Exploring Cell Therapy for Hearing Loss: Updates on the ReSonance™ Program with Brian Culley, CEO of Lineage Cell Therapeutics

Hello and welcome to another episode of this Week in Hearing. I’m your host, Brian Taylor. And this week we have Brian Culley, who’s the CEO of Lineage Cell Therapeutics, and he’s here to discuss their preclinical trial success with Resonance and auditory neuron cell transplant for the treatment of hearing loss. Welcome, Brian, to the broadcast. Thanks, Brian. It’s my pleasure to be here. Before we dive into auditory neuron cell transplants and the results of your pre clinical trials, could you tell us a little bit about yourself and about Lineage and the mission of your company? Certainly. So Lineage is one of the leading cell transplant companies. So our technology is based on our ability to manufacture in the laboratory environment, specific cells of the human body. And then we transplant those cells in diseases or conditions where the native or normal cell is destroyed or dysfunctional. So it’s sort of like biological replacement parts. We replace the missing cells in order to restore the function that you would normally have. Well, this is a very hot topic amongst our audience, so we’re really happy to have you on tonight. Tell us a little bit about your background before you were CEO of the company. What are some of the things that you’ve done? You know, I’ve got a fairly diverse background in the space. I think it served me well. I used to do drug discovery, so I used to wear a white lab coat, and, you know, I called myself a jean jockey and all that sort of thing. Over the years, I got involved in business development. So that’s the buying and selling of the rights to develop different therapeutic candidates. And then about 15 years ago was the first opportunity I had to become the CEO of a company. And so this is my third time doing it. And I absolutely love the way the intersection of science and business and really using my background to try to make the best possible decisions. That’s great. Lets dive into the topic of the Resonance preclinical study. Could you share with us, Brian, some of the most significant outcomes of that study? And how do those outcomes shape the next steps? Yeah, we’re really pleased. I mean, this is an exciting new application of cell transplants. So we are manufacturing auditory neurons, and we deliver them in an animal model. And we’re really looking to see if the cells can be successfully delivered, if they are durable. How long do they remain present for? Do they migrate? Can they get into the inner ear? So we treated the animals in a way that imitates the loss of hearing, and then we deliver ourselves maybe to the modiolus, maybe to the scala tympani. But really this is just to say, can we get the cells into the right place successfully? Do we see them there, or are they getting cleared out immediately? And if we are able, as we were able, to see that those were successful, then the next step is to move on to functional models. So we will ask questions about whether we can either preserve or retain or regain hearing in these same animal models. I think a good next question is I think if you could give a little clarity around this term, I’ve already used it a couple times. Pre clinical study or pre clinical trial. What do we mean by that? How does that kind of fit into the broader context of bringing something like this to market? Yeah, before therapy is available to patients there are three broad groups or categories of work. You can think of these as just sort of laboratory, basic discovery research. That’s where you would be working with the cells in the lab, trying to figure out how to make them, how do they behave, how do you scale them so that you can make this an affordable therapy. The next step before going into human testing is typically animal testing. So you would do a number of different studies in an animal setting. The type of species depends on what you’re trying to demonstrate. But you’re looking at things like safety and basic efficacy. And then you can move on to the third category, which is, of course, human testing. And you don’t want to do human testing without completing steps one and two. But ultimately that’s the really exciting part is the human testing. And then if you have cleared the lab work, and you cleared the preclinical animal work, and you clear the human testing successfully, then you have developed a new therapy that people can enjoy the benefits of. And about how long, typically, does that entire process take? Seven lifetimes, it seems. You know, it varies. There are averages and data out there. You often hear numbers like 10 to 12 years, but it really depends. For example, with our program with auditory neurons to address hearing loss, we were able to go from the very first step of the process, which was to decide that we wanted to do this project. We got into animal testing in just one year. Thats extraordinarily fast, and there are reasons for that. So there’s tremendous variability on how long it takes to get a new therapy approved. And it’s because it’s critically important that the treatment is Helping people and not causing harm. And there’s a lot of work that has to be done to prove that. No doubt about it. So tell us a little bit about how might this therapy improve outcomes for patients? You know, I’m thinking people that might be struggling with hearing aids or cochlear implants. How might this benefit them? Well probably your audience is well versed in, you know, how sound waves reach the hair cells and, and then they release glutamate to stimulate the auditory neurons. But in some settings, those auditory neurons are either dysfunctional or destroyed. They can be absent. And so we are manufacturing the auditory neuron so that those hair cells have something to hand off to, so that they have the system and the architecture to be able to move that signal into the cochlear nucleolus and into the brain. Those handoffs occur are very similar to other work that we’re doing in the eye and in the spinal cord. It’s all around neuronal interactions and maintaining a nice, clear signal so that those sound waves can be picked up and interpreted. So if you don’t have the machinery, you don’t have the ability to make those connections. So we’re replacing some of the machinery or some of the architecture that allows people to be able to convert that stimulus into a message that makes sense in their brain. You mentioned some of the other areas that you’re involved in around vision and so on and so forth. Can you tell us a little bit about some of the other projects you’re involved in and maybe how they relate to what you’re doing with auditory neurons? Yes, the setting of macular degeneration, which is one of the leading causes of blindness. The dry form of macular degeneration. The hallmark of that condition is the loss of a specialized retina cell. So we manufacture retina cells as replacement cells. We transplant those to the eye to help people preserve or regain vision. And actually, that project is partnered with Roche in an almost $700 million alliance, a global alliance we have for that program. We also manufacture oligodendrocyte progenitors, which are one of the glial cells that make up the spinal cord. So, of course, you can imagine that as your brain says, I want my hand to grasp that electrical impulse has to be carried by a cellular message. And if that connection is absent because you, you know, fell on your skiing trip or your mountain bike and you destroyed that part of your cellular connectivity we can manufacture that connection in the lab, transplanted into patients to help them make the connection between their brain and their upper extremity mobility. So it has very similar parallels to what we’re doing in the ear insofar as we’re trying to take that external stimulus and give it that connection, replacing the cell type that’s missing or deficient and restoring the function, in this case the ability to hear. So there are a lot of parallels with the approaches that we have in the eye and the spinal cord. And frankly, you can think of a lot of different places where if you lose a cell type function, you might want to replace it. And bone marrow transplants have been around for 80 years and they’re really probably the highest and best example of it. Very successful therapy, life saving therapy. So back to the cell therapy for hearing. Could you tell us what are some of the expected challenges that you foresee around moving from The pre clinical to the clinical trials? You know, they’re really the standard testing that’s required for programs like this. You want to demonstrate that the material you’re making is pure, that you have characterized it very well and you understand it that it has potency. You know, we want to make sure that we are doing, giving the patient the best opportunity to have a benefit. So all of the regulatory hurdles that are common in cell therapy or cell transplantation are applicable to us as well. Delivery can be a tricky idea in cell transplants. You know, many people might be thinking about injecting cells into a vein and they go do wonderful things in the body. Thats really not our approach. We have to deliver the cells right to the area where they’re deficient. They’re not traveling through the body and finding out where to go. They must be delivered to the right place. So it’s a very delicate transplant of cells. So these are all very standard and normal and expected requirements. They all carry some risk, but usually those risks can be overcome with additional testing and demonstration that a procedure and the material are safe and well tolerated. If I remember right, this preclinical trial, this study that we’re talking about was conducted at the University of Michigan. Am I right about that? Yeah, absolutely correct. Yeah Yep. Do you expect to be. Is this an ongoing partnership with the University of Michigan? Do you have any long term goals associated with them that you could share with us? Yeah, these kinds of relationships between industry and academia are really common in biotech. It helps a company like ours obtain technical and intellectual expertise. Oftentimes these arrangements are affordable. They help the universities and the students because they can generate publications and intellectual property rights. And so there are a lot of different ways that both parties can benefit. We are not a hearing loss company. Right. We are actually a cell manufacturing company. So we have to go to outside sources to get the expertise, whether that’s the eye, the brain, the spinal cord, the ear. And so the University of Michigan alliance is an example of one of those beneficial strategic interactions that Lineage has entered into for the furtherance of our product candidates. Good to know. Are there any other universities that you typically work with? You can imagine that oftentimes some of the leading universities, they attract the best and brightest professors. And so it’s not that difficult to figure out who’s, well published, who’s doing exceptional work, and approach them and say we have this interesting thing. Would you like to collaborate? Sometimes you actually do find in surprising places some pockets of excellence that might be really suitable for, for you. But you know, we’ll go to where the highest and best quality work is being done. You know, of course, the mind races to places like Stanford and Harvard, but you’d be surprised. Oftentimes you can, you can find some exceptional alliances and thought leadership in places all around the world. That’s great. Good to know. I think probably the most important question that a lot of our audience has is since many of them are hearing care professionals, they work with folks with hearing loss all the time. And they’re wondering how do you see Resonance fitting into the broader scope of hearing healthcare? Yeah, I think Resonance as a cell transplant can play well in the sandbox, so to speak. Whether that’s alongside cochlear implants, which probably a really natural pairing for this technology, but also hearing aids or other assisted listening devices. Thats one of the nice benefits about cell transplants and cell therapy is that usually you don’t have to make a choice. Do I want to try the cell transplant or do I want to do a cochlear implant? Theres no reason that these technologies can’t be potentially additive used sequentially. You know, you wouldn’t want to simultaneously administer other types of cells into the inner ear at the same time. That would be very strange. But in terms of some of the mechanical or engineering solutions, solutions that are available and potentially even additional small molecules you know, Some small molecule, (i.e. pill) type therapies could probably work well alongside a cell transplant. So that’s one of the really great things about working in this space is we don’t see ourselves as competing against those other modalities. But perhaps those are some great combined solutions that cell transplants could work well with or they could work well with us. And the target population is individuals with auditory neuropathy, is that right? Yeah we’re actually, because it’s so early, we’re still trying to refine the best patient population. Commonly, what a company would do is identify what they consider to be the really best or ideal target patients to demonstrate that their technology can deliver a large benefit, and then from there start to explore more of the peripheral ideas on where you might find a benefit. So we don’t, at this point, we don’t have a really tight grip on what we think the perfect candidate for this technology would be, but that is something that you would naturally normally develop over time. And that has been our experience in other places. We started with some very severe patients in the eye, and we moved over into less severe patients, and that’s where we really saw the biggest benefits. So something like that might be very likely to be the path that we follow with hearing loss as well. Start with people who have the most profound and severe defects, ensuring that we are delivering and tolerating the therapy. And then from there maybe move earlier into people who have got less severe deficiencies so that we can see those and measure those benefits in an easier way. Final question for you, Brian, that is where can people learn more about what your company is doing? Yeah Lineage Cell Therapeutics is a publicly traded company, so lineagecell.com is where we can be found. There’s a lot of information about the work we’re doing there. People can see some really pretty pictures of some of the cell transplant results that we have and learn about the company more broadly. Great. The guest this week is Brian Cully, CEO of Lineage Cell Therapeutics. Brian, thank you very much for taking some time out of your busy schedule to be with us. Thanks so much, Brian. Just a reminder for your listeners that Lineage Cell Therapeutics is a publicly traded company, and people can understand the risks and opportunities of investing in Lineage through the filings that we make with the securities and Exchange Commission at SEC.gov