Episode 60: Rachel Haines - VP of Clinical Development & Operations, Rinri Therapeutics

In this episode, Rachel Haines from Rinri Therapeutics joins us to discuss the possibilities of cell therapy for hearing loss. Our conversation with Rachel goes beyond just scientific innovation; we also explore the potential impact of Rinri's upcoming human trials, which are based on Professor Marcelo Rivolta's groundbreaking work. By delving into the challenges and excitement of pioneering clinical trials in uncharted territory, we envision a future where natural hearing restoration could become a reality.

First In Human is a biotech-focused podcast that interviews industry leaders and investors to learn about their journey to in-human clinical trials. Presented by Vial, a tech-enabled CRO, hosted by Simon Burns, CEO & Co-Founder. Episodes launch weekly on Tuesdays. To view the full transcript of this episode, click here.

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Chapters

• 0:07 Pioneering Cell Therapy for Hearing Loss
• 10:12 Challenges and Future of Hearing Restoration
• 18:13 Discussion on RINRI Research Progress

Transcript

Speaker 1: 0:07

You are listening to First in Human, where we interview industry leaders and investors to learn about their journey to in-human clinical trials Presented by Vile, a tech-enabled CRO Hosted by Simon Burns, CEO and co-founder. Featuring special guest host, Amy DelMedico, VP of Ophthalmology. For this episode, we are joined by Rachel Haynes, VP of Clinical Development and Operations at Rinri Therapeutics, to discuss their pioneering approach to addressing global hearing loss through innovative cell therapy research.

Speaker 2: 0:42

Hello everyone. I'm Amy DelMedico and I'm VP of Therapeutic Strategy at Vile. I'm here today with Rachel Haynes from Rinry Therapeutics. Rachel, would you like to tell us a bit about yourself and Rinry?

Speaker 3: 0:55

Hi Amy. I am the Vice President of Clinical Development and Clinical Operations at Rinry Therapeutics. We were a biotech that was established in 2018 based on some early data from Professor Marcelo Revolta's lab at the University of Sheffield, which demonstrated we could take photic neural progenitor cells and differentiate and expand them, and these cells were capable of becoming mature auditory neurons. In his early work, we demonstrated that auditory brain stem response recovery in a general model of auditory neuropathy was possible, and RINRI was founded to translate that into patient benefit.

Speaker 2: 1:38

That's fascinating. Thank you. I wanted to ask you some specific questions, but I'm going to start off with a more general one, and that is what makes hearing loss such a significant global issue, and how does RINRI aim to address this challenge through its research?

Speaker 3: 1:55

Right. So hearing loss actually, the estimates of how many people it affects globally varies widely, but it's situated somewhere, probably conservatively, around 500 million people globally being affected, and I think any of us, once we get to middle age, notice that hearing does become more difficult, even just in social situations and when there's lots of competing background noise. So we're not just thinking about hearing loss as something that affects people who are born deaf, but it really affects the majority of us, whether it's ourselves directly or people that we care for or people that we love, throughout the whole life cycle. So not only does it affect so many people, but there's a lot of long-term consequences for hearing loss for patients individually, but also the macroeconomic issues around hearing loss. Granted, it's not life-limiting, but the impacts are massive in terms of people's feeling of belonging, communicating, access to education, accessibility in the workplace and really having those meaningful relationships with people in a society that is largely an auditory world that we live in. And, of course, for some individuals, the deaf community and sign language is their main mode of communication and we are absolutely not looking to solve a problem for those people for whom hearing loss is not a problem. It is a wonderful culture to be part of. But there are people who want to be part of the hearing world because that's the culture they grew up in, and we do need to address this issue from those people who are looking for it.

Speaker 3: 3:44

We do need to address this issue from those people who are looking for it. We also know, beyond being a significant issue, it's a condition that many people don't seek treatment for. Currently, we have some great technology with hearing aids and cochlear implants, which we have continued to develop in our field, but these do not restore natural hearing and people are often very reticent to take them up for whatever reason. There's lots of stigma attached to them and at present we don't have any licensed therapeutics for hearing or restoration of hearing. And there's something that Rinri and colleagues of ours in gene therapy have been working really hard at, and Rinri in particular. We really believe in our approach to it, because hearing loss is essentially a cellular problem and what Rinri is doing is offering a cellular solution for the cellular problem. And, rinri, we believe that cell therapy really is the future to treat these bigger problems of hearing loss.

Speaker 2: 4:54

Yeah, I mean, when you think about it, especially as we have an aging population, it would impact most of us in some way or another, and it's surprising that more therapeutics aren't being developed. So it's really interesting to hear what you're doing.

Speaker 3: 5:07

And it's really interesting. So in age-related hearing loss that you're talking about, that's what we call presbycusis and which is the target of our first product in our pipeline. And we know that in the aging hearing model it is the auditory neurons which are degrading or dying and that precedes the hair cell loss. So in hearing loss you have two types of cells which are important, which is the hair cells and the auditory neurons. And when you are given a hearing aid, a hearing aid amplifies that sound, so it makes it louder. So if the hair cells are not working as well as they used to and there's some fatigue there or some have died off, the hearing aid is going to make that sound louder. That will be helpful in terms of people with more mild or moderate hearing losses. But then, once you have a more severe or profound loss, that's where something like a cochlear implant might be offered. And the cochlear implant essentially replaces the hair cells and stimulates the auditory nerve directly. So at present you can have a hearing aid which amplifies the sounds or a cochlear implant which replaces the hair cells In both of those instances, if the problem is at the neural level, so at the auditory nerve level, if you have populations of auditory neurons which have died off or are dysfunctioning, neither of those are going to help.

Speaker 3: 6:43

So that's what you see often, especially in an aging model, where people may get a hearing aid but they're still really unsatisfied with using it socially because it's not helping their speech and noise. And we know that it's actually that neural function which is helping us do that speech and noise processing. And then, equally, when you have a cochlear implant, you are replacing the hair cells. When you have a cochlear implant, you are replacing the hair cells but you're not treating any issue that might stem from the auditory neurons themselves. So it's part of the solution.

Speaker 3: 7:19

These are fantastic technologies which have been life-changing for many, but they don't replace natural hearing and with that comes a very big discrepancy between outcomes of people who get hearing aids and cochlear implants. There's a lot of unexplained variation how well people do with them and also people who do use them, as I said, oftentimes find it very difficult to use them in situations with speech and noise competing sound signals and often report. A big challenge is fatigue, because it's really difficult when you are listening with something less than optimal, with something less than optimal, less than natural hearing, to do what is essentially a very complex task of listening in noise, and it is very rare that we are actually not listening within a context of background noise.

Speaker 2: 8:22

Thank you for the background. For those that aren't familiar, I wondered if you could elaborate on the landscape of hearing research today and why it might be challenging to design clinical trials specifically for hearing-related conditions.

Speaker 3: 8:37

Oh, the list of challenges is absolutely immense and very daunting, but extremely exciting. Also a really great time to be working in hearing. I remember being a postgrad student many years ago and actually hearing Professor Marcelo Revolta talk about some of his early work and thinking, wow, that's science fiction and it's so exciting that it's here now. It's really exciting that in the last three months some colleagues of ours from gene therapy companies have been reporting some very early positive data for children with autofurling deficiency and their gene therapy data is really encouraging that regenerative therapies for hearing are possible. They're just there, right in front of us and that's great. Gene therapy is really good for the patient population. That's been developed for these children with a monogeneic cause to their hearing loss and that's going to be transformative for these children. But we know that hearing loss in most instances of hearing loss are not monogeneic, are actually acquired. So, for example, in age-related hearing loss, and it's not genetic factors that drive that alone and you're going to have people who are too old to benefit from these gene therapies for gene therapy once they do develop a problem with hearing, and that's why we're proposing a cellular solution for cellular hearing loss cellular hearing loss.

Speaker 3: 10:12

What are the challenges in doing that Many. First of all, it's always hard being the first to do something. Second of all, actually one of the motivations that got me into clinical operations, originally coming from a background as a hearing scientist, was seeing that in my field 20 years ago, we weren't doing trials and hearing. Why weren't we doing trials and hearing? Well, because most of our treatments were devices or interventions. The wealth of clinical trial methodology has come from a drug therapeutics background, so we don't actually even now, as of 2024, in our field have tons of expertise about conducting trials More and more every year. I've been absolutely privileged to be able, over the course of my career, to design and oversee the running of several hearing trials. But even for me, this is the first time I'm doing a trial in an ATMP in this field, because it hasn't existed before. That's absolutely amazing Because we don't have many trials.

Speaker 3: 11:19

Another challenge is outcomes. Even patient-reported outcome measures that we may have in our field are designed to really capture maybe sort of more incremental changes that hearing aid might be able to offer. A cochlear implant might be able to offer not some of the big, very life-changing or very sensitive changes that a therapeutic could offer Actually in hearing. A big challenge for us in terms of pushing clinical development forward is we don't even diagnose by etiology.

Speaker 3: 11:52

We give somebody a hearing test and we measure how bad their hearing is essentially and decide what solution we're going to offer them based on the magnitude of their hearing loss. So we can't even tell you whether somebody has a hearing loss because of the hair cells or because of the auditory neurons. We don't know. We don't have those diagnostics now. We just have increasing amount of well, one, genetic data, which is still a work in progress, and then electrophysiological methods that are allowing us slowly to unpick this. So diagnostics is a big challenge for us. And another really simple thing you're giving somebody an advanced therapy and in our case we are first going into people with profound hearing loss. So they will be getting a cochlear implant to replace the hair cells. They will be getting RIN cell one at the same time as the cochlear implant to regenerate those auditory neurons.

Speaker 2: 12:59

It's really interesting what you were saying about diagnostics, because it's sort of equivalent to giving somebody an eye test, isn't it? And saying well, you know, you've lost this much vision, we're going to guess what treatment you need. So I'd never really thought about it like that. In terms of hearing loss, it's really interesting, and you're obviously at the cutting edge, which is fascinating. I wondered how Rinri's approach to generating cells for hearing restoration differs from traditional methods and what advantages it might offer in terms of efficacy and safety for patients. It is really different.

Speaker 3: 13:31

As I was saying before, when you are giving a hearing aid an amplifying sound or giving a cochlear implant and electrically stimulating the auditory nerve, you're not restoring natural hearing. You're not restoring natural hearing. Hearing aid has certain auditory processing limitations and a cochlear implant is essentially creating electric hearing. I don't know if you've ever heard a simulation of a cochlear implant, a vocoded speech, really fascinating but it's not restoring normal hearing. So what we are saying is by regenerating auditory cells we will be able to restore natural hearing. That is our end goal. So that's very different from the traditional methods, which aren't a complete treatment treatment, and so in terms of efficacy, we can really hope and expect that by regenerating the cells that allow us to hear that cannot regenerate on their own in humans, we will be addressing the main complaints and challenges that patients with hearing loss face, even when they have aiding. It's that fatigue, it's the difficulty of being able to understand speech and noise using communication in those really social situations that are so meaningful to us as humans, as we connect.

Speaker 3: 15:08

In terms of safety, we don't have any therapeutics to compare it to.

Speaker 3: 15:12

We can look at our surgical approach that we have developed at Renry and compare that to the standard cochlear implant surgery that has an excellent safety profile.

Speaker 3: 15:23

We've done some real cutting edge research around developing this brand new surgical access going through the round window into the internal auditory canal and getting the cells exactly in the place that they need to grow. That's never been done before but we've showed that this is safe. We've used synchrotron and micro CT imaging as we're doing that surgery and scanning the temporal bones and showing how we are able to go in and not damage any of the internal structures like the facial nerve and the cochlear artery, and so we don't feel this is any more risky than regular cochlear implantation surgery. But we still have so much to learn and that's really exciting going into the first in human and it is one of the reasons that for our first in human trial, we've taken this approach to be doing a randomized open label trial because we don't have safety data to compare it against when we want to be evaluating the safety of what we're doing. We want a really good data set of control participants to compare that against.

Speaker 2: 16:39

That's so interesting and very exciting stage to be at as well. Thank you, I just had one final question just to wrap things up. I wondered what sort of excites you the most about the future of the industry? Are there any sort of visions of the landscape that you think are coming up?

Speaker 3: 16:54

I'm so excited, as a hearing scientist by heart, for all the clinical development work that we've done and how we're going to keep building on that. What we can keep developing in terms of our surgical access, in terms of our diagnostics, in terms of our outcome measures, is so fascinating, you know, scientifically, but also for how meaningful it is to patients. Really, at the heart of RINRI, and what we've been doing has been working collaboratively with patients and families and key opinion leaders across the globe to really design not just our trials but their end product to be what people want it to be, and with the end goal in mind of reconnecting people to the auditory world. And the clinical development that we have in the pipeline is just so exciting. I'm looking forward to us making meaningful contributions not just to developing this therapy but for diagnostics of hearing and eventually expanding our indication, for example, into monotherapies for people with more mild forms of hearing loss. We are on the precipice of something big, and it's just an immense privilege to be part of it.

Speaker 2: 18:13

Rachel, thank you very much for the discussion today. It was an absolute pleasure and really interesting to learn more about RINRI.

Speaker 3: 18:19

Thank you. It's been great talking to you and I'm really excited to hopefully speak again someday about what we've learned from our first in-human trial. Sounds good. We'd love to have you back. Thank you so much, Amy.

Speaker 1: 18:40

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