Eloxx Pharmaceuticals, Inc. (ELOX) November 9, 2026 Conference Transcript

Thank you again for joining us at the Guggenheim Healthcare Innovation Conference. I'm Vamo Devon, one of the biopharm analysts here. Joined up on the stage on the Guggenheim side, Arsini Chavezvili from the team. And next in this room, we have the ELOX Pharmaceuticals team. Next to me is Sumit Agarwal, CEO, and John Wolford, the Vice President of Corporate Development. So thanks so much for both of you joining us. Happy to have you again. So maybe just I think it's a starting point for people who are not as familiar with ELOX. This story, if you can give a little bit of the background, a little bit of a journey to get to where you are now, and then we'll talk about your asset.

Yeah, sure. So, you know, we've been public now for almost eight years when we went through. A bit of a cathartic time three years ago, but last, in June, we raised money to prosecute both our programs. We have a, we're focused on rare kidney diseases, and we have two programs, one in Alport syndrome and the other in autosomal dominant polycystic kidney disease, ADPKD, and we're targeting nonsense mutations, which are a subset of these diseases with our lead asset, exalurin. We've learned a lot about our drug. The drug has been trialed in 145 subjects, so we have almost 90 patient months, subject months of exposure, so very good safety profile so far, and we've had data that showed we could reverse the structural damage that is associated with Alport syndrome, which is really a functional cure if you can see it extend over a longer period of time.

Okay, great. So let's talk about Axelor, and maybe just before we get into the two different indications, just the product itself, the mechanism, and how it's working under them.

So the mechanism of the drug is PTC read-through. So when you have a nonsense mutation, a nonsense mutation is a mutation in the gene where instead of a regular ATCG, you have a stop. And it causes a formation of a premature termination codon. And what this drug does is it reads past that premature termination codon and inserts an amino acid that results in full-length proteins getting formed again. This was a mechanism first described about 30 years ago when observed with gentamicin. So it's an aminoglycoside like gentamicin, which is specifically engineered to not have the two liabilities that gentamicin antibiotics have, which are one, antibiotic activity, and second, mitochondrial toxicity. So the drug has almost no mitochondrial, no antibiotic activity, and has almost two log, two orders of magnitude, a lower mitochondrial toxicity. And what that means is you don't see the kidney talks or the hearing loss that would normally be expected to be seen with aminoglycoside antibiotics. So we've taken this molecule and really applied it to the kidney space, and having learned a lot from our earlier program, cystic fibrosis, both we learned about safety, we learned about the thresholds of exposure we need for efficacy. And in the kidney, like aminoglycoside antibiotics, the drug gets taken up in a much larger exposure in the kidney itself. So at the doses we're treating these patients, we have a 43-fold exposure in the kidney relative to plasma. And just for contrast, the lung exposure to plasma is only one-to-one, so we can get about 30 to 35 micromolar of exposure, if you look at the AUC over 24 hours, in the kidney versus only one micromolar in the plasma. And that helps us achieve the PKPD that we need to have for efficacy in all our programs.

Okay, and you touched on this, but you do have some biopsy data that kind of...

Yeah, so if I sort of double-click into the Alport data we have, we treated three patients that had an Alport nonsense mutation in a collagen 4 gene. So Alport is a disease that's caused by mutations in one of three collagen 4 genes, collagen 4, A3, A4, or A5, and these patients It's had a mutation in collagen A4. After eight weeks of treatment, all the three patients, when you looked under the microscope, the biopsies, we saw a remodeling of the kidney. So the two main elements of the kidney filtration structure are the glomerulus and the proximal tubules. The glomerulus is where the bulk of the filtration occurs. So in Alport syndrome, the glomerulus basement membrane gets irregular and becomes leaky, and then you have foot processes that attach to the glomerulus basement membrane that start to efface or flatten out. And after eight weeks, we saw the glomerulus basement membrane become more normal, and the foot process effacement reached about 80% of normal, starting with about 50% of normal.

Okay, great. So then that's now led you obviously to, you did the RAISE and you're starting the exact trial. So you can just talk about that, sort of the development, following the biopsy results, how you sort of planned out phase two.

Yeah. So, you know, what was very clear in Alport syndrome, when we were just thinking about the design of the study, functionally you need to see a change in proteinuria. However, When you look at the natural history of the disease, the progression of proteinuria occurs at a much more rapid pace. So the median age at kidney failure in these patients is 23 years old. So we needed to look at an endpoint that was aligned with the drug's mechanism of action and could minimize the risk of a false negative. We chose, therefore, to use a biopsy endpoint rather than proteinuria as our primary endpoint. Proteinuria is a secondary endpoint in the study, and the two things that we wanted to do in the next study, which is the exact study, it's a phase 2 study, was to trial the drug in more patients. Over a longer duration, and maybe three things, and the third was to have a placebo group because of the progressive nature of the disease, without a placebo group, it's really difficult to interrogate how significant of an impact you've had on the disease, right? Because in most clinical trials in Alport, you see up to a 50% increase in proteinuria in 16 weeks. In our study, initially, we saw no change. But if you overlay that with a 50% increase, then that would be a very significant improvement in proteinuria as well.

Okay, so now maybe touch on the progress you're making here in terms of site activation, getting the space too long.

Yeah, so we've announced that we dosed our first patients in September. We continue to screen patients and activate more sites. We hired a new chief medical officer coming out of Novartis a couple of weeks back, and so that's helped us. A kick into high gear, our U.S. site activation. We're also opening sites in France and India where we just recently got approval. And so right now we think we're tracking to a mid-year 2027 for the data readout for the primary endpoint, which is at 16 weeks. And we'll be able to give an update in January of how that's going. The next couple of months are pretty critical for us to make sure we can put our foot on the pedal and get that recruitment up and going. We're working with Natera in the U.S., working with registries, data in the U.K. and Europe and India to find patients. You know, these are roughly, Alport is about 60,000 patients in the U.S., and 77% of those are nonsense mutations, about 4,000 patients. So it's an ultra-rare segment of a rare population. So it's a lot of work to find patients, and we're doing our best to work with the size that do genotyping and are able to find patients.

Okay, perfect, and then maybe you can talk about what you're, so it sounds like, so it's still on track, you know, for mid-next year. What do you hope to see at 16 weeks? And then does that sort of lead to potential discussion with the FDA about some sort of accelerated path, or is it really then kind of seeing the 32-week data later?

Yeah, so, you know, the, like I said, the primary endpoint is a change in filtration slit density, which is a quantitative measure for process of placement. We have secondary endpoints of UPCR and other biopsy endpoints. We saw a 50% increase in FSD in our Phase IIa, and when we look at the relationship between UPCR and FSD, that should translate to a robust improvement in UPCR. So our operating assumption is that from a clinical trial perspective, this trial is... Oversized for a 25% increase in FSD. So we only need about 12 patients to have at least a 25% increase in FSD. And that's sort of our 20 to 25% is what we expect targeting as an increase. Why that much? All the prior work that has been done in looking at foot process effacement across diseases has shown that even a 10% improvement in FSD can have a material impact on the progression of disease.

Okay. And then what about proteinuria? Yes.

So you asked also the question of FDA and how did that. So we would go to the FDA at the end of the primary endpoint readout. We have a very constructive relationship, a dialogue with the FDA. They want to see proteinuria and FSD correlations. They don't have to be stat-sig. So, you know, we have done a fair amount of modeling looking at the relationship between FSD and proteinuria based on published literature in Alport and other diseases. What we see is about a doubling of FSD leads to a 70% reduction in UPCR. Obviously, that's got high variability, but that's the general trend. And you would expect to see that, just think of what we're essentially doing is closing a hole that is formed in the kidney. So as you close the hole, you go from a fully open hole to 50%, you should expect to see a significant reduction. We've not been able to, because of the variability in UPCR, we don't really have a bogey for UPCR. Our bogey is on FSD. Because the bogey on UPCR depends on what happens in placebo as much as what happens on the drug side and how much variability you have in proteinuria. We are doing a lot of things to make sure we minimize the variability. We're taking three proteinuria readings, first morning void. But the FDA hasn't told us that we need a bogey. One thing that folks may not be aware of is there is a working group called ASCENT that's been put together by the Alport Syndrome Foundation in the U.S. It's a global working group looking at surrogate endpoints for approval of drugs in Alport Syndrome, just like you had Parasol with FSGS. And the first kind of data that they showed was that even a 10% improvement in UPCR leads to clinically relevant reductions in or improvement in heart endpoints of kidney failure or reduction in 50% EGFR.

Okay, so maybe the last couple ones on Alport is going to turn over to Arsenio on the ADPKD side. You touched a little bit on the commercial, the size of the market at least. What do you see as sort of the commercial opportunity? Maybe if you can talk about any sort of other products that might be in development.

So, you know, we're very focused on nonsense mutation Alport syndrome because the drug mechanism is very specific to that. We don't see any competing products in that area. And there are a few competing trials, but none of them have shown robust preclinical data that would suggest very large effect sizes. So we don't really see any competition there. We're working on some pricing work on our own, but, you know, this has become the ultra-rare nature of the population. If you just take the global market is about 7,000, 8,000 patients between Europe, the U.S., and Japan, we are doing some work to start the regulatory process in Japan as well, you'd expect to get pricing in this $500,000 to $700,000 per patient per year, so that translates to about a $4 billion TAM opportunity in Alport globally.

Okay, all right, let me turn it to Arseny.

Yep, so to help frame the ADPKD discussion, maybe you could help us understand how that disease is different from Alport, how the unmet need is different, and then it is the same mechanism. Sure, sure. All of that, sorry.

Yeah, so it's the largest genetic disease, genetic kidney disease. It's obviously different in a couple of different ways. One, the disease is caused by different genes. There are two genes, PKD1 and PKD2. They code for the polycystin 1 and polycystin 2 protein that together form a complex that's an ion channel transport, just like you have in other diseases. The progression of the disease is relatively stable. These patients develop cysts in the kidney, and the kidney expands over time as the cysts grow. The cysts usually are formed because the patients have a germline mutation, and then they develop a spontaneous second mutation in the second allele. So it's what's known as a haploid insufficiency plus second hit hypothesis. The, on average, they're about in the mid-30s to low-40s at the age of diagnosis, and they progress, you know, the EGFR slope is pretty stable by, in these diseases, so, now. That's the disease. There's only one drug that's approved. It's called Tolvaptan, and it's very difficult to tolerate. It's got polyuria and liver safety issues, but it's short of 50% reduction in the rate of growth of kidney volume, which is the endpoint that the FDA looks at for accelerated approval. Now, there are similarities between Alport and PKD as we think about it. So they're both caused obviously by a protein. In both diseases, there's very broad and robust evidence showing that when you restore the protein, you can reverse the disease. So, in animal data and critically in PKD, now, Farrah Burson, the drug that Regulus was developing and now is being developed by Novartis, showed that even in three months, you can increase protein that leads to a differential change in the TKV growth. So, in that regard, it's very similar because we're changing the structure of the kidney with an Alport, And here, too, the disease is a structural disease because you're trying to change the size of the kidney.

Okay, and you mentioned in Alpert there are 7,000 patients globally, 4,000 in the U.S. is your target. How are you thinking about the opportunity in ADPKD?

So there are about, depending on which reports, there's about 26% to 30% of PKD patients that have a nonsense mutation. In the U.S., the range of estimates is between 140,000 and 200,000 all PKD patients. And globally, you've mostly doubled that number. So as we think about the total PKD market globally, we think it's closer to about 100,000 patients globally. And again, if you look at IGAN as a proxy for the BAF and the April drugs as a proxy for the pricing you could get on a disease-modifying agent, about $400,000. So that's obviously a huge number, just 100,000 patients times 400,000 is a huge number. In TAM, right, obviously, addressable market will be lower because we don't address patients that have an EGFR below 30, so anyone kidney failure, and all these patients progress at different rates, so we likely will have upper cutoffs on EGFR, so we think that the addressable market is probably half of that, so it's still 50,000 patients times. $400,000 is still a $20 billion market.

And can we talk about your development program in ADPKD, and what, from your Alfred experience, would you be able to leverage in that program?

Sure. So, we have four sets of preclinical data that support moving into PKD. The first is data showing that when you treat organoids, kidney organoids that have been made from iPSC cells, you see a 50% of wild-type protein expression, and you see a significant reduction in the organoid volumes and the number of new cysts formed as well as the growth in the existing cysts. Second, we have data from primary epithelial cells in patients showing we have a robust increase in transcripts of PKD1 and PKD2 and an improvement in the phenotype of the epithelial cells. The third is data from PKD cysts from patients that showed that when you treat those cysts with our drug, we see a reduction in the cyst volume and cyst growth. And the fourth is up. Preclinical data in cells, in vitro, in vitro preclinical data, where we see about a 3% Protein expression leading to a downstream regulation of the proliferation pathways. So those are the four things. So based on that, we've decided that it makes sense to go to include all PKD patients that have nonsense mutations, the PKD1 and PKD2. So if you look at some of the trials out there, they're mostly focusing on PKD1. We don't think we need to do that. Second, We are including patients that have a slightly lower volume growth. So these are patients that have an MIC or Mayo Image Classification 1B. So most companies are focused on 1C, Ds, and Es for their rapid progressors. Given the mechanism, we don't need to do that. And the third, we have the target engagement from our Alport study, and we know that the drug concentrates in the kidney and the proximal tubules and the cysts. That's where a lot of the megalin is found, which is the primary reason for uptake of the drug. So we've taken the same PKPD from Alport and applied it to ADPKD. When you put it all together, the trial is designed to show an improvement in TKV. It is a one-year study, one-to-one placebo control. We chose one year because that gives you the opportunity to have a discussion with the FDA for a breakthrough designation as well as a path potentially to accelerate approval. And 60 patients was really to ensure we had, while not the full safety data set that the FDA required, which is 100 patient years of safety data, so in the context of a rare disease, a robust safety data set.

Okay, and what is the timeline?

So we expect to start enrolling our first patient in third quarter of next year. And with a 52-week study design, you have data readout in the first half of 2029.

Understood. Let me turn it over back to Womble for a minute.

Yeah, so just a couple of things more on the corporate side then. So, one, if you can share kind of your current cash position and your runway going forward as we have these upcoming events.

Sure. So we announced, we ended the second quarter with $62 million, and we have not yet provided our 3Q financials. They should be available shortly. You know, we will update then, but, you know, we announced in the second quarter we expect that cash to last into mid-2028, And so that's where we are from a cash perspective, which will give you the output data readout and initiation of the PKD study.

Okay. And then this mechanism, I guess, is there potential to look at other indications, whether it's kidney or...? Yeah.

So really, we have a very broad preclinical data set, including in the kidney. It works in pretty much every nonsense mutation. So yes, there is. How we sequence that development is still a TBD. I think our view is that something like a platform designation with the FDA is a more appropriate development path for the kidney. And then for other diseases, you know, we have to understand the PK to ensure we get enough drug. But clearly, there was a study published in 2017 in DMD patients that showed robust protein expression in these patients that were treated with gentamicin twice a week. There's data Showing. Robust restoration of these skin cells in RDB and JB patients. There's a lot to do. I think the limiting factor for us beyond just bandwidth and cash is making sure we do the right preclinical studies to investigate the exposure of PK of the drug in the relevant cells.

Okay. I think we can leave it there. Thanks so much for joining us. Obviously, congrats on getting, it's been a long time to get to where you are. So great to see the progress and look forward to seeing the data. Thank you for having us and thank you for the questions.

Okay, great, thank you.