Thank you. Welcome back to Oppenheimer's 36th Annual Healthcare Life Sciences Conference. I'm Leland Gershell, one of the analysts with the biotech team, here at OpCo, and really thrilled to have with us, Climb Bio, with whom we'll be holding a fireside chat over the next half hour or so. On behalf of Climb, we have Edgar Charles, who's the company's Chief Medical Officer, as well as Susan Altschuller, who's CFO. If you have any questions of your own that you want to have us weave in, please put those in through the portal. Welcome, Susan and Edgar. Thank you, Leland. Great to be here. Thank you. Pleasure to be here. Great. As many of you know, but maybe not everyone, the team at Climb is building a company around B-cell and autoantibody-driven diseases. You know, you're going after these, you know, immune-mediated diseases that are, you know, pretty serious, can be heterogeneous, and often, you know, diagnosed somewhat late with some very interesting therapeutic assets. Wondering, you know, as you focus on your two assets, budoprutug and also the anti-APRIL, you know, both of these came in from the outside, and just wanted to hear kind of, you know, Climb's overall value proposition with the strategy of maybe looking for either undiscovered or overlooked assets that might have tremendous opportunities that others haven't been able to see. Yeah. Thanks, Leland. I think that, you know, Climb's whole genesis was about developing differentiated monoclonal antibody therapeutics for immune-mediated diseases, using clinically validated targets like CD19 or APRIL. The monoclonal antibody, or monoclonal antibody modality just allows you to more broadly impact a greater population of patients, not just in the most severe in the academic centers. We think that there's just. In these diseases, there's well-established endpoints and pathways. We were looking for something that could be more, that you have the target, with an antibody approach versus T-cell engagers or TCEs, it's a safer, more amenable community dosing regimen. When I think about CD19 and Budo, that asset was brought in. It had been overlooked. I think CD19, clearly, there's a strong rationale in PMN. The B cells that produce the pathogenic antibody are all CD19 positive. There's a real strong rationale. We have phase IB data in five patients that is quite compelling. That premise of being overlooked because folks were maybe skipping to the CAR-Ts, as you know, there's a bunch there, but the only CD19 on the market is UPLIZNA. We are the one in development. We think that we're there in rare neuro and kind of focused in that space. We see a lot of white space for our antibody elsewhere. With our APRIL asset, we wanted something truly differentiated, knowing how competitive the space is. We believe APRIL only is the right approach, given, we don't think BAFF is doing anything, on the efficacy side, in IgAN in particular, but may have an additional immunosuppressive liability. The differentiating factor for our antibody is the sweeper approach, which we'll go into later, that we think we could have two to three times the half-life of the standard of care in IgAN, but also potentially more potent, deeper IgA reduction. That's a terrific overview. Let's talk a bit, you know, about Budo per se, and its program. This is, as you said, it's an anti-CD19 monoclonal antibody, presently given IV, although you all are developing a sub-Q format as well. You know, the kind of the lead indication there is primary membranous nephropathy or PMN. This is an indication that's attracted, you know, quite a bit of biopharma attention, positive late-stage data for obinutuzumab out of Roche, which came out, I think, earlier this month, and there's, you know, other programs, you know, using CD38, BAFF APRIL as well. You know, maybe if you could, you know, Dr. Charles, maybe frame for us kind of the unmet need here and sort of what would be the advantages and rationale for proceeding CD19 in this setting. Yeah. You know, PMN is a disease which is really coming more into the forefront of people's attention. It's really the leading cause of nephrotic proteinuria worldwide in non-diabetic adults, and there are no approved agents. There is a lot of interest in development of new agents to improve upon the current treatment paradigm, which rests upon off-label usage of various agents such as calcineurin inhibitor, cyclophosphamide, and rituximab as a B-cell depleting agent. We think that the field is ripe for B-cell disruption, depletion as a therapeutic modality in PMN, and we think rituximab has provided some proof of concept, and obinutuzumab likely will as well. We think that the CD19 target is really the best target for B-cell depletion in autoantibody-mediated diseases such as PMN. In PMN, there's a clear pathophysiologic link between the anti-PLA2R antibody, in most cases, to the disease process, and removal of cells that produce those autoantibodies, as well as the cells that give rise to those cells that produce the autoantibodies, we think will be very effective in patients. CD19 is expressed early in the B-cell lineage, well through the plasmablast, even through the plasma cell stage, on a substantial subset of plasma cells, and it's those later-stage plasmablasts and plasma cells that produce the autoantibodies. I think that by targeting CD19, we have the potential to deplete the cells that produce the autoantibodies, as well as, lead to a certain degree of reset that could prevent those cells from becoming reestablished in the second place. We're embarking on a study following our phase one B study, in which we saw very promising results in PMN. In five of the patients that were studied, that were evaluable, that received the full dose regimen, we saw profound B-cell depletions in the periphery, followed by immunologic response in the subjects that had PLA2R antibodies that were detectable at baseline. We saw those improvements mirrored by reductions in protein. In all five evaluable patients had a proteinuria response, either partial or complete remission, and 60% or three out of the five had complete remission. And those remissions were stable throughout up to three years off of treatment, which we thought was really encouraging as well, showing that not only did budoprutug have the potential for a deep, meaningful clinical improvement, but also an improvement that was durable. We've taken that one step further in the next study, and are currently enrolling phase 2 study. We're looking at three ascending dose regimens of budoprutug, given IV in PMN patients who are nephrotic, and we'll be looking at B-cell depletion. We'll be looking at immunologic response as measured by PLA2R antibody reduction, and importantly, proteinuria response as measured by UPCR. We'll consider when, if we can achieve robust peripheral B-cell depletion, immunologic remission, and improvements in proteinuria, with the expected safety tolerability of an anti-CD19 monoclonal antibody. Terrific. That study is up and running. It's enrolling patients. I think, had you guided to a look from that data by the end of this year? That's correct. We'll have some data at the end of this year. Those will be some initial results in the study looking at B-cell depletion, the immunologic response, and some directional improvements in proteinuria. Great. Just to sort of, you know, jump ahead, but don't want to give short shrift to the other indications, but we do have a sub-Q formulation that's moving quickly through its initial clinical work, phase 1 healthy volunteer data coming in the coming months. You know, what are your thoughts there in terms of, I guess, advantages of having both in development and maybe, you know, sub-Q could that leapfrog the IV? You know, how do we. You know, what's your I guess, we'll have to wait for the data to fully inform us, but just kind of interested in your current thoughts here. Yeah, you know, we're pleased. During development of the formulation, we've seen that we've been able to manufacture at a high concentration with low viscosity, which should enable sub-Q administration at tolerable patient volumes that are pleasing for patients. You know, we think a sub-Q formulation, if available, could provide additional treatment options to patients, and that may be more relevant in some diseases rather than others. We think that this provides optionality not only for patients and providers, but also ourselves some development flexibility in terms of, you know, how we choose which route of administration to pursue for a given indication. For diseases where there is repeat chronic administration, a sub-Q injection makes a lot of sense. We do expect to have fairly limited dose burdens of budoprutug, but even so, you know, I think patients would want to have limited time that would be required for infusions in the doctor's office. They'd like the flexibility of at home or in clinic administration. Great. Yes, as I mentioned, you guys also have immune thrombocytopenic purpura, ITP, as well as lupus that you're engaged with in terms of development of budoprutug. Could you tell us more a bit about, you know, these indications? I mean, ITP, there are some options there. Lupus is maybe fewer and further between, perhaps more challenging from a development point of view, but maybe, you know, tell us a bit about those and the unmet needs as we look toward, you know, what would be, I think, interim data coming in those settings as well. Yeah. ITP is another classic autoantibody driven disease, where there's a clear linkage between autoantibodies against platelet surface glycoproteins and platelet destruction. There are several agents on the market for ITP, but they're, typically, when patients come off of agents, they relapse, or the agents themselves don't have durable remission, and in complete remission. I think there's a clear need for newer therapies that are safe, well-tolerated, and lead to a better platelet response and a more durable platelet response. That brings us to an anti-CD19 monoclonal, which, for all the reasons I mentioned before in PMN, is providing a good rationale to go forward in PMN, also apply to ITP. Because budoprutug as an anti-CD19 monoclonal, will target the B cells, giving rise to the autoantibody-producing plasma cells and plasmablast, and should be able to lead to a decrease in those pathogenic autoantibodies, and to a certain degree, a B cell reset that would lead to a durable remission of disease. We also have the advantage in ITP of being able to have a pretty objective readout in a clinical setting. Platelets are very objective, and we can get a very crisp readout of efficacy in a fairly limited amount of time, whereas in other diseases, that can be somewhat more difficult. We think ITP is very amenable to our next study to interrogate patients in. We've already started to enroll in the ITP study, looking again, at ascending dose cohorts with a dose expansion phase, once we've settled on an optimal dose. We'll be looking at B-cell depletion to give us an indication of our PD effects at the chosen dose, as well as platelet responses, which we will be interrogating on routine, frequent intervals, and assessing for durability of disease remission. One thing I would add, just Leland, is we're moving forward in the IV formulation with sub-Q for, you know, PMN. We could bridge if we need to, but given the dosing regimen, the four doses, two doses, and then six months apart, and not knowing if we're how frequent we'd have to redose, you might not need a sub-Q formulation. We're really trying to match the profile of the product with the disease of interest. Yeah, no, that makes sense. We had mentioned UPLIZNA earlier. That's, you know, the approved CD19 inhibitor, approved for some rare diseases, and that's now out of Amgen, from its acquisition of Horizon a few years ago. I mean, what, you know, any learnings we can that Climb can benefit from or, we as investors can benefit from? I think. The launch? Yeah. We're the MG launch, we're, you know, encouraged by looking forward. I think the broader adoption of CD19 antibody approach is quite compelling. One of the key learnings we saw from them is once you have identified your dose, you can rapidly move into pivotal trials directly in additional indications. I think that's the key learning that we've leveraged from them. You know, I think the other thing, UPLIZNA doesn't have a sub-Q formulation, that's another piece that we would have to offer that they don't. I think that it's a great benchmark for us to kinda look towards in terms of an antibody approach in CD19 and what it can impart for these autoimmune-driven diseases. Yeah. No, in that same similarly, I'm not sure, Edgar, if you had somewhere to add there, but. Yeah, that's exactly right. I think again, it brings us to optionality, which I think patients and providers really appreciate. Excellent. You know, the CD19 area has been populated by a number of cell therapies, right? The antibody's kind of coming more recently. You know, to what degree do you think the market is gonna treat these or bifurcate between the two? Given, again, our experience with, you know, sort of those CAR T, anti-CD19 CAR Ts, now we have, you know, budo coming down the pike. We don't really see it as so much bifurcation. I think, like, with the cell therapies and CAR-T, that's gonna be reserved for the most severe patients at academic centers, where you're having to carefully monitor for CRS or ICANS, whereas the antibody approach can just be administered in that academic setting or more broadly in the community. I believe that it's not bifurcation. I think that the cell therapies are probably more limited by the risk tolerance around them and that, versus I think that an antibody approach could serve across the board. Excellent. Yeah, no, it looks like lots of potential here, and we'll be getting some informative data readout soon from the budo program. We're all watching out for those. Let's talk a little bit about 116. That's the anti-APRIL, a more recent addition to your pipeline. I think just as exciting. Quite exciting, actually, given what's, you know, what we're seeing in kind of the IgAN, IgA nephropathy space and the opportunity for an anti-APRIL. We have, you know, approved drugs that have been available for some time, like, you know, those target the RAS pathway and SGLT2, and then, you know, more recently, we've had an anti-APRIL, also some, you know, some others. Kind of, you know, there's a very big investor awareness and interest in the IgAN space, you have, you know, Travere's sparsentan is launching, that's an Endothelin A and Angiotensin II receptor dual antagonist. Maybe just, you know, it would be great for you guys to provide us sort of an update on the current and shifting treatment paradigm in IgAN, and you know, what has you confident that an asset like CLYM116, you know, could be positioned to deliver meaningful value? I guess, Dr. Charles. It's quite exciting and wonderful to be in, at a time when we're undergoing a treatment revolution for a disease such as IgAN, which is, you know, affects, you know, a substantial number of patients worldwide. You're quite right to point out that the treatment paradigm is shifting. There was recent KDIGO guidance that was updated late last year that really emphasized a two-prong approach towards treatment of IgAN. Addressing the ongoing nephron loss with agents such as RAS inhibitors and endothelin receptor antagonists and blood pressure control, lifestyle modifications, coupled with a targeted approach to address the upstream drivers of disease in a targeted fashion. APRIL is a clear driver of IgAN biology, and targeting APRIL will become part of the mainstay of treatment of IgAN. We firmly believe that. The results that we're seeing from Sibeprenlimab are quite encouraging. You know, we see that with Sibeprenlimab, targeting of APRIL and reduction of APRIL levels leads to reduction of IgA and improvements in UPCR and eGFR, at least in phase 2. We're awaiting the phase 3 eGFR results. There have been clear linkages between reduction of APRIL and preservation of nephrons, which is quite encouraging. We think we can do even better, and we think there's room on the table that's been left for improved efficacy, with dose optimization, with an antibody against APRIL that effectively clears APRIL from the circulation like CLYM116 does. As you mentioned, it's a novel sweeper antibody. It has a pH-dependent bind and release mechanism for APRIL, that effectively captures APRIL in the periphery and then targets it for destruction in the endosome. That confers some potential potency and PK advantages, which has the potential to allow us to effectively deplete APRIL or reduce it to very low levels over the course of the dosing interval. We think that we could have an even better reduction in IgA, and an improved dosing regimen beyond the Q4 weeks with Sibeprenlimab. We're hoping for at least, if not better, improvements in IgA, which would translate into improved proteinuria remission rates, as well as improved patient convenience through more acceptable dosing. Yeah, no, we did see some pretty compelling preclinical data, you know, you versus Sibeprenlimab. Anything further to highlight from those those comparisons? Yeah. So we ran some studies in non-human primates that we find really, really to be very encouraging. So we went head-to-head with Sibeprenlimab in our NHP models, and we saw improved IgA reduction, so better IgA reductions that was more durable throughout at least 60 days to 90 days after the dose was administered. We saw a half-life that was 2 to 3 times that of Sibeprenlimab. That gives us encouragement that we can have a dosing regimen that allows us to achieve either 8-week or perhaps every 12-week dosing when we go into IgAN patients. Yeah, speaking of which, how are you thinking of the endpoints, you know, in, you know, terms of IgAN proteinuria, eGFR, changes, biomarkers? How, you know, what would you consider to be kind of a quote, "win," in sort of, you know, early clinical data that would really be exciting for you to put this into late-stage development? We're very much interested in looking at IgA, and as I mentioned, we have a clear line between what has been shown in non-human primates and healthy volunteers and IgAN patients. We can map directly on that line what we need to see to be competitive. We're gonna be looking at IgA very closely. We'll eventually be looking at UPCR in any registrational trial, and of course, eGFR slope stabilization. For our first read, IgA is going to be very important for us. As the most immediate PD marker, we're gonna be looking at full APRIL suppression over the dosing interval. Excellent. Okay, you know, and, as we look at, you know, the other IgAN programs out there are combination strategies that are being looked at. You know, maybe a little bit early, but what are your thoughts today? You know, monotherapy for 116 or a backbone, could there be others that it may kind of orthogonally work well with? You know, and how might that impact your commercial plans, your, development and then eventual commercial plans? Yeah, we see this. I think that for us, just stepping back, we think that APRIL only is the best approach in IgA nephropathy. The APRIL BAFF, we don't think BAFF is adding additional efficacy in this patient population, but maybe opens you up to additional immunosuppressive risk. When we think about combination therapy with, like, the kidney preservation, kidney function therapeutics, we see that happening broadly. Disease-modifying combinations, I think our approach is monotherapy at the moment, and we think that with 116, we can replicate what we saw in the NHPs, that's gonna hold up and be a very strong profile. Just as I think about the market going forward, it's amazing that now nephrologists have a tool or multiple tools in their toolkit to start helping these patients, but there's still a lot of efficacy, convenience, and safety that's left on the table. That's where we think that the next generation, like our 116, which is the longer acting, but also potentially more potent, could come in, and this is gonna be a chronic and a switching market. That's where we see 116 coming into play. Yeah. Terrific. Susan, I mean, you guys obviously have a lot of optionality and opportunity in front of you with multiple indications and these two assets, and maybe you'll be looking to bring on some more to, you know, to follow those. Kind of just curious, as you think about developing Climb as a company, you know, what your thoughts are there in terms of working with others? Going it alone, maybe geography kind of based approaches. Just curious to hear your thoughts. I mean, I think right now we've been very clear in what we as a small company of Climb could bring forth ourselves. In fact, like a PMN pivotal trial is around 150 patients, that is within our ability to deliver. If we really saw potential for Budo in something like SLE, as we're talking about, that's more of a translational experiment right now, that could warrant a partnership opportunity, et cetera. I think that what we wanna do is just make sure that we know that what we bring forward in Climb is further developing that profile, but that we can credibly deliver it as a small biotech, which we can across IgAN, PMN, et cetera. Yeah. You guys, you've been successful in financing, so you've got, a good amount of cash. I believe your runway takes you into 2028. Is that right? Yes, yes. More than 12 months beyond all the readouts this year, but that being said, you know, if we will have opportunities to bolster that balance sheet with success to raise for potential pivotal trials and additional indications. Yeah, yeah, terrific. Will we see, by the way, longer term, I know you've had actually quite a bit of long-term follow-up on some of those initial budo patients in PMN. Will we see kind of more extended data from those or? No, unfortunately, that trial was ended, and so actually the four patients that we were able to follow for those three years, that was after the fact kind of going. It's, it, we won't have longer term follow-up from that. We're I think that with the data that we have coming this year, that's going to be what's most looked at and valued. Yeah. I think pretty remarkable that three of the four remained in complete remission and I don't believe required any further immunosuppressive therapy, so. Right ... clearly bodes very well. I would encourage investors to look at some of your recent ASN presentations. Again, to review the 116's differentiation from Sibeprenlimab, which was, I think, on a poster also at ASN. Of course, these are all available, I'm sure, from both of you. Maybe, Leland, just to, like, be crystal clear with everybody, we have 5 clinical data readouts this year. We'll have our healthy volunteer sub-Q data for budo in the first half. Mid-year, we'll have our healthy volunteer data for 116, the IgAN program. In the second half, we'll have initial data from budo in ITP, SLE, and PMN. We've got a lot to look forward to this year. Great. Thanks. You saved me from having to make sure I got everything in the right order, but it's a lot to look forward to. It's great to see your stock moving in the right direction, and I think we're seeing a lot of institutional investor interest in Climb Bio. You know, keep on keeping on, so to speak. It was great to have both of you here, and thank you all for Zooming into the session, and I hope everybody enjoys the rest of their conference. Thanks so much. Thank you. Thanks.