Manufacturing Auditory Neurons with Brian Culley, CEO of Lineage Cell Therapeutics.

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May 22, 2023

The idea of manufacturing auditory neurons that can be used to replace those damaged by disease is closer to reality that you may think.

This week, Brian Culley, CEO of Lineage Cell Therapeutics returns to discuss a collaboration with the University of Michigan with an initial focus of studying cell therapy for auditory neuropathy spectrum disorders, a condition that affects about 10% of children with hearing loss.

Full Episode Transcript

Hello, and welcome to another episode of this Week in Hearing. I’m Brian Taylor, and our topic this week is auditory neuronal cell therapy. And here to discuss this topic making his second appearance at this Week in Hearing is Brian Culley, CEO of Lineage Cell Therapeutics. Welcome back, Brian. Great to have you with us. It is my pleasure. Thanks. Brian, I thought we’d start the conversation. It’s been more than a year since we had you on. If we could maybe if you could remind our viewers about the topic of allogeneic therapy, what it is, and why hearing care professionals should probably know a little bit about it. Thank you. A lot has happened in the last year. So our basic approach as a biotech company is to develop a therapy to help people with hearing loss. But we’re taking a very different kind of approach to the problem. We are manufacturing auditory neurons in the lab, and then we aim to transplant those auditory neurons into the inner ear because through a number of different ways that people can lose their hearings, most commonly from age, these auditory neurons can sometimes become dysfunctional or destroyed. And so if you replace those auditory neurons, replace the parts that are broken, you may be able to either slow the further loss of hearing or you may be able to regain hearing with respect to allogeneic, that’s a technical term of the art, which really means that the cells which we use would be applicable to anyone. We grow these cells in the laboratory. We don’t have to make them specific or unique to each individual. The cells that we grow could be mass produced and then utilized in any patient around the world that they were approved to do so. And I know before we talk about how you use that therapy with hearing, you’ve been involved in some other areas too macular degeneration, spinal cord injuries. Can you maybe share a little bit about your work in those areas? Yeah. The reason we’re able to go into hearing loss is because we’ve had some success in related areas. So the general approach of manufacturing what we’ll call just replacement parts or replacement cells has been most profoundly illustrated in our macular degeneration program, where we manufacture a very specific type of cell that comprises part of your retina and you rely on for vision. That program has gone into clinical testing. It had some fascinating and wonderful early stage data, and it led to an alliance with Roche and Genentech, which is probably the number one pharmaceutical company in the world in ophthalmology, and the value of that deal was $670 million dollars. So obviously, they see something really interesting with our approach. And what we’re trying to do is repeat that success. We want to manufacture the cells that comprise your spinal cord to help people who suffer spinal cord injury regain mobility. And more recently, we started the Auditory Neuron Program, where we hope to manufacture and transplant these cells in order to help people with their loss of hearing. And I know a few months ago, you announced a collaboration with the University of Michigan with initial focus on studying cell therapy for auditory neuropathy. So could you tell us a little bit about this collaboration with the University of Michigan? Yes. This all came about a lot faster than we planned. But what we’re particularly good at is figuring out how to make a specific cell type and then scaling it up. That work went very quickly. What we don’t have in house is we don’t have the models, the experimental techniques specific to hearing loss. So the University of Michigan and the investigator which we’re collaborating with there, they have some models or they have the experience to develop some models where we can start to transplant the cells that we manufacture. We transplant them into a specific or one of a couple of different species of animals. And what we’re focused on with the University of Michigan is first, just making sure that we can figure out how and where to place the cells and then to see that they’re durable. We want to see how long they last after they’ve transplanted. All of these are early activities that ultimately can lead to and support human testing, which is, of course, where we ultimately want to go. That sounds pretty exciting. I know that auditory neuropathy, last time I checked, was about 10% of cases of sensorineural hearing loss in children were folks that had auditory neuropathy conditions. So it’s pretty exciting. A lot of people, no doubt about it. Yeah. One of the very interesting aspects of cell therapy compared to, say, gene therapy, is that when you replace the entire cell, you maybe don’t care so much why it’s dysfunctional or why it’s absent. So there’s incredible complexity in cells, and sometimes one little part of the cell is broken, and people try to fix that with small molecules or antibodies or maybe gene therapy. But by replacing the entire cell, you become a little bit indifferent to why it’s absent. So some people lose hearing, as you know, from certain types of chemotherapy. Some people lose it from concussive explosives. Some people just grow old and lose their hearing. Perhaps we don’t know yet, but perhaps many different types of hearing loss could be addressed by this particular and unique approach. No that’s… Could you give us any more insight into the progress. I know, you made the announcement on the collaboration with the University of Michigan back in February. Could you maybe lay out a little bit of a timeline or a roadmap as far as how you see the collaboration unfolding and what you expect to find? Yeah, ultimately, of course, the data determines your pace of progress. But I’m so excited that we were able to go from essentially a concept, I mean, literally the idea of maybe we should make auditory neurons to the point where we’re now in the preclinical testing. And to do that in just one year, that’s much faster than an industry norm. I don’t know if we’ll be able to continue that pace. But what we’re doing right now, I just saw, I literally last week saw the very first images of our cells that had been transplanted into the cochlea and be able to see those images. Now we’re going to look at questions like durability and placement and see what happens to these cells over time. So I expect we’ll be working in these preclinical models for probably a couple of years, but then we should be in a position to talk to the FDA about going into human testing. But these are new technologies and it’s really hard to know how long they’ll take. But so far we’ve been able to move pretty quickly and I’m very proud of the team for their ability to do that. Yeah, that’s great. I have one sort of final crystal ball question, and that is how do you see this type of approach with transplanting cells? How do you see that working in a stand side by side with other clinical approaches like cochlear implants, hearing aids? What’s your thoughts on this approach as an intervention? Yeah, it would be wonderful if it was able to displace those. If you transplant cells and they’re durable, they’ll last in your ear as long as you last. So you don’t have to replace the battery of these cells. They have their own batteries. So I think that while it would be nice to imagine a one time transplant that’s essentially curative in a way that’s a very ambitious goal, I think more realistically that this approach could be complementary. There are tools and techniques, of course, to amplify sound, but the sound going from the hair cells through the auditory nerve fibers, it doesn’t matter how strong the signal is at the hair cell, it has to hand off that information somewhere. If you don’t have that auditory nerve fiber, that information is not going anywhere. So I can imagine that we could have both sides, the amplification and the conductivity of that electrical impulse through the chemical reactions, which are necessary, that they could be really complementary and drive better outcomes for patients in either one alone. Good to know. One final question. I’m kind of curious about. What other conditions, what other areas of the body is your company, Lineage Cell Therapeutics? What are you looking at? Well, the cells that we begin with are essentially unprogrammed. They’re blank. And we have the instructions to tell them to become auditory neurons or retina cells or the cells of your spinal cord. They have within them the programming to become any of the 200 cell types of the human body. So I could imagine a future where we’re working on cardiomyocytes for heart failure, or we could be working on liver cells or all sorts of oncology applications. Essentially, with adequate resources, we could go into a lot of different areas. We have already begun a program with photoreceptors, a different kind of cell type of the eye. So we have a few unannounced things that we’re thinking about still. So the sky, perhaps, is the limit. It’s a new technology, and it’s an exciting new branch of medicine. Well, and it reminds me how important basic bioscience is to anybody that’s in the healthcare hearing, healthcare space. Your company is a good reminder of just how important all that is. Yeah, it really is. And this has not been done before. There are companies out there that work with stem cells, but I’m not sure those cells, what they’re able to do or not able to do. But by manufacturing the actual cell that normally belongs in your ear, we think we have a reasonable chance at showing something really exciting, very interesting. Brian Culley, CEO of Lineage Cell therapeutics. Thanks for taking some time out of your busy schedule to be with at this week in hearing. It’s been my pleasure. We’ll have another year of progress sometime ahead. Talk to you next year, I hope. Thank you so much. All right. Thanks, Brian.

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About the Panel

Brian Culley joined Lineage as Chief Executive Officer in September 2018. Prior to joining Lineage, Mr. Culley served from August 2017 to September 2018 as interim Chief Executive Officer at Artemis Therapeutics, Inc. (ATMS). Mr. Culley previously served as Chief Executive Officer of Mast Therapeutics, Inc. (MSTX), from 2010, and was also a member of its board of directors from 2011, until Mast’s merger with Savara, Inc. (SVRA) in April 2017. Mr. Culley served from 2007 to 2010 as Mast’s Chief Business Officer and Senior Vice President, from 2006 to 2007 as Mast’s Senior Vice President, Business Development, and from 2004 to 2006 as Mast’s Vice President, Business Development. From 2002 until 2004, Mr. Culley was Director of Business Development and Marketing for Immusol, Inc. From 1999 until 2000, he worked at the University of California, San Diego (UCSD) Department of Technology Transfer & Intellectual Property Services and from 1996 to 1999 he conducted drug development research for Neurocrine Biosciences, Inc. (NBIX). Mr. Culley has also served on the Board of Orphagen Pharmaceuticals, Inc. since May 2017. Mr. Culley has more than 25 years of business and scientific experience in the life sciences industry. He received a B.S. in biology from Boston College, a masters in biochemistry and molecular biology from the University of California, Santa Barbara, and an M.B.A. from The Johnson School of Business at Cornell University.

Brian Taylor, AuD, is the senior director of audiology for Signia. He is also the editor of Audiology Practices, a quarterly journal of the Academy of Doctors of Audiology, editor-at-large for Hearing Health and Technology Matters and adjunct instructor at the University of Wisconsin.

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