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Welcome to BIOTECH NATION !!! With understandable interviews requiring no background in science, BTN attracts a wide global audience. From everyday people looking for hope in treatments in development, to bioentrepreneurs interested in the experience of their fellow travelers, to venture capitalists looking for possibilities in cutting-edge breakthroughs, to scientists simply interested in the work of others, BioTech Nation is the voice of human endeavor, driving science to new realities for everyone. These interviews are drawn directly from the public radio program, "Tech Nation", which also can be heard in numerous global radio and podcasting venues.
It's one thing to treat the symptoms. It's quite another to treat the whole disease, which is why Lineage Cell Therapeutics of San Diego focuses on whole cell replacement. After significant early results, Lineage is now working in collaboration with Genentech on its first target, dry age related macular degeneration. Brian Culley is its CEO. Brian, welcome back to the program.
Brian Culley:Well, thank you. It's a pleasure to be here, Moira.
Dr. Moira Gunn:Now, Brian, a lot has happened at Lineage since we last spoke, and we'll get to your big picture later in the interview. But I was thinking we could start here. Lineage does what's called whole cell replacement therapy. That means you could receive whole cells in a particular place in your body so they could start working. When do we need new cells in our body?
Dr. Moira Gunn:And are some cells better candidates for replacement than others?
Brian Culley:Well, much as we'd all like to live for a very long time, sometimes certain bits and pieces of our body start to break down. The wear and tear of aging leads to a lot of degenerative diseases that, of course, your audience is familiar with. So in certain cases, if it were possible to manufacture and replace those cells that are becoming dysfunctional or breaking down and being destroyed, it might be able to regain function. And absolutely, there are some places where it appears to be more attractive to do that than others, and those are no not surprisingly areas that we focus on.
Dr. Moira Gunn:So let's talk about your most advanced treatment, and you've taken on a big one. You know, while there are treatments to slow the progression of this medical condition, there are no approved treatments to reverse it much less just stop it and that is dry age related macular degeneration. And in fact you're talking about its late stage where there is something called geographic atrophy. Tell us about dry age related macular degeneration and its progressive vision loss, obviously. And what is geographic atrophy?
Brian Culley:Well, dry age dry age related macular degeneration or dry AMD is one of the leading causes of blindness in this country. It's a terrible disease. And the hallmark feature of dry AMD is the progressive loss or death of very specialized retina cells called RPE. As those cells die off, because they're not able to do their job, you you feel the impact of their death in the form of vision loss. And it occurs first with your central vision, you lose the ability to focus on faces or your phone, and it progressively expands outwards until you lose your entire field of vision.
Brian Culley:And this condition is one that is a great example of degenerative diseases that might be repaired by cellular transplants because it's a very specific type of cell. And if you can make that cell in the lab and transplant it to a person, you might be able to maybe restore some of that vision that they've lost due to the process of normal process of aging.
Dr. Moira Gunn:Now in the late stage, there is something called geographic atrophy. What's that?
Brian Culley:So as the cells of the retina, these specialized RPE cells die off, they tend to leave behind a toxic spot and and that area can grow. It becomes much like a wound that is expanding outwards or a rot in the back of your eye. So the geographic atrophy is that part of your retina, which is experiencing the loss of these RPE cells. And eventually, it can become large enough that you can see it unaided. It can become several millimeters around in a in a circle and it its hallmark is that the cells have died off in that area.
Brian Culley:So, of course, you cannot use that area as part of your visual field.
Dr. Moira Gunn:So your vision has been degrading. When you have the geographic atrophy, is is that can you tell when you're the person looking through your eyes?
Brian Culley:Yeah. It's a great, you know, it needs an expert opinion, but it's a it's a great question because there are some people who have very large areas of damage that still have some decent vision and then some other people who are unlucky that they might have a very small area of damage, but their vision is massively impaired. It all depends on which part of your retina you're really relying on as the preferred part for your visual performance. But overall, as these areas get bigger because you're aging and they cannot regrow naturally, your vision field will get smaller and you will become increasingly subjected to the debilitating effects of vision loss.
Dr. Moira Gunn:And it's called geographic because it's in a particular place on each person.
Brian Culley:Yes. It's an atrophic area that is bounded by and you can take pictures of it. It it's almost like looking at an aerial image of a forest fire. You can tell where the trees have burned and you can tell where they're still preserved and healthy.
Dr. Moira Gunn:Now there are actually 2 approved drugs currently approved for this condition, and they slow the progress of the vision loss. How are they different from what Lineage is doing?
Brian Culley:Those two approved products are traditional pharmaceuticals, meaning they these are, agents that address just one part of what's going wrong in a cell. But in the case of the degeneration of dry AMD, it's not just one part of the cell that's broken, it's the entire cell. Literally, the cells are destroyed and cleared out. So our view and our differentiating feature is that we are not trying to fix just one part of the cellular process like inflammation, but rather fixing everything simultaneously with a brand new RPE cell. That is what makes us very different from the competitors that are available today.
Dr. Moira Gunn:Now since we last talked, you've had a very successful phase one trial. Tell us about phase 1. How many subjects, what cells did you give them, and what happened?
Brian Culley:Well, in the phase one study, there were 24 people who received treatment with with our RPE cells. This was the first time that this clinical trial, that this experimental therapeutic was attempted in in humans. And so it's a safety study and we're mostly focusing on how to deliver the cells and where they go and how long do they persist. But a funny thing happened somewhere around 14th patient. Somebody had an extraordinarily good outcome and as we continue to investigate that, what we found was that the RPE cells that we were delivering were beginning to incorporate into the person's retina and actually seem to be replenishing or restoring the retina in areas of damage.
Brian Culley:And this is important because this is something which cannot happen naturally. At the same time that we are seeing these anatomical changes that we think were improvement, we also were observing that these people could see better. So we had both function and anatomical changes moving in a promising direction, and that's what made the phase one clinical study so exciting.
Dr. Moira Gunn:Now how do you tell that they can see better?
Brian Culley:Well, just like going to the registry of motor vehicles and looking at an eye chart and counting letters, some of the same tools are used by retina specialists. And so one way of measuring how well or poorly someone can see is simply counting the letters, and you can be wearing your glasses. It's called best corrected visual acuity and you can be counting how many letters someone is able to see, but there there are all sorts of other assessments, how well they read in low light. And, of course, the eye having a window, it allows you to use high powered imaging technology. So you can take very high resolution photos of a person's retina and see exactly what's going on in real time.
Dr. Moira Gunn:So it's a little bit between the e I think e is the first letter, as I recall, the only one I memorized. And so it's like, actually, your vision does get better. You know, as the person, your vision is improving. And with this these sort of imaging technologies or insight technologies, we'll call them, you could actually see that the cells were in there and they were multiplied?
Brian Culley:Yes. As with a lot of interventional therapeutics, you're you're looking for directional indicators that things are, logically linked together. So if you see anatomical changes that are occurring that you accept as as positive, I. E. You have more retinal tissue to work with and coupled with that, you have improvements on multiple assessments, you really begin to believe that those things are interrelated.
Brian Culley:And the converse, of course, is also true. If you deliver a therapy to someone and you don't see any anatomical changes and you don't see any performance or functional changes, you probably start questioning whether that intervention does anything for the patient at all.
Dr. Moira Gunn:How long did it take before there were any positive, you know, results after being treated?
Brian Culley:Well, I think the most powerful statement about positive results is how long they last. So we recently had, an announcement about patients having an increase of vision that had been persisting for at least 2 years and we continue to follow those patients. But the anatomical changes could happen very quickly, sometimes within months, often within weeks, and also in some cases even with days after treatment.
Dr. Moira Gunn:Now are these the patient's own cells? I mean, aren't all our cells personal? Aren't they different?
Brian Culley:Well, the eye is immunopro which means it can tolerate the introduction of foreign material much better than, say, your bloodstream. So the cells that we generate and manufacture and deliver to patients come from cell lines and are grown in the lab, and they really are believed to be suitable for all patients. In fact, we've never had a report of rejection of these cells from any of the patients that have been on our clinical trials.
Dr. Moira Gunn:So, basically, you can have a general set of cells, and you could deliver them pretty much to everybody.
Brian Culley:Yes. And one of the big advantages when you use the same cell line as your source for all of your treatments Is it the cost of that production and manufacturing is going to be, in every case that I can imagine, far lower than if you make a specialized custom therapy for each person?
Dr. Moira Gunn:Now you're in phase 2, and now you're also in partnership with Genentech. And they are leading the phase 2 trials, and they are currently enrolling. Tell us about that trial and and tell us about if people are interested how they might be able to enroll.
Brian Culley:Well, our work in phase one caught the attention of one of the very top ophthalmology pharmaceutical companies in in Roche and and in particular, their Genentech division. So we entered into a partnership and they are now running a trial that is open in 5 different centers across the US and an additional center in Israel. And if people go visit clinicaltrials.gov and they search for the word op region, they can find a list of those sites or they can just contact Linea Cell Therapeutics at our contact or info emails, and we can help direct them as needed.
Dr. Moira Gunn:Now will this be substantially different than phase 1?
Brian Culley:There are different objectives from different clinical trials. So our phase 1 was purely about safety and tolerability. Genentech is running a trial which they call a surgical optimization study because we know that it's important for the cells to get to the right location, I e, the area of damage. There are different ways of delivering cells, different methods, and even different tools that you could employ. So Genentech is focused on the next step in development, which is figuring out is there a optimal way of delivering these cells to the eye, And there probably is, so they've been tasked with taking that on.
Dr. Moira Gunn:So lineage is not sitting on their laurels by any, stretch of the imagination. I know you are working on other applications here. In general, what else might these cells be used for and what are you working on first?
Brian Culley:Well, these cells are perfect for the eye, but the human body is made up of at least 200 different types of cells. So we have a clinical stage program in spinal cord injury where we manufacture replacement cells of the spinal cord to help people who have suffered from one of those injuries, hopefully, regain mobility and improved quality of life and independence. And we also have an even earlier program in hearing loss because just like in the eye, you can over time begin to lose your hearing because certain cells are dying off. So if we can manufacture those cells and place them into the correct location in the ear, perhaps we can slow the loss of hearing or even regain hearing that was otherwise thought to be irrevocably missing.
Dr. Moira Gunn:I have to say if this is like all science, you're just gonna keep learning things as you go, just as you happen to learn that those cells that went directly into the the geographic atrophy area, they were the most effective right there.
Brian Culley:This approach that we are utilizing of cell transplantation is a new field of medicine, and we see really exciting things happening in Parkinson's and diabetes, and it's been long desired from the field to find a way to be able to deliver cells and restore function. And we're just feeling very privileged that we're one of a a small number of companies that is finding some success with this approach.
Dr. Moira Gunn:Well, Brian, thank you so much for coming in, and come back sooner than 4 years next time. Alright?
Brian Culley:No doubt we'll have a lot to say even sooner than that. Thank you.
Dr. Moira Gunn:Brian Culley is the CEO of Lineage Cell Therapeutics in San Diego. For enrollment information about Lineage's latest clinical trial with Genentech, email info at lineagecell.com. That's lineage, l I n e a g e, lineagecell.com.