019 a very broad collaboration with them that gives us exclusive access to all the patents coming from Pasteur in the field of the genetics of hearing. So once we have proof-of-concept data, they present them to Sensorion. If we like it, we can actually start proof-of-concept together.
The outcome of that relationship is actually two programs in development with them. I have to say that was quite a coup for Sensorion because at the moment we signed the deal with the Institut Pasteur, they've been courted by actually some other players. The fact that they picked us triggered the interest of blue-chip, you know, like really high-quality investors that were, I would say, interested by this and somewhat bet on the Institut Pasteur and the potential of Sensorion to start building a gene therapy franchise. Thank you. Just one more here. We've spoken a bit about patient recruitment. There were some challenges in that in regards to the otoferlin program. Could you tell us a bit about those challenges? There were some challenges. You mean Sensorion had challenges or? We can skip over that question if it's not.
Any other questions from the floor? Perfect. Thank you very much.
Thank you. Thanks for your.