Hi everyone, my name's Alexa Kim. I'm an analyst with the Healthcare Investment Banking team. Thank you for joining us for the Bolt Biotherapeutics presentation. I would like to introduce Randall Schatzman, CEO, and I will hand it off to you. Thank you, Alexa. Thank you, Alexa. you, Alexa. Appreciate the introduction. And thanks to the TD Cowen team for the invitation to speak today, and for those listeners who are listening in, for taking the time to understand the Bolt story. I'm joined today by Dr. Edith Perez, who's Bolt's Chief Medical Officer, and Willie Quinn, Bolt's Chief Financial Officer, and we will be happy to answer questions after my prepared remarks here. So at Bolt, what we're doing is pioneering a new approach to targeted immunotherapy for cancer with the intention of delivering better outcomes for patients overall. We focus on the innate immune system and, in particular, the myeloid cells within the tumor microenvironment and quite literally bring a patient's immune system to their tumor, train it to recognize that tumor, and then ultimately eliminate it. In so doing, we leave the host with an immunologic memory of their cancer, and we believe the promise of that is extended duration of response for patients. And I'll show you a little bit of data today that reinforces both of those notions. So we will be making some forward-looking statements today, and I encourage listeners to go to our SEC filings to understand the risks of our business. 2023 was a year of great progress for us at Bolt. Edith and her team were able to successfully complete our first dose escalation trial of our lead agent, which we call BDC-1001. And with that generated what we believe are some really promising phase I results. Overall, what they demonstrated was an ability of BDC-1001 to deliver an overall response rate of 29% in patients who express HER2 in their cancers. We were able to also demonstrate a similar response rate in combination with nivolumab and ultimately successfully chose a recommended phase II dose, in this case of 20 mg per kilogram every two weeks, to move forward into a number of phase II studies, which I'm gonna tell you more about today. Interestingly, and I think most important for agents like this where we're using very potent immune stimulants, the team was able to demonstrate that BDC-1001 was well tolerated amongst the many patients that were treated in that phase I study. But based on that data, we've made the commitment now to move forward in multiple phase II studies that I'm gonna tell you a little bit more about today in four tumor types, with significant data updates throughout 2024 that investors can look forward to. In parallel with those studies, we've continued to focus on and deepen our overall therapeutic pipeline. We have a second agent now in phase I studies, which we call BDC-3042, which I'll tell you a little bit more about in a minute. And we haven't been riding on our laurels along the way. We've continued to advance our ISAC payload technology, and our intention is to nominate what we call a next-gen ISAC to our pipeline with a clinical candidate sometime later in 2024. In addition, we've made great progress with our several corporate partners that we have along the way. We find ourselves. We reported a good war chest at the end of Q3 of 2023, $141 million in cash, which allows us to reach all of the milestones related to 1001 as well as progress with 3042, and in addition carries us through 2025. So what's different about the approach that we're taking? I wanted to take a couple minutes just to distinguish the approach that we're making versus others that are in the space. I think importantly, and first and foremost amongst these, is that, as compared with a traditional antibody-drug conjugate where the payload is a cytotoxin, in this case, we aren't using cytotoxics. We're using a potent immune stimulator, in this case, one that activates toll-like receptors seven and eight, within the myeloid cell. The way we construct these molecules is very intentional, and it's about providing safety, in the face of having systemic administration of a potent immune stimulator. And so we use for that a non-cleavable stable linker, to conjugate these payloads to the carrier antibody, which doesn't allow the payload to come off, and that provides a significant benefit safety-wise. And in addition, the linker payloads that we use are all designed to be cell impermeable. And as such, should the linker payload come off in systemic circulation, it's not able to enter the immune cells systemically and therefore can't cause significant immune stimulation or cytokine release syndrome that others have seen in the space. Importantly, the targeting antibody that we use, and in the case of BDC-1001, this is a biosimilar of trastuzumab targeting the HER2 antigen on the surface of tumors. This is really about geolocating the ISAC to the surface of the tumor cell itself. And then importantly, it's the Fc region of the antibody that interacts, and I'll show you a little bit more about the MOA in a minute, but it interacts with the Fc receptors on the tumor-resident myeloid cells and stimulates tumor cell killing and also neoantigen presentation. And this is where the retraining of the patient's immune system to recognize their own cancer in a very personalized sense comes to bear. So thinking about the mechanism of action in this case, the way these molecules are constructed, we're able to systemically administer our Boltbody ISACs. And what happens is that that agent then binds the tumor-localizing surface antigen on the tumor cell, okay? And once done, it's now the Fc receptor that's interacting with excuse me, the Fc domain that's interacting with Fc receptors on the surface of the myeloid cells. And then what happens is that stimulates a phagocytosis event where now this blue myeloid cell phagocytizes not just the cancer cell, but the ISAC agent itself. And so with that, a couple of important things happen. First of all, the payload now is able to interact with the toll-like receptors that are intracellular in that myeloid cell. And in so doing, we stimulate the secretion of cytokines and chemokines. And what that allows the system to do then is attract new fresh immune cells into the tumor microenvironment and begin impacting the tumor itself. But in addition, once that cancer cell is internalized by the myeloid cell, itself is broken down, and the pieces of that cancer cell are now presented to the immune system as neoantigens on the surface of that myeloid cell. So we've got a couple of things going on. We've got an early killing of the cancer cell by the myeloid cell itself, but an amplification of the system in what we would call a biologic bystander effect, which now attracts new immune cells into the tumor, in particular T cells that get trained to recognize that cancer and come back and kill it. So we're using this technology to develop a deep pipeline of agents. And I'm gonna tell you a little bit more about each of these in depth today. But first and foremost among these is the what we call our lead agent, which is the BDC-1001 ISAC targeting HER2 expressing tumors in multiple phase II studies now. BDC-3042, which is a novel approach to activating and binding myeloid cells through an expressed receptor called Dectin-2, and that's in phase I studies. As I mentioned earlier, a commitment to naming a new clinical candidate for a next-gen ISAC as we move through the year. Then I'll update you on our corporate collaborations. Looks like we lost a couple of names there. So let's talk about the BDC-1001 program first. As I mentioned, what this is, is BDC-1001 is a biosimilar of trastuzumab to which we stably conjugate a potent small molecule agonist of Toll-like receptors seven and eight. It's a dual agonist in this case. As I mentioned earlier, we've successfully completed a phase I study in 2023, which demonstrated a 29% overall response rate either as monotherapy or in combination with nivolumab and importantly demonstrated evidence of activation of both the innate and the adaptive immune systems per the mechanism of action that I just took you through. We believe the safety box and the way we construct these molecules is now checked, and I'll show you a little bit of detail on the safety profile of these. And we now have multiple phase II studies ongoing in four different cancer types, in this case breast, colorectal, endometrial, and gastric, that we'll be reporting out preliminary data on in 2024. So I wanted to take you through a little bit of the data that Edith and her team generated on this phase I study. And what you can see here is a classic waterfall plot, showing—excuse me—different, a number of these. Each of these is a patient and their cancer types on here. And again, as I said earlier, this is the patients that are at our recommended phase II dose of 20 mg per kg every two weeks. Alone is sort of the rose color that's on here, and then the blue purplish color is in combination with nivo. And what you can see is, again, with monotherapy, we were able to report complete response as well as multiple partial responses. Overall, there was a 43% disease control rate. These are patients who've benefited from the agent for longer than six months, which is significant, and a little over half achieved tumor shrinkage in this case. Combination with nivo was actually quite similar, 29% achieving partial responses, a little over half disease control over six months. But in this case, more patients achieving tumor shrinkage in this case. One of the important aspects, as I mentioned, of this mechanism of action is that by leaving a patient with overall immune memory of their cancer, we believe that the duration of response overall will benefit these patients in a significant way. And interestingly, what we found is shown in this spider plot of patients that were treated at our recommended phase II dose in this study. We found that three of these patients, as detailed by the longer lines that are here, receive benefit for much longer than a year in this case. And we think that's a real positive outcome for this agent. We talked a little bit about the safety profile. Again, the major safety signals that we saw in this that were greater than 10% were infusion-related reactions or fatigue, is about the worst that we saw. We didn't see any drug-related alopecia or ILD that's been reported with many other agents that are out there. And I think importantly for us as we move this thing forward is that this favorable safety profile is going to allow us to explore combinations of BDC-1001 with other agents, because of the safe profile that it delivers. So I wanted to highlight one of the patients that the team had on the study that benefited from this agent. And this was a patient who had microsatellite stable biliary tract carcinoma in this case, but had a significant response. You can see the scans of this patient here. Here's the two lesions that were identified in the liver in this case. This is before treatment at baseline. Then you can see is after 18 weeks of therapy, these lesions are significantly reduced overall, a reduction of about 60%. The team was able to get before and after tumor biopsies from this patient and with that explore what's going on with the biomarkers that would be indicators of our mechanism of action in this case. And again, was able to demonstrate a strong upregulation activation of myeloid cells through the Toll-like receptor, infiltration of myeloid cells and other immune cells into the tumor microenvironment. But importantly, in this case, it was a 500% increase in CD8 T cell infiltration and a 400% increase in inactivation of those T cells, which is what we wanted to see in terms of bridging from the starting innate immune system over into the adaptive immune system. And this is where the majority of the, the tumor kill will be, but as well as the, the resident immunologic memory that we're looking for to have in each of these patients as well. So, of interest to us, and I think significantly, what the team was able to do is obtain before and after, before treatment and after treatment, tumor biopsies from many of the patients that were included in the study. Significantly, what they were able to demonstrate through RNA-seq, in this case shown on this slide, is that patients who responded had significant increases in signaling for the innate immunity for various aspects of that, whether you were a non-responder as shown by the gold here versus the clinical responders. You can see this significant increase among the responders, both innate immunity as well as adaptive immunity measures as well. We think this is a really positive outcome demonstrating that the MOA is working, and beginning to start to give us clues as to which patients are the responders, and which are not. Based on that successful phase I study, we considered it significant enough that we wanted to invest in multiple phase II studies going forward. That program, which is ongoing now, is highlighted on this slide. You can see we're building off the original phase I dose escalation study with three phase II dose expansions looking at, in this case, colorectal, endometrial, and gastroesophageal cancers. These are as monotherapy initially. Then there's a threshold that we've designed into this where we'll make a decision as to whether to ultimately initiate expansions that have combination with nivolumab in this case, in combination with our partner, BMS. Overall, these cohorts will be about 33 patients in size. In parallel with that, we started an independent randomized phase II study looking at breast cancer of BDC-1001 either alone as monotherapy or in combination with pertuzumab in this case. And as well, these are both Simon two-stage designs and we're anticipating being able to get the first cut of data off of these during 2024. What I wanted to do then is highlight a little bit of the rationale of why we think the pertuzumab combination with BDC-1001 is both interesting yet significant. This isn't the typical combination where you take a separate biology and combine the two hoping for an additive or even a synergistic effect. In this case, what pertuzumab does, and we have data to demonstrate this is that actually leverages one of the aspects of our mechanism of action. In this case, it increases the Fc clustering on myeloid cells such that we increase the phagocytosis that we get. When we look at this in preclinical models, what we found is that the combination actually is much better than either of the drugs alone. That's shown here looking at responses in preclinical models with three different tumor types. And what you can see is that as compared with a combination of pertuzumab and trastuzumab, BDC-1001 has an improved effect across all of these cancers. But if you combine that BDC-1001 with pertuzumab, you get an even more significant benefit for, in this case. So we'll be looking for that in comparison, in our breast cancer patient studies, in that separate phase II study as we move forward. So in addition to BDC-1001, we're taking a, what I think is a, an interesting, independent approach to activating the innate immune system, in this case targeting myeloid cells within the tumor microenvironment with an agent that we call BDC-3042, which is a first-in-class Dectin-2 agonist. And what this is in particular is an antibody that binds a surface receptor on myeloid cells called Dectin-2 and agonizes that receptor such that, well, what we can do is, is actually activate the myeloid cells in a different way than we do, but similar to, to what we do with the Toll-like receptor agonists, and convert that what's a, a tumor supportive phenotype within those tumor resident macrophages into a tumor destructive phenotype. And we've got some good data that supports that preclinically, but we've moved this agent into phase I studies. And I'm gonna tell you a little bit more about what that is, in just a second here. So the mechanism of action here, is in some sense is similar to what we're doing with our ISACs. We can systemically administer BDC-3042 as a, a naked antibody. It seeks out and binds tumor resident macrophages in the tumor, that Dectin-2 receptor, which is overexpressed in these tumor resident macrophages. And in binding those, actually activates that macrophage as we do when we're similar to when we're stimulating with the toll-like receptors to secrete cytokines and chemokines. Again, bring in fresh immune cells into the tumor itself and train those cells to recognize the cancer cell and ultimately eliminate it. So again, we start with an innate immune response, bridge into an adaptive immune response, and get our tumor kill based on that. Interestingly, Dectin-2 expression is increased in a significant fashion in tumors relative to normal tissues. And some of that data is shown here. And what you can see is that the blue is actually expression levels in normal tissue. And I'm highlighting breast cancer here. But in the breast cancer, you can see a significant increase in expression of this and thus makes it, I we think, an important tag for both identifying and stimulating the macrophages in those tumors. But you can see this is broadly increased and expressed across a large number of different tumor types. And we think thus makes BDC-3042 probably appropriate for a larger number of, of different cancers as we move this forward through development. So some of our early preclinical data, we think is quite exciting. And what I'm showing you here is tumor growth inhibition, comparing BDC-3042 versus what we think is one of the, the benchmarks in the field, in this case, pembrolizumab, addressing PD-1. And you can see that BDC-3042 is able to cause tumor growth inhibition in a much more significant fashion than pembro does in this particular model. This is a, a model of triple negative breast cancer in this case. Then importantly, when we compare pembrolizumab versus 3042, and then we combine the two, we get yet a further improved effect on this. This is something that we'll be exploring in the clinic as we move forward. With those positive results, we've engaged in a phase I dose escalation study of BDC-3042 and a number of different tumor types that are listed here, but include triple negative breast cancer like the preclinical data that you just saw, renal cell, colorectal, head and neck, small cell lung cancer, and ovarian cancer. So far we've completed safely the first three cohorts of this study. We continue to progress up through the dose escalation itself, moving into the fourth cohort at this point. We're getting into what we believe will be the pharmacologic dose levels that are important to for getting a disease response in these patients. And when we get through the fifth cohort, we will then begin combining the agent in this case with a PD-1 inhibitor, to see if, as with our preclinical data, we can enhance the tumor kill effect when we do that. And this will happen a little bit later this year. So our expectation is that there will be some information flow from this study as 2024 moves along. So what I did wanna highlight for you as well is the interactions that we're having with our important key collaborators that continue to invest in the advancement of our technology for the improvement of their own pipelines. And in particular, these include Genmab, Innovent, and Toray. I wanted to mention Genmab in particular because this is what we believe is one of the next generation of ISACs that will ultimately move into the clinic. And that is putting an immune stimulating payload, in this case, on a bispecific antibody that has two different biologies brought to the table with the, the two active arms of the antibody itself. All of these collaborations, the partners are funding all of the discovery, early development up through proof of concept, in the clinic. And, at Bolt, we have opportunities then to, opt in and co-invest, at that point in time. But right now, all of this technology development and discovery is, is being funded by, by these important partners. So in summary then, I just wanted to wrap up with highlighting what I've already told you today, which is we've got some important progress that we've made with BDC-1001 and BDC-3042, both clinical-stage programs. BDC-1001 will have multiple phase IIs that are gonna read out in 2024. But we believe the data that we've got to date is really quite compelling, both in terms of efficacy and the safety profile that we've seen so far. BDC-3042 is an alternative approach to activating the innate immune system, and again, the phase I study of that should have some data reveal later in 2023 as well. Then finally, as I mentioned earlier, a good cash position, $141 million reported at the end of Q3 of last year, which puts us in a position to get through all of these important key milestones this year, but allows us to continue to operate even for a full year past those, so that we can continue development in the case of success, but also have plenty of runway for raising money to keep the organization up and going. So with that, I'll end my remarks and be happy to open the floor for questions if people have those. Yes. No, we're the sole company at this point. So it's both a first-in-class but unique to Bolt. Any other questions? Have my colleagues here who would be happy to join in and add to the dialogue if you guys have 'em? If not, I thank everybody for your attention and appreciate the questions.