Hello ladies and gentlemen. Thank you and welcome to Vincerx Investor Call, which will review preliminary clinical data from its phase 1 dose escalation study of VIP236 and provide an update on pipeline progress, including for VIP943. All participants are in a listen-only mode. If you have any questions, you are welcome to add them to the chat function. At the end of the call, we will conduct a Q&A session. As a reminder, today's call is being recorded. With that, I will hand the call over to Dr. Ahmed Hamdy, Chief Executive Officer, who will make introductory comments. Good afternoon. Welcome, everyone, and thank you for joining us today. Next slides, please. This is our Safe Harbor. Today I'm joined by two of the luminaries in the world of oncology. If you go to the next slide, please. Dr. Uma Borate, a Clinical Associate Professor at the Division of Hematology at Ohio State. And Dr. Vivek Subbiah, the Chief, Early-Phase Drug Development at Sarah Cannon Research Institute. Next slide, please. This is our agenda today. We're going to give a company overview, then Dr. Subbiah will talk about evolution of the camptothecins and the treatments. I will present our phase 1 dose escalation with VIP236, have a discussion. Then Dr. Borate will present the unmet medical need in AML and where 943 can be an opportunity. I'll give an update on the dose escalation study with preliminary safety and PK, then we're going to have some discussions on VIP943, followed by questions and answers. Next slide. At Vincerx, we aspire to conquer cancer by addressing unmet medical need with paradigm-shifting therapeutics. Next slide. Our pipeline consists of VersAptx, a versatile, adaptable, next-generation bioconjugation platform. With this platform, we are capable of conjugating different targets, whether small molecules or antibodies, to different types of payloads with different linkers that cleave intra- or extracellular, depending on the treatment that we're going after. Our first to the clinic from this VersAptx platform is VIP236 that is geared for advanced metastatic solid tumors. The target is an alpha-v beta-3 with an optimized camptothecin as the payload. It's a first-in-class. We also have our first ADC in the clinic, VIP943, which is best-in-class anti-CD123 with a novel linker that cleaves legumain and a kinesin spindle protein inhibitor as the payload with a CellTrapper. We additionally have VIP924, which is first-in-class ADC with an anti-CXCR5 with the same linker and the same payload, geared for B-cell malignancies. We also have our P-TEFb enitociclib that we've reported on earlier this year, where we had combinations with venetoclax with partial responders in three out of five peripheral T-cell lymphoma and a double-hit diffuse large B-cell lymphoma in combination with venetoclax at the earlier dose cohorts. We also have had monotherapy activity with enitociclib in double-hit diffuse large B-cell in the form of complete responders for three and a half years and two and a half years. Next slide, please. With that, I'll pass it to Dr. Subbiah. Next slide. Vivek, please. Thank you so much for giving me the platform to talk about this. Again, camptothecin-derived therapies, as we all know, have been a cornerstone for treating cancer for decades. Again, we now, in 2024, as we all know, we moved from the tyrosine kinase to the IO era, and now we are in the hottest of the hottest ADC era. Let's talk about how we got here. First-generation ADCs were highly potent, but it came with many liabilities, including severe toxicities and issues with drug resistance. The second-generation camptothecins came in the form of antibody-derived conjugates. So, the recent approvals of Trodelvy/Enhertu and, as you all know, the Enhertu recently got approved in the tissue agnostic setting last week as well show that the potency of camptothecins can be enhanced with tumor-directed targeting not only in specific tumors but across multiple tumors. However, even with these second-generation ADCs, still we have toxicities associated with the first-generation camptothecins and added the ADC toxicities. So again, we have a payload here with the camptothecin that works. It's been proven time and again in the clinic, but we can see here its efficacy of the payload is limited by pretty serious safety challenges and the toxicities and liabilities that we have. So in this context, VIP236 represents an innovative approach to treating a broad range of solid tumors. And interestingly, VIP236 was designed to deliver its optimized camptothecin payload directly into the tumor tissues to overcome the severe toxicities and the transporter liabilities present and seen in the first-generation camptothecins. Again, personally to me, this is innovation. Again, this is exciting. This is what exactly we need now, right? We are seeing a lot of me-too ADCs. We need to move on from me-too ADCs to Me-better novel ADCs with unique mechanisms of action. We need drugs that use new and selective targets. We need linkers that cleave specifically and selectively release. Most importantly, we need payloads that are novel. Again, I repeat this, that we need to evolve from me-too ADCs to Me-better novel ADCs with unique mechanism of action. We can go on to the next slide. Thank you, Dr. Subbiah. This is very helpful to set up the stage here for me to talk about our initial data from our dose escalation trial. If you go to the next slide, please. As mentioned, VIP236 is in dose escalation phase 1 trial in all-comers metastatic solid tumors. The study is designed to find a safe schedule and dose and to further look at clinical activity. The initial dosing schedule had five patients with two days on, five days off. Now we are in the current dosing schedule, which dosed once every three weeks, where we have 15 patients. And that's the data I'll be presenting today. We're going to be showing the safety and efficacy of those 15 patients. We have escalated all the way to cohort six, and you can see where we are right now. We're currently enrolling patients on cohort six. We're going to be talking about the current 15 patients. Next slide, please. This study is in all-comers solid tumors, heavily pretreated, as you can see, with all different types of malignancies. These are the type of patients that you'd see in a dose escalation. Once we reach a biologically active dose, then we can expand in specific populations that would be sensitive to this kind of treatment. Next slide, please. From efficacy perspective, we are seeing exciting dose-dependent clinical activity with tumor reduction happening at the third dosing level of 0.6 milligram per kilogram. 7 patients have achieved stable disease, including tumor reduction. As the study progresses and we move into more efficacious doses, we expect to see deeper responses and as patients continue on the study. If we go to the next slide, please. We have seen durable disease control across multiple types of solid tumors. As you can see, it is a very difficult patient population here with different types of malignancies that have failed multiple priors, and they're currently on the trial with disease control. We've had patients on the trial for an extended period of time. Mind you, each cycle is 21 days. The efficacy is at the end of cycle 2, which means patients have only received 2 doses. Next slide, please. From safety perspective, VIP236 is showing a differentiated and a favorable safety profile. Most notably, there's no life-threatening diarrhea as seen with other camptothecins, and Dr. Subbiah mentioned earlier. And this shows the mechanism of action and tuning out the toxicity that has been seen with other camptothecin payloads that can lead to severe diarrhea. And we have not had any patient discontinue due to adverse events. We've had three patients with neutropenia, a couple needed supportive care, and one was quite transient. So, I'm going to turn it here to Vivek and ask your initial reaction on the data that we just presented. Again, thank you so much for sharing this data. So again, when I see the waterfall, the swim plots, and the adverse events, the dose imminent clinical activity we are seeing at this point in the dose escalation study is exciting here. Again, as a Phase 1 early-phase investigator who dealt with so many of these ADCs, clearly your drug here, VIP236, has a clearly differentiated safety profile that sets it apart from other recent approved camptothecins. Again, you don't see diarrhea. You don't see ILD. I think that's a major issue that we are seeing, ILD, diarrhea. And again, as clinical investigators, we want to make sure that the drug is safe. So, to me here, you have a drug that is safe. You found a good dosing schedule, and you're clearly seeing tumor reductions. So again, with these three slides, I would say you clearly have a drug in your hands. So, it is important here to continue the dose escalation, find your efficacious dose, and optimize the dose, and then use the data from this study to go into expansion cohorts for specific indications. So again, bottom line is that clearly you have a drug that is safe. Now you need to continue enroll more patients as much as possible, get the dose, get the efficacious dose, get a nice schedule, optimize the dose, and then take it from there. And kudos to your team for getting a drug really from the bench to the bedside. Well, thank you, Dr. Subbiah. Would you mind, please, commenting on the type of patients that we have been seeing in this study? As I mentioned, we've had all-comers phase 1 trial. So obviously, there's different sarcomas. There's colon cancer. Would you mind commenting on the type of patients that you see in our waterfall plot? Again, this is typical of our all-comers solid tumor phase 1 study, right? So again, you see clearly you see colorectal cancer. You see sarcoma. Again, as we all know, sarcoma was one of the toughest cancers that don't respond to anything, right? We are needing drugs in this space. So, if you clearly see any signal of activity in a tumor like this type of sarcoma, clear evidence of reduction of size, I think clearly it's a drug. And most importantly, you see a lot of CRC patients, even in the dose escalation patients with stability, right? I think it's important to note that all the 3 drugs that got approved recently, right, regorafenib, fruquintinib, and Lonsurf, none of them had an overall response rate. They were 1%, 1.6%, and 2% respectively. So again, all the colorectal cancer drugs are all from PFS benefit, not from response benefit. What you showed in the swimplot, right, it was clearly showing that the drug can be dosed repeatedly. Again, you have a patient more than 150 days, right? So again, these can all be early indications of a PFS benefit. And you have multiple tumor types. I think clearly you have a safe drug here. Well, thanks, Dr. Subbiah. I really agree with you, and I'm really excited to continue progressing and adding more patients on our trial and in dose escalation. Later this summer, we're going to be able to share additional data that we have along with patients that have been on the trial currently to show the length of time they've been on the trial and also at higher doses if we can see deeper responses. Later in the year, we'll be choosing expansion cohorts in monotherapy and combinations to go after. Thank you, Dr. Subbiah. You're welcome. Thank you. Thank you. Appreciate it. Now we're going to move on progressing. Dr. Borate will give us a brief description of AML with where the unmet medical need and where our VIP943 with an anti-CD123 with our novel linker and payload, where can it play in the space of AML, MDS, and B-ALL? Dr. Borate? Thank you so much, Dr. Hamdy, for the opportunity. I hope everybody can hear me okay. You can hear it quite well. Thank you. Wonderful. So, as many of you on the call may already know, AML stands for acute myeloid leukemia. It's unfortunately one of the most aggressive leukemias that we see in older patients and one of the most common aggressive leukemia we see in adults. The incidence of AML is growing. There were about 75,000 cases diagnosed globally in 2022. And I think the thing about AML that is interesting is our mainstay of treatment still and I use the word unfortunately because it is somewhat unfortunate that the mainstay of therapy for AML continues to really be chemotherapy. As many of you know, chemotherapy is not targeted. It's very broad. It has pretty broad side effects. And so for younger AML patients, I would say for over 4, 5, 6 decades, we really use the same chemotherapy. We call it 7+3. It's two agents. They're cytotoxic. For older patients now, we also use a combination of chemotherapy, which is less intensive. They're called a group of agents called hypomethylating agents. Then we add a drug, a BCL-2 inhibitor, venetoclax. So, these are sort of the mainstay of therapies that we have for our patients. But unfortunately, they're really not as effective as we would like them to be. We have made some progress in the last few years. We do have what we call more targeted specific therapies where they target specific mutations like IDH1. There's a drug called ivosidenib or FLT3. There's a drug called gilteritinib. But these are few and far between because these mutations really don't represent a majority of our AML patients. So, there's a big opportunity and I think a big unmet need for patients that do not have these targetable mutations. So, I think what's unique about a myeloid marker that is CD123 specifically, which we're going to talk about, is that it is expressed on AML cells, these leukemia blasts, independent of their genetic subtype. I think the other thing that I think is unique about CD123 is the more poor risk the disease is, including a mutation called TP53, which we know is extremely high risk, it seems to correlate with increased CD123 expression, which is really something that we can use, we can target, we can exploit because now we have the opportunity to treat patients that express CD123 with a targeted agent. I'll turn it over to Dr. Hamdy, and you'll hear more about the safety profile of VIP943. You've heard about the linker, the payload, and you've heard about the safety in solid tumors. I think this is a really good opportunity for a drug like this in the AML space. Thank you. Thank you so much, Dr. Borate. If we go to the next slide, please. Next slide. So, VIP943 is our first ADC from our VersAptx platform. It targets anti-CD123 with an antibody that's an internalizing antibody, bringing with it our payload and our linker that cleaves in the lysosome by an enzyme called legumain that's highly expressed in the tumor tissue over the normal tissue, releasing kinesin spindle protein as our payload with our proprietary CellTrapper technology, allowing it to accumulate inside the cell until the kinesin protein is present, killing the cell, and then not going into neighboring tissue, thus improving the safety and efficacy of our ADC. So, this construct of ADC is designed to solve problems associated with current ADCs that cleave nonspecifically before reaching the target and payloads that can leak out of the cell, causing bystander effect. Next slide, please. So, in our phase 1 dose escalation in CD123-positive AML, high-risk MDS, and B-ALL, the primary endpoint is looking for safety and tolerability and obviously response rate and PK. We started at 0.2 milligram per kilogram. In our first cohort, we enrolled 2 AML patients and 1 B-ALL. In the second dose cohort, 0.4, we enrolled 3 AML and 1 high-risk MDS. And we currently have completed dosing and awaiting our DLT period for our third cohort where we have 4 AML patients. Of the initial 2 dose cohorts, all patients have completed DLT period with no DLTs. 7 for 7 in each of the dose cohorts have completed the DLT period. Next slide. From safety perspective, VIP943 shows a very favorable safety profile, very well tolerated. Most notably, all patients completed the 28-day dose-limiting toxicity period. In my experience, I've done several AML programs. I've never seen 3 for 3 in the first cohort and 4 for 4 in the second cohort complete the study. I feel that this is very exciting, especially in a very aggressive type of malignancy like acute myeloid leukemia. Additionally, we didn't have anybody with any adverse events or any dose reductions. As of today, we're waiting to assess our dose-limiting toxicity with our third dose cohort. Later in the year, in the summer, we'll be updated on this trial. As you can see from this slide now, the VIP943 PK data from both the 0.2 mg and the 0.4 mg, the PK analysis of the first two cohorts looks very promising with very, very low circulating payloads. That's by design shows that our payload is internalizing and it's not cleaved in circulation. That helps with our safety profile. We're working on our receptor occupancy data from these cohorts. And I can tell you we're starting to see evidence of target engagement with approximately 60% reduction in receptor occupancy of the CD123. But obviously, we're still in dose escalation, and we will be reporting on this data later in the year. Next slide. By EHA, actually, not later in the year. Dr. Borate, I'm just going to stop here and get your thoughts and what you were thinking about the seven patients that have completed the DLT period and your thoughts of the safety profile and PK profile. Yeah, thank you for that question. I think what really stands out to me is what you just said. I treat AML patients for a living. And I will say these patients - and correct me if I'm wrong - when they come onto the study, they're relapsed refractory. They've gone through multiple lines of therapy and are usually, at this point, fairly sick. So, for all of the patients in both these cohorts to have completed the DLT period and continue on therapy is fairly unique. And I think it really speaks to the safety profile that you've observed so far. I think it's very encouraging to see how little of the payload is in circulation because, as we all know, this may contribute to some off-target, undesirable effects. And so I think those are two definitely unique things with the way the study has gone so far. I hope to see that continue. Thank you very much. I hope it continues. So far, in our third dose cohort, patients are continuing quite well. Hopefully, all will complete the 28th DLT period. We will be sharing that data. Before we go to questions, let's go to the next slide, please, which is our upcoming milestones. So you can see later this summer, we'll continue reporting on our dose escalation at the 1 milligram and beyond and the expansions that we intend later in the year. In 943 on or around EHA, we will update on safety and efficacy with the current trial. Also in June, we will be updating on our collaboration with the NIH in combination with venetoclax in peripheral T-cell lymphoma and double-hit diffuse large B-cell lymphoma. With that, I'm going to go to questions. I believe there are some questions coming in. Okay. First question. Since VIP236 is first in class, doesn't this mean that it's a very risky molecule? Well, that's a great question. Well, the VIP236 is a novel drug that is composed of two known components, a payload that is a well-known anti-cancer drug, which is a camptothecin class that Dr. Subbiah just described a few minutes ago. And it's optimized for high permeability and low efflux and has higher accumulation in the tumor tissue. In our preclinical data, we have shown that we have 10-fold higher accumulation of the payload in the tumor tissue versus the plasma. And it's also optimized to overcome known issues with camptothecins, like being pumped out of the cell by transporter overexpression. And also, we designed it to tweak out some of the toxicities associated with other camptothecins, for example, the life-threatening diarrhea. That's because of the chemical modification that has been done to prevent the delayed diarrhea that happens with other camptothecins where there is a release of SN-38 and the glucuronidation. I believe there was also a question on that. I hope I answered it. Secondly, the target is an alpha-v beta-3, which is an integrin that's highly expressed in advanced metastatic malignancies and activated endothelium. It has been targeted in the past as an anti-angiogenic and is used in targeting moieties for RGD scans. We are using it as a targeting moiety to release our payload in the tumor microenvironment. So as novel VIP236 is and being first in class, but it utilizes well-established components that offers a unique approach with lower risk profile while still being innovative, like Dr. Subbiah was describing earlier, that this small molecule drug conjugate is a novel approach to known payloads. Dr. Subbiah, anything else to add on the novelty of 236? I don't know. I'm not hearing. Maybe Vivek, you're on mute. Oh, great. Okay. Can you hear me now? Yes. Yeah. All right. Great. Again, as I mentioned earlier, what we are seeing here again, we are in the AACR meeting, and hopefully, you will see in the ASCO meeting as well. We have so many ADCs with the same payloads going after the same targets. Again, I said earlier, it is an ADC era. We need a breath of fresh air with new targets and new payloads. We know proof of concept that camptothecins work. I think this is a novel idea. You've clearly shown that in your phase 1 study that you're showing we are seeing safety and tolerability. Again, you have a drug here, right? So, you really need more patients here. You really need more patients with multiple tumor types. Then expand on with specific tumor types. You need to really pick some tumor types where we can clearly show some activity and move on. Yeah. Great. Thank you. Another very interesting question came here. VIP236, how good is what you're seeing compared to other similar compounds? Interesting. Okay. Well, although we should not do cross-trial comparisons, but obviously, internally, we look at other compounds to benchmark ourselves and where we are. And we compare to Trodelvy, for example, where in their phase 1 dose escalation in 21 patients, they had 16 stable diseases as their best response. And eventually, 2 patients have achieved PR after being on this study 2-8 months. So, it takes time for deepening the responses, as described in Trodelvy. So, I think we're tracking well. We're still in dose escalation. We are seeing dose-dependent tumor reduction and patients staying on the study for 168 days and so forth and with a very good safety profile. So I feel that we are tracking well as compared to other similar antibody-drug conjugates like Trodelvy, for example. I don't know, Dr. Subbiah, your thoughts. I'm trying to be very careful in comparing across programs in phase 1 settings. But that's your space. And you see drugs in phase 1 settings all the time. So, I wanted your feedback. Well, again, as we see in early phase Trodelvy study, the phase 1 did not have more than one or two partial responses, I believe. And time to response, it took some time between, I think, two months and eight months. So, it's known that it takes time for solid tumors to respond, right? Again, unlike TKIs, the response may take longer in solid tumors than hematologic malignancies. So, I think this is what we would expect from an ADC novel study that is clearly active in an early-phase solid tumor. Again, I think you just need to escalate. And you have a dose. You have a schedule already. You have a schedule. You need to escalate and so continue to enroll more patients here. And what was described in your waterfall plots, swim plots, is consistent for all common phase 1 studies with multiple malignancies. Like I mentioned earlier, having the early signals of clinical activity, right? You showed proof of concept at this point. And this dose escalation study is exciting. I think I am enthusiastic as an early-phase investigator. Again, we just need to add more patients and expand the study. So you have a bottom line is this, right? You have a nice safety profile. You have a good schedule that is tolerable. And this is what you expect of a study like yours at this time point. Beautiful. Thank you so much. Another question is, when do you expect to get to efficacious doses? Well, we're approaching exposures that we believe are in the efficacious range. We showed earlier that we have tumor reduction started at the 0.6 milligram per kilogram. It was very well tolerated. We continued past the 0.6 to the 0.8. We're currently about to start dosing the 1 milligram. We expect to see deeper responses in the next few months with higher doses. Also, we have to think of dose optimizations and minimally biologically active. So we're approaching the ranges of efficacious doses as we continue escalating, then eventually expanding in different patient populations. Okay. Well, I got the same question again for when will you reach efficacious doses in VIP943? Well, we're currently dosing cohort 3, which is the 0.7 milligram per kilogram. We've done quite a bit of preclinical work in different types of models. So, depending on which model that's being used to correlate the human equivalent dose, so somewhere between the third and fifth dose cohort, we would expect to be in the efficacious ranges. And we're currently, as I mentioned, dosing our third dose cohort with 4 AML patients. And we're going to be updating on that in cohort 3 and 4 on or around EHA in the summer. Okay. Another very interesting question here. Isn't targeting CD123 associated with a lot of toxicities? Well, yes. I mean, CD123 has been tested with other programs. And there is an approved drug in BPDCN called Elzonris that comes with quite a bit of toxicity. I'm going to ask Dr. Borate to give her thoughts on other CD123s. Given our program currently in CD123 with 11 patients dosed and not seeing the toxicities associated with other CD123s, I'll let Dr. Borate comment on that. Sure. So as you just mentioned, the one approved CD123 targeting drug is Elzonris. And I think the biggest toxicities that we worry about when we first treat a patient is cytokine release syndrome, where patients get really sick. They get pretty hypotensive. They have a lot of peripheral edema, and especially worse if their albumin is low. And a lot of times, patients are hospitalized and are observed very carefully for this. And there's several other CD123 targeting agents in development. Some of them have the same sort of toxicities, including requiring hospitalization and sort of prophylactic treatment against this. And it's typically the more the disease burden, the more you can sort of expect these toxicities. So, I think that's what I think is a little unique about VIP943 is we haven't really seen those types of toxicities. We haven't seen fulminant and CRS. We haven't seen where patients have had to stop treatment early or be hospitalized for prolonged periods of time. I think with any AML study, some of, again, hospitalization and things like that come with the territory. But as far as I'm aware, we really haven't seen that type of toxicity specifically with VIP943 that's required. As Dr. Hamdy mentioned, significant dose reductions, dose delays, or patients not being able to complete that first cycle, that DLT period, they've all been DLT-valuable. So, I think that's really encouraging. And as was mentioned with the other molecule, I think the proof of the pudding is in escalating and adding more patients and really seeing, as you get higher to higher doses, what responses and the toxicity profile looks like. But so far, I think that's looking really encouraging. As he mentioned, that's some data that will hopefully be available in the near future. Well, great. Thank you. Another question. Will your ADC technology work in solid tumors? Well, just to be clear, I mean, we have a small molecule drug conjugate that is geared for solid tumors. We have currently two ADCs that are geared for hematological malignancies. But our research and development team has been working diligently on more innovations. And actually, this morning, in the preclinical poster sessions in innovations in ADC technology platform, we actually presented that our effector chemistry, which is basically legumain and the cleavable kinesin spindle protein payloads, was adaptable to various aspects of different types of biologies. And that we compared ourselves to Trodelvy and Enhertu in our poster this morning to approved ADCs with different linkers and payloads. And we actually show that we have, in solid tumors, up to 40-fold improvement over those other ADCs. So, will our ADC technology work in solid tumors? Absolutely. And we fear that our preclinical data supports that. And we'll be sharing more results as we add to it. Okay. I think we have time for one more question. Will there be patient selection for VIP236? Yes, we are collecting patient samples. And we're doing quite a bit of retroactive biomarker work, which could help to inform our dose optimization and patient selection and enrichment. Okay. I think this is all the time we have for questions. But we'll be happy to address on one-on-ones or in further communications. And I thank you very much for your time and attention today and being with us. And with that, we'll end our webcast. Thank you very much. Thank you for your participation in today's conference. This does conclude the program. You may now.