Ladies and gentlemen, welcome to the Hansa Biopharma AB investor presentation. For the first part of this call, all participants will be in a listen-only mode, and afterwards there will be a question and answer session. This call is being recorded. I'll now hand the word over to CEO Søren Tulstrup. Please begin.
Thank you, operator g ood morning, and welcome to the Hansa Biopharma conference call on the partnership agreement in gene therapy with Sarepta Therapeutics announced earlier today. I'm Søren Tulstrup, CEO of Hansa Biopharma. With me today, I have our Chief Scientific Officer and Chief Operating Officer, Christian Kjellman, and Chief Financial Officer, Donato Spota, as well as our Head of Investor Relations, Klaus Sindahl.
Our presentation should take about 10 to 15 minutes, and after that we'll take your questions. Now please turn to slide two. Please allow me to draw your attention to our forward-looking statement, which applies to this presentation. Please turn to slide three. On today's call, we'll go through the scope of the Hansa-Sarepta partnership, and we'll discuss the issues with neutralizing antibodies in gene therapy.
Further, we will review the highlights from our recent article in Nature Medicine on preclinical results from studies for Imlifidase as pretreatment for neutralizing antibodies against AAV vectors used for gene therapy. We'll then proceed to outline the structure of the partnership and the associated economics. Finally, we'll discuss the gene therapy opportunity in Duchenne and Limb-Girdle diseases before opening up for Q&As. Please turn to slide four.
This morning, Hansa Biopharma and Sarepta Therapeutics announced that the two companies have entered into an agreement for the development and commercialization of Imlifidase as pretreatment prior to the administration of gene therapy in two selected indications. This is the first partnership in gene therapy for Hansa Biopharma and serves as a landmark milestone as we expand our enzyme technology platform beyond transplantation and acute autoimmune diseases.
The announcement of the collaboration with Sarepta follows on the heels of the positive opinion adopted by the CHMP of the European Medicines Agency just last week on Imlifidase for kidney transplant in Europe, and further underpins the unique features of Imlifidase as a potential pretreatment for patients with neutralizing antibodies to adeno-associated virus. The structure of the partnership is intended to leverage the two companies' key competencies in their respective fields.
Hansa will provide Sarepta with access to our immunomodulatory enzyme technology and our know-how and strong experience in developing antibody-cleaving enzymes, as well as a drug product. Sarepta will utilize their cutting-edge science and market leadership within gene therapy for neuromuscular diseases and experience with neutralizing antibody-positive patients to develop, obtain regulatory approval for, and eventually promote Imlifidase to the market as a pretreatment ahead of their gene therapies.
The scope of the agreement with Sarepta Therapeutics specifically includes an indication exclusive license for Sarepta to develop and promote Imlifidase globally as a pretreatment in two gene therapy indications, namely Duchenne Muscular Dystrophy and Limb-Girdle muscular dystrophy.
The collaboration with Sarepta provides Hansa with significant potential economics through incremental Imlifidase sales, but also a participation in the incremental value unlocked in gene therapy through the upfront and potential milestone payments, as well as royalties on any gene therapy sales enabled by pretreatment with Imlifidase in NAb-positive patients.
In conclusion, we're very excited about this partnership with Sarepta, which represents a significant step into the gene therapy space for Hansa Biopharma, and we look forward to engaging in collaborative efforts to enable a broader range of patients to get access to breakthrough gene therapy. For this, I will hand over to Christian to go through the medical aspects of Imlifidase in the context of gene therapy. Christian, please.
Thank you, Søren. Please turn to slide five. This is a fantastic opportunity for us n ow we start to talk a little bit about the neutralizing antibodies. Neutralizing antibodies or NAb, as you can also call them, they are a significant barrier in gene therapy because these antibodies prevent the effective transfer of the gene therapy vector to the target cell.
In gene therapy, it's estimated that between 5% to 70%, up to 70% of patients have antibodies to different types of AAV vectors that is used. The vectors that we are talking about here in this collaboration, there is about 15% to 20% of the patients that have these neutralizing antibodies. Patients that have these neutralizing antibodies, the consequence is that they are excluded from clinical studies, and they may be excluded from future gene therapy treatment.
It's our hypothesis at Hansa that Imlifidase, with its unique IgG-cleaving activity, have the potential to eliminate these neutralizing antibodies, and that it can be used as a pretreatment prior to gene therapy. In that way, Imlifidase can enable gene therapy in this group of patients that are excluded from the therapy. This is illustrated in slide five, as you can see.
So far, Hansa has conducted four phase 2 studies in kidney transplantation with Imlifidase. We have demonstrated good safety profile and very strong efficacy data w e have met all the primary and secondary endpoints in our clinical study. As we announced just a few days ago, this has led the CHMP of the European Medicines Agency to adopt a positive opinion for a market approval of Imlifidase in kidney transplantation in Europe.
To go back a little bit to Imlifidase is a highly effective enzyme. It has a very rapid onset, a very rapid and effective action, and it's highly specific towards IgG. In fact, we have demonstrated that Imlifidase can inactivate IgG in less than two hours after infusion in patients. Already two hours after infusion, the antibody levels are below detectable level. Please turn to slide six.
Imlifidase or IdeS was recently published by Leborgne et al. in Nature Medicine, a very high-ranked medical journal. They demonstrated or tested Imlifidase in three preclinical models in the context of gene therapy. The outcome of all these studies is very encouraging to us. What they did was that they tested Imlifidase in one hemophilia mouse model. They tested it in a non-human primate as a treatment, Imlifidase ahead of gene therapy treatment.
They also tested the effect of Imlifidase on antibodies to AAV vectors in human plasma in vitro. This preclinical evaluation looks very good t he data looks very good and very promising. To the left here, you can see the data from a mouse model. This is a model where they passively transferred. What they did was that they injected human gamma globulin because human gamma globulin contains these naturally occurring antibodies to this immune therapy vector.
What they could demonstrate was that the presence of these antibodies, there were no or very little transfection of the gene therapy vectors b ut if the mice were pretreated with IdeS Imlifidase, there was a very efficient liver gene transfer of the vector.
From that, they moved on to non-human primates. Non-human primates have naturally occurring antibodies to AAV similar to humans. They tested Imlifidase as a treatment ahead of the gene therapy. They could demonstrate that Imlifidase enhanced the liver transduction of the gene vector, and they could also see that it resulted in expression of Factor H, which was the gene that they transferred in this model. Very positive data.
To the right, you can see that they moved on to testing the activity of Imlifidase to reduce the level of anti-AAV antibodies. They tested it in healthy donors. They also showed that they could reduce the levels and activity of the antibodies in patients with a genetic disease i n this case, it was Crigler-Najjar syndrome. They concluded that Imlifidase provide a potential solution to overcome the problem with the preexisting antibodies to AAV-based gene therapy. With this, I'd like to hand over to Donato to take you through the structure and financials of the new collaboration. Donato, please.
Thank you, Christian. Please turn to slide seven. As highlighted by Søren earlier, this is the first partnership in gene therapy for Hansa Biopharma and serves as a landmark milestone for the company as we expand our enzyme technology beyond transplantation and autoimmune diseases.
This is really a unique opportunity for both companies to combine efforts and use Hansa's antibody-cleaving enzyme technology to potentially enable access to gene therapy for a much broader range of patients. Concretely, we will work with Sarepta in the area of Duchenne and Limb-Girdle muscular dystrophy diseases to unlock significant additional potential in both indications where there is a very high unmet medical need. It's estimated that 15% to 20% of patients in each of these indications have preexisting antibodies to AAV-based gene therapy, which prevents the patients from being treated.
Under the agreement with Sarepta, Hansa grants them an exclusive license to develop and promote Imlifidase as a potential pretreatment prior to the administration of gene therapy in Duchenne and Limb-Girdle for patients with neutralizing antibodies to AAV. Sarepta will be responsible for conducting and financing all preclinical and clinical studies to develop Imlifidase, as well as any potential subsequent regulatory approval. Hansa will support the development program with know-how and existing data and regulatory assets, as well as by supplying Imlifidase for development purposes free of charge.
Under the terms of the license, Hansa will receive $10 million upfront and will be eligible for up to $397.5 million in milestone payments upon achievement of certain predefined development, regulatory, and sales milestones, with sales milestones accounting for the majority of such potential payments.
In addition, Hansa will book all sales of Imlifidase and earn high single-digit to mid-teens royalties on Sarepta's incremental gene therapy sales when treating NAb-positive patients enabled through pre-treatment with Imlifidase. With that, I hand back to Christian to provide some insights on Duchenne and Limb-Girdle. Christian, please.
Thank you, Donato. Please turn to slide eight. Sarepta obtained a global and exclusive license to Imlifidase in Duchenne and Limb-Girdle. Both the Duchenne and Limb-Girdle are rare genetic diseases with a very high unmet medical need. Duchenne is caused by a mutation in the DMD gene. It's a gene encoding the protein dystrophin. It is an irreversible progressive disease that causes the muscles in the body to become weak and damaged over time.
It's eventually fatal, and there is no cure today. Duchenne affects one in 3,500 to 5,000 males born worldwide, and that's equivalent to approximately 400 to 500 new cases every year in the U.S. Duchenne causes the muscles in the body to become weak, and most patients are wheelchair-dependent already by the age of 12.
Eventually, the heart and breathing muscles can be affected, and that can potentially cause fatal complications. Limb-Girdle muscular dystrophy, or LGMD, that is also genetic and disease, and it's clinically heterogeneous. It's a group of rare muscular dystrophies. It's characterized by progressive muscle wasting. It often predominantly affects the hips and shoulder muscles.
Eventually it progresses to the arms and legs. It has an autosomal pattern of inheritance, and there is currently no cure or treatment to the disease. Limb-Girdle can be caused by single gene defects. There are several subtypes, up to 30 different subtypes of the disease. It affects specific proteins within the muscle cells, including proteins responsible for keeping the muscle membranes intact. The global prevalence of Limb-Girdle is approximately 1.63 per 100,000 individuals.
Taken together, it's estimated that 15% to 20% of the patients that suffer from Duchenne as well as Limb-Girdle, they have these pre-existing antibodies to the gene therapy vectors. As I said before, this prevents them from being treated with the gene therapy i t prevents them from even participating in the clinical studies. This is the group of patients that we are targeting with this collaboration. With this, I hand back to Søren.
This now concludes our presentation, and we're now ready to take questions from the audience. Operator, please begin.
Thank you. If you wish to ask a question, please press five star on your telephone keypad. To withdraw your question again, you may do so by pressing five star again. We will have a brief pause while questions are being registered. The first question we have is from the line of Angelica. Please go ahead. Your line will now be unmuted. Angelica? We will take the next question i t's from the line of [Unintelligible] Please go ahead y our line will now be unmuted.
Oh, hi. First of all, thank you for taking my question, and congratulations on achieving this other milestone for Imlifidase and i have two questions, if I may. Appreciating you might not be able to go full disclosure, but any input will be appreciated. First of all, can you speak a bit about what is Sarepta's development plan for Imlifidase? Would they start with preclinical trials, and how do they plan to move that into clinical trials? Do they give any updates on how the timelines will work for that?
Thanks again for that question. No, we're not gonna go into details around Sarepta's plans here. Clearly what is needed first is some preclinical studies to look at the safety and efficacy of Imlifidase as pretreatment of the specific Sarepta therapy. Hopefully this will move into the clinic. We, you know, can't be specific around the timeline, but hopefully it can move into the clinic at some point towards the latter half of next year, I would think.
All right. My next question is, can you give us any idea on how the milestones has been structured? Is that more loaded towards, preclinical studies, clinical or, towards registration and sales?
[Non-English content] Donato speak to that. As usual, again, it's skewed towards sales milestones, right? There's certainly also very significant development and regulatory milestones involved i don't know, Donato, if you wanna chime in here, that's your own setup.
Yeah. This is Donato speaking. I'm confirming what Søren just said. I mean, the major part of the milestones is certainly related to sales, so achieving certain sales milestones. There is a smaller portion that is related to development and a bigger portion that is also related to regulatory, achieving regulatory milestones. I think you could say that the further the program gets de-risked, the greater the level of our participation is going to be.
Thanks, Donato.
Great. Thank you very much.
Thanks, [Unintelligible]
No further questions. That's it. Thank you.
Thanks.
The next question is from the line of Joseph from Rx SECURITIES. Please go ahead. Your line will now be unmuted.
Good morning. Thanks for taking my questions c ongrats on a good deal. Just further on those milestones, could you possibly confirm what you expect the first one to be? What event that would be linked to? Then is there any kind of clause for Sarepta having first right refusal in indications outside DMD and Limb-Girdle? Thanks.
Thanks, Joseph. No, we're not gonna go into the details around the structure of the milestones. So I can't provide more granularity there. As far as the clause is concerned, I don't know, Donato, if you wanna comment on that.
Well, obviously, Sarepta is the leading in muscular dystrophy and there's certainly an ability to speak again if what we're intending to do here in DMD and Limb-Girdle turns out to be positive.
Absolutely. I mean, this is the initial focus, and then obviously there's scope for enlargement of the deal overall.
Sure. Okay. Just to clarify, there would be nothing to stop you also doing deals with other players for other indications?
Absolutely not, no t his is a specific deal around these two indications. As you know, there is a very broad range of ongoing programs in the gene therapy space. For many of these programs, the issue with neutralizing antibodies is a real one. It's a real challenge. Clearly we have a lot of interest currently w e have a number of ongoing discussions. We're very happy that we've been able to make this deal with a leading player in this space, you know, muscular diseases and also a leading player overall in the gene therapy space. We believe Sarepta is a very good partner for us.
Okay, great. Thanks, Søren. Thanks, Donato. Congrats again.
Thank you, Joseph.
The next question we have is from the line of Nishant Lahoti. Please go ahead. Your line will now be unmuted.
Hi, this is Zori Karamanolis from RBC. Thank you for taking my question and c ongratulations again on the news today. Just one question. Given that the launch in Europe is coming up soon, could you share your thoughts on how perhaps this deal has changed or how you think now about the launch price from Imlifidase?
Thanks, Zori, for that question. Yes, you're right w e expect to launch Imlifidase for enabling kidney transplant in highly sensitized patients in Europe towards the end of this year. We're busy preparing for that very significant launch. There are no immediate impacts from the deal that we made today with Sarepta. Certainly we will move on with the preparatory activities, and we have the resources necessary to take care of that.
Okay, because obviously you're not thinking whether now, given this deal, would provide further upside that an additional indication. You will try to launch with the highest price, I would imagine.
I'm sorry, I didn't get that part of your question. The price, again, we have a very clear strategy as we've discussed. We see, you know, dialysis costs as the relevant benchmark here. We expect to obtain premium pricing across the countries in Europe as we launch here. Again, there's no direct impact on the pricing strategy.
Clearly, if you look at the gene therapy space, that is definitely a premium pricing territory. As per this agreement, we will benefit fully from the sales of Imlifidase also for, you know, this usage as, you know, pretreatment. Clearly we envisage, you know, a premium pricing for that effort as well.
Great. Thank you very much. Congratulations again.
The next question is from the line of Mr. Naresh. Please go ahead, your line will now be unmuted.
Hi there, it's Naresh Chouhan from Intron Health. Thanks for taking my questions. A couple of questions, please f irst one, on Imlifidase, with lentiviral vectors p resumably it would work in both Lenti and AAV c an you just confirm that? Obviously, that opens up the market for you.
Secondly, do you know how many patients develop IgM or IgA neutralizing antibodies in DMD or LGMD and/or more broadly, for diseases where gene therapy may be added to the obviously diminish the potential of Imlifidase of helping those patients s o just trying to get a sense as to how well we understand the antibody responses to these vectors. Thank you.
Thanks for those, questions. I think I will hand over to you, Christian.
Yeah. Thank you. I can start with the second question, and then I might ask you to repeat the first question.
Sure.
The second question was about IgA or IgM versus IgG. What is known about these vectors is that they are highly immunogenic, that we have been exposed to these epitopes, these vectors before. It is a very similar situation to what we are facing in kidney transplantation. It is an immunological event that occurred long ago.
The predominant response to the vectors is an IgG response. I'm sure there is also a component of IgM involved. The neutralizing, I mean, the IgG antibodies is the dominating antibodies, is the highest affinity antibodies i t is where the focus clearly is when it comes to the neutralizing antibodies i t's IgG driven.
Thank you.
Repeated.
The first question was, obviously this deal is from an AAV vector. Presumably Imlifidase would also work for Lentiviral vectors, and obviously then opens up the potential for even further penetration in this market.
Yeah. To be honest, I haven't dug into the problems with neutralizing antibodies when it comes to Lentiviral vectors. Presumably, I would expect that to be a similar problem and we can provide a similar solution. Yeah.
Okay, great. Thank you very much.
As a reminder, if you have a question for the speakers, please press five star on your telephone keypad. Our next question is from the line of Niklas Sundberg. Please go ahead. Your line will now be unmuted.
Yeah. Hi, and congratulations on the Sarepta deal. Could you give any more details on the regulatory pathway going forward for Imlifidase in gene therapy? Since this approval will be limited to Sarepta's product, if I read the press release correctly. Would you need a new clinical program or regulatory pathway if you would partner with another company, so to say? Thank you.
Well, thanks for that question, and I'll hand over to Christian for a few words on this. Overall, yes, and we need a specific label for this that is specific for the combination or the use of Imlifidase as pretreatment to the Sarepta gene therapies t hat's clear t hey similarly need that in their label. That's the setup C hristian, if you had some additional comments.
Yeah. I think you said it very clearly. Yes, this is the first step. Of course, the clinical studies will be an investigation with Imlifidase together with these specific gene vectors t hat will be, of course, reflected in the regulatory pathway forward and the potential first labels on this indication. Of course, somewhere along the road, there is opportunity to potentially a more broader label for gene AAV gene therapy vectors i f that's, I mean, under this collaboration, it's clearly these diseases, these gene therapy vectors in combination with Imlifidase t hat's the path forward.
Yeah. Thank you. I came in a bit late to the call, but I don't know if this has already been answered, but a follow-up. How is this deal structured if you want to strike other deals with other companies?
This is a deal that is specific for the indications that are part of this collaboration agreement w e clearly have the ability to strike similar deals for other indications with other companies. This is a very good, I think, first entry into the overall gene therapy space w e're happy to work with a strong player like Sarepta for these diseases. We are in discussions with a range of leading players for a range of indications.
Okay. Thank you very much. That's all for me.
As there are no further questions at this moment, I will hand it back to the speakers for any closing remarks.
Thank you, operator. Thank you everyone for participating today and for the questions. Have a nice day. We look forward to staying in contact. Thank you.
Thank you.