Ready to get started. All right, thanks everyone for joining us here, on the second annual Guggenheim Healthcare Innovation Conference. I'm Vamil Divan , one of the biopharma analysts here at Guggenheim. Joining us in this room next, we have the Eledon Pharmaceuticals team. We did have one victim to some of the travel issues, who was not able to join us, and that's the CEO, Dave Gros. But we do have Steve Perrin, President and CSO of the company. We'll run through the story. Obviously, you know, a lot of activity in the Eledon story over the last little bit here.
Maybe before we dive to, you know, last week's data at ASN and, you know, kind of takeaways from that, maybe just sort of, for people less familiar with the story, give an overview on sort of how Eledon came together, the path to where you are now, and then we'll talk about, you know, last week and steps forward.
Sure. Thank you for inviting Eledon to present today. Eledon Pharmaceuticals is developing tegoprubart, an anti-CD40 Ligand antibody, focusing on transplant as a primary indication. There are a couple of reasons for that. A lot of it is historical in that blocking CD40 Ligand has been one of the most potent ways to prevent transplant rejection in multiple species over time, including mice, rats, nonhuman primates. Our goal is to replace tacrolimus or cyclosporine as the cornerstone immunosuppressant to prevent transplant rejection. We want to do that regardless of the type of transplant, be it heart, kidney, liver, cells, where the organ came from, including both allograft as well as xenograft transplant.
Okay. Great. Maybe just to sort of frame that, the opportunity, let's talk about tacrolimus. Obviously, you've been on the market for quite some time, a lot of challenges. Maybe you can talk through sort of the issues that tacrolimus poses to doctors and patients and how you're hoping to, you know, advance the care of these patients beyond that.
Sure. Tacrolimus was approved about 30 years ago, in a noninferiority study, against the standard of care at that time, cyclosporine. It showed a better, a better safety profile than cyclosporine did at the time. Tacrolimus, although it's a pretty good drug at preventing transplant rejection in the first 12 months, has both immediate and long-term toxicities that make it very challenging from a healthcare perspective, in doctors as well as for patients, including cardiovascular tox with increased hypertension. It has nephrotoxicity, so it's actually toxic and hurts the actual organ in the context of kidney transplant that you're trying to protect. Patients that have gotten other types of either organ or cellular-based transplants, such as cardiac and liver transplants, eventually see the same type of nephrotoxicity that one sees in a kidney transplant population.
The nephrotoxicity is a significant side effect and a problem. There's also metabolic toxicities. It's toxic to the beta cells in your pancreas. About 20%-30% of patients on TAC end up getting new-onset diabetes, which requires patient care for life, and it's quite debilitating. Finally, there's also a whole host of neurological toxicities that are associated with tacrolimus, including brain fog and tremors, which are quite debilitating to patients, leading to compliance issues and, you know, long-term longer-term risk of graft rejection post one-year transplant.
Okay. Great. You've had a couple big data readouts recently, the phase 1b additional data from that back in August, and then obviously the phase II last week. Maybe we walk through the program that you've developed here for tegoprubart and some of these data releases, and we'll go from there.
Sure. With our focus on transplant, our lead indications has been kidney transplant, driven by the fact that kidney transplants are the biggest market, the most number of transplants that are done, for kidney, about 25,000 per year in the U.S. and about 25,000 in Europe. That has been our main focus. We historically have been running several different parallel clinical trials in transplant, an open-label phase I study that was initially mostly ex-U.S. to understand how to integrate tegoprubart into a CNI-free regimen, with the rest of polypharmacy that's required to prevent transplant rejection. We launched a phase II trial called BESTOW about two years ago that was going to try to basically look and see if we could compete against tacrolimus in a superiority design.
And if you want, I could go through the trial design in more detail if you'd like.
Yeah. I think it'd be helpful to frame that, the design, and then let's talk about sort of the results.
Sure. Standard of care immunosuppression for the prevention of transplant rejection requires two different phases. There is a phase of induction therapy, if you will, around the time of transplant that usually is a high dose of methylprednisolone combined with ATG for T-cell depletion and T-cell control. Often there is also prednisone that is started around the time of transplant and then tapered down to a lower dose, usually over the first month. Standard of care has a tacrolimus dose that is initially a little higher, and then over time they try to get it to a lower trough level. The goal of the BESTOW study was to basically keep as much of the immunosuppression the same between the two arms as we could, but replace tacrolimus with tegoprubart as the cornerstone immunosuppressant to prevent rejection.
The BESTOW study was a much bigger study than our phase I study that I just described. It was a more global study. It enrolled about 120 patients total, randomized 60 per arm, enrolled in the U.S., Europe, Canada, Australia, and Brazil. The primary endpoint, it was powered as a superiority design to examine kidney function, compare the compare and the TAC arm to the Tego arm, and it was powered to detect a nine-point difference between the two arms. For secondary endpoints, we collected things for the standard noninferiority endpoint that's historically been used for approval of drugs in kidney transplant, including patient and graft survival, biopsy-proven rejection, and then additional secondary endpoints around potential new surrogate endpoints such as IBOX, as well as all of the serious side effects that I just mentioned for tacrolimus.
Okay. Great. You presented the phase II last Thursday. Feels like it's been a while since it came out, but just less than a week. We can talk through the results and then just sort of the feedback you received from the community at ASN.
Sure. Yep, we released our data last week at Kidney Week. Really exciting data from my perspective. I've been working on this drug for over 10 years, and I've been working on CD40 Ligand for over 30 years. It's been kind of a long road getting tegoprubart to this first great readout in a fairly large, phase II study. The data exceeded all of our expectations for the most part, right? We have consistently seen some of the best kidney function that one has ever seen in a clinical trial, with eGFRs in the high 90s, often in the low 70s in some of our cohorts in the phase I. We saw that again in the BESTOW study. The surprise that we got there was the TAC arm performed significantly better than what we would have estimated historically.
We powered our study based on historical data where most of the time, if you talk to doctors treating patients with TAC, or if you look at historical trials such as the Iscalimab study, mean eGFRs on TAC tend to be in the 50s, mid 50s- low 50s. We were surprised when TAC came in at a mean of 66. We missed the primary by three points. With that said, longitudinally, if you look at any time point in our study, and if you look at any subgroup, we pretty much beat TAC across the line. In some of the subgroup analyses, we actually beat TAC by as much as 10 points, including living donors, patients that received poor quality kidneys, as measured by KDPI. If you start combining some of those parameters, the deltas actually got bigger and bigger.
If you actually stratify as a continuous variable across kidney quality with KDPI and living donor, it actually reached statistical significance in the study. Amazingly, we also hit a couple of other things that was quite exciting that, you know, you might not have expected how profound it was, but we actually hit the noninferiority endpoint. The study was not powered to hit the regulatory approved endpoint for transplant on 12 months, which is noninferiority on patient survival, graft survival, and acute rejection, but we actually hit it even though the study was not powered to do so. The real big, big win was when you compare the safety profile for the two arms. I mean, all of the toxicities that I described for TAC actually showed up in a 12-month study. We saw an incredibly large delta or nuance of diabetes between the TAC and Tego arms.
We saw hypertension imbalances with higher on the TAC compared to the Tego arm. We saw delayed graft function was a big component that we saw, that patients post-kidney transplant, it often sometimes takes your kidneys a while to start functioning and producing urine, and you have to be on dialysis during that timeframe. There was a significant delta in the duration in numbers of people that had delayed graft function on the TAC arm compared to the Tego arm. The neurological outcomes were also quite profound where there was an incredible amount of tremors in the CNI arm compared to the Tego arm.
Okay. I know you've only had this data for like three weeks now, so I'm just, I think you're still going through the details, but is there anything in this population or the way the patient was managed that could explain why the TAC arm did better than what we've seen historically?
To your point, we're a couple of weeks into the data, but yes, we've had some clues, and some of it is just the nature of clinical trials, right? Unlike real-world data where patients aren't managed as carefully, in the context of a clinical trial setting, patients go into the clinic as often as they want. You know, we obviously paid for and managed this study, and we wanted doctors to give patients the best possible care that they could, but it was incredible to us how frequent visits often were in the TAC arm compared to real world. Because they've been using this drug for 30 years, they have a very good understanding of how to manage and control the trough levels of TAC, exquisitely as long as they're seeing their patients often enough, which they did in our study.
So that probably contributed to why there was very, very good kidney function on the TAC arm compared to what you might see in real-world data.
Okay. That's interesting. Okay. So then maybe thinking about the data you have now, I think your next steps would be kind of analyzing it some more, then getting in front of the FDA. Maybe we can just talk about what are the next steps, what should we expect to hear from the company next?
Yeah. Clearly the team is now transitioning post-BESTOW to next step, which is to design and launch and execute a phase III study in kidney transplant. We've had some earlier dialogues with the agency to get some clarity about what that might look like, including that a single phase III study would be sufficient. They've been guiding us for a long time that the endpoint at 12 months would be the noninferiority endpoint that we've utilized for a long, long time in kidney transplant. As I mentioned, there is a new surrogate endpoint that the FDA is currently reviewing. It's called IBOX.
It was approved in Europe about a year ago as a secondary endpoint, but the consortia that's been promoting the utilization and approval of IBOX is trying to guide it a little bit differently here in the U.S. where they're advocating for a subset of the IBOX components, which I could describe to you if you'd like. It's called abbreviated IBOX, could be utilized as a co-primary endpoint alongside the composite endpoint for approval, which expands the label, if you will. I mean, it's kind of like taking, we call it two bites of the apple. You don't have to hit your IBOX as an endpoint if you hit your noninferiority for approval, but if you do, it can give you some better details on your label post-approval.
Okay. All right. Maybe one question here, just obviously from a market reaction to the data on Thursday was pretty negative. What do you think is the disconnect in terms of what, like what, based on your conversation with investors before and after relative to your expectations and kind of what sounds like pretty positive feedback from the, you know, kidney community? What do you think the investors are missing?
Obviously we have a lot of different constituents. The doctors and nephrologists at the meeting have been incredibly excited about our data to the point that the inbounds from them have been pretty incredible. There's also a great podcast that was conducted post-ASN, if you haven't listened to it, that really summarizes a lot of components of the meeting, but because we're a late-breaking abstract, starting at about a minute 12 out of that one-hour podcast, three different KOLs talk about our data and how remarkable it actually is from a safety perspective in particular, and how exciting that could be for them and for patients. It's definitely worth listening to. Safety alone is something that people have really, really focused on, that people, I think, have been incredibly surprised at how good our safety was at 12 months compared to TAC.
People know that those toxicities that I've described associated with TAC are cumulative. You're going to see them accumulate year after year after year, and we've seen that in other studies. I think that that was one of the most exciting pieces. What I think the investment community missed a little bit is they thought that we had to beat TAC in the superiority component of our study, and that really was just a primary endpoint in a phase II study that we could have had safety be the primary endpoint. We kind of shot for the fences on that outcome. If TAC didn't overperform and behave more like historical, we probably would have hit it. I think what the investors didn't do is go past the tagline that we missed our primary endpoint.
We hit the noninferiority endpoint, and we really hit a grand slam home run on all of the safety pieces.
Okay. Okay. Great. Let's, looking beyond that a little bit, as we think about the opportunity moving into phase III, can you just talk about sort of the commercial dynamics here that you'd have to think about as a company? I think the other thing that, as we've talked to people about the Eledon story over the last year, the last launch in kidney transplant was Belatacept, which didn't do quite as well as people were expecting. Your thoughts on Belatacept, sort of maybe why it didn't, you know, sort of become the blockbuster people thought it might be, and then how would tegoprubart be a different outcome?
Sure. I mean, one thing with, so Bela is a good drug, right? If you look at the Bela data that's been published in the literature, you know, the 12, three, or seven-year data for Bela looked quite striking. It was approved 15 years ago. At that time, one of the disconnects, I think, was that people didn't understand that eGFR was the best long-term predictor of graft function. At that time, there was a conception that biopsy-proven rejection rates was actually the best predictor, and we now know that there's a lot of data to suggest that actually BPAR rates don't have anything to do with predicting long-term graft function, and that's one of the reasons why it's not a component of IBOX. When Bea launched, their goal was to launch on safety, for one thing.
Second of all, the study, because of the timing on when BMS launched that study, they actually were not comparing themselves to the approved standard of care, which was tacrolimus. They actually went against cyclosporine, which TAC had beaten in that noninferiority study. I think those complicated the launch a little bit. I think the third piece was on the safety side, they had a couple of minor hiccups, if you will. It has a black box in liver transplant because when they went into their liver transplant studies, they saw some deaths, and it also had a higher incidence of PTLD. We still see that today. It's not real common, but it's something that happens, and that scares people, which is probably why Bela only has about an 8% of de novo kidney transplant market share.
Okay. All right. So let's go beyond kidney. As you mentioned, the goal would be, you know, for all transplants potentially. So you do have the islet cell program going on with the University of Chicago. Maybe you can talk about islet cell and then other sort of opportunities you have beyond, de novo kidney.
Yeah. Our second focus has been both islet cell and xenotransplant. In islet cell, we have an ongoing study as an IST, as you mentioned, with Dr. Rokowski at University of Chicago. He's been fairly outspoken about the data, as has the diabetes community. He got five of his six patients off exogenous insulin very quickly after their islet cell transplant. It's a pretty minimal immunosuppressive regimen compared to what we see in kidney transplant because protecting cells doesn't require quite as much immunosuppression. Tego is really the foundation and cornerstone of that. Historically, islet cell transplant has not been well adopted in the patient community because no one wants to go and get an islet cell transplant and basically swap out their diabetes for the toxicities associated with TAC. We think that this is an amazing opportunity.
Our goal here is to facilitate Dr. Rokowski and supply drugs so we can get nine patients enrolled. Once we have about a year data on those nine patients, we intend to go to the agency and start to discuss what a phase I, II, III strategy for approval of Tego and the prevention of islet cell transplant rejection would look like. There is some guidance out there that what they've guided to Vertex as well as to CellTrans. Vertex has their terminally differentiated islet cells that are, I think they completed enrollment of their phase III recently. CellTrans got approval about two years ago for cadaveric islets. They got approved on about 22 patients of data, and Vertex's guidance has been 48.
We think we'll be somewhere in that frame, but we want to take that nine patients' worth of data, which we're quite hopeful will be quite excited about, and go and get some guidance from the agency on what a registrational type study might look like in islet cell transplant.
Okay. And then the latest round, xeno?
Xenotransplant, as people know, has made exciting progress in the last couple of years. If, you know, recently, unfortunately, we had a minor setback with the person that probably had had the longest kidney transplant, which was an eGenesis kidney, that was on tegoprubart and several other immunosuppressive medications, made it out about 10 months post-transplant. If you had asked me a year and a half to two years ago that we would have had somebody go out that far on a xeno kidney transplant, I probably would have laughed. And he actually did quite well. We still have a third patient that Massachusetts General Hospital has done that still has a viable kidney and is doing well.
What's happening now, I think, in the community with the approval of United Therapeutics, IND path towards approval that's being run primarily right now out of New York University, and eGenesis also has approval for their path forward in kidney transplant, xenotransplant. I think we're going to see the clinical trial protocols really start to add some better constraints about what we're doing with patients as far as what type of patients we can enroll, how healthy they are. The compassionate use patients were patients that were pretty sick. I'm hoping that as we start launching the clinical studies next year, rather than compassionate use studies, we'll see some good progress on how to utilize xeno kidneys in the context of tegoprubart and the other immunosuppressive drugs to prevent rejection.
Okay. Great. Maybe the last couple of questions I have, one is sort of the competitive landscape. We get this question a lot too because there are other companies with CD40s, CD40 Ligands. What are you seeing out there competitively in terms of it? It seems like a lot of the CD40s are on other indications, but just what are you seeing in the transplant space, from competitors?
Yeah. Right now, we're the only company that's in transplant for the prevention of de novo rejection, with a sponsored study for blocking CD40 Ligand. Obviously, the other competing molecules from Sanofi, Biogen, Amgen are focusing on the larger autoimmune indications, if you will, with Sanofi focusing on MS, Biogen UCB rather just reported positive phase III data about a year ago in lupus, and Amgen's reported positive phase II data in Sjögren's syndrome and RA. I think the exciting thing about this target with the competitors and with our drug is after 30 years of people wondering if CD40 Ligand was a validated target, I think the checkbox there is yes. It's clearly working in multiple indications.
With our primary focus on kidney transplant and we're the only ones in transplant, I think we have a great opportunity to really make an impact and transform immunosuppression for transplant medicine in the next few years.
Okay. Great. Maybe last minute or two here, capital position. I know you're sort of in the middle of this raise now this week. Can you just share, whatever you can in terms of your current position? What's your runway? Then tied to that, is there one of the next catalysts we should look for within that runway for investors to be aware of?
Sure. As of September, I think we've reported that we had about $90 million in cash. As you mentioned, we're in the process of closing a raise this week, which we're hoping would extend that cash runway out to Q1 2027. That gives us a little bit more runway compared to what we would have had just with the $90 million in cash for September. What we're guiding for for next year for catalysts would be clear regulatory guidance on all three of our indications. Have an end of phase II meeting with the agency about what a phase III trial would look like in kidney transplant so that we can execute and launch that study by the end of next year to get clearer guidance beyond what an islet cell registrational study would look like so that we can transition our investigator-initiated study with Dr.
Rokowski into more of a multi-center islet cell transplant study, if you will, heading towards what might be a registrational study. Finally, eGenesis announced that they got FDA approval on what an IND plan would look like for kidney xenotransplantation with 33 patients of data. Tego's the cornerstone of that immunosuppressive regimen. We need to go to the agency and basically articulate what the approval plan would be for tegoprubart as part of xeno kidney transplant rejection.
Okay. Sounds great. You know, I'd agree with you on the xenotransplant comments. Like, you know, the progress we've seen there is pretty remarkable over the last couple of years. And interesting that eGenesis has chosen, you know, tegoprubart to be the backbone there. Thanks so much again for attending the conference. We'll see how things progress here over the next little bit, and we'll be watching closely.
Thank you.
Thank you. Appreciate it.
Thanks.
Thank you.