This week we tackle cell and gene therapy for hearing loss. To help us better understand the potential of allogeneic cell therapy we asked Brian Culley, CEO of Lineage Cell Therapeutics to describe how it works and how these types of pharmacologic treatments could stand side-by-side existing treatments such as hearing aids and cochlear implants.
Brian Taylor 0:09
Welcome to This week in Hearing. I’m Brian Taylor. And today we’re going to be tackling the topic of cell and gene therapy for hearing loss. And with us to discuss that today is the CEO of Lineage Cell Therapeutics, Brian Culley. Brian, I want to welcome you to this episode of This Week in hearing.
Brian Culley 0:28
Well thank you, Brian, pleasure to be here.
Brian Taylor 0:30
I thought before we tackle the topic, it would be good if you could tell us a little bit about your background, and your company Lineage Cell Therapeutics,
Brian Culley 0:38
I’d be delighted to. So I have a background in basic research, basic science, I used to wear a lab coat and manipulate DNA for many years. Through my career now, which has, I guess, just recently passed 30 years in this industry, I have evolved over to the business side of our industry, still relying on my scientific background, of course, but I’ve actually been a CEO of three different publicly traded companies, and in particular, at Lineage. This is now I guess, about three and one half years that I’ve been running this company.
Brian Taylor 1:15
Okay. Well, I think our viewers probably are mainly hearing care professionals and those interested in the hearing care space. I’m guessing that most of them haven’t heard of Lineage Cell therapeutics. So maybe tell us a little bit about what you all do.
Brian Culley 1:30
So Lineage Cell Therapeutics is a regenerative medicine biotech company, and what we do is we manufacture specific types of cells, which comprise your body. And then we use those cells, those whole cells as medicine. So we do this from cell lines. And what’s really unique about the cell lines that we use, is they have the ability to become any of the cell types of your body. So we have cells, which are able to make bone cells or blood cells, or hair cells or auditory neurons for for hearing loss. So it really is an amazing, powerful cell therapy technology.
Brian Taylor 2:12
Well, and I see from a recent press release, since you’re kind of new to the hearing care space, it seems like in that press release, you talk about lineage cell therapeutics, being a company that’s developing allogeneic cell therapies for unmet medical needs. So maybe, let’s dive into some of the details around these unmet medical needs and how you see allogeneic cell therapies working inside of the hearing care, space.
Brian Culley 2:40
Yeah, so within the very broad category of cell therapy, which is to say, using cells as medicine, there are two big categories. One is a autologous and the other is allogeneic. We only do allogeneic, I’ll describe them this way autologous would be using the cells from a patient, expanding them a number and putting them back into the patient. Now that’s very bespoke, it’s very custom. It’s one treatment for one person allogeneic is taking cells and expanding them in number, and then using those cells as medicine for potentially millions of different people. So it’s the same material every time. And the really powerful advantage of an allogeneic approach is that, of course, you’re making the same medicine for everyone. So the cost advantages are very attractive compared to autologous approaches.
Brian Taylor 3:36
I see. Could you maybe tell us a little bit about Lineage – What other unmet medical needs have you tried to tackle?
Brian Culley 3:46
Yeah, this is, this has been such a fun ride for me over the last few years, because I didn’t know really that much about the power of cell therapy when I joined the company. But we have right now three clinical programs. And in each case, we manufacture a different type of cell. So we can manufacture pure populations of retinal cells. And that’s to treat one of the leading causes of blindness. And we recently announced a nearly $700 million deal with one of the major pharmaceutical companies Roche and Genentech for that program. Then, and that’s based on clinical data that we’ve that we’ve generated. We also have a program in spinal cord injury. Now, of course, we don’t make retina cells for the spinal cord injury, we manufacture what are called oligodendrocytes. And so that’s part of the equipment, which comprises your spinal cord and carries the electrical impulses and what we’re trying to do in that program is help people regain more of their upper extremity mobility. We want people to be able to manipulate their wheelchair and use the phone. We also have a cancer program we make cells of the immune in the innate immune cell called the dendritic cell. That’s an important player in your immune response. And so those three clinical stage programs are now joined by the newcomer in our in our lineup, which is treating hearing loss by manufacturing auditory neurons.
Brian Taylor 5:07
So tell us about that I know I read in the in the press release that you’re looking to evaluate auditory neuronal cell transplants for the treatment of hearing loss. So tell us more.
Brian Culley 5:18
How’s that work? Yeah. You know, interestingly, this, this is something we initiated on the heels of our successful retina program. And that’s because not just because the retina program was so valuable to us, but because there are many parallels. So just like in our retina program, where we manufacture a very specific type of cell, and carefully administer it into a sub retinal area in your eye, where we’ve been able to recover lost tissue and help people to be able to see better, conceptually, it’s the same approach you have within your inner ear. Within the cochlea, you have specialized cells, a lot of people are familiar with hair cells, and the role of the hair cell in the inner ear. But there also are auditory neurons, which connect with the auditory nerve, which is responsible for taking the sound waves and converting it into electrical impulses. So that you can your brain can can process that that sound and understand it as a speech or whatever kind of sound it is. And in a number of different conditions, you can lose the function or even have total cell death of those auditory neurons. So our strategy is really straightforward. It’s very simple. We can manufacture auditory neurons, place them into the inner ear. And if they survive and are functional, we think they may be able to help preserve hearing, or even improve hearing.
Brian Taylor 6:40
So I guess the next question would be what types of hearing loss specifically might these might this cell therapy, what types of hearing loss might benefit from it?
Brian Culley 6:51
Yeah, we can’t wait to find out. So one of the things, again, that we’re borrowing from the retina program is that when you replace an entire cell, it doesn’t usually matter too much to you why that cell is dysfunctional. So if you think about the complexity of biology, you know that that auditory neuron might be dysfunctional due to any number of pathways that are going wrong. But if you replace the entire cell, you’re sort of addressing everything, which to us would suggest that there may be a very large opportunity to treat a wide range of different hearing losses. So there are some some folks that are focused on things like their chemotherapy induced hearing loss. There is of course, trauma, there is age. For us, if we are able to deliver functional auditory neurons, and they can do the job of your of your normal neuron, we may be able to help a very large number of individuals, but that will be part of our clinical testing is to try and refine that and figure out who really is most responsive to this type of therapy?
Brian Taylor 7:54
Yeah, that’s really interesting. Tell us a little bit more if you could about the clinical trial process. With this type of therapy, what that looks like, what the roadmap might be that kind of thing, if you could,
Brian Culley 8:06
yes, one of the great frustrations in this space is that there really are very few pharmacologic solutions. Now, of course, we have the mechanical solutions, we have things like hearing aids and cochlear implants. But in terms of medicine, the way that we think about it, there’s very little to go by, however, the FDA does have a very well trodden process for how you test the safety and efficacy of new therapies. So what we’re doing right now is we’re working to scale up the manufacturing of these cells, we will be testing them in animal models, and that will provide the evidence to the FDA that we can go into a human setting, I expect that we would start with humans that have very poor hearing, because initially, we just want to taste test the safety and tolerability of this. But as we gain comfort with the delivery of the cells, their safety and their tolerability and their durability, then we’ll start to move into patients that have only partial hearing loss and really try and refine what the right patient population is. Eventually, I would hope and expect that we would be testing hundreds, perhaps 1000s of people with this medicine in order to demonstrate that it can be a very powerful new technology for the hearing loss patient population.
Brian Taylor 9:25
Yeah, that’s really exciting. I think many of our viewers are probably interested in this kind of approach to hearing loss, also probably a little bit nervous, because they might be afraid that it’s going to take some of their traditional hearing aid or cochlear implant business. So, I guess, looking at this commercially, and I know that, you know, no one has a crystal ball and you really can’t predict the future but just as a general topic, gene or cell therapy. How do you envision that being when do you envision that be being offered commercially?
Brian Culley 10:01
Yeah, I’d like to mention that from a commercial perspective, I don’t think we’re really in the business of trying to displace other technologies. If you if you think about the use of cells, being able to stimulate those cells to keep them healthy and happy, any of those technologies, I think would be additive. I get that question often with our spinal cord program, are you trying to replace electro stimulation or physical therapy? No, we welcome it, I think those those approaches would be even better when using cells. So I think from from a business perspective, we can play very well in the sandbox with others. But it is frustrating that it’s a very long road, any sort of clinical testing is always a long road. But this field of cell therapy has actually made some incredible progress over the last five or six years in terms of manufacturing, scale, and purity, reproducibility. So I know, it’s always that notion of oh, you know, this is five or 10 years in the future. And that’s probably true. But I think it’s probably real now, instead of just something that people say,
Brian Taylor 11:08
Yeah, that makes sense. Well, I love what you say about how the this therapy stands side by side with more traditional approaches, I think that many of our viewers will find that to be really helpful and maybe ease their their nervousness about some of these kinds of new approaches that are not really there to threaten them, but to really only enhance and what they do with their patients.
Brian Culley 11:30
Certainly, if you have a, if you have a device that is intended to stimulate those auditory neurons, if you provide more neurons, I would think that that would be beneficial.
Brian Taylor 11:41
Yeah, that’s pretty interesting to think that maybe hearing aids and cell therapy could kind of work in tandem, to help a person hear even better. Right. That’s pretty interesting. So now that we’re kind of at the end of our time with you, I’d like you to maybe share with us some final thoughts about your company about the the general approach of allogeneic, cell therapy, anything at all that you want our viewers to kind of remember, as we wind down here?
Brian Culley 12:10
Well, I think that maybe your viewers will remember 10-15 years ago, there was a lot of excitement about cell therapy, and then we really didn’t see the products delivered from that technology. But now it’s happening. And it’s really exciting. I think there’s going to be explosive growth in this field. And we’re really at Lineage trying to help lead this and pioneer this new branch of medicine, because sometimes cells can do things that small molecules and antibodies can’t accomplish. And I think we’re all seeing that happening right now.
Brian Taylor 12:39
Yeah, it’s exciting. Well, Brian Culley, the CEO of lineage cell therapeutics, thank you for your time. So happy that you could spend a few minutes with us here at This Week in Hearing.
Brian Culley 12:51
Thank you, Brian. I appreciate your time too.
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.