Welcome everybody to today's R&D Day of Heidelberg Pharma. It's my pleasure to welcome you here today and to present our technology to develop novel ADC drugs for targeted and highly effective cancer treatment. Please note our safe harbor statement about our forward-looking statements. My name is Andreas Pahl. I'm the Chief Executive Officer of Heidelberg Pharma since February 1st of this year. Before CEO, I served as the Chief Scientific Officer for many years at Heidelberg Pharma in developing the technology and the clinical assets of Heidelberg Pharma. With me is András Strassz, our Chief Medical Officer, who joined a couple of years ago at Heidelberg Pharma, after having done clinical development in a few other companies, and gaining experience in the oncology space for early clinical development. In addition to our company presenters, we have two external presenters where you find the bios on the next slide. Rakesh Dixit is a world-renowned expert in this ADC space. He has worked for several companies, especially for MedImmune, AstraZeneca, where he did a lot of ADC drug development. Since a couple of years, he is an independent consultant consulting many companies in the space of ADC drug development. He will give an overview about the non-clinical data of HDP-101, which will be the focus of today's presentation. He will be followed by Jonathan Kaufman, who is an Associate Professor of Hematology and Medical Oncology at Emory University School of Medicine in Atlanta, USA. He's one investigator of our HDP-101 clinical trial, and he has been on from the first cohort on and treated several patients by himself. So he has first-hand experience of HDP-101-treated patients. In his presentation, he will be give a major update about the HDP-101 trial, especially about the last, the fifth cohort. We have seen already objective responses and partial remissions in these patients, which makes us very excited about our HDP-101 drug. On the next slide, please let me introduce first our company. So the mission is to build a world-class ADC pipeline but the use of differentiated ADC technologies. We spent quite some years into develop our platform technologies, but the development is finished and we are now what we call in the plug-and-play mode. So we can identify new targets with new antibodies, put this in our platform, and we are able to develop from a new target to IND and ADC development candidate in three years. We protected our platform with several IP families, and especially in the field of Amanitin and its mode of action, we believe we have a strong monopoly which keeps other players in the field away. We are, to the best of our knowledge, the only company in the world developing Amanitin as a new payload for antibody-drug conjugates. We also established a supply chain for the GMP manufacturing of Amanitin and Amanitin-based ADCs. We completed 5 GMP batches already. In addition, we have strong partners. Huadong Medicine is a China-based company who is focusing on China Plus territories, which take our drugs and develops and market these drugs for these territories. Takeda has obtained a license for our technologies, so they use it for their own targets and antibodies and to develop with our technology new ADCs. The latest addition to the partnerships a few weeks ago that we signed a deal with HealthCare Royalty, from Telix Pharma, where we were able to sell a royalty stream partially to that company, which gives us further financing of the company. We are, meanwhile, a clinical stage company. Our lead program, which will be the focus of today, HDP-101 and multiple myeloma, is in a dose escalation trial. We have seen the first objective responses and partial remissions in patients, and this will be the focus of the clinical presentation of the day. Later this year, we will file the CTA for our next candidate, HDP-102, and we expect first patient in this year. Two additional clinical trial applications are in preparation for next year. We have a highly experienced leadership team, roughly 105 employees, really having the expertise for the platform, the technology in our house. The cash runway is now until mid-2025, but we expect from the royalty deed further milestone payment by the end of the year of $75 million, which gives further financing of our clinical pipeline. On the next slide, please, as a reminder, the patient is the focus of all our efforts. One of the biggest challenges in oncology is resistance. One out of two human beings will be diagnosed with cancer in their lifetime, and more than 90% of these cancer patients will die by cancer because of drug resistance. So that's one of the biggest unmet medical needs in the space of cancer. On the next slide, you just see an example of a journey of a cancer patient. So that's a melanoma patient you see on part A before the treatment of the melanoma growing under the skin of this patient. With today's standard of care, you can really treat this patient very well. The slide on part B, it looks like this patient is cured after a few weeks. But what happens, and this is the common observation, tumor cells get resistant to standard of care, the tumor relapses, and on slide on part C, you see the regrowth of the tumor, and that patient died a few weeks later on. We desperately need new drugs with new mode of action to overcome the resistance of cancer cells. That's the mission of our company. We want to create value through the development of best-in-class ADCs. We are really focusing our expertise in the ADC space. We are scouting, partnering, and doing in-licensing for targets and antibodies. And then we combine this with our toolbox of proprietary payloads and generate new antibody-drug conjugate candidates. And with our research and development expertise, we then further develop these ADCs into clinical candidates in the early clinical development. Then we look for partnering, co-development, or we retain territorial rights for potential commercialization. That's the business model of Heidelberg Pharma. On the next slide, you see the focus of today's presentation because our lead programs are based on a new payload, which is called Amanitin, which is a main representative of a unique class of natural toxins. It basically comes from the poisonous green death cap mushroom. It's a bicyclic octopeptide. It has some exceptionally biophysical properties like stability and hydrophilicity, which makes it very different here, as you see with the red bar, from all the other payloads. So this gives rise to unique properties with regard to the CMC of this payload. What is also very unique about the Alpha-Amanitin is its mechanism of action. It's a specific inhibitor of the RNA polymerase II. What you see on the right part of that slide, that almost all fundamental processes of cellular metabolism, has been exploited for cancer therapy. But only one specific part of this one, namely the eukaryotic transcription, has never been used for cancer therapy. Amanitin is the only compound known in the world to be an inhibitor of the RNA polymerase II. So this was the core idea to exploit and harness this compound for cancer therapy. And we used the ADC technology to make that compound, amenable, applicable to cancer therapy. One very specific feature, what we believe is very important, very differentiating, it has a cell cycle independent mechanism. So we can even kill dormant tumor cells, which is in contrast to the other payloads. Furthermore, the intracellular concentration of the RNA polymerase II is very low. So we have a one-on-one binding, and we need to deliver a rather small amount of toxin molecules to the tumor cell in order to achieve cell killing. Last but not least, for the supply chain, we made Amanitin synthetically accessible. As mentioned, we have the GMP manufacturing, and we protected these processes by IP. On the next slide, you see a brief comparison how RNA polymerase II inhibitor Amanitin fits into the landscape of payloads. You see the well-known tubulin inhibitors like maytansine and auristatins. You see DNA damaging agents and the new one, the topoisomerase inhibitors. And you see the differentiation of the Amanitin. So we are a medium potency agent, which is the trend in the space that these ultra-high potent payloads usually suffer from toxicities. We have a hydrophilic payload. We can overcome resistance. We have never found any tumor cell which was resistant to the Amanitin, to its mode of action. We are active on non-dividing cells. We have a biomarker, which is also the only payload in the space where we have a platform-wide biomarker to be exploited for clinical development. And as already mentioned, we have target and mode of action exclusivity for the Amanitin. So there are no copycat versions of the Amanitin known. And its mechanism of cytotoxicity is radically, radically different from conventional chemotherapy. In contrast to all others, it has never been used as a small molecule in cancer therapy. So every patient will be naive to the Amanitin when delivered to the patient. On the next slide, you see the development of our platform. So the result, what I call the plug-and-play mode. So we optimize, and I call it, we harness the ADC technology to make Amanitin applicable to cancer therapy. On the right, we're just grafting the regions from the antibody which recognize the target on our standard backbone. The standard backbone in blue was optimized for the Amanitin. We screen for the best positions for a site-specific conjugation. We optimized the drug-to-antibody ratio, and we found that the 2.0 is sufficient, specifically conjugated to an engineered cysteine on the antibody. Furthermore, we do Fc silencing. We truly believe that the potency of our payload is sufficient to kill the tumor cells. And we want to avoid unspecific interaction with non-tumor cells via the Fc receptor. So that's the reason why we do Fc silencing on our antibody drug conjugates. And then in red, you see the Amanitin as a warhead with a differentiated mode of action, the three hallmarks. We kill dormant tumor cells, we overcome resistance, and we have a predictive biomarker. And with the synthetic Amanitin derivatives we found by our synthetic process, we have improved properties over the natural compound. On the next slide, you will see a summary why we believe that we can further differentiate from the current cancer therapies, which has, which has limitations. As what I have shown you in the beginning, in the pictures of the patient, the standard therapy is good in debugging the tumor, but you have some cells, most people call them cancer stem cells, CSC, which survive, which are getting dormant, and survive and become resistant to the standard therapy. And in the long term, these cells lead to the regrowth of the tumor and to the minimal survival increase of the patients in the relapse. Our payload is different. We not only debulk the tumor, but we also kill these cancer stem cells because our payload is able to eliminate non-dividing cells and cancer stem cells. So we truly believe that the long-term response is improved with the application of ATAC into cancer therapy, again, with the mechanism of cytotoxicity, which is radically different from conventional chemotherapy. On the next slide, you see a summary of preclinical features of our ATAC, where we believe that this can turn in potential clinical benefits. The efficacy against dormant tumor cells can probably lead to longer progression-free survivals in these patients. We have seen efficacy in very low target-expressing tumor cells, which we believe can lead to deeper responses and higher response rates. The mode of action is radically new to all patients. We can overcome the resistance. In particular, for the HDP-101, which is important, we haven't seen ocular toxicity for the Amanitin. So we have a superior safety profile, and Jonathan will point later to this, feature of our HDP-101 drug, which we have now proved already in the patients, in the dose escalation trial. And last but not least, not mentioned here, with the 17p deletion, we have a biomarker, where we can stratify patients and which leads to an accelerated approval and breakthrough designation. On this slide, you see our growing pipeline of proprietary and partner programs. Pursuing the success of HDP-101 and multiple myeloma, we already started the development of follow-up programs. HDP-102 is a program which targets CD37 and non-Hodgkin lymphoma, and we are planning to submit the clinical trial application later this year and even have the first patient for that program later this year for non-Hodgkin lymphoma. This program will be followed by HDP-103, which is targeting PSMA and prostate cancer, another program using the Amanitin as a payload, and we are highly confident that we can make a difference to these prostate cancer patients. The next program, HDP-104, has been down-prioritized now. We are focusing now on the eighth program, HDP-201, targeting GCC. This will be the first program based on our new payload platform, which is based on a topo-1 inhibitor, where we identified a new linker with a new solubilizer for topoisomerase I inhibitors. We are very excited to run this program for colorectal cancer targeting GCC. HDP-103 and HDP-101 will be submitted for clinical trial application later in 2025. In addition, Takeda is also very excited about technology. They're pursuing actively the first own ATAC program on a proprietary target, and they are verifying the progress of IND-enabling studies in the clinical development. On the last slide, you see the summary of our upcoming catalyst to become a leading global ADC player. We really believe that these multiple inflection points coming from these four different clinical development programs have a huge potential to increase the company valuation significantly. As mentioned, we expect the approval of the clinical trial application for HDP-102 soon and having the first patient in by the end of this year. In addition, we expect also the recommended phase II dose of HDP-101 by the end of this year, which will be followed by the extension cohorts and the expansion part of the trial for the HDP-101 program. Next year, then we will have the clinical trial applications for HDP-103 and HDP-201. Through the upcoming years, also we will see then the recommended phase II doses for the programs HDP-102 and HDP-103. Our partners are very active. They are as excited as we. So Huadong is actively starting the clinical development of HDP-101 in China, and is, let's say, enrolling patients as soon as we have reached the recommended phase II dose for the HDP-101. And as mentioned, Takeda conducts IND-enabling studies. And with this, I would like to conclude my introductory presentation. Already thank everybody for attendance. And I'm handing over to Rakesh, who's giving a non-clinical overview about the HDP-101 program. Thank you. Thank you, Andreas, for a very kind introduction. My name is Rakesh Dixit. I'm an Advisor and Consultant for Heidelberg Pharma. And today, I'm going to present some important points about this ATAC molecule, HDP-101. It is a BCMA-targeting ATAC. And I'm going to present some of the key points on the pharmacology and safety of this molecule. So we can go to the next slide, which basically tells me, which basically describes about the differentiated profile of HDP-101. So what makes it unique, given, you know, BCMA therapeutics area is very crowded, but this molecule stands out quite well in many ways. Because of its potent payload, which is a very potent inhibitor of RNA polymerase II, you can see on the left-hand side, very, very far left, you can see it's highly efficacious even in the tumor cells that have very low expression of BCMA, which is very unique because not many therapies work in the low BCMA-expressing marker myeloma cells. And it's because of the potency of the payload, we can kill the, you know, very low-expressing BCMA tumor cells. And on the dashed line, you can see that it doesn't harm the healthy cells, which is very unique. In the middle, you can see that it's actually much more efficacious with the current ADC, which has been approved. And then it was withdrawn by the company because of safety issues on ocular toxicity. And then likelihood it might come back. But in any case, the HDP-101 is way a lot more potent than the current BCMA MMAF ADC, which uses a microtubule inhibitor, again, showing that the potency of the RNA polymerase II inhibitor is extremely good. And that's why we are seeing very good tumor killing activity. On the far right, you can see the right-hand side that in the multiple myeloma tumor cells, where the current therapy, like elotuzumab and Pom combination, versus daratumumab, where you also see resistance, where you see resistance against these multiple myeloma cells, BCMA, the HDP-101 is extremely active. So you can see from this slide, you can say it's very active in low BCMA-expressing cells, much more efficacious than the current approved BCMA ADC. And the third also in resistant tumor cells. So I can go to the next slide. Here, it's important to also understand the pharmacokinetics of the HDP-101 in both monkeys and humans in cancer patients. You can clearly see that a lot of similarities between in the pharmacokinetics profile between animal studies and in the human studies. On the right-hand side, you can see that despite the differences in doses, you're seeing a pretty similar exposure, suggesting that the kinetics is, at least on the qualitative level as well as quantitative, there's a lot of similarities in the exposure profile, including the half-life, Cmax, and the ADC. Another important thing to note is that the PK is linear between doses, which is also a very important thing. Despite the half-life of 12 days, which in my opinion is not easy to achieve with any ADC molecule, we are seeing a very good half-life of the molecule. Despite that, we don't see an accumulation of drug. The most important thing to note is that there is no free Amanitin or minimal Amanitin circulating in the systemic circulation. Next slide. This slide actually talks about the pivotal GLP toxicology study that we ran for IND filing. You can clearly see in this slide that the adverse effect profile we are seeing for this drug is actually related to the free payload, which basically intracellular release of the payload. You see because Amanitin is well known to cause liver and kidney dysfunction, that's what we're seeing. But unlike the MMAF ADCs, we don't see any ocular changes. We're not seeing any neurotoxicity. We're not seeing any effects on the cardiovascular system. The toxicity profile is almost reflective of the payload, which is Amanitin. We see transient thrombocytopenia, which you'll expect from the MOA of the molecule. But it's transient, it's reversible. So that on the right-hand side, you can see as soon as you dose, you do see depletion in the platelets. And then during that time, it's transient, so it comes back. And then again, you give the next dose, it comes down again and comes back. Again, suggesting that there is no direct killing of the platelets by HDP-101 because those in vitro studies have been done directly with the ADC, and we don't see direct killing of the platelets. And also, we don't see any major effects on the bone marrow progenitors that are making the platelets. So that's really important because thrombocytopenia is fairly common in multiple myeloma patients, and that's something we had to pay a lot of attention to. We do see some changes in the clotting times, but you expect when you have RNA polymerase II inhibitor that affects the protein synthesis, that some of the clotting factors in this could be also affected at fairly high doses. Next slide. Here you can see also that in terms of the liver enzyme elevation, we are still remaining below the threshold for a very high increase in ALT and AST. These are the two important liver enzymes that reflect the liver function test. You can clearly see that we are well below those numbers. Same kind of profile we also see in cancer patients that the biomarkers of liver function tests like ALT and AST increases are, you know, somewhat identical between monkeys and humans. Actually, we can easily monitor the liver toxicity by looking at the rise of the ALT and AST. Next slide. Here's a very quick on the mechanism of Amanitin ADC action. So, I mean, we all know that alpha-Amanitin, which is present in certain mushrooms, when you ingest it, it goes through absorption through GI tract, small intestine. And then it makes it to liver. And in the liver, Amanitin binds to a transporter called OATP1B3. And the transporter is responsible for intake of this inside the hepatocytes, where it inhibits this target, RNA polymerase II. And that results in liver toxicity. Some of that Amanitin can also get reabsorbed back through enterohepatic circulation. And that can also be responsible for liver tox. And also because it's a, you know, it's a peptide molecule that can also, with a similar mechanism, can also produce some renal toxicity as well. Next slide. It'll be here. And so just to comment on three important mechanisms of liver toxicity caused by the ATAC or Amanitin-based ADCs. So in the first instance, that the ADC, intact ADC, does not bind to the OATP1B3. So that is not direct entrance of the intact ADC. However, once the ADC makes into liver through some non-specific mechanism, which could be through Fcγ receptor, macropinocytosis, mannose receptors, multiple mechanisms could be involved. And once it's taken there, and then the Amanitin is released by lysosomal proteases, then you start seeing that free Amanitin that can bind to the OATP1B3 transporters. And that's how it gets inside the liver hepatocytes. And then where it can affect the RNA polymerase II, it causes apoptosis, protein synthesis, inhibition, and apoptosis, and causing oxidative stress. And that is responsible for the death of the liver cells. So clearly you can see it's not the free Amanitin, which is very minimal in circulation, it's actually the Amanitin released inside the cell that is responsible for liver toxin. And that's really important to understand that the ADC itself does not have any binding to OATP1B3. It's the free Amanitin payload. That's what, especially that one releases intracellularly. And also the free Amanitin is a polar molecule. And that has, you know, that cannot be entered into cell that easily because of polarity. And the one last slide is this is an important slide where we did an extensive PKPD modeling using the non-human primate toxicology data as well as several mouse models where we look at the efficacious dose, plasma levels, and then we also look at the drug levels in monkeys and then try to model it. What is clear from this data is that at the human equivalent dose, as where we have seen the, you know, you know, tolerability problems in monkey studies, is about 0.75 mg/kg. That equivalent dose for human is about 0.25 mg/kg, as you see in the black lines. And you can see that if you look at the dose response modeling, you can clearly see that we will be able to maintain fairly good concentrations of drug, ADC concentration, well above the tumor inhibition concentration, at least I will say 100 micrograms per kg dose and above. Our goal is not to move it up to 250 micrograms per kg dose, which was shown to be toxic in monkeys equivalent dose. So I think you can see that we are seeing activity in clinical trials at substantially lower doses, and which is also good news that we are still below the threshold of toxic doses. So I think it's all good news for this molecule and it's just providing good therapeutic index to continue moving forward. So this is where I'm going to end my presentation. Thank you. Hi, my name is Jonathan Kaufman from Emory University in Atlanta, Georgia. On behalf of Heidelberg Pharma, I'd like to present a study update on HDP-101, a first-in-human study of a novel BCMA-targeted antibody-drug conjugate. In this slide, you will see the overview of the study as a whole. Again, as noted in previous presentations, HDP-101 is an antibody-drug conjugate targeting BCMA. We'll initially do a phase I study to establish a safe dose using a novel dose escalation adaptive study design with 15-25 patients approximately. Then once we establish the right dose and schedule, we will have a recommended phase II dose. Then in that recommended phase II dose, there will be 30 patients stratified by the amount of 17p deletion, patients who have essentially no 17p deletion, less than 10% of the myeloma cells with the 17p. Those patients with a moderate amount of 17p deletion, 10%-59%. Then a minimum of 10 patients who have the greater than 60% 17p deletion. In terms of the study scheme, there is a screening period with relapsed refractory patients who have no or limited therapeutic options, will then go to the screening period in enrollment, followed by the cycle one with the DLT observation period in that 21 days. Again, HDP-101 is administered intravenously every 21 days. Then cycle two and beyond, given every three weeks, we'll have ongoing tumor and toxicity assessment. Treatment will end upon adverse reactions or investigator/patient decision. Finally, there'll be a follow-up period for subsequent treatments and survival. We have had 18 patients so far, seven females and 11 males. They were enrolled in five different cohorts at 20, 30, 60, 80, and the most recent cohort of 100 micrograms per kilogram. The median age was 70 years old, which is typical of a relapsed refractory myeloma patient population. They were heavily pretreated and had multi-drug resistance and a median prior lines of 6.5 prior lines of therapy with a range of two to 15. On this next slide is an overview of the efficacy data. You'll see this with the swimmer's plot. To orient you to the slide, the bars in red are those patients who have achieved, who had PD. The bars in blue are those patients with stable disease. You'll see in the top here, all three in the 100 microgram per kilogram cohort, three IMWG responders at a PR. Highlighting in the green box is this one individual who had both prior BCMA and GPRC5D exposure previously. This patient's achieved a PR and nearly a VGPR, a deepening of the response with a 90% reduction in the amount of myeloma in the patient. This slide highlights the most common adverse events to HDP-101. You'll see in these beginning cohorts, there's very little systemic toxicity. There is what was noted as adverse events with hematologic toxicity. In these very early cohorts, most of these AEs are likely due to disease. When we get to the dose where we had responses, what you'll note is that all of the six patients did develop thrombocytopenia. Two-thirds of the patients developed grade three or four thrombocytopenia. I will highlight this in the next few slides. The other thing we saw is in one subject, again, I'll highlight in the next slide, had increased AST and ALT and required a dose reduction. What is really critical about this AE table is not what we see, but it's what we don't see. We don't see any ocular toxicity. Ocular toxicity has really hampered other BCMA-targeted antibody-drug conjugates in this space. There's no ocular toxicity, no renal toxicity, no infusion-related reactions. My overall myelosuppression is minimal if any. What we've seen is thrombocytopenia, which I'll talk about in a moment. While we saw transient increase in ALT and AST, we saw no liver dysfunction. There were no DLTs in cohorts one through four. In cohort five, we saw three DLTs related to transient thrombocytopenia. After cohort five, based on the DLT rules, we have switched to a dose optimization strategy. I will show you that strategy in a few slides. In this slide, you'll see the one patient who developed transient AST and ALT elevation. This was cohort five, again, the 100 micrograms per kilogram dose, cycle one. The patient had grade three AST and ALT. Subsequently, there was a dose reduction and no further increase in ALT. AST, again, this was transient, resolved within a week. The bilirubin remained normal. There was no downstream liver dysfunction. In this slide, we'll focus on the platelet levels in cohort five. What you'll see here is that there was a rapid and transient thrombocytopenia. Again, three of the patients met criteria for DLT in this scenario. Importantly, outside of the one patient in this cohort who had dose reduction for the AST and ALT, there was no dose, no further, no dose reductions in the other five patients. You'll see here there was not ongoing thrombocytopenia. So it was really only after that first dose, and it was transient. We saw no other signs of myelosuppression. We found no evidence of direct toxic effect on platelets or the megakaryocytes. In order to overcome this transient significant thrombocytopenia, we have developed a dose optimization strategies after a detailed safety analysis. You'll see now that we have three optimization schedules. We'll have Arm A, which is dosing every three weeks with premedications. We have Arm B with using weekly dosing. Then we have Arm C, where the first cycle is associated with a split dose and then every three weeks. Our hope is that we can maintain the dose intensity at that 100 micrograms per kilogram eventually, while minimizing the thrombocytopenia. I'd like to finally comment about where I think this is, where this falls in the current myeloma space. Firstly, we know that BCMA is a well-validated target in myeloma. The current approved BCMA targeted medications are CAR T cells and bispecifics, which are not appropriate for all patients. We're really missing an antibody-drug conjugate that can be given to all patients and that is given on a once-every-three-week basis. We're really missing a drug for our 17p deletion patients. So what we see here is a proof of principle that this medication does have efficacy in the relapse refractory patient population. As a proof of principle, we saw efficacy in a patient with prior BCMA and GPRC5D exposure. Very importantly, and again, I'll reiterate it, what other antibody-drug conjugates have suffered from is ocular toxicity. We have not seen any ocular toxicity to date. With that, I believe that this drug is right for further development. I remain very hopeful. For this, I would like to hand the call back to George for any web questions. Over to you, George. Hi, George. Please unmute. Thank you. Apologies. Hello. My name is George Badescu. I'm Chief Business Officer at Heidelberg Pharma. And I'm going to read out questions we received through the web interface. There were a number of questions on this topic, so I tried to group them together. The first question is related to Magenta Therapeutics who have encountered issues in the clinic. Have you seen any similar toxicities in the HDP-101 trial? András, if you want to start answering the question. Yeah, thank you so much, George. So my name is András Strassz. I'm the Chief Medical Officer of Heidelberg Pharma. And as I can tell you, on the tested doses so far, we haven't encountered anything similar to the Magenta cases. And as a matter of fact, we overcome the dose where Magenta already had a patient passed away on these unlikely or unfortunate lung issues. And after that cases, we implemented extra safety features in our study by having checked the patient previously entering the study and on study. And despite this really thorough check, we have not seen any cases which could be related to our drug as of today. And we concluded based on our assessment that those cases were really most likely due to the target and not related to the technology itself. Thank you very much. The second question is related to the future of the trial. Do you intend to dose higher? How many more cohorts do you intend to recruit? András, if you can take this question. Yes, thank you. Definitely, we would like to escalate the dose furthermore. We will open up this study. Actually, the study is currently open for recruitment for these dose optimization cohorts. If any of our strategies, or if all of them, are addressing the issues, we will definitely escalate the dose. As we encountered quite a number of patients responding to the drug on the 100 micrograms per kilogram, we have strong reason to believe that our sweet spot, our recommended phase II dose is not far from these dose cohorts. Thank you very much. The next group of questions is related to Blenrep. So the question is, how do you compare it to Blenrep, the other well-known ADC targeting BCMA? Is Blenrep a competitor? And I would hand over this question to Jonathan. Yeah. Yeah, thanks so much. I think on some levels, I tried to mention this when I reviewed the data. Comparing Blenrep and HDP-101, they are both antibody-drug conjugates that target BCMA. The toxicity is what has really limited Blenrep's ability to be used widely and the challenges behind using Blenrep. And primarily, that toxicity is ocular toxicity. And it was the ocular toxicity and the failure to meet their primary endpoint on their phase III study that led to the removal of Blenrep from the conditional approval, both the United States as well as in Europe. And we've seen the preliminary data that they now have a positive phase III study. So that really only addresses the efficacy part of Blenrep. And there's no real fix for the toxicity part of Blenrep. And so the ocular toxicity will remain. The challenges of giving the drug will remain. As a proof of principle, we know that it's an effective drug. We saw in this most recent cohort efficacy with HDP-101 as an antibody-drug conjugate targeting BCMA. We have not seen any ocular toxicity. We don't anticipate any ocular toxicity. I think between that and the fact that there's predicted efficacy in the 17p deletion patient population represent differentiators between Blenrep and 101. Maybe I can add some features from the Amanitin on the mode of action to remind everybody. Amanitin is able to kill non-dividing cells. We know the myeloma are non-dividing cells. We have seen this in our data. This is far outcompeting the payload Blenrep is using. We also have the potential to address very low-expressing target antigen cells. We believe the preclinical profile is supporting. Jonathan has said that we are very well positioned versus the Blenrep. Thank you very much. The next question, can you give an update on the sixth cohort? Were you able to recruit patients? In general, given the promising data of the fifth cohort, is it now easier to recruit patients? András, I think this one is for you. Yes, thank you so much. Definitely easier to recruit more patients. So I already can share, but maybe Jonathan could add to that later, that we feel the enthusiasm from our investigators. And we already had no issues enrolling patients in the last couple of cohorts. So cohort number three and four were enrolling really fast. And we do anticipate the same after all the approvals are in place. So we already opened up this cohort for enrollment. But of course, as you know, we have to have the approvals in each and every country and almost for each and every site individually. But I think the enrollment, we have no issues. Maybe Jonathan? Yeah, I think there's a real excitement about the efficacy signal that came out in the last cohort. And so this is going to be a study that where in the first handful of cohorts, it's a more narrow population of patients that would accept. But now that we see that efficacy signal, I think accrual and there's been a real good team of investigators put together will go rapidly through this cohort. Thank you very much. A following question from that is asking for an update on the patients' continued treatment on the fifth cohort. Can you give an update on their disease status? Yes, yes, definitely. Thank you so much. So we have still two ongoing patients from this last cohort, which means quite remarkable because they started treatment before Christmas last year. And they are still ongoing. One of them are in a really, as Jonathan already mentioned, in a really deep response, almost achieved VGPR, which means that 90% of the circulating or 90% of the M-protein, which is produced by the myeloma, is gone from this patient. And the trend is still declining. So we really hope that in the next couple of cohorts, these patients will even deepen the response. Thank you very much, András. The next question is, what is the current state of knowledge regarding the development of resistance to Amanitin? And what strategies does Heidelberg Pharma pursue to monitor and manage potential resistance to HDP-101 in the clinic? Andreas? Yeah, maybe I can take this question. Amanitin is a very new payload. It has never been used in oncology. So every patient will be naive to Amanitin, even not as a small molecule it was ever used. And we have never come across any tumor cell that was resistant to Amanitin. We have seen this, let's say, in translational data. So we believe there is no a priori resistance to the Amanitin. And of course, we will monitor the patients. We are not saying that we cure the cancer for the rest of the life. But we are very confident that we can break resistance, that we give the patients a good duration of response. And of course, we are monitoring if patients develop resistance. We will, let's say, do some translational studies in order to understand what possible mechanisms of resistance may develop against the Amanitin. Thank you very much. The next group of questions relates to the del17p status of patients. Can you say which of the six patients that showed progression have a TP53 deletion trait? Yes, thank you so much. The phase I study part for the dose escalation part is open for 17p deleted patients, but not exclusive for 17p deleted patients. We enroll all kinds of patients. And as of today, none of our enrolled patients showed definitive 17p deletion. We tested all of them, but none of them has definitive 17p deletion. We will address this question in the phase II portion of the study because in the phase II portion, as you know, we will stratify this patient on the 17p status. And we will enroll at least 10 patients in that portion of the study who have definitive, which means more than 60% of the myeloma cells showing 17p deletion in their bone marrow sample. As of today, we don't have any data on that. Hopefully, with the phase II portion, we can answer this question. Excellent. Thank you very much for that. The next question, András, I think is for you as well. Can you give an update on the preparation of a phase I study for HDP-101 in China? Yes. As you know, we have the partner Huadong Medicine, but we don't initiate this study in China before recommended phase II dose. So our current plan is to include them into the phase II portion of the study. Okay, thank you very much. I picked the next question. Again, there are several questions on this topic. This question says, you regularly participate in industry conferences. After the publication of the data on the fifth cohort on HDP-101, what kind of market feedback have you received? Have you noticed a pickup in interest of the scientific community related to the ATAC technology and HDP-101? Perhaps, Andreas, you can start answering this question. Yeah, sure. We presented as announced a poster at AACR. It was a very crowded poster. So András was presenting and 3.5 hours for the whole time, he was overwhelmed by people looking at the poster, talking to the poster. I believe also the investigators see more, let's say, interest in the program. As we are progressing, as Jonathan put on the table, with the responses we see now, we see a huge interest in our technology, in the ATAC technology, and also in the HDP-101 program. And of course, also, we will continue business discussion. We see, let's say, huge interest also for the asset from possible partners in that space. Thank you very much. There are a number of questions related to whether we are concerned about liver toxins. Andreas, you can start. András, please go ahead. Yeah, maybe also Rakesh and Jonathan can comment on this one. So we did quite a good job, let's say, in the preclinical studies. We understand this very well. So we are not concerned. I believe the clinical data now shows that we, let's say, see responses without significant liver toxins. So I'm not concerned, but I'm happy to hear the comments of the external people from Rakesh and Jonathan about that. So let me comment on that. I think what we have seen, at least from the animal studies, the liver toxicity is a function of dose. If you don't achieve very high doses, it's unlikely you are going to see the extreme liver toxicity you see with Amanitin poisoning. So that's the biggest hope for me. The second thing we, as I tried to explain in my mechanism of action slide, that free Amanitin is unable to cross the membrane. So it's not liver toxic by itself. In order for the liver toxicity to happen, the entire molecule ADC has to get into liver. And that's, again, dose related. And when it gets into liver, then the payload gets removed and then binds to the transporter on the hepatocytes. And that causes toxicity. So clearly, it's a dose-related process. Since we are still well below the doses where we have seen the high degree of liver toxicity in monkeys, I think I'm extremely hopeful that we won't reach that dose level or see that kind of extreme DLT of these severe liver toxicities. Jonathan, you want to comment on something? Yeah, I agree. I mean, I think the patient who had the transient increase ALT and AST was my patient. And very clearly, this elevation of AST and ALT was transient. It was not associated with liver toxicity. And there were confounding variables during the administration of the medication. And so there really is no evidence that I've seen, having looked at all the data of liver toxicity. Also, I would like to comment on resistance. I think there was a question. So I wanted to add what Andreas said. I think one thing we know that how tumors develop resistance, they typically develop resistance against the payload. And payload resistance is quite often through what I call P-gp transporter, efflux transporters. And since Amanitin does not bind to efflux transporter, so that means you have a less chance of seeing that kind of resistance process. And that's also a positive thing compared to, let's see, other auristatin-like molecules, MMAE, or other payloads, which are a very good substrate for P-gp transporters. So I think that gives me hope that we will not see the payload-based resistance, of course. Also, even if we lose the BCMA target, and since we have shown the data that even the drug can work even in a very low BCMA expression BCMA cell, that also gives me hope that you will have much better chance of not seeing resistance, either due to target loss or due to payload resistance. Yeah. Thank you very much. We are coming close to the top of the hour. We're going to take one more question despite receiving many questions still. One question is, have you tested HDP-101 in cells from BCMA-treated patients, either with bispecifics or CAR-Ts? András, do you want to take this question, I suppose? Yes, actually, because you asked this question maybe preclinically, but we have clinical evidence because one of our patients and eventually that patient who had the deepest response in our study received prior treatment with the GPRC5D targeting bispecifics and with the BCMA targeting CAR-T. And that patient failed both treatments or progressed on this treatment. So there is clear evidence that our drug is effective post-BCMA targeting and post-GPRC5D targeting drugs on top of everything else because most of our patients received all other treatment modalities that you can imagine for myeloma patients. Thank you very much. We will stop here. However, thank you very much for all your questions. There are a number of questions that we were not able to answer. Please get in touch with us separately, and we'll be very happy to answer the questions. And now I'm going to hand over to Andreas for some closing remarks. Yes, thanks, George. Thanks, everybody, our external collaborators presenting, giving answers, the people of Heidelberg Pharma contributing not only to this R&D Day, but to all the work and the programs we have right here. Thanks, everybody outside for questions and attending. We are very excited. I hope we could excite you as well as we are about the potential of our technology and our first program, the HDP-101. I believe everybody agrees ADCs are now a frontier modality in oncology. They are proven. We are a strong believer, and I believe the data shows that the payload is the most important piece of the ADC because this makes a difference what payload you are delivering to the cell. Everybody is now looking in the world what is coming after the Topo I payload class, the next new hot payload. We are the most advanced, clinically advanced new payload in that space. We believe with today's, let's say, first glimpse of the data, we can demonstrate it works clinically. We have a therapeutic window. We are able also, like what András was mentioning with that patient, we can break resistance. As a last reminder, we have a radical new mode of action, never seen, never used in any patient. So no cancer cell is resistant to Amanitin. So we have all the potential to really, let's say, bring a new class of payload to the patients. We are working on a new program.