Good morning, and welcome to the NextCure virtual KOL event. At this time, all attendees are in a listen-only mode, and a question and answer session will follow the formal presentations. As a reminder, this call is being recorded, and a replay will be made available on the NextCure website following the conclusion of the event. I'd now like to turn the call over to your host, Michael Richman, President and Chief Executive Officer at NextCure. Please go ahead, Michael. Thank you, operator. Good morning, everyone, thank you for joining us as we discuss the highlights from yesterday's ASCO 2026 conference poster presentation of preliminary phase I trial results from SIM0505. Before we begin, I want to remind you that this presentation contains forward-looking statements, and we encourage you to review our latest SEC filings for a full breakdown of risks and uncertainties related to any forward-looking statements we make during today's presentation. To introduce today's speakers, joining me today is NextCure's Chief Medical Officer, Dr. Udayan Guha, and three prominent key opinion leaders. First, Dr. Rakesh Dixit is a member of our scientific advisory board and a recognized ADC expert who has developed several approved agents. Next, Dr. Ursula Matulonis is Chief of the Division of Gynecologic Oncology at the Dana-Farber Cancer Institute and also a member of our scientific advisory board. Dr. Matulonis has served as a principal investigator for landmark trials in ovarian cancer, including the SORAYA trial that led to the approval of mirvetuximab in platinum-resistant ovarian cancer. Finally, Dr. Beryl Manning-Geist is Assistant Professor of Gynecologic Oncology at the Emory University School of Medicine. Dr. Manning-Geist is an active clinical investigator specializing in targeted therapies for gynecologic malignancies and is one of the clinical investigators on the SIM0505 study. I want to start by thanking our speakers for their time and insights. We also want to recognize our co-development partner at Simcere Zaiming, whose collaboration has been integral to advancing SIM0505. The next slide introduces today's agenda. During today's call, I will start with a few opening comments. After that, I will hand the call to Dr. Rakesh Dixit, who will discuss the differentiation of SIM0505, a CDH6 targeting antibody-drug conjugate, or ADC. Next, Dr. Ursula Matulonis will then summarize highlights of initial dose escalation clinical data from the phase I study presented at the conference. Finally, following their presentations, Dr. Beryl Manning-Geist, a principal investigator from Emory University, will discuss the unmet need in platinum-resistant ovarian cancer, as well as uterine serous carcinoma and share her SIM0505 clinical experience with our chief medical officer. I will close the formal call with an outline of the next steps and development path forward for SIM0505. At the end of the webcast, we will host a Q&A question. As a reminder, the audio slides from this webcast will be available on the NextCure website later today. In slide five, entitled SIM0505 Demonstrated Best-in-Class Potential in Gynecologic Cancers. Today we are reviewing the first clinical data reported for SIM0505 presented yesterday at ASCO 2026. Platinum-resistant ovarian cancer and uterine serous carcinoma remain two of the most challenging gynecologic cancers to treat, with significant unmet need. We believe SIM0505 has the potential to be best-in-class treatment for these patients. SIM0505 achieved a 55% overall response rate in gynecologic cancers at therapeutic doses. This included a 52.9% response rate in ovarian cancer and a 66.7% in uterine serous carcinoma. The safety and tolerability profile has been favorable in heavily pretreated patients. phase I dose optimization is currently underway, with a focus on platinum-resistant ovarian cancer and uterine serous carcinoma. In this next slide, I will now turn the webcast over to Rakesh. Good morning. Thank you, Michael, for a great introduction. What I will describe in the couple of slides what differentiate SIM0505 compared to similar ADCs targeting CDH6 target. Can I have the next slide, please? As you may know that there are three components of ADCs. Of course, the target antigen, the linker payload, and how do you make it? First, we start with the target. As Michael mentioned, CDH6 is a, cadherin, additional molecule, Cadherin-6. It's highly overexpressed in multiple solid tumors, especially ovarian and uterine cancers, as well as renal and non-small cell lung cancer. That's what it makes it very highly attractive because the expression levels are pretty high in these cancers. It becomes a really great target for ADCs. Also now it is a validated clinical target, it makes it even much better. First I will describe the part of the molecule which starts with the antibody part of the CDH6. What is so unique about this antibody? One uniqueness about this antibody compared to very similar ADCs, which are also targeting CDH6 from other pharmaceutical companies. It has a very unique epitope targeting. Why that is important is because this particular epitope is much more exposed, and which means that the antibody can bind much more tightly to target. Doing that, it can internalize much better. Also we can target low-expressing CDH6 cancers. The second part of this molecule is the linker. Linker is GGFG linker. This is tetrapeptide linker, very similar to what Daiichi Sankyo has used. It's a clinically validated linker used in multiple successful ADC programs. The most important feature of this particular construct is the payload. This is a camptothecin-based payload, not too dissimilar to DXd and exatecan, but highly modified to provide a better conjugation and reduce the hydrophobicity. We are using DAR8 because we know that DAR8 means eight molecules of the payload in each antibody molecule. It helps to deliver more payload to tumors and get better efficacy. Can I have the next slide, please? I'm going to spend a little bit more time on this particular slide to explain to you where the differentiation comes from. As I explained to you earlier that the antibody targets the extracellular domain, EC1 epitope on CDH6, and this particular epitope is on distal side, so it's much more exposed to external surface. That means the antibody can bind much more efficiently. By doing that with high affinity, we also have shown that you have much better internalization. It also gives us much better pharmacokinetic proportionality as well as because the antibody is not that hydrophobic, it also reduces the aggregation. The next part of the differentiation is the payload, and I'm going to spend a little bit more time on the payload. Although payload is related to camptothecin, the topoisomerase I inhibitor, which is now being used almost in 60% of all new ADCs, very well-validated payload. What is so unique about this payload is that this payload has much more reduced hydrophobicity. Why the hydrophobicity of the payload is important? First is when you're using a DAR8 molecule, the hydrophobicity can increase. If you have very hydrophobic payload, it can substantially increase the aggregation. When you increase the aggregation, what happens is that your ADCs start behaving like immune complexes. Those immune complexes can get off-target tissues, immune cells, and cause a lot of toxicities, not to mention the immunogenicity problems and also manufacturing problems. In addition to that, because hydrophilic nature, it does not lose its permeability power. It has a really good bystander effect. It can cross the membrane efficiently once it releases the lysosomes of the tumor cells. Why that bystander effect is important? The bystander effect allows to get into more heterogeneous tumors where the expression level is not homogeneous. You can kill a neighboring cell, which does not have the expression of your target. It's a very important property. Also what is important, because we have reduced the hydrophobicity of payload, that allows us to keep the molecule a lot more stable because hydrophobic ADC are not very stable, and they can release the payload prematurely in the circulation. That's also very important. All these properties of the payload, along with the well-validated linker and a unique antibody design, with a novel epitope targeting, helps us to explain why this molecule is so differentiated. We believe this differentiation will likely result in better tolerability and a better efficacy relative to other ADCs that target the same target. Can I have next slide? With this, my presentation, I will now pass on to Dr. Ursula Matulonis. She is going to present the clinical phase I dose-escalation data. Thank you. Thank you, Rakesh. It is a pleasure to participate today and share my thoughts on the gynecologic cancer treatment landscape and also to discuss the initial data set from the phase I dose-escalation trial of SIM0505. Before we turn to the data, I want to take a moment to review the current treatment landscape and unmet need in ovarian cancer. Ovarian cancer is now the sixth leading cause of cancer-related death among women in the U.S., with a median age of 63. The good news is that survival is improving, but the incidence seems to have plateaued. There are now about 21,000 new cases predicted of ovarian cancer in 2026 in the U.S. Symptoms are often vague and quite subtle. Most patients are diagnosed at late stages because of the biology of this cancer and the lack of an early detection test. The overall five-year survival rate is about 51%, with survival worse for patients diagnosed at later stages, Stage 3 or 4. For patients with Stage 1 cancer, they have survival approaching 90% at five years. Currently, the prevalence is about 250,000 women living with ovarian cancer in the U.S., that will assuredly continue to increase. At initial diagnosis, treatment consists of surgery followed by platinum and taxane chemotherapy, with or without bevacizumab. Sometimes, if patients have high tumor burden, they will start with neoadjuvant chemotherapy prior to surgery. Luckily, survival has improved for this cancer. We talked about before, maintenance therapies consist of continuation of bevacizumab as well as addition of a PARP inhibitor for homologous recombination deficient ovarian cancers. Most of our patients will recur, and once platinum resistance develops, response rates drop to as low as 10% up to 20% or so, with a median overall survival closer to 11 months. Moving on to Uterine serous carcinoma. Uterine serous carcinoma is a rare but highly aggressive subtype of an endometrial cancer. Its incidence is rising in the U.S. It accounts for 10% of uterine cancers, but nearly 40% of uterine cancer-related death. It is driven by P53 mutations and alterations in MYC, HER2, and Cyclin E1, as well as others. It typically arises in post-menopausal women, most commonly presenting with abnormal or post-menopausal bleeding. More than half the patients present with Stage III or IV disease at diagnosis, contributing to its disproportionate mortality burden. Risk factors of serous carcinoma include advancing age, a history of breast cancer and tamoxifen use, and hereditary breast ovarian cancer syndrome. We're not really sure why the incidence of this cancer is rising significantly in the U.S. I would like to focus on the SIM0505 program and provide a summary of the initial phase I dose escalation results. Next slide. The dose escalation segment of the phase I trial included initial six cohorts and two added intermediate doses in the therapeutic range, boxed in red. CDH6 is highly expressed in gynecologic cancers, patients were enrolled regardless of their cancer's CDH6 expression levels. A retrospective analysis of CDH6 expression levels in the phase I study is currently ongoing. SIM0505 is given intravenously once every three weeks. The dose escalation portion focused on three primary tumor types: ovarian cancer, uterine serous carcinoma, and renal cell carcinoma. A total of 59 patients were enrolled, with 25 from the U.S. and 34 from China. Next slide. The study enrolled heavily pretreated patients. The majority of study patients had an ECOG performance of one. I want to bring your attention to three important demographic factors for this study: the ECOG performance status, pretreatment level, and metastatic tumor burden. We can start with performance status. In the clinic, we use ECOG scale to quantify a patient's daily functional abilities. ECOG 0 represents full active patients. They have no symptoms related to their cancer, and they can carry out all activities without restriction. ECOG 1 describes some symptoms, but ambulatory patients who are restricted in physically strenuous activity, but they can do light or sedentary work. Patients with ECOG 0 consistently show superior overall survival and lower rates of serious adverse events compared to ECOG 1. Notably, 73% of patients in this study had a baseline ECOG score of 1. Moving to the prior treatment regimens at the bottom of the table. Patients in the study had a median number of five prior regimens, which is quite a lot. There's a range of between one up to 12. This really indicates an exceptionally heavily pretreated and advanced treatment-refractory patient population. Finally, FIGO Stage 4 metastatic tumor burden and stage. As you know, the staging system helps to understand how far a cancer has spread and how aggressive that cancer looks under the microscope, so the grade. For uterine serous cancers, that grade is always a three. FIGO Stage 4 indicates that the cancer has metastasized to distant organs, such as the lungs or lymph nodes outside the abdomen, as well as the possibility of intraparenchymal liver metastases. 75% of ovary and uterine serous cancer patients in the study had a FIGO stage of 4. In the backdrop of this heavily pretreated advanced stage gynecologic cancer population, I believe that SIM0505 has demonstrated an exceptionally promising response rate. Next slide, please. The overall safety profile of SIM0505 is both manageable and tolerable, as you can see in this slide. 54% of patients in the study experienced Grade 3 or greater treatment-emergent adverse events. I believe this is very acceptable for an antibody drug conjugate like SIM0505, given the drug's strong early efficacy, manageable side effect profile, and low discontinuation rates. I'll note that the two reported Grade 5 treatment-emergent adverse events were determined to be unrelated to the study drug. I also want to draw your attention to two other items: low discontinuation rate and manageable interstitial lung disease, or ILD, or pneumonitis risk. Discontinuation from treatment-related adverse events occurred in only three patients in this dataset. Interstitial lung disease, or ILD, or pneumonitis is a known class effect toxicity for ADCs that utilize Topo1 inhibitors as well as other payloads. Compared to its peers, this study reported a low level of ILD risk measured by one Grade 1 and one Grade 2 episode of ILD. Based on this initial data set, I believe the ILD risk appears highly manageable. Next slide. I'd like to delve a little bit more deeply into the safety profile of SIM0505. On this slide, we show a summary of the most common treatment emergent adverse events occurring at a frequency of 10% or higher. Most of the treatment emergent adverse events were Grade 1 and 2 events noted in light blue color. Grade 3 and 4 events noted in dark blue were primarily comprised of expected heme toxicities, such as anemia and decreased neutrophil counts. Overall, a maximal tolerated dose, or MTD, has not yet been reached. Escalation continued up to 9.6 milligrams, where the first dose-limiting toxicity, or DLT, was observed. In conclusion, SIM0505 demonstrates a highly favorable safety profile, notably requiring no primary prophylaxis for neutropenia or thrombocytopenia. Next slide, please. This swimmer plot demonstrates patient data organized by dose level with the lowest dose at the top. Patient's unique ID number, geography, tumor type, and number of prior lines of treatment are listed on the y-axis of the chart. Looking at the clinical activity, confirmed responses are shown as yellow triangles, while unconfirmed responses are represented by orange triangles, with blue arrows to denote patients who continue on study. Notably, we see strong efficacy in heavily pre-treated patients. Furthermore, four of these responses occurred after the initial six-week scan. I am highly encouraged by the early durability observed in SIM0505-treated patients. I would also call out particular attention to the early durability of these responses. Seven patients with a response have reached six months, with all but one still on treatment. One patient with ovarian cancer has now been on treatment beyond nine months. Next slide, please. Let's focus on the main data that was presented at ASCO 2026. The data cut presented here at ASCO is based on response data for patients with gynecologic cancers treated at therapeutic doses with at least 12 weeks of follow-up. There were 20 evaluable patients in this group. This slide summarizes the overall and gynecologic cancer breakdowns, showing a 55% response rate, including a 52.9% response rate in ovarian cancer and 66.7% in uterine serous carcinoma. The 55% response rate includes two patients with unconfirmed responses, and of these two patients, we are awaiting follow-up scans for one patient. These are very encouraging results in a heavily pre-treated population in a first-in-human phase I study. I'll discuss the breakdown of ovarian and uterine serous carcinoma patients in more detail in the next few slides. Next slide, please. The swimmer plot on this slide illustrates the depth and durability of response observed in ovarian cancer patients treated with SIM0505. Nine of 17 evaluable patients with ovarian cancer achieved a partial response for an overall response rate of 52.9%. Responses were observed across dose levels, reflecting broad activity of SIM0505. Several patients continue on treatment, providing early signals of durability. These results are encouraging in a heavily pre-treated population. Next slide, please. The waterfall plot demonstrates tumor shrinkage across dose levels, with the greatest reductions observed at 6.4 mg and 8.0 mg per kilo. Up to 70% tumor shrinkage was observed at the 6.4 mg per kilo dose level. Based on response rate, depth of tumor shrinkage, durability, and follow-up time, the 6.4 mg per kilo dose has been selected as the anchor dose for the optimization study. The 5.6 mg and 7.2 mg per kilo dose levels, which opened late last year, will serve as bookend doses in the optimization study. Next slide, please. In this spider plot, you can see 15 out of 17 patients had tumor shrinkage, and importantly, tumor shrinkage continues to deepen with continued treatment. Next slide, please. Before closing, I want to highlight the early but encouraging data in uterine serous carcinoma. Current treatment relies on platinum-based chemotherapies, representing a significant unmet medical need. While the data set is small, the signals are quite encouraging. Of the three patients with at least 12 weeks of follow-up, two achieved a partial response for an overall response rate of 66.7%. Of note, we observed a response at the lowest dose cohort of 1.6 mg per kilo and an additional early response at 7.2 mg per kilo, which has not yet reached the 12-week assessment mark. Looking at the top swimmer lane, the patient at the 6.4 mg per kilo dose has now surpassed 24 weeks or six months on treatment. Together, these early data points are incredibly promising. Next slide, please. Finally, the uterine serous carcinoma spider plot demonstrates continued tumor shrinkage and a deepening of the patient response on subsequent scans, a pattern reproducing the findings in ovarian cancer. Notably, the patient at the 6.4 mg per kilo dose has been on study for more than six months and is still ongoing. I look forward to seeing additional data as NextCure plans to enroll more patients. Next slide, please. I would now like to introduce Dr. Udayan Guha, NextCure's Chief Medical Officer. He'll be discussing the SIM0505 clinical experience with Dr. Beryl Manning-Geist, who is a Principal Investigator from Emory University. Thank you, Dr. Matulonis. Good morning, Dr. Manning-Geist. Thank you for participating in today's webcast. Before we get started, it would be helpful to share your background and area of expertise with our audience. Absolutely. Thank you guys for having me. It's a pleasure to join you all today and discuss SIM0505. I joined Emory's Winship Cancer Institute two years ago after completing my training at Memorial Sloan Kettering Cancer Center. I joined Emory really with a mandate to expand clinical trials in the metro Atlanta area for a patient population that's historically been underrepresented and underserved in clinical trials. Here at Emory, I run the GYN clinical trials portfolio, and I also help run our institution's phase I trials, including SIM0505. More broadly, I'm an editorial board member of GYN-ONC, I serve on SGO's Clinical Practice Committee, and I'm an early career new investigator for NRG Oncology. Thank you. That's great. Can you provide a little about the demographics of the patients you are treating with SIM0505? Yeah. It's a good question, Udayan. I think that there's three points that are really important to emphasize here. The first that Dr. Matulonis really spoke about is that this is a heavily pretreated population, and women are starting on this trial with the sequelae of that pretreatment. My patients have bone marrows that have seen five, six, seven, eight, even nine prior treatments. We'll get more into kind of the associated toxicities with SIM0505, but I think it's really one of the extraordinary features of this drug. I have a patient, for example, with nine prior treatments, and she's required no dose reduction, and she has a durable response. This is a heavily pretreated population. I think we just saw a slide showing a median of five prior lines of treatment with up to 12. As a result of that, patients have significant baseline symptoms. In the broader population, about 73% had an ECOG score of 1. That's kind of the first point. The second point here that I want to emphasize, I kind of alluded to this in my introduction, is that the patient population that I'm privileged to serve here at Emory looks a little bit different from some of our other trials, right? These are not kind of your affluent, healthy patients in general. My patients have diabetes. They're smokers. They're almost universally obese. Most patients that I've treated on this trial, I've treated about 15 patients so far, self-identify as non-white, about 75% of my patient population. This population that is represented here in the data presented thus far, it's representative. I think that's what the FDA wants to see in modern oncology trials when they're considering drug approvals, to really see what real-world administration of this drug looks like, I'd argue that we're doing that. I think the third thing that I want to comment on is the efficacy that we've seen in this drug. It extends past ovarian cancer, which is also exciting. The group that we've touched on a little bit are these uterine cancer patients, right? We see a lot of these patients in the Southeast, and these patients are exceptionally hard to treat. In ovarian cancer, we've seen a little bit of a boom in terms of the antibody-drug conjugate landscape, and we've seen some new targeted approvals. For example, Dr. Matulonis's mirvetuximab trial. We haven't really seen similar tools for our toolbox in uterine serous cancer patients. We've enrolled both those patients on this trial here at Emory, and we've seen some robust, some early, and some durable responses for both patient populations. All right. That's a great overview of demography. Being that SIM0505 is a topoisomerase inhibitor ADC, which inherently has side effects, can you provide some insights into your experience with SIM0505 managing safety and tolerability? ILD, as we all know, is a class effect of DXd and several topo payload ADCs. It might be helpful to have your share of your experience and perspectives on ILD. I'll kind of split this into two answers. We're going to talk about tolerability first, and then I'll delve a little bit more into the ILD question because it's important, especially with kind of the antibody drug conjugates that are emerging. For the tolerability question, that one's key here, right? I've treated kind of as I alluded to, about 13 patients. I think by the end of next week, I'll have 20 patients on trial. As a general overview, right, of the tolerability of this drug, my phase I clinic is staffed by a team of four nurse practitioners, right? They see patients across all of our phase I trials here at Emory. The SIM0505 trial is by far their favorite, and that's because these patients do well, right? They have energy. They have some nausea, but it's not terrible. It's manageable kind of with the medications and support that we can give. Their disease shrinks, and so we'll get more into that later. It doesn't mean that there are no toxicities, right? The toxicities that I've seen in my patient population are primarily anemia, so I have patients that may need an occasional blood transfusion. I think that that's a side effect for patients that is acceptable, right? Not all side effects are created equal. When we look at some of these drugs that have ocular toxicity, having interference with your vision, that's an unacceptable side effect to a lot of patients, and I get that, right? It significantly interferes with quality of life. Whereas needing a blood transfusion occasionally, that is generally a more acceptable kind of side effect and intervention for patients. The other thing is neutropenia, right? With a lot of these Topo1 payloads, we see decreases in white blood cell counts, and neutropenia can be fairly significant. I think with this trial, I've seen no febrile neutropenia, and the neutropenias that I have seen have been very easily supported with G-CSF, and it's important to state and kind of note that I'm not kind of universally giving that to all of my patients, right? My patients that are higher risk or my patients who go on to develop, maybe I do intervene, but the majority of my patients don't start on that kind of reflex prophylaxis on this drug. I think that those are kind of some of the most important points in terms of safety and tolerability in a real-world setting. There was a second part to your question, right? The point about ILD, and I think that this is gaining a lot of press, and I think that Gynecologic Oncology as a field has taken ILD very seriously and importantly so because some of the drugs that we're using as standard of care agents do develop this, right? When we take a step back and we think about drug-induced ILD or pneumonitis as kind of a synonym there, it represents really a leading cause of treatment-related death in ADC clinical trials. We've seen that in some of the CDH6 ADC peers. It's really important to recognize how significant that can be. ILD, I think, is far more common than previously thought, right? We're paying more attention to it. We're noticing those ground glass opacities on CT scans, and so we're getting a little bit more savvy to these off-target toxicities. People are paying more attention to some of those subtleties and findings, or your patient complaining of exertional shortness of breath, maybe things that we wouldn't pay attention to before. With SIM0505, what's been exciting is kind of the relative lack of ILD, right? There have been, I think we commented on two episodes with this drug of ILD, both Grade 1 and Grade 2, so there have been no Grade 3s. We've been able to kind of, because of the lack of ILD, dose patients with a DAR of eight at kind of these relatively higher doses compared to peers, right? Because it's only a Grade 1 and Grade 2, with many of these patients with Grade 1 and even some patients with Grade 2, rechallenge is still acceptable. I don't think that ILD has necessarily been limiting for this drug in the way that it has been or is going to be for some of its ADC peers. All right. That's great. Thank you for the good overview of your patient safety. Now let's get an understanding of how your patients are responding and insights you can share there. Yeah. I think that we saw some of that from Dr. Matulonis' presentation. What patients have been so excited about is these are often women who have told that they don't really have other options necessarily, right? Where standard of care regimens are often producing response rates that are certainly less than 15%, often less than 10%. It isn't just that these patients are cracking that 30% tumor volume shrinkage to be classified as a partial response. I have patients with 40%, 50%, 60% response rates to this drug. I think that the depth and durability of this response, it's a little bit harder to comment on the durability kind of beyond the first nine cycles. I think I have some patients who've reached nine cycles at this point in time. These patients still are having ongoing response. They're still having excellent tolerability. When we think about cancer drugs in general, especially in oncology, everything is weighing the pros and cons, the risks and benefits of treatment, right? What is the side effect profile? Is this medication worth it, right? With SIM0505, at least for my patients, we've found something that's highly effective, seems to be quite durable, and importantly, it's highly tolerable. It's kind of the trifecta there. Great. All right, now you are treating some USC, uterine serous carcinoma, patients with SIM0505, and as I mentioned earlier, we are very encouraged by small data set, but the responses that we are getting. Welcome your perspective on treating USC with SIM0505. Yeah. I think that uterine serous cancer is, in its advanced stages, a more challenging disease to treat than your platinum-resistant ovarian cancer. That's because the pace of spread, the pace of growth, is much higher in these patients, in my experience. These patients tend to do worse more quickly. Since lenvatinib and pembrolizumab gained FDA approval, we haven't really had any significant slam dunks in uterine serous cancer outside the HER2-amplified tumors, which represent the minority. The patient that I have on study now, she's had, I think at this point, I think over 60% of her tumor shrank, and she's due for cycle 8 here shortly. Again, this is a patient where I don't have options for her right after her carboplatin immunotherapy and her lenvatinib and pembrolizumab. This particular patient, I really don't have anything to offer her. To be able to find something where she can have a response is pretty remarkable. All right. Thank you. Those were my questions. Thanks for sharing your perspectives. We really appreciate. Thank you, Udayan. Looking ahead, we recently announced the initiation of our dose optimization study for SIM0505. In this randomized trial for patients with platinum-resistant ovarian cancer, PROC, we are advancing three dose levels: 5.6 mg 6.4 mg, and 7.2 mgs per kg, alongside an additional backfill cohort in USC. The goal is to identify the optimal dose to advance to a pivotal registrational trial, which we estimate will begin in the second half of 2027. Next slide, please. Today, we shared the first clinical data reported for SIM0505, presented yesterday in a poster at ASCO 2026. SIM0505 achieved a 55% overall response rate in gynecologic cancers at therapeutic doses, including 52.9% in ovarian cancer and 66.7% in uterine serous carcinoma. The safety and tolerability profile has been favorable in heavily pre-treated patients. Phase I dose optimization is currently underway with a focus on platinum-resistant ovarian cancer and USC subjects. We believe SIM0505 has the potential to be a best-in-class treatment and to address the significant unmet need that remains in these two challenging gynecologic cancers. We want to thank today's speakers and collaborators, as well as our co-development partner, Simcere Zaiming, whose collaboration has been essential to advancing SIM0505 to this milestone. We look forward to your questions. Thank you. Thanks again to all the panel members for presenting at today's KOL event. Even more importantly, thanks for all the important work you do for patients and for the ongoing SIM0505 clinical trial. I'd also like to thank Doctors Guha and Doctors Manning-Geist for the informative discussion and the real-life and real-time experiences in treating patients with SIM0505. Before we get to the Q&A, I'd like to just start with a few just general questions for our panel. Maybe first we'll start with you, Dr. Matulonis, regarding all of the exciting work being done in the ADC field as it relates to treating gynecologic cancers. While we're seeing a lot of significant progress, Dr. Manning-Geist had talked about managing the risk-benefit. The question that always comes back to us is, what about the non-responders? What about even with those 40%, 50%, 60% response rate, what about the patients that are progressing? I guess the question for you is: Is there room for multiple ADCs targeting various targets on these various tumor types? Yeah, Michael, thank you so much. I think it's a great question, and I think a lot of us, myself and Dr. Manning-Geist are thinking about that right now as we are presented with a number of at least certainly Topo1 antibody-drug conjugates. I think, at least at the initial aspect when we're thinking about single agent Topo1 ADCs, response rates seem very good. I think Dr. Manning-Geist did a great job explaining for patients who are heavily pretreated, that ovarian cancer and uterine serous carcinoma can still respond to treatment. I think that is an important observation in itself, where I think, in the past, it was thought, "Well, gosh, someone's had so many previous lines, the response rate of that drug is going to be close to 0%." That's clearly not the case here. That is a very exciting observation that we now have medications available for our patients who are heavily pretreated and those who are not heavily pretreated, that are going to result in very impressive response rates, close to 60%, which is really unheard of in high-grade serous ovarian cancer, certainly uterine serous endometrial cancer, in the recurrent setting. I think that's really exciting. We're going to look at toxicities. SIM0505 clearly is a very well-tolerated drug. I think Dr. Manning-Geist brought up a very important point about the low risk of ILD, and that is not the case of all ADCs. In certain antibody conjugates, if any level of symptomatic ILD occurs, we have to stop the drug, even if the patient is having a response. I think, in the future will be potentially combinations of medications. It really is looking like a very exciting new avenue. Looking at ADCs as single agents, but also in the future for combinations as well. Great response. Thanks for sharing that. Dr. Manning-Geist, you talked a lot about the SIM0505 CDH6 ADC program. How do you think that fits in this crowded area of multiple ADCs with different targets? I think that there are some things that are known and some things that are unknown, right? As Dr. Matulonis said, there's probably two qualities to the ADC that can induce resistance. It could be resistance to the targets, in this case CDH6. It could be resistance to the Topo1 payload. In terms of understanding how that resistance plays into sequencing of therapies or whether multiple therapies can be used, that remains an unknown. We don't know. We don't know if a Topo1 after Topo1 is going to have efficacy in any kind of robust way. When we think a little bit more about which drug to choose and what setting, I think that many of us for the start, when we're using single agent ADCs, are going to be basing that decision off of tolerability. Whichever ADC has a lower likelihood of inducing ILD, I think a lot of providers are going to be pivoting towards that. If we look at our experience with PARP inhibitors, for example, providers are using drugs that have a lower likelihood of inducing profound thrombocytopenia, for example, when you compare our PARPs on market. I think the toxicity profile is going to be very important as we consider which single agent to use. Emerging data, I think, are going to help us understand sequencing of therapies and whether resistance is more to the protein of target to the Topo1, or if it's both, and how we can distinguish which case is driving resistance. I think as Dr. Matulonis kind of pointed out, as we use these treatments in combination, be it with VEGF inhibition immunotherapy or others, or other cytotoxics really. How do we leverage the doublet therapy to overcome mechanisms of resistance? Great. Thanks for that informative response. Finally, Dr. Dixit, you've been in the ADC field for a real long time, and I'd love to get your thoughts on some of the next generation approaches people are taking, and how do we prioritize the use of these different ADCs when these tumors express multiple targets? I think this is a really excellent question, Mike. Can you hear me okay? Yeah. Yes. I think the way I look at ADCs, how they actually work. First thing, they do require target expression because without target expression, they cannot get in inside the tumor because internalization is critical, unlike the small molecule chemo drug, where they come through diffusion process. Here, you have to bring them in. That means target expression becomes really important. For example, let's see if you're trying on the folate receptor ADC, like ELAHERE, and patients are relapsing on that one. In that case, you also look at what is the reason they're relapsing. Are they not responding to the payload, or the target is not enough for that molecule? You look at, also in the biopsies, you look at whether you are seeing a very high expression of CDH6 as a part of resistance or refractory nature. You treat with SIM0505. The advantage here, in my opinion, would be that the payload used with the ELAHERE is a microtubule poison. Okay. Now you're coming with a topoisomerase inhibitor, which is a very different MOA. This will avoid treating with a two topoisomerase in sequence, which we know they don't work that well, because once you develop resistance against one topoisomerase inhibitor ADC, then likely you're going to develop against the next one. If resistance is likely due to some changes in topoisomerase binding site to the camptothecin-type-like molecule. The third one will be that you can also, if you see that patients are advancing or not responding that well to CDH6 ADC, then you could consider a B7-H4 ADC, which also very highly expressed, which has a different payload. Now instead of topoisomerase payload that it has, now it has MMAE-type payload. I think switching the payload becomes very important as well as the target expression. First I will start with a very high expression target ADC with a different payload, differentiated payload, and then switch over to a different target. These cross-resistance against different payloads and target expressions are extremely important in these combination settings. Yeah. Great. Thank you so much, Dr. Dixit. I have so many more questions, but I know we have a number of individuals that have called in with some additional questions. I'll turn it over to Tara, who will kindly introduce some of our questioners. Great. Thank you, Michael. Yes, our first question comes from Emily Bodnar at H.C. Wainwright. Please go ahead, Emily. Hi. Good morning, guys. Thanks for taking the questions and congrats on all the progress and great data. Maybe for the first one, if you can discuss Cadherin-6 expression and if that had any correlation with the responses that you saw. I know you mentioned that you could potentially have activity in low Cadherin-6-expressing patients. I'm curious if you're planning to evaluate that in later stages of the trial, in phase II and beyond. Maybe for a second question, if you can discuss differences in baseline characteristics from the other Cadherin-6 data we've seen, and how that differs given your very late-line patients that you've enrolled. Thanks. Great. Thanks for that question, Emily. Maybe we'll start with you, Ursula, with respect to the impact on CDH6 expression. I think that it's an interesting question, certainly may offer some differentiation amongst the different drugs. I think R-DXd has presented, Dr. Moore has presented data on CDH6 expression. Certainly, I think that gives one more confidence that an active Topo1 ADC against CDH6 can have levels of response across different expression levels of CDH6. Certainly CDH6 is expressed pretty ubiquitously in ovarian cancer, at least in high-grade serous ovarian cancer. If you look at that graph that she's represented, the responses are definitely more sort of clumped at the higher CDH6 levels. I think it'll be important for all these drugs, certainly and for SIM0505, to also take a look at this and disclose that data, to show that this is a drug that, regardless of CDH6 expression, will have efficacy. Great. Thanks, Dr. Matulonis. Tara, should we take our next question? Yes. Thank you for your questions, Emily. Our next question will come from Christopher Liu at Lucid Capital Markets. Christopher, you may go ahead. It looks like he may be having some tech issues, so I am just going to bring in the next analyst, and we will go back to him after. Our next question comes from Yuan Zhi at B. Riley. Please go ahead. Good morning. Thank you for taking our questions. Maybe first, in the current phase I trial, what's the response rate of 0505 in patients who are refractory to the folate receptor ADC mirv? Great. Thanks for that question, Yuan. We'll start with that first question. Dr. Matulonis, since you presented some of the data, and we've been talking about some of these patients, any thoughts on that? Yeah. I think that's a great question. I don't think that data has been publicly disclosed yet, or the answer to that question has been disclosed yet, and maybe Udayan has an answer to that. Yeah. I think certainly, as Dr. Dixit mentioned, that one would anticipate that if a patient who's a high expresser for Folate receptor alpha receives mirvetuximab soravtansine progresses through it, that a Topo1 payload, since the payloads are different, should have a chance of response. I think that is being looked at right now, but I would certainly anticipate that that would be the case. More data will tell us for sure. Yeah. Dr. Guha, would you like to add to that? Yeah. Just to add, this is a great question. We are actively looking into this. The good thing is we have many patients. In the poster, we showed 11 patients with mirvetuximab treated, but these are all from U.S., recent patients in the intermediate dose levels. We show, though, one patient at the 6.4 mg dose level from U.S. with nine prior lines of therapy, including mirvetuximab, who is having a prolonged response with a good shrinkage of tumor and everything, almost reaching six months. We have to continue looking into that. This is important because in the R-DXd study, at least what was presented in ESMO 2023, they did not have many such patients, three or four patients, if I remember correctly. We have to really look into this more carefully and have more such patients. In the U.S., we are getting those. If I can add to that anecdotally, I have multiple prior patients with mirvetuximab exposure, some of whom have rolled, I believe, directly onto this treatment and who have response to this. As Dr. Matulonis kind of pointed out, the protein of interest here, folate receptor versus CDH6. CDH6 is certainly more highly expressed in ovarian cancer compared to folate receptor or what we consider expression, right? CDH6 is more expressed, it's a different protein, and it's a different payload. I would be surprised to see if that specifically was associated with increased resistance to SIM0505. Got it. That's very helpful. Did you have another question, Yuan? Yes. Since your trial enrolled both the patient from China and the U.S., I'm curious if there is any difference in terms of TRAEs reported by investigators there? Dr. Guha, you may be best positioned to talk about. Yeah. The patients. Right. We have not shown the data separately for safety in China and U.S. Overall, we are looking into this actively, and we don't see any big difference in the Grade 3, 4s that we are getting in the actual safety events like AEs. Where there is some difference is how they are treated or managed. Like for example, Grade 3, 4 thrombocytopenias in China, a lot of times they get admitted because of the difficulty and availability of platelet transfusions, so they preemptively admit those patients. That does not happen in the U.S. That could be the main difference, and that may be increasing our SAE rate a little bit. That's so far that we have noticed. Great. Thank you. In view of time, Christopher, thanks for joining us. Would you like to ask some questions? Yes, I would. Can you guys hear me now? Yes, we can. Thank you. Okay, perfect. Yeah. Congrats on the data, and thanks for the question. One of the R-Dxd posters at ASCO had some interesting data on exposure and its correlation to ORR and PFS, where higher exposure levels led to significantly greater numbers of both. Two questions on that. How much read-through is there to SIM0505, and how might the exposure levels for SIM0505 at the key dose levels compare to those exposure levels we saw with R-Dxd? Dr. Matulonis, would you like to address that initially? Udayan may be a better person to ask, since I have not seen access to that sort of exposure data for SIM0505. In answer to the question about the R-Dxd, I think that's really interesting. That's why obviously probably higher doses, and I think the other unknown factor here is how the payload, how the linker, how the antibody all interact to continue to deliver payload into the cancer cell itself. There may be differences amongst the different drugs. Udayan, I'll let you answer about the exposure data. Yeah. No, thanks, Dr. Matulonis. I can start, and also Dr. Dixit can comment on this. I have noticed that results that, Christopher, you were talking about, and even in our study, like the preliminary exposure response analysis that we do, there is definitely a correlation. As in any ADC you would expect. Now, having said that, we have definitely reached about 9.6 mg with a DAR of eight, and two patients there are having response beyond six months and tolerating. I know, the other part of that question could be what dose levels we went into the dose optimization. We went from 5.6 mg-7.2 mg, but 8 mg has also been overall tolerable without any G-CSF or things like that. I know we are doing the dose optimization now up to 7.2 mg, but 8 mg is also available if needed. Later on in different studies, this can be definitely explored. There is definitely an exposure-response relationship. Dr. Dixit, you want to comment anything more? Yeah. Thanks, Udayan, I had opportunity to visit that poster actually at the ASCO yesterday. What was interesting that they also commented on effect of the body weight on the exposure. The heavier patients tend to have a little bit more free payload, and that also resulted in more toxicity. It's not only the exposure that you're increasing, you're also exposing patients to the free payload, which is not a good thing. Because free payload will lead to more toxicity, especially something like DXd, which has a very high bystander effect. I would have said that having done a lot of topoisomerase ADCs in my career, since my days from AstraZeneca, I would say this is one of the best-tolerated topoisomerase ADCs despite it has a DAR8, eight molecule per antibody. Most DAR8 exatecan ADCs are not even tolerated beyond three to four mg/kg. You already have improved tolerability quite a bit. Clearly, we all know that higher the exposure, better efficacy you are going to see. However, it has to be balanced with therapeutic index, because higher exposure, especially for the free payload, could lead to more toxicity. That was one of the points that I captured from that poster from BioNTech, that they were worried about, although they are seeing higher exposures and can give a better responses, but they have to play around with the doses because of the withdrawal rate was high, and patients were just not able to tolerate. Also, DXd has lot more incidents of ILD. It could be potentially related to the linker payload combination much more than any other topoisomerase inhibitors I have seen. DXd type of linker payload combination has lot more incidents of ILD, which we are not seeing it here, at least on the serious ILD. That also explained that our free payload exposure is much lower than what you see with DXd-based ADC. I have an added point to that. I think those are really interesting observations. That certainly occurred when we were dose escalating mirvetuximab soravtansine, that the higher doses led to obviously more ocular toxicities and hence the dosing there was adjusted ideal body weight. In one of our sessions at ASCO on Sunday, I think we had a conversation at the ADC education session about larger patients with higher weights. That may not be happening on phase I trial. Phase I trials may be, we'll see. Very fortunately, this drug is not giving large substances or large amounts of ILD. As we're using these drugs more in the real world, we're going to have to be really mindful of the excess toxicities, and certainly ILD is going to be one of them, especially in patients who have larger body weights and have larger BMIs. One more- Yeah, go ahead, Christopher. Yeah, go ahead. I was just going to say one more quick question, if I may. Dr. Guha, you mentioned that the 8 mg per kg dose level was relatively tolerable. I guess what was the thought process behind the current dose optimization dose range being at 7.2 mg on the highest then? It's overall tolerable without G-CSF and all that. The percentage of Grade 3 goes up. We have a table in the poster you can see. It's still overall, like neutropenia, thrombocytopenia rate across all dose levels is about 23%. It goes to 50% at 8 mg and 9.6 mg, which is still very good, actually. I mean, 50% without any G-CSF and all that. Some of those patients needed dose reduction. For FDA, they are looking not just like you can treat the patient and it is overall tolerable, but also these rates and drug interruption, dose reduction, all these things are very important. That's why we opened the intermediate dose level of 7.2 mg. We think that 6.4 mg is our anchor dose. If we can go to 7.2 mg, that'll be great. Obviously, we'll keep looking at the data and as I mentioned in later stages, 8 mg, we can also consider, but that may need some G-CSF or something. Thank you. Yeah. Thanks, Christopher. Well, at this time, it's probably time to conclude our key opinion leader meeting. I'd really like to personally thank Dr. Manning-Geist, Dr. Dixit, Dr. Matulonis, and our Chief Medical Officer, Dr. Guha, for their impressive comments and a great discussion. I think we all learned a lot today. In addition to thanking the speakers, I'd like to also thank everyone who asked a question. I'd like to thank the audience for taking the time out of their busy schedules. Finally, I'd like to thank our partner, Centaurus IM. Thanks again to all of you. Thank you. Thank you.