Ladies and gentlemen, thank you for standing by and welcome to the Eloxx Pharmaceuticals Webcast to discuss the unmet need in Alport syndrome and additional clinical data results from the top line ELX-02 phase II clinical trial. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. I would now like to turn the conference over to your first speaker today, Sumit Aggarwal, Eloxx's President and Chief Executive Officer. Sumit, you may begin.
Thank you. Welcome everyone listening to the call today. We're excited about sharing the Alport syndrome overview and our results in ELX-02. This is a very exciting time for Eloxx as we plan our pivotal study in Alport. On the next slide, you'll see that we're going to be making some forward-looking statements. Please refer to our SEC documents for detailed risk factors. Turning over to the agenda on the next slide. We're really excited to have Professors Rachel Lennon and Detlef Bockenhauer join us, in addition to my team of Dr. Ali Hariri, Dr. Vijay Modur, and myself. We'll be talking through the overview of Alport syndrome, perspectives on clinical development. Dr. Bockenhauer will present the results, and then Dr. Ali Hariri will wrap up with our next steps in Alport syndrome. At Eloxx, our focus is on developing treatments for patients with nonsense mutations.
These patients have a premature stop codon, which results in a loss of function because they have truncated proteins. What we do with our small molecule gene therapy agents is create or restore full-length protein. ELX-02, which is the topic of the discussion today, is going to be advanced into Alport syndrome. We have a second drug, ZKN-013, that is ready to start phase I, having recently approved by the FDA for its IND. I want to thank Professor Rachel Lennon for joining us. She is a Professor of Nephrology, a Consulting Pediatric Nephrologist, Director of the Wellcome Centre for Cell-Matrix Research, and a Director of the Stoneygate and Kidney Research UK Alport Research Hub. Also joining us is Professor Detlef Bockenhauer.
He is Professor and Chair of Pediatric Nephrology at Leuven, Honorary Consultant at Great Ormond Street Hospital in London, and the Principal Investigator of ELX-02 in our phase II trial for Alport syndrome. Along with Professors Lennon and Bockenhauer, on next slide, number seven, you'll see I'm being joined by my leadership team, Dr. Vijay Modur and Dr. Ali Hariri. Vijay is our Head of Research and Development. He has 20-plus years in translation and drug development, and most recently led the venglustat polycystic kidney disease and Fabry programs at Sanofi. Our Chief Medical Officer, Dr. Ali Hariri, has led multiple programs in rare kidney diseases, including lademirsen for Alport syndrome and was the clinical lead for venglustat. He also secured full approval for Fabrazyme. Now, let me turn it over to Dr. Rachel Lennon to provide you an overview of Alport syndrome.
Thank you, Sumit. Let's go to slide nine. I'll start by introducing Alport syndrome, which is a rare, progressive hereditary kidney disorder. It's caused by variants in collagen IV genes. Just in terms of setting the scene there, the three genes that are affected are COL4A3, A4, and A5. COL4A5 is on the X chromosome and causes X-linked Alport syndrome, which is the commonest type. That accounts for 85%. Recessive Alport syndrome is in 15%. As we've heard already, this presentation is focusing on the nonsense variants, which are the most severe, and over 70 of those have been described. All in all, these collagen IV variants cause abnormally fragile basement membranes. Basement membranes are in all of our blood vessels. They're in the tiny blood vessels in the kidney capillaries, which filter our blood.
You can see in the image on the right, a healthy capillary with a normal basement membrane, that's the GBM. On the right, this is what the Alport GBM looks like. It's split, it's irregular, it's thickened, and it doesn't work. It's crucial to understand that this is a disorder of basement membranes, and these collagen IV variants lead to abnormal and damaged basement membranes over lifetime, and that's progressive. All of the variants do affect the collagen IV protein in basement membranes, but the nonsense variants are the ones that lead to truncated proteins, very little of the collagen IV gets out into the basement membrane, and so they are the most severe. As I'll go on to show, this leads to leakage of blood and protein from the blood into the urine and onwards to progressive chronic kidney disease.
Right now, in the clinical setting, we have very few options for patients with Alport syndrome. Right now, in terms of our current standard of care, that's limited to drugs that block the renin-angiotensin-aldosterone pathway or RAS blockade. Next slide. Just to review that in terms of the disease pathogenesis and the clinical manifestation, this Alport syndrome is primarily caused by those genetic changes. That's the cause of the disease. There's a progressive deterioration in those basement membranes affecting the kidney filters, affecting kidney function. We can see that clinically in different stages. The earliest stage that we'll pick up in children under the age of five is leakage of blood cells into the urine. Then in the children that have the more severe phenotypes, they will develop fairly early on proteinuria, certainly under the age of 10.
With these more severe variants, with the truncating variants, this will be earlier. There's blood leaking, that's hematuria, and proteinuria, which is the early features. Unless we're able to control that proteinuria, there's progressive damage to those kidney filters over time and loss of kidney function, leading to kidney failure in the most severe cases. Next slide. Just to highlight the differences between X-linked Alport syndrome and autosomal Alport syndrome, as I mentioned, the affected genes there are COL4A5 on the X chromosome for X-linked, and this will, in males, cause the most severe phenotype. The share of Alport syndrome there is around 30%, but right now, our counseling to families and affected individuals is that there's 100% chance of the disease leading to end-stage kidney disease. Heterozygous male are the most severe with the COL4A5 variant.
In the autosomal group, it's the recessive, where there's two abnormal copies of either the COL4A3 or the COL4A4 or a combination of the two. That accounts for 15%. Of those recessive combinations of the gene changes, 100% of those will also progress to end-stage kidney disease with the current therapies that we have. Next slide. We're now on slide 12. I'll just highlight the importance of these nonsense mutations that affect both those with the X-linked and the autosomal recessive types of Alport syndrome. In terms of prevalence, COL4A5, that causes X-linked Alport syndrome, that's estimated to be around one in 2,000. Certainly, we're getting those sorts of numbers now that we're looking at big genetic sequencing studies. In terms of the frequency of individuals with those nonsense variants, that's around 6% or 7%.
Looking at COL4A3 or A4, it's rarer, around one in 40,000, and about 10% of those will have these nonsense variants. Next slide. If you have a nonsense variant compared to what we call a missense variant, where you will still get some protein produced, that does make a difference. The slide that you're seeing now is recent data from the U.K. Rare Disease Registry, RaDaR Registry. What you can see highlighted by the circle on the left and on the fifth column, the differences in age of diagnosis by the type of the gene that's affected, by the gender, and by the variant type. The ones that are presenting much earlier on, at an earlier age, are the ones where the gene is affecting the protein length. Moving on to the next slide.
We also know, they're presenting at an early stage, they're also getting into trouble at an earlier stage. Patients with truncated protein reach end-stage kidney disease at younger ages. Again, this is data from the U.K. RaDaR Registry showing the age if we compare the missense versus the truncated variants. In COL4A5, you can see the comparison is getting to requiring dialysis or transplant at the age of 50, with the truncated at the age of 30 years. A substantial difference. When you look at the autosomal disease, that's 20 to 24 years, the difference there between missense and truncated variants. That's just from the U.K. data. Next slide. Now on slide 15.
The other really important thing to highlight in the background here for Alport syndrome is. Across the world, I would say the large majority of diagnosis still comes from clinical presentation. There are very few scenarios where there is a genetic diagnosis that is made at the outset. Perhaps we're now moving into an era where newborn screening will change that, but right now it's clinical presentation. Kidney disease is silent. Unless you go looking for it, you won't find it. Unless patients present, you won't necessarily know. This really lovely study from the group at Columbia University in New York highlights exactly that point. They took 3,000 individuals with end-stage kidney disease and performed unbiased genetic testing with whole exome sequencing. What they identified was a genetic variant that would've been clinically actionable in one in 10 of those individuals.
If you take the whole cluster of those genes, which you can see in the pie chart on the left, 30% of those genetic variants, clinically actionable genetic variants, were in the collagen or Alport genes. This highlights that actually there's likely to be a fair number of undiagnosed individuals out there. On the right, what you can see is how some of these individuals might be misclassified in terms of their diagnosis. A standard way that we evaluate kidney disease is with kidney biopsy. Here are a series of biopsy terms. Alport syndrome or thin basement membrane disease, FSGS, GN, or NOS, these are all terms that we use to describe the patterns that we see on kidney biopsies. That doesn't necessarily tell the story if you have an underlying genetic cause of the kidney disease.
In clinical practice now, we increasingly move towards combining genetic studies with biopsy studies. Actually, in many cases now we're performing genetic studies as the first line investigation. Next slide. I'll just now move on to talk about the current treatment options and perspectives for clinical developments in Alport syndrome. On to slide 17. The first thing to say is that there's no approved therapy currently for Alport syndrome. Our current standard of care is supportive care. That involves the early initiation of ACE inhibitors or angiotensin receptor blockers. We know from retrospective studies that starting these therapies will extend kidney survival by over a decade. They're retrospective studies, but they've been reproduced in a number of different geographical settings.
I've focused so far entirely on the kidney side of Alport syndrome, but a really important phenotype that our patients remind us to think about in terms of unmet need is the sensorineural hearing loss. The biggest thing for the young people coming to my clinic is the fact that they need to wear a hearing aid, and they're less concerned about the protein in their urine or their kidney phenotype at that stage. Hearing is a major phenotype that is also an unmet need. Supportive therapy for kidney disease as it progresses, well, that is fairly standard in terms of chronic kidney disease management. Ultimately these individuals will progress with our best standard of care right now to requiring dialysis or a kidney transplant. Next slide.
Effective therapies must be able to measure the impact on that disease progression, and as I said earlier on, Alport syndrome is a progressive disease caused by that genetic defect in the basement membrane collagen. Thinking about those different stages, there is the progressive damage to the basement membrane, the leaking of protein, and the decline in kidney function. We can look at the basement membrane with biopsies and using various modes of microscopy. Typically, electron microscopy will tell us the information that is fairly characteristic of that abnormal basement membrane in Alport syndrome. Easier assessment is with the collection of urine, and measurement of protein. Is it present? Is it increased? Is it reduced?
This is a really vital and routine monitoring that we perform in the clinic, and similarly, the GFR and the change in GFR and that decline to GFR that we see over time. In terms of the drug examples, I've just highlighted two at the bottom there in addition to ELX-02, bardoxolone and the anti-miR-21 therapy, which I'll go into in a little bit more on the detail on the next slide. Within the Alport syndrome community internationally, it's been a really fascinating time over the last 5 years to have the first clinical trials come through in Alport syndrome. Those that have been specific for Alport syndrome have been with these two agents. bardoxolone, an Nrf2 activator, failed to gain regulatory approval and was associated with increased proteinuria.
Certainly lessons learned from that example, one of the earliest concerns that we had even before the trials got underway was that actually this was working against the-- by increasing glomerular pressure and increasing proteinuria, it was going against what we were trying to achieve with our standard of care. This had early concerns. Another factor about the bardoxolone study that many of us were concerned about was the absence of any preclinical data. It's not always possible to do preclinical studies, animal studies, for every therapy option that may come through, but that was definitely possible for the bardoxolone study, and that didn't go through. The anti-miR-21 therapy actually did have really quite convincing preclinical studies in the Alport mouse. About a year ago, that trial was stopped and failed on futility analysis.
I guess that's one of the examples where although there is preclinical data, not all of that will translate into efficacy in the patient setting. Next slide. This is just really, I think this is the last slide before I hand over to Detlef, but this is just really to highlight the importance of proteinuria, in terms of the progression of disease in Alport syndrome. To see a reduction-- once we see persistent proteinuria in patients with Alport syndrome, our objective is to reduce that, to lower that. As I said earlier, that is known to extend kidney survival. With whatever treatment we can bring to our patients in the future, the goal would ultimately be to extend kidney survival, that is lifelong. We're not there yet, for sure, with ACE inhibitors and angiotensin receptor blockers, but a reduction is a good thing.
In other clinical settings with inflammatory disorders, we can think of this in terms of remission. Proteinuria reduction or remission is what we're wanting to achieve with therapy. When we're thinking about changes in proteinuria, what's important to remember with Alport syndrome is that once that proteinuria has started, once we see it and it's there persistently, we try and bring it down with therapy. It is, in my clinical experience, we do not see spontaneous remission here. That's just an important point to make. With that, I'm going to hand over to Professor Bockenhauer. Thank you.
Yes. I'm going to take you now to the trial, which is outlined here on slide 22, the results from the first three patients. This trial was the initial pilot study to test the compound ELX-02 in patients, you can see the inclusion criteria on the left of the slide. They obviously had to have a nonsense mutation because this is how the drug works. They had to be older than six years. They had to have a reasonable eGFR, we also call it CKD stage II or I, an eGFR greater than 60, they had to have proteinuria as obviously a sign that there was serious disease ongoing. They were receiving the study drug as a subcutaneous injection every day for two months. Because proteinuria can be quite variable, proteinuria was assessed at two-week time points in between.
They always provided two samples, again, to get the best assessment and minimize the variability. We had a total of eight protein measurements in these patients, they also had a biopsy before the study drug at the end of the study drug, which was designed to look at the expression of COL4A5. All of the three patients that have been done so far are still in the follow-up period. On the next slide, again, to remind of the outcome measure, mainly with proteinuria remission, which is typically defined as a 50% reduction of the protein-creatinine ratio. That's what the UPCR stands for, which is a common way of assessing protein in the urine, or of the protein-creatinine ratio essentially normalizing by being less than 300 milligrams per gram in the urine.
Important, spontaneous remission in this disease has not been described. It's possible in some other glomerular diseases, this is a chronic progressive disease, we do not see spontaneous remission. If there is an improvement in the proteinuria, this really has to do with the effect of the drug. In the next slide now, we see the patient characteristics. Two children, age 13, a young adult. They all have the autosomal recessive form of Alport syndrome, which, as Professor Lennon just outlined, is the most serious form of Alport syndrome, where in the U.K. registry data, they typically reach end-stage kidney disease at the beginning of their third decade of life. They all were compound heterozygous, they had the nonsense mutation on one copy of the gene. On the other copy was a different, a missense mutation.
They all had the same nonsense mutation, which reflects the genetic makeup in the U.K., where this particular nonsense mutation is just the most commonly found, this serine 969X. All were treated with the ACE inhibitor that Professor Lennon mentioned earlier before. In this case, it was enalapril. They all had still acceptable creatinine, the eGFR criteria was fulfilled, you can see they all had substantial proteinuria. Now in the next slide 25, we come to the results. In orange, you see the historical data. About a year before the trial started, which was available for the first two patients, not for the third one. In blue, you see the proteinuria at baseline before the drug was started, in green, you see the proteinuria during the treatment, assessing the effect of the drug.
You can see that in one of these 3 patients, there has been a substantial reduction in the proteinuria, pretty much half of it. It is consistent with a remission of proteinuria. It was only in one of these patients. Spontaneous remission does not occur in this disease, so this is likely to reflect the drug effect. If you want to look at these data in a little bit more detail, for this patient who had the remission. The first one at baseline is the protein, obviously, where there is no drug working yet. That's the values that were obtained before the drug was started. As the drug starts, we see a reduction in the proteinuria. There is this outlier here at week 6, which unfortunately was a sample that was obtained right before the Easter holidays.
This sample was not carried out as it was supposed to be, meaning it was supposed to be analyzed within 48 hours of obtaining it. Because if the sample stands around, deteriorates, that leads to a false high reading. This was standing around, I think, for 6 or 7 days before it was finally analyzed. This is why this sample had actually been taken out of the calculation that you've seen before. The value of this protein-creatinine ratio reduction of 49% reflects the results at week 2, 4 and 8. Once the drug was stopped, there appears to be, again, an increase in the protein which would be consistent with the drug wearing off.
If we go to the next slide, we see the results in the other 2 patients, where we really have not seen any sustained effect of the drug. The protein is pretty much all over the place, but there is no obvious effect of the drug to be seen. In the next slide, we can see what was the disease. Unfortunately, it was assessed for COL4A5. COL4A4, COL4A3 and COL4A5, they come together to form a joint protein. The idea was that if collagen IV is improved, we will see also more COL4A5. There was a relatively high expression of the COL4A5 before, there will have to be further tests now to be done to actually specifically assess COL4A4, and these results are not available yet. With that, I will hand over to Dr. Hariri.
Thank you, Professor Lennon and Professor Bockenhauer. I am excited to tell you about the future of our program. Next slide, please. As a reminder, ELX-02 is a designer aminoglycoside which has the potential to treat inherited disease caused by nonsense or premature stop mutations. This has been tested, next slide, in a variety of genetic diseases, both in preclinical and in clinical settings for Alport and cystic fibrosis. Next slide. ELX-02 is safe and well-tolerated. A total of 148 patients and healthy individuals are exposed to ELX-02. The most common AE is mild injection site reaction. No new findings was in Alport patients that had CKD in this trial. What about efficacy? ELX-02 treatment in cystic fibrosis patients with nonsense mutation showed efficacy signal even at low drug levels. Let's focus on the left panel. Improvement of sweat chloride increases with high baseline sweat chloride.
Sweat chloride is an excellent biomarker for cystic fibrosis. Similarly, as a clinical finding, upon treatment with ELX-02, FEV1 % increases in a subset of patients, six out of 13, at an increase of 2.83. Upon cessation of the drug, we had a decline of FEV1 of -5.8. How can we strengthen the efficacy signal by increasing the drug level? We'll go to the kidney. There is a preferential uptake of ELX-02 in the kidney. As is shown here, we see 50 times higher levels of ELX-02 in kidney compared to lung or plasma. This is why we are in Alport. Let's see the results again. Dr. Bockenhauer shared with you that one of three patients had proteinuria reduction leading to remission. This result was consistent over time during the treatment, and it reversed after the treatment stopped. These results are very important.
Let me tell you why they're important. A patient like the patient who had response had -22 ml decline of eGFR over one year. This is based on the RaDaR U.K. registry data. This is important because a patient like him, over a course of five years, will reach ESRD and will be on dialysis, approximately. The severity of disease, combined with our exciting results, moved us to go to a pivotal trial. This trial is open label based on ELX-02 disease remission rate of 30%, which translates to 16 patients. The duration of treatment is six months. Why six months? The longer treatment leads to accumulation of collagen IV, which has a long half-life, and this accumulation will result in deeper response in remission and proteinuria reduction. The endpoint of this trial is remission defined based on proteinuria reduction. Why do we think this is a reasonable endpoint?
It's a reasonable endpoint. In slide 38, we show that remission based on proteinuria reduction is as good as eGFR slope or time to ESRD in many FDA communications. Recently, in lupus nephritis, two drugs were approved, voclosporin and BENLYSTA, based on remission in lupus nephritis. In addition, in other communications, for example, for membranous nephropathy, we know that remission is an acceptable endpoint. There may still be two questions for you regarding the pivotal trial. They are shown in slide 39. Is one patient data sufficient to proceed? As Professor Lennon and Professor Bockenhauer mentioned, this spontaneous remission in this genetic disease is very unlikely, and even as low as one in 10 patients showing remission would be adequate and sufficient to get approval. For example, in BENLYSTA, that was the situation. The second question, is an open label acceptable for seeking approval?
Spontaneous remission, again, we talked about it, that's an unlikely event to happen, so there's no need for a placebo. In addition, the rapid progression of Alport in these patients does not justify treating patients with placebo. We are losing time, and time is kidney. Only 6% of Alport patients have these kind of mutations, so it's a very small group of population, and it makes it difficult to execute the trial. Finally, the presence of excellent registries, as I showed the data to you and Professor Lennon showed the data, allows us to use those registries. At the end, in summary, we have a very exciting program in Alport. As a nephrologist, I'm delighted that we have the potential to help patients with very severe disease. On that note, I hand it to Sumit Aggarwal, our CEO.
Thank you, Ali. Turning to now slide 41. I first want to simply thank Professors Lennon and Bockenhauer for taking out valuable time to discuss their perspectives on Alport syndrome and share our results. Before I open this up for questions, I just want to remind everyone why we are here. We think that ELX-02 has the potential for the first gene therapy for these Alport patients that have nonsense mutations. What you heard today was there's a high unmet need in these patients. Current options have limited benefit, and prior therapies have failed. ELX-02 has already shown clinical signal in cystic fibrosis. We have seen a robust treatment effect in our Alport phase II study, as you've now heard repeatedly. We are ready to move into an open-label pivotal trial with remission rates as our endpoint.
Thank you very much for joining the call, and let me now open it up for questions. Operator?
As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Hartaj Singh from Oppenheimer.
Great. Thank you. Thanks for the updates. Really appreciate the detailed presentation, everyone. Just first, a specific question, Sumit, then a couple of questions for the KOLs. One is, do you think that giving six months of treatment versus the previous eight weeks can also make a difference in terms of getting enough drug into the target tissue of choice? Maybe increase the chances of more patients seeing an effect? That's number one. I just got a couple of follow-ups with the KOLs after that one.
Sure. Let me turn it over to Ali, who can answer that question. Ali?
Thanks, Hartaj, for that question. The longer duration of treatment will lead to accumulation of collagen IV, which has a half-life of about four weeks. We need about five half-lives in order to reach the maximum accumulation. In also three half-lives, we will have 80% of the accumulation. This means that by six months, we will have reached the maximum accumulation, and as such, different thresholds of collagen IV accumulation that may exist in different patients can overcome. Yes, we will see a bigger effect in proteinuria reduction and a larger number of patients who will reach remission.
Yep. Great. Thank you, Ali. Then just to follow up, Dr. Lennon went over a couple of the drugs that didn't get across the finish line. I guess my question is broad to her, which is that in her experience in these drug development trials, I know that she probably does not participate in discussions with regulatory authorities. Dr. Lennon, do you feel the unmet need is high enough in this area that regulatory authorities would be more flexible for the kind of a pivotal design that Eloxx is proposing, from your experience?
Yeah, it's a great question. It's the commonest genetic kidney disorder affecting glomeruli, and I think in terms of the data that I shared there on the patients that we don't yet know about, perhaps this is going to be more of an issue the more we're performing genetic sequencing, the more patients we'll have. I guess to go to seek approval, I think we already have a sufficiently strong case as the two trials I mentioned there, the anti-miR-21 and the bardoxolone studies, have shown. These are severe phenotypes with patients requiring dialysis and often several transplants during their lifetime. In terms of the burden of disease and the cost to healthcare, then that's already substantial. I think that's going to be important in terms of those conversations with the approvers.
I guess the other thing that I didn't really mention, of the two studies that didn't make it across the line, the biological plausibility was not as strong as we have in this case. As we've heard, if we can increase the amount of type IV collagen in those critical basement membranes, there's already strong animal data to say that we can extend kidney survival. This really does have biological plausibility that the other two studies didn't have.
No, thank you, Dr. Lennon. That's very helpful. Just my last question, Dr. Bockenhauer, and good hearing you again, on the two patients that didn't seem to see an effect, was there any kind of background, any comorbidities or background medicines or any other issues that you could kind of focus on? I guess that's a roundabout way of asking that, could the inclusion/exclusion criteria of a potential pivotal study be tweaked to sort of get patients who you think might have a better chance of responding? I know it's a small patient population.
Yeah. I think that is the main problem. It really is on an anecdotal level right now. It's very, very difficult to say. I personally cannot really see any critical difference between these patients. I think the one who had the remission was on the lowest dose of the ACE inhibitor, maybe it's more obvious with that. That is all speculation, I don't really see that we can say we need to tweak these criteria in order to get a better insight into this.
Yeah. Dr. Bockenhauer, do you think that extending the dosing duration could increase the probability of these patients, for example, the two that did not respond? Do you think that that might have given a better chance? I know it's a hypothetical question, it's just any thoughts there.
The finding of this one remission is, of course, tantalizing. Yeah, I would like to have it tested out further. I am not the biological expert. I think Rachel Lennon will be much better suited to say is there biological plausibility, because that really is her expertise. One of the things that for me is the key question is, yeah, if we just give it for longer period of time, will that increase our chances of see a better effect? I don't know. Do you, Rachel, want to say anything about that?
Yeah. I agree with you. I think this is really tantalizing data so far, and we want to see more. I think our understanding of type IV collagen biology, its secretion, we know it's highly restricted. It comes from these specialized kidney podocytes, and somehow they manage to weave it into those basement membranes. It would not surprise me if that needs longer to happen. Dr. Hariri mentioned the turnover rates. There's also going to be inbuilt sensor mechanisms in these cells that are going to regulate and keep actually quite tight control over that type IV collagen. We don't understand those mechanisms yet, but my instinctive response is that extended timeframe will help us to understand whether these interesting initial observations can be maintained.
Yep. No, fantastic to you both. Last question, I apologize. Last one is, assuming a pivotal trial was to begin whenever the next 3, 6, 12 months, I guess, how excited are you in terms of just the patients? I know that Eloxx has been able to recruit three patients, Dr. Bockenhauer, I believe, from your site fairly quickly in the last six to nine months, I believe. How do you think patient recruitment could look like if a pivotal trial got going? Thank you for all the questions.
Perhaps I can say something about that. I know that the two patients that were at my center at Great Ormond Street were very keen to continue. There were three other patients that were lined up to join in the trial. I think from adult side, there were also several more patients that were interested. I do think that that should be possible. I have not really explored with other centers here. I'm now in Belgium. I used to be in London until last month. I could easily imagine that if Eloxx were to decide to do the trial here as well, we could also recruit patients here.
Great. Thank you very much. Thanks for all the questions.
Thank you. One moment for our next question. Our next question comes from the line of Tony Butler from EF Hutton.
Thanks very much. Dr. Lennon, I wanted to explore this concept on biological plausibility that you've referenced, especially in the context of collagen IV expression. Do you really need the immunofluorescence from COL4A5 to actually circle back and say that biology's been completed, if you will, at least if you wanted to think about it circularly. More importantly, if one thinks that greater collagen can be, at least in the basement membrane, can be formed with longer dosing, would one not also want to actually test, for example, prior to a pivotal study, a 6-month, one or two, three patients, whatever it may be, to then demonstrate that there's a greater amount of immunofluorescence of COL4A5, then therefore there is an absolute biological dose response, at least that can be afforded to the study?
Just strikes me as being a higher probability for a pivotal study to be successful.
Sure. Yes, I can jump in with my initial thoughts on that. I think you're absolutely right to give confidence that the drug is achieving its purpose of inducing the synthesis secretion and incorporation of the Alport collagen into the basement membrane. The more evidence that there is to show that it's there where it should be, with pre and post kidney biopsies, would be very encouraging. I think the COL4A5 is problematic because COL4A5 also contributes to another collagen IV network. It forms a trimer to make an alpha 5, alpha 5, alpha 6 network. In the three individuals that we've heard about so far, actually, the change, that COL4A5 was not the best to discriminate between any difference there. In an ideal world, you would see evidence of the 3, 4, 5 network in the GBM. How do you do that?
Well, immunofluorescence is one option, and there are a range of tools and antibodies that could be used and optimized to do that. The other readout is with something very different, using mass spectrometry, where you laser capture the glomeruli, solubilize, analyze through mass spectrometry and proteomics. That's what we're planning to do together with Eloxx here in Manchester. We'll take over and see whether we can work up a better analysis with immunofluorescence, looking at all 3 of those collagen IV chains, the alpha 3, the alpha 4, the alpha 5, and also with laser capture proteomics. I think that's probably throwing the best of technology at the question of whether the drug is able to induce the incorporation of the Alport network following treatment.
Tony, this is Ali Hariri. I just want to mention that because the trial that we are proposing is an open label, we, in a way, accomplish that because on a continuous basis, we are looking at the results of the trial in patients and how the proteinuria and remission changes. Thanks.
Thank you, Dr. Hariri. Thank you, Dr. Lennon. I appreciate the commentary. I think the only one thing, Dr. Hariri, I would just note, correct me if I'm wrong, it's almost a retrospective look once the trial started, as opposed to the possibility, right, that there would exist a higher probability of that outcome given the tools that Dr. Lennon mentioned, at least two, I think, of alpha 3, 4, and 5 immunofluorescence and then the mass spec, which gives you tremendous confidence that the six-month duration of dosing is really spot on. I'm not saying it's not otherwise, but it's again, one of prediction, right?
Right. I appreciate your point. It's the proteinuria reduction because it's an objective endpoint, it's a quantitative endpoint rather than if I understand your point, if it was a patient-reported outcome, it would be a different scenario. In this case, what we do is on a regular basis, we actually check the results. Considering the size of the trial, that we will have 16 patients, it's going more into the details of the molecular mechanism might be challenging. Thanks.
Appreciate that. Thank you both. Very helpful.
Thank you. At this time, I would now like to turn the conference back over to Sumit Aggarwal for closing remarks.
Thank you. Thank you everyone for joining the call. I want to extend a special thanks to Professors Rachel Lennon and Detlef Bockenhauer for taking precious time out of their day to share their experiences with Alport and the results for our trial. We look forward to starting our pivotal study and sharing the results and progress of our program as we move forward. Thank you.
This concludes today's conference call. Thank you for participating. You may now disconnect.