Good afternoon, everybody, and welcome to this special event with Hansa Biopharma. With me today, I have the Global Franchise Lead, Autoimmune Diseases, Elisabeth Sonesson. Just a couple of practical issues before we start the event. If you want to pose some questions, please do it just under the video screen, and I will forward them to Elisabeth during the presentation. The presentation today is a deep dive into autoimmune diseases. With that said, I would like to welcome Elisabeth. Welcome, Elisabeth.
Thank you, Claus. Thank you very much. Good afternoon, everyone. Thank you a lot for providing the opportunity for us to present at this event. I'm happy to represent Hansa Biopharma. As Claus said, my name is Elisabeth, and I work as a global franchise lead for the autoimmune indications at Hansa.
Just before-
And before-
Sorry, Elisabeth, just before we start-
Yes.
could you give us a very briefly introduction to Elisabeth.
To myself?
Yeah, to yourself.
Yes, of course. You're interested in me, too. Okay, I'm... I have a background within clinical development, biotech companies, some larger pharmaceutical industry, working in the industry since approximately 2,000. Prior to that, I have a PhD in Microbiology. You can say I've been in research with heart and soul for a long time, and now, in this position, I'm trying to move towards more commercial development of our products.
Thanks a lot.
Thank you. Before moving into the presentation, I just have to show you this quickly, the forward-looking statements that we have in the presentation. Hansa Biopharma, then. We're a commercial stage biopharmaceutical company, and we're based in Lund, in Southern Sweden, where we have our head office, but we have operations throughout other countries in Europe, and also in the U.S., where we just recently opened our first office, actually, on the East Coast. Our main product then, or our only product, is Idefirix, where we have gained conditional approval with EMA for desensitization of highly sensitized kidney transplant patients. And our technology that we have within the company has been validated across three different areas. Firstly, what I just mentioned, through the conditional approval with EMA.
Secondly, through our positive data that we presented last autumn in the American Journal of Nephrology, sorry, where we presented the outcome of a phase II trial in anti-GBM. Thirdly, it's been validated through our collaborations within gene therapy with Sarepta, AskBio, and most recently, Genethon. Over the last years, Hansa has grown immensely, and we're now over 160 employees. We have, I would say, it's a highly competent team of colleagues with an average experience within the life science business of over 20 years. Moving to the next slide, the backbone of Hansa consists of our enzyme, imlifidase. This is a unique enzyme that specifically cleaves all subtypes of human IgG.
It's derived from a bacteria, Streptococcus pyogenes, which is a human pathogen that causes tonsillitis, that is halsfluss in Swedish. It exerts its mode of action by cleaving human IgG into two parts. Those two fragments that are created cannot anymore activate the immune system, so that's the key specificity of the enzyme. If you look to the right in the slide, you will see that after only a 15-minute infusion of imlifidase, we will lower the IgG in circulation to below detection limits within hours after the infusion. The IgG levels remains at this very low level for up to seven days before the level of IgG again starts to increase. The enzyme will deactivate IgG, both in circulation or, and IgG that is bound to its antigen.
It's this IgG-free window that creates the opportunity that we see, both within desensitization and prior to transplantation, but also within acute autoimmune diseases, which I'll show you later on. I can just mention also in this slide that this is, as I said, a very fast and efficient mode of action, and experts in the field have actually compared one dose of imlifidase that can be given in 15 minutes, and compared that to five consecutive rounds of plasma exchange, and that would take somewhere around five to 10 days to achieve. Very fast and very efficient, and very much easier to do than plasma exchange, obviously. As I already said, we have a broad clinical pipeline across several indications.
At the top of this slide you can see the two phase III trials that we have ongoing within the kidney transplantation franchise. The first one is a post-approval efficacy study, where we have to complete that study in order to turn the conditional approval into a full approval with EMA. The second study is what we call ConfIdeS, which is the pivotal study that we run in the US. This study is currently enrolling patients, and the aim is to have it fully completely enrolled by the end of this year, and to subsequently submit the BLA during next year. We jump to the bottom of the picture, you will see our various programs within gene therapy, where we have already announced that we will enter clinical stage with Sarepta.
my guess is that Genethon will not be very much late after, because there it's also well-advanced plans to start in the clinical studies. In the middle you will see three projects then within the auto alloimmune franchise, which is the anti-GBM study, which is just embarking into phase III, AMR and GBS, and I'll come back to all of those three later on in my presentation. This point I can just mention that for anti-GBM, we're super happy because this morning we announced that we had the first patient in this important trial, and it was actually two patients in, so we have only 48 to go there. I'll talk more about that trial later on. This is then the platform that we're working with at Hansa.
You can see that we are divided into four franchises: transplantation, autoimmune diseases, something called new therapies, including oncology and gene therapy. This is to maximize the potential to develop our platform within all those fields without internal competition. It's a way to maximizing the potential of our technology. We have in the middle of the circle you see the backbone of Hansa, imlifidase. The circles around it represents how we try to grow that platform, because as I said, imlifidase is a bacterial protein with the limitations that we can only provide a single dose or two doses within a very short timeframe, which in turn limits us in relation to which indications are suitable to develop imlifidase within.
What we're doing is that we're looking both at combination therapies, where we can add on other molecules, to have a longer effect that imlifidase kickstarts. We've done that, for example, in our collaboration with argenx, by combining imlifidase with their FcRn inhibitor called efgartigimod. We also have the outermost circle there, the projects where we develop our second generation and third generation molecules that are version of the enzyme that aims towards a potential multiple dosing by decreasing the immunogenicity, the intrinsic immunogenicity of the molecule. That would then enable us to work beyond the indications that we are limited with imlifidase.
Let me see. With that, we'll move into autoimmunity. What is autoimmunity? Well, it is when your immune system cannot distinguish between self and foreign, and by mistake, the immune system attacks your own structures and cells, which will lead to destruction of those cells eventually. The reasons behind autoimmune diseases can vary. It can be genetic disposition, or it can be external factors, like, for example, a virus infection or a bacterial infection that causes this. In general, approximately 3%-5% of the population will, on a yearly basis, come down with some type of autoimmune disease. It's more common in women than in men, so 75% in women and 25% of the autoimmune diseases are in men.
You can see that there's a whole large variety of different types of autoimmune diseases, most of them, I would say, are chronic, and thus not suitable for imlifidase development. There are also a lot of acute monophasic diseases that are a good fit for imlifidase. We'll narrow it down to talk about those indications. I can also say to this slide that, as you see, autoimmune diseases can be in all different parts of your body, ranging from lungs, brain, to kidney, GI tract, and so on, and skin. This is a number of indications that could be suitable for imlifidase development. The things that we look for to be a good match is that it should obviously be an autoimmune disease that is driven by IgG molecules.
As I said, it should be acute and monophasic in order to make sense to develop with a single-dose molecule. There are several of those out there. One very good model indication is anti-GBM, which I told you about just before, and I will talk some more detail about and describing that indication moving on now. Anti-GBM, it's also called anti-glomerular basement membrane disease. It's an ultra rare, even, acute autoimmune disease. It's approximately 1.5 person in a million that is affected by this disease on a yearly basis. It's extremely severe in the sense that only one-third of the patients that come down with anti-GBM will have functioning kidney a half year later. Two-thirds will not.
Even a certain percentage of the patients will eventually die, because what happens is that these pathological antibodies, they bind to a certain structure in the kidneys called the glomerular basement membrane, and these structures are also present in the lung, and if it also attacks the lung, it will give rise to bleeding and high mortality rate. It's very severe and very important that the disease is diagnosed early on, and that any treatment is initiated early on then. Last year, there was a publication showing the positive outcome of a phase II trial in anti-GBM with imlifidase. Here, 15 patients were given imlifidase on top of standard of care, and the patients that were included in the study were those with the worst prognosis.
It wasn't any anti-GBM patient; it was the ones that were deemed to do really badly in their disease. At the end of the study, at six months out, it was 2/3 of the patients that had functioning kidneys, and that should be compared to a similar cohort of historical control patients with the same bad prognosis, where only 18% of the patients had functioning kidneys at 6 months. We were extremely encouraged by these results, and this was an investigator-initiated trial that was done by Professor Mårten Segelmark. As we were really intrigued by the results, we decided to move on to a phase III study, and that is the study that I referred to before that actually just included the first two patients.
This is a study where 50 patients will be randomized to receive either standard of care or standard of care, plus Imlifidase. They're randomized 1 :1 to this. Will be 25 patients in each arm.
[Foreign Language]
We will... In this trial, we will evaluate the kidney function at sitwo months in 2 ways. We will both look at the kidney function in, by measuring the filtration rate of the kidney, but also in a more simple way, to say whether or not the patient is dependent on dialysis at six months. That's our primary endpoint. A secondary endpoint, we will also evaluate lung function. As you know, the antibodies also attack the lung, and other secondary parameters of interest in this patient population. Looking to the right in the slide, you will see a graph that depicts how we think that imlifidase works in this disease.
You will see the purple line, the horizontal line, that's a level that is called the toxic level of the pathological antibody, and this is a very low level, and any concentration above that will be called toxic. That means that this is when the antibody starts to harm the organ, whether it's kidney or lung or both. At a certain time, the patient is diagnosed, and you initiate the treatment, and the blue line then depicts what happen after plasma exchange. As you see, it's a bumpy road downwards, whereas if you give imlifidase, the IgGs will go down to essentially zero immediately and stay there for a certain number of days. As I said, this is an acute and monophasic disease.
We believe that this very fast, efficient removal of all antibodies, including the dangerous antibodies in this case, will have a good impact on the prognosis for the patients. With that said, any returning antibodies will, of course, be removed by plasma exchange here later on in the disease progress. The phase III study we are doing is built on to show that this fast and efficient reduction in anti-GBM antibodies will translate into a clinically meaningful outcome for the patients. That takes me into the second indication within the franchise, and that's a completely different indication. It's a neurological disorder called Guillain-Barré syndrome. It's also an aggressive and acute and monophasic autoimmune disease, but here, it's the peripheral nervous system that is attacked. It usually starts by an infection.
It could be Campylobacter jejuni infection or a virus infection. A few weeks later, antibodies are produced. These antibodies, by mistake, cross-react with structures in the peripheral nerves and give rise to nerve damage. The symptoms then is that you get a symmetrically spreading paralysis of the extremities, starting in arms and legs, and it spreads throughout the body. It can be very severe in case that it reaches the respiratory muscles, so you end up in a ventilator. Quite a large, a third approximately of the patients will need ventilation at some point during this disease, very dangerous disease.
Approximately, as much as 80% of the persons will be ambulatory for periods, and many patients have lingering symptoms, including pain, fatigue, depression, and so on, that makes everyday life difficult, even long after the disease has healed as such. We're performing a phase II single arm study in this indication, where we take severe GBS patients, treat them with imlifidase on top of standard of care, and we evaluate safety and also efficacy parameters in this single arm setting. We announced that the enrollment was completed in March this year. Now, the patients will continue within the study until later this autumn, and we will work towards having some top-line data to present at the end of the year.
It's worth to remember that this is a single arm study. When it comes to efficacy parameters, we are going to compare ourselves to an external cohort receiving only standard of care, where we can compare the efficacy to a matched cohort of patients, and that will happen during 2024. That brings me to the last slide and also the last indication in the franchise, and this is where we go from autoimmunity to alloimmunity. Alloimmunity is also an unwanted immunological attack towards tissue in your body. The difference is that in this case, it's not your own tissue, it's a transplanted organ, in this case, a kidney.
AMR stands for antibody-mediated rejection, and we are running a phase II trial, as a randomized trial, where patients receive either plasma exchange and standard of care, in addition to that, imlifidase, or only standard of care. It's designed to show that the DSAs, which is the donor-specific antibodies, are removed better with imlifidase compared to plasma exchange. We communicated that towards the end of last year, that we met the primary endpoint, showing that imlifidase significantly better removed the donor-specific antibodies compared to plasma exchange. Now, AMR is an indication where there are no approved medications so far. The treatment guidelines that are followed is built on quite low evidence.
There are some ingredients that must be there, and that is that there's a strive towards stopping tissue damage, and also striving towards removing donor-specific antibodies that will cause this damage to the tissue as soon as possible. That's where we see the opportunity for imlifidase. Right now, the team is working then on putting the data together, analyzing the data, and putting that into a report, and the target is to make the full data available towards the end of this year, the second half of this year. With that, I think that's all from me, so I'm happy to take any questions.
Thanks a lot, Elisabeth. Thank you a lot for running us through the autoimmune program. There's one question here, and for the audience, please post your questions, and I will pass them on to Elisabeth. There's a question here about imlifidase. As it is of today, you can give it once to acute patients, but you're not allowed to give it to chronic patients, and that's probably because you have to repeat it. Do you solve this problem with the NiceR platform?
Well, that's the whole goal with the NiceR program.
Yes
... but we don't know that until we have evaluated it. I think there will always be a challenge to give repeat dosing with bacterial enzymes, but there are ways around it. There's also other ways than the NiceR platform, as I said, with combining with other modalities that also reduce IgG or that modulates the immune system in any way.
Wow.
That would. There's also another thing to that question is that also within chronic autoimmune diseases, for instance, there's episodes in the disease where patients may favor from an acute treatment. There are flares, and there's acute worsening in several indications. That might be also within chronic indications, opportunities for an acute treatment.
Okay. Like, one thing is imlifidase, which is, of course, as you've mentioned in the beginning, you have a lot of possibilities to broaden the scope of treatment, with next generation, so on and so forth. Why have you chosen anti-GBM, GBS, and AMR as the primary interest right now? Could you elaborate a little on that, please?
Yes. As I mentioned before, the most important thing is that the indication matches the mode of action. We need to know that it's driven by pathological IgG antibodies. We need to know that it's a monophasic disease, that it's not as opposed to chronic. We also need to know that there is a large unmet medical need, so that there is a point of doing the clinical development. Those indications that we have started with are the ones that best match those criteria, and that's the, gives us the best probability of success.
Of course, that's, that makes sense. Well, it's fair to say you're focused on rare diseases. If you compare that to, you know, to a normal life science company, and you look into the different phases from EMA or from FDA, why do you have to test out your products or projects on a smaller cohort of patients compared to a normal life science companies? Could you tell the audience a little about that?
Um-
Do you understand the question?
I think I understand your question. It's not that if you do clinical development in a disease that does not affect a lot of people, you can do smaller clinical studies. That's not a rule because the regulators, of course, wants to know that it's safe, first of all, in this patient population, and that they want to know that the patient population has a benefit. Depending on what the regulatory demand is to have an effect on in terms of endpoints...
Mm
... that is what sets the size of the clinical study. We're fortunate in, for example, anti-GBM, it's a relatively small phase III, you know, 25 + 25.
Mm.
That is possible for two reasons. One reason is that we see such a dramatic effect with the imlifidase. You know, we saw 18% recovered kidney function in the historical control versus 67% in the imlifidase-treated patients. That's a great difference.
Mm.
That enables us to make a smaller study, but also that the regulator has approved that we measure kidney function, which is a much easier endpoint as compared to, for instance, when you do more cardiac studies, where you have to look at how many live and how many die at the end of the study. You have to do much larger studies to reach an event that is more not occurring so often, as we do. We measure just function and see a difference in function.
Mm.
That's, in a statistical way, much easier to show in a smaller population.
Is it difficult to find these patients, though? As you mentioned in your presentation, we talk about very small numbers.
Mm.
Even if you look at, I could imagine it doesn't matter whether it's an American, an European, or an Asian or African people, it's more or less prevalent in all types of populations, but with a very low, with a very low target group.
Exactly. That's a major challenge, of course, because if you work with chronic rare diseases, you work closely with patient organizations, with patients' families, et cetera, and can identify patients in advance and, you know, work with them. In our case, it's you can't know in advance when the next patient or where the next patient will come. What we do is to ensure that we have hospitals with large catchment areas activated to include any patient that turns up in this large, so millions of people, essentially, in the catchment area. You can also work through hospital networks so that surrounding hospitals refer any patients that turns up to the central hospital where the study is ongoing.
It's very much being sure to retain all possible patients in a certain area where you have the study ongoing.
Thanks a lot. There's a question, what is the expected regulatory path forward with AMR?
Oh, that's a very good question. Historically, the regulators have been what I talked about before regarding endpoints, regulators for AMR studies, that's probably why there are no existing approved drugs out there right now. They would need studies that show beneficial in terms of graft survival. That means that you would probably need to do very extensive studies, not only extensive in number of patients, but also in time, how long you follow up patients to be enabled to see a difference between the two arms on such a hard endpoint. The other thing is that the disease as such. There is still very, it's not very precise diagnosis.
There's several types of AMRs, so the risk is that you end up with a trial with patients that vary too much in their baseline characteristics, so it's hard to evaluate. The regulatory pathway in AMR is not an easy one, and it will for sure need close dialog with the regulators, and we're not there yet, so I can't speak firmly for this.
Of course. Thanks a lot for your great input. If we get back to your slide on the superiority with Idefirix compared to today's treatment, and today's treatment is only valid in anti-GBM and GBS, as I understood your presentation. There's no treatment for AMR as of today.
Yeah, there are no approved treatments in AMR.
Approved
... of treatments, yes. Mm.
Okay, sorry. Do you see superiority, both in terms of clinical and commercial perspectives when it comes to imlifidase, and plasma treatment?
A clinical superiority is something you show in a phase III trial. We have not completed yet a phase III trial.
No.
I can't. The studies are designed to be able to show clinical superiority compared to standard of care. Obviously, if the benefit for the patient is also matched, you know, with. I'm not a health economic specialist, but there also has to be a risk-benefit in terms of that Idefirix costs more, but it also saves more lives in the end. Yes, if it. I'm not sure I understand the question completely.
No, that's fair enough. I will repeat it then because. When you look into your graph, and of course, you don't have your phase III study released yet, if we look into the graph you've shown on the PowerPoint there, you see a big difference between plasma treatment and imlifidase treatment. If you derive anything from that, and of course, it's early days and it's speculations, you see an improvement in that clinical trial. Is that also, when it comes to commercial perspective, is it actually commercial viable or bring to the market?
You're talking about AMR specifically and this graph? Yes.
Yes.
What this graph shows is the effect on donor-specific antibodies. It doesn't show the effect on kidney function, which is what we would have to show in a phase III trial.
Okay.
I don't know. There's an echo here, but...
Do you have an echo on your side? I don't have an echo.
Yeah, yeah.
I can try. When I ask a question, I mute, so we don't have the echo thing.
Thank you.
Yes. Well, let's carry on. Let's see if there's other questions coming in here. Yeah, there's a more top-down question here about prioritization. How do you, from a financial and scientific staff resource, prioritize the different projects? Could you elaborate a little on that? Are you
Yeah, yeah
... looking at the market size, or, you know, are you, are you looking into the rare disease, or how do you prioritize?
I would say that Can you please mute? It's still an echo here.
Yeah, of course. I'm mute.
Thank you. It's a multidimensional prioritization, obviously market size is one of them. I would think that for being a small company in the rare disease area, time to regulatory approval is a very important factor, a quicker approval pathway is very much favored. Also, feasibility in terms of a phase III trial, that we can actually think that we can do this with the resourcing we have and the competencies we have in the company. Looking at probability of success from many angles, not only the size of the market, but that's only one piece of the puzzle, I would say, obviously, biological rationale is the number one.
Again, an unmet medical need.
Thanks a lot, Elisabeth. If we could dive a little into the regulatory bodies, and if you focus on autoimmune diseases, both in FDA and EMA, do they have the right competencies in place? This is a fairly new market, that's fair to say, and how do you see that, and the infrastructure-
Mm
... and those challenges working with the products like you do?
Yeah. great question. It's I think our experience so far is that the regulators are very, if we take anti-GBM as an example, that they are, you know, they encourage us to develop a treatment for these patients that have so few options. They're very it's a collaborative interaction, I would say. Obviously, they cannot be expert in a disease, like so small as this one, so they have to, but they are competent people, they're knowledgeable people, so they make themselves experts, I would say, to have a meaningful dialogue with us. We have to I think we have had more challenges from my experience, not in the disease-specific discussions, but more in understanding imlifidase in the context of the disease, because it's so special mode of action.
It has so many implications that you have to educate the regulators again, and again, and again about the molecule as such.
actually, Idefirix, the approval of Idefirix is, this is paving the way for you in other indications?
Yeah, you can say so. Absolutely. EMA obviously have already given us conditional approval, and they are well aware of the molecule and our other programs, obviously. Yes. With FDA, we've also had, for many years, a dialogue, so they're also becoming more and more familiar with the Idefirix. Yes.
Thanks a lot. Let's, please post your questions if you have any. There's one more coming here. At what rate do you expect to recruit centers the anti-GBM study?
In what way do we expect to recruit centers in the anti-GBM study?
In what rate do you expect.
Rate.
Yeah, sorry.
Rate, well, the centers, it's essential for a study that will recruit 50 patients like this one, to have the centers up and running as soon as possible. Obviously, what you do is you have to await approval to start the study from the respective regulators, and after that, you work with getting the hospitals up and running. Not until they are up and running and have study drug at sites, they can start to recruit patients. We can- as I alluded to before, if the question also refers to the rate of including patients in the study, that is something that we can have no control over, other than ensuring that the hospital's catchment areas are large enough to, by probability, have patients in the time period where it's open for recruitment to come in to give the 50 patients.
Also, I would say the phase II publication was great in the way that it paved path for higher interest for the disease as such, and showing the impact of imlifidase, so that makes it easier to get hospitals interested and doctors aware.
Thanks a lot, Elisabeth. There's a question here about pricing, and it's fair if you don't want to answer it, but I ask it anyway.
Yes.
It's always sensitive. Do you see that the different indications you have, that imlifidase will be priced more or less the same?
I would love to have a colleague from my market access division here, but I don't. I prefer not to respond to that because I'm not an expert, I'm afraid, but it's obviously something that we're working closely on. I can also say that the goal is to have the same pricing, but we don't know until we have negotiated with the various bodies for that.
Thanks a lot. If there's any more questions, please post your questions. Otherwise, I could ask a small question. Goes more on Idefirix as it's approved in Europe, and you see more and more countries sign up. You have the four largest markets already, I know. Have you seen any kind of off-label use of imlifidase for other indications?
Yes. Off-label use is nothing I can talk about in detail because we're not allowed to promote off-label use, as you know. Obviously, when the, like a publication, again, like the publication on GBM increases the interest for the compound, and obviously, that will lead physician to do what they can. If they're not part of a clinical study, off-label use is the only option to get hold of imlifidase. Yes, we can see an increased interest.
Thanks a lot. That's interesting in a longer term perspective, for sure, so you broaden out your scope. I don't think there's any more questions so far, Elisabeth. It's been a very good run-through of other treatments with the imlifidase. By that said, I would, first of all, thank you all for the great questions. I'd like to thank you.
Thank you.
With that said, have a very nice day, and thanks a lot, Elisabeth, for participating here.
Thank you, Claus, for giving me the opportunity.