Restoring Hearing Loss with Novel Therapeutics with Laurence Reid CEO of Decibel Tx

 

Did you know that hearing loss is one of the largest areas of unmet need in medicine? It affects approximately 466 million people worldwide, including 48 million people in the United States. 

Today's guest Laurence Reid, CEO of Decibel Therapeutics dives deeper into meeting that unmet need. Decibel Therapeutics has architected a whole platform to restore hearing and balance loss. With several treatments in their pipeline now, one in phase 1 clinical trials, they’re making great progress. Learn more about how Decibel started, current pipeline, and the future of biotech industry. 

About Laurence Reid, Ph.D.
Laurence joined Decibel in January 2020. He previously served as an entrepreneur in residence at Third Rock Ventures, where he focused on novel drug discovery and development opportunities. Before that, Laurence was CEO of Warp Drive Bio, a small molecule company focused on novel oncology and antibiotic drug discovery based on natural products, until its merger with Revolution Medicines in 2018. Prior to that, he was the senior vice president and chief business officer of Alnylam Pharmaceuticals, where he was responsible for the company’s business development, finance and legal functions. Before coming to Alnylam, Laurence was the chief business officer at Ensemble Discovery, where he led the company’s strategic planning and corporate development efforts. Laurence previously spent ten years at Millennium Pharmaceuticals in a range of general management and business development positions. In addition to his professional interests, Laurence is a board member of the Possible Project, a board member of Garuda Therapeutics and board advisor to Life Science Cares. He earned his Ph.D. from King’s College London and his B.A. from Cambridge University.

About Decibel
Despite the overwhelming burden of hearing loss and balance disorders, the search for therapeutics to treat these conditions remains one of the largest areas of unmet needs in medicine. At Decibel, we are exclusively focused on discovering and developing transformative treatments to restore and improve hearing and balance. We have assembled a highly experienced scientific team and built a unique platform to achieve this goal.

Show notes

Pictures of the inner ear: https://www.decibeltx.com/our-approach/

Previous episodes: https://www.qualio.com/from-lab-to-launch-podcast

Apply to be on the show: https://forms.gle/uUH2YtCFxJHrVGeL8

Music by keldez

Transcript

Transcript is automatically generated. Please kindly excuse any grammatical and spelling errors.   

Kelly Stanton: 

Hi, everyone. Thanks for joining the show today. I'm Kelly from Qualio and I'm your host here from lab to launch. If you haven't already please subscribe and give us a review on Apple or Spotify. We'd appreciate that. And if you want to be on the show, please see the application linked in the show notes. We've had a lot of people reach out and we absolutely love connecting with you. Today's guest is Laurence Reid, CEO of Decibel Therapeutics. Did you know that hearing loss is one of the largest areas of unmet need in medicine, it affects approximately 466 million people worldwide, including 48 million people in the United States. We'll get more into the details of this with Laurence, but Decibel has architected a whole platform to restore hearing and balance loss with several treatments to their pipeline now, one in phase one clinical trials, they're making some great progress here. Also, if you want to see some really stunning images of the inner ear taken from their microscope, check out the gallery on their website, linked below in the show notes. So without further ado, let's talk to Laurence. Hi Laurence. How are you doing today?

Laurence Reid: 

I'm good. Hi Kelly. How are you? Thanks so much. Love, love the introduction. And certaintly can recommend the graphics. The ear is an organ that lends itself to some of the most amazing imagery I've ever experienced in, in my in my career and in biotech. But anyway, thanks. Thanks very much for having us. I'm excited to be with you and chat a little bit more about about Decibel and what we're up to. Thanks for the intro.

Kelly Stanton: 

Awesome. I love the, that the technology that's enabled us to take some of those images way better than my biology textbook from high school. That's for sure. We have indeed. Since we've come so far, tell us a little bit about your mission at Decibel and what you guys are up to.

Laurence Reid: 

Yeah, no, I'd love to. Thanks very much for the opportunity. I'm going to be a little bit of the wet blanket out of the gate. And I'm going to remind your listeners that I do serve as the CEO of a public company. And I'm happy to talk to you about the things going on at Decibel and where we're going. Those, what I've referred to as forward looking statements. And I'm going to remind you that they come with risks and unknowns and We will do our best to execute, but there are no guarantees and the biotech welders, as I'm sure you all probably live every day. Yeah yeah, so high level at Decibel our mission is to bring innovative new medicines to people who are challenged with all different forms of hearing loss and balance disorders. It's that simple? What's exciting about it. There are many things that are exciting about that. But there are no therapies today, no pharmaceutical products of any description for people who suffer from any form of hearing also balance disorders. You conveyed the numbers and the magnitude of the challenge, you know, and therefore the opportunity to change the lives of so many people around the world, which is so exciting. And I think motivating to all of us who work in this small field, it's a real paradox that despite that massive set of opportunities and needs global needs as you mentioned, that it's such a. Scientifically there are the uh, as being quite a difficult organ to work with. I think we've opened it up, but I would like you to elaborate in many ways. And in recently, But it's also not an area where the large pharmaceutical companies have historically invested very much. That's going to change. It has to change for the reasons that you said, but right now the playing field, there are really a sort of handful so as small companies, we like to think of Decibel as a leader amongst that cadre but a number of small companies who are really at the Vanguard of innovation in this field. And we're looking forward to welcoming some big farmer up of that field over the next few years, but it's it's a very, it's a really exciting time in the field of novel therapeutics. I think about hearing loss and balance disorders.

Kelly Stanton: 

Absolutely. Tell us a little bit about the launch of Decibel and how you guys got.

Laurence Reid: 

Yeah long before my time I've been there, I've been, had the privilege to be the CEO now for a little bit over a couple of years. The company itself is approximately six years old. Now what he's been told was a sort of formal launch and investment. We were financed that in 2016, by a syndicate that was led by Third Rock Ventures together with GV Google ventures as they were GV as they now are. And our friends at SR1. So outstanding group of investors and the company had been worked on on third Rock's model, as you're probably aware is to nurture these ideas inside the venture firm for, sometimes a couple of years before they decide these things are ready. For prime time, I had friends back then who worked on Decibel before it was Decibel and took them a while, looking at different opportunities. Believing that the time was right for innovation and molecular innovation to bring new therapies to people suffering from hearing loss. But they had a couple of goals and how they were going to get started, whether we're going to get some technology from some big pharma and one or two other sources that bumped around and ultimately they believe they had the right start the right startup team. And as they launched the company in 2016 and the company also, a mere six years old has had a, a winding road as it's not atypical for early stage biotechs. I think very much you thought when these companies get started, they have a certain set of ideas, projects, sentences and some of those workout, some of them don't, I think Decibel w it was no different early on, started off the with a lot of some biology that's involved in signaling directly between the sense 3000, the brain protein factors that have been quite well characterized in the brain over the last two or three decades that didn't lend itself to, fast paths forward for for the kind of therapeutics that we were looking for. We've also explored over the course of the company's short history what were the avenues in terms of genetic forms of hearing loss spent some time to think about tinnitus, which is a real challenge for the many people we under the umbrella of hearing loss and other things about more acquired forms of hearing loss. And it's really just in the last two, three years that we really focused down that, that our initial pipeline is being built around genetic forms of hearing loss and with a focus on gene therapy, which we think is going to be has the potential to be really an outstanding technology. To bring therapy and pharmacology to the inner ear. I'm going to talk more about that, but let's say so it's been an evolution even relatively early in the company's life, but, but what binds all that together, I think is that my predecessors really built an outstanding scientific team and also technologies that the Decibel has been one of the leaders of deploying modern genetic genomic technologies into the inner ear to really expand on molecular understanding of the cells of the inner ear in ways that we believe allow um, almost a molecular infrastructure for which we're going to develop new therapies that, you know, in years to come.

Kelly Stanton: 

Swell. And that leads very nicely into the next question about prioritizing your pipeline. I noticed that you've got one auto protection therapeutic and phase one clinical trial. Way to go! always love to see when companies get that far along. What advice would you give your peers in the biotech space about prioritizing your pipeline.

Laurence Reid: 

Yeah, it's a great question on there. There are people more experienced and more able to talk about that question than me, that I can give you a little bit of color from Decibel. What I think we've learned about our pipeline and one can do our lessons there. Our most interesting paradox that decimal that our most advanced program is a small molecule program for the prevention of odor toxicity caused by a cisplatin based chemotherapy. So patients who receive a cisplatin, many of them to kill on the higher doses can actually have a pretty severe loss of hearing which has not been given the recognition but that it deserves mainly because it plays out in the context of, people's lives are on the line. And the hearing loss is going to be a significant challenge for them in the years after they hopefully get cured, but it's not, it's not the priority at the time. But off, so that's our first product and it really came out of the those sort of early years of Decibel when we were exploring different ways, different biological routes to build a product pipeline and we're driven primarily by biology. And so that product is in is it a clinical phase one based study? And there will be some proof of concept data hopefully being shared during the first half of this year. But behind that, where we were at a Decibel was a belief that as we really came to understand the molecular basis of self-determination in the inner ear and understand the biology and understand how to think about therapeutics and how to deliver therapeutics to the interagency quick digression, your inner ear is that tiny organ that's enclosed in both. And inside your skull, it's actually rather hard to access. And there are various routes that we've, that have been devised injections and other ways to get there. And we use a surgical route that, that cut through the bone to get our gene therapy to where we want it to act. But it's. But we really felt gene therapy could be a, the basis of a platform for a pipeline of therapeutics for the NRA. And so what do we learn from that? I think we learn that, that you're constantly using signs to reflect on how you build your pipeline. What are you learning about, your favorite field? So we had our own toxicity program. Which has a standalone asset we think is really important, but in terms of building a pipeline and therefore to have the chance to create a company that can be sustainable over years and hopefully decades to come, that we were looking for, where were the opportunities to, to be able to take a therapeutic approach and then repeat it as it started to work we felt. So the last three years or so, the gene therapy can really be that leverageable repeatable platform for the inner ear and our lead program is we prioritize. So that's been how we've shifted up a pipeline to wet. Buildup prioritize based on where we can really build a, be sustainable over the long-term. I think that's been a driver and that's often a driver when people are building a company around a platform rather than mystery, perhaps a particular piece of biology. And so on the back of that, you start looking for where are the opportunities that can both be viable products if they succeed, but also. Validate your thinking and your platform by providing a clinical readout in the short term, relatively short term, that can actually give you belief in the platform and the approach that you're taking. And our lead program treats allergy therapy, excuse me is designed to treat a condition known as Vodafone and related hearing loss. People children who are born with a profound form of hearing loss caused by mutations in the gene. And what we liked about that as a place to start was that those children are born profoundly deaf. So any ability to instate a hearing signal from there, any area back to their brain would be an advance. Measurable in animal studies, very easy when we have genetic bubbles of this condition, but ultimately, in the human beings and secondly on bone without a foal and also they have either unable to signal from the inner ear to the brain, the concept of sound but they're inner ear and their ear from what we can tell in animal models, I, don't not human natural history studies the ear and appears to be intact. And so we believe that being able to introduce a gene to rescue the genetic flow postnatally in these children has a chance to fix the signal. Obviously, there's still a lot of unknowns and risks involved in the human clinical trial. But that we have an opportunity where we think that the chance of recovery of that hearing functionality postnatally. W we think it was the best place to get started and we have other products coming in behind it and our pipeline named monogenic also monogenic genetic forms of hearing loss, where we're going to use, try and use a gene therapy. But they get more complicated. Off-road we think is a really fantastic place. So what is it. We learned about the biology of the inner ear. We learned how to develop drugs, that deliver drugs and there safely. And we learned about why gene therapy could be really powerful in the area where the technology was able to deliver genes. And we picked through targets where we felt we could look at the clinical study that would eventually rate and a, where could we get a signal that would be. Robustly measured, quantitative objective, reliable, relatively short term, and against a patient population where their background, they knew that there is appear to be intact. Gave us what we think so far. Good of clinical success. That's what we've done. A Decibel, a little bit of learning in there. And so I'm not going to use like a lot of different platforms. I was lucky not to be out on the island while it really expanded its focus on genetic diseases of the liver and the lead program that which became, an approved drug was for TTR amyloidosis. And it was a, just a very clearly defined targets in the liver. Target, you have had to measure it when you want to measure. As we went into clinical trials, so some analogies.

Kelly Stanton: 

Nice. Yeah, that's exciting. I spent some time in the cochlear implant space in in my career. So I'm quite familiar with, the talking about the varying causes of those losses. And yeah, there's, it's interesting because of course you want to empowered her children who are born deaf to hear as soon as possible so that they can develop their speech patterns and all those kinds of things. But it's interesting cause it's very, it's a tough decision to make. If you do a cochlear implant, that's very invasive. And so it's th the idea that we could restore normal hearing in, in places, directly in the locations in ways that are maybe not as invasive and destructive to the existing structures. That's pretty exciting technology. It

Laurence Reid: 

is. Kelly that you just do add enough ideas with you, and I could talk about that for the rest of the night. I think cochlear implants are one level remarkable technology and Children who have Vodafone and deficiency. They are the standard of care today in the developed world is to provide them with with one or two cochlear implants. You touched on an even more important point, which is that, children born. Profound hearing loss, such as children with another phone inefficiency that medically we refer to that as a neurodevelopmental emergency and it really reflects exactly what you said, that all of our. Learning is driven by language and social interactions with our parents, with our families, ultimately with art, with our school playmates and teachers and hearing is really at the core of that. And Born profoundly with profound hearing loss is severely impaired or inhibited in their ability to communicate with all of those people in defendant ultimately has a significant potential impact on their cognitive development. And there are, there is the quality of that can extend well into adult. And a cochlear implant is a wonderful technology. We believe that would be gene therapy. There's the possibility based on some of our animals studies that we're going to be able to restore signaling from from the brain to the brain, excuse me, from the inner ear that might indicate. Physiological form of hearing in these children ready for the first time cochlear implants. Really it's a fairly coarse form of hearing and it it's enabled. Strong social interactions fitting for compared to profound hearing loss. But reasonable, we, we believe that if you have a child with a cochlear implant and drop them into a regular school clots through that, they're probably going to understand all that. They're going to pick up about a third. I got half of what's going on. And if you think about that learning and social environment, it's really quite challenging and it's, the, this is not, these are assistive devices that don't really curing and in a sense, the challenge that these children are born with and as a site, long way to go with therapy and there's only been one clinical trial so far, but yeah. Multiple Navid in the coming years, but the chance to really take hearing loss in these children to a to a quality, a disease modification that we think, could be maybe very significant relative to the current devices technology.

Kelly Stanton: 

Definitely. I know parents wrestle with that, and knowing and it was fascinating for me. I know, as an engineer in the thin device integrity I really had this impression that this medical device was just going to restore their hearing. But when you look at taking, analog signals, for example, and converting that to a digital signal there's a depth that's lost. It's when you compress. Analog hearing into digital. And so you're right. The, while it does restore some very coarse hearing it isn't that's a pretty exciting. Yeah, different perspectives. That's interesting. So tell us a little bit about the amplify program then. So if we switch over to addressing auditory neuropathy instead we'd love to know a little bit more about why you decided to collaborate with another company. That's invitation, I believe to bring about a second.

Laurence Reid: 

Yeah it's a great question. The industry, the biotech industry, collaboration with people who have complimentary skills and resources is is a fundamental aspect of how we build our companies and and help up products from the market. One of the challenges, It because it's such a new field and our genetic hearing loss is doesn't today have a therapeutic benefit that one of our main needs is to educate physicians and the population about the importance of genetics in hearing loss. And there are many different forms of genetic forms of hearing loss and. So we partnered with is a fantastic leading genetic testing company. And, we experts in the area. We know a lot about the genetics of hearing loss with sort of drug developers, but we're not a genetic testing company. And with that was not part of our business model. So we partnered with at VTA we're actually. With them offering a free genetic testing service and that service in children who have an order for neuropathy, which is the inability to signal from the inner ear to the brain that we're assaying about 200 genes that are candidates to be genetic causes of hearing loss in patients who, who provide a genetic sample. And, the first three, the primary goal is to begin to educate. Physicians primarily. And and then families as well about the importance of genetics in hearing all. So obviously that's where ultimately where we think the first generation of therapies are gonna come from. So it was designed to be an educational program that would provide a service that has. To families even advance of the therapies in terms of managing expectations of perhaps their child's trajectory in terms of the physiology and the challenges that they may be about to encounter. So there's some utility in what we measure. But it was to start with, it's an educational program about the importance of genetics within the whole field of of hearing.

Kelly Stanton: 

Nice. That leads to the next question then. Quite nicely. How do you see the industry evolving over the next five?

Laurence Reid: 

Yeah. So it's it. It's a good question. I think some of my colleagues in the industry would answer that one differently. So I'm going to give you my answer and you can put that their ideas. You started off with the numbers, hearing loss of such a massive opportunity, but of course, hearing. Like many common diseases is, there, there are many different forms of funerals. We've been talking about a lot about genetics. Genetics is actually a minority cause of hearing loss. Hearing is mediated by special sensory cells. School has cells in your inner ear. We lose those. Everybody loses those almost linearly over the course of your life. So sooner or later, We're all going to start to have some degree of challenge with hearing. And it's about the rate. So ultimately there are, a large part of that population is just due to a natural attrition of hairstyles. Other people are unfortunate enough to lose it, hassle levels and therefore functionality of. Are there any area due to environmental insults? So we had noise being, obviously many veterans suffer from from hearing challenges. There are some kinds of chemicals and pharmaceuticals that can cause fairly severe forms of hearing loss, so that there's a multitude of different ways that we, the people lose their hearing. And biologically, those might look very different in terms of etiology of of those diseases. We liked genetics as really understanding this form of hearing loss is caused by a defect in this gene. And I think now that that some of the earliest breakthroughs may be able to be enabled by by gene therapy, treating very specific, relatively rare forms of hearing loss. And then I think the real. I would say holy grails within our field. They're probably intertwined medically, but not completely understood. One is so the first. We have much more common acquired forms of hearing loss. And can we either hold or reverse the process of hassle? Also, we have ideas about how that might happen with gene therapy that are very early in our research earlier in our research pipeline. And I think they will probably follow off to some of these genetic foams. I've met another big problem, which I think is a hard problem is tinnitus, which can be a very. Very challenging condition. That is probably a potential to be more better understood the level of the of the fiddling with it within the brain. And that's the other real holy grail of these fields, but very difficult. And that's the whole area we will call it, I think over the next several years, as we continue to understand, certainly into the brain from the ear. That hopefully solutions will start to reveal themselves there, but it's really the other piece of another major piece of the

Kelly Stanton: 

definitely at biology is nothing is not complex. One more question and then we'll head towards wrapping her up. If you could go back and tell yourself something at the start of your career. What would that be?

Laurence Reid: 

This is such a great question. I don't know what you guys come up with this question, talking about drugs for the ear. Let's ask Laurence to reveal his foibles. I, it is a great question. I think I would say two things and they're going to appear like a classic. Paradox to the app. So I would say the two things that most profoundly dropped into my thick skull over the past 25 years were firstly, be yourself, but understand how yourself, impact your colleagues around you and thereby how it can live. Your limit your path to try and get done the things that you want to be, that you want to do. And I can provide a little bit of color, on that. And quite a funny story when I was having, I was on the being a business development guy for much of my career. And my first manager at millennium was a gentleman called Steve Holtzman, who was, one of the leading. Business thinkers and industry of the past. won't even put a number on that of the past decades. And he was doing my performance review and he was like, Mach and I, we really like to play poker with you some time. Which was his way of telling me that Laurence does not have a poker face and maybe there's a business development person I needed to learn. So I tried to do that for a couple of years and just failed. And eventually I decided, okay, that's not going to be my route. I'm not going to do this like a poker game and I'm going to come up business development. It was me and it, which I think people generally have found to be this guy's pretty straightforward. What he's going to tell us what he needs and he'll be fat and he'll listen to what you need. And that was me being me and not trying to be a poker player, that I was clearly gonna fail it being. So that was for me getting more comfortable with, trying to about being myself rather than. An aspiration, would not want to play poker with Steve-O Almac because I would lose horribly as he well knew. But I think later in my career, it's you have to understand that. Being yourself impact to other people and can get in the way of achieving what you want to achieve. And, I grew up in a culture in the UK that, loved a good argument. I love a good argument. And, but in a work environment, you have to go that full fully. And I realized a few years ago that how I got into debates and in a work environment was often getting in the way of what I was doing. Achieve with, in a collaborative way with colleagues who I enjoyed working with them, wanting to try and do exciting things with, and it was getting in my way. And I just really think about how my normal self was impacting them and their appreciation of what we might do together. So it was the second big luck. So the two things go there's slightly intention, but that's what it's like. So be yourself, but understanding how yourself impacts other people, is how. Yeah,

Kelly Stanton: 

no, that's interesting. We here at Qualia we're really big on being authentic, we don't want to be, we don't want to feel contrived or, that sort of thing. Yeah, but just because you're authentically, you doesn't mean that somebody else. And being authentically themselves, it's not necessarily going to be a good match. So yeah, it's

Laurence Reid: 

interesting. No, I think that's exactly right. Ultimately it depends. Don't understanding of, the kind of people you want to, you want to work with them that you choose to work with as people that you can enjoy working with them, being yourself and being impactful while being yourself, the two things you need to solve.

Kelly Stanton: 

Definitely. Thank you so much for your time today. Laurence, where can people go to learn more follow along and connect with you?

Laurence Reid: 

Oh so we have a wonderful website full of great pictures of of the inner ear, the incredible cell biology that my colleagues do. That's Decibel tx.com and we're on LinkedIn and Twitter. And I also show up myself from time to time on LinkedIn and Twitter. And I'm always happy to engage with people interested in anything to do with novel innovations for therapies for the inner area. So appreciate that. And thanks for pretty much for having me. I enjoyed the discussion.