Hansa Biopharma AB (publ) (HNSA) Earnings Call Transcript & Summary

Yes. Welcome to this digital event with Hansa Biopharma. My name is Henrik Ekman. I'm equity analyst at the HC Andersen Capital. And it's a pleasure for me to introduce Lena Winstedt from Hansa Biopharma, who will take us through a presentation of the gene therapy area within Hansa. The primary focus is to get a better basic understanding for the area. And as always, the format is that we will have a presentation, and then there will be opportunity to ask questions afterwards, which you are welcome to -- the audience is welcome to put forward in the chat, and I will do my best to try and forward the question to Lena when she's done her presentation. So with that, Lena, a very warm welcome to you. And we are very excited to hear of this part of Hansa, which we are not used to hear about so much. So please take us through your presentation of the gene therapy area.

Thank you. I just want to show you or tell you that this presentation will contain some forward-looking statements. Yes. So I just want to tell you a little bit about Hansa as a company today because I think most of you see Hansa as a kidney transplantation-focused company. And it is true that we have our first drug, Idefirix or imlifidase, approved in Europe for kidney transplantation. But Hansa today is so much more. And everything we do so at this point is based on our validated technology with enzyme -- an enzyme derived from bacteria, when we talk about Idefirix, which can cleave IgG. And we do have ongoing programs in many areas for this fantastic platform molecules. If you -- I just want to show this very quickly. We have, to the upper right, we have the transplantation, which is the most advanced program for Hansa. We also have, to the upper left, all the autoimmune diseases where we see huge potential for imlifidase and the new enzyme -- IgG-cleaving enzymes we have. We're also working in oncology and with the new therapies. And here, we have the second and third-generation molecules, which we call with one common name, NiceR, better versions of imlifidase basically. But today, I will be focusing on the gene therapy area and what Hansa is able to do there. So fancy figure. So why is gene therapy so interesting? I think gene therapy as such is very much like science fiction. I've been working with this for a while now, but I still sometimes think it's science fiction. Because you can, by introducing a correct gene or a healthy gene into a living human, you can actually cure extremely severe disease. So with that said, of course, there is a significant unmet need. There are -- even though the field is pretty young, there is much data proving the concept of gene therapy both in animal but also, to some extent, in people. There is, though, a problem with gene therapy. And it is that the most commonly used technique for gene therapy uses viral vectors. It's like the capsule of the virus is used to get the gene into the human body. This comes with a problem because most people, even small children, have seen those viruses before or similar viruses, which means that the immune response has reacted and produced antibodies. And this means that some patients can't be treated with gene therapy because the antibodies make the body closed to the viral vectors. And this is where Hansa and Idefirix or imlifidase comes in. Here, we can use or IgG-cleaving enzymes to remove the antibodies and enable the gene therapy. I will show you. And this is, of course, has to be made together with various gene therapy companies. So our strategy is to partner with gene therapy companies, use our technology to enable treatment with their drug. I will show you a little bit about the technicalities. So if you look in #1 here to the left, this moon lander is actually a viral vector. And this is the capsule where you have the correct gene, a healthy gene or a piece of a gene inserted into this virus particle in this figure. You have the Ys here attached to the capsid. Those are the IgG antibodies. When they are attached to the capsule, they -- the capsule or capsid can't enter into the cell. So you infuse it into the blood vessel. The capsid searches its way to -- through the cell, but it can't enter because it's covered by the antibodies. When you use imlifidase, you can cleave off part of the antibodies, and this makes the viral vector to be able to enter the cell, get into the cell and release the gene. So this is the basic concept on how imlifidase works to enable the treatment. And this is just to show you that there are different types of viral vectors. They have different numbers: 1, 2, 5, 3, 7 and 8 and so on. And those are specific for specific organ tissues. So for example, AAV8 can enter into liver cells, and it can also enter into muscle. So if you look to the right, for example, you have the rh74 to the far right. That is a modified version of AAV8. And that is Sarepta's molecule, which we are working together with them on. It's specific for muscle. So you can sort of choose your virus to decide where you want to direct your gene therapy. And I should also say that the ones that are directed to the liver can be used for various indications. Because when you enter into the liver, you can actually have an effect in most of the body. Okay. Let's go on. So here, you can see how -- why we are concerned about antibodies in gene therapy. Those are the different vectors, and it's -- here, it's also indicated where they are directed. And if you look to, for example, AAV-rh74, the Sarepta vector, we're working with it. It says again directed against muscle tissue. And up to 20% of patients who need gene therapy have antibodies against this vector. This means there is a drug that can potentially cure this severe disease, and -- but you can't use it because you can't get it into the cells. And you can see there's a wide range of prevalence for antibodies against those different vectors. I should mention AAV2, which is a very common vector because it's easy to work with, it is easy to get the gene into the vector, but a lot of people have antibodies against it. So the concept I just showed you with removing antibodies to introduce the gene therapy into body has been proved in preclinical models. And there was a publication about a year ago how imlifidase could enable gene therapy treatment in mice and in monkeys with preformed antibodies. Let's start with the figure to the left, where we have a mouse model expression -- expressing a so-called reporter gene. It's just a gene who produces something, a dye or something that can be measured easily. And you have day 0 to 28 on the x-axis down here. And then you have the activity of the gene on the y-axis. And if you look to -- if you look down here on the black ones, black dots, you can see that if you have mice with antibodies against AAVs, those capsids, you don't get any expression of the protein. If you look at the blue one, here you have mice without antibodies, and you get quite a high expression of the reporter gene. If you have mice with antibodies but you pretreat them with IdeS or imlifidase, then you achieve as high expression of the protein as if they didn't have any antibodies. So you could actually remove the antibodies, get the viral vectors into the body of the mice, and they express the protein. The middle figure here shows exactly the same thing, but in another way and in monkeys. And these are actually monkeys with -- who lack Factor VIII, so these are hemophilic monkeys. And here, you can see you have the same effect. If you have the antibodies, the black box, you don't have any expression of Factor VIII. If you pretreat with IdeS, imlifidase, you get the expression of Factor VIII. To the right, you can see that you can remove those anti-AAV antibodies from patients as well. In the right figure, to the left is healthy subjects, healthy volunteers, and to the right is showing patients. You can see that you can significantly lower the amount of antibodies in those. So as I mentioned before, Hansa has an agreement with Sarepta Therapeutics. And the deal is that Sarepta will get access to Hansa's imlifidase for pretreatment in 2 of their -- initially, 2 of their programs in 2 different indications, and I will show you them as well. Sarepta will perform preclinical and clinical studies. They will get the regulatory approvals, and they will be responsible for promoting imlifidase together with their gene therapy product. This is all done in very close connection with quite a big team from Hansa supporting Sarepta with all our knowledge around our enzymes and, of course, yes, in terms of regulatory and what it can do and what we can show so far. And this is an extremely interesting and exciting cooperation, I must say. I think -- both companies agree that this is so exciting, and we're -- yes, we're just thrilled about it. So this is the first partnership we have, but we are also currently talking to a number of other gene therapy companies, trying to spread out our technology on various indications in the gene therapy area and also various tissue targets. And I think this will be -- imlifidase will be used for most of the gene therapy treatments to be able to reach those patients that cannot be treated today. Here is just to show the ongoing programs within gene therapy. So you have various, more or less, strange diseases, which you probably haven't heard very much about before, I hadn't before I started to work with gene therapy. But you can see that there are a lot of programs within this world, and we have the companies below the name of the disease. We are working with Duchenne muscular dystrophy and limb-girdle muscular dystrophy together with Sarepta at this point. Both those are in clinical phase with Sarepta, although just in patients without antibodies so far. So I will tell you a little bit about those diseases. Duchenne muscular dystrophy, it's a rare fatal neuromuscular disease. It's inherited with -- it's just 1 mutation in 1 gene, but that can be located at different places within that gene. It gives, however, muscle weakness. And this is diagnosed in children, usually between the age of 3 and 5, and most patients will have to use a wheelchair at the age of 11. They get cardiac and respiratory muscle deterioration, which eventually becomes life-threatening. And the prevalence is 1 of about 3,000 to 5,000 male births. So it's not that uncommon. And yes, it says here, from Sarepta's ongoing study, that about 15% of the patients have preexisting antibodies, yes. And Sarepta now has treated 77 Duchenne patients in clinical trials. And they have been able to show that the protein which is lacking, the dystrophin, the gene therapy protein product has a stable expression in up to 3 years. So the patients that were treated earliest has a 3-year follow-up now. And you can also see that they improve in their functionality, muscular functionality, of course. Then we have the limb-girdle, which is also part of the Sarepta deal. And limb-girdle muscular dystrophy, it's also about muscle weakness. It's also caused by defect in a gene. And there are several types of muscular dystrophy, depending on where the mutation is. And the global prevalence is about -- it says 1.63 per 100,000 individuals. And the same here, we're using the same vector for this program, so the prevalence of preexisting antibodies in the patient population is about 15%. There is an ongoing study right now in limb-girdle with Sarepta, with Sarepta's product only, and they have 1- and 2-year follow-up periods for those patients. It shows a good safety profile and a robust expression of the gene therapy product. Also, those patients show improved muscular functionality. Yes, I think that was all from me.

Very good. Thank you so much, Lena. That was very interesting. And as you put it yourself, it's almost like science fiction. And I can't help, just on the first note, to think that, throughout the presentation, there are phrases like it may have relevance, that idea is and you're exploring the opportunities and so on. So just to better understand, to what extent is this just a conceptual good idea? Or how real is this?

Yes. Actually, we can -- see if I can -- so if you look at this publication in emerging medicine, this is very -- I mean those are clear data. You can show that you can remove -- you can show, for example, here in the mice, I think this figure is very clear. You can show, if you have antibodies, you can't make the gene therapy work. If you remove the antibodies with imlifidase, it works as well as in the body of mouse. Also, if you look at the monkeys, but also in patients, it's very clear that you can remove the antibodies. So this is not -- I mean, for me, as a scientist, this is very clear. The concept is working. What we haven't done so far is, of course, we haven't pretreated a patient and looked at gene expression over time. That's the next step. But I can't see any reason why that wouldn't work. Of course, it will work. It's just a matter of being patient.

Because I think the reduction in antibodies as -- if we take the parallel, as IdeS is trying to manage kidney transplantation, there is a huge reduction. So is gene therapy within -- used by -- in connection with gene therapy, is the reduction level, does that need to be at a certain level, sort of 100%? Or is it just as it -- reduces a little, it's actually working? How is that working?

Yes. Actually, when you do experiments in monkeys, imlifidase is not very efficient in monkeys. You can only remove some of the antibodies. But still, you have a very good effect. So the answer is probably, you only have to remove some of the antibodies to achieve an effect. However, imlifidase is very efficient. And -- I mean we've tried various IgG antibodies. And if you look at the total IgG amount in antibody and efficacy almost removes everything. So this is not an issue for efficiency. Or it will remove enough antibodies to enable the gene therapy, I'm convinced.

There is a question here from the audience. If you will test for AAVs in patient then, what is your comment on that?

Is that the AAV antibodies? Or -- I think that's the question.

I think that is what is meant, yes.

Yes, so if this experiment will be repeated in patients, I think that's the question. Yes. Yes, she says. Yes, we will. So this is what we are working together with Sarepta. We're now in a preclinical stage aiming for going into the clinic with this product, yes.

And there is a follow-up question from the audience as well regarding the potential competing molecule from Genovis. Can you comment on that? Or are you familiar with...

We -- well, I think -- it should probably be Genovis, yes? It's -- yes, so we are aware of that. But we are very confident with our IP situation. That's the only thing I...

Okay. Yes. Regarding the deal with Sarepta, now they are very keen to use IdeS to give better gene therapy. But how is the deal structured in terms of if -- if it doesn't work -- if it works to reduce from your product, but the gene therapy doesn't work, does that mean that you won't get paid? Or how -- do you know how the deal is structured in that way?

Yes. Well, of course, the gene therapy has to be approved. Because if the gene therapy is not approved, if it doesn't work, it will not get approved, of course. And then you don't have a product which you would like to enable the treatment also in antibody-positive patients. However, Sarepta is the most advanced company within Duchenne's muscular dystrophy, and it just very recently disclosed good results from the 3-year follow-up. I mentioned it very briefly. And you can see improvement, you can see stable expression of the gene product, the microdystrophin. And you could also see how that affects those boys with improvement in muscular functionality. And also limb-girdle, I would say it's a bit earlier, but it looks at least as promising as Duchenne, so it seems to be very effective.

And of course, you have -- as said here, it's an exclusivity agreement with Sarepta regarding these 2 indications. But that -- just to be clear, so you can do all sorts of deals with other partners? It doesn't have to be Sarepta and other indications? You're free to do that?

Yes. So all other indications are free for other partners until we close a new deal, of course.

Yes. There is this -- and also on the slide, you mentioned this potential milestones of up to USD 400 million. Can you elaborate a little bit about what's sort of the time frame? Or what should we expect in terms of -- because you got an upfront payment of $10 million. But what is the likely potential time frame for this additional USD 400 million?

Yes. I can speak in more general terms because we haven't disclosed any time lines for this development, but you would normally expect that you have a preclinical phase of some time depending on how far -- now it's a bit special situation with the 2 products. One is approved in Europe. The other one is not approved. But you would, when you combine 2 products, still want to do some preclinical work before applying for a clinical trial. And then that will take some time to get it approved to start and perhaps also to be agreed with regulatory authorities, that this would be something that they would like to see. You can always push through a clinical study, but you want to make it good for approval of the combination. And that could take like 6 to 12 months. And then you can start a clinical study, which may take -- depending on what you want to see, but -- about a year maybe. Maybe you can do a readout earlier to see protein expression, but then you want to follow the patients and so on. So very difficult. But I wouldn't give any specific time lines for that at this time.

But it's -- the time is running here. So perhaps it's -- you're already touching upon what must be the last question here from the audience regarding the likely news flow and time line for this typical -- different data from different clinical phases. So -- and you already touched upon that. You said something about within 12 to 18 months will we see the first results? Or what was it?

I wouldn't say.

No. Okay. So we -- but we -- everybody will, of course, be looking forward to follow the news flow regarding these studies and the gene therapy in general. Lena Winstedt, thank you very much. It's been very interesting to hear about the area. Thank you for this time.

Thank you.

Thank you.