Good morning everyone and welcome to Oncopeptides' Capital Markets update. My name is David, Head of communications and IR here at Oncopeptides. It's great to see so many of you joining us online. Today's program will take you through both the science and strategy behind Oncopeptides from our CEO Sofia Heigis , who will open with how we're bringing hope through science via insights from our main owner, HealthCap, two perspectives from leading global experts on multiple myeloma, and finally, a look at where we go from here as a company and as an investment case. Before we begin, a brief. The scientific experts joining us today are independent medical professionals and their views are their own. The presentations may include forward looking statements, so please see our full disclaimer in the slides. All former disclosures will also be available in the presentation materials online there.
Now let's start this morning off with Oncopeptides' CEO Sofia Heigis who will set the stage and show how Oncopeptides is turning science into tangible process for patients and investors alike. So Sofia.
Thank you so much, David. Oncopeptides is a small global biotech that is focused on both research and commercialization of medicines for difficult to treat diseases with high unmet needs. To make such a company successful, we need hard work, we need resilience, we need a lot of different competencies in people. We obviously need an experienced board of directors, management, we need team members that are walking the extra mile every day. We need our current partners and we need future partners to expand our business. We need prescribers, physicians that are using our drugs that can inform us and advise us how the drug is working in real life. We do need researchers and investigators that can advance the science. Together with us, we need life science investors that are long term committed in good and bad times.
We do need analysts and a broad shareholder base with a good understanding of our business. The purpose of today is really to ensure that we get an external perspective on our business, that we enhance the understanding of our core business, and that we do get a better understanding about the future opportunities that we have at Oncopeptides. I am thrilled to see representation from all of these different groups attending this meeting today because together we can achieve more and make Oncopeptides a very successful company. I would like to start with a brief introduction on where we stand here and now to ensure that we stand on common grounds. In the third quarter of 2025 we saw sales of just about SEK 20 million.
That is the year- over- year growth of 174% and the fourth consecutive quarter of growth for our European commercialization. That is where we are here. Now we are very much focused on building the foundation from the Pepaxti launch in Europe. In parallel, we are looking to be able to bring Pepaxti to patients across the globe through partnerships. We are also progressing our pipeline in the preclinic with small means, supported by grants and external collaborators. If we put all of these pillars together, there is a great potential for this company and today will be all about you understanding that a bit better. If we start to focus in on our European commercialization, that is giving us solid ground under our feet
Our ambition has all the time been to launch as fast as possible with a price that is reflecting our innovation, ensuring that we can generate value for both patients and shareholders. When you launch in Europe, it is a fairly complex market with a lot of different rules, regulations, price systems. You need to know what you are doing. We made a thorough assessment and we divided Europe into different phases. I am happy today to be able to say that we have reached the key markets in the first and the second phase. Those markets are Germany, Austria, Spain, and Italy. Those markets can make Oncopeptides profitable by the end of 2026. We are of course continuing to work on providing Pepaxti to more patients by running market access processes and looking for partners in, for example, Central Eastern Europe, where we currently have active discussions.
This is the progress of our launch. We started off with basically very little preparedness. We had to build a team. During 2023 we managed to negotiate the price and in the beginning of 2024 we had a full team in Germany, we had a negotiated price and we can really start to broaden our footprint. I'm thrilled that we have two German specialists here today, representing both the academic setting and the office-based setting. I'm sure that you will gain a better understanding of the German market from them. In Spain we managed to negotiate the price in record time. It only took us five months and that was in the beginning of last year. You have to go for regional access. Today I'm so proud to be able to say that all the potential patients in Spain can get access to Pepaxti.
That is not usual because usually you have some regions where you hardly ever get access. It is very well done by the team. As you can see here, we are broadening the footprint all the time in Spain as well. We have the second largest market, Italy, where we got the price this year and the market access process takes longer there and that meant we also had more time to prepare ourselves. Italy is a more centralized market and the strong launch uptake we have seen in Italy is a lot due to that. There are only specialized hematologists treating with Pepaxti and they have experience from before, so they do understand the drug and how to use it.
Today or by the end of Q3, we had more than 550 patients across Europe and we are so proud to be able to make a difference to their and their relatives' lives. We see a positive clinical experience that is spreading and we will discuss that much more during the panel today. We also have an endorsement on European level being included in the guidelines. That is important because they are commonly referred to. There we have a clear and strong position and recommendation. What is it then that we are launching, our flagship drug, Pepaxti. It is the very first peptide drug conjugate coming out of our platform. I joined Oncopeptides five years ago and I did that due to that I got inspired by the people, but also intrigued by this specific mode of action.
The peptide drug conjugates are very lipophilic, enables them to diffuse passively into all the cells as there is a lipophilic or fat loving membrane around all the cells. Inside of the cells there are small scissors or enzymes that are cutting them or hydrolyzing them into pieces, releasing a cytotoxic payload. This payload is more hydrophilic, which means that it's entrapped inside of the cell and you get an enrichment of cytotoxic agents inside of the cell. This is then ensuring that the cell can be damaged and going to cell death by apoptosis through damage of both the DNA and the nucleus. Lately we've also realized that we have a dual mechanism where we also damage the mitochondrial DNA. This is super exciting. What's important to note is that this mechanism of action is independent of the immune system of the T cells.
There is also no receptor that is needed. We can overcome many of the resistance mechanisms for that. Meaning that we are really complementing other therapies in this space. If we look at the different aspects of treatment in the late line setting, there is still a high unmet need because even though there are many drugs available, the treatment options are diminishing. The patients have seen a lot of side effects and their quality of life is usually reduced. To have an alternative that is addressing the concept of this trinity with a balanced efficacy, safety, and quality of life is of utter importance. We will discuss that a lot more with our experts today and hear from our experts online about that.
We will also hear about the treatment landscape, how it has rapidly been evolving, how there are many different treatment options, but where Pepaxti still have unique position and a very strong place to take. We should acknowledge that when it comes to bringing a product from preclinic to clinic out to the market, it takes time and it is costly. A biotech company will struggle if they do not have a committed and long-term life science investor by their side. For Oncopeptides, HealthCap, which is a European venture firm investing globally in life science, they have built and backed more than 130 companies. They have brought more than 45 companies to the stock exchange and they have done numerous trade sales.
They have an investment strategy that fits Oncopeptides very well where they are focusing on breakthrough therapies and high unmet needs so they can really support patients suffering from these conditions. I would like to say a warm welcome to Dr. Björn Odlander , the founder and the managing partner of HealthCap.
Thank you Sofia.
Thank you, Björn, for taking time to be with us today. I joined Oncopeptides in 2020. I've only been here for five years. HealthCap has been here much longer. I am curious to hear a bit about the history. Back in 2011, when you decided to invest in Oncopeptides, why did you and the team decide to do so? What was the reasoning?
Yeah, you know, in a way you've said it all in your introduction and also about our investment philosophy because what we look for is unmet medical need and we believe very strongly in precision medicine. By understanding the pathology of the disease, understanding the mechanism of the intervention you want to develop, you reduce the risk a lot in your development programs. By doing this you can, you know, all medical development is about effect and side effect. As you outlined, the mechanism for entrapment of a cytotoxic compound intracellularly was what intrigued us. We could also see that this apparently worked. It worked theoretically, but also in practice. That is where we entered. We had preclinical data supporting the theory. It talked very well into our investment strategy. It is as simple as that.
Yeah, yeah. When I was kind of, I was reminding myself exactly how you express your investment strategy. I also realized why. I am happy to hear confirmed from you.
You know, it works. Yeah, our companies have brought more than 35 approved new medical, new chemical entities to the market over the 30 years we've been active.
Yeah.
That's around 4%-5% of all FDA approved drugs that come out of our portfolio. With this strategy, of course, a lot of people, a lot have come. It's not only us, of course, but it shows that the venture capital investment strategy, the way to organize industry with smaller companies, more independent groups, not big organizations, is a very agile and effective way of developing drugs.
Yeah. I'm super impressed by you. You're doing a really good job. It's fair to say that it's been a roller coaster with Oncopeptides, maybe with some of your other projects as well, but maybe this has been one of the most challenging ones from time. How do you view the journey?
You know, I think the U.S. experience with the FDA is still confusing to me. We were, of course, because we did not really understand the reasoning behind FDA's actions, let that be. However, we were of course very pleased when Europe took the total opposite stance and endorsed the whole theory and the clinical data and gave the full approval. It was a roller coaster. It is a roller coaster in a way. The technology apparently works and you are on the rollout of this in a very successful way. I am the one who is impressed.
Thank you so much. You are still the largest owner of Oncopeptides. You have continued to invest and you continue to kind of keep your share. What is motivating you to stay in Oncopeptides and in general in companies and continuously engage?
I think the nice thing of being a life science investor, investing in developing new drugs, is that you also have an ethical dimension of what you're doing. Our team, we're a lot of medical doctors in the team, we're highly motivated to bring this new opportunity to patients because it fills an unmet medical need among patients. That's highly motivating. We believe in the technology. It would be stupid to give up.
Right.
I must here say also that we have had a great understanding from our ultimate owners, our limited partners who provide us with the capital to invest. They have believed in us and our interpretation of the situation. Of course it was a bit shaky when the FDA took the opposite stance.
It's always shaken when you have a lot of uncertainty. Right. When you don't know what's ongoing, what they need to find the facts. I'm also, of course, very happy that we managed to put the facts in place for Europe. I'm very thankful for HealthCap and, of course, our partners and investors continuing to have confidence in us because there is much more to gain here.
Yeah. We are totally convinced about that and we're very happy. That launch in Europe obviously successful. You know, the thing now being included in guidelines, that's also to me as a medical doctor. I remember when I studied hematology many months ago and, you know, it was quite confusing, all the different setups, how you treat patients. I realized also then that the guidelines are so important because it's sort of the total aggregation of key opinion leaders and doctors' view on how to treat patients. A lot of doctors look at this to get guidance. I think that's a major achievement to get into the guidelines.
Yes, it's always important to have a clear position not only for the company, but also for the patients. You really can target the right patients and get a high success rate. We will discuss that throughout the day when we'll talk a lot about the real world data that is being generated that I find super exciting. Thank you so much for taking time for having me. Yes, of course.
Thank you, Sofia. Thank you, Dr. Odlander., for that perspective. Now let's dig even deeper into the science and to the disease itself, multiple myeloma. That is to help understand the medical landscape and where Pepaxti and other emerging technologies fit in. We're joined by Professor Sebastian Theurich from LMU University Hospital in Munich, one of Europe's leading experts in multiple myeloma and immunotherapy.
Thank you, David, for the nice introduction. Dear colleagues, thanks. It's my pleasure to give you an overview about the treatment landscape of multiple myeloma in the current century.
To start with an overview. I. Would like to point out that multiple myeloma is a rare disease if you have all cancer types in mind. But it's the most common hematologic malignancy with about 13% of all hematologic cancers. The median age is about 62 years. Males are more affected than females and the incidence is about 5 per 100,000 inhabitants per year. On the other hand, the incidence rates have been rising during the last decades and the reasons for that are not really clear. Environmental factors, lifestyle factors and so forth are discussed. So but it is expected that the incidence of multiple myeloma will rise also in the upcoming years. So, to bring us all on the same page, where does multiple myeloma really origins from?
It arises from activated B cells that differentiate into plasma cells that eventually can transform into malignant plasma cells that then produce antibodies in the bone marrow. These antibodies can be measured in the blood or in the urine of a patient as a monoclonal antibody spectrum. This is shown here in the immunofixation analysis. However, multiple myeloma needs defined criteria to indicate treatment. This is defined by the so-called CRAB criteria. This is an acronym for calcium elevation in the blood, renal damage, anemia, and bone lesions. Recently, those CRAB criteria were updated with additional factors such as free light chain increases, more than 60% of plasma cells in the bone marrow, and bone lesions in the MRI.
It is not the immediate detection of the monoclonal antibodies in the blood that indicates a treatment, but it is the early detection of end organ damage that brings a patient to treatment. The treatment landscape has tremendously changed during the last 20 years. With the invention and development of melphalan in the last century, back in the late 1950s, the development has been marked by milestones such as the intensification of melphalan, high-dose melphalan. The landscape changed tremendously with the development or approval of IMiDs, so immunomodulatory agents, proteasome inhibitors, and more recently monoclonal antibodies raised against CD38 and other targets. Very recently, immunotherapies that engage T cells and also CAR T- cells have been developed and changed the landscape of multiple myeloma profoundly. This is mirrored by improved survival of myeloma patients.
In contrast to the median overall survival which has been estimated with about one to two years in the last century, in the 1960s, this raised to up to 10 years median overall survival in the beginning of the 2000 years.
So f ive-fold increase, at least five-fold increase of the median overall survival in myeloma patients due to innovation and the development of new drugs. This is estimate overall survival curve that also includes the newest combinatory treatments that include CD38 antibodies and a triplet of an IMiDs, proteasome inhibitor, and dexamethasone, mirrored here by the Perseus and Cepheus study data. Coming to the clinical guidelines that have been recently published by the EHA-EMN network, you can see that still in newly diagnosed myeloma patients that have an indication for treatment, the first decision is, is the patient eligible for transplant? For intensification of treatment or not, this is still the case. However, this regimen or this decision is challenged by running clinical trials that include novel immunotherapies that might challenge the position and indication and need of high-dose chemotherapy.
That is really something that put a high burden on the patients from the clinical perspective. On the other hand, the induction treatment in first line is a quadrupled treatment that includes CD38 antibody, an IMiD, so lenalidomide, bortezomib, and dexamethasone. This interestingly has been approved for both groups, for the fit patients and also for the unfit patients if a first relapse occurs. For the second line treatment, the guidelines differentiate between the anti-CD38 exposure of a patient and the refractory status of that, and also the exposure towards lenalidomide or the refractoriness towards this drug. Depending on this decision tree, you can already appreciate that we have numerous regimens that can be offered to patients. That is really kind of a tailored, personalized treatment.
However, if you go into details, you will find that the current recommendations for the second- line treatment more or less all include BCMA targeting treatments. I will go into details to that a little bit later. Upon further relapse, second- line, third- line or later treatments, the guidelines recommend, also depending on the pre-treatment of the patient, also of the clinical status of the patient and the refractoriness of the patient, certain regimens. As mentioned before, Melphalan has been awarded one B recommendation in this guideline. Coming back to BCMA targeted treatments, what is BCMA? BCMA is a molecule, a protein. B-cell maturation antigen is the name. This BCMA is expressed on plasma cells and also myeloma cells.
It's kind of specifically expressed in those cell types and not expressed in other immune cells or other tissues, making it an ideal target for myeloma treatment. We have several options to target BCMA on myeloma. The first is CAR T- cells that have been engineered to specifically target BCMA. We have bispecific T cell engagers or bispecific antibodies that recognize BCMA on the myeloma cell and also activate the T cell on the other side of the antibody and activate the T cell response, thereby destroying the myeloma cell. Thirdly, we have antibody drug conjugates that have a payload conjugated to an antibody that are then internalized into the myeloma cell by binding or upon binding on BCMA.
Currently, approvals in Germany are here for the second- line treatment Cilta-cel which is the BCMA CAR T- cell product, currently the only approved product in this regard in Germany. Also, the antibody drug conjugate combination belantamab. For the fourth line treatments, we have approval for a number of bispecific antibodies targeting BCMA. What is the problem or what are our clinical challenges with all these innovative treatments? I can tell you, I have not brought survival curves to convince you that this or to show you that these immunotherapies are highly effective, but rather I would like to share with you information that has been generated during the application of those drugs in the clinical practice.
We have learned that infection is one or is the major threat to the patients after all these kinds of BCMA targeted drugs in a more or less increased fashion. The probability to develop potentially lethal infection increases by the time after BCMA targeted treatment. We have also learned that substitution of immunoglobulins to the patients is a highly effective method to prevent the increased infection risks. This is what we currently do. Even after one shot CAR T-cell treatment, the patient has to come to the hospital or to the practice to receive those immunoglobulins to decrease the risk of infections. Another factor that can diminish the efficacy of immunotherapy is the continuous activation of T cells by bispecific antibodies that kind of exhaust the T cells by the continuous activation of the T cells.
This also then diminishes the efficacy of the antimyeloma activity. We have learned that stretching the intervals between the antibody administration can ameliorate these effects and reactivate the T cells. This also can decrease infection complications. However, coming to the third drug here targeting BCMA, which is belantamab, the antibody drug conjugate, this has been associated with a specific side effect, namely ocular events, keratopathy that can lead to decreased vision of the patients. You see some examples from a patient perspective here on the slide. Another fact that we have been learning or learning went to a learning curve was the sequencing or how can we give BCMA targeted treatments one after another? Can we start with bispecific antibodies and then proceed to CAR T-cell treatment on the same antigen? This, to be fair, is not a good idea.
Currently, although the data is not super solid and large, includes not the largest patient numbers. We have learned from the clinical practice that pre-exposure to a BCMA targeting drug can, or it does, diminish the efficacy of CAR T-cell treatment by several percent. Another fact is that CAR T- cells need to be produced. That is autologous T cells from the patient that have to be taken from the patients by leukapheresis, shipped to the lab, transduced with the lentiviral construct to express the CAR in the T cells, and have been expanded. This process lasts between four-six weeks when we can get, or when we get, the product back to the clinics. This is in contrast to the bispecific antibodies and antibody drug conjugates which are off-the-shelf available.
This long term during that we need to bridge time wise to CAR T- cell treatment is indeed a matter of clinical relevance because most patients with myeloma in this stage and relapsed myeloma, they have an indication or the need for a bridging therapy. We cannot immediately transfer the patient to CAR T- cell treatment and just wait the six to eight weeks before without doing anything. The patient needs treatment before the CAR T- cell treatment. Most of the patients that we are currently seeing in our clinical hospital and our clinical practice are not first relapsed patients, but it's later relapse stages or later than third or fourth line of therapy. These patients have been through a number of pre-treatments and of course this induces comorbidities, organ damage, and also resistance of the myeloma cells itself.
That's kind of a challenge to find the optimal bridging therapy that reduces the myeloma burden before CAR T-cell treatment, but on the other hand does not harm the hematopoiesis, so the blood production of the patient, and put the patient at a higher risk of, for example, experiencing an infection before CAR T-cell treatment, because of course we would not like to put a patient into danger. What are the best options for this bridging regimen? This is really, really patient specific. There is not a one size fits all solution. It depends on the age of the patients, the comorbidities of the patients, of course, the pre-treatment of the patient, and the suspected resistance of myeloma cells and refractoriness of myeloma cells to myeloma-targeted drugs. It is also the aggressiveness of the disease.
A highly aggressive, aggressive myeloma needs treatment with chemotherapy or novel chemotherapeutic agents to really shrink the tumor load down in a short period of time, and in this, and I'm super sorry for obviously being the slides a bit destroyed, in this indication or in this situation, I do see melflufen as a very potential and potent drug because it combines the high lipophilicity, as you have heard before, that circumvents the development of resistant mechanisms before. It also has shown activity in high-risk myeloma patients, including TP53 mutated myeloma cells or deletion 17p as cytogenetic high-risk markers, including also extramedullary disease. You can imagine that the farther the patient has developed relapses, the higher the risk for extramedullary disease is. That means the myeloma is spreading around, leaves the bone marrow, and infiltrates organs or even soft tissues.
In this situation, melphalan has shown efficacy in the OCEAN study that led to the approval of the drug. This slide should show you that aminopeptidases, so the small scissors as you mentioned and heard before within a myeloma cell, are highly expressed. This is the mechanism how melflufen is trapped in the myeloma cell. One thought, currently just a hypothesis, but maybe or I'm sure future studies will find the answer, is how is the situation in immune cells? Because what you want in myeloma cells in myeloma patients is that the CAR T- cell treatment and the immune compartment is not too much affected by a treatment against the myeloma. This slide shows you just an example of one aminopeptidase and the expression of this particular aminopeptidase, LAP3, in different immune cells.
What you can appreciate is that this immunopeptidase is highly expressed only in a very few number of immune cells which have regulatory, so immunosuppressive, properties. This raises the hypothesis that maybe due to different aminopeptidase expression patterns, melflufen might be beneficial as a drug before immunotherapy because it preserves active immune cells while depleting regulatory immune cells. Again, this is a hypothesis, this is not data based so far. On the other hand, preclinical data has shown that melflufen can overcome high risk mutations that occur during later lines of treatment in the patient. This led to the approval of melflufen for the fourth line of myeloma treatment in combination with dexamethasone, triple-class refractory disease, and progression of last treatment. To note, and this is important, this is something we learned from the OCEAN study.
It's mostly effective in patients that have not been under high dose melphalan. So an alkylating treatment before or the period from that high dose melphalan treatment is more than three years. I would like to end my presentation with a patient case from my practice that illustrates several aspects. It illustrates that an 83-year-old patient can be treated over a long period of time. This patient course lasted at least over 10 years. We went through the COVID pandemic and you see that kind of unconventional changes of treatment regimens, you see just the abbreviations here, were made, so careful and cautious changes of the treatment regimens because we were those days afraid of putting the patient too much under immunosuppression, increasing COVID risk. At one point we needed to change the regimen entirely.
Here we began with a BCMA-directed drug, belantamab, and the patient responded very well. After a year, relapsed, and then we went to melflufen because at that time the patient was over 80. We started with melflufen with a slightly reduced dose that was well tolerated. As you can appreciate here in the plot, the IgA as the myeloma marker fell down very, very, very rapidly. The response to melflufen lasts also over approximately one year. The interesting part is we then went to another BCMA-targeted immunotherapy by teclistamab. This again was. Here again the patient was responsive to that treatment, indicating that even after one year of melflufen treatment we did not expect to exhaust the immune system tremendously.
Finally, I would like to just point out that our treatment decisions in multiple myeloma have developed in a very complicated way, which is very good for the patients because we can really decide on a patient-based basis what is the best treatment option for the patient. We have numerous options to select. Important factors that drive our treatment decisions are, of course, the clinical status of the patient. Frailty, the disease activity, disease factors such as cytogenetic or genetic risks, manifestations, the treatment history, but also patient-centered factors like lifestyle and patient preferences. With that, it is always a shared decision making that you do as a physician with a myeloma patient, because as you have seen, the treatments are so effective nowadays that the treatment history lasts over a very long period of time.
I would like to thank you for your attention.
To you too, Professor Theurich, for that insightful overview. You will be back later in the event for the Q& A session. If you have any questions for Professor Theurich or anyone else speaking, please post them through the online Q& A function. We'll now hear a short reflection from one of the world's foremost myeloma clinicians, Maria- Victoria Mateos from the Salamanca University Hospital , and she will share her view from everyday clinical practice
Hello to everyone. My name is Maria- Victoria Mateos and I work as hematologist and Director of the Myeloma Unit at the University Hospital of Salamanca in Spain. It is a great pleasure for me to be here with you today talking about the multiple myeloma treatment landscape and because of a lot of innovation and because of unmet medical needs, the multiple myeloma therapy is rapidly evolving. There have been three main drug classes in multiple myeloma basically based on proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies, and the vast majority of the myeloma patients receive these three main drug classes throughout the first lines of therapy. When patients have received PI, IMiDs, and anti-CD38 monoclonal antibodies, myeloma patients become triple class exposed, in the majority of the cases triple class refractory, and this was an unmet medical need.
T cell redirecting therapies including CAR T- cells as well as bispecific monoclonal antibodies, antibody drug conjugates, have been highly effective in the triple class exposure and refractory myeloma population, addressing the needs for triple class refractory myeloma patients. It is true that if we go to the European guidelines recently published for the management of patients with multiple myeloma, together with these strategies we have new compounds, and this is the case of melflufen with a specific and different mechanism of action that has demonstrated also to be effective in this triple class exposed and refractory population. Together, all these strategies reflect a realistic and expanding treatment landscape for patients with advanced multiple myeloma.
The key aspect is how to select the appropriate therapy for each specific patient with multiple myeloma, especially when myeloma patients become already triple class exposed and triple class refractory and we have to consider many creative disease, morbidity, risk assessment, lifestyle, but the treatment history is one of the most relevant ones. Today, if we discuss about melflufen, it is true that once the patients are triple plus exposed and triple plus refractory, but even if these patients have already received the T cell redirecting therapies, it is possible to position melflufen in this situation.
Sometimes it is also possible to use it as a break in therapy before the use of the T cell redirecting therapy because of its ability in order to reduce the tumor burden and of course in order to support this positioning for melflufen there has been several clinical studies. Horizon, first one, phase II clinical study in which melflufen plus dexamethasone showed to be effective in this population representing an unmet medical need. Following Horizon, Ocean trial was a phase III clinical study comparing melflufen plus dexamethasone with pomalidomide and dexamethasone, and in the population non-eligible for autologous stem cell transplantation or those patients in which the transplant was performed at least three years before, melflufen plus dexamethasone resulted in a significant benefit in progression-free survival with a clear trend towards a benefit also in overall survival.
In addition, we can add this information with the adequate, predictable, and manageable toxicity profile. Also, with the fact that the health-related quality of life has been maintained in these relapsed refractory myeloma patients treated with melflufen and dexamethasone, and especially in the phase III in comparison with pomalidomide and dexamethasone. In addition, you have to know that melflufen is delivered once a month as a 30-minute IV infusion. It is not required for hospitalization, no premedication, and no specialized centers required for its administration. Today, you have to know that the Trinity concept is something crucial for managing patients with multiple myeloma. This Trinity concept integrates efficacy, safety, and quality of life, and melflufen can be positioned as a differentiated therapy that delivers durable clinical benefit while maintaining patient well-being, a balance critical for long-term subsection. Thank you very much for your attention.
We will now continue along the team and move into discussion here in the room focused on clinical experience with Pepaxti. With the help of the Trinity concept as a backdrop, I am pleased to welcome Professor Claudio Cerchione from Istituto Romagnolo per lo Studio dei Tumori in Italy and Professor Klaus Fenchel who leads the Oncology Versorgungszentrum Saalfeld. The conversation will be moderated by Sofia Heigis of Oncopeptides. I hope I pronounced that okay at least.
Thank you so much, David, and [Foreign language], Professor Cerchione.
[Foreign language], Sofia. I'm delighted to be with you.
It's so great that you are here and [Foreign language] , Professor Fenchel,
It's an honor to be here. Thank you so much.
Fantastic. Clinical trials are the foundation for regulatory approvals. We all know that. They are designed in a specific way. When a product is approved, you can generate real world data through case reports, case series, or you can run real world studies as we do at Oncopeptides. I would like to start to give our audience an understanding with your help. If you would like to start, Professor Cerchione, can you explain what differences there are between patients that are in clinical trials versus in real life?
Sure. There is a huge difference between a patient enrolled in a clinical trial and in real world. Because we know perfectly that in clinical trial we have inclusion criteria that perfectly have to match with the population in which that drug will be used after the approval. This inclusion criteria often excludes some patients that have some comorbidities that are also frequent in our real world. Patients that had, for example, another cancer, even if it has been cured. We have some preclusions for including some real patients, but that do not match with the characteristic of clinical trial. It is normal if we ever to arrive to a registration of a drug, we have to ultra select our patients.
While in real world we see some patients that are in some way also less motivated than the ones that are in clinical trial in terms of capability to come to the institutions, logistics. There are also a series of the driver that we have to come and particularly also sometimes the characteristic of the disease itself that is not matching exactly with the one of the clinical tests that you have available, but is in line with the registered characteristic. I think that there is a huge difference. In the same time, real world is the patients that we treat more. We have absolutely to care about what we have in front of us every day in our old patients' rooms. That's why it's important to have a drug that can be used for every patient as possible.
Thank you so much.
Pleasure.
Professor Fenchel, why do you find it important to generate this data and publish it?
Yeah, let me say it a little bit more pronounced. Clinical studies and real world data, they are not just another way. It is completely different. Because if you perform a clinical trial, clearly there are different ways to think about it. As a researcher, you need to look for positive results because only positive results will be published and you get famous. On the side of the company, you need the positive results to get a license and earn money. Therefore, you try to exclude every patient, like Claudio pointed out, which may differ from your goal and therefore the ideal clinical trial would be to give your substance to healthy athletes like your son in the Caretto World Championship, but not to the patients we see on our daily base. Therefore, the real world data are the thing we are strongly needed.
This is the thing which we can apply to our daily practice. Because my patients are not healthy athletes, they are old, they are comorbid. In these real world data you often see problems or things which are not mentioned in these healthy young patients who are in the clinical data. In real world data you are looking on the patients typically much longer than in the clinical trial. Therefore, on this long run you may see effects, positive or negative, which are not included in the clinical trial data.
Thank you so much. I should mention that you also now working or having an office-based clinic and commonly my understanding, and we will probably discuss this more later on, but you really see the real world patients in your clinic.
Of course, my patients are not 32 years old and fit. Oh, sorry, I thought I pointed out my patients are not 32 years old and fit for transplantation. The only small amount is fit for transplantation. The majority is up to 80 and they are comorbid. We do need data from this real world for our patients.
Thank you so much. As already has been mentioned today, there are three important aspects when treating patients: efficacy, safety, and quality of life. We will discuss these different pieces a bit. We start with efficacy. Professor, how do you define efficacy in simple terms? How do you prioritize the matter of efficacy in earlier line patients versus later line patients?
Thank you for this question, Sofia. I think that efficacy is the main endpoint in the earlier line of treatment. When we are in front of a young patient, fit patient, we have seen the brilliant overviews before. We are going to be more and more ambitious. Efficacy means to in young patients to aim to obtain the deepest responses possible which could be correlate with MRD negativity. Minimal residual disease negative means that we do not have any sign of disease. This is for the young fit patient. In elderly patient in frontal line, we call the care at the similar endpoint but going towards the following line of therapy. We start to balance between several aspects we consider to obtain an efficacy because this means to stop the disease. Efficacy could be absolutely correlated with the safety.
With the reducing as much as possible of the adverse events. Because a patient with adverse events does not live in a correct way, goes often to the hospital, needs a lot of supportive care, needs a lot of help for caregivers, for the entourage that is with him. He is in some way also related to people that live with him. We have also to consider the quality of life that particularly in later lines of treatments became an important concept. Because if we speak with the patient after three, four lines of therapy, they want also in some way to refresh from the lot of treatments that they have obtained during the year and want to enjoy the life, the nephew, the hobbies and so on. I particularly love the Trinity concept.
The idea that going toward the following lines of therapy, we have to balance between these aspects. In some way we have to find a compromise between obtaining the best efficacy as possible, but with the very good tolerability of treatment. Also, we are reducing the overload of the treatment, so not so many access to the hospital, not so many access for additional therapies. We have seen that we are going in a new immunotherapy world, but bispecific antibodies, CAR- T need a lot of supportive care, need intravenous immunoglobulins. This means to live a lot of days in the hospital. A patient with a lot of lines of therapy, who can stay at home, can be administered as much as possible in domestic setting.
The drug, like the ones that we are speaking about today, with the once a month administration, correlate perfectly with the Trinity concept.
Thank you so much. You are welcome. Talking about Pepaxti. We start with you, Professor Fenchel. From your experience, in which patients can Pepaxti give a meaningful efficacy?
I love this concept of this wording of Trinity as a Catholic. It is very important to us. In contrast—sorry, Claudio—in contrast to the Italian way, I would say the meaning of this trinity of the quality of life is also very important in younger patients within the first line treatment, because still myeloma, and it will last, is an uncurable disease. Therefore, the quality of life is as meaningful as the efficacy. Coming back to your initial question, which patient leads to your initial question, because actually melphalan is licensed for the fourth line and it is very well adapted to every our patient. If a patient comes in my office, he has had the typical formal treatments. I do not have to calculate if he can get melflufen. He can get melflufen. It is very easy because it is a very good known drug.
An alkylating agent, we learned 50 years ago. It is given to him very safely. We did this in our patients, even in severe renal insufficiency without any problems. It worked very well and is highly efficient.
Thank you so much. Professor Cerchione, you also do have experience from Pepaxti. Do you have anything to add based on your experience?
I think this is a fantastic drug for covering a patient that are in some way not eligible for new immunotherapies. Patients that need also bridge therapy. Because we know that, for example, patients waiting for CAR- T need a time for the preparation for the delivery of these cellular therapies. In some way this is also useful, really useful for patients in which we need to switch to a totally different mechanism of action. We are going in a world in which we have many drugs active against BCMA. We have many similar mechanism of action, but some patients are in some way or became in some way mono refractory. The idea to catch the chemosensitivities of our patient could be a perfect way to the idea to use melflufen to integrate melflufen in our daily practice.
I think that the idea to have a drug that has the best schedule in the therapeutic panorama that we have today. This is the only drug that we can administrate one time a month. I think that this is another particular situation that permits us to use Pepaxti in many patients that have also a not favorable logistic. We know that not every patient lives close to the institution where we administer the drug, that yet to come once a month and to be managed by distance during the blood checking and so on, is also a perfect way for people living in other cities and in some way also in countryside and so on. I think that we are discovering many good positionings for this drug. It is the unique drug in the new world of myeloma.
Because this is the only drug that has a totally different mechanism of action.
Thank you so much. We have already been touching a bit upon safety. Safety is always a concern. It's a concern for the patient, obviously for you as physicians, I think for regulatory authorities, obviously, but also payers. If we start with you now again, Professor Cerchione, how do you consider safety when you make your treatment decisions?
Safety is absolutely important. First, when we consider safety, we have also to consider the condition at the time zero when we start the treatment, because some patient in some way is coming with the previous comorbidities from other treatment, not in perfect conditions. In some way we have to consider the general situation in the moment in which we start the treatment. Safety is a really important problem because we know that a patient developing adverse events in some way could become less Saturn, could reduce the compliance to the treatment, and moreover could also need more access to the hospital, could need more cures, more visits, and so on. I think that a safe treatment means to have the patient in some way compliant, to continue that therapy, to in some way take the best from the treatment that we are ongoing.
Also, in some way, we see that a treatment that is not particularly safe could also be more expensive, not only in terms of money, but expensive in terms of access, in terms of need of personnel, of people that care for that patient. I think when we consider a treatment, we have to consider the package. At 360 degrees, a patient that needs to come to the hospital for adverse events means that the son or daughter should come with him, should lose the day of work, and so on. A patient that has a safe treatment can stay at home, can enjoy life, can in some way dedicate to the disease only the days in which the treatment has been planned. This is a particularly important point when we think about safety. We have to think not only of short-term safety, but also long-term safety.
Also in this sense I can say that melflufen is fantastic because I have never seen a strong toxicity, a high grade adverse event. I think that this is another way to consider this drug useful also for really elderly patients with big comorbidities, without strong caregivers and so on. Some patients live alone. This is another important point. If the drug gives some adverse events also post infusion, this could be a problem for patients not having strong caregivers. I think we have to consider all this point when we decide the best treatment for every patient. Deciding also according to safety means to personalize more and more the choice of the treatment.
Thank you so much. Professor Fenchel, do you have anything to add?
I fully apply to this saying, although this 360 degree of vision because especially for me as an office-based physician who works only from Monday to Friday, I'm a lazy guy. As you see, if the patient comes into trouble in Professor Cerchione's unit, he can delegate the work to some assistants. I have to do it by myself. I am strongly affected by a therapy which does not make any problems and Pepaxti does not make any. We did not see any side effects seen with other drugs, polyneuropathy, blindness or something else. It is working very well. Some hematotoxicity can appear. We did not see it in our patients. As I pointed out, even in renal insufficiency, a situation in which a myeloma patient typically comes, it is very easy to give melflufen.
We did it in such an effective way that we are able to send this data to the American Society of Hematology, where we can present this data in December.
That's fantastic.
I'm proud about it.
Yes, you should be. We are also proud about being able to make such a difference to those patients because they are really the patients that are out there in the real world. Thank you for sharing. Professor Cerchione, you mentioned before that you do not have seen any kind of concerns about safety and that it is easily manageable. What do you think about cytopenias in general? Because that is, if we look at the trials, the side effect that we see with melflufen. How do you manage them?
Sofia? I think that dermatologists are absolutely not afraid about cytopenia. This is our daily bread. We every day counteract with cytopenias, anemia, thrombocytopenia and so on. I think that we know perfectly how to manage these adverse events. I think that there is absolutely no drug that gives any hematologic adverse events, particularly later lines. Moreover, also in this case, let's consider the patient at time zero, also inside the trial, because a patient that has been previously treated for autologous stem cell transplantation, other regimen and so on, has also related to the toxicity to the other regimens. We have to consider at first this. I think that we know perfectly to in some way increase the counts of our blood cell with the growth factor and to protect the patient with prophylaxis, adequate weight, antibiotic, antiviral prophylaxis we do every day.
I think that compared also with other drugs that we use in the same regimen, melflufen is absolutely not toxic, neither from a hematological point of view. I have treated several patients, also strong patients from the disease, from the point of view of the disease. I have never seen some hematological toxicity that blocked me to continue the treatment. This is the important point of view.
Thank you so much. Now we are getting down to what is maybe the most important at the end of the day, and that's the quality of life for the patients, because they are not only patients, they are also people. Right? We have been touching upon this, but I would like you to continue to elaborate a bit on. We start with you, Professor Fenchel. What does quality of life really mean to your patients with relapsed refractory multiple myeloma?
Very important question. As I pointed out, quality of life is one of the main, if not the main concern in our daily practice. I may cite Dame Cicely Saunders. It is not only adding days to life, it is adding life to days. This is the most important thing we can give to our patients because they do not have anything from a therapy which prolongs their life for four weeks if for these four weeks they are spending six months in hospital.
In q uality of life may be, like Sebastian pointed out, on the way of life the patient is living. For example, two of my patients are colleagues who are running still their practice. For them, it is important to continue with the life without any great toxicities. Therefore, quality of life means maybe something else for each patient. On the long run, it is the main important goal we can deliver. As Claudio pointed out, it helps to keep the patient on therapy because he is compliant if he sees he can live on his life without any restrictions.
This is done with Melphalan
and Professor Cerchione. How does it influence the physician's treatment choice? I think you have been talking about this a bit. To summarize, what are the important aspects?
I think we have to discuss with the patient about the options that we have available. We should more and more be influenced as much as we go with the following line of therapies. I think that the treatment that in some way takes the patient more at home than in the hospital is particularly important because some years ago in every presented patient we had like a palliative care, like containing care. Now we can have a treatment that is at the same time active, but not overloading the patient's life. That, as Professor Klaus Fenchel was saying, these are. We have to recover the life of our patients. We have not to in some way increase simply the survival. We have to increase a survival of quality. I think that a man or woman that enjoys nephews, the family, is obvious, is a cares.
I think that is the best way in which we can prolong his life. We have not only to increase in terms of timing, but we have to increase the quality of life that he is going to live. I think that this can happen with the drug with a so comfortable schedule and so comfortable safety profile. I want that my key message is that we have to discuss with the patient about the options that we have, also discussing in this sense what is the price to pay for obtaining that treatment. I think that in this way, particularly in every procedure, the patient, we can take the shoes together, we can guide our patients as caregivers, but we have to present what is going to be that treatment in a global situation, in a global view.
I love how you said it, Professor Fenchel, and how you are describing it, how you are not only adding days to your life, but life to your days. I think that's something we can all relate to. I think it's a beautiful description of quality of life.
I have to admit it is stolen. It is stolen from Dame Cecily Saunders.
I'm sorry, stolen with pride. Last question. It's obviously very important to the patients, to the relatives, but why is it important to you as a physician and why is it important to the payers? Because I know you are in contact with payers probably every single day in Germany.
Yeah. Also, Professor Theurich mentioned the costs of treatment after bispecifics and CAR- Ts with immunoglobulins, for example, if you have such side effects and you have to treat them, this is very costly. The cost givers are interested in drugs which work without such effects. If you have to give immunoglobulins for at least one year, at least it is EUR 1,000 per month, so it will add rapidly up to an enormous amount. Therefore, taxpayers are interested in having drugs without such effects.
Is it the same situation in Italy, from your viewpoint?
Not only from the cost of immunoglobulins, but in some way also from the cost of the staff of the hospital that cares the patients for supposed supportive care and so on. We block a place in the hospital because usually we perform intravenous immunoglobulin in some regions to spare some money. Moreover, these immunoglobulins came from donors. So we have also in some way a lack in some period of donors and so on. I think we have to consider also in this case, and moreover, a patient that needs immunoglobulins could have some infections. With the use of antibiotics, with potential recovery and so on. We have to consider that we have also in this case to balance safety and efficacy.
I think also in this case also for payers, for your investors, that the idea to have a drug that has a totally different mechanism of action is something that we need in myeloma, because in some patients we really need to switch to another solution. Some patients are unfortunately totally refractory to immunotherapy and we need another solution. I think that melflufen can be considered in same time a back to the past and back to the future treatment. Because this is a drug that we had used in the past, but we are using in a new way with a better tolerability. I think that we have not only to consider the data that we are seeing from the registrative trials because in our real world we are going to see more and more surprises.
Some patients are in treatment also in my countries from several years with very good tolerability and they are really enjoying the life. I think this is the best message that we have to consider. Not simply the median expectation of response, but the range of response that we are going to see. Also, in some way, the patients reported outcomes that tolerate very well this treatment and love to have only one day per month dedicated to the administration of therapy.
I will steal that one with pride. What did you say? Back to the past.
Back to the past and back to the future at the same time.
Fantastico.
New slogan together with the trinity. We will use also this.
Excellent.
Here's an LB for Michael J. Fox.
Yes, yes.
It's time to start to wrap up. Try in one sentence if you can. You may use two if you want to. How would you explain why Pepaxti melflufen is so important to today's treatment landscape? I'll start with you, Professor Fenchel.
One sentence. Okay. It's an old but prominent wine like Bordeaux or Pomerol, only in new tubes. A fascinating way of delivering a known drug with certainty into your target. Marvelous.
Approved, Professor. Jakob Lindberg.
Effectiveness, very good. Tolerability, no exclusion of any patients. We have no preclusion to use this drug in any category of patients. Also big comorbidities, renal failure. Everyone can be treated with this drug. This is something of particularly important because I underline and also the idea of positioning also as bridge therapy. This is another use that we are doing a lot in clinical practice. In 110 cents, efficacy, tolerability, no limits for every patient.
Thank you so much. Working as intensively as we do at Oncopeptides with the product, it is confirming and it is also rewarding to hear you speak about how it acts in real life and how it can be positioned. Because as I said in the beginning of my talk today, we are dependent on getting that information and that advice to ensure that the right patients get Pepaxti at the end of the day. I would like to thank you so much for taking time being here and online, and then we will move on to the next part. Thank you so much.
Thank you.
Bye.
Thank you to the professors and also to Sevilla for moderating and also for everyone else that has been participating in this first half of our capital markets update. It's now time for a short break and we're amazingly actually a bit ahead of schedule. We will be back at 10:30 A.M. in about 12 minutes and we hope to see you then. Welcome back. We'll now widen the lens beyond Europe starting in Japan. We will then cross the Pacific Ocean and to the U.S. before finishing up with the presentation from Sofia Heigis on Oncopeptides as an investment and answer questions from the audience. The multiple myeloma landscape in Japan is evolving rapidly. To guide us through this we have Professor Shinsuke Iida from Nagoya City University who will give us an update on the clinical landscape and trends shaping treatment in Japan.
Hello, this is Dr. Shinsuke Iida, I'm working at Nagoya City University Hospital. I'm going to show you the positioning of melflufen capacity in the treatment sequence of the patients with multiple myeloma in Japan. Here I show you my COI in Japan. Since the approval of bortezomib in 2006, three types of proteasome inhibitors, three types of immunomodulatory drugs, and three types of antibody drugs including anti-CD38 antibodies and anti-SLAMF7 antibody have been approved for immunotherapy. Ide-cel CAR T-cell therapy was approved in 2022 followed by the bispecific antibody elranatamab in 2024 and subsequently teclistamab and talquetamab were approved in 2025 and also in the same year, combination therapy with antibody drug conjugate belantamab mafodotin was also approved.
The guidelines from the Japanese Society of Hematology and the Japanese Society of Myeloma recommended induction therapy with bortezomib, lenalidomide, dexamethasone, BLD therapy as a standard treatment for newly diagnosed transplant-eligible patients with multiple myeloma. However, in 2025 the four-drug combination therapies such as Dara-BLD and Isa-BLD therapies were approved for transplant-ineligible patients. Dara- LD, lenalidomide, dexamethasone, and Dara- MPB, also called as BMP therapy, were previously the recommended treatments. However, in 2025 Dara-BLD and Isa-BLD therapy were also added to the recommended treatment. This slide shows a post-transplant survival period from a prospective registry study conducted by the Japanese Society of Hematology. For patients with newly diagnosed multiple myeloma and treated between 2016 and 2018 when anti-CD38 antibody use was not possible as frontline therapy, the 3-year survival rate was 70% with a median survival of approximately 70 months.
However, in transplant ineligible patients on the right panel, the median survival did not reach five years, representing unsatisfactory results. Majority of the multiple myeloma patients experience recurrent disease. This slide shows the prognosis for the triple class exposed relapsed or refractory multiple myeloma patients who relapsed after treatment with at least one proteasome inhibitor, one immunomodulatory drug, and one anti-CD38 antibody, analyzed from Medical Data Vision Claim database in Japan. Being triple class exposed resulted in a median survival of 17.4 months thereafter, and treatment for triple class exposed RRMM has been an unmet need, but the development of immunotherapies like CAR- T therapy and anti-BCMA and CD3 bispecific antibodies has improved prognosis. While the overall response rate with CAR T- cell is 71%, patients achieving less than complete response have short response durations, and even those reaching CR often relapse gradually.
Similarly with bispecific antibodies like elranatamab, one-third of patients do not respond and even responders achieving less than CR often relapse. Early RRMM patients frequently have lymphopenia and T cell dysfunction, which can also hinder the efficacy of immunotherapies. Melflufen, a peptide drug conjugate, is highly internalized into plasma cells and acts as an alkylating agent, causing DNA damage. It can be expected to have some efficacy even in exposed RRMM patients. In the HORIZON study, which included 76% of RRMM patients resistant to both proteasome inhibitors and IMiDs, an overall response rate of 29% was demonstrated. Administration every four weeks allows for outpatient treatment offering high convenience. Results from the OCEAN study, a randomized phase three trial comparing melflufen dexamethasone with pomalidomide dexamethasone therapy in RRMM patients with prior two to four regimens including lenalidomide and proteasome inhibitor are presented in the ITT population.
The PFS benefit of melflufen dexamethasone therapy was modest. However, in patients who had not undergone autologous hematopoietic stem cell transplantation or who relapsed more than three years after transplantation, a significant benefit was demonstrated with a hazard ratio of 0.58 and a median PFS of 9.3 months. Patients who relapsed early after receiving high dose melflufen therapy prior to SCT are thought to have reduced sensitivity to alkylating agents. Conversely, in the era where proteasome inhibitor IMiDs and anti-CD38 antibody therapy have become key drugs in early lines of treatment, these results indicate that alkylating agents retain efficacy even in late relapse. Grade 3-4 adverse events are primarily hematologic toxicities, necessitating vigilance for infections. However, it can be managed with appropriate prophylaxis, drug holidays, preventive antibodies, and use of G-CSF.
Should melflufen become available in Japan, it could become an option for triple-class refractory cases or relapses following immunotherapies. Proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies are used as key drugs in the frontline treatment and in the salvage setting of early relapse in multiple myeloma. Now in Japan, in the day-to-day relapse of myeloma, CAR- T and bispecific antibody therapy are chosen in triple-class exposed refractory patients. One third to one half of the patients can achieve CR and show long-term efficacy by immunotherapy, while the remaining patients do not respond to immunotherapy or show early relapse even after immunotherapy. Thus, melflufen is a good option as a salvage therapy for the patients who do not respond to immunotherapy or those who respond transiently and eventually develop relapse. Also, melflufen can be chosen for the triple-class with T- cell exhaustion.
It can be conveniently given every four weeks in the outpatient clinic as melphalan is an alkylating agent. Early relapsed patients within three years after high dose melphalan with ASCT came to show resistance to similar alkylators in patients who are naive to alkylators or those who receive ASCT and relapse after three years. Melflufen is an alternative and good choice as salvage regimen in patients with rrmm. This is a conclusion. Thank you very much for your attention.
We'll now shift focus to the U.S. where Oncopeptides' proprietary PDC platform could help shape the next generation of treatments. Sharing his perspective is Professor Paul Richardson from Dana-Farber Cancer Institute in Boston. He's one of the most respected global leaders in multiple myeloma research.
Hello, this is Dr. Shinsuke.
Hello, everyone. My name is Dr. Paul Richardson and I serve as the R.J. Corman Professor of Medicine and the Clinical Program Leader, as well as Director of Clinical Research and at the Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute in Boston, Massachusetts. It's my privilege today to talk to you about what I see from my own personal perspective of the evolving role of peptide drug conjugates as part of myeloma therapeutics. In that context, I really wanted to sort of share with you some background pathobiology first and then talk to you about the evolving treatment landscape for myeloma and then help perhaps understand what I consider the real potential and value of peptide drug conjugates in this rapidly evolving but still very challenging treatment space. First and foremost, myeloma is not one disease.
It's really important to recognize its complexity both at diagnosis and then at relapse, and to understand that genomic events and a really remarkable phenomenon called clonal evolution that essentially arises from myeloma cell stemness with numerous mechanisms of resistance emerge. When we think about treatment, it's very important to realize perhaps some basic principles that on the one hand, one size does not fit all and we need to be highly tailored in our therapy, but two, we need all our therapeutic options during the natural history of the disease in any particular patient. This slide seeks to try and summarize that. As you can see, there's tremendous genomic complexity within the disease itself. These are whole genome sequencing studies of what we call WGS images of patients during the course of their natural history of the disease.
This is a patient at diagnosis with over 5,000 mutations, and then at relapse, these more than double to over 12,000. This is after sequential therapies. I think the important point to recognize here is that as we throw our arms around this kind of complexity at relapse, we need agents that actually target stemness, in a sense within the disease process as well as also at the same time leveraging the immune system and so forth. I really show on the right side of this slide some of the complexities and challenges of what we deal with in the relapse setting, in particular extramedullary escape, which has become a major therapeutic challenge in the setting of modern treatments and in particular immune therapy. To meet this challenge, the good news is that we have multiple treatments either currently approved or certainly under investigation.
I'm seeking to summarize them here for you to show backbone and standard of care agents over here on the left, including immunomodulators, proteasome inhibitors, monoclonal antibodies, and certainly in the European health jurisdictions, the availability of histone deacetylase inhibitors. In the context of recent approvals and particularly therapies utilized in later relapse, I've sought to show you here antibody drug conjugates, targeted therapies under which venetoclax comfortably falls, as well as melflufen, selinexor, and other agents. I would bring your attention here to the role of melflufen, recognizing that it targets stemness in the disease. Selinexor has an XPO1 mechanism and venetoclax targets a specific abnormality, translocation 11;14 or BCL2 overexpression. These therefore constitute really targeted therapies. We'll talk more about the mechanism for melflufen in a moment.
Over here on the right of the slide, I'm really summarizing CAR T therapies, bispecifics, and then in the newer era of novel oral therapies, the really remarkable data around the cell mods as well as others that are evolving, including P300 inhibition and more. Very importantly, as we think about the therapeutic landscape, I'm really trying to show you what I see as a critical role of melflufen in this tapestry of therapeutic strategies. I think as you can think about the new era of immunotherapy for relapsed myeloma and indeed newly diagnosed disease, I would argue that there is a strong rationale for the positioning of peptide drug conjugates into this repertoire, not least of which because we've come to recognize the real challenge of what we call immune exhaustion, which means that basically constantly leveraging the immune system literally runs out of steam.
We must have the ability not only to target stemness and to target the disease in a very different and non cross-resistant fashion, but we must use strategies that will then allow immunogenicity to emerge. We have preliminary evidence that peptide drug conjugates may actually provide a unique strategy to do so. As we think about this, what is melflufen all about? You have heard already very nicely about a lot of the science underpinning it, and I just want to spend a little bit of time on that because I think it is important to emphasize this is not simply a traditional chemotherapeutic, far from it. It is actually an ability to deliver a warhead in a highly targeted fashion, leveraging the immunopeptidase systems into the tumor cell selectively, with the cytotoxic payload being released by a peptidase-driven hydrolysis of the parent drug.
This basically irreversibly damages not only tumor and DNA and induces apoptosis, but critically mitochondrial DNA. At the same time, I think it's important to appreciate what's over on the left side of the slide here, that melflufen rapidly enters the cell due to its lipophilicity, which is really important, and specific diffusion characteristics. It's truly a highly targeted agent with selective delivery to the tumor cell. As we think about agents like peptide drug conjugates and antibody drug conjugates, remarkably they have some similarities. The preclinical evidence is very striking for this. As I just showed previously on the figure, there is clear evidence that melflufen works in melphalan resistant cells and basically we are therefore able to leverage this.
What is really important to note is that the cytotoxicity of melflufen in myeloma is not affected by co-culture with supportive cells that may confer resistance. What is particularly important is its activity in 17p deleted myeloma and this potential for enhanced upregulation of calreticulin and immunogenicity, which I touched upon. I think very importantly, there is this enhanced immunopeptidase activity in extramedullary disease, which may explain its potency in this setting, which we will come to in a moment. I show on the right side of the slide here how m elflufen is able to demonstrate preclinically from patient-derived samples, superior efficacy over melphalan in myeloma. Very importantly, in patient-derived material, we have been able to validate this observation. In terms of our mouse modeling, this basically is summarized here.
As you can see, I mentioned this a moment ago, but clearly melflufen is able to overcome melphalan resistance. At the same time, when we look at our in vivo modeling, you can see here the control and the melphalan group doing actually relatively similarly poorly. There is a significant, significant improvement with the use of melflufen in this setting. This was earlier data, but helps really to sort of crystallize some of the original promise preclinically, that then led to us not only conducting an exhaustive phase one study that clearly established dose and schedule for the drug, but then rapidly taking this to a phase two setting in the HORIZON trial. I think very importantly showing in almost 160 patients a response rate that was consistent at around 30%, a clinical benefit rate reflected by minimal response or better in 45%.
Very importantly, activity in extramedullary disease, as well as a consistent signal in triple-class refractory patients. This actually provided the bedrock for the accelerated approval of melflufen and dexamethasone in both the European and U.S. healthcare jurisdictions. Now, the OCEAN study you'll have heard about, and this showed it met its primary endpoint, it demonstrated a PFS benefit. I think what's terribly important is to understand that this study was challenging. It basically conferred melflufen index against pomalidomide index. It's important to note that studies in this setting where there's been MOA against MOA, be it venetoclax in the CANOVA study, be it belantamab mafodotin in the DREAMM-3 study, have actually proved very challenging in interpreting their outcomes, not least of which both DREAMM-3 and CANOVA actually failed to meet their primary endpoint. In striking contrast, of course, melflufen did meet its primary endpoint.
What was particularly important is that when you looked at subgroups that were biologically rational, age, prior transplant and so forth, you saw important benefits for melflufen and dex over the powerful comparator of pomalidomide and dexamethasone. Also recognizing that if you position melflufen too close to transplant, the resistance in the transplant-exposed patients within three years was striking. Similarly also, and this is important in understanding the data, the performance of pomalidomide in these younger post-transplant patients was that much better. Important to recognize the rationale for the subgroups. This is of course why the European Medicines Agency not only approved the use of melflufen in the advanced setting, but even went further than that and approved it in first relapse. What about combination strategies?
I think the real promise of melflufen in my view lies when it's combined with combination strategies. In this regard, the ANCHOR data, the OP-104 study, clearly shows that when you combine melflufen either with bortezomib and dexamethasone, or daratumumab and dexamethasone, the results are really striking. You can see here an overall response rate of 73% with about a third of patients achieving VGPR or better. These are refractory patients of course, so important to bear that in mind. Second of all, when you combine melflufen with bortezomib, the results are arguably very similar and very promising with an overall response rate of 78%, about a third of patients achieving VGPR as well, and the median PFS being a striking 15 months, with a median overall survival exceeding 33 months.
This platform in my view is ripe for further development and of course, melflufen-daratumumab was already explored in the context of the LIGHTHOUSE study. This study unfortunately had to be closed prematurely after 50+ patients were enrolled, 27 per arm. Even then, as you can see, compared to a daratumumab control, the PFS benefit was striking, even despite the small number. When you look at the actual relevant subgroups, in other words, patients who are greater than three years from transplant, even though these numbers, again we have to be careful because they're relatively modest, you can see here that the hazard ratio is really quite remarkable at 0.06 with a very obviously impressive P value. Again, I think this is really promising data for the combination approaches.
I think critically as we think about melflufen and obviously it's performing well in those healthcare jurisdictions where it's approved, I think as we think about the future, we need to go actually into this space with even more excitement. Given all this excitement around both ANCHOR, LIGHTHOUSE, and I think the really consistency of results seen first with HORIZON and then frankly with when you break into the subgroups, particularly what we saw as the important positives from OCEAN, including of course the full approval from the European Medicines Agency, which I think is a ringing endorsement for the drug in itself. I think as we look to the future, we need to think about next generation peptide drug conjugates. I'm particularly excited by the promise of OPD5 preclinically and this is exquisitely active.
At the same time there are next generation peptide conjugates even beyond OPD5, including OPDC3, which preclinically show remarkable promise. My hope for this class of drugs is that we'll continue to develop them as even more efficacious, more active and well tolerated drugs. It's important to note, and I didn't get a chance to touch on this before, but the toxicity profiles are very consistent, they're myelosuppression primarily, which is something for us as hematologists, oncologists that we can readily manage. The important positives is that our patients do not see alopecia, which is hair loss, or mucositis. The infection signals are remarkably, and as you can see even in this last slide of the Lighthouse trial, the balance of toxicities between the daratumumab base control and the combination approach are remarkably similar and remarkably, again, manageable, which I think is a key message.
The other point is that as we further develop this particular strategy of targeting stemness in this disease, we're going to actually be very well placed to be able to take advantage of immune exhaustion and other challenges that we face, particularly in the immune therapy era. I think I see promise for this as a platform not only in the relapse space more broadly, but in particular after BCMA targeted approaches have failed. One could even argue that combining it with bispecifics in a rational fashion may make great sense, particularly if one considers the very compelling data around the use of melflufen and bortezomib and dexamethasone in this setting. At the same time I can say that I think the promise of OPD5, which may be even more efficacious and less toxic, I think is particularly exciting.
Putting it all together, I'm very hopeful for the promise of melflufen as we go forward. I'm very hopeful for the promise of OPD5 as a next generation approach. I think what's particularly exciting, and this I think is a final point to sort of close on, is that the real world experience that we've seen emerging since melflufen's approval in Europe, and indeed for the short period that the drug was available in the United States, on its accelerated approval pathway, we've seen a consistency of signal in those real world data which are very similar, if not even better to the studies that I've just shown you. With that in mind, I'm very hopeful for the future of peptide drug conjugates as an integral part of therapeutics in myeloma management. I want to thank you very much for your kind attention.
We have now heard from experts across the world and together they painted a very clear picture. The medical need is high and Oncopeptides is well positioned to help address this. With that, it's time to turn back to the company perspective. Sofia Heigis will now take us through where Oncopeptides stands today and where we are heading next. First, Sofia, maybe a few words reflecting on the videos that we just saw.
Yes, so we have seen, we've heard experts from our key markets in Europe today, from Germany, Spain, Italy. We now heard from professors from Japan and the U.S. I think it's very consistent. The patients are out there. There is a high unmet need. The real world looks different from clinical trials and we have a great potential to grab to be able to generate value for these patients, but also of course to be able to generate value for our shareholders. This is where we stand here and now, and if we look at Oncopeptides as an investment case, I showed this picture before today, our core business is very much focused around our European commercialization where we are aiming to take us to solid ground and profitability by the end of 2026.
In parallel we are working to provide patients with Pepaxti in other parts of the world where obviously the Japanese market is of great interest to us. What we are not talking that much about now that I will get more into detail today is our pipeline because currently we are progressing in preclinical and I will tell much more about what that means. Knowing what we know and seeing the multiple opportunities, we know that there is a bright future also long term. As I said, all of these different pillars added up together can create a very successful company that can make a lot of difference to patients both across the globe in multiple indications and disease areas and generate a lot of shareholder value. Why should one invest in Oncopeptides? Already here and now we have a growth momentum.
We're showing that we can make a difference to patients and we have a fair addressable market potential in Europe of SEK 1.5 billion. It's based on that we have a full approval and we now also have a foundation to stand on in our key markets. We are working on strategic expansion and our pipeline is truly exciting. We have been talking a lot about Europe. I hope you have gained a lot of insights about the European patients and the views from the European experts. We will have a Q & A later on when there is more chance to get even more understanding and clarity. Our focus is really to drive this launch and we have seen a very positive trend that can take us to profitability.
This trend is really driven by the real world performance of Pepaxti and how we can see that this product is really working and how we can see the different positions for Pepaxti growing as a complement to immunotherapy. When it comes to partnerships, we have different types of partnerships and we have this because we want to be able to bring Pepaxti to as many patients as possible across the globe because we know there is a high unmet need. We heard it from Japan, we heard it from the U.S., but there are also patients in quite complex geographies like Africa, Middle East, where there today is no experience or awareness about Pepaxti. To ensure that we explore those markets, we have signed a partnership with the World Orphan Drug Alliance.
They have small member companies that are focused on rare disease and specialty care products and they are currently exploring, discussing with experts to understand if there is a need for Pepaxti and if we should go further in those markets. There is an opportunistic potential in such geographies, but there is also a clear potential in other geographies where we do have experts that are asking for Pepaxti and such country is South Korea. They actually pushed South Korean companies to come to us to license in Pepaxti, which we did. That company is currently working towards regulatory submission and it is called SCbio with great support from the experts and early access programs going on. One very important geography obviously is Japan.
As we heard from Professor Iida, Japan has a growing patient population, they have an aging population overall and they also have a lot of drugs available, meaning that many patients do move on to the late line setting. We have a favorable regulatory landscape for Pepaxti because we had formal discussions with the regulatory authority and we have a path forward on how to get Pepaxti approved. The market access process in Japan is swift compared to Europe, so you can get fairly fast access to the market. As confirmed by Professor Iida, there is a high unmet need. As he said, 30%-50% of the patients respond well to immunotherapy. There are many, many patients that need something else and then Pepaxti can be an option.
If we look at Japan size wise, considering of course the population and the level of pricing, et cetera, we can reflect it to the German potential in Europe. When it comes to those negotiations and discussions I mentioned many times, this takes time because there are a lot of processes and governance in such discussions. We have several interested partners because it is, I would say, a favorable deal and we are really working towards a win-win deal and we are currently in late stage due diligence. I commonly talk a lot about Europe and our partnerships. Today I will focus a bit more on Oncopeptides' pipeline to give you an idea of potential opportunities going forward for this company.
We have heard many experts today talk about the promise of the peptide drug conjugate platform and there are multiple opportunities that are global across different indications. Here we are building on a proof of concept with Pepaxti. We know there is a peptide drug conjugate really working in clinic and we can build from that. When it comes to the SPiKEs platform, that is a truly innovative platform with small affibody constructs that are engaging natural killer cells. Super exciting global potential. This platform could span all the way from oncology, hematology to autoimmune disease. If we look at the different assets, we have the ability at Oncopeptides to generate many PDCs and SPiKEs with different types of targets.
We have started and assets we have currently that are getting closer to becoming IND ready, which means that they are getting closer to getting to clinic and human beings, are OPD5, OPDC3 for the PDC platform, and OPSP1 for the SPiKEs platform. I will speak much more about these assets thinking about how to get there. I mentioned before our goal here and now is to become a profitable company, and we are working in pre clinic with small means, supported by grants, collaborators to progress. We have a bit little lot of exciting findings, and we are obviously looking into how we can, in partnerships or by other means, be able to progress our pipeline to really be able to realize the value both mid and long term from these assets and to really be able to make a difference for more patients.
I'm commonly talking about as a pharmacist, this is kind of the core of my education and I'm commonly talking about the preclinical progress. What does it mean if you have not done this yourself or if you are not in the field of pharmaceutical development? To put it quite simple and to try to structure it a bit. What we do is that we look at the pharmacology of the drug and the preclinical proof of concept. To put it simple, it means how is this drug working? What is the mode of action? That is of course serving you the different opportunities when you know how different diseases are appearing on how to match this drug with different indications. We also look at safety and toxicology. You have to do toxicology studies most cases in animal models.
The pharmacology you can study in cell based assets but here you need to move into animals to see how it's working in vivo or in a living model. You also look at pharmacokinetics and pharmacodynamics. This is very important because it's about how the drug is going through the body, how it's broken down, how it's excreted. This really matters to how you can dose the drug, the efficacy of the drug, but also the safety of the drug. To get a good understanding of the pharmacokinetics and dynamics is also critical. Last but definitely not least, you need to do chemistry manufacturing and controls called CMC. That is when you start to look at how you can produce your drug and how you can do it in a safe and repetitive manner.
You can really scale your production first for clinical trials and later on, of course for the commercial market. The preclinical development, it takes time, but it can really shorten the time to market because if you do it right, you can really find the right target populations, the right disease areas, indications for your drug. That is of course a major competitive advantage. If we move into the PDC platform, here we have Pepaxti we've been talking about, so we do have the clinical proof of concept, which is important to know that the class of drugs is really working in at least one type of disease and in human beings.
It is very clear that the PDC platform can, in many different tumor types, complement immunotherapy, as it is completely independent of immunotherapy and can also overcome resistance mechanisms, which is ensuring that we can provide an improved chemotherapy or alkylator. It is the only one of its kind. I mean, there is no one else developing PDCs as we do and it is highly combinable. Professor Richardson mentioned how we have done combination studies with Pepaxti and, based on the safety profile, you can combine Pepaxti with many different drugs and that is also an advantage in many different tumor types. Here we have an opportunity for both hematological as well as solid tumors. This is just to show, because we have been looking at the mode of actions many times today, but all of the PDCs, they are working based on the same smart principle.
In our research site we can optimize the PDCs for certain indications or diseases. We can also optimize the entrapment of the cytotoxic enrichment inside of the cell, which we have done with one of our PDCs. This is a map for the different PDCs and our current thinking on different opportunities. We have seen that melflufen, and we know that melflufen or Pepaxti is already out in the market, and here we are generating the very important real world data. OPD5, we heard from Professor Richardson, has a great opportunity as a combination PDC, and we are running a gliopep project that I will talk a bit more about that is focused on glioblastoma. We have OPDC3 where we have exciting data in multiple indications.
Just to summarize for OPD5, here we do have a global opportunity as a combination PDC for relapsed refractory in multiple myeloma patients. Even though that market is crowded, there is still a need for PDCs because immunotherapies are not curing the patients. When the patients cannot tolerate or cannot respond to immunotherapies, a PDC is needed and to combine it will probably or most likely enhance the efficacy based on all the data we have. We had a lot of learnings from the Pepaxti program and this means that we know how to develop this in combination and we have a significantly de-risked clinical development program from that perspective.
We also have been in contact with the FDA and we have agreed on a clear path moving ahead for this US and what we are doing currently at Oncopeptides, because this seems all very clear, is of course to look into when and how we can get funding for this. We are discussing with several different partners that may be interested in this area. When it comes to OPDC3, we have been working to optimize the entrapment inside of the cell of the cytotoxic agent. It is also a different alkylating payload that comes with OPDC3 that we have designed ourselves. It is quite different from melflufen and more suited for other types of tumors. The preclinical data we have supports that it is very highly active in AML, in lymphoma, in triple negative breast cancer, and in ovarian cancer cells.
All those different types of cancer types do have treatment options today. There is still a high unmet need for the aggressive relapses. Also with OPDC3 we have the combination synergies demonstrated with immunotherapies and cytotoxics. This could be all the way developed as a combination. Here we have a long patent all the way until 2042 without any extensions and of course a global opportunity. I will move to talking a bit beyond multiple myeloma because commonly we are very focused and that's our everyday, we are very focused on multiple myeloma and launching Pepaxti in Europe. A company also needs to think about the midterm and the long term. Here we have different opportunities. These are just examples of what we are looking at currently.
As you can see, we have the PDC platform on the top and the SPiKEs platform at the bottom. The opportunities we are seeking are where we believe that our assets can really make a difference, where we see growing markets. Growing markets means that there is a very high unmet need. There will be, if you find an asset to treat glioblastoma or these autoimmune diseases that I will talk more about, a willingness to pay for these innovations. Let's talk a bit about glioblastoma and why we are excited about this opportunity. Oncopeptides, this is a brain tumor with a very high unmet need and obviously a growing market potential given that the population is aging and usually this tumor comes in the later part of their life. It is one of the most aggressive brain cancers.
It grows fast, it always relapses and there is no cure. Two to three people per 100,000 each year get this. As I said, the diagnosis is usually above the age of 60. With aging population, the market will grow with better therapies. The market will grow because there is a poor survival today, even with treatment. Radiation, surgery patients live only about 12-15 months after they got their diagnosis. New brain penetrating therapies are urgently needed. When we talk about the brain, it is very clever and it is needed for all of us that we have a quite strong barrier around the brain. To get drugs into the brain is complicated. That is the first aspect you need to explore when you are developing drugs for brain tumor.
Because if you don't get your drug into the brain, it won't do any good even if you have effect in, for example, in vitro or in cell preclinical studies. Today all treatments still dominate and that's alkylating agents, conventional old alkylating agents. There are very few new options because a lot of trials have failed. There has been a lot of efforts, there are still a lot of efforts and there are pipelines with a lot of development of, for example, immunotherapies. It is difficult for most drugs to reach the brain and only some patients respond. If we look at for the standard of care today, for example, there are resistance mechanisms being developed. Only a subgroup of the patients can actually get support from, for example, temozolamide, which is the standard of care.
So far, even if there are studies ongoing, there is no immunotherapy approved because it has not really worked so far. As I said, it is a very short survival and a tremendous high unmet need. This is exactly the type of disease that Oncopeptides commonly get excited about because we can really make a difference here. If we look at the market potential, this is from different types of reports and it is always very difficult to predict what is going to happen the coming 10 years. The prediction is that the unmet need is so high, so if you get therapies approved, you will get pricing that reflects the high unmet need. The market is considered to grow both with, of course, more therapies, but also with an aging population. It is a sizeable market, even if it is a rare disease.
There is definitely a fast to market opportunity here where if you show good data early on, you can most likely get an accelerated approval in, for example, the U.S. and potentially a conditional approval in Europe as well. Why do we believe that the PDCs have potential to help patients with brain tumors such as glioblastoma? It is difficult to penetrate the blood-brain barrier and we have that confirmed. With OPD5 we have showed promising preclinical data in a consortium where we have done collaborations around glioblastoma and we actually got innovation grants to do this because there is such a high unmet need. We have seen that OPD5 is one of the drugs that are penetrating and getting into the brain to the highest extent when they look at broad assays and there are even some published results about this.
That is the first step to understand. We also know of course from Pepaxti that we have in real life that physicians tell us on patient by patient cases that you see reductions of metastasis in the brain. We have all reasons to believe that the PDC such as melflufen or OPD5 in this case can really penetrate the blood-brain barrier. That is the first step to take. The second step to take is to understand whether we have a tumor killing effect. We have very recent results that are not yet published from animal models that show that we really have a strong tumor reduction in preclinical models. We are super excited about this opportunity because there is a very high unmet need and there is great market potential.
We do believe that we are starting to see, even though there is work still to be done in the preclinic, that we have a strong therapeutic rationale and a differentiated mode of action, that is logic. We understand why we see these results, which is always important. As Björn's mentioned earlier today when we talked about how HealthCap is assessing different investment opportunities and there is a potential for a fast track to market with accelerated approval should we see positive results. The SPiKE platform comes with a different opportunity because it is very different from the PDCs. The SPiKEs are small polypeptide-based innate killer engagers. What does that mean? It is a very complicated name. Let me try to explain this simple.
We have, to the left we have the natural killer cell which is part of the innate immune system and it expresses CD16A. To the right we have a sick cell. This can be a tumor cell or it can be an autoimmune cell that is expressing BCMA. I think that Professor Theurich explained the differentiation of B cells very well earlier on. I will get back to this again to remind you of what we're talking about. The opportunity here with our affibody is that as you can see and as you will see on the next slide, it's a quite small compound and it's basically a bispecific smaller antibody, if to put it very, very simple. What is then the potential for this platform and for our first candidate drug that is then bispecific for CD16A and BCMA?
With a smaller compound you get higher proximity, so closer binding with the potential for higher activity. This has been an issue with NK cell engagers to really be able to show meaningful efficacy. Based on the clinical data that is out there so far it's not a lot, but we believe that we have a real differentiator here. We also see in the pre clinic that we have very good tissue penetration. When we look at spheroids of tissue and we light them up, we can see that the affibodies are distributed in all of the spheroid while antibodies are only distributed on the surface. This means you can penetrate tumors much deeper. We also heard about immune exhaustion today, that the immune system gets exhausted and it is important for the immune system to rest in between treatments.
With such a small compound you get an excretion through the kidneys, which means that the NK cells get the time to recharge. We believe that there is potential for a more durable therapy. We know that this is super exciting. When we talk about the SPiKEs platform to other pharma companies and biotechs, because we are open, obviously out there scanning the market, exploring interest for collaborations, this is a point that everyone is getting excited about. Also the tolerability, because we heard today that the T- cell engagers have very good efficacy, but they come with a lot of infections. There is a risk for cytokine release syndrome, which is a very severe state and requires hospitalization. There is also neurotoxicity. Compared to T- cell engagers, what the clinical data on NK cell engagers is showing is that they are very tolerable.
It is also logic based on how the NK cell is working in the immune system that there should not be a risk for this adverse event. As I said, the SPiKEs have the opportunity in both oncology, hematology as well as immunology. Now we will get a bit into immunology because that we have also not been talking a lot about. I think it is time for us to start to educate all of us in this area because we believe it is a significant opportunity. Very simple, autoimmune disease covers a wide range of conditions and many of them have high unmet medical needs.
What has happened already been proven and seen is that the bispecific engagers, the T- cell engagers, they are now developed for cancer, but they do have a potential in autoimmune disease because it has been demonstrated that they are effective in clearing self-targeting antibodies. What does that mean when you have autoimmune disease? The immune system is getting confused, to put it very simple, and starts to produce autoantibodies. These autoantibodies are attacking your own tissue and organs. That is the autoimmune disease. If we look into pipelines for autoimmune disease, most competitors are focused on CD19, CD20 targets, whereas OPSP1 is, as I showed previously, targeting BCMA, and to target BCMA provides better targeting of antibody producer plasma cells while sparing other B cells. I will also explain this in a very short while.
One reason to believe that the SPiKEs really have a place here is because if you think of the characteristics of the disease and you think of our SPiKEs versus, for example, T cell engagers, the characteristic is that there is low short-term mortality or there is a lower risk to die short term from these diseases than, for example, aggressive tumors. It is more of a substantial long-term morbidity. The patients are sick over a very long time. When we look at T- cell engagers, they are characterized by a very aggressive and high level of immediate activity and that comes with side effects. While our SPiKEs, we do have the reception to believe that there is a potential here to provide an immunotherapy that is more like a hand in the glove.
The characteristics of our NK cells with more durable efficacy and better tolerability fit better to these diseases or have the potential to fit better to these diseases. This is what we are exploring in the preclinic currently, obviously, and thinking of how to be able to demonstrate this. Talking about the differentiation with BCMA, as we are quite unique there with our BCMA targeting affibody or spike, it is expressed on the plasma cells. This is the B cell differentiation. B cells are part of the immune system and they differentiate and mature into different cells that are producing antibodies. You have short-lived and you have long-lived plasma cells. When you have autoimmune disease, they start to produce these autoantibodies that are attacking your own tissues.
What we know is that BCMA is expressed on both the short-lived and the long-lived, but they're not expressed in the beginning. This means that there is a potential to really target the sick cells but spare the early B cell pool, which may be very important. There are multiple opportunities here. Just to try to be a bit more specific, I will exemplify with two different diseases or indications where we see that the BCMA target could be a very good target. Lupus nephritis, this is basically a complication of SLE, which is an autoimmune disease. Here you have the autoantibodies attacking your kidneys and you basically risk kidney failure and that you have to be run on dialysis or transplant your kidneys. It is a very dizzy and life-threatening manifestation.
Currently there are treatments but with very limited efficacy. As you can see here, the market is projected to grow. Exactly how much, I think it's difficult to say because it depends on the pipelines of different drugs, etc. This is an indication where we see that there is a high unmet need. We have a unique drug that can target the plasma cells here when it comes to CTD. This is a result of underlying connective tissue disease and it hurts the lungs. You get fibrosis in the lungs, which can lead to respiratory failure, which is obviously also very severe and life threatening. Again, there is a lack of therapies here.
These are only two of the autoimmune indications where we believe that our first candidate drug OPSP1 can fit like a hand in the glove based on the preclinical data we have now. We of course have more work to be done. If we summarize the potential for SPiKEs in autoimmune disease, there is a large unmet need and there is a market potential. We have a novel and unique platform here and it is very differentiated from all other immunotherapy and we believe it fits multiple disease areas and indications and we find that autoimmune disease is in addition to the already kind of threads we have been going on for in oncology, hematology.
Now you got a picture of where we are here and now you got the picture of how we are aiming to work towards profitability but also what we are doing in preclinic. Just to remind you, right now we are focusing on Europe. We're focusing to become profitable. We have a growth momentum and it's based on the real world experience with Pepaxti that we see. Now we are broadening the usage and understanding of Pepaxti in Europe in our key markets. We're working on the strategic expansion but we are also progressing our pipeline in preclinic and we start to see some very exciting opportunities that we will get back to when we advance even more. By that I would like to open up for Q& A. Yeah.
have covered a lot of ground today from science to strategy. As you said, let's open up for some questions from those watching online. I would like to ask Professor Theurich and Fenchel to come back up on stage. While I do that, I have a couple of different sources of our questions. Sofia, if we start with you, and maybe this is a question you can kind of distribute to our guests as well. One question we do receive, of course, a lot is why does it take so long to get uptake of Pepaxti in Germany? Ah. now we can.
Yeah, so let me start, then you can reflect a bit. I think it's fantastic that we have representation from both academia and from the office-based setting because you can elaborate. What I usually say and what we also see is that Germany has a lot of physicians that are prescribing multiple myeloma drugs, which means that it takes a lot of time and it's also not easy to generate understanding or awareness in Germany because it's very scattered and it's sometimes difficult for pharma companies to access physicians over and over again. We are getting there and I think that currently we have a very good foundation. Maybe we should have been here when we launched once upon a time, but the team has done a fantastic job and we are now starting to generate this really positive experience.
I would like to maybe have you elaborate a bit more on this question because now I'm commenting on your healthcare system and how you are structured. Professor Theurich, would you like to start?
Yes, I try to, because as you already mentioned, the healthcare system and the reimbursement system, the structures are really complicated in Germany. We have these two sectors, the clinical sector and the outpatient or office-based sector with completely different reimbursement structures. I would like to point to a more context-wise problem because this m elflufen and prescribing melflufen and the acceptance of a new drug is not restricted to melflufen because in my opinion and experience it happened to a number of other drugs also. Every innovation needs time to be introduced into clinical practice. What physicians do is that they rely on ground that they feel comfortable and safe in terms of safety for the patient. I would not prescribe a drug that I do not know and I would not prescribe a drug that I feel uncomfortable with.
This is the case for example for the distribution for bispecific antibodies in the office-based medicine. This is more restricted, restricted and focused to the clinical centers and academic centers because of the side effects that you already mentioned in the beginning. That has been the case for daratumumab, the anti-CD38 antibody, because it is associated with an immediate or can be associated with an infusion reaction which was supposed to be severe, but we learned how to deal with it, right? It takes time to deal with all aspects of a new drug to generate a safety profile that everybody knows and feels comfortable with in the sense of saving the patient. With melflufen, last sentence is maybe another fact. It's not the safety. The safety is not the issue.
It's maybe more the connection to Melphalan as a drug that has been known for more than 50 years. The perception and the appreciation that melflufen is really different in the delivery, in the dosing, in the side effect profile compared to classic Melphalan. This needs to be distributed. In Germany we need communication, so we need to talk to each other. We need to distribute the experiences that we made in the study centers or clinical centers that are using the drugs. Also you in an office-based setting need to talk to each other. We all need to talk to each other and exchange those experiences. This also takes time.
Yes, yes, Professor Fenchel. Yeah.
In the world, the Germans are the bad guys. Like always. It could take so long with us. You have to see, in my former life in Italy, for example, myeloma is concentrated on some specialized centers. I do not know the number correctly. I think it's around 300 at the best. In Germany we have those 45 academic centers. We have around 300 hospitals with a quality of more or less good. We have 600 office-based physicians. We treat every month 70,000 patients. To give all this knowledge to everyone who is installed in these therapies takes a little bit longer than in a centralized country like France or Italy. I think that's one of the reasons. The other reason is we are in Germany. We have the opportunity to be hematologists and oncologists in one way.
Myeloma is not the only thing I'm treating and therefore it is also a little bit more spreading around.
When you say, just to make that very clear to the audience, when you say you treat 70,000, that is more than myeloma. I mean, can you give some examples? What are you treating?
Yeah, that's. Myeloma is not the majority in my office. It's breast cancer, it's lung cancer, it's gastrointestinal, the more often cancer. They all come to our office. I'm responsible for 2,000 in a month. That's. Myeloma is not the majority.
It's impressive, you need to be a generalist, but still get all the new information about all the different tumor types.
I understand, but this makes it so interesting.
Yeah, yeah, of course it does. Of course it does. It's a very dynamic job. You have different patients every meeting. Yeah, yeah. From a pharma industry perspective, I mean, I have a long experience from AstraZeneca. I had 20 launches when I left AstraZeneca and I was the head of Nordic Baltics from a medical regulatory, patient safety perspective. In my medical department, we were responsible for the launches and we were always pointing to Germany and did not understand why the uptake was so fast. Nordic is not the kind of, or Nordic Baltic, it's not the fastest region. I learned this already back then and that's why I knew when we started to launch the fast that this will take time, then it's difficult to say how long time. Right.
Because when you like you're talking if there is a positive experience and if there is an exchange and you start to get it rolling, my experience is that Germany is usually proving to have a very nice potential for new drugs over time.
To say we are a solid rock, but if we are rolling, you can't stop us.
Exactly. You're so good at this.
Yes, yes, yes.
Was that. Are you satisfied with the answer, David?
I am. We'll come back to a bit of the science, but more practical questions. There's a lot of interest, of course, on you gave an update on Japan. Could you elaborate a bit on the timeline there?
Yes, I understand that many are asking about the timeline and as I say, many times it would be irresponsible of me to give a timeline because I'm not in control of the timeline. What we are in control of is of course that we are moving with the speed we can move with, but that we are also choosing the best possible partner. It's easy to say short term, I just want to have a partner. I just want to get this going. I want upfront payment and et cetera, like money in the bank. If you look at this from a launch perspective and that the purpose here is really to bring Pepaxti to patients, you need to have a company that you really believe in that match our company that we believe can make a smashing launch in Japan.
We have several different options, but we have been advancing with companies that we really believe in and where we believe we are finding a win win deal. That is why it takes time. We will of course keep the market posted on our progress when we have something to check. It is advancing.
Great. This was directed to Professor Fenchel, but maybe anyone who wants to weigh in, you can. You have described how multiple myeloma remains incurable despite many new drugs. What are the biggest remaining gaps for patients?
I mean, I might start so as you. If you imagine that a plasma cell, and you were talking about long-lived plasma cells, which is the origin of multiple myeloma, the plasma cell, if this cell was generated by nature for surviving over not years, but decades, sometimes lifelong, you can imagine that there are mechanisms within the plasma cell that are also present in the myeloma cell that make this cell so resistant. Right. Another fact is that the heterogeneity, genetically but also biologically, of multiple myeloma is high. We are not treating one specific clone, but we are treating multiple clones from the very beginning on. They develop over time and they acquire resistances.
I think immunotherapy therapy has the potential in very early stages maybe to suppress or bring down the myeloma cell number to a level where the own immune system can deal with it and maybe eradicate this. This is hope for the future. It's still, as you said, an incurable disease. For the mechanisms or aspects that I briefly talk, try to mention so I.
Can put up the ball he laid in front of my feet. I'm not a soccer player, I'm a bad soccer player. This long living cell shows us we have to. It is not a short run, it's not 100 m sprint, it is more a marathon. It's a lifelong marathon. Therefore it is strongly needed that you have drugs which can be given a long time or which can be given in the last line in between. You have to have multiple options to treat your patient. Therefore melphalan is wonderful for us.
Maybe one last remark, because Professor Richardson pointed this out, addressing stemness and stemness factors in myeloma cells. That could be an aspect also that we try to find the sweet spot to eradicate also the myeloma stem cells, if they exist, but the stem cell features that some very immature or de-differentiated myeloma cells might have, for example, with a drug that really enters the core of the cell, such as melflufen.
Sofia, we've heard a lot today about clinical innovation and commercial execution. For those who aren't experts, what do you think will ultimately determine Pepaxti's chance of becoming a long-term success in the future?
The real world experience, how the product behaves in the real world and of course our resilience to work with the product over time. Because the launch has many different phases. I always say that even, even if we have some time since approval, based on where we were standing at approval, our launch is in the very beginning. Now it's first now when we have full access in Spain, when we have some kind of understanding awareness in Germany, because we did not have that at first and where we also entered Italy with 90% regional access. For me it's all about ensuring that Pepaxti is getting to the right patients, because we see that it can support those patients. That is why we are here to be honest. That of course also generates value for the company. Pepaxti is the very first PDC.
It kind of sets the tone for the platform as well. There we have the opportunity to help many more patients over time and as Dr. Richardson says, really launch a new drug class with not only one product but many products and reach different kind of tumor types and so on and so forth. I believe that the launch of Pepaxti is really critical to the success of Oncopeptides and our kind of hard work, resilience, and the positive experience that we are generating will make it.
Okay. Sticking with you, Sofia, you mentioned partnerships in the presentation and what does partner smartly is the question. What does partner smartly mean in practice?
I alluded to it a bit before, but I can elaborate it a bit more when I talked about Japan. Partner smartly is finding the right partner for the market you are looking at. That means that it should be a partner that has the right, of course, competencies, capabilities, that has the right in that, that has the right expertise about your disease areas, in our case multiple myeloma, and that has the right people to work with the product. That is why we have two different types of partnerships at Oncopeptides because we know that there is a lot of complexity in many regions. It is very difficult to launch a drug in Africa, for example.
We also know that there are patients and given that our partner is really eager and want to be able to demonstrate that there is an opportunity, we enter that partnership. Just to give one example, when it comes to licensing deals, this is more of a kind of it's not lifelong, but when you enter a licensing deal you sign up for something that I would argue should be much more permanent, even if that can of course also be terminated. You are really looking for a partner that can both pull through a regulatory approval, market access and commercialize on your behalf or on both companies' behalfs. You have several different aspects. I think that many that have heard me many times, I am a people person. I think you know, every business is generated by people.
I also look at the people we discuss with, how they are behaving, how responsive they are, how knowledgeable they are, the culture the company comes with, because that's a sign of commercial success as well. Finding that win-win situation and ensuring you really do that is important.
Something completely different. Market value of Japan. I know you touched upon it, but repeat.
Yeah. If you look at the population of Japan, I think there are around 120 million now. I think it's one of the few countries that is from one perspective shrinking because of fewer children being born. The older population, the aging population, is growing. The population size is higher than Germany, but the market access process is slightly different and the incidence of multiple myeloma is actually slightly lower. I don't know if you know why, I don't think anyone really knows. All in all, when we have been looking at this, we can conclude that Japan should probably mirror the potential of Germany. Germany is our largest European market. We have said that Germany itself stands for approximately 25% of Europe.
Sorry, I'm reading at the same time as I'm listening and I want to get to all the questions. If there's something that we believe has been answered already, we're not gonna repeat that. Here's the question regarding—I just saw it. Can you, and maybe difficult, but maybe give it a chance at least, can you please elaborate a bit, Sofia, on the success that you mentioned in preclinical data from the two platforms compared to completion? I think the question has to do a bit with how far along you see the assets within the two different platforms being, where launch is the end point, so to speak.
Two very different platforms, both in the way they are, the drugs, how they behave, but also our experience. The PDC platform, we have Pepaxti that makes us comfortable and confident with the platform. We've done research on that platform for much longer time and we have the clinical proof of concept basically and we are really, really good at, I'm super proud of our researchers, they are really good at optimizing these PDCs. We have a library of PDCs, but the two assets that I was talking about, they are getting closer to becoming IND ready. What does that mean? IND ready means that you have all the information you need to be able to submit a new investigational drug application to regulatory authorities. That means that you send in documentation to the regulators to get approval to start a phase one study.
The phase I study is a clinical trial and the first time you kind of get into humans. Before that you do in vitro trials in cells or experiments in cells, or you do in vivo in models. Where we are with both our PDCs is that we are getting closer to becoming IND ready. There is still CMC work done. For those of you who listened carefully before, that's when you kind of formulate your drug and kind of ensure that the production is scalable and that you have an approved safe kind of batch for your trials. That is where the PDC platform stands.
When it comes to these kind of opportunities we have where I will mention glioblastoma again because I'm really, I mean the patients with brain tumors and glioblastoma and I've seen it in close proximity of my family, it's terrible. It's changing the personality of the person and it's happening very, very rapidly. If we can make a difference there. As I said with the confirmation of the blood-brain barrier with the animal experiments and studies we have done, we are really kind of hopeful, but there is still some more work to be done to ensure that we go right. We are really looking into how to manage that because it is exciting for sure. SPiKEs platform, very different, no proof of concept. This is what we call a high risk, high reward platform because it's something completely new.
With that being new, you need to do quite a lot of preclinical work to be as comfortable as possible when you make your investment into the phase I trial. We have some CMC but quite a lot of CMC left because it is a different type of drug to produce. We are still also not kind of set down the stick in the ground on what indications, but we do believe that autoimmunity and to continue to explore that and those types of indications is very interesting.
Thank you. This is a good question. I don't know who wants to answer, but is there any difference between Pepaxti and all the other drugs? That's a big comparator. In general, all the other drugs, in regard of patients becoming refractory.
I do not have a patient actually who is refractory to Pepaxti. It works, maybe it will come, but I do not have anyway.
I mean, yeah, sure at some point relapse occurs or refract occurs. However, I mean if we are talking about melflufen as a drug, I think we should not talk about the indication as like a fourth and online treatment because we should see the patient's course and the journey. And as I try to allude with my, with my single case, they can be very, very long. And a patient, a myeloma patient can be on several treatments. If we are now focusing on the immunotherapies, there is a need for in between therapies. These in between therapies can be long, as long as they work right, to reinduce response, to reactivate the immune system, to reset that. It is not just the classic indication fourth line. If it works, it is good.
If there is refractoriness, you stop that, you can rechallenge, you can retreat. You can put drugs with that kind of mechanism, not immune activating mechanism, but immune saving, potentially immune saving mechanisms in between immunotherapeutic drugs. There are several other examples that can be used also. That makes me happy as a physician because I am able to select specifically the best drug for the patient and for the patient's individual condition.
That's needed when you have a very heterogeneous disease. I think you know, asking about refractoriness, I assume that today patients are not always refractory to all the drugs, right? They are exposed and they progress. To your point, you can, you know, play around. May sound a bit simple because it's not that simple, but the tumor is really advancing. Maybe this is—may I ask a question? Of course, because I'm always so curious. What I hear from many of your colleagues is that the immunotherapies and, for example, daratumumab, are also changing how the tumor is evolving, with a lot more extramedullary disease and with different characters that we are not really—I mean, you probably start to see it. My question is, do you agree to that?
Of course, myeloma is starting to become, you know, a different disease than how you knew it from 10.
Years back, as Dr. Theurich pointed out, not every myeloma patient is the same or not every myeloma is the same. In the course of the disease, it changes its behavior. You are more than happy if you have different ways to attack these enemy.
Multiple myeloma from the very beginning, this is like the data that we have now is very heterogeneous, genetically heterogeneous, but also from the growth behavior, heterogeneous. You can have responsive lesion of myeloma responsive to drug A and a second lesion being resistant to the same drug and vice versa. That makes it so complicated, but it also is the base. This is for the need of specific and multiple drugs and treatment opportunities to really address all these specific and different situations.
Thank you so much.
Sofia, you mentioned the U.S. briefly, is clinical pathway with the FDA. Agreed. Next step, present your suggestions on how to run the study.
When we say agree with what you do is that you send in protocol to the FDA for a study and the ones who followed our journey in the U.S. The FDA had some questions on dosing, et cetera. We would have to start with the dosing study. That is agreed. That protocol is kind of agreed to. For us it's more about finding a way to do this.
Okay, thank you. We're getting a lot of questions and that's fantastic. We're going to take a couple more, but we also have to start wrapping up because we're getting out of time. This is in Swedish. I'll try to translate it. When do the sales in South Korea and the MENA countries kick off and will there be upfront payments? I know South Korea versus the MENA are different, so maybe give a little background.
Yes. Different types of partners. The partnerships we have for MENA, which is Middle East and North Africa, are more kind of royalty based. We have not sold the license. If there would be a license, then we would be the license holder. We have collaboration for our partners to work with medical affairs activities in those countries. It means that if they sell, they get a split, we get the majority of sales, and they get a smaller share, of course, for their work and to be able to pay for their resources and have some profit. That is how that works. There are no milestone payments in that type of deal. When it comes to South Korea.
South Korea has around 50 million people, but you do not access all of the people in South Korea, which makes the market potential in South Korea you cannot really reflect it to a 50 million country. In Europe, like Spain is close to 50 million, but it is slightly smaller. Having said that, we did enter a licensing deal because we found a partner that had all the kind of capacity from regulatory to commercial. We got a small symbolic upfront payment because we had not done anything for South Korea. It was really the physicians and experts pushing for this, pushing the company and we assessed the company and we agreed to go for it. They had no idea of will this be approved by regulatory authority or not, are there further studies needed or not? That is kind of the process they are going through currently.
In that deal, given that it is a licensing deal, we still have some milestone payments when certain events kick in. At the end of the day we also have a royalty split where we get the majority of the sales for South Korea.
Thank you. The last question, if there's something we've missed by any chance? Because there's a lot to read through. We'll definitely follow up in our other channels, maybe on Oncopeptides talks or something similar. Sofia, looking across everything we've seen today, from Europe to Japan and the U.S., from PDCs to SPiKEs and from multiple myeloma and beyond, what gives you the most confidence about the future of Oncopeptides?
It is how we are supporting patients here and now. That is the foundation we need to stand on. It is our own people and our collaborators. I mean, I think we heard a lot about Pepaxti today, the different perspectives from Spain, Italy, U.S., Japan. For me, knowing this area, it has almost become a bit repetitive. We discussed that, you and I, that it is very similar across. If we can see this kind of good response for patients from a PDC in Europe, knowing that our mode of action is really translated into benefit, there are oceans of opportunities. It is really what I am seeing, hearing about every day that makes me very, very confident.
Okay, I think that's a good closing answer. I thank the professors for joining for the Q& A session as well. I just thank myself for moderating this day and leave Sofia on the stage for closing remarks.
Thank you so much and thank you. In the beginning, I said that it requires a lot of collaboration, hard work, efforts, and I think that this day has demonstrated that for all of us, all the important stakeholders of Oncopeptides to contribute to us being that very high pillar and a very successful company. We wanted to give you external perspectives, we wanted to give you a good understanding of our core business. I wanted to open the door a bit to the future to show you some of the opportunities that we have not been talking that much about, but that our researchers are super excited about together with their collaborators, and that we are of course assessing and exploring in different ways. I hope that you have gotten some food for thought. I hope you feel we stand on common ground.
As David said, if you have questions that we have not responded to, we will read through every one you have submitted, but you can also get back to us after this and we are happy to address those directly or in Oncopeptides in the near future. Thank you so much for your listening, for your engagement, and thank you for putting trust and confidence in Oncopeptides.