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

Good morning, everyone. My name is Antoine Attali. I'm a member of the JPMorgan Health Care Investment Banking team. Thank you all for joining us today. It is my pleasure to introduce Soren Tulstrup, the CEO of Hansa Biopharma. [Operator Instructions] Soren, back to you.

Thank you very much. Good morning, good afternoon, everyone, and thank you for your interest in Hansa Biopharma. I'm Soren Tulstrup, President and CEO of the company. Before I start, just on Slide 2, the usual warning that my presentation today contains forward-looking statements. And as such, you should apply usual caution. Please move to Slide 3. For those of you who are not familiar with the company, Hansa Biopharma was founded back in 2007 as a spin-out from Lund University in Southern Sweden. And really, the genesis of the company was the identification of an enzyme, today known as imlifidase and has the unique property that it very fast and effectively cleaves IgG. And it was thought that, that could have therapeutic utility within a number of broad therapeutic areas. And so the company was founded with an initial focus on developing imlifidase as a drug candidate for enabling kidney transplants in so-called highly sensitized patients. If you then fast forward 14 years, today, we are a commercial stage company. We've seen very significant progress over the past couple of years. And last year, 2020, despite, of course, being a very challenging year for humanity overall, was a very successful one for the company, a year where we saw significant progress and where we achieved triple validation of our platform. First, we managed to get conditional approval for Idefirix in Europe for enabling kidney transplants in highly sensitized patients. Second, we generated very promising and encouraging data from our first Phase II trial in the autoimmune disease space in a disease called anti-GBM, data that we think act as a proof-of-concept for the promise and the potential of our platform in the broader disease space of autoimmune diseases. And third, we also entered into a collaboration with Sarepta therapeutics in the promising area of gene therapy with a focus on developing imlifidase as pretreatment to enable gene therapy in patients that have neutralizing antibodies against the vectors used. So a very successful 2020. Looking at Idefirix for enabling kidney transplants in highly sensitized patients, we see very significant commercial potential in Europe. This is the first and only drug approved with that indication. And if you're highly sensitized today, and you have an organ available from a deceased donor, you're essentially more likely to die waiting for a lifesaving kidney transplant than actually being transplanted. So there is a high degree of unmet medical need for that indication and that product. We've also, over the past few years, significantly expanded the organizational footprint of Hansa Biopharma. Today, we are more than 100 employees. And even though we are still a young organization, if you look at the average number of years of experience in the life science industry of our employees, it's more than 20 years. So it's a highly experienced team. It's also a very international team. We have team members from more than 20 different nationalities currently. In 2020, we also continued our efforts to raise capital successfully, in 2020, through a heavily oversubscribed placement of shares, raising $121 million. And when we add that to existing cash, we have a runway into 2023. Now please move to Slide 4, and I'll just spend a minute or so on the mechanism of action of our platform, as illustrated by our lead asset, imlifidase. So imlifidase is produced by a human pathogen called Streptococcus pyogenes as part of its defense against the human immune system. And what it does is it very fast and effectively cleaves IgG just below the so-called hinge section, creating a F(ab')2 and an Fc component, thereby rendering the molecule inactive almost immediately. It is highly specific to IgG does not affect other IGs, and it targets all subtypes of IgG. And what happens, and if you look at the right-hand side of the slide, is that essentially, within a couple of hours from a 15-minute infusion, you see IgG levels drop to below detectable levels. And they stay down there for approximately 7 days before gradually bouncing back. And then within a month or so, you're back to normal. And it's within that window that there is a therapeutic utility of imlifidase in the other enzymes that we're developing. Now please move to Slide #5, where you'll see some of the growth vectors that we see for our platform. Imlifidase is very efficacious, works very fast, is generally well tolerated and safe. But given the fact that it is produced by a human pathogen, it has a limitation that it is immunogenic, and therefore, we're not developing it for repeat dosing scenarios. But still, for that molecule, there is quite a number of relevant indication universes and specific indications within those universes. So if you look at the slide here, already, we're active, as I've talked to, in the transplant space. We have an approved product for enabling kidney transplants. We are also investigating imlifidase as a potential drug candidate for treating antibody rejection episodes post-transplant -- kidney transplant patients and beyond the kidney, obviously, there are other organs in transplant situations where you have challenges stemming from sensitization. For instance, with heart transplants and lung transplants and bone marrow transplants. So there's a number of growth vectors in the transplant universe for imlifidase. Also, as you'll see and as I've talked to, we're already active in the autoimmune disease space for imlifidase. We're targeting so-called monophasic acute autoimmune diseases where you only have 1 attack. And if the patient heals successfully with that attack, the patient is generally okay. We have 2 ongoing programs there, 1 in anti-GBM, which I mentioned previously; and the second is in Guillain-Barre syndrome. But there's a number of other similar diseases in the acute monophasic autoimmune disease space. Then we have taken a first step into the gene therapy space, looking at developing imlifidase as potential pretreatment to enable gene therapy in patients with pre-existing neutralizing antibodies. Our collaboration with a Sarepta is focused on limb-girdle muscular dystrophy and Duchenne muscular dystrophy. But beyond these 2 indications where Sarepta has exclusivity, there's obviously a large number of gene therapy programs currently active where there are issues with pre-existing neutralizing antibodies, depending on the vector used, the specific indication and the patients. So we are not developing imlifidase for repeat-dosing scenarios. We are developing our next-generation of enzymes under the heading NiceR. And if you look at the right-hand side of the slide here, that opens up, of course, a very large universe of potential indications. Clearly, there are situations in the transplant space where repeat dosing would be relevant and add value, especially post-transplant. There is also a number of chronic autoimmune diseases where you would want efficacy beyond the maintenance therapy when you have flares. In the gene therapy space, clearly, there's a number of gene therapies that will have to be administered several times. And then you have the issue of neutralizing antibodies that develop post the first gene therapy administration. So that's a relevant space for the next-generation enzymes. And finally, there is the broad space of oncology where we are hard at work trying to generate proof of mechanism that our platform can actually enhance the efficacy of immuno-oncology therapies. So as you see, broadly speaking, there is a lot of growth opportunities for our platform. Now please move to Slide #6. In order to fully capture the value that we intend to create over the years with our platform, we have put in place a very well-defined value-creation model as depicted on Slide 6 here. At the core of this model, we have our platform, our IgG cleaving enzymes. And then as you move towards the commercialization and the uptake at the patient level. It is our intention to remain in control of most of the value chain elements all the way from discovery through patient uptake and the bits. We need to own all of these value chain elements, but it certainly means that we intend to have control and capture an appropriate part of the economic upside generated. So as we approach the commercialization stage, our model essentially bifurcates in those areas where we have the assets needed, the experience and the skills in order to ensure a successful commercialization and where the target audiences are concentrated. It is our intent, by default, to commercialize our products ourselves. So that would apply to the transplantation space as well as a number of the autoimmune diseases that we are targeting. In other areas, where we need access to complementary assets and where the target audiences and the marketplace, overall, is much more fragmented and risky to operate in. It is our default position to go via a partnering strategy. So that would apply to the gene therapy space, as you've seen already, as well as the oncology space. And then the income streams that we're envisaging will be a mixture, really, of sales of upfront payments, of milestone payments and royalty payments. Now please move to Slide #7. So we have 3 very, very [indiscernible] as we move into 2021. The first of these is to make sure that we fully exploit the potential we see of our platform within the 4 broad indication, whereas, I just mentioned, i.e., transplantation, autoimmune diseases, gene therapy and oncology. And to that end, we have established 4 franchises with fully dedicated personnel, who is in charge of developing a valuable pipeline of drug candidates and commercializing them once we get approval, either on our own or in collaboration with partners. Second key priority is to fully exploit the significant commercial potential we see for our lead assets, Idefirix, for enabling kidney transplants in highly sensitized patients. Here, we have already achieved approval in Europe. And obviously, we need to successfully launch this product, which is potentially happening as we speak. We're also looking to gain access to markets where we can build off of the European approval to get access in the short term. And we clearly see significant potential for Idefirix in the U.S. Here, we've agreed with the FDA that we need to run a trial against standard of care in the U.S. for these patients, which is essentially to remain on the wait list and hoping against hope for the kidney allocation system in the U.S. to deliver a kidney that is a good enough fit before the patient dies. So we'll have to run that trial, and I'll get back to where we stand there. The third key priority we have is -- then is to continue the successful buildout of our organization. We currently have a very strong R&D team in place. We also have a core commercial team in place. But as we grow our portfolio of products and as we launch the product in additional markets, obviously, we'll build up that capacity. And as we do that, we will make sure we remain versatile, agile and flexible. Now please move to Slide #8, and I'll talk a little bit about the specific opportunity we see for Idefirix in Europe. It's a launch that we're very excited about. So looking at the market in Europe, there are approximately 100,000 patients end stage renal disease patients on dialysis that either are on the wait list for a life-saving kidney transplant or should be on the wait list. Of these, if you look at the distribution of these, approximately 10% to 15% of those would be categorized as being highly sensitized, and meaning that because of a previous transplant, a blood transfusion or multiple pregnancies, their immune system has become primed to such an extent that it is very difficult for them actually to find a kidney that is a good enough fit for them. So that is the target that we are after. Difficult -- or very difficult to transplant highly sensitized patients that have an organ from a deceased donor, which is the majority of the transplant situations in Europe. Please move to Slide #9. So as you look at the European landscape, unfortunately, Europe is not transplanting 100,000 patients a year. There is a significant undersupply of organs. And therefore, only 1 in 5 or so are transplanted on an annual basis. And not surprisingly, the majority of the volume is in the top 5 countries, led by the U.K., but also in the Nordic countries, in the Netherlands, in Austria and a few other countries are there significant transplant volumes on an annual basis, and the majority of these transplant situations are where the patient has an organ from a deceased donor. Please move to Slide #10. So just to make sure that I send a very clear message here that the target audience here is very, very concentrated. If we look at the large countries in Europe, essentially 70% to 80% of the volume of kidney transplants are taken care of by a handful of clinics in each of these countries. And of course, in the smaller countries, it's even fewer clinics. So it's really a very manageable number of clinics that we're targeting. We're really launching Idefirix in Europe on a clinic-by-clinic basis rather than on a country-by-country basis. But obviously, there are early-access and early-launch countries and later-access, later-launch countries from a pricing and reimbursement perspective. So what we aim to do in 2021 is to make sure that we initiate some of the key centers in Europe either through commercial sales, and that'll be in the early-launch countries, or via the post-approval study commitment that we've signed up to as part of the conditional approval in Europe. So we'll run that study in the later launch countries, and that's an excellent way actually to generate positive experiences in the countries where it will take a little bit longer to get it. Please move on to Slide #11. I just want to give a very high-level overview of our pipeline. So we talk about Idefirix for enabling kidney transplants in highly sensitized patients. We're launching in Europe, essentially as we speak. We're preparing to initiate a study in the U.S. We are currently discussing the study protocol with the FDA. And hopefully, we'll have green light from the FDA in the near term, so that we can initiate this trial. And if we do that this year and depending on, of course, the impact of the COVID-19 situation, hopefully, we should be in a position to submit a BLA under the accelerated approval pathway by 2023. Looking at our Phase II projects. We have a second project ongoing in the transplant space. That is for antibody-mediated rejection episodes or AMR. Quite a broad range of patients, actually, suffer from these episodes post a transplant, depending on their degree of sensitization pretransplant. Up to 30% or so had these episodes. They are manageable, to a certain extent, with existing therapies and interventions, including plasma exchange, but not optimally. And so we see significant potential for our platform in that indication. And as I said, we have an ongoing Phase II study in that indication. We also have 2 ongoing Phase II projects in the acute autoimmune disease space, anti-GBM. We've had a high level readout. I'll talk about that in just a minute. And the Guillain-Barre syndrome study is currently enrolling patients just as the AMR study. Then looking at the preclinical activities. As I mentioned early on, we entered into collaboration with Sarepta last year. And preclinical activities already ongoing with the imlifidase as potential pretreatment for the Sarepta interventions in limb-girdle and Duchenne muscular dystrophy. We also have preclinical work with our next-generation of enzymes, the NiceR enzymes. We have a lead candidate that looks very promising, and we are intending to complete IND-enabling tox studies this year. And then finally, the oncology space, as I talked to earlier, we're hard at work trying to generate proof of mechanism, which we hope to complete this year. Now please move on to Slide #12. So I'll just talk to the status and outlook for our ongoing Phase II trials, anti-GBM. And I'll get back to the results. We have generated very promising proof-of-concept data there. And the next step essentially is then to discuss these results, to roll them out in more granularity, of course, but also to discuss the results with the regulatory authorities, both in the U.S. and in Europe and agree on the next step here, the design of the next study. As far as AMR and Guillain-Barre syndrome are concerned, we initiated patient enrollment there prior to the explosion of the COVID-19 pandemic. Given the developments there, the COVID-19 pandemic and its impact -- potential impact on data integrity, et cetera, we decided to halt patient enrollment for a little bit more than 2 quarters last year. We have just decided to -- we initiate patient enrollment on a center-by-center basis, and we currently have 4 patients enrolled in the AMR study out of the target of 30. And we have a total of 5 patients in the Guillain-Barre syndrome study out of a total of also 30. So hopefully, again, depending on the development of the escalating COVID-19 situation, we should be in a position to fully enroll these studies by the end of the year, and they're both 12-month studies. So again, we should hopefully have data by the end of next year. Please move to Slide #13. So as promised, let me just spend a minute on the very encouraging data that we have communicated from the just completed Phase II trial in anti-GBM. Anti-GBM is an ultra-rare disease, very serious disease that affects the kidney. It affects approximately 1.5 million or so out of 1 million. And it is, as I said, very serious. 2 out of 3 of patients lose their kidney function and end up in dialysis. There is no approved therapy currently on the market. So looking at our data sets, going into the study, and we had 15 patients enrolled in this study. 2 out of 3 were already on [ dialysis ] and so they're quite severe. Going out of the study, 2 out of 3 were off of dialysis. So the study demonstrated the ability of imlifidase, not only through preserve those that were not on -- preserve the kidney function of those patients that were not on dialysis going into the study, it also demonstrated the ability to actually lift out some of those patients that were already on dialysis. So very, very encouraging data. And as I said, we're currently discussing or getting ready to discuss these results in more detail with the regulatory authorities in Europe and in the U.S. Please move on now to Slide #14. I just wanted to briefly discuss the approach we are taking and the promise we're seeing for our next-generation of enzymes for repeat dosing. So obviously, you don't want IgG levels down below detectable for a sustained period of time. But clearly, just looking at the chronic autoimmune disease space, there are IgG-mediated chronic autoimmune diseases where you have flares either annually or more often. And in those situations, you need impact and efficacy beyond what the maintenance therapy can give you. There are also situations where you want induction therapy, and then you also want to have this added efficacy when you have flares or relapses, right? So that is the approach we're taking, and we're seeing quite a number of relevant diseases in the chronic autoimmune disease space. Please move to Slide #15. In the gene therapy space, it is clearly a challenge for a lot of the gene therapy companies to deal with pre-existing neutralizing antibodies. Up to 70% of patients have these antibodies. Again, depending on the vector, the specific vector that is being used, the specific indication and the specific selection and age of the patients. And our approach really is that imlifidase and other enzymes should be able to cleave and inactivate these neutralizing antibodies almost immediately, create a window of opportunity for the gene therapy to be administered and the transduction of the healthy gene to take place. And if you move to Slide #16, data has already been generated, preclinical data indicating this potential of imlifidase. Imlifidase has been studied in several different models with mice and with nonhuman primates in different diseases. And the data clearly demonstrate that imlifidase was able to, not only knock out the neutralizing antibodies, but also to create an environment where transduction of the healthy gene could take place. So very promising and interesting data from the study that was published in Nature recently. Please move on to Slide #17. As discussed, we have taken a partnering strategy here, and we have recently entered into a collaboration with Sarepta Therapeutics. We are bringing our platform to the table and in our experience in the immunology field and Sarepta, obviously, are bringing their gene therapy skills and experience and assets to the table here. They have exclusivity for 2 indications only, and that is limb-girdle muscular dystrophy and Duchenne muscular dystrophy. We will be booking the sales of imlifidase. Sarepta will be developing imlifidase as a pretreatment. But we will be booking the sales of the resulting product once approved, even though Sarepta will be marketing it. And we are also qualified for milestone payments, up to approximately $400 million plus royalties on the sale of the Sarepta gene therapies enabled by imlifidase, up to mid-teens. So we are very happy with this collaboration, and it's off to a very good start, and there is currently ongoing preclinical work at the Sarepta side of things. So with this, I'm coming to my final slide. As I hope I've been able to communicate, a lot has happened over the past couple of years. 2020 was a very, very successful and, overall, transformative year for the company. 2021 looks to be a very, very exciting year as well. We are rolling out Idefirix in Europe, and we're hoping to generate the first positive experiences in key centers in Europe this year. We are also looking to complete IND-enabling tox studies of our lead molecule for the next-generation of enzymes for repeat dosing. And we hope to enroll, fully, both the AMR and the Guillain-Barre Phase II trial this year. And then next year looks to be just an exciting year where we should have data readout from the Guillain-Barre syndrome and AMR trials and where we should complete enrollment in the U.S. study for enabling kidney transplants in highly sensitized patients. The study that, hopefully, in 2023, would lead to us being in a position to submit a BLA. And in 2023, obviously, also, there might be additional data readouts from other studies in the gene therapy space as well as other initiatives that we are planning. So very exciting future ahead, and I look forward to keeping you all updated. And with this, I turn over to the Q&A session. [Operator Instructions] Thank you. So I don't see any questions at this point in time. [Operator Instructions] Okay. It looks like there are no questions. [Operator Instructions] And if I don't see any questions, I think, Marissa, that will just complete this session. Perfect. Well, thank you very much, once again. It was a pleasure connecting, and we look forward to keeping you updated. Thank you. Bye-bye.