Thank you very much for inviting me to speak at the conference today. I'm going to give a slightly different talk than I often do, to give an overview of the company and really talk about how we're focusing Meira on our late-stage clinical pipeline, which is two late-stage programs, as well as probably the most exciting use of our in-vivo delivery system, which we've developed from our riboswitch technology. And we've been doing this over the last six to nine months, and I'm really excited to have the opportunity to talk to you about the way we've streamlined the company today. So Meira was formed as a genetic medicines company, but really to focus on using DNA as a new pharmaceutical modality to be able to deliver any therapeutic peptide or hormone or biologic drug to diseases that can't necessarily be addressed by other pharmaceutical modalities.
But in having that idea and in building that technology, we needed to set up an entire company that allowed us to support the delivery of the DNA and the delivery of those peptides, hormones, and antibodies. So we initiated with a pipeline. Initially, we focused not on inherited diseases, which a lot of gene therapy does, but we focused on small doses, locally delivered in areas that were immune suppressed. And that took us into the eye, where we had a portfolio of inherited retinal diseases, which we partnered with Johnson & Johnson. In addition, the salivary gland, where we target xerostomia that occurs after radiation treatment for head and neck cancer, and also local delivery in the brain, where we actually have a disease-modifying effect on Parkinson's patients who no longer respond adequately to dopamine.
In addition, we built manufacturing, initially one site, now end-to-end manufacturing, which is some of the leading manufacturing capabilities for viral vectors in the world. Every one of our vectors is optimized from capsid, promoter, translation. We do that using AI as well as human testing. And I'll move on to our riboswitch technology, which we've now implemented for in vivo delivery of fast-acting agonist peptides and hormones. So first of all, our pipeline. As I mentioned, we were indication agnostic. We chose small doses, locally delivered, and that allowed us to manufacture at low cost the viral vector required. And in fact, as a consequence of this, we currently have three of our programs in late stage and with the potential filings in 2025, 2026, 2027. Large patient populations, unmet need, each has strong data, and small doses means low cost of goods.
Our first program is one of the partnered programs with Johnson & Johnson, which we sold back to them at the end of last year. It's currently in phase three, reading out later this year. We sold them the program, and we entered into a commercial manufacturing agreement with them so that we will make money on the launch. We received $115 million so far, and there's about $285 million milestones, one-off milestones on approval in Europe and the U.S. for that program. But we are no longer the owner of this program. And in fact, we have separated out our entire ophthalmology pipeline, infrastructure, and capabilities into a separate entity, which we are discussing with potential partners. Our second program, radiation induced xerostomia, I'll talk about in a moment, and Parkinson's, another large indication. So in the area of clinical, we're really focusing on these two areas.
But the first is aquaporin. I will just bring you to the data. We presented extremely strong data six weeks ago or so at the AAOM that was incredibly well received. We showed completely unprecedented improvements in PROs, so the measure of xerostomia, as well as saliva. And that's really supported the enrollment in an ongoing phase II, which we've designed with all the criteria that the FDA discussed with us that they wanted to see for a phase III approvable study.
In addition, because we manufacture this material ourselves and we have very strong regulatory interactions globally, the FDA approached us nine months after we filed the IND and told us that if we used one particular assay, which we are doing and can do, our manufactured material would allow us to consider this a pivotal study, which is the reason that there is a potential filing for this indication in 2026. This is a really interesting disease in that it is a large population for a genetic medicine. There are target patients, 170,000 in this country, with 15,000 new patients a year. These are patients who've been cured of head and neck cancer. They have all suffered, everyone treated with radiation for head and neck cancer, actually get xerostomia. They can't produce saliva.
However, about 30% or 40% of those patients never recover the ability to produce saliva and have long-term xerostomia, which is a disaster for their way of life in a way that I hadn't really understood until we started talking to the physicians and patients. They cannot exercise because they can't breathe faster to walk fast. They can't eat. They have to sip every few hours. These are the patients for whom no drugs work. And we were able to not only fully cure some of those patients, but we had the biggest impact ever seen on saliva production as well as xerostomia symptoms. This is a very low cost of goods. The patients are all sitting with health insurance, seeing their physicians every year. And this is a market that we can readily address internally. It's not just radiation-induced xerostomia that this exact same vector addresses.
This is a pipeline in a product. Sjögren's syndrome, we are ready to open an IND in Sjögren's, which in preclinical models has been shown to have very similar effects on dry mouth to what we've seen in radiation-induced xerostomia models. In addition, many of you will be aware that the new prostate cancer drugs have a very severe side effect, which is, in fact, xerostomia. So while we look at radiation-induced xerostomia from head and neck cancer, there's another label expanding phase III we could do in these newly xerostomic prostate cancer patients, a huge and expanding market. And finally, we are currently doing IND-enabling studies to use treatment before radiation and prevent xerostomia in all patients that are treated. So you can appreciate this one viral vector currently in a pivotal study has a very large market, even larger than the large market for radiation-induced xerostomia.
Our second late-stage program is in Parkinson's. And here, we actually circumvent the issues caused by dopamine lack and dopamine treatment. So all patients with Parkinson's actually stop responding to dopamine. They can no longer control their movement with sufficiently high levels of dopamine that don't give them side effects. There is a very well-validated mechanism for circumventing this hyperactivation of the subthalamic nucleus, which occurs in these patients. And that is by delivering the repressor of activity, GABA, to the subthalamic nucleus, very similar to what's done in deep brain stimulation, which targets the same spot in the brain.
We have the only positive sham-controlled phase II study ever achieved in Parkinson's disease with gene or cell therapy or growth factor therapy, which shows that by delivering the GABA enzyme, the enzyme that makes the repressive neurotransmitter GABA specifically to this tiny locus in the brain, we're able to return motor function to these patients. In addition, we're able to show that through FDG-PET, we have actually caused a recircuitry of the brain, so disease-modifying. So we've circumvented that need for dopamine in these patients with very strong motor symptom data. And we've manufactured this material to commercial grade in our own facilities, and we are preparing for phase III. And again, in discussions with partners, to move this forward in a global phase III program next year.
So I have mentioned our pipeline and the focus on those two programs, xerostomia by ourselves, Parkinson's, hopefully in collaboration with a larger company to globally market that to neurologists. The next silo that we have, I'll quickly mention, is our manufacturing. This is something I'm very proud of at Meira. When we first started the company eight years ago, nine years ago now, we built our own manufacturing facility because there was not capacity in the industry. We worked with regulatory agencies to build the first of our two GMP facilities. We importantly made this state-of-the-art single-use facility, single-use capabilities, and highly flexible and scalable. What that means is every room has its own air handling that you can move in a 100-liter bioreactor, move it out the next day into the same suite, scale up 20-fold with a 2,000 L bioreactor.
That's what we mean by scalable and flexible so that we start our INDs with commercial-ready process in commercial-ready facilities, which has a huge regulatory and time implication. Over the last eight years, it's been important for us to bring in plasmid production, not only for cost of goods, but also for speed of manufacturing. As I mentioned earlier, we're the commercial manufacturer for J&J's first gene therapy for retinitis pigmentosa. We had to build our own QC facility because the current CDMOs are unable to release material in a timely fashion for an effective launch. We have our own fill and finish. We have a Specials license, which I won't talk about now. And really importantly, we spent eight years developing a proprietary manufacturing process, which is best in class for full ratio and yield.
We've done this not for one vector, but for more than 20 different viral vectors from pre-GMP. We have made over 50 batches of GMP material successfully. This has resulted in really strong regulatory relationships throughout the world. I mentioned that with respect to our xerostomia program, also feeding into our Parkinson's program. But why do we care about this? Why do we care that we have end-to-end manufacturing? Number one, speed. So we can probably speed the clinical development from IND to BLA for any program that we manufacture by two to three years with a significant reduction in development timelines to beat competition and increase the ROI on any product that we manufacture and develop.
Cost of goods with the same process, if you were to do the same process, manufacturing in-house, 50% less than if we were to manufacture outside based on plasmid and QC, which are the highest cost of outside manufacturing. That doesn't include a probably one log improvement in cost of goods from our very high-yield process. And in addition to that, there's a valuation floor to the company. We've recently been audited by a company called Dark Horse, who came with a very positive report on all of our infrastructure and all of our people. They went to every site over a couple of weeks, interviewed 120 people, and they came back and thanked us for allowing them to see our infrastructure and processes and said that they hadn't seen anywhere in the world such comprehensive or high-quality manufacturing. So this included CDMOs, pharma companies, and biotech companies.
You can appreciate that some CDMOs, for example, have been acquired for many hundreds of millions over the last six to nine months. We know that our infrastructure, our process, and the number of batches we've done exceeds what some of those have actually achieved before they were sold. Next-generation vector optimization. One has to do this. Every aspect of your genetic medicine has to be optimized to really maximize the outcome for patients. However, there is another really important aspect to this optimization. We focus on everything: capsids, promoters, vectorization technology, which increases expression using the same promoters by up to 10-fold. We have data over the last nine years that we can give to our AI models and generate new promoters for specific cells. We test everything in human organoids. So we don't just make technology that works in man.
And when we look at the improvements in potency we get, it's not trivial. We can get three or more logs improvement in the potency on a vector-per-vector basis. Now, that's important for patients that these drugs work, but it's got really big implications for cost of goods. A three-log improvement in potency means a three-log lower dose, which means 0.1% cost of goods. Very important when I move to the next topic, which is treating some of the largest diseases that are out there. In fact, one of the most talked about, thought about, and focused on disease indications at the moment, which is metabolic disease, which turns out to be the problem that our gene control system exquisitely solves.
So we've developed a way of controlling the production of RNA from any DNA template, whether it's delivered as naked DNA, whether it's CRISPRed into a cell, whether it's delivered by AAV or lenti. We can precisely control the RNA and then protein that's produced by that template. We've done this for antibodies, peptides, hormones across the board. And in multiple cell types, we've shown in vivo efficacy. But the place where this is having the most obvious but nevertheless surprising impact is when we deliver short-acting agonists in a physiological timeframe. And that is in metabolic disease where we provide a solution for efficacy using gut peptides for muscle loss, delivering myokines for fat regain, delivering adipokines like leptin.
And because we in vivo deliver, i.e., the body makes these short-acting peptides in the physiological form, we don't have the manufacturing barrier to entry that currently exists for both oral as well as injectable peptides. In addition, cell therapy is another area where agonist receptors, when delivered in CAR-T, the CAR, if you control that CAR and deliver it in a pulsatile fashion, it massively, not trivially, but massively improves the efficacy of those CAR-T cells. So what is our switch? Essentially, you put a DNA template into the body. It can be in cells. It can be any delivery mechanism. And into that DNA template, we put a cassette, which allows us precise control of RNA production from that DNA template when you deliver a small molecule.
I'm not going into the mechanism now, but essentially, one small molecule delivered allows the splicing out of this control cassette, a perfect messenger RNA. Because a splicing event occurs, this is irreversible. So one small molecule makes one message. With no small molecule, that entire message is degraded in all cells by nonsense-mediated decay, a ubiquitous process that gets rid of, in some cases, 30% of the transcripts in any cell. So we do not squelch it. Universal process. This slide, I'm just going to spend a minute on to show you how incredibly precise this is. We set out to make a switch, turn RNA production on or off using a small molecule that's oral. And we can screen. We've got many small molecules that we screen for. And this was one of our first in vivo experiments.
What I'm showing you here is the expression of a marker gene, luciferase. This top blue line is a luciferase construct delivered to the liver that is unregulated. A normal luciferase gene that it's on is exactly the same gene, but it's got our control cassette in it. And you can see you add a small molecule at dose of 10 mg per kg. You get that much produced. 30, that much produced. You get a really clear dose-response of luciferase expression in the liver. The peak comes on and off. When you look at the individual mice making up this blue line here, you see a spread of expression just like you normally see in hemophilia, right? About half a log. However, if you look at the controlled expression, every mouse expresses virtually the same amount of luciferase based on the dose of the small molecule.
So we were super pleased about this. Really precise control, real accuracy in dose response. Then we put the exact same construct into muscle. And here you can see constitutively active, and it's going along very similar to what you see in the liver. And then we gave the mice exactly the same small molecule, same protocol, 10, 30, and you see the dose response. But the shape of the curve was different. So we asked the CRO, "Did you give them an extra dose? Why is the curve different?" They went, "No, it's exactly the same." So we went back and we looked at the biodistribution, tissue biodistribution of this particular small molecule in a mouse following a single oral dose. The liver, here in blue, the molecule goes in and out. A little peak, exactly like we see in our luciferase expression.
However, the muscle, we hadn't previously realized, it goes in, it accumulates, and then it goes out, which is precisely reflected in the pattern of expression of the gene in the muscle. Why I show you this slide is to really illustrate that we haven't produced a switch. We've produced an incredibly sensitive sensor for small molecules that's so sensitive it can actually distinguish the tissue biodistribution differences between liver and muscle following one oral dose in a mouse. And this precision and sensitivity allows us to deliver very clear and precise doses of any biologic therapeutic encoded by DNA. We screen for small molecules. We have multiple small molecules with different pK. I'm not going to go into that. And here are some of the functions that we have been able to show using this control system: vectorized antibodies, CNS expression using blood-brain barrier penetrant small molecules.
Same for the eye. We can put genes for AMD in the eye, all of these different activities. But the two places where we really are completely differentiated from anything the pharma industry is able to do to date is the delivery of agonist receptors and agonist peptides. These are some of the library of drugs that we have regulated and shown efficacy in vivo. Every pharma company's favorite antibody, cell therapy, basically CAR-T work four times better than they do with an unregulated, the approved CAR-T, hormones and peptides, and nucleases. First sign that things work better when you control them in a physiological way came when we looked at CAR-T. And I'll go through this super fast. So Carl June's approved anti-CD19 constitutive. This is what's approved. We knock in our control system.
And what you can see here is you give increasing small molecule, you activate an increasing amount of CAR on the surface to slightly higher than constitutive. That's shown in this graph as well. Constitutive dose response of the CAR on the surface. You remove the small molecule, you activate, you remove the small molecule, the CAR cycles off the surface. It's no longer expressed. When we then go and look at CAR expression, low levels of CAR expression, actually, when we look at cytotoxicity, that's shown here, you get stronger cytotoxicity than when you had the constitutively active CAR. And we're like, "Oh, really? Low receptor density is supposed to be more active, but that's interesting." Likewise here, same. Lower level of CAR than in constitutive, and it works better. So we went to primary T cells.
And these are controlled T cells, totally naive T cells that will make T memory cells. This is the profile of the approved anti-CD19 where it's unusual and they're more mature and not as functional. And these are RiboCAR, our T cells, where all we're doing is rather than having constitutive receptor, we are actually turning it on and off with a small molecule. Okay? They are identical to naive T cells. Likewise, they're not exhausted. They don't have increased exhaustion markers. This is the approved anti-CD19 CAR-T. When you look at function, that's the approved CAR-T. This is a dose response in function. 4x more cytotoxic on a cell-per-cell basis. When you look at proliferation, approved anti-CD19 proliferation. So what we've actually done is by physiologically controlling CAR, we get highly functional physiological CAR-T. When you put them into a tumor model, this is the approved model.
Notice, 2E6 cells don't cure the tumor. 6E6 cells do. When you have the RiboCAR, so this is just switched on, once-a-day pill, no small molecule, you don't cure the tumor. Small molecule, daily, you cure the tumor with only 2E6 cells. We've made super potent, totally normal CAR-T cells where you don't need CAR to manufacture, where you put them into the body, and once a small molecule is not there, those are no longer CAR-T. They just sit there as memory cells. Really powerful. Where this we think is having the greatest impact is in peptides and hormones. So we have regulated, this is dose response of many peptides and hormones: EPO, growth hormone, PTH, insulin, the incretins. So we thought to ourselves, everyone knows GLP-1 works. It's one of the biggest drugs out there. How do you make it better?
The whole industry is looking at adding new gut peptides. So we thought it's super easy for us to just put in a construct where we add GLP-1, GIP, glucagon. And we did that. And we made a whole library of triple, double combination peptides. And we started looking at them. And then what we did is the following experiment. We compared the activity, the efficacy of constantly active gut peptides to gut peptides that were physiologically activated with oral small molecules. So it's like comparing long-acting synthetic peptides that may be injected once a week, so that driving receptor activity all the time, to physiological short-acting peptides delivered as the body delivers them, but using an oral pill. Now, this is a bit of a complicated slide, but this line here, the dark blue line control, is a DIO mouse.
This light blue line is that mouse or that group of mice treated with GLP-1, GIP. As you can see, there's a big improvement in their weight. This is essentially the GLP-1, GIP combination that exists in a number of drugs today. We were pleased we'd made that. Then what we did is the same combination, GLP-1, GIP, we put the construct in and we controlled it. We gave these mice an oral drug once a day. Look what happens. Bam. They lose weight way faster and lean. This is a lean mouse, way more than the constantly active GLP-1, GIP. Here is just weight loss. This is using the once-a-day. Why is this a zigzag line? It was actually a mistake, but it was really informative. It's a zigzag line because these mice were not dosed on the weekend.
Our scientists left on Friday and didn't come back until later on Monday morning. So what you can see is the dose that we're giving is just sufficient to make them lose weight, but you don't give that dose, and guess what? They start eating Saturday morning. This was a long weekend, so they didn't get it for five days. Interestingly, we always look at postprandial glucose. These are the two controls. This is persistently activating the GLP-1, GIP receptors through constitutive activation. And you can see control, but much better postprandial control. Super important for microvascular care in diabetes. Sugar is toxic, and you want it in the blood for as little time as possible. So we made a GLP-1, GIP glucagon. We heard you add glucagon, you'll lose loads more weight. And indeed, that's what we saw. DIO mouse here in dark blue.
This is the controlled construct with no small molecule. Low dose of small molecule, you're starting to lose weight. Mid dose of small molecule, you're losing a good bit of weight. But look what happens when you use the right dose of small molecule. Bam. This, by the way, they were dosed on the weekend. Bam, straight down. Here you can see the weight loss graph. And this is a very potent GLP-1, GIP, glucagon. But when you speak to physicians, they are concerned that glucagon, because it causes gluconeogenesis, is going to increase the risk of diabetes. So 16 weeks after daily treatment, we looked at what happens in postprandial glucose control. So these are the controls. Very bad at controlling. This dotted line is what happens when you have persistent GLP-1, GIP, glucagon for those 16 weeks. Disastrous glucose control, right?
This is what happens when you give GLP-1, GIP, glucagon with a daily oral dose in the short-acting physiological form. Low dose, you get some control. Look at the dose that causes weight loss. Bam. Really, really good postprandial glucose control in the presence of glucagon 16 weeks after treatment. So by delivering these short-acting agonists in a physiological way, we do two things. Number one, it turns out that in systems that are homeostatic and responsive, like metabolic systems are, things short-acting like GLP-1 for a good reason. They need to turn off to be responsive again. If they're persistently on, other systems try and switch them off. You have to give higher and higher doses to keep getting efficacy. So it seems that in these systems, you need short-acting physiological time frames in order to get maximum efficacy.
Number two is by physiologically delivering even things like glucagon, we're able to get the massive weight loss and circumvent the tolerability toxicity that you see with long-acting glucagon. In addition to efficacy, which is really remarkable, we've also addressed efficacy and tolerability other than using myostatin and activin inhibitors to block the inhibition of muscle down regulation. What we have done is we have taken the actual mediators of muscle strength, of fat metabolism, of bone strength, and of cognitive flexibility and appetite suppression that come from the muscles. They're called myokines. This is what activin inhibitors and myostatin work on. And we can deliver physiological myokines, which have impacts across the board. They mimic exercise. Exercise and muscle strength are absolutely essential in aging, as well as for frailty. Muscle and exercise are the one thing that can help cognitive flexibility, Alzheimer's and Parkinson's as you get old.
So the loss of muscle due to starvation is not only essentially important in frailty, it's also important in all the cognitive issues that occur in aging. Fat regain, we can deliver natural leptin. We can completely prevent the regaining of fat. And by the way, because we're driving the production of these peptides in vivo with an oral small molecule, we totally circumvent the need for massive production of peptides outside the body. So what I've shown you today is a company with late-stage clinical programs, the infrastructure from manufacturing to vector development to support a pipeline of programs that are addressing some of the biggest problems in one of the biggest indications that are out there, small molecules going into the clinic at the end of this year, and the vectors that address muscle loss, efficacy, and tolerability.
When I say efficacy, massive efficacy improvements in metabolic disease and other responsive systems, those will be going into the clinic sometime next year. Thank you very much for your attention.