All right. Okay, I think we're ready to get started here. Thanks, everyone, again for joining us for the inaugural Guggenheim Healthcare Innovation Conference on day three here. The caffeine flowing, getting through to the third day. I'm Paul Little, for those of you who don't know me, one of the bio-pharma analysts here at Guggenheim, joined on the stage by our Sydney Szabolcs, Vamil Divan from the team. And then next up in this room, we have Eledon Pharmaceuticals, and we have David-Alexandre Gros, who's the CEO, Steve Perrin, President and CSO of the company. Thank you so much for joining us. We've sort of gotten to know this Eledon team more recently, so it's been a fun story to kind of get to know you guys. Obviously, made a lot of progress.
Maybe just to kind of start things off, if you can just give a little overview for people maybe who are newer to the story on sort of kind of the history of the company, where you've gotten to now, and then we'll dive deeper on the kind of upcoming events.
Sure. Thank you very much for having us. It's exciting to be here, and congrats on the conference going so well. In terms of the history of Eledon, we are focused on anti-CD40 ligand, and specifically the use of an anti-CD40 ligand as a novel way to prevent the rejection, so the immune attack, on transplanted organs. The company was founded in late 2020, so just over four years ago, by taking tegoprubart to go our lead asset out of a nonprofit and merging it into a public company shell. So once we did that, we were able to create Eledon, and over the subsequent four years, we've now been advancing it in transplant.
So we currently have three trials that are going on in kidney transplantation, a phase 1b and a phase 2, where we're looking to replace tacrolimus, which is the current standard of care, with tegoprubart, and then a long-term extension study where patients can roll over from either the phase 1b or the phase 2 study. Next, we have a phase 2 study that's ongoing in islet cell transplantation. So again, we're using tegoprubart to prevent the rejection of those transplanted islet cells. And finally, we've completed some human transplants with xenotransplantation, so the use of, in this case, pig organs in humans.
So we did a heart with United Therapeutics at the University of Maryland and a kidney here in Boston at Mass General with eGenesis.
Okay, great. So maybe I think there's been a lot of activity in the renal space, I think, over the last few years, especially in IgA and FSGS and other areas. Transplant, maybe not as much. So maybe you can just sort of frame the overall sort of transplantation market, the number of patients, the number of kind of potential addressable population that you have out there.
Sure. So there are about 50,000. If we look at the United States, there are about 50,000 transplants that are done every year. The majority of those, about 27,000, are kidney transplants. So the largest indication for kidney transplantation is kidney. It's a market that is large dollar-wise, but is small from a ceiling point perspective. So it's almost rare disease-like in that way. To give you a sense of the potential market, if we look at the current standard of care that we're looking to replace, so tacrolimus. Tacrolimus is an old drug. It was first approved in 1994. It peaked at $3.5 billion in revenues in the 2000s. And Astellas was the originator. And in fact, last year, so in 2023, Astellas still did almost $1.5 billion in branded revenues with tacrolimus. So it's pretty striking how large that product remains.
If we look historically, the cornerstone drug before tacrolimus was cyclosporine. That was a drug that was Sandoz, now Novartis, and that was approved in 1983. And cyclosporine was one of the first blockbusters. It was one of the best-selling drugs at the time. It peaked at about $1.5 billion in revenues. So large dollars. But from a call point perspective, there are relatively few centers that do transplant medicine. There are about 200-250 hospitals in the U.S. So one needs a small sales force, maybe 20 or 30 people, to be able to cover all of those centers, although, as I just pointed out, the potential revenues here are quite large.
Okay, great. So then in terms of your lead asset here, the CD40 ligand mechanism, can you just sort of talk about that? Is there a development of that for this condition and maybe a little bit of the early data supporting the development?
Sure. I'll turn it over to Steve, who's the inventor of the molecule and has been working on the space for a long time.
Sure. Thank you. Yeah, as David-Alexandre just pointed out, this is not a new target. The receptor and the ligand were discovered way back in the 1980s. They were initially characterized as being really critical receptors on the cell surface of immune cells that then activates the immune system to foreign pathogens or in the context of transplant, recognizing that something is not you, such as a transplanted organ, and basically activating the immune system to eliminate that. Antibodies were then developed and brought into preclinical studies, initially in autoimmune indications and rodents, in mice in particular, showing that if you block this pathway, it had very profound effects on not only T-cell-mediated autoimmune diseases like rheumatoid arthritis or multiple sclerosis, but also B-cell-mediated diseases like lupus nephritis and Sjögren's syndrome.
Then when antibodies were made that could work in primates, monkeys as an example, it became apparent that blocking this pathway is the most effective way to prevent transplant rejection. Even today, 30 years later, blocking CD40 ligand is the most effective way to prevent transplant rejection in multiple different species.
Okay. So perfect. So let's talk then about the clinical sort of program to date. And you mentioned some ongoing trials, some recent data updates and stuff obviously coming. So maybe just give us an overview of the program and where it stands right now.
Sure. So in kidney transplantation, as I mentioned, we have two studies that are going on in parallel, a phase 1b and a phase 2. What we're looking to do is to replace tacrolimus as the cornerstone standard of care. So today, for chronic immunosuppression, so the patients that get a transplant will be on immunosuppression their whole lives. If they stop to take their immunosuppressants, the immune system will activate and immediately attack the organ. So the standard of care in kidney transplant is tacrolimus taken with a mycophenolate as well as steroids. So what we're looking to do is to use standard of care, and we're just removing the tac to replace it with tegoprubart. The reason why we're doing that is that tacrolimus has a number of toxicities.
The first one is that it's directly toxic to kidneys, so it's nephrotoxic. And as a result, if we look at even patients that had heart transplants or lung transplants, so they have healthy kidneys, one in 10 of them will end up needing either dialysis or a kidney transplant after a decade. And it's not that their underlying heart or lung disease ends up destroying the kidneys. It's the tacrolimus. So this is well known. The other effects of tacrolimus are causing diabetes. So it's beta cell toxic. It's toxic to the cells that make the insulin. And it also causes hypertension. And this is particularly ironic in the case of kidney transplant because the two most common reasons why patients need a kidney transplant in the first place are hypertension and diabetes.
In the case of kidney transplantation, we have both direct as well as indirect toxicities specifically to the transplanted kidney. And finally, there are a whole slew of other side effects, including brain fog, headaches. I mentioned hypertension. And as a result, what we're looking to do is to remove the tacrolimus. And we believe that if we can do so, that can allow transplanted kidneys to do better. Our primary endpoint, and it's the feedback that we got from the FDA, is eGFR. So that's kidney function. Right now, our phase 1b is a single-arm open-label study. Our phase 2 is a controlled study. We have one arm on tac, one arm that is on tegoprubart.
They use standard of care, again, so the only change versus standard of care is in the arm where we're removing the tegoprubart. We've presented data on the first 13 subjects in our phase 1b. We did that at ATC last year, and there we showed a benefit in terms of eGFR function that was in the range of 30% to about 90% above historical standard of care, depending on the time point. We've continued to enroll in that phase 1b, and so we expect to announce the next update middle of next year, so probably at the next ATC. In terms of the phase 2, that is 120 patient studies, 60 in each arm, so 60 on tac, 60 on tegoprubart. We finished enrollment in that study in the third quarter.
As a result, since it's a 12-month endpoint, we expect to report out data from that study in the fourth quarter of next year. So that covers kidney transplant. In terms of islet cell transplantation, we have a phase 1, sorry, phase 2 that's ongoing as an investigator-sponsored trial out of the University of Chicago. We recently presented data on the first three subjects. And we expect to enroll all nine subjects in that study and to be able to give an update on how well they're doing in about a year. So we're now close to a lot of important data for the company, the phase 2s from both the kidney as well as the islet cell studies.
Once we have the data in hand in a year, assuming that data is positive, we would then go to the FDA to talk about what phase 3s could look like.
Okay, great. Let me turn it to our study and then just dive a little deeper on these trials.
So on the phase 2 kidney transplant trial, can you talk about the enrollment, sort of like how the enrollment went and relatedly, how concentrated is this market in terms of the number of transplantation practices and the number of patients that are attached to those practices?
Sure. So enrollment went very well. We completed enrollment in that phase 2 about four to five months ahead of schedule. So to give you a sense of the desire in the community for a new option versus tacrolimus, we had overwhelming demand from physicians to enroll in the study. We're enrolling around the world. So this is not concentrated. About two-thirds of the sites are in the U.S. The rest are in Canada, Brazil, the U.K., France, Germany, and Spain.
Okay. And then in terms of the readout that might come in the fourth quarter of next year, what are you hoping to see there in terms of efficacy, eGFR separation, and then also what are you watching for as far as safety?
Sure. Steve, maybe I'll turn it over to you.
Sure. The study is powered, as Gros indicated. The primary endpoints are the difference in eGFR between the two arms. The study is powered to detect a nine-point difference with 80% power between the two arms, so that would achieve our superiority endpoint over standard of care, and then secondary endpoints are, as you indicated, safety, tolerability. We're looking at a panel of biomarkers along with that on how we're modulating the immune system in the two arms. And the typical classes of safeties that one would be looking at for this drug class would be infection, opportunistic infections, malignancies, and such.
Especially the side effects of Tac. What we'd like to show is that we're not having the historical side effects of Tac, such as increase in hypertension, increase in hyperglycemia, post-transplant new-onset diabetes, tremors, which is probably what patients hate the most, or the Tac tremors, brain fogs, headaches, and the like.
And then similar questions on the islet cell program. What sort of patients are you enrolling? How is enrollment going? And then what are you looking for as far as the readout?
Enrollment is going well. We've been quite good at enrolling at the pace that we said we would enroll. In this study, when we announced it at the beginning of the year, we said we would enroll one patient a quarter in the second, third, and fourth quarter of this year, which is exactly what we've done. The data that we reported two weeks ago was thus on these three patients that were out about two weeks, three months, and six months. There, the primary endpoints are, of course, safety and tolerability. But these patients have very hard-to-control Type 1 diabetes, a type of diabetes that's now called high risk or very high risk, T1D. It used to be called brittle diabetes. These are patients that, despite the best care possible, fluctuate very quickly between very high levels of blood sugar and very low levels.
This isn't because they don't know how to control their blood sugars. One of the three patients is a cardiologist. He obviously understands the disease. It's just that the type of Type 1 diabetes that he has makes him unable to consistently control where his blood sugars are at. As a result, we want to look at our ability to normalize the blood sugar levels in the near term. That's done by looking at whether the blood sugars are within the normal range or close to the normal range. In terms of the specific endpoints, we'll look at A1C, which is a marker, of course, of how high the blood sugars are on average. Then we'll look at severe hypoglycemic events, so when their blood sugars drop dangerously low.
To take a step back, what is the competitive landscape in this space? What other CD40 ligand antibodies are out there? What other programs are out there? What are they studied for? That would be very helpful.
Sure. Steve.
Yeah. So there's multiple other programs targeting the ligand. Sanofi has a program in there. Antibody probably is the most similar to tegoprubart's antibody. They're focusing their efforts on multiple sclerosis, where they reported positive data from phase 2 and have now launched multiple phase 3 studies in MS. In addition to them, there's a partnership between Biogen and UCB with an anti-CD40 ligand that they've had in development for lupus nephritis. They just announced positive phase 3 data in that program this year. And then Amgen also has a molecule that they licensed from their Horizon acquisition. And they're focusing that asset on rheumatoid arthritis and Sjögren's syndrome.
At least at a high level, what are some of the differences between these molecules and between these programs?
There are some significant differences. As I alluded to, our antibody is very similar to the Sanofi antibody. They're both full antibodies that are IgG1. And we've crippled Fc effector function by making amino acid changes in a certain portion of the molecule to cripple Fc effector function. Biogen UCB took a very different strategy to eliminate Fc effector function. They're working with a pegylated Fab. And then the Horizon molecule that was developed by Viela Bio that's now at Amgen is actually a peptide inhibitor of CD40 ligand binding that's fused to human serum albumin. So very different biological formats for those four molecules.
As a result, if you compare our molecules to the Amgen or to the Biogen UCB molecules, we see we have two to three times their half-lives. They've also shown antidrug antibodies at levels which we don't see. We haven't shown any ADAs.
Relatedly, can you talk about how it's going to be administered, how frequently, and how it's going to be presented?
Initially, it'll be IV every three weeks. We've completed non-human primate work for subcutaneous formulation. But for transplant, the market doesn't really need that. It would if we were going into just more general population inflammatory conditions. If you think about it, patients that have a kidney transplant typically were on dialysis beforehand. So they're getting multiple hours of dialysis every other day. So compared to that, a once every three weeks or once a month transplant is quite easy.
Let me pass it back to Vamil.
Yeah. So maybe a couple of questions just to follow up on some of that. So obviously, better questions to ask those companies, but sense of why they're focusing on those areas versus transplant. It seems like it's an open field for you. Any sort of competitive intelligence on why?
I mean, it's hard to answer for other people. Of course, Sanofi has a long history in multiple sclerosis. They're one of the major players in MS already. So it would be, I assume, a natural place for them to be. They acquired a company called Provention to prevent the progression of type 1 diabetes in children, and they've announced that they're going to look to develop their antibody in that indication as well, so as a next-gen prevention, if you will, again, very tied to where they've invested in in the past. In terms of Biogen, we know why Biogen picked lupus and why Amgen is looking at Sjögren's , which is three million Americans without an approved drug, or in Amgen's case, rheumatoid arthritis. I think these are very large, broad indications, and so they could make a lot of sense for a larger company to go after.
Transplant, compared to that, could be viewed as a smaller, more niche indication. So that might be niche for them. But for us, it's perfect. It would allow us to have a multi-billion-dollar franchise with a very targeted call point that we could do.
And then you mentioned before you're also doing some work on the xenotransplant side. Again, sort of mechanistically, is there differences there? I just don't know the science well enough in terms of how likely is it to work in what you're doing in kidney or islet cell versus the likelihood of it being successful on the xenotransplant side?
Sure. Maybe I'll Steve.
Yeah. As I mentioned in the introduction to the biology around the target, historically, blocking CD40 ligand in allotransplant, where you're transplanting within a species to this day, is the most effective way to prevent allotransplant rejection. We're starting to see that same story unfold in the context of xenotransplant rejection, where you're putting an organ from one species into another. The primate data would suggest that blocking CD40 ligand is going to be a critical component to translate those technologies into human studies. Eledon's been very supportive there, where we've supported two human xenotransplants to date, a cardiac transplant at University of Maryland, as well as a kidney xenotransplant that was done here in Boston at Mass General.
We have preclinical collaborations going on around the world. We are involved in preclinical work from here to Europe to China to Japan.
Okay, and then maybe again, kind of going back to the history part and how you got into here, it's obviously a little bit of a different story just in terms of how you obtained the asset and then how you went public. I'm trying to just get a sense in terms of the conversations with investors, and how much is that sort of kind of still an overhang on the company or kind of questions you get around where you because it feels like a very big opportunity for you to potentially have and maybe still not being fully appreciated by the street.
Yeah. So we were born in an unusual way, which unfortunately pegged us at a low price. Now, when we created Eledon, so we did the reverse merger, the pre-money, if you will, was the value that we acquired the asset for. So we acquired this asset for about $72 million in tech value. So you can think of that as our pre-money. Now, we, or I at the time, was negotiating on behalf of Eledon. So if I could have, I would have been I could have acquired the asset for a dollar. That doesn't mean the asset would have been worth a dollar. It means that's what I acquired the asset for. But that would have been the pre-money.
As a result, we've had, I think, a low valuation since we started with this low pre-money that was really artificial, right, because it wasn't based on where a bunch of VCs wanted to back a company going public. It was based on where a group of individuals were able to acquire an asset. Historically, we've also been quite tightly held, which has also been great because our investors have continued to back us, but also played a role, I think, in being able in kind of keeping our share price within a specific range. That said, we've recently been able to raise capital. We brought in a terrific group of new investors a few weeks back. That deal was done at a premium to the market.
So, while in the past we've been under the radar, I think if we look at the fact that we did a deal that was oversubscribed and that was done at a premium, right? Well, most deals, as you know, are done at a discount, right? So, 52-week high and a premium, that shows the enthusiasm that is beginning to build here.
Okay, and maybe just to lay out the groundwork here for the next year, so we have obviously some data coming up. Maybe you can just kind of summarize what we should be focused on and then now post this deal, sort of where your capital position, your cash runway.
Sure. So over the next 12 months, the big readouts, as I mentioned, are going to be in kidney transplant, our phase 2 data, as well as we expect about nine patients' worth of data in islet cell transplantation. That'll be fourth quarter of next year, so about a year from now. Before that, we'll provide an updated readout from the phase 1b in kidney transplantation. That should be in the middle of the year, around the summertime, most likely at ATC, which is the big transplant conference and where we have presented our phase 1b data in the past. You might also see some more preclinical work get presented or published, so that could be in things like liver transplantation as well as xenotransplantation. In terms of cash position, now that we've done this raise, we have sufficient capital to get us to the end of 2026.
So that's going to allow us to flip over the cards in the fourth quarter of next year and still have over a year of cash in the bank.
Okay. All right. Congrats on all the progress. Obviously, interesting story and a big year ahead. Look forward to staying in touch as we go forward here.