Hi, good afternoon, everyone. I'm Farzin Haque, one of the biotech analysts at Jefferies. It's my pleasure to introduce Renée Aguiar-Lucander, who is the CEO of Hansa Biopharma. This is the fireside chat format, so thank you for joining us today. For those who are new to the story, can you provide a one-minute introduction to Hansa and the platform?
Sure. Hansa is really built around a novel and quite unique platform in terms of enzymes that very, very effectively and efficiently cleaves IgG. Basically, within two to six hours of administration, the enzymes really can reduce IgG by more than 95%. Basically, it really takes out your immune system very, very efficiently, both intravascularly and extravascularly. This is really then applied in a variety of areas. We are looking at highly sensitized patients on the waiting list for kidney transplant. It was a recent Phase III we read out. We are also looking at administration prior to gene therapy, where, again, there are a lot of patients, actually, who have antibodies against AAV vectors, which are the predominant delivery mechanisms for gene therapy. This could be both in clinical trials as well as in commercial settings.
Finally, there are some IgG-mediated autoimmune diseases, such as anti-GBM and GBS. Those are really the applications at the moment that we're looking at from a kind of disease area perspective.
Great intro. The bigger picture question, like, what is the addressable market opportunity for in the kidney transplant settings in the U.S. and also touch on the EU?
In terms of highly sensitized patients, usually that's defined as anyone with a CPRA score of 80% or above. If you look at kind of the waitlist in the U.S., there are about 100,000 patients on the waitlist, and about 15% of those are actually then considered highly sensitized. If you then break that down, you also then have about, out of those 15,000 patients, about 7,000 of those patients actually have a CPRA score of 98% and above. There is a really significant unmet medical need in this area because, basically, there's really nothing else on the market today, and there's nothing else that physicians can use to effectively and safely really kind of desensitize these patients prior to a kidney transplant.
You started, you have guided to filing by year-end for the BLA. Where do you currently stand in the process?
In terms of, we read out the data in September. Our plan really is to try and be very efficient and effective and to file our BLA before the year-end. I would say that, internally, we are well on track to meet that deadline. We're still very much working towards filing the BLA before the year-end. We would apply for priority review because this has, it's an orphan indication. We have fast-track designation. Obviously, it's a significant unmet medical need with nothing else approved. We think we have a very high probability of getting priority review. That would then mean that we would have a potential approval towards the end of August next year.
Pretty fast coming up there on the corner.
Yeah.
What are your expectations for the label? If you apply for the priority review, it'll be an accelerated approval label. Could FDA limit the scope to Phase III population, or could they expand to more general population with high unmet needs?
This is obviously something that we're going to find out when we have label negotiations with the FDA. Obviously, the clinical trial that we ran, the Phase III clinical trial with 64 patients, actually, we had an active arm and a control arm in that study. The p-value of that study came out to be 0.0001. We do think that, in terms of kind of clinical evidence, this actually really shows the lack of alternatives on the market today and really kind of the strength in terms of what the drug can achieve. The patient or the Phase III trial really was studied in patients with a CPRA score of over 99.9%.
This is a really, really, really kind of extremely difficult kind of patient population, obviously, because it's highly unlikely that these patients will actually ever get a natural match of an organ simply because you have a 0.01% chance of really kind of doing that. Obviously, there is always an opportunity for the FDA to kind of go with the actual just kind of study population. It's certainly something that's possible. However, I believe that this drug is obviously not something that's kind of dose-dependent. Actually, I mean, in terms of what it does, it truly only cleaves IgG. It's not like if it runs out of IgG, it starts cleaving other things. There's no off-label. There's no kind of off-target issues that we've found to date that are of any kind of seriousness or concern.
I would say that, actually, this is something medical professionals and transplant surgeons, I'd say, would look at this and basically kind of say, well, would they not use this in a patient that has 99% or 98.7%? I think that, in terms of label, we hope that the FDA would be amenable to look at this in the context of really highly sensitized patients. Again, we can obviously not, it might absolutely be the case that they want to just go with the study population. Even to the extent that they do, it is my strong view that the physicians will practice medicine responsibly.
Makes sense. For those in the audience, like Hansa hosted two prominent KOL surgeons last week. Please do check the replay. It is very insightful as it tells you what the unmet need is and how the Phase III data fits in the clinical treatment paradigm. For Renée, maybe to start off with the unmet need, how quickly do you think the transplant centers could start using the drug? What is the earliest since after approval?
Yeah. This, again, I think, is really kind of interesting because I think those KOLs that actually were on this call made it also very clear that in this population that we studied, certainly, the vast majority of patients that go through kidney transplants today, the organs come from deceased donors. It is 80% or so that come from deceased donors. In that setting, there really is not anything else out there in the market that they can use because of the time limitation, et cetera. They also made it clear that, actually, in terms of PLEX, IVIG, et cetera, that is actually not something that they use even today on living donors because the outcomes have not actually been very good. This is clearly something that is a significant need for them if they actually ever want to kind of give these patients hope about having a transplant.
My view is actually that we ran a Phase III with about 25 centers in the U.S. There are quite a lot of KOLs who have experience of this drug, have seen it work. This trial has been going on for a couple of years. We do think that there will be fairly quick uptake, particularly across those centers, obviously, that have experience from this and are familiar with the drug and how it works. I think that we'll see reasonably good. I would say that it wouldn't be the drug will be able to be kind of ordered upon approval. I mean, there's no reason to believe that we won't be able to kind of launch the drug reasonably quickly after approval.
After that, I think, obviously, there is a plan to kind of roll out this to other centers who are not part of the kind of Phase III. Obviously, in the U.S., it's a very kind of concentrated market. There are about 100 transplant centers in the U.S. that represent about 80% of all transplants that are conducted in the U.S. Considering that 25 of them are already part of our Phase III, actually, we are going to have a very organized kind of rollout and educational program, et cetera, for those other centers who are not part of the Phase III. Obviously, we benefit from the fact that there is a large number of KOLs and transplant surgeons who are already familiar with the drug.
Great. Looking ahead, this would be for accelerated approval.
Yes.
What steps do you need to take to transition to full approval?
In the actual design, the way that it was kind of set up from the beginning, there is a long-term follow-up in place. This is just to kind of follow these patients longer term to then see kind of long-term graft survival, overall survival, et cetera. That's the typical kind of outcome that the FDA would be looking for. What we have seen, though, actually, and there's been quite a lot of papers published about this, and again, I think it was mentioned in that KOL discussion, is that, in general, I would say in transplant, it's not specifically even for these patients, but you would have, basically, if you get to a 12-month point and looking at kidney function at 12 months, that point is actually considered to be very reliable as a predictor of long-term outcomes.
Obviously, in the Phase III that we read out, that was really kind of the endpoint of the Phase III. The endpoint really was kidney function or eGFR at 12 months post-randomization. Basically, we feel very good about kind of how we what the situation looks like on a long-term outcome basis, considering that we had very, very good 12-month kind of eGFR data in the actual active arm. We feel that that is something that, again, if you look at kind of when there tends to be kind of complications or issues generally in transplant patients, a lot of that will take place in the first 12 months.
Makes sense. You have the five-year data coming up from the EU confirmatory study.
That's correct.
Maybe talk about that and then how it can also help for the US as well.
Yeah. In Europe, actually, the company did something that was a little bit kind of in a different order. There was a kind of small Phase II open trial that they brought to EMA that was actually conducted mainly in the US, but there were two European centers as well involved in that. EMA really felt that this is a huge unmet medical need, so they really were willing to kind of give an accelerated approval very early on on the basis of that data. They did require a Phase III trial. That Phase III trial is ongoing in Europe. It's called the PAES study. It's basically recruited 50 patients to be transplanted. The EMA did not require kind of a control arm to be in place in conjunction with that kind of active arm.
That kind of trial was actually fully enrolled in Q1 of this year. That will read out, hopefully, I would say mid-year next year is reasonable, I think, to assume that is going to read out. The endpoint of that is, again, 12 months graft survival in terms of and kidney function. That is, again, eGFR and graft survival on a 12-month basis. EMA will also be looking at a comparator, I would say, a non-comparative arm, but still a group of patients who have also been transplanted who are not highly sensitized to get a sense, basically, of how that compares. That will be the basis for full approval in Europe.
We would hope that that data will read out in the middle of the year next year, and we would then be filing for full approval. I think, based on all the data we have now, all the Phase II trials, the Phase III trial that we've just run, and the fact that, obviously, it has been approved in Europe for a couple of years already and commercially used, I think they know we feel very comfortable about the fact that, obviously, this drug works and it does what it's supposed to do. Again, we're feeling good about the actual ability to get full convert our conditional approval to a full approval in Europe.
Makes sense. Coming back to the U.S., what is the status of the U.S. commercial readiness?
In the U.S., obviously, we brought together a highly experienced team with a lot of experience in terms of both kind of rolling out and introducing products into the US, but also specifically in the renal space. I think, from that perspective, we have a senior team that has all of the kind of skills both in terms of medical affairs, market access. Those are the two first areas that we were going to really focus on. That will obviously be followed by kind of the commercial kind of effort to bring that on board as well. I think that we are, well, we're doing, obviously, some, we're in the midst of doing some pricing research. We're doing some other kind of work.
Really, it's to kind of formalize this plan and this rollout plan to all the different kind of transplant centers and to really kind of, I think this is a very much a kind of medical affairs-driven launch in a way because it's really about educating the hospital group because I think it's a bit of an account selling because you have an HLA director, you have a nephrologist, transplant surgeon, et cetera. They need to understand how you go about actually what's called delisting these patients. Because these patients have a very, very huge amount of antibodies, they never get an organ offer. That's obviously the fundamental problem, or they rarely get an organ offer that will match naturally.
In order to do this, obviously, you need to delist or remove some of those antigens from the profile of the patient in order to be able to get an actual organ offer through the organ allocation system. Once you have that organ, you can then treat that patient with Imlifidase and actually transplant an organ that kind of technically would have a positive crossmatch. This is really what Imlifidase enables, is that kind of operation. You need to kind of have that kind of educational background and understand how to deal with these patients, how that works in order to kind of then get these kind of organ, get that kind of opportunity for these patients. That is really kind of part of the rollout plan.
Obviously, the Phase III data that we read out, obviously, we're also hoping to have a full publication of that in June timeframe at the ATC. I think that will obviously also very much help this whole process in terms of physicians, as I keep on saying, they don't actually kind of they don't go to these events. They don't listen to press releases. They want to actually see things either at a Congress conference or in a publication. I think this will be really important. That will further, I think, just educate the kind of the transplant community. I think we have to be very clear. I mean, transplant surgeons have not had a huge amount of innovation, right? They really, really have not had a lot of drugs come to them.
They are super excited about getting something that they can actually use on label that has actually been studied for their patients and has this kind of substantial amount of evidence. This is really kind of how we're doing in the US. I think we're well down the plan of what we need to do in order to kind of be ready to launch upon approval.
Makes sense. You have some valuable insights from the European Health Technology Assessment, or its HTA processes. How does that inform the U.S. budget impact and the cost-effectiveness models for the Medicare and commercial coverage?
Obviously, in Europe, I mean, the company can't set its own price. Really, it's a negotiation with each country. The countries really do carry out quite a substantial health economic analysis. Prices are really given to the company in terms of what the country is willing to kind of accept. The pricing in Europe is list prices about $300,000–$350,000 per treatment. That really then is derived from the fact that that is a price which turns out to be either cost-neutral or cost-beneficial to the country when it looks at this in terms of medical need and cost, et cetera, and what it can bear. I think from that perspective, I think that's important. Obviously, in the U.S., cost of dialysis is actually much higher than it is in Europe.
We will be carrying out a very broad, we will be very well informed about all the different kind of components that go into making a pricing decision. We will announce a price in the U.S. upon approval. I do think, obviously, in terms of this market access, this is an inpatient procedure. This will be part of the DRG code. We will really kind of follow the same path that's been done, well, kind of paved by companies that, for example, work in the CAR-T space. We will apply for an NTAP, which is kind of an add-on payment for kind of novel drugs. Hospitals will use kind of outlier payments. We are exploring a variety of ways to kind of obviously facilitate and make this as easy as possible for hospitals to use.
Again, the feedback that we've had from kind of the hospitals that have been part of the Phase III is that they do not think that this is going to be a significant hurdle in terms of from that perspective.
Great. You mentioned about the EUR 300,000–EUR 350,000. What about the U.S. pricing? Any thoughts on how you're thinking about it?
Again, I mean, I think that we'll really kind of we haven't announced a price. We will kind of we'll carry out a very kind of informed pricing research work in order to kind of get there. Again, I would say that this is something where I don't think that we need to price this extremely high. I think that it's already been proven that it has great benefits from a health economics perspective at the level of $300,000–$350,000. I think we will kind of we will work with all components of the payer system to get to the right price.
Got it. Last week, like the KOLs mentioned, that basically imlifidase stands out versus IVIGs and standard of care. Are you tracking any other competing programs in clinic that can potentially come up?
Actually, I mean, we're always tracking everything in renal just because we're curious and we need to kind of stay sure what's going on. Actually, in terms of looking at anyone looking at either kind of desensitization for kidney, desensitization for gene therapy, there are actually no clinical trials. There are no late-stage clinical trials being conducted either in Europe or in the U.S., as far as we can find. This is really kind of part of the really attractive profile of this company and this business is that there really is nothing else out there that can compete with the speed and the enormous amount of data that we now have in the clinic, both from kind of clinical and real-world evidence. There are over 200 patients that have already been using this drug, both kind of in the clinic and commercially.
I think we feel from that perspective, we feel very good about where we are.
Yeah, I'm looking forward to the launch on that. We are also waiting for the top-line data from Phase III in anti-GBM, which is also like a glomerular kidney disease, basement membrane disease. What should we look for in terms of outcome measures and clinical significance?
This is an ultra-rare disease, kind of like a vasculitis, that actually kind of affects both the kidney and also lung tissue. It is actually really quite, it's an acute kind of onset. Unfortunately, today, with kind of standard of care, which is, again, kind of PLEX and corticosteroids, high-dose of corticosteroids, et cetera, with all of that that's kind of available off label, the actual kind of, I would say, kidney survival for these kind of patients after six months is somewhere like 20%–25%. It is a really severe kind of disease, really. There is nothing approved for it today. We are planning to read out the Phase III before the year end. It is 50 patients. They have basically been kind of, it's one-to-one study. The endpoint, again, is actually kidney function at six months.
There is also a very important kind of key secondary outcome that really kind of looks at dialysis dependency. Have you actually had these patients kind of have to be on dialysis during this period of time? Or have we actually managed to kind of retain the kidney function for these patients with Imlifidase? This obviously goes back to the idea that if you really can kind of reduce these kind of IgG antibodies very rapidly and quickly, and quickly after diagnosis, you will then be expected to have a much lesser impact on the overall kind of disease development than if you have to go through weeks and weeks and weeks of a slow kind of reduction of IgG. Those are the endpoints that we are looking for. We are also very excited about that.
I think that will also then kind of give us an insight in terms of how this works in general, I think, kind of for autoimmune diseases that are IgG mediated.
You can file for approval based on that Phase III, right?
We can file for approval on the basis of that Phase III, yeah. What we're planning to do is, obviously, we would at that point in time already kind of we would file one BLA at a time. We would kind of plan to do the file the kidney-related BLA before the end of the year. Once that is actually approved, we'd file an sBLA for anti-GBM. That will also allow us for kind of for the U.S. organization to roll out kind of this in kidney for kind of kidney desensitization. Maybe nine to twelve months later, there'd be another kind of product that they could also then kind of bring to physicians and nephrologists in the area of anti-GBM.
Got it. We also have a few minutes left. Pipeline has Hansa 5487, which is a second-gen IgG cleaving enzyme. So maybe talk about the update on this program that we should expect and when it might enter clinic, indications, so forth.
Yeah. So this is actually something, so obviously, I've been at Hansa now for about six months. And so this is something that I kind of wanted to really do some work on externally. So we've done market research. We've had KOL interactions, interviews, et cetera, to try and really kind of find out what would make most sense in terms of target for kind of 5487. Because obviously, as we know, there's been a lot of development in kind of maintenance therapies around kind of autoimmune diseases. And we have to take that into account if you're going to run a clinical trial of something that has to do with more acute exacerbations and flares. So what we've actually kind of, and we've heard also from the physicians, is really we're going to take 5487 into GBS. So we're going to really have a second franchise.
We're planning for that to be, we're hoping for that to be, quite a very late-stage trial, considering that we already have Phase II data from imlifidase. We're going to interact with the FDA kind of early in the new year. Once we file the BLA, that is something else we can start working on. We're hoping to have some feedback from the FDA in kind of Q2 of next year with regards to the clinical design and what we really need to do. Because again, GBS is an IgG mediated disease. We have very good supportive Phase II data from imlifidase. Nothing's approved in this area. KOLs are very supportive in terms of the data that we presented, which we did a couple of months ago at the kind of European Congress.
That's really what we're going to do with the hope to really kind of bring that forward on a very kind of accelerated basis.
Will that be on your own or with a partner?
We're going to start on our own. I think the benefit of having that be a separate, this is obviously neurology. Guillain-Barré is a neurological disease, so it gives us quite a lot of flexibility. We could potentially out-license this in various geographies where we do not intend to take it forward ourselves. That could kind of help with some of the development costs, for sure. We could also potentially partner it. When we decide to partner it will really depend on when we start incurring higher costs because we're not really going to incur a lot of costs next year. That would really be a 2027 kind of decision, I think, because 2026 we can certainly manage on our own and start taking that into the clinic.
It'll also depend on, obviously, how attractive potential partners might find it and, yeah, what other decisions might be then. We'll see.
We are almost out of time. To close out, what is your cash position? And then what is the runway and any major milestones we should be looking out?
Yeah. At the end of Q3, we had about $93 million of cash on the balance sheet. That will take us into 2027. That basically means that whether we get priority review or standard review, it will certainly take us through an approval at priority review that will allow us to launch the product in the US. In terms of kind of milestones, obviously, we have anti-GBM reading out the Phase III. We have the BLA filing for the kidney desensitization in kidney. We then have the PAES kind of European trial reading out for a full approval in the middle of 2026. Obviously, in February 2026, we are going to hopefully then also get our PDUFA date for the acceptance of the file and the PDUFA date for kidney.
In kind of the around mid-year or kind of Q2, we'll hopefully also be able to announce kind of what the trial design, timing, et cetera, would look like for a trial in GBS.
Thank you so much.
Thank you.