Good afternoon and welcome to the Bolt Biotherapeutics BDC-3042 phase 1 dose escalation study and Clinical Programs Update conference call. At this time, all participants are in a listen only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would now like to hand the call over to Sarah Nemec, Senior Vice President of Finance and Principal Accounting Officer. Please go ahead. Thank you and good afternoon everyone. The slides for today's call are available under Events and Presentations in the Investors section of our company's website and are available on the webcast platform. For those who are logged into the webcast for today's event, we suggest that you follow along with the slides at your own pace. Before we begin, I'd like to remind everyone that during this call we will be making forward looking statements that are subject to a number of risks and uncertainties. These may cause our actual results to differ materially and I encourage you to read our SEC filings for more details on these risks and uncertainties. You are cautioned not to place any undue reliance on these forward looking statements and Bolt disclaims any obligation to update such statements. Earlier today we presented our first quarter results including cash, cash equivalents and marketable securities totaling $58 million as of March 31. This is expected to fund multiple key milestones including our phase I dose escalation trial for BDC-4182 through mid-2026. We continue to reduce costs while actively developing products to treat patients with cancer with activities such as our recently announced sale of lab equipment for proceeds of approximately $1 million and our second sublease which will help to reduce our operating costs going forward. While we would be happy to entertain questions on our financials, the focus of today's call will be on the data from our phase I dose escalation clinical trial of BDC-3042, which was presented at the American Association for Cancer Research Annual Meeting in Chicago last week. With this in mind, I'd like to introduce the presenters. We are honored to have Dr. Ecaterina Dumbrava, Associate Professor at the University of Texas MD Anderson Cancer Center and investigator for the BDC-3042 program, joins us today to further discuss the BDC-3042 data. Also joining us today are several members from the Bolt Biotherapeutics team, including Willie Quinn, our President and CEO, Justin Kenkel, Senior Principal Scientist, Grant Yonehiro, Chief Operating Officer and Chief Business Officer, and Jakob Dupont, Board Director and Senior Clinical Advisor. We also have additional team members available for the question and answer session after our prepared remarks. I will now turn the call over to our CEO, Willie Quinn, who will provide an overview of our topics from today. Thanks, Sarah. I'll start my comments on slide 6 if you're following along with us. As background for those unfamiliar with Bolt, we are harnessing the power of the immune system to improve lives and eradicate cancer. We are developing several programs including BDC-3042, a first-in-class dectin-2 agonist antibody, and BDC-4182, a next-generation Boltb ody Immune-Stimulating Antibody Conjugate, or ISAC, targeting Claudin 18.2. BDC-4182 is the most advanced program using next-generation linker payloads from our Boltb ody ISAC platform, and I'm excited to announce that we have opened enrollment for the first-in-human phase I study of BDC-4182 in gastric and gastroesophageal cancer. The Boltb ody ISAC platform is the basis for our collaborations with Genmab and Toray and for our proprietary pipeline. In our Genmab collaboration, we have now advanced two product candidates into development and continue to research and develop additional programs. Turning to the agenda on slide 7, today we will walk through the background on BDC-3042, including an explanation of how this drug candidate works and the steps we took to prepare for our clinical trial. This section will be presented by Justin Kenkel, PhD, who started exploring the impact of dectin-2 agonism on tumor growth back when he was in the Engelman Lab at Stanford. Dr. Dumbrava will discuss the phase I results from her perspective as an investigator in the clinical trial. Grant Yonehiro, our Chief Business Officer, will then discuss our plans for partnering BDC-3042. We will then shift gears to discuss our Claudin 18.2 targeting Boltbody ISAC BDC-4182 and its clinical development plan presented by our Board Director and Senior Clinical Advisor, Dr. Dupont. I will then return for some concluding remarks and we look forward to answering any questions you may have. I'll now turn the call over to Justin Kenkel, Senior Principal Scientist here at Bolt Bio, to discuss the mechanism of action for BDC-3042 and our preclinical development. Justin? Thank you, Willie. I'm happy to be here today to go over some background on BDC-3042 or dectin-2 antibody, which we view as a really unique and promising new approach to treat cancer. Moving to slide 9. Dectin-2 is a pattern recognition receptor that is normally involved in sensing and responding to foreign pathogens, but what we have found is that the receptor is expressed by tumor-associated macrophages or TAMs across a wide range of cancers. Now, TAMs are known to typically be tumor supportive and immunosuppressive. Our goal with BDC-3042 is to engage and agonize the dectin-2 receptor on TAMs and thereby convert them into tumor-destructive cells that promote anti-tumor immune responses. Another important thing to note is that tumor and PD-1 blockers like pembrolizumab and nivolumab have been shown to lead to an upregulation of dectin-2 expression in the tumor microenvironment, which when taken clinically suggests that tumors could be more responsive to BDC-3042 in the post-checkpoint inhibitor setting and that combining 3042 with checkpoint inhibitors could be a particularly powerful combination. Dr. Dumbrava will go over in more detail with you the results from our first-in-human study, but overall we've been very encouraged with what we've seen and believe the results show support for the development. To briefly summarize, 3042 has appeared safe and has been well tolerated at adult levels tested. It is clearly biologically active. We are seeing evidence of target engagement and immune stimulation in line with our expectations based on the preclinical work. It has a good PK profile which should enable more convenient dosing regimens and we are seeing promising signs of antitumor activity with a single agent, in particular in non-small cell lung cancer in the overlapping post-checkpoint inhibitor setting and at the highest dose level tested, and again Dr. Dumbrava will go over more of the clinical details with you later in the presentation. Moving to slide 10, BDC-3042 is the first clinical-stage agent targeting dectin-2, which is a novel IO target that we consider to be well differentiated from other myelo-directed programs. For BDC-3042, it is an agonistic antibody targeting an activating receptor, which contrasts with many of the recent efforts at myeloid reprogramming, which have often involved blocking antibodies targeting inhibitory receptors. As shown in the figure on the right, dectin-2 is known for its role in stimulating innate and adaptive immune responses against fungi and other microbes. What we are doing, in essence, is trying to harness these activities to stimulate more potent immune responses against tumors. Indeed, we have shown preclinically that dectin-2 agonists can activate and reprogram TAMs, leading to enhanced CD8 T cell responses, complete tumor regression in some cases, and the induction of immunological memory. While of course toxicity can be a great concern with immune agonists, dectin-2 has a very favorable expression profile with low expression in most normal tissues as well as on circulating immune cell populations, which we think are important factors underlying the safety of our approach. Moving to slide 11, we have found that dectin-2 is expressed on TAMs across many cancers and as shown here, its gene expression is higher in tumors relative to normal tissues across virtually every type of cancer included in the analysis here. We think there could be a large opportunity to ultimately treat many different types of cancer with the potential for broad applicability similar to checkpoint inhibitors. I would note as well the low expression of dectin-2 in most normal tissues as shown in the blue, which again could help to explain the encouraging safety profile that we're seeing with 3042 in the clinic. Moving to slide 12. Now, looking at dectin-2 expression at the cellular level, we find the highest expression on macrophages within tumors, with little to no expression on non-myeloid cells or even on most other myeloid cell populations. On the left, we're showing that dectin-2 is expressed on macrophages in various types of immune tumor samples, including cases of breast cancer, colorectal cancer, lung cancer, and ovarian pancreatic cancer. On the right, we see a similar expression profile in the same genetic mouse models that we use in our preclinical studies, including in this model of bladder cancer, as shown here. Moving to Slide 13, we developed an IHC assay for dectin-2 so we could conduct a broader survey of its expression across human cancers. We also analyzed over 600 samples using both tissue microarrays and whole tissue sections from seven different tumor types. Notably, we detected dectin-2 expression in every whole tissue section that we examined. We also confirmed through this effort that non-small cell lung cancer looked like a promising indication on the basis of dectin-2 expression, with 40%-50% of cases showing 1% or more total tumor area staining positive for dectin-2. Slide 14, we pursued the development of BDC-3042 in part due to compelling preclinical results like those shown here. Note that 3042 does not cross-react with mouse dectin-2, so we're using here a natural ligand of the receptor, a fungal extract known as mannan, as a surrogate agonist for these studies. As you can see, specific administration of the agonist shown in the blue curves elicits tumor regression in these two syngeneic tumor models, including a model of bladder cancer as shown on the left as well as a model of pancreatic cancer as shown on the right. Very importantly, the therapeutic effects of the agonist were blocked when mice were pretreated with the dectin-2 blocking antibody, confirming that engagement with dectin-2 is driving the antitumor activity that we see here. Moving to slide 15, one of the main goals with 3042 and dectin-2 agonist therapy more generally is to reprogram antigen presenting cells like TAMs into cells that enhance and support T cell responses, which of course are critical for deep and durable antitumor immune responses as shown on the left. We do find in fact that if we deplete CD8 T cells as shown in the red curve, the surrogate agonist loses efficacy, confirming that in the induction of cytotoxic effective T2 responses is a major mechanism of action. Importantly, we saw on the right that mice that experienced complete femoral regression following dectin-2 agonist therapy would reject those same tumors upon being rechallenged, indicating the induction of a strong adaptive immune response of immune memory against that tumor cell line, but not to an unrelated tumor cell line that the mouse had not been exposed to before, in this case the MC38 tumor cell line. Now this slide 16. Moving on to some key preclinical work with BDC-3042, we performed numerous studies evaluating the binding of the antibody to cells in human tumor samples, in the cases shown here to colorectal cancer, non-small cell lung cancer, and ovarian cancer samples, and found, as expected, that 3042 preferentially bound to macrophages within those samples, as shown on the right. We also looked at the ability of the antibody to activate the macrophages within those samples in ex vivo functional assays and found that 3042 was able to elicit robust cytokine responses, with some of the strongest responses that we noted in the lung cancer samples. Slide 17. Finally, and again, because 3042 does not cross-react with the mouse protein, we had to use mice with humanized immune systems to study 3042 in vivo. These models of course come with significant limitations, including a lot of donor variability, but as shown in the example on the left, BDC-3042 inhibited tumor growth relative to an ISO control antibody as well as to the PD-1 antibody pembrolizumab. While pembrolizumab has demonstrated efficacy in this model, in other published studies, as we saw in the middle panel, we observed greater tumor growth inhibition with BDC-3042 relative to pembrolizumab across nine different cohorts of humanized mice generated using distinct donors. Finally, on the right, similar to what we've seen with surrogate agonist and syngeneic models, BDC-3042 modulated the tumor immune compartment in these mice in various ways, causing an increase in overall immune cell infiltration, a favorable shift towards CD8 T cells, and changes in activation markers on TAMs that indicate reprogramming toward a more immunostimulatory phenotype. With that background on BDC-3042, I now turn the call over to Dr. Ecaterina Dumbrava, investigator for the BDC-3042 clinical trial and an Associate Professor of Investigational Cancer Therapeutics at MD Anderson. Dr. Dumbrava? Thank you so much, Justin, for the great introduction. It was an honor to present the preliminary results of this phase I clinical trial with BDC-3042 at the AACR meeting earlier this year just a few weeks ago. Just a quick reminder is that, as Justin said, this is a phase I first-in-human study evaluating the BDC-3042, and this is a first-in-class, and it was tested in patients with metastatic solid tumors. Here you can see on slide 19, you can see the dose escalation across seven dose levels, and the first three had an accelerated titration with just one subject per cohort, and after that was following a Bayesian Optimal Interval Design. A total of 17 patients were enrolled, including two patients with non-small cell lung cancer who are still continuing to be on treatment. If you go to the next slide on slide 20 you will see the demographics and what I would really want to highlight is that these patients were heavily pretreated. You can see that in median patients had four prior lines of treatment, some of them had even eight lines of prior treatments, 41% received prior immunotherapy and you can see that almost half of patients enrolled were patients with colorectal cancer who were MS stable. We had three patients with non-small cell lung cancer including the two in cohort seven for which the treatment is still ongoing. On slide 21 you can see a quick summary of the safety. What I can share is that this was very well tolerated. We have not seen grade four or five drug related AEs, we have not seen drug related SAEs and in fact we have not identified any dose limiting toxicities up to 10 mg/ kg every two weeks. One patient had a drug related infusion reaction that was well managed and did not reoccur. We had no drug related treatment discontinuations. Running phase I clinical trials this is so important, safety, making sure that for our patients, especially that for this phase I trial, the primary objective was to evaluate the safety and tolerability of the BDC-3042. If you go to the next slide on slide 22 you can see the treatment related AEs that we only had two that were higher than grade three and all were grade one or two. This was very, very well tolerated. The grade 3 was increasing amylase and lipase and the patient who had muscle weakness. On the next slide you can see a beautiful translational data. We can see that by increasing the dose we can see increasing the cytokines and these are cytokines that they are pro-inflammatory and also chemokines that really support even more the further development and combination. On the next slide you can see that the BDC has a very similar profile to what we see in preclinical models. It is so beautiful to see the preclinical and mirrored after that in humans. Really seeing and really proving our hypothesis. On the next slide, on slide 25, you can see that this has a typical PK characteristics of an antibody with a half life that is about 20 days. We have not observed any ADAs to date in any of the patients. The most exciting slide is on slide 26. You can see that the waterfall plot in patients, especially with lung cancer, the three patients that are here in green, all of them had some reduction in the tumor size. These are patients with lung cancer who had four prior lines of treatment or more and they still respond to this. You can also see that 4 out of the 5 patients who had prior anti-PD-1 or PD-L1 inhibitors still had reduction in the tumor size. If you look carefully at this waterfall plot, you can see that most patients are in the range of stable disease. However, for the patients who achieve the partial response, the patient with the non-small cell lung cancer that is still ongoing at 18 weeks. I will give you a little bit more update in the following slides. If you go to slide 27, you can see the duration of response. Even if some patients did not achieve a PR, being stable is very meaningful for patients. You can see that, for example, the first patient was on treatment for 18 weeks. That is really significant for patients who are colorectal cancer. You can see that all the non-small cell lung cancer patients had more than two prior lines of treatment. On slide 28 is the patient who had a partial response. You can see her history. She had a very aggressive non-small cell lung cancer, a lung adenocarcinoma with a KRAS mutation and also with PD-L1 50%. She had from the beginning brain metastasis and the right adrenal gland metastasis. She had chemotherapy and immunotherapy. She had radiation in November 2023. After that, she started a second line treatment with another chemotherapy and immunotherapy. She had another retroperitoneal radiation because there was significant tumor growth in that area. She started on a targeted therapy for KRAS and had progression in the brain and received radiation. In November 2024, she was involved in this study. I do want to mention that the adrenal gland lesion was growing. Even if it was in an area that was previously irradiated, it was growing and she had a grade 1 infusion reaction and a grade 1 increase amylase. All those are really manageable. She had, in February, at her restaging, she had on the brain MRI, there was a questionable lesion that w as s till considered indeterminate, but the consensus w as t o go ahead and treat. That is why she had the brain radiation without really developing new brain metastasis. It was more a discussion between her and the radiation oncologist as she was just telling us that she cannot live with the idea that she has something in the brain that is not treated, but it was not really progression in the brain. Now we have, when we presented this, it was an unconfirmed partial response. I can share that now, since the presentation at AACR, we had the confirmation of the partial response and the patient is doing fabulous. She is telling me that she is able to live and that she feels normal, she has no side effects. That is what we really want to hear from our patient is that we develop better treatments that help with their survival, but also that we give them a good quality of life. The next slide is really a summary of everything that I have mentioned, is that this is a well tolerated drug, up to 10 mg/ kg every two weeks. We are seeing early clinical support for the mechanism of action. It has a favorable PK profile. I truly believe that this is showing promising signs of efficacy in non small cell lung cancer, especially in a NTPD1 refractory setting. Both our patients with non small cell lung cancer are still continuing on treatment. With that I will hand it over to Grant to be able to further discuss about partnering. Thank you very much, doctor. Thank you very much, Dr. Dumbrava. Appreciate that. If you go to slide 31, I just wanted to briefly mention Bolt's effort to find a partner to rapidly develop and optimize the commercialization of 3042. We initiated this process with our disclosure at AACR on April 25. We have multiple parties in both confidential and nonconfidential discussions. Our goal is to get a nonbinding term sheet by June 6, in a fairly rapid time frame. Any interested parties should feel free to contact me for this effort. We look forward to parties' interests. With that, it's my pleasure to introduce Bolt's Senior Clinical Advisor, Dr. Jakob Dupont. Dr. Dupont has deep experience in developing oncology therapeutics and he's an executive partner at Sofinnova Investments and on our board. Turning it over to Jakob here. Thanks, Grant. It's great to be with you all today. I have the great pleasure of speaking to you about BDC-4182, which is Bolt's next important drug in the pipeline. If we turn to slide number 33, you can see here a representation of BDC-4182. It is a first-in-class Claudin 18.2 Boltbody ISAC program. It's next generation. We're very excited to bring this into the clinic. As Willie mentioned, the trial is now open in Australia. I'm really looking forward to bringing patients onto that trial. As you know, Claudin 18.2 is a clinically validated target. This is really illustrated by the approval of zolbetuximab for gastric cancer. That particular naked antibody does target the very highest expressors of Claudin 18.2 gastric cancer. That really provides validation for the target. With Bolt's BDC-4182, we think there is, with a unique mechanism of action, potential to bring better options for patients, not only as monotherapy but also in combination with other therapies as well. The opportunity we see here is to expand the market and to improve the outcomes for patients. Now, over the next few slides, we're going to be speaking to you about the profile of BDC-4182, where we believe we've created a best-in-class profile for this drug and the target product profile to expand the market beyond tumors that are merely, that are just the high expressors. We want to capture the moderate and the lower expressors as well. We want to have a profile of a drug that outperforms some of the ADCs that are in clinical development now. We believe we have some pretty interesting mechanistic studies about the unique characteristics of this particular therapeutic candidate. Over the course of this year and the next few months, we think there are some key inflection points for this program. On the one hand, we do anticipate the initiation of enrollment of the clinical trial and also some early clinical data as soon as the early part of next year. If we go to slide number 34, we'll jump in now to some of the preclinical data that the research team here at Bolt was able to create and really careful efforts here. As described, we really wanted to make a therapeutic candidate that had the potential to be superior to antibody-drug conjugates, specifically ones that had an MMAE payload or TOPO1 payload. In this particular set of experiments. On slide 34, the MC38 colorectal cancer cell line was modified to express low levels of Claudin 18.2. You can see here in the experiment on the left, the Bolt ISAC outperformed the Claudin 18.2 MMAE ADC, especially in that low expressing population. At higher expression levels, the ADC and the ISAC performed at similar levels. On the right hand side, you can see once again that the ISAC against Claudin 18.2 outperformed TOPO 1 ADC in that low expressing tumor model. If we move to slide number 35, another piece of preclinical data here that really set the IND filing up and really made us feel like we had a target product profile that brought something unique potentially to patients. Here we're looking at the induction of immunological memory and the epitope spreading in our preclinical experiments. Here on the left you see a similar type of experiment as you saw on the previous slide, where moderate doses of the Claudin 18.2 ISAC really led to tumor regressions and these mice were actually tumor free. What was done here is the mice were allowed to remain treatment free for 26 days to assure that they were cured and then they were rechallenged, and those are the panels on the right hand side. On the upper panel you could see rechallenging with the MC38 tumor expressing low levels of Claudin 18.2, there was no ability for the tumor to regrow, especially when the T cells were present as opposed to where T cell depletion occurred, where again there was regrowth of the tumor. This really speaks to immunological memory that's induced by the Claudin 18.2 ISAC. Interestingly, in the lower right hand panel here, the cured mice were rechallenged with MC38 tumors that did not express Claudin 18.2. Here again the T cell memory was able to keep those mice in a cured state. Speaking to epitope spreading here, which we think is quite important to the mechanism of action. If we move to slide number 36. This is the clinical trial for the BDC-4182 clinical trial. As I mentioned, this is open to enrollment. This is open in Australia and it is enrolling patients with Claudin 18.2 expressing tumors. That is advanced gastric and gastroesophageal tumors as well. We expect that we will be within the therapeutic range when we get up towards cohort number three. We look forward to providing you with clinical updates towards the beginning of next year. It's now my pleasure to hand back to both CEO Willie Quinn for a few concluding thoughts. Willie? Thank you, Jakob. Thank you all again for joining our call today. I'll start on slide 38 with a review of our pipeline. We are pleased by the promising phase I data for BDC-3042, including its favorable safety profile, dose dependent biologic activity, and monotherapy antitumor activity. We believe this program is best suited for partnering and we look forward to working with a collaborator who can help accelerate its development and bring this promising treatment to patients. We've made great progress with our Claudin 18.2 ISAC BDC-4182, opening the trial for enrollment in April. We continue to be on track to treat our first patient this quarter and look forward to updating the investor community on our progress at AACR. We also presented posters on our two proprietary ISAC programs targeting CEA and PD-L1. After a period of relative neglect for the ISAC mechanism. It was gratifying to see strong interest in our posters and to note that Pfizer also presented a poster on a PD-L1 ISAC program at AACR. Finally, I'll once again mention our collaboration programs and note that we're now working with Genmab to advance two development programs and also have additional R&D programs in development. The Genmab ISAC programs and the Toray Caprin-1 ISAC program are all paid for by our collaboration partners through early clinical proof of concept, providing a cost-efficient way for us to continue to develop our pipeline and platform. I'll move to slide 39 for some final thoughts. Our team at Bolt looks forward to updating you on our progress on our preclinical and clinical programs for BDC-4182. We expect to have some near-term updates on recruitment as we start treating patients for BDC-3042. The next big milestone for the program will be partner selection, which we expect by the fall. In today's biotech financing environment, our watchword continues to be efficiency as we work to efficiently develop product candidates that could improve lives and eradicate cancer. With that, I thank you all for joining us today. We will now open the call for Q & A. In addition to those who spoke on our call today, we're also joined by additional Bolt Bio team members and we can introduce them as we go. We look forward to your questions. Operator? As a reminder to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one. Again, please stand by while we compile the Q& A roster. Our first question comes from Daina Graybosch with Leerink Partners. Your line is open. Hi. Thanks guys. Thanks for the question. Maybe two for me. 1. I wonder if you can talk about the dose escalation of the dectin-2 agonist, and I realize you're done escalating, and I wonder if you think you've maximized out this dose or whether with a partner you think that further dose exploration. A nd this is for Dr. Dumbrava, is warranted given the chemokines, cytokine safety and efficacy you've seen thus far. I will ask another one after the answer here. Great. Dr. Dumbrava, you want to go ahead and tackle that one for us? Sure. Thank you so much for that question. Of course I want to explore this in more patients and I will start by answering that dectin-2 expression was available in all available patient tumor biopsies and when we looked at large datasets, we also have seen that mRNA expression of dectin-2 was present in nearly all solid tumors. I will answer your questions in two parts while saying that one is, is that we do believe that this could be investigated in other tumor types than non-small cell lung cancer. Also, if we do a partner then possibly with a running design that we would look at different schedules. Given that the BDC-3042 has a 20 day half-life in this trial in the dose escalation, it does potentially allow for a less frequent dosing that in this way for a partner that, for example, has a schedule of every three weeks. I think that would be possible as well. Yes, to answer your question. Wow. Then my second question is I hear you that it has potential potentially across solid tumors, but the signal's strong in lung cancer. I wonder, Justin, if you can tell us maybe why. Like do you have any hypotheses for why the TAMs are expressing it higher here in lung and what they call about the potential for this mechanism to be more effective, I guess than we've seen with prior TAM targeted therapies ultimately in the clinic? Thanks. I think one key thing is as we noted that the lung patients all had seen prior anti-PD-1 therapy within 12 months. They may have been particularly well primed for a Dectin-2 agonist because they may have been shown further upregulation, inductive expression on the macrophages in their tumors. I think that the key thing is that especially as we were seeking single agent efficacy signals, lung obviously is a bit more of an immunogenic tumor. There probably is some better pre-existing T cell response in those tumors that we were able to further enhance with our antibody. I think those are key features. I think we hope obviously to be able to see similar things in other tumor types, maybe in particular in combination with checkpoint inhibitors or other therapies. I think those are maybe part of the reason for the stronger signal on lung cancer in this case. Maybe Dr. Dumbrava, if you have anything to add. I know the clinical perspective could be really helpful here too. Yes, no, I agree with you. And just as a reminder, these patients were refractory. My patient had two different rounds of chemo immunotherapy and she progressed on all that. To see a response after that to any treatment is so exciting from the clinical standpoint. I think experts exploring that with a combination would even deepen these responses. Great. Thank you. Thank you. Our next question comes from Stephen Willey with Stifel. Your line is open. Yeah, good afternoon. Thanks for taking the questions and for hosting. Maybe one for Dr. Dumbrava. Appreciate the additional information regarding the post AACR confirmation of the partial response that was seen. I was wondering if you could also maybe provide an update of the second 10 mg/ kg lung cancer patient who had stable disease and was still on therapy, I think as of week 15 or so. Is that patient still on drug? I believe that patient is still on treatment. Now, at the data that we presented at the AACR, both these patients were on treatment. I am just so excited for my patient that I disclosed that she had a confirmed partial response. That is something that, again, as I mentioned previously, her heavily pretreated and complicated history and to see a prolonged response with such a good quality of life is something that I was very pleasantly surprised. You. To see this, the preclinical data, really the hypothesis proven in patients. I do not know the answer for the other patient, but I believe that at the time when we presented, which was just two weeks ago, she was on treatment. Okay, thanks. Maybe for the company on 4182, can you just maybe talk a little bit about how you're gating enrollment with respect to Claudin 18.2 expression within the dose escalation portion of the study? Do you have any guardrails or, I guess, any eligibility criteria that's established, and do you hope to, whether it's prospectively or retrospectively, be able to recapitulate some of that activity in lower Claudin 18.2 expressing tumors relative to what we've seen with the naked antibodies? Yeah, it's a great question, Steve. I'm going to ask Dr. Dupont to take that one. As you know, we think about balancing the probability of success and the expansion of the market. Yep, absolutely. The study is open, as we discussed, we're going into gastric and gastroesophageal cancer, where again, that's where you find high prevalence of Claudin 18.2 expression in those tumor types. Obviously, there are other tumors that also have Claudin 18.2 expression, but we've really gone to, you know, where the money is, so to speak. There, obviously, the approved drug is just going after that. The very highest expressors, we are asking for expression of Claudin 18.2, but it's not excluded to just the very highest expressors. We're also doing backfill patients on the various cohorts to get a more robust clinical experience there. The intent of the protocol is definitely to enroll patients with Claudin 18.2 expression. There will also be capture of tumor tissue from patients on the study so that we can do further analysis and do our own confirmation of level of expression and so forth. I do think we see the opportunity certainly as to broaden the market in patients that have varying levels of Claudin 18.2 expression. Okay, great. Thanks for taking the questions. Thank you. As a reminder to ask a question, please press star one one on your telephone and wait for your name to be announced again. That is star one one to ask a question. Our next question comes from Chad Messer with Lake Street. Your line is open. Great. Yeah, really appreciate the update and the call. Just on 3042. Super exciting results in lung. I know some of my colleagues have already asked why you think lung might have sort of popped to the top of the list, but can you remind us, like, you guys had specific tumor types that you were looking at? PNBC, RCC, CRC, melanoma. Was that based on dectin expression and dectin expression on the tumor cells or in the macro? Can you just remind us why you are interested in that subset to begin with? Yeah, Chad, it's a great question. I'm going to hand this over to Justin to take us back to that kind of decision heading into the IND and structuring the trial. I'd say a large part of it was due to the dectin-2 expression as far as we could glean at the time. Obviously, we eventually developed an IHC assay for dectin-2, but prior to that we were mainly relying on gene expression data that was out there publicly available. Those tumor types that you listed did generally show some good expression, with one being the highest expressor generally of the tumor types that we looked at. We note as well that there was some expression in some other tumor types. I would say tumor negative breast cancer in particular looked like an attractive one based on some kind of subtype analysis that we have been doing as well. I'd say in our earliest studies on dectin-2, we were looking at various tumor types as well in our mouse tumor models, looking at some additional types like bladder cancer and pancreatic cancer. Ultimately, we made a decision to focus on the ones that we did because of the potential, you know, large markets for those tumor types as well as, you know, some of the additional considerations as far as it relates to immunogenicity of the tumors and the like. Yeah, again, expression was the main factor, but there were other considerations as well in terms of the, you know, the market opportunity as well as the just kind of what's known about the immunogenicity of certain tumor types like lung cancer and melanoma. I agree. One additional comment on the non-small cell lung cancer. We also note that two of those three were at the 10 mg/ kg and those were the only ones we had at 10 mg/ kg. We also think we're getting to a dose, as you can see, by some of the peripheral biomarkers that might have influenced seeing more in those patients too. All right, yeah, appreciate that color. Maybe just one on 4182, the quad. You have got an approved drug out there that it is indicated for. Call it, I think it is 38% or something of the gastric cancer market out there. How low do you guys think you? May be able to get? What I really want to get a handle on is how much of the market do you think you can get based on what you know? Now obviously we'll learn more over time. Are we talking 75%, 80%, 90%? How much past that 38% do you think that you can address with your ability to go after lower Claudin 18.2 expression? Maybe I'll start with that one and then I'll hand it off to the rest of the team if they want to add color. I think you're laying it out really well, Chad. You know, the approved label for at least 75% expression, IHC2+ is about 38% of the market. Ultimately we are hoping we can capture all of the expressing patients. I think as you consider development pathway, you don't want to go for everything and swing for the fence from the very, very beginning. We do want to make sure we characterize the drug appropriately, emphasize how well it does in higher expressing patients, and then explore how low we can go. I think that's what we're going to see in our trial is a mix of different expression levels and we will learn how it does. Certainly, preclinically we were able to go quite low IHC 1 + and outperform all of the ADCs we compared against, including MMAE and TOPO1. So anything to add on the. Yeah, this is Jakob Dupont and just I think what Willie said is correct. It was the preclinical data did capture those IC1+, and those are the experiments that we went through earlier in the slides. I do think that we will get more information on the de expression level in the clinical patients. Again, the target product profile that the research team was really going after here was to really go down on the level of expression and try to help more patients that had a broader range of expression. I do think about the example of in HER2 where they were able to capture the moderate, the low and the ultra low patients. A lot of it just has to do with how good is the technology. We do think that this has a very robust efficacy profile, at least preclinically, which is why we're excited to test it in the clinic. Of course, we're going to also, this is Grant. We also are aware of what cutoffs other competitors have been using. We will consider that as we think about how to differentiate our drug relative to competitors, whether that's efficacy in the same level of expression or efficacy at lower levels of expression. All right, it will be exciting to hear how you. Go after that as you get into the clinic. Looking forward to seeing how low you guys can go. Thank you. Thanks, Chad. Thank you. Our next question comes from Daina Graybosch with Leerink Partners. Your line is open. Thanks for letting me go again. I have two more. Dr. Dumbrava, I wonder if you could characterize your patient with an adrenal lesion that had the confirmed artery response. Can you help us understand how big that lesion was and relative maybe to some of the stable diseases that you've seen some shrinkage? Have you seen any shrinkage in large lesions? On the cognizant point to ISAC, can you remind us why this ISAC is different from the first generation Bolt had, Boltb ody with HER2, and also more broadly the other HER2 ISACs out there that either failed for lack of maybe strong efficacy, but also for a lot of toxicity? Why she would be excited that this was going to work when the others, multiple companies, did not targeting HER2. We will let Dr. Dumbrava answer that question about her patient and then we can jump in here with the team to answer the question about next-gen ISACs. Thank you for that question. That is true that for certain treatments the size of the tumor is important. The target lesion is about 2 cm. It is a real reduction of partial response in a lesion that was growing after in an area where she had radiation. Very, very aggressive. Great. On the next gen question, I think it's a really good one. I'm going to ask Grant to tackle that question because in our partner discussions he's routinely asked that exact question. Yes. We improved it across the board and we looked for antibodies that worked better with our mechanism of action. You know, certainly driving ADCP as the first step in our mechanization was important. We tested a variety of antibodies instead of just taking trastuzumab to demonstrate that on the antibody front, we did look at various different bioconjugation methods and found some that we felt worked better. We used a more optimal bioconjugation method for this. Then our linker payload was more active and more potent. Certainly we've been working on this since our 1001 days and we've been working on this with Genmab certainly to get better linker payloads. We are using these next generation linker payloads that are different than the competition. When you look at Novartis, you know, they certainly had a lot of immunogenicity with their linker payload. You know, we have not seen that with ours. We have various methods that we use to minimize the risk of immunogenicity and assess that as best we can preclinically. We have had linker payloads that we have deprioritized because of concerns about immunogenicity. When you look at safety, we also have managed to increase the activity of our ISACs while maintaining an attractive safety profile as demonstrated by our non GLP and GLP tox studies with those that look better than ADCs in terms of toxicity that we have seen in those studies. That is something that we have been thoughtful about and actually found ways where we could increase activity on fronts that we think drive efficacy without increasing activity on assays that we think might be safety related. We combine all that in what we refer to as our next gen ISAC platform and hopefully that addresses that question sufficiently full. Can you just maybe the very last point you made, can you clarify that a little bit more? It sounds like you were screening and you had some assays that predicted what you thought were potency in humans and assays that you thought predicted toxicity past ISACs. You screen encounter screens. We have historically had a lot of assays to evaluate and select ISACs as well as linker payloads that are, you know, precursors to our ISACs on down the road. We have screened over 1,000 different linker payloads and you generated probably many more than that in terms of certain chemistry to evaluate. We have come up with a number of novel structures that we have intellectual property filed on that we think are favorable and it's not just obvious that it's more TLR7 or more TLR8 or something like that that I think a lot of people look at. That is correct. We do have screening that we use in getting to next gen ISAC payloads. Thank you. I'm showing no further questions at this time. I would now like to turn it back to Willie Quinn for closing remarks. Thank you again for joining us today and for the good questions and engagement. We continue to believe in the long term potential of our product candidates to improve the lives of patients with cancer and we look forward to continuing to keep you updated on our progress. Goodbye. This concludes today's conference call. Thank you for participating. You may now disconnect.