All right. Good afternoon, everyone. Thanks for joining us here, day three of the Leerink Partners Global Healthcare Conference. My name's Thomas Smith. I'm one of the Senior Biotech Analysts here at Leerink, and it's my pleasure to welcome our next company up to the stage, Eledon Pharmaceuticals, represented today by CEO David-Alexandre Gros. David-Alexandre, thanks for joining us.
Good to see you. Thank you for...
Likewise
for inviting us. Of course, I'll be making some forward-looking statements today, so encourage everyone listening to look at our public disclosures.
Yep. 2025, big year of data generation. You had some important top-line data from your phase 2 BESTOW study for your CD40 ligand tegoprubart in kidney transplant. Huge year, milestone year. Maybe talk about like just kinda set the stage for the company, talk about progress in 2025, and then what you're looking forward to most in 2026.
Sure. You know, I think progress of the company has been going on very fast. It's striking to me to think that five years ago, or just over five years in with Eledon, and five years ago, we had one non-human primate's worth of data in allograft transplantation. Now, five years later, we're sitting here, and we've had over 100 humans post-transplant that have taken tegoprubart to protect their transplanted organs, and that's included allotransplantation kidney, islet cell, of course, as well as both heart and kidney xenotransplantation. In terms of last year, as you mentioned, a very data-rich year. In kidney transplantation, we reported out data from both our phase 1b study, so the single arm study, as well as the controlled study, which was our phase 2 BESTOW.
I think the key takeaway of that data is multiple fold. One is it looks like tegoprubart is protecting transplanted kidneys, and it's doing so in a way that has dramatically improved safety versus the historical standard of care, which is tacrolimus. If we look at the BESTOW data, what came out of that was first that even though we weren't powered to do so, we did hit the non-inferiority endpoint. It's a triple endpoint in terms of survival, patient survival, organ survival, and rejection. That would be the provable endpoint that we would expect. It's a historical provable endpoint. It's the one that we would expect the FDA to require from us moving forward. It had safety that was really night and day versus standard of care.
Last year, we also started or continued to show data in islet cell transplantation, here we're looking at patients that have the very high risk type of Type 1 diabetes, where they get both high highs and low lows in terms of their blood sugars. We reported out data on the first six patients. All six of them were able to get completely off insulin, so they went from very high risk diabetes, very hard to control diabetes, to being functionally cured of the disease. No more insulin, and importantly, none of them had any severe hypoglycemic events after transplantation. When it comes to xenotransplantation, of course, we were able to transplant some more kidney xenotransplantation patients. For this year, all of these programs are moving forward.
In terms of kidney transplantation, we expect to go talk to the FDA about path to approval, phase 3 design. We should be doing that next quarter, and that would put us in a position to launch a phase 3 by the end of the year. We're going to give long-term data, so long-term data update from our phase 1b and phase 2 studies, and we'll probably do that either in June or in the September timeframe. There are some conferences there. From islet cell transplantation, this week there's a conference in Barcelona where we'll be giving an update.
There's more news coming up very fast, although for people here who are looking at social media, our patients have been advocating for themselves and describing their experiences, which gives a little bit of a hint in terms of what's happening. We expect, as we had guided beforehand, to take our first 10 subjects' worth of data and go talk to the agency about what path to approval could look like. Again, that would allow us to talk to the agency towards the middle of the year. Then we'll continue to do xenotransplantation. Yesterday, as you might have seen, we did announce that the FDA granted us Orphan Drug Designation in liver transplantation, and we expect to start a liver IST probably by the end of the year as well.
Small company, but a lot's happening as we begin to move into registrational path studies.
Yeah. A lot going on. I wanna start, tegoprubart in renal transplant. Maybe we could start with the dataset most recently presented, and you're gonna have updates later this year from the same one, phase 1b study. Longer treatment duration, longer follow-up, maybe just describe at a high level like what, you know, what you're seeing there on eGFR graft viability and also importantly safety, which for you is a potentially key differentiator versus tacrolimus.
Sure. As I started to mention, we saw in terms of the phase 2 the historical approvable endpoint, which is non-inferiority versus standard of care, there on that triple endpoint, so death, loss of organ and rejection, we were in the non-inferior range versus historical. We were looking at showing superiority on kidney function, and there we showed a numerical superiority but not a statistical superiority. The reason we believe we didn't show that the statistical superiority had to do with just distribution of the highest quality deceased donor organs where there were disproportionately more of these organs that ended up going into the tac arm as opposed to that ended up going to the tegoprubart arm. We saw the tac arm do overall very well in terms of eGFR compared to historicals.
You know, the eGFR is icing on the cake. That's going beyond what the FDA has asked for approval. We do, you know, believe and hope that we'll be able to show, continue to show better separation of the curves, and that's one of the things that we'll be looking at, of course, at the 18- and 24-month time point. That'll be the data that we'll have to update in terms of June or September if we present in one of the big meetings then. In terms of safety that you just brought up, I think the safety delta between tacrolimus and tegoprubart was striking.
To give you some examples, tacrolimus, one in four patients had tremors versus about 1% or 2% of the patients that had tremors in the tegoprubart arm. Similarly, we saw multiple times the levels of new-onset diabetes post-transplant in the tac arm. We saw more bacteremia, more sepsis, more hypertension, multiple times the number of hypertensive crises. The tac arm even had about five patients, 5% of the patients that experienced heart failure versus none in the tegoprubart arm. Taken overall, we could, you know, this data supports a very strong safety profile. That's, you know, it's really consistent with both what we saw in the phase 1b on tegoprubart and what's now being reported by patients out on social media from their post-islet cell transplantation.
That's great. So in BESTOW, you know, you were initially aiming for superiority on eGFR, massive tacrolimus outperformance in this study. Like, what is the latest thinking around what may have driven that? Like, what are the implications of that as you're thinking about, like, a phase three trial design?
Sure. What we believe this was tied to principally was the quality of the organs, the deceased donor organs that ended up being given to the tac arm as opposed to the tegoprubart arm. Transplanted kidneys are graded, and it's a grading that goes from one - 100. 1 is the best, it's good to be number one, and 100 is the worst. Typically, organs that are above an 85, and the score above an 80 are actually discarded. People don't really transplant them because the organ quality isn't high enough. By pure chance, you would expect that about 40%-45% of the organs in a study would come from the highest quality kidneys, just if you multiply that out.
What we found was on the tegoprubart arm, we had 37% of the deceased donor kidneys that were from this highest quality group versus 57% in the tac arm. 20% delta, right? Two-thirds difference, right? 20% over or 50%, 60% difference in terms of tac, the how many of those organs ended up in the tac arm versus the tegoprubart arm. Those are the highest quality organs, and the thought is they might be because they're so high quality, they might just perform better and be more resistant to tac than your typical average organ.
The implications for us means that as we think about phase 3, obviously we'll have a much larger patient population, but we'll need to think about distribution and make sure that the highest quality organs are evenly distributed between the two arms.
Yeah. Stratification based on organ quality.
Exactly, which we did not do in the phase 2.
Yeah. Okay. Understood. I guess coming out of the BESTOW readout, I agree with, like, the safety tolerability profile difference striking. How have you, I guess, evaluated the potential value that can be driven with a kind of inline on efficacy, non-inferior on efficacy, but better safety tolerability, I guess making the sort of pharmacoeconomic benefit, like argument around improved quality of life, no new onset tremors, like reduced onset tremor, new onset diabetes, like the cost savings that could be realized there. Like, just how has your thinking around the value proposition changed and I guess how to communicate that?
Sure. What's nice here looking at our safety is in the safety differences between the two arms, there is something for every group, too, to be happy about. From the patient perspective, the number one complaint that we hear from patients regarding tacrolimus are the CNS effects, in particular the tremors and the brain fog. The, as I mentioned, we saw one in four patients that were on tacrolimus in our study, right? Despite excellent control, as evidenced by the eGFRs, one in four patients still developed a tremor when they were on tac. That is the number one complaint that patients have. When we talk to physicians, the number one complaints that the physicians bring up is the Type 1 diabetes post-transplant, post-transplant new onset diabetes.
In patients that did not have pre-existing diabetes, about one in six or one in seven developed diabetes within the first 12 months post their transplant versus a fraction of that, I think 1/7 of that, if I remember correctly, on the tegoprubart arm. Finally, when it comes to payers and the hospitals, we saw a difference in delayed graft function. That is how many patients post-transplant go back on dialysis. This is typically inpatient dialysis. Someone gets their transplant, the kidney doesn't start to work, and in about three days they're told, "We're sorry, we need to put you back on dialysis, and let's see, you know, when your kidneys begin to go." What we saw were more frequent delayed graft function on tacrolimus.
About 14% of the patients on tegoprubart experienced delayed graft function versus 25% of the patients on tacrolimus. When patients on tacrolimus received dialysis, they received dialysis for 1.5 extra days versus tegoprubart. If you multiply that out, what that means is in the deceased donor category, for every 100 patients that would receive tacrolimus versus tegoprubart, we would expect an extra 115 days of extra days on inpatient dialysis for the tac arm. Obviously that has a direct, just pharmacoeconomic implication. Here when we look at the safety, you know, the safety is really differentiated and allows one to highlight which aspect of safety matters most to their group.
That makes sense. One of the other aspects of the program that we've gotten questions from investors on is around acute rejection. The way we've framed this is basically not all acute rejection is created equally. The sort of severity matters, like what is actually happening matters. Just describe for us like what you saw in BESTOW between tegoprubart and tacrolimus and when you think about clinical use, like what is actually clinically relevant?
Sure. You know, we think in our minds that when we talk about rejection, that means organ loss. Let me just start by highlighting that here rejection doesn't mean organ loss. Rejection means there's an immune flare. The body notices the organ, and the immune system activates itself. The rejection today, all of the categorization around rejection are based on looking at tac. This is gross diagnosis. This is done on pathology looking at a slide. We're not talking, right? They see T cells, they see B cells, right, lymphocyte infiltration. They're not looking at which specific subsets are being involved. This is a gross diagnosis based on biopsy. Interestingly, it is not associated with long-term organ performance.
If we look at the best predictive algorithm in terms of how long an organ is likely to survive, which is iBox, rejection is not included in iBox. What we saw was, again, overall, from the primary endpoint, we were not inferior to the standard of care. We did have numerically more patients on the tegoprubart arm that experienced a rejection versus on the tacrolimus arm, about 5%-6% more. When patients experienced a rejection, if that rejection was treated and those patients remained on tegoprubart, they actually did better than tegoprubart patients that never experienced a rejection to begin with. They finished with higher kidney function, with higher eGFRs. We saw that both in the phase 1b study as well as in the phase 2 study.
Got it.
Overall, I think for us, the take, you know, we are seeing a difference. We did see a difference in rejection, but we think it's. There is no sign that this could impact the long-term outcomes in terms of the kidneys. Finally, you know, rejection is a safety issue, and you need to think about the implications because patients here are experiencing lots of side effects, as we saw from the safety profile. Even if you said, "Okay, David-Alexandre," right? "What's the impact of these extra, let's call it six," right? "For every 100 patients, six patients that experience a rejection versus tacrolimus." Let's assume all of these patients get admitted back to the hospital, and let's assume that they each spend two days in the hospital.
We're talking about an extra 12 days in the hospital post those additional rejections. But remember, we were just talking about delayed graft function. For every 100 patients that received the deceased donor, the delta is 115 days in the hospital. The delta between the two remains dramatic.
You're going to go to FDA, and you're looking for alignment on a phase 3 program. Just remind us, you know, the key questions that you're looking to get answered and, yeah, how you're thinking about the design, size, length of follow-up that would be required.
Sure. We think it's going to be a one-year endpoint, the historical triple endpoint, so non-inferiority. We'll go to the agency to talk to make sure that is how the agency is feeling. The agency is considering potentially the use of iBox as a secondary endpoint. That would be an additional endpoint, but we'd still have to hit the primary endpoint in order to get approved, so we don't think it matters that much, from our perspective in terms of trial design. The agency had already communicated to us they wanna see a minimum of 300 patients with 12 months of data, so that drives the minimum size per arm. We'll get all of that clarification from the agency when we go talk to them soon.
Yep. Great. You brought up iBox. I guess what's the latest on the iBox front? They were going through the qualification process.
They continue to go through.
Yep.
We're all waiting to hear back.
Yep. Okay.
We'll see whether iBox will be considered a co-primary endpoint, which could be an upside if someone were to be able to hit it, or if the FDA will prefer to keep it as a secondary endpoint. Regardless, we're gonna look at iBox.
Yeah.
We're gonna look at eGFR, of course.
Right. I guess knowing what we know from BESTOW, like did the BESTOW data change the way you think about iBox or I guess an ability to outperform Tac on iBox?
No. 80% of iBox is eGFR. Since we didn't show stat sig on eGFR, it makes it very hard to show a delta on iBox.
Yep. Okay. Let's talk a little bit about the market opportunity and yeah, just frame for us what you would initially be targeting, and then there's also a substantial number of patients who are on Tac currently who've already you know experienced kidney transplant. I guess the strategy to potentially switch them from tacrolimus to tegoprubart.
In terms of switch, from a labeling perspective, that is its own label, and so we would need to run a study in order to go after those patients commercially. Otherwise, what we're looking at is de novo indication, and so it's for the 27,000 or so Americans that are getting transplanted every year, we'd be looking to have a new option for them. We believe using the design that we've been discussing, that all of those patients would be eligible for tegoprubart. The question is around, you know, how much market share would we be able to get and how quickly. Tacrolimus, if you go back in history, when tacrolimus was approved, it was approved non-inferior and safer to cyclosporine, and it took 90% of the market.
What we're looking to do is to do to tacrolimus what it did to cyclosporine.
Just remind us how you're thinking about sort of the payer dynamics around like how could you potentially price tegoprubart in the context of a kidney transplant procedure?
We haven't provided guidance in terms of pricing, but there, you know, there could be. This is an expensive area. These procedures are very expensive. Transplants can cost hundreds of thousands of dollars a year, and the alternative, of course, is dialysis. Dialysis, despite, from a quality of life being brutal for patients that need to be on machines for hours a day, every other day, or overnight multiple times a week, survival is less than five years. Average survival is less than five years in the United States, and for that, the cost of dialysis is over $100,000 a year. We think with everything we've discussed, there's plenty of room to achieve pricing that would be appropriate for new medicine.
There's a biologic, Bristol Myers Squibb's Nulojix or belatacept, that's approved and used in this setting. What we've heard anecdotally from KOLs, it seems to very much vary center to center, their level of adoption within renal transplant. I guess how do you think about the profile of tegoprubart relative to Bela? Maybe Bristol doesn't explicitly break out what the sales of Nulojix are, but again, longitudinally for us, the KOL feedback seems to be like greater adoption. What's the latest, I guess, you're hearing on that?
Sure. We're not competing against belatacept. The drug that we're competing against is tacrolimus. Bela tacept never became standard of care for a number of reasons, including the fact that when they launched, if we go back 15 years, they didn't launch comparing themselves to tacrolimus, the standard of care. They launched showing that they were non-inferior to cyclosporine. They were when they went from a commercial perspective, they were trying to sell the fact that they were non-inferior to a drug that the physicians had stopped using. The pitch was, of course, that belatacept was safer, but belatacept, during its studies, saw both PML and PTLD, and so there was a sense in the community. They also got a black box. In liver transplants, they saw increased death for the patients that were on belatacept.
There was the sense in the community that you weren't seeing greater efficacy, potentially not even non-inferior efficacy versus tacrolimus, and you were just trading off some of the side effects of tacrolimus for the potential in PML and PTLD. Belatacept never became standard of care, and then, of course, a few years later, where they were manufacturing in Puerto Rico was hit during the hurricane, and they weren't able to supply. Despite all of that, about two years ago, there was a paper that came out that showed that they were getting about 7%-8% market share, as far as we know, without really any marketing support. They were able to get good uptake. It shows you just the level of unmet need here. What we're looking to do is to develop a drug correctly.
We're not comparing it against the old standard, we're comparing it against the current standard. To date, we haven't seen PML and PTLD. Of course, yesterday we just announced that we received Orphan Drug for liver transplant, so we'll look to begin a liver IST later this year. If we can show good efficacy in liver the same way we showed in human liver, the same way we showed in non-human primate liver, then that too would help differentiate us from belatacept.
Yeah. That makes sense. It's just, it's a very interesting analog given all of the deficiencies that you lay out. Okay. I wanna talk in the last couple of minutes that we have about islet cell. Really interesting data coming out of University of Chicago. You alluded to the patients posting their experiences on TikTok. Maybe just, like, help us think through how we're gonna formalize this program when we take data to FDA and maybe how tegoprubart could fit in given some of the other emerging islet cell technologies that are also advancing.
Sure. The data in islet cell transplantation has received and continues to receive quite a lot of attention. I mean, there have been posts that have been viewed millions of times from some of the patients that have decided to do this all on their own. The last update we gave were on our first six subjects, and all six subjects were able to get completely off insulin. We now have about 13 subjects that have been transplanted, 12 de novo, one switch. We're going to take the data from these subjects in another few months, and we'll go see the FDA to talk about path to approval. We expect to have clarity and to be able to come back and tell investors path to approval later on this year.
This would be using deceased donor islets. People donate their kidneys, their hearts, and at the same time, they would donate their pancreases from which the islets are derived. The way this plays with all of the man-made or the manufactured stem cell-derived islets, for those that aren't immunoevasive or for those that might be somewhat immunoevasive, but not fully immunoevasive, and we believe that's the majority of what's being worked on today, you know, our goal would be to become the immunomodulator of choice for them. If we're able to work with deceased donor islets, we should be able to work with those islets as well. Earlier this week, tied to that, we also announced. We didn't announce. Our new partners announced a collaboration with us on some preclinical islets.
We're moving forward in islets with both the deceased donors, which is what's available, as well as man-made islets, which is what's coming.
Seems like a very, interesting strategic partnership opportunity.
Well, it's just like xenotransplantation, what we're looking to do is to collaborate with as many people as we can. We're not looking to pick the winner. We wanna be able to work with as many people as possible and then, you know, let the best technology succeed.
Yep. That makes sense to me. Just in the last 30 seconds we have, remind us on cash runway and, yeah, where that gets you as we think about launching a phase 3 study for tegoprubart and Renal and some of the other endeavors you outlined.
Sure. We finished last year with just over $130 in the bank, and so that gives us cash into the second quarter of next year.
Cool.
Allows us to do everything that we've spoken about this year and gives us some flexibility in terms of the optimal timing to be able to raise new financing if necessary.
Yep. Makes sense. All right. Well, unfortunately.
Of course, assuming we keep all the programs moving forward, if we were to switch on when we moved, then that could extend the runway at all.
Yep
as well.
Makes sense. All right. Well, yeah, unfortunately, we're a little bit over time.
Thank you.
Thank you, David-Alexandre, for joining us, and we'll stay tuned to the Eledon story.
Good to see you. Thank you.