Good morning, everyone. I'm Farzin Haque of the biotech analyst at Jefferies. It's my pleasure to introduce Renée Aguiar-Lucander, CEO of Hansa Biopharma. This is the fireside chat format, so thank you for joining us today, Renée. For those who are new to the story, maybe provide a quick intro to the company.
Sure. Hansa Biopharma has a novel platform, first in class, of IgG degrader. These are enzymes that can cleave all classes of IgG, both intra and extravascularly. Basically within two to six hours, it can cleave IgG to more than 95% of baseline. This is really a very effective, targeted way to very rapidly reduce IgG. We basically have a focus on kidney transplant patients who are highly sensitized, and also highly sensitized patients in need of gene therapy, where these antibodies really cause an issue for dosing. We also have a second enzyme in the pipeline, who we are targeting a rare autoimmune disease called Guillain-Barré.
Maybe to start off with the bigger picture question, talk about the unmet need in the highly sensitized kidney transplant patients, and what is the addressable market opportunity for imlifidase, that's your lead drug, in this setting in the U.S.?
Sure. In the U.S. today, there are about 100,000 patients on the kidney wait list. Out of those, about 15% are categorized as being highly sensitized. That's really that they have a cPRA score in excess of 80. That basically means that they have a less than a 20% chance to find a naturally matching organ. Out of those 15%, about half of them have a cPRA score above 98. Obviously for those patients, we're now down to less than 2% probability of finding a matching organ. Finally, for those patients who really have an extraordinarily high sensitization degree of 99.9 or above, there's about 3,500 patients on the wait list today in the U.S. This really is a very significant unmet medical need.
I think that for us, this is over a $1 billion market opportunity for imlifidase, as there really today are nothing approved for this category of patients. Really the available drugs out there just do not have the ability to really reduce IgG effectively rapidly enough to create a opportunity for this patient group.
Great. For those who are not familiar, they top-lined the phase III data, which is positive, and then you have a late breaker coming up at ATC meeting later this month. What should we expect to see beyond the top line disclosure last year?
Sure. Obviously this is going to be apart from the top line, which obviously was the primary endpoint of eGFR at 12 months. This will also cover obviously baseline characteristics, demographics. It'll talk about the secondary endpoint, graft survival, overall survival, and also look at DSA levels, et cetera. Safety, obviously, more safety characterization. This will be a much broader presentation of the data from the phase III.
You'll have a KOL event to contextualize the data as well, right?
Exactly. On the 25th of June, we're also hosting a capital markets day in New York and via link. We're going to have four very highly regarded KOLs who are going to be in the position of really talking about the use of imlifidase both in the phase III, how they would contextualize the data, and really put it into practice, and how this would be potentially used, if approved.
You already submitted the BLA. You have the PDUFA coming up on December 19th for accelerated approval. Can you comment on how the review process has been going and the type of questions you are getting from the FDA?
I would say that it's a very typical review process. Nothing out of the ordinary. This is really, as you would expect, focused on the clinical data that we've submitted, and requests for certain analysis, et cetera, to just understand and contextualize the data.
Are there any specific post-marketing commitments that the FDA has outlined for conversion to full approval?
At this point, obviously, this is something that we would expect to get confirmed or really get detailed towards the end of this review process. I guess our expectations would be that this might entail longer term follow-up of the patient population. This is something we'd have to wait and see what the FDA would require.
What are your expectations for the label? Could FDA potentially limit it to the scope of the phase III population, like less than 0.1% chance of finding a kidney? Could it extend to broader, maybe 98%, maybe 80%?
Right. Obviously again, label negotiations is something that we would expect to have later in the year. Obviously from a just looking at the drug and its characteristics, and the really significant unmet medical need, I think that the phase III trial really with its P value of less than 0.0001, really showed that there is really no alternatives for this patient population. What we've seen from all of the data sets that we've had so far with this drug is that these patients stay on dialysis for very long time. We also know that obviously there is a significant amount of highly sensitized patients, around 2,500 each year, that are removed from the wait list due to the fact that they've died or they become too compromised to remain on the wait list.
My view really is that by limiting this to that very small. It's a significant number of patients, it's about 3,500 patients, but yet for the FDA to basically feel like someone with 99, cPRA score of 99 would not warrant having the opportunity to have a transplant. I hope that we're going to be able to have pragmatic and constructive conversations with the FDA to really outline the benefits for a broader population than just the study population. In Europe, obviously, where the drug has been approved, the label says highly sensitized patients, and it's really up to practice of medicine by the physicians to choose who the patients are who are appropriate for this kind of therapy. What we've seen is that the vast majority of transplants in Europe have really taken place in patients who have a cPRA score of 95 and above.
There are some clearly who are all the way down to 80, but I would say the majority of patients fall into that category. I think it is our hope that we will be able to have those kind of conversations with FDA. Also, I think that you don't have safety issues that would be of more concern if you have 98 in cPRA score than 99. I think that we will see. Obviously, that conversation is to come. We feel confident about really the unmet medical need and the ability of physicians and transplant surgeons to really choose the appropriate patients for this therapy.
Just to double-click on the safety aspect, I don't think people understand that the drug is cleared out of the system. It's not a chronic drug. It's a one-time.
Yeah.
Can you elaborate on that more, why that is so important?
This obviously, really, this drug really enables, it creates a window of opportunity. Basically, it has that very rapid effect in terms of cleaving IgG in two places and really just degrading IgG very rapidly. Once that effect has taken place, really there is no, as you said, there's no consequence beyond that. It does not stay in the system. This really just means that your body will obviously continue to create IgG. This is not a B-cell modulator, so obviously the creation of IgG continues. That means that you'll have maybe a five- to seven-day window when IgG will remain low. Obviously over that period of time, the body will obviously reconstitute IgG. This really is just an ability to create that window to enable this kind of transplantation to take place or a dosing of gene therapy.
The fact that obviously your immune system, your IgG will come back, but it is to kind of just have that window of opportunity to create this possibility for this patient population who otherwise will remain on dialysis for very extended periods of time and a lot of times will never have an organ offer, despite being very high up on the actual kidney wait list.
Makes sense. Last week you had the positive EU confirmatory long-term data from the PAES study, P-A-E-S study. Do you plan to supplement the data to the FDA for potential full approval, or is the base case for accelerated approval based on the U.S. data only?
Obviously, the PAES data is not required for the approval in the U.S. Really, the requirement for accelerated approval in the U.S. is really based on the ConfIdeS study, and the phase II studies that are supportive to that study. This would not be a requirement, but obviously, regulators often ask for other data sets that they are aware of are available. Obviously, to the extent that the FDA would be interested in receiving or having selective or full PAES data, obviously we would be happy to provide that to them. It is not a basis for approval.
Switching to the commercials aspect, what is the status of the U.S. commercial readiness? Maybe talk about the CMC manufacturing, sales team build-up along that way.
Sure. Obviously we have a full leadership team in place in the U.S., and we also have now really a full field-based team, both of medical affairs as well as market access liaisons. This team is now really focusing on going out and collecting information, making sure that we have the information that is appropriate in terms of the target market or those hospitals that carry out kidney transplants in the U.S. There are about 200 centers that carry out kidney transplants in the U.S., and 100 of those centers represent about 80% of the volume. What we are now doing is really trying to map out and understand what is the structure internally in these hospitals, because these are obviously team-based kind of activities that these kind of transplantations rely on.
It's really to understand the hospitals, their logistics, their systems, their processes, their teams, so that we can be as well prepared as possible to understand exactly. There are some hospitals, obviously, that are very familiar with imlifidase, so have been part of the phase III. There are 25 of those hospitals already in the U.S. Obviously we are probably going to have different waves of clinical readiness amongst the different hospitals. We will hopefully have as much information as we can to really be able to launch the product in these various waves of hospitals where we believe that they will become clinically ready over time based on the data that we can present, based on the information that we have, et cetera. I think that's really what we're doing right now.
Obviously, the drug has already been commercially available in Europe for several years, so obviously in terms of manufacturing, we have produced many commercial batches of the product already. We have no plans to change the manufacturing setup for the U.S. Really, it's a focus on, in a compliant way, really being as prepared as we possibly can with as much information with regards to that kind of target market of 200 hospitals, as much as we possibly can.
Makes sense. One of the pushbacks that you had in Europe was challenges with the organ allocation system. What learnings from Europe inform your U.S. market access strategy, and how is the U.S. organ allocation system different from Europe?
I think one obvious point, obviously, that in the U.S. you have one centralized organ allocation system. In Europe, this is a very, very fragmented kind of system where you have regional, you have local organ allocation systems. They're not all necessarily following the same rules. It's a much more customized kind of approach that you need to have in Europe. I think in the U.S., as I said, it's kind of a one system for all of the U.S. Obviously there is a recognition in the U.S. of the fact that highly sensitized patients, they're given, let's call it additional points in terms of actually getting them a little bit higher up the list.
Because there is a recognition of the fact that because there is a low probability of a match, that you really want these patients to have as high a probability as possible to actually have an organ allocated to them. I think that that obviously is something that has already been implemented in the U.S. I think that it's great from that patient group's perspective that there is a recognition of this need. I think despite that, unfortunately what we see, obviously, is that these patients remain on the waiting list for very, very extended periods of time. Highly sensitized patients, kind of the median time on the wait list is seven years. Obviously with the knowledge of five-year survival on dialysis being about 40%-50%, this is obviously not ideal from anyone's perspective.
I think that this is one of the major benefits of having a more centralized system and a clear structure in terms of how organ allocations take place.
Perfect. You also have valuable insights from the European HTA, or the health technology assessment processes. How does that inform the U.S. budget impact and effectiveness, specifically because of the Medicare and the commercial coverage differences here?
Sure. I think that obviously in Europe, there's not an opportunity for companies to set the pricing themselves. It's really made from a negotiation on a country-by-country basis. That analysis is really a health economic analysis that's the basis for the pricing. What we've seen in Europe on the basis of that analysis that's been carried out by the various countries, average list price in Europe for the treatment is about EUR 350,000 per treatment. This obviously shows that from a kind of health economics perspective carried out in Europe, there is a recognition of the fact that this would be beneficial or neutral or beneficial to the system at that level of pricing. Obviously we have carried out a pricing research in the U.S., and that's very recently concluded.
Actually, I don't have the outcomes of that yet, but I know that it's been concluded. I think that is just really to try and again inform us and make sure that we understand how different pricing levels would be perceived both from a Medicare and from a commercial insurance perspective. I think this is obviously very important. We will announce the price at time of launch. I think, again, if we look at some of this data that we've generated, and if you look at, for example, the recent PAES data that we read out in Europe, that patient population in the imlifidase, Idefirix arm, really the average time on dialysis of those patients was eight and a half years.
If you think about that in the context of the U.S., if you just take similar numbers over here, that is becoming close to $1 million of cost in terms of dialysis. Obviously I think there is a real recognition of the fact that from the financial perspective as well, dialysis is very costly. Obviously, it has a very, very negative impact on quality of life. I think there is a real recognition of the value of imlifidase and this drug, and the benefit that the system could potentially also draw from this in terms of not having to spend that amount of money on the dialysis patients. As well as having a very significant positive impact in terms of these patients being able to go back and study, go back and work, have a much more normal life.
Makes sense. Given the majority of the U.S. kidney transplant patients fall under Medicare DRG is what it's called, and what is the exact timeline for securing a NTAP or new technology add-on payment, essentially to support the hospital economic aspects?
Yes. NTAP is obviously a system where you make an application once a year. That is in October. In order to be eligible to make that application, you need to either have an approved product or have a BLA under review. This October would be the first time that the company's able to actually apply for an NTAP, which we intend to do. I think if you look at the criteria for approval, we certainly believe that we fulfill those criteria. Basically that process takes a year. Basically, if you're eligible and approved, then basically it will take effect in a year's time. Basically in October the following year. This is obviously a process that's been used by other drugs as well. For example, the CAR-Ts also use this.
This is obviously an ability that there is a DRG code for transplantation that's established. This would be another established amount that the hospitals could benefit from. Any additional cost for the hospital would be covered through hospital outlier payments that basically the hospitals do on an everyday basis. There are things where they will provide CMS with requests for coverage of outlier payments in excess of things that are covered by other codes. That would really be the approach that we would take. As I said, this has been established by other drug categories such as the CAR-T very successfully. This is the same kind of pathway that we're planning to follow.
Got it. As you finalize the specialty pharma networks that you plan to leverage, are there any logistical friction points? Basically, how do you make sure that the drug is available within that 12 to 24-hour window from the deceased donor?
We intend to have a 3PL, logistically from a process perspective, we'd have a 3PL and then specialty pharmacies. The hospitals would then be able to acquire the drug from those specialty pharmacies. Basically what we'd expect is that the hospitals would want to have this drug available. Because obviously the issue with all of these situations in transplant is basically that you don't know when you might actually receive an organ. It could be 1:00 A.M., it could be 6:00 A.M., it could be 3:00 P.M. It could be within a week, a day. You just don't have the predictability that way. The assumption would be that this is something that the hospital would have on the shelf available once they make a decision that they want to try and actually transplant a highly sensitized patient.
This would be an actual choice that the hospital would make that choice because they would most likely have to go in and actually de-list some of the antigens of this patient in order to enable that patient to get an organ allocation to start with. Once that decision is made, we would expect the hospital to also have made the decision to have the drug available due to that lack of predictability of when an organ might be available. We're obviously also going to work throughout the time when we are approved. We'll obviously also try to work with hospitals in terms of trying to see if there is anything else that we can do or should do in order to facilitate any logistics or any of their demands from a procurement perspective.
This would technically be a buy and bill sort of thing, right?
That is what we would say.
They will buy.
Yes.
Okay. You'll be recognizing the revenues upfront. Okay. You have referenced the CAR-T launch. Having successfully used this whole NTAP and the Medicare outlier payments, so how confident are you that the transplant centers have the administrative infrastructure in place to process these claims?
Again, I think obviously looking at this as part of what I was mentioning before is obviously this is part of what we are also trying to establish in terms of having our field-based staff interacting with the hospitals and trying to establish if there is a difference in terms of that approach, for example, in hospitals.
Yeah.
I am sure that there are differences amongst these hospitals in the U.S. I'm sure there's certainly going to be some, I think, who are very comfortable and have this very well established. There may be other hospitals where there is a requirement to assist and to walk through how that process would work, et cetera. I think that is all part and parcel, again, of the preparations that we're making in order to be as well prepared as possible, to really address whatever needs that the hospital really has in order to be able to utilize imlifidase.
Makes sense.
Last month you announced EUR 115 million licensing agreement with SERB. For the European and the MENA rights to Idefirix. Just curious, why is there no consideration for royalties on sales, given that past readouts are so overwhelmingly positive?
I think that obviously We ran a competitive process.
Yeah.
I would say that there was quite a lot of interest for the platform in Europe and for the drug in Europe. Obviously, you have different structures that you can apply. We could obviously have used a different structure. I think, obviously the upfront would've been substantially smaller. I think this would probably have been much less capital upfront, and then you would've had maybe milestones, royalties, et cetera, coming over time. I think that, from our perspective, I think that we felt that this approach was really beneficial for a variety of reasons. I also think that it really values the franchise that the company's built. I think it really reflects the fact that there is a great deal of focus on really trying to maximize access to the drug for patients in Europe. I think there's a very successful reimbursement guidelines now in place.
I think with the additional resources, expertise, and focus really that SERB can bring to this product, I think that is really what we were looking for, and I think it's going to be very exciting for patients in Europe to have that kind of stronger backing of the product. I think from our perspective, this capital obviously really puts us in a position to truly have a very robust launch in the U.S. I think it also gives us a lot of optionality in terms of additional capital raising, et cetera, as we think that this is a very concentrated call point, and we think is going to be a cost-effective launch that we can have in the U.S.
Again, I think this capital brings us not only the ability to have a robust launch and do all the things we really need to do, but also it puts us on a way to potentially having a path to profitability on the basis of having access to this capital. From that perspective, I think for us, it was the best kind of structure that we felt was most appropriate for the company at this time.
Makes sense. On the competitive dynamic side, clearly, imlifidase stands out and versus the alternative standard of care. Can you talk about any other competing programs that are potentially in clinic and you're tracking besides the IVIg PLEX regimens that are used today?
Right. I would say that there's not a specific program that seems to be targeting this area. There's obviously a general focus on IgG degraders overall. There's quite a few of those. The vast majority of those programs are obviously focused on chronic dosing, not really in this acute, very specific area. Obviously, we are following the broader, all the developments in the broader category. In terms of really focusing on this, and I think importantly, what we look at here is obviously not just the highly sensitized patients and the ability to address that patient group, but also the fact that what we see in the U.S. system is that there are about 27,000 transplants done each year from deceased donors.
If you look at that as a data set, there is about 9,000 organs were harvested each year that are not actually used in transplant patients. There's a very significant amount of organs that are going unused today. If you look at the statistic you can find on this is about 60% of those are due to the fact that no match is found. I do think that this is probably a combination of long ischemic times, transport, the fact that you have a wait list and time goes by.
I think that actually if approved, I think this is another area where hopefully imlifidase can actually not only help the highly sensitized patients to get the same level of access, but also potentially really broaden the availability of organs, which I think is something that is in the interest of everybody, as we know that having a transplant is life changing and transformational. I think if imlifidase can actually contribute to the fact that we can have more patients being able to be transplant due to the fact that you can not have to be limited by it having to be an absolutely perfect match, I think that's another way where we hope that the product can actually contribute to more patients being able to benefit from a transplant.
Great. We're almost out of time, but in closing, can you also quickly run through the HNSA-5487 GBS setup and then your cash runway and milestones we should look forward in the next six months?
Sure. In terms of milestones, obviously, we're having the presentation, as you mentioned, at the ATC at the end of this month. I think that will obviously be the first time that broader set of phase III data is going to be available to the physician community. I think that's really important. I think that obviously the closing of the deal with SERB, we're looking to close that hopefully in July timeframe. That is subject to FDI review. We obviously have a filing with EMA for the conversion of conditional approval to full approval. We would look to do that in Q4. We have our Capital Markets Day, which I hope people will listen into on the 25th of June. Obviously we have a very important date coming up in Q4.
December 19th
for the PDUFA date where we hope to obviously be able to get an approval for imlifidase in the U.S. In terms of cash on a pro forma basis, as of Q1, which is the last quarter we reported, assuming that the SERB transaction were to close on a pro forma basis, we would have about $200 million of cash on the balance sheet on a pro forma basis. We believe that that will comfortably take us well into 2028. In terms of There was a third part of your question.
HNSA-5487.
There we go.
just for the GBS
HNSA-5487. Actually, we're in conversations at the moment with the FDA with regards to the design.
Design
of that clinical trial. The intent is still to start a clinical trial before the end of this year. We are still trying to work out some of the details in terms of that design with the FDA. I was hoping to be able to share that at this timeframe, but we're probably about a month away from having that final information. We're going to have to come back on that.
Thank you so much, Renée.
Thank you.