All righty. Thanks so much. Been a great conference. Really enjoyed it. My name's Akash Tewari. I head our pharma and biotech efforts on the research side here at Jefferies, and we have Climb Bio, a company that we adjacently track because we cover Jade, and certainly a space where I think there's going to be multiple winners. I'm really excited to host the management team, and also reconnect with Susan, who, she and I used to talk about IP with SOLIRIS back in the day. It was a lot of fun. Now she's on to. There's a connection. This is true. SOLIRIS to ULTOMIRIS. That is true. Clearly onto even bigger and better things at Climb. Why don't I hand it off to you for intro remarks, and we'll get going. Thanks. Yes, excited to be here with Climb. We are a clinical-stage company. We have two antibody approaches in renal disease and other autoimmune diseases. Our lead program is our CD19 monoclonal antibody, Budoprutug, that is in development in phase II for PMN, in phase I-B for ITP and SLE, we can go through the cadence of readouts there. We just had a spotlight event for Budo in early May, we presented data showing that with our CD19 antibody, we have the ability to formulate as a subQ formulation, which gives us even that much more optionality. Very exciting. More data to come this year and next for Budo. Our second clinical-stage asset is our APRIL-only monoclonal antibody that has the sweeper mechanism, which is pH-dependent binding to APRIL. It's the technology that was used similarly from SOLIRIS to ULTOMIRIS. That has the potential to be a best-in-class, next generation asset in IgA nephropathy. We'll go into more detail there, just because I know that Jade had data earlier this week. Yeah. It's ERA, so we could start there and then talk about Budo. Absolutely, yeah. Let's start with the anti-APRIL, and I'd love to get your take about, A, the Jade data set, but also really what's broadly going on, I think, in this space, because I think there's certainly a lot of moving parts. Let's hit on this. Any thoughts you had on the Jade data set, what they were able to show, and how that may apply to your program as well? I would say very validating in terms of the next generation approach and potential value creation that only CLYM116 and Jade have the potential to create. Lots of progress and excitement in IgA nephropathy, but this first generation of assets is at best dosed monthly. They're getting to around 50% IgA reduction, they have some safety liabilities. We believe that we, and then what Jade showed, that you can actually win on multiple legs of the stool because there's a lot of room left open. In terms of the data, again, we think that they showed that they were able to get clearly every eight week dosing, with modeling get to 12 weeks. We think that every two month or every three month dosing is quite compelling for these patients who are diagnosed in their 20s or 30s, and they're going to need chronic dosing. I think it's a great step forward and there's still a lot of room for both of us to be wildly successful in this very large market. Understood. No, I think that makes sense. Frankly, I think that's a tone that both management teams have struck, even pre-ERA, which is always nice to see. I remember we did some diligence on your program as well when we were looking at ERA, and the thing that we've always It's difficult to model this, is can you get to, let's say, quarterly dosing with a single subcutaneous injection in maintenance? That's always really hard because no one seems to give their dose, no one seems to give their actual potency. That certainly seems like post the Jade data set, something that they're quite confident on being able to deliver. I'm curious for your program as well, again, a higher bar than maybe just initial expectations, but is that a possibility with your program as well, subQ maintenance on quarterly? What we have set out as the target product profile, which Susan alluded to, is we take it in a tiered perspective. First we look at safety, APRIL has been very good safety tolerability profile. We expect no issues there. The second piece is efficacy. Obviously this is a very young patient population. You want to ensure that they're not moving to dialysis or ultimately kidney failure would need a transplant. We're going to want to ensure that we hit that efficacy bar, that was set with the first-generation agents, we're looking to potentially improve beyond that, our NHP data suggests that there is the potential there. I think we're going to want to ensure that we maximize efficacy, and that's looking at APRIL suppression as well as IgA suppression in healthy volunteers over the dosing interval. I think that third tier is dosing and convenience, which we completely agree is, in this particular patient population, really critical. This is a young patient group, they have busy lives. We want to make sure they stay on therapy and that they're compliant over which is going to be a lifetime of therapy. Obviously if you're able to improve that dose frequency, I think that's going to be critically important. I think we'll look at all of those parameters, but with the sweeper technology, we really feel that there's the potential to not only extend the half-life with the LALA mutation that we have, but also with the sweeper show enhanced effects over time on the PD parameters that are really going to lead to a more improved clinical profile. Yeah. To just directly answer your question, like, Is every eight-week or every 12-week maintenance a possibility? That remains the possibility... Yeah -for us. Yes. Understood. I think the other thing, you're absolutely right in terms of when we look at your non-human primate data, you have similar potency, at least it looks like that to sibeprenlimab, but the sweeper kicks in on the tail, right? I think that's quite important. Certainly, I think as you get to steady state trough, that effect will amplify if anything else. The question also becomes, I think when you talk to, let's say, our friends at Biohaven, or we cover argenx, and there'll be a view of, "Look, I don't know if we can get better depth reduction or if it even really matters," because eGFR is your downstream thing, and it might be a little more forgiving. We'll try to improve on onset of effect. Right? You can do that with a degrader, you can do that with a sweeper, that we at least see with the data from argenx. I'm curious with your product profile as well. Certainly, the non-human primate data suggests you get the depth and tail effect of a sweeper technology. Do you think you're going to get the same onset of effect that you could see as well? For example, that not only do you get to, let's say, 70% IgA reduction, but that can happen, let's say, in a month. Yeah. I think with the degraders, I think their profile is really that very rapid onset, and I think Biohaven has even talked... Yeah -about onset within hours. I think we believe that the APRIL mechanism works fairly quickly when you think about a chronic condition. You're looking at APRIL nadirs in the four-week timeframe, you're seeing reductions within weeks. The IgA follows closely thereafter. I think it's, for this disease population, still a fairly rapid onset of effect as you think about those biomarkers that will ultimately impact the proteinuria and eGFR. Is there a world in which a patient comes in with very elevated proteinuria where you need that very rapid onset? I think maybe that's more the area where a degrader could play. For a chronic therapy for a lifelong condition, we think anti-APRIL is a great approach. Makes sense. Akash. Yeah An interesting thing, I think everybody has focused on eGFR, but there was the recent NKF and FDA summit at the end of April. Sure. Really, it seems like the renal division is. Or the- going strong. Yeah a highlight of the FDA right now. I think that there's just growing recognition that proteinuria lowering and keeping it low below the 0.3- Yeah is translating into eGFR stabilization. We do get questions. I think that the question is, it's not just about the median, it's can you get more patients to target over the long- term as well. No. Yeah. Certainly if you look at the sibe data and you do the stratification, whether it's on weight, whether it's on ADAs, I think to your point, getting everyone right-shifting the curve on exposure in of itself I think could have more consistency in response. I think that's absolutely right. One of the things that I find quite fascinating is I don't think we know enough about APRIL biology. Manoj is on my team, who's much smarter than me, who's told me I'm wrong, but I have this theory when I look at, for example, the VOR data. I get it, you're not going to replicate in gMG that MG-ADL placebo response. I get it. There's a durability of response and a depth of response, and it's not a particularly good B-cell drop. Right? I look at the VOR molecule as good anti-APRIL, not as potent in terms of BAFF. There's a dose response. I cover argenx. We've learned, looking at FcRns, a really nice tight relationship between IgG reduction and MG-ADL response. That curve doesn't work when you get 20% IgG reduction with the VOR molecule with the depth of MG-ADL response they get. I almost think, hey, APRIL's doing more than we realize. When you look at the biology, if you suppress anti-APRIL, you also make BCMA functionally silent. There's stuff going on here that I don't think we all fully understand. I'm curious what your team's view is in terms of where APRIL can work and where can it not, right? Do you think APRIL inhibition alone can actually be much more dramatic than maybe the traditional dogma right now? I think that there's a possibility I think that on the APRIL BAFF and the BAFF side of the equation for IgAN, we're not seeing any real benefit. Yeah It has the safety liability. When we think about where we will take 116 beyond IgAN, clearly there's a rationale for Sjögren's and other indications, but I think that right now our focus is preliminarily on generating these data, getting into an IgAN pivotal moving forward, and the nice thing is that with the ongoing studies in APRIL biology being better understood, we can actually make fast decisions following on from where others are going to say where else we would expand into. Would there ever be appetite to, let's say, take this into myasthenia gravis? Or no, because you feel like it's very tightly correlated with IgG reduction? I think we would look and explore where we think APRIL biology would have the impact, and I think you hit on as we look at even our NHP data, you saw dramatic effects in IgA and IgM, less so in IgG. I think for IgAN, that works perfectly. Other IgM-driven diseases, I think, would certainly be on the table. I think something that's primarily IgG driven. I'm not sure you get the reduction with APRIL there. Understood. Okay. Well, both companies disagree with me on this one. I will say IgM seems to have a role in CIDP and gMG as well. Understood. Now, when we step back, we're going to get a few more data sets, including when we cover Vertex, we get the full pove data. I'm curious about your understanding of what the FDA needs for monitoring requirements. Sibe got approved. I don't think people appreciate this, there were eight cases of hypogamm mild with that, if you look at their multidose linear. It's not like anti-APRIL doesn't show that. They did not have a monitoring requirement. Looking at Vertex's commentary, I think externally, they've been very clear. Like, yeah, we have some cases of hypogamm, but we're not having serious infections, ergo, we filed for accelerated approval. We're very excited about the data. We think it should be supported for a broad-based approval without monitoring requirements. You've had interactions with the FDA, and this is a nebulous issue. How do you think about whether you have a monitoring requirement or not? What is the bar? Is it the infections or is it the hypogamm itself? It's challenging. We can't speak for the conversations they've had because we also don't have a BAFF component. Yeah. I think that the question that we have, and that when we're talking to KOLs in particular, is more of the long-term risk. Yeah. That's the question of the trade-off and balance, because you might not be seeing it, but over a couple of years, and these are young, healthy patients, does it open them up? We haven't had major discussions on monitoring with our approach, but I could see it going either way because it's theoretical more than actual. Yeah. For the record, I think at 80 mg per kg, we think there's a really nice safety profile with pove, but trying to get more information here. We can throw it either way. I think maybe just lastly, you mentioned consistency of exposure. When you look at sibe, and we can talk about the ADAs, but then we can also talk about the fact that it's subQ, and there's probably some limit in terms of what they can fit into an auto-injector. Do you feel like there is actually room to improve UPCR? Whether it's scientific or not is a different question. It's probably not scientific, but let's say a company had a six handle versus something in the 50, I think people would be like, "Oh, okay, that is differentiated." Do you think that there is actually room left on the table in terms of UPCR improvement that pove couldn't test because they were limited by BAFF inhibition, they couldn't hammer APRIL enough, and then sibe couldn't because, again, they were limited by their dose or ADAs? Yeah. I think if you look at the sibe phase II, it does show that there's room for improvement there. The middle dose, their 4 mg per kg, which roughly equivalent to their 400 fixed dose, they saw APRIL sort of creep back up within the dosing interval. When you look at the IgA reductions and the proteinuria reductions, they weren't as great as they were with the 8 mg per kg dose. I think they showed more dramatic IgA reductions. They showed greater proteinuria reductions, which I think importantly, what we believe is that it got more patients to target. at that higher dose. I think the ability to dose up and even over time get a little bit more proteinuria reduction, you might see within the spread, because you're looking at medians. The spread and getting more patients to that target level, I think is going to become critically important as more agents become available, and I think that's the benefit of if you can do just a bit more you could probably get more of those patients. Sure. Well, KDIGO updated the guidelines that you're targeting 0.3 grams versus 0.5 grams because showing that even the low levels of proteinuria are imparting kidney damage over the long- term. We do think that there's room there. Understood. Maybe stepping back, again, there seems like a lot of different disease states where anti-APRIL can work, and you might not be first in IgAN, sure, but I think how you guys develop this drug, and I think this is going to be a relevant conversation even for Budo as well, sometimes it's the drug, but it's also really the strategy and the approach. When you think about how you're going to develop this asset versus how your peers think about this class of drugs, how do you plan to stand out? Are there indications where you're confident you can actually be first in class? Well, I think that the standing out and how we're going to progress, I think that what is underappreciated about our path forward is our collaboration with our partner Mabworks in China. We have our healthy SAD/MAD study going on in Australia. They have a parallel study in China with SAD in healthies and MAD in IgAN patients. We do think that that's going to provide us with more data, more dose-ranging data, et cetera. When we do our spotlight event later in the summer, we'll disclose Mabworks' plans, our plans, and then how we go forward together. We do think that that's an asset in terms of being able to accelerate the development process. Interesting. I know in China you often have these academic-sponsored studies, or you can do basket approach trials. I think that's something that we've seen argenx tap into as well. Is that potentially avenues that, again, are available in China that may not be available in Australia or the U.S.? Yeah, I think potentially. As Susan said, I think our focus at the moment is really on IgAN and shoring up that development path there. I think coming as sort of that next generation, a lot is known about the biology, we can focus on those differentiating parameters. We're already thinking about what would be our presentation at launch. Right is optimal. I think you can do a lot of optimization to make sure you're in a really good position at launch, which when you're first and paving the way and learning about the biology and what's possible, perhaps you don't have the foresight to be able to do yet. Understood. Now, wait, has ERA happened yet? It's happening. It's happening. Yeah. Okay. I'm not that crazy. Okay, it's happening. You guys are going to give modeling data. What are you going to give at ERA? Have you already given it? It's tomorrow. Okay, tomorrow. Yeah. All right. Okay, what should we get at ERA versus, it sounds like there's going to be another data disclosure as we get to maybe ASN, help us understand, and maybe not, what's getting dropped when? Yeah. I think tomorrow is our presentation at ERA, and from the abstract, you can see what we're going to share is translational modeling from the NHP data to healthy volunteers, the basis on which we designed our phase I approach. You'll also get the design and doses that we're looking at in phase I and also what our partner is evaluating. I think you'll get a really fulsome picture of our phase I strategy. We'll also have some of the initial safety data from the ongoing studies. Okay. It'll be a first piece, and then what the data that everyone is more eagerly anticipating is that PK/PD data which we've said will be later in the summer. Okay. Understood. You mentioned ASN, that's the other major kidney- Yeah meeting in the second half of the year. There is potential for us and for Mabworks to have additional data disclosed this year, but we haven't. Yeah laid out that plan yet. Right. We wouldn't be surprised. Okay. Okay. It's also tricky. Have you guys disclosed the doses you're taking? Not yet. That's tomorrow. Okay. Yes. Having disclosed the dose is not surprising, but so maybe intent is the question, right? With Jade too, they're like, "Hey, we're thinking about this level exposure. There's one dose which is going to be much higher, and that's more of a safety test." What are the doses that you're taking in terms of, let's say, what you anticipate your induction dose to be and what you anticipate your maintenance dose to be? Are any of those doses getting tested in the back half of this year? Are there other exposures that you're pointing investors to that you're going to be observing? I think what we saw was in the NHP data, we looked at 6 mgs per kg and 30 mgs per kg. We've said that we thought that 6 mgs per kg was really in that clinically relevant range. We tested 30 ultimately to push a dose and to look at a dose that was equivalent to a higher dose that sibe looked at in their NHP studies. I think we saw a better profile with our 6 mgs per kg relative to sibe, which we've shared. We kind of projected out into phase I what that range would look like to give us some safety coverage, both lower and higher, and also give us a really robust data set upon which to model. Yeah. Importantly, our phase I also has a MAD component. Okay. We'll be able to model some accumulation and the like as we think about repeat dosing. Understood. All right. That's enough on APRIL. Let's hit on Budo. Susan, for you, kind of the same question, because look, we've seen some I can comment on, some we can't. For example, Gilead bought [audio disortion], that's a good example. There's a lot of BCMA/CD3s out there, right? Gilead bought that company partially because I think it's the strategy, it's the approach, it's the way that they're thinking about modulating autoimmune diseases, and I think that sometimes differentiates just as much as the products themselves do as well. You guys are in a similar situation. Everyone's heard of CD19 at this point. What is your approach? What is your strategy that you think is different that will really start to stand out? Yeah. At our Budo spotlight, I underwrote joining Climb on Budo alone. Wow. Yeah. Because there has been so much interest on CD19 with the CAR T or TCEs, and it's almost like we went to the complex modalities where you're at risk for CRS or ICANS, and you're going to be treated at the academic center. The beauty of a naked monoclonal antibody approach to CD19 is that the community nephrologist can dose the patient or a hematologist can dose the patient. UPLIZNA is a great analog for uptake of a. Yeah CD19 antibody. We know that we have the subQ formulation that's differentiating, and we're going into different indications. I think that for us, and that's why the data that we had at the low dose for Budo at five patients in the Phase I-B proof of concept, really were compelling even at those low doses. As you dose up, are you getting more durability of response, et cetera? The nice thing with an antibody is you can re-dose it, and one thing, stepping back, in the five patients of data where we saw a complete B-cell response, PLA2R seronegativity. Yeah 60% complete renal response, that study, again, was stopped early, but we were able to have follow-up data on four of those patients, and three of the four didn't need any additional immunosuppression after just those initial doses of Budo for three years. The question is, with an antibody approach that's safe, for some patients, do you have a treatment-free interval? Can it be a reset? I think also just the safety profile of Budo and just the antibody approach. Yeah is so much more amenable, and it's kind of funny to me that we skipped over that. That's a really good point. Yeah. Certainly, I think the UPLIZNA story is proving that out. We'll hit on the Fc then on the safety. On efficacy alone, there's levels of B-cell reduction, right? We've got RITUXAN, which again gets you peripheral reduction, but it doesn't get into the spleen and the lymph nodes very famously. It doesn't get that level. There's the CAR T and the things that really get there. When you think about Budo, have you shown the ability to completely deplete the spleen? Is the whole pitch, we're not giving up anything by not having a CD3. In fact, we're getting the exact same level of B-cell reduction. That's the question, and that's why we're going to be dosing up to C. I think that we've already generated a high sensitivity B-cell assay where we can assess 0.4 cells per microliter. We really do think you need to fully deplete the B cells to have that reset. The question is in what portion of patients and how many can you get there? That's the experiment, but do you have to get to that level with an antibody approach that you do with a CAR T? Not necessarily, that's why we're dosing up and exploring. Sure. Any lessons you learned from UPLIZNA with the CD19 depleter? Was there an upper limit there that it got to a certain point, but it couldn't really get to a CAR T level? UPLIZNA, it's a CD19, it's B-cell depleter just like ours. They went for an NMOSD. This was the Horizon drug from Viela Bio. It wasn't like they optimized for what we're trying to optimize to see as you dose up, is this an immune reset approach? With an NMOSD, as you know, if you have a flare, you could be debilitated completely. Yeah. I think that the premise was always chronic. It also looked like RITUXAN, to be honest. Yeah. The other piece versus RITUXAN is that with the CD19 approach, you're getting the plasmablasts, but you're preserving the long-lived plasma cells, which is really why it's the Goldilocks target w e like to say, for the antibody approach in diseases like PMN. Can you talk a bit, it's like the dosing, but what have you optimized with the molecule that is maybe different than UPLIZNA? Picomolar affinity to CD19, enhanced ADCC, and we don't know why UPLIZNA doesn't have a subQ formulation. We know it was assessed back in the day, they don't. That and indication strategy have been the clear differentiators. Understood. It doesn't get talked about enough. I think you're onto something that's quite important, which is, again, you're on these autoimmune conditions. I think to get on IVIG chronically, probably not ideal, and also just exhausting your T cells. That's theoretical. Are there any data points you can point to us where it's like, look, maybe it's in oncology with the CD3s, where you feel like there is a debilitating impact of chronic T cell exhaustion? Our approach is harnessing the NK cell approach. I think with the CD3 and the T cell approach, that's why I think the promise of TCEs was you'd have CAR-T-like efficacy, but the safety of an antibody, and we're not necessarily seeing that. The question is, can you get very good efficacy with the antibody approach? Could you get CAR-T-like efficacy at the right doses? One of the other pieces you asked about the spleen. It's hard to get biopsy data. In SLE, we have a parallel study we opened in China because in the U.S. you have to start at subtherapeutic doses, and we'll be trying to get biopsy data from LN patients in that study. We don't think it's necessary, but we do want to answer that question for ourselves. Understood. Maybe just lastly as we wrap up here, in terms of are there any combination approaches with Budo and the anti-APRIL that you're thinking about? Really, no, they're two distinct molecules, two distinct profiles. That's not really our long-term approach. We just have to ask what you're excited about. I'm hearing this theme of combination is going to become increasingly important. We're very convinced argenx is going to be actually a combination story over the next few years. I think we think combinations are going to come, but is it like complement and APRIL? Yeah. We see that as being a trend going forward, definitely. We haven't really contemplated Budo. Yeah just also the dosing paradigm is different in terms of being able to target CD19, deplete the B cells, and you're dosed every six months versus. That's why we don't think that the CD38 or BCMA approaches are the right approaches, particularly for PMN. Oh, interesting. Can you expand on that a bit? Yeah. In terms of, again, the Goldilocks target, you're depleting the plasmablasts, but you're preserving the long-lived plasma cells so that you. Yeah. You You don't have to get revaccinated. Yes, exactly. Okay. That makes sense. We are out of time. This was a great conversation. Yeah. Yeah. Thank you. Not surprising at all. I really do appreciate your attendance and thanks so much. Yes speaking tomorrow. The rest of the year. The rest of the year. Exactly. Great. Thank you.