Good afternoon, and welcome to the Fusion Pharmaceuticals announces FPI-1434 Interim Phase 1 Data Conference Call. All participants will be in listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star then one on your telephone keypad. To withdraw your question, please press star then two. Please note that this event is being recorded. I would now like to turn the conference over to Amanda Cray, Head of Investor Relations. Please go ahead. Thank you, Megan. Thank you all for joining today's call. Please note that we have slides we'll be referring to posted in the Events and Presentations section of the Fusion website. With us from management on the call today are Chief Executive Officer, John Valliant, Chief Financial Officer, John Crowley, Chief Medical Officer, Dmitri Bobilev, Chief Technology Officer, Eric Burak, Chief Scientific Officer, Christopher Leamon, and President and Chief Business Officer, Mohit Rawat. After our prepared remarks, we'll open the call for questions. During today's call, we will be making a number of forward-looking statements based on current beliefs and expectations. Our actual results may differ materially from such statements. Descriptions of the risks and uncertainties associated with Fusion's business are included in our SEC filings, which can be accessed either on our website or at sec.gov. With that, I'll turn the call over to John Valliant. Thanks, Amanda, and good afternoon, everyone. We are pleased to provide an overview of the preliminary phase 1 data for FPI-1434, reported today at the Society of Nuclear Medicine and Molecular Imaging annual meeting. FPI-1434 is our first next-generation antibody-drug conjugate and our second-most advanced pipeline program, following our lead, FPI-2265. We are excited to share these results as to date, there has been limited available data on antibody-based targeted alpha therapies, or TATs, against novel targets. We have worked diligently to optimize our approach to dosing based on the available data available from this phase 1 study, which we believe is promising and challenges convention. Before we dive into the details, please turn to Slide 3. Fusion's objective from the outset was to develop a diversified pipeline of targeted alpha therapies, pursuing both novel and validated targets, utilizing various targeting vehicles. We continue to make progress as we advance our pipeline of four clinical programs based on two small molecules and two antibodies. ADCs have shown tremendous success recently, due in large part to the recognition for the need of more potent toxins. We believe that the greater potency of alpha emitters in place of conventional chemical toxins underscores the evolution of ADCs and is a significant yet untapped opportunity to create TATs in areas of high unmet need. For small molecules and well-known targets like PSMA, there is substantial clinical experience through both investigator and industry-sponsored trials, which allow for the identification of the optimal patient population and dosing paradigm. For example, our lead small molecule program, FPI-2265, has proof of concept already based on experience in more than 250 patients with this class of targeted alpha therapy. For antibody tests like FPI-1434, particularly against a target like IGF-1R, there is comparatively less experience and no industry-sponsored phase 1 studies against any target to build on. Consequently, learnings from this multi-part study have taken us a step further towards unlocking the potential of antibody-based paths as next-generation ADCs. There are parallels with the early days of ADC development, when understanding the target, linker, dosing paradigm, and pharmacokinetics were critical elements that needed to be optimized. The development path for FPI-1434 required a stepwise approach that involved multiple phases. We believe the resulting learnings can be applied to our other TATs, potentially allowing for the creation of important new treatment options for patients. Turning to Slide 4 and an overview of the results to date. As I noted, we took a stepwise development path through 3 parts, each akin to a separate phase 1 study. The single ascending dose portion, the multiple ascending dose portion, and the cold-hot dosing regimen, following encouraging results from a cold antibody substudy, which we reported in June last year at the SNMMI. Following good safety results in the single dose portion of the FPI-1434 study, reported again at SNMMI in June 2021, we moved into the multiple ascending dose portion of the study. Patients dosed at 55 and 75 kilobecquerels per kilogram experienced dose-limiting toxicities, notably thrombocytopenia. In parallel, data from the cold antibody substudy was suggesting the potential to improve the therapeutic index. Rather than continuing multi-dosing in hot only at a lower dose, we prioritize the cold hot regimen going forward. In the first cohort in the cold hot dosing regimen, we observed exposures equivalent to approximately 40 kilobecquerels per kilogram in hot only, with a significantly improved safety profile. Essentially, with cold antibody, we could give lower injected doses, but deliver more of the radiation into the tumor. More for less, if you will. With this approach, 2 heavily pre-treated patients dosed at 15 kilobecquerels per kilogram, received 3 and 5 cycles, with stable disease as their best response. While it is certainly prudent to not overinterpret stable disease, the results from the first cohort in an all-comer patient population, coupled with the patients staying on treatment for six to eight weeks, six to eight-week long cycles, is, in our view, a positive sign. Later in this presentation, Chris will walk you through our hypothesis regarding the mechanism behind the cold antibody, and why we believe this is a, critical learning that we can leverage for other antibody-based TATs. The data is a step forward in dispelling some of the dogma around antibodies and is supportive of them being effective tools to create differentiated TATs. While it is a limited number of patients, the excellent safety profile and dosimetry using a cold hot dosing regimen is enabling us to continue dose escalating, and we look forward to sharing that data in due course. With that as an overview, I'll turn it over to Dmitri to walk you through the preliminary results. Thank you, John. Turning to Slide 6. I will begin by summarizing the history of FPI-1434 development program. We began the study with a single ascending dose escalation portion, evaluating dose levels of 10, 20, and 40 kilobecquerel per kilogram. The results of this part of the study were presented at the SNMMI annual meeting in June 2021. Based on good safety and imaging results, we considered the single dose escalation portion of the study completed. We moved into the multi-dose portion of the study, evaluating doses of 55 and 75 kilobecquerel per kilogram. In parallel with the ongoing multi-dose portion, we began exploration of the cold antibody substudy. This was an imaging study evaluating the impact of pre-dose of unlabeled or cold antibody at doses of either half milligram or one and a half milligram per kilogram. The cold antibody pre-dose was followed by a dose of the imaging agent to show the impact of pre-dose on dosimetry and pharmacokinetics. The results of the cold antibody substudy were reported to SNMMI meeting last year. Will be highlighted later in this presentation. We amended the study protocol to incorporate the cold hot dosing regimen in the next portion of the study. The selected regimen consisted of pre-dose of a half milligram per kilogram of cold antibody, followed by administration of the hot dose of FPI-1434. Data presented today by Dr. Pandit- Taskar demonstrated that the 15 kilobecquerel per kilogram cold hot regimen allowed us to reach comparable exposure to 40 kilobecquerel per kilogram of the hot regimen only. We have prioritized the cold hot dosing regimen. We are currently enrolling patients at the second dose level of 25 kilobecquerel per kilogram. The phase 1 trial with its 3+3 dose escalation design, went through several steps with key decision points along the way. The Safety Review Committee reviewed the emerging safety and imaging data from each cohort following completion of a 6 to 8-week long DLT period per patient. Each time, we amended the protocol before transitioning to a new portion. The amendments were reviewed by institutional ethics, scientific, and radiation safety committees at each site. Importantly, the FPI-1434 imaging analog was given to each patient, and the images were required to show drug uptake with a 2 to 1 tumor-to-background ratio. These imaging studies are extensive, multi-day procedures designed to collect dosimetry data in addition to determining overall patient eligibility. All this design and logistical complexities resulted in longer timelines as compared to a more typical dose escalation studies of non-radiopharmaceutical drug candidates. I turn into Slide 7. The study in non-human primates, which will be discussed later by Chris, showed the ability to change the pharmacokinetics of FPI-1434, to increase exposure without adverse impact on safety profile. With those results, we moved forward with a cold antibody substudy, where each patient listed as their own control. Specifically, a patient was imaged with the indium-labeled version of 1434, and then two weeks later, the imaging was repeated, this time with pre-administration of the cold antibody. The results showed the ability to tune the PK, as illustrated in the image, where you can see increased tumor uptake and decreased uptake in the spleen. Turning to Slide 8. We see the impact of the cold antibody pre-dose on pharmacokinetics and platelet counts as observed in the 15 kilobecquerel per kilogram cold and hot cohort. On the graph on the left, the plasma levels of FPI-1434 at 15 kilobecquerel in cold and hot administration, the black curve are comparable or higher than any of the PK curves measured with the hot-only cohort patients. This represents a substantial increase in exposure with the cold-hot dosing. On the right panel, showing the platelet count changes, we see that despite the exposure at 15 kilobecquerel per kilogram being comparable to 40 kilobecquerel per kilogram of hot only, we do not see a substantial decline in platelets as 15 kilobecquerel, whereas we see significant declines below 50% of initial blood counts at the 40 kilobecquerel per kilogram dosing. Turning to Slide 9 to review the safety results. Dose-dependent blood count changes were observed throughout the hot-only dose escalation portion. The most commonly observed adverse events were dose-dependent thrombocytopenia. With the hot-only dosing, declines in blood counts were mild at 10 and 20 kilobecquerel, with a trend to increase incidence and severity at 40 kilobecquerel per kilogram. Hematological toxicity was pronounced at doses of 55 kilobecquerel per kilogram and above in hot-only administration. When we look at the rightmost column on this table, showing the cold-hot dosing regimen data and recalling that the exposure at 15 kilobecquerel hot, cold-hot dose is comparable to 40 hot only, we only see a single instance of grade 1 thrombocytopenia. There was no trend in non-hematological adverse events overall throughout the study. Despite early concerns over IGF-1R expression in some tissues, we've seen no significant effect on organ function or biomarkers related to IGF-1R pathway, including impact on glucose level across all cohorts in the study. Turning to Slide 10. With the addition of cold antibody pre-dose, we have observed increased overall systemic exposure, but not increased radiation dose to critical organs. As you see in the image on the left, from our cold antibody substudy, we see a significant reduction in uptake in the spleen, which is a major repository for platelets, for example. That the tables on the right demonstrate, at 15 kilobecquerel, the absorbed dose was within 7% of the organ dose limits. When we're calculating the dose that we might be able to administer, we see that the addition of cold antibody can potentially double the radiation dose to the tumor compared to hot only, and deliver up to approximately 60 gray to the tumor without exceeding normal organ dosimetry limits. Turning to Slide 11 to highlight additional early data. Two of three patients at 15 kilobecquerels per kilogram cohort reported stable disease as their best response with repeated cycles of treatment. As an example, we present a case of a heavily pretreated metastatic ovarian cancer patient who progressed on multiple lines of chemotherapy and PARP inhibitors. This patient was on study for approximately eight months. The patient has not experienced any high-grade toxicity and was able to receive five doses. Recalling that exposure at 15 kilobecquerels is substantially increased, the fact that this patient tolerated five doses well while experiencing disease stabilization, is particularly encouraging, since our estimates suggest that 15 kilobecquerels per kilogram is still a suboptimal dose with respect to efficacy. In summary, on Slide 12, we're encouraged by the results of the first cohort of cold-hot dosing regimen, which demonstrated an increase in plasma levels at 15 kilobecquerel, making exposure comparable to 40 kilobecquerel hot only, leading to increased tumor doses and without high-grade adverse events. With the increase in exposure, we expect nearly doubling of radiation dose to the tumor. We believe this cold antibody pre-dose regimen has the potential to improve the therapeutic index. In addition, the low normal organ absorbed doses within 7% of protocol-defined limits are signifying the ability to continue dose escalation. We look forward to report the results of cohort 2 using 25 kilobecquerel per kilogram, which is currently enrolling, around the end of this year. With that, I will turn it over to Chris to further scale the scientific rationale for the cold antibody strategy. Thanks, Dmitri. Turning to Slide 14. We know that with radiolabeled antibodies, potential sources of myelosuppression are bone marrow exposure, organ exposure, particularly within the liver and spleen, and when considering thrombocytopenia, possible direct binding of the antibody to platelets or even megakaryocytes. On Slide 15, we illustrate the rationale for what we've been describing as our cold antibody pre-dosing approach. Conceptually, pre-dosing with unlabeled or cold antibody can potentially saturate normal tissue sinks by blocking endogenous antibody binding sites. As illustrated here, cold antibody may also improve the pharmacokinetics of FPI-1434, and drive an increase in binding of our drug to the tumors. In practice, we pre-inject the cold antibody, called FPI-1175, to block access to normal tissue, such as circulating platelets, as shown here as just one example. When we inject a hot dose of FPI-1434, less of it will accumulate within the non-tumor tissue. With this approach, we may also increase the amount of circulating drug, which consequently could have the positive effect of allowing greater tumor exposure of FPI-1434. Importantly, the tumor does not become saturated with a small amount of cold pre-dosed antibody, basically because the tumor cells express substantially more of the IGF-1R target receptors compared to cells in normal tissues. Turning to Slide 16, there is some limited evidence in the literature that IGF-1R is found on platelets. We therefore initiated a study to examine IGF-1R expression levels across the cellular lineage, starting from CD34 positive stem cells, to megakaryocytes, and then to platelets. All of which to better understand if this non-target expression could viably be considered a contributor to the clinically observed thrombocytopenia. As illustrated by the bar graph on the left side of this slide, our research fortunately revealed that CD34-positive stem cells did not display much, if any, specific binding of our drug. Neither really did platelets. However, megakaryocytes, which are progenitor cells of platelets, expressed more IGF-1R than the platelets, but far less than what is observed in our core preclinical tumor model, COLO 205. Compared to COLO 205 xenografts, which represent one of our responsive but low IGF-1R expressing tumor models with roughly 16,000 IGF-1R binding sites per tumor cell, one can see that megakaryocytes bind about half as much. This was a surprise, but we later found that FPI-1434's binding to megakaryocytes could be blocked with increasing amounts of unlabeled or cold antibody, as shown in the graph on the right. These results indicated that FPI-1434's binding to megakaryocytes was specific. Based on these results, we suspected that the observed clinical thrombocytopenia may be caused in part by targeting IGF-1R expressed on bone marrow-derived megakaryocytes. Turning to Slide 17, as we began to consider whether the cold antibody dosing regimen could be a potential solution to the observed clinical thrombocytopenia, we also considered whether the cold antibody could increase the AUC or systemic exposure to possibly cause an increase in bone marrow toxicity. Looking back at the results from our original non-human primate tox study that we ran prior to initiating the phase 1 clinical study, we had pushed the dose level to a point where myelosuppression, including thrombocytopenia, was observed. More recently, we repeated this study, adding the addition of cold antibody while testing two different FPI-1434 dose levels: a safe dose at 37 kilobecquerels per kilogram and a known toxic dose at 148 kilobecquerels per kilogram. With the safe dose, we saw a near 30-fold increase in systemic exposure to a point which far exceeded the exposure level of the known toxic hot only dose that had caused thrombocytopenia. In other words, we more than doubled the systemic exposure that was previously associated with toxicity, yet that increase had no negative impact on platelet levels or any other meaningful toxicity. These results provided us with evidence that the cold antibody predosing approach could potentially block or significantly reduce clinical thrombocytopenia. This approach could also potentially allow us to push to higher FPI-1434 dose levels in a safer way. On Slide 18, you'll see that data emerging from our trials show that the addition of cold antibody does indeed increase systemic exposure. Looking at the graph on the left, the blue curve represents plasma levels of FPI-1434 from patients receiving a 0.5 milligram per kilogram pre-injected cold antibody, and that translates to a greater than an 11-fold increase in systemic exposure over that from patients not receiving the cold antibody. These results are in line with what we had observed in the non-human primates. Turning to Slide 19, we also collected SPECT images of patients receiving the cold antibody to gain a better understanding of its impact on tumor to non-tumor accumulation. Representative images shown at the bottom left are from a hormone receptor-positive, HER2-negative breast cancer patient. We can see how clarity is maintained in the tumor while accumulation in normal tissues decrease. In fact, we saw tumor-to-background ratios of nearly 20 to 1 in this patient. In a second patient with metastatic prostate cancer, one can easily see in the image on the right, that spleen uptake was substantially decreased by 42%, while with the pre-injection of the cold antibody. We also saw liver uptake decrease by 15%, while at the same time, tumor uptake actually increased by an average of 47%. Taken together, we now know the cold antibody is not blocking access to the tumor IGF-1R, like it is blocking access within normal tissues. In summary, on Slide 20, we confirmed IGF-1R is expressed on thrombocytes and megakaryocytes. However, tumor cells express far more of this important cancer target. FPI-1434 can target the megakaryocyte population in the bone marrow and spleen, which could contribute to any FPI-1434-related thrombocytopenia that we had observed in the hot-only phase 1 cohort. By pre-dosing cold antibody prior to the administration of FPI-1434, we're seeing a substantial increase in systemic exposure, combined with an increase in tumor-to-background ratio. We're very excited about the pre-injected cold antibody approach. We look forward to reviewing the data from our next cohort, which is currently underway. Thanks, Chris. In summary, on Slide 22, we feel that the results from the cold-hot dosing regimen are encouraging, in that they show the potential to increase the therapeutic index and the ability to multi-dose patients up to five cycles so far. Delivering more dose to tumors at lower injected dose is an attractive feature of the cold-hot dosing paradigm. In addition, the dosimetry data in key organs indicates there's opportunity to further increase the injected dose. We also feel we can leverage the learnings from the FPI-1434 trial, specifically the hot-cold dosing results, for other antibody programs, notably FPI-2068, our antibody-based TAT targeting EGFR cMET. This is the first of up to three potential targets emerging from our collaboration with AstraZeneca. From our perspective, IGF-1R remains an attractive pan-tumor target that we feel is complementary to our pipeline of TATs that have the potential to expand the radiopharmaceutical field beyond the focus on prostate and neuroendocrine tumor therapies. To this end, we continue to believe TATs derived from antibodies represent next generation ADCs, with the potential to address a broad array of tumor types in areas of high unmet medical need. Regarding our next steps for the 1434 development program, as Dmitri noted, we are currently enrolling patients in the second cohort of the cold-hot dosing portion of the study at a dose level of 25 kilobecquerels per kilogram. We expect to report the results from this cohort around the end of this year. We are now happy to open the call up for questions. Operator? We will now begin the question and answer session. To ask a question, you may press star, then one on your touchtone phone. If you are using a speakerphone, please pick up your handset before pressing the keys. If at any time your question has been addressed and you would like to withdraw your question, please press star, then two. Please limit yourself to one question. Our first question comes from Mike Ulz with Morgan Stanley. Please go ahead. Taking the question. Maybe just on the cold-hot dosing regimen, what do you think is the optimal dose range? Do you think 25 kilobecquerels per kilogram is sort of in that range or might you have to go higher? Thanks. To address this question, we need to reference some external data sources that we are aware of the doses that might potentially be or are proven to be efficacious. The dose in the range of 100 kilobecquerel is shown to be active in multiple diseases. The program of FPI-2265, which we are running right now, 100 kilobecquerel, is a recognized dose to show significant clinical activity. With this benchmark in mind, right now, we think that 25 kilobecquerel might be closer to the efficacious dose. However, with 100 kilobecquerel target, we might be able to escalate further or use to reach this dose level using multi dose strategy. Got it. Thank you. The next question comes from David Nierengarten with Wedbush Securities. Please go ahead. Hey, thanks for taking the question. On Slide 18, on the PK parameters, sorry about the background noise. On the PK parameters, it looks still kind of variable. I was just wondering if you would need, in the future, to have each patient, you know, continue to serve as their own control, or, you know, kind of how would you standardize dosing for patients, and different patients and different antigens? Thanks. Thank you. Good question. It is important to note that strategy of using patient as its own control was utilized in cold antibody substudy, that the purpose of the study was to identify the role of cold antibody. Now that this role has been established, that we will no longer be using patient for with multiple dosimetric studies before enrollment into activity studies. Again, it was a step in the program that allow us to select the dose of cold antibody and to confirm the impact of cold antibody on biodistribution. Thanks. Our next question comes from Faisal Khurshid with SVB Securities. Please go ahead. Hi, guys. Thanks for taking the question. I just wanted to ask a couple clarifying questions on the cases of stable disease. One, for the ovarian cancer patient, was this a patient who was actively progressing at the time of study entry? Can you provide any details on the other patients that had stable disease? Patients with ovarian cancer, let's address first. Per eligibility criterion phase 1 study, patients should have documented progression before entering into the study and exhausted available standard of care treatments. The decision to on patient's eligibility is done by investigator, and given that we enroll in highly credible investigators and including highly credible investigators in our study, we believe that this condition by the patient was met. Regarding your second question, it was about the patient 2. The patient 2 was a patient pretreated with a PitNET tumor. It's a pituitary neuroendocrine tumor. It was received and progressed on available standard options. Our next question comes from Justin Walsh with Jones Trading. Please go ahead. Hi, thanks for taking the questions. Do you expect any added complexities with respect to regulatory considerations or approvability when incorporating a cold antibody? Maybe just in general, how well do you think the FDA recognizes the strategy? Okay. Thanks, Justin, for the question. I mean, what's important to note is that all radiopharmaceuticals with antibodies in them have cold antibody already, so we don't see it as a barrier. Bexxar and Zevalin had a similar component to them, so we think there's a pathway going forward, and it's a simple IV infusion of the antibody shortly before the treatment. We don't see that as being a particular barrier. Got it. Thanks. A quick follow-up for me. Is this the plan still to do a pembro, like, checkpoint inhibitor combination, the trial after you get the recommended phase 2 dose here? Yeah. There's no changes in our plans with respect to the combinations. We always said that what we want to do is identify the optimal dosing regimen, and the recommended phase 2 dose, and then leverage that IP that we have around combining actinium with checkpoints, which we actually see as, you know, there's increasing evidence to support the benefits of that combination, going forward. Our next question comes from Andy Hsieh with William Blair. Please go ahead. Great. Thanks for taking the question. Maybe two parts, if you don't mind. One is really about dose response. In the single ascending dose cohort, just maybe kind of describe qualitatively what you've seen in terms of dose response and also may the six patients in the hot only. Kind of related to that, moving to the cold antibody component, should we expect activity at that dose? I guess this is relevant, not only for the FPI-1434, but also for FPI-2068, just, you know, from some highly active bispecifics in that arena. Thanks. Maybe doing the first part of your question. Our prediction from preclinical models was that it was a range of about around 80 to 160 kilobecquerels per kilogram total dose. We really, with those single doses, you're not getting into the range where you would expect to see antitumor activity in those cases. That's not something that we expected. Sorry, could you repeat your second part of your question? I'm not sure we caught that. Yeah. The second part had to do with potential antitumor activity of the cold antibody, just, you know, from a broader sense of, you know, just trying to delineate between those two components. I guess the genesis of the question is really on the bispecific aspects, right? FPI-2068, there's, you mentioned about the cold antibody component, being incorporated into the clinical trial plan. I'm just curious, first of all, at that dose, do you expect the cold component having clinical activity, so that we can actually delineate these the multi-component aspect of the regimen? With FPI-1434, one of the nice things about that antibody is it had already been in the clinic. We know what those doses were, and we're at a far lower dose than one that you would expect to see clinical activity. As actually Dmitri pointed out, one of the concerns about early on about going after IGF-1R, is that you would see evidence of impact by going after I... the blocking the IGF-1R system, which we do not see in this particular study. The mass dose that we pre-dose with, we don't expect that to contribute in any significant way to the activity. In FPI-2068, obviously, this is experimental. We haven't really provided a lot of detail on that study because we're just initiating after the following approval of the IND. Again, with radiopharmaceuticals, the mass dose is so low, you're really, the activity is driven by the actinium, not by the presence of the cold protein. Got it. Very helpful. Thank you. The next question comes from Andrew Tsai with Jefferies. Please go ahead. Hey, thanks for taking my questions. Good afternoon. You know, how many patients worth of data can we expect by year-end 2023? Would it be 3.3 patients at 25, hot, cold? Or would you consider dosing a larger number of patients? And in what tumor types, specifically? Thank you. Thank you for this question. The study continues to be an all-comer study using imaging criteria for patient selection. We don't expect, and we don't select any specific disease type for going into the study. What do we do expect by the end of the year that the cohort using 3+3 design, we will see 3 patients worth of data at minimum. There is no reason to expand it until we see unless we see those limits in toxicity. At this point, we plan for 3 patients data. Thank you very much. The next question comes from Yuan Zhi with B. Riley Securities. Please go ahead. Thank you for taking my question. Can you help us to put this data in context? Was there another clinical trial used and cold antibody to improve the therapeutic impacts, maybe in the ADC space? Sorry about my background. What was the result there, or what we can learn from there? Thank you. Yeah, thanks for that question. There has been some evidence published early on about the use of cold antibody. Particularly one to reference is the J591 development. Neeta Pandit-Taskar published, I think, in 2008, optimizing the mass dose of that antibody, and I think her conclusion was around 50 milligrams total dose of cold to move forward with that. You know, the results that we have to date with 1434, we did explore the cold antibody sub-study, a couple different dose levels, and we chose the 0.5 milligram per kilogram to move forward with it, because it gave us the best result. Got it. Thank you for taking our questions. The next question comes from Boris Peaker with Cowen. Please go ahead. Great. Just to follow up more on this, cold pre-dosing, I guess kind of a two-part question. First is, if the approach is based on a much harder, higher target expression in the tumor than the healthy tissue, could you get the same result by just significantly lowering the dose and providing more continuous dosing, but just a little lower level? Kind of the second part to it, do you think this cold, hot dosing strategy would work for, beta emitters like Lutetium, or you think this is primarily more focused on things like actinium? Maybe we'll go in reverse order of the question. I think one of the things, Boris, that we found intriguing is that by significantly increasing the exposure and the circulation time and not seeing the corresponding impact on myelosuppression from the non-human primate data that Chris described, you know, part of that, we feel, is the short path length of the alpha, the benefits of keeping it in circulation for long periods of time. Really, from the data, you know, we do think highlights another potential advantage of alphas. Chris? The level of cold antibody, as mentioned, we have settled on a half milligram per kilogram. It seems to be very effective and, you know, we can actually correlate that with preclinical studies as well. You know, moving forward, that will be the regimen. Maybe I'll just ask Eric to comment as well. Boris, were you talking about the cold antibody or the hot antibody? No [crosstalk] First, the hot antibody. I'm just thinking that if you're making an argument that this cold/hot treatment works because of a higher expression level on the tumor tissue, and that the lower expression essentially being blocked out across the board on all tissues, could you just give a low level of a hot antibody altogether, and it should just be less on the off-target activity that way as well? It's an interesting question, and I think the thing to remember is that when you give the cold antibody, what you're doing is you're blocking the sink. By going in with that amount of material, even if you started to Once you drop that material away, you still run into the same issues of hot going into the sink. By giving that small amount of cold, what you do is you block the native tissue just enough, still have those open sites on the tumor, you can come in at that lower dose and use the pharmacokinetics now of the regimen to actually push more drug into the tumor. That's exactly what we're seeing. That's why we're trying to optimize the regimen, because we're getting the added benefit of both added pharmacokinetics and reduced toxicity. Great. Thanks for taking my question. The next question comes from Rahul Sarugaser with Raymond James. Please go ahead. Good afternoon, folks. Thanks so much for taking our questions. I think my question was mostly answered in the last one, but I am just gonna sort of clarify. Could you maybe clarify why the 0.5 milligram cold dose is optimal? Do you think it could be iterated on to fine-tune the dose? Maybe the part B, do you think it's also possible to tune that cold dose based on a patient-specific tumor IGFR expression? Yeah, I'll take that one. Why the half a milligram per kilogram? Please recall that we did run a cold antibody sub-study, based on imaging, and we looked at a couple different cold antibody dose levels. Not only the pharmacokinetics but also the tumor-to-background ratio was measured in that study. Consistently, we saw that the half milligram per kilogram yielded the best results. Now, it is an interesting question about, you know, the types of tumors and how much IGF-1R is expressed. We haven't disclosed what indications that we may proceed with when we expand this study. That's still an ongoing investigation. We do have some that are favored. Obviously, selecting those that have the highest degrees of expression would be favored. We don't quite know yet, you know, if. Well, I'll just leave it at that. I think that the tumors do, you know, invariably, you're gonna see different levels of expression of IGF-1R across indications. Again, our selection going forward will be for those indications that generally will have the higher levels. Great. Thanks for taking our question. The next question comes from David Martin with Bloom Burton. Please go ahead. Thanks for taking my questions. With the increased AUC in circulation time, with the cold dosing, are there any tissues that could suffer because of the increased AUC in circulating time? Or does this have to bind to kill the cells? As John mentioned a moment ago, we believe this is a strong feature of an alpha-emitting radiopharmaceutical because of the particle only traveling one to three cell layers deep. You know, I think the question about use of cold antibody with a beta-emitting probe is something that should be answered, not by us, but we suspect that that may not be a favorable situation by keeping a beta emitter in circulation for a longer period of time. Certainly for our approach with the alpha, we're not seeing a skewed distribution that is creating a more harmful situation by any means, quite the opposite. That's proven, at least to us, with the cleaner images, if you will, the increase in tumor accumulation, all are working in our favor by delivering more to the tumor and less to the non-tumor tissues. What about the kidneys? I didn't see any signal of nephrotoxicity. We're clean there? Yeah, the answer is yes, we are clean, so we don't see any non-hematological toxicity so far. In addition to that, if the poster highlights the dosimetry data, which is again, we're using an analog, imaging analog, and we do not see increase in kidney dose in the dosimetry predicted dose with use of cold antibody. Thank you. Again, if you have a question, please press star then one. Our next question comes from Kemp Dolliver with Brookline Capital Markets. Please go ahead. Thank you. You had 1 subject who has had 5 doses which is higher than what we've typically seen with RLTs. You know, how is that impacting your thinking with regard to the potential for dosing beyond that, you know, that number? Also, how you're thinking about the length, you know, the dosing cycle also. At this point, we are utilizing six-week cycle duration. Going back to this specific patient who received five doses, this patient, duration of treatment, such patients would have limited in duration of treatment using two factors. Actually, three factors. One is duration of disease control, which may be a certain limitation for number of doses that we will be able to deliver. Second is the dosimetry limit that has been implemented in this protocol, as discussed with the FDA. The third is actual safety. If we do not see a safety event and disease is under control, we haven't reached dosimetry limits, in this case it's 15 terabecquerels, was at the level less than a 7%. You can imagine that we could have continued treatment of this patient beyond five doses. Great, thank you. This concludes our question and answer session. I would like to turn the conference back over to John Valliant. I'd like to thank everybody for joining our conference call today. Thank you. The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.