All right, good afternoon, everyone. Welcome to Guggenheim Emerging Outlook Biotech Summit 2026. My name is Yatin Suneja, one of the biotech analysts here at the firm. It is my pleasure to welcome our next presenting company, Climb Bio. From the company here, we have two executives. We have Susan Altschuller, who is the Chief Financial Officer, and then we also have Perrin Wilson, she's the Chief Business Officer. So I will be having a fireside chat with ladies here. But before we start, maybe I'm gonna hand it over to you, Susan, to make some opening comment, just orient investor, you know, on the upcoming milestones, and then we go into some of the questions that I have prepared for you guys. Great, wonderful. So, we at Climb are focused on autoimmune diseases, and we have two antibodies in the clinic, and we have five clinical data readouts this year, which we're really looking forward to. So for our monoclonal antibody targeting CD19, we will have data on in healthy volunteers for the subq formulation in the first half, and then in the second half, we will have initial data from the phase 1b study in ITP, the phase 1b study in SLE, and initial data from the phase 2 study in PMN in the second half. And then our second antibody is an APRIL-only antibody that has a sweeper mechanism of action, for IgA nephropathy, and those data will be mid-year. So, a lot to look forward to, a lot to come, and... So that's kind of what we're tracking towards. Thank you, Susan. So I think, so I'm gonna come back to the APRIL. First we want to address the CD19, but definitely that's where I think we're seeing more interest in the recent days. But let's go through the CD19. Could you just talk about the uniqueness of the antibody relative to UPLIZNA, the depleter? Because I think right now we're seeing more... So there is a depleter approach and an inhibitor approach. So just help us understand, where are you? How are you thinking about indication prioritization? Obviously, you have these three indications, but how are you thinking about indication prioritizations? Stepping back, UPLIZNA is the only CD19 antibody approved and on the market, and they have had great success and focus; they've so articulated on the rare neuro space. Yeah. We believe that we haven't done head-to-head exactly, but we, you know, we have greater affinity to CD19. We hope to have a subQ formulation option that UPLIZNA doesn't have. But really, there hasn't been much in terms of antibodies for CD19, that's really it, relative- that are depleters. Yeah. We've always said we believe that the depleting mechanism of action in these diseases is critically important, so that's where we see ourselves playing. And again, UPLIZNA and Amgen, they focused on that area- Yeah ... we're in different spaces as well. Got it. And then with regard to your subq formulation development, is the goal to have both IV and subq? Because I think there are this Part B and Part D dynamic that comes into play, or just have a subq? No, no. So we're, we're actually working through that strategy now. I think that subq is going to provide us a differentiated option. We have to see how the data play out, because in the phase 1b study in PMN, the four doses of budoprutug, three of the four patients that were followed for three years didn't need additional immunosuppression, and that's dosed just those, you know, every six months. So with the subq, we think that provides great optionality. You could bridge from IV to subq, but for some indications, that, that dosing paradigm of six months IV is going to be sufficient. So more to come as we further characterize the subq dosing, regimen, and then we'll be selective about where we go with that. Got it. Got it. So, let's start with the PMN as an indication. Could you just walk us through what is the opportunity there, what are some of the key endpoints, and what exactly have you generated in that indication? Perrin, you wanna take that one? Yeah, sure. Yeah. In PMN today, there are no approved therapies. You know, CNIs are used, patients are on, you know, ACE inhibition- ... and rituximab is used off-label and traditionally considered the standard of care. However, there's a huge unmet need there, 'cause rituximab really only gets about 10% of patients after 1 year to a complete renal remission, which is that gold standard of where you want patients to be. And even after 2 years, only about 35% of patients achieve that complete renal remission. And so, you know, that is going to be the approvable endpoint, achieving a proteinuria level of less than 0.3 grams per gram. And in our early phase 1b study, which Susan alluded to, we had 8 patients, 5 of which were evaluable and had the 4 full doses of budoprutug. In that study, we were able to achieve a 60% complete remission rate, and 100% of the patients that came in as PLA2R antibody positive achieved a serological remission. Mm. So we think that is really compelling proof of concept data in this indication, and really against early data from some of the other agents, sets us up for a potential best in disease profile. Where we are now is in the phase 2 study, which is really picking up from where that phase 1b study left off. From that study, we'll really hone in on a phase 3 dose, and then move forward to pivotal trial. Got it. The phase 2 started in November, right? It's about a 45-patient study. Mm-hmm. I think you're testing three doses. Right ... could you help me understand what are these doses, why are you testing three doses, and then how do they compare to the phase 1b, especially those five patients where you had the evaluable patients? Yeah. So the phase 1b was really a low dose, so 100-200 milligrams, and that's where we achieved, you know, that, the really, intriguing proof of concept. So that phase 2 study, we haven't disclosed the doses, but what we can say is that the low dose is effectively quite equivalent to what we had studied previously, and we're stepping up from there. Budoprutug was originally studied in oncology and B-cell malignancies, and there, they studied up to 1,000-... And so we do have a very large therapeutic window with budo, and I think, you know, the long-term safety profile of UPLIZNA lends to the fact that you can dose quite high in these patients. And so what we're really looking for is a dose here that achieves significant B-cell depletion, achieves the serologic remission levels- Yeah. That really would put patients towards proteinuria improvement. Got it. And then the three doses, obviously, you didn't disclose, but what about the schedule? Like, how is it? Is it the injection? It's in cycles, in 6-month cycles. On day 0 and day 14, patients receive an injection, and then the second cycle in 6 months. Like traditional. Like you've been UPLIZNA, like that. rituximab, UPLIZNA, obinutuzumab like. Yeah, all done, yeah. You know, as Susan alluded to, you know, in that—after that first year of therapy, three out of the four patients that we were able to follow for a long period of time didn't require additional immunological intervention. Got it. In terms of the renal response, like, what is a good, data set? Or in other words, like, what, how would you characterize success in this phase two, which I understand this is more of a dose finding, but still people will be focused on the SA, on the efficacy, right? Correct. So what is the, I think we'd like to be able to achieve what we did—achieved in the phase 1b study. I think that would be very compelling, a very compelling outcome. I think for us, though, you know, certainly we will follow the patients for proteinuria, but we will be able to select a dose off the B-cell depletion and PLA2R, because those are just very predictive, and PLA2R in and of itself is a predictive and prognostic biomarker for PMN. Okay, two questions on this, and I'll move on. How big is the market? How many patients are there or addressable patients? And then what is the regulatory strategy in the sense that you need one study, two study? Where do we stand? Yeah. So I think it's a, you know, a really untapped opportunity. There's about 70,000 patients in the U.S. with PMN. Two-thirds of those patients are gonna be that moderate to severe patient, which is going to require therapeutic intervention. And so, you know, large opportunity of potential patients with a very high unmet need. This is a very severe and debilitating disease, really necessitating treatment in those patients. And then in terms of the path to approval, it's really one phase 3 study, about 150 patients- Mm-hmm ... with proteinuria that complete renal remission as the primary endpoint. And there's a couple of precedent studies. You know, Obinutuzumab's Majesty study is probably the most prominent and top of mind for folks- Yeah ... but looking at a 104-week endpoint. Got it. Got it. And then, not to jump to the APRIL or IgAN side, are the physicians similar? Is there an overlap between this? Is it treated by the same physicians? Yeah, by nephrologists. By all nephrologists. Mm-hmm. I'd say sort of even pairs with your- Yeah, very synergistic. Very synergistic. Okay, very good. A choice of ITP, I mean, that is an interesting area where, you know, the commercial success has not been there. So I'm just curious, is it just more of a proof of mechanism to establish it, or is an indication of interest? Yep. So I think the rationale of going in ITP are data sets that show even post rituximab positive, CD19-positive B cells. And what we've seen, despite all the progress, is that in these more refractory patients, you're only having 20% have a durable platelet response. So what we thought with ITP, there's a strong rationale for the CD19, and it's a great biomarker-driven disease with B cells and platelet counts to get that the proof of concept and the right dosing in a non-renal indication. We know the bar is high. You have to have higher than that 20% durable response. But again, that is something that we as Climb could bring into a pivotal pretty rapidly with the right dose. Okay. Then SLE, obviously, bigger indication. There is a lot of, I would say, data on B-cell depletion. So how is your program sort of positioned there? We see, so we see PMN and ITP, something that Climb can, you know, bring forward ourselves. SLE, because we had to start at subtherapeutic doses per requirements for any you know- Yeah ... study in this space, it's more of a translational experiment- Okay ... because we know that it's a more heterogeneous, it's a larger population, and, and the pivotal trials are, you know, 1,000-patient, two trials, et cetera. So, we're trying to see if we can get a true immune reset with an antibody in SLE, but that is more translational, more to come on that in terms of kind of... We also just cleared the IND for a parallel SLE study in China, where we- Okay ... will enroll lupus nephritis patients and aim to get some, tissue-level depletion data- Got it ... via biopsy. Got it. So still more on the translation, those two. Mm-hmm. Now, if we step back, obviously, PMN, very straightforward, path forward, path forward from a regulatory standpoint, 150 patient study. How are you thinking about other indication in order to maximize? What type of indication you would pick? Are there more in the nephrology side or more on the hematology side with the ITP? I think that's what we're working through right now, and I think that the sub-Q formulation—for some indications, the IV formulation is going to be optimal, but with the sub-Q, there's potential to bring it into different indications or to bridge patients. So more to come on that in terms of kind of the beyond PMN, ITP strategy. But, with proof of concept, there's a strong rationale using a CD19 in many other- Got it ... autoimmune diseases. Got it. Yeah. All right, so then maybe move on to 116. I think that's a unique antibody in the sense that it has a sweeper mechanism. Could you explain to us what exactly it is, how exactly it is differentiated from first generation either anti-APRIL or other BAFF and APRIL? Yeah. So when we set out looking for a potential second pipeline program, I think we wanted something that was truly differentiated, and we found the Mabworks 116 sweeper antibody. So for us, it had something that wasn't just half-life extension. It has half-life extension, but it also combines with this sweeper mechanism, which is really pH-dependent binding. Mm-hmm. It binds APRIL, the ligand, at a very high affinity at neutral pH, so serum pH. In the periphery, it binds the APRIL, but then when it internalizes into the cell at the low endosome pH, it actually releases APRIL. And so the APRIL then is degraded- Yeah ... through the cell mechanism, but because of the high FcRn binding, the antibody is actually recycled back out to the surface- Yeah to bind up more, more APRIL. So, you know, sweeper mechanisms, this is not the first sweeper. Yeah. I think there's many examples of that, but, you know, the benefit here is potential for higher potency, higher activity, and a longer half-life. And so I think those, you know, that was the differentiation angle we were looking at. We brought the asset in at very early days. Mm-hmm. It was a very, you know, small pilot NHP experiment that- Yeah ... showed some positive signals, and what we did in kind of bringing that into Climb is we really want to put it to the test. So we did a head-to-head study with NHPs, looking at 116 relative to sibeprenlimab. Yeah. And so there, we really showed the potential for a longer half-life, so two- to threefold longer half-life than Sibi, and then, potentially better activity. So we looked at IgA suppression and saw up to a 70% or greater baseline, from baseline suppression in IgA, whereas Sibi was only able to achieve a 50% suppression in the same experiment. And so really signaling potential for, for better activity at clinically relevant doses. And then, you know, we're putting that now to the test in, a, a healthy, you know, human, healthy volunteer study in a phase 1, really looking at what 116 can achieve in humans. Got it. When we think of this first generation of APRIL, APRIL BAFFs- Yeah. It's great progress- Mm-hmm ... for patients who have had very limited options, but they've left efficacy on the table. You know, these patients are diagnosed young, in their twenties and thirties, and they're gonna need chronic therapy. Even very low levels of proteinuria are- Yeah ... putting you on the track to dialysis or transplant. So the efficacy left on the table and the dosing interval are actually very critical- Got it ... for this space. So, obviously, more convenience, right? I think that's where we are seeing a lot of development from long-acting, even pharma is going there. So, I think I'm with you on that. How would you envision... So given that at least in NHP, you are seeing 2-3 times longer half-life than Sibi, how are you envisioning when you go into the clinic? What sort of a frequency? I think that's what our ongoing study is going to answer. Okay. So we're gonna really understand the PK/PD effects in human subjects, and we'll be able to answer that from our ongoing study. I think we're hoping for at least that, you know, every 8 week, you know, potentially every 12 week, that's what we're gonna- That you- We'll have the answer to that question. Got it. And then, you know, obviously, there are two approaches, right? You have an APRIL-specific approach, and then there are BAFF and APRIL, where you bring in the B-cell component to it. What is your view? Like, how... But obviously, you went with APRIL-specific. Mm-hmm. What are the benefits of it in your view? Yeah. When we made the decision, actually, the sibeprenlimab and the atacicept data wasn't out yet, the phase III data. Mm-hmm. So we really made it based on the differentiation of the antibody and the promise for APRIL. And then I think we were really you know pleased to see that you know our hypothesis of APRIL only being sufficient in IgAN was true. And I think you know with the BAFF you would have expected potentially to see more inflammation you know more suppression of IgA better proteinuria control and that really didn't play out in those phase III studies. So you know in our mind APRIL only is really the the best path for IgAN and that BAFF component really isn't attributing anything to the efficacy but does leave you open for potential long-term immunosuppression via BAFF which has shown in you know increased infection rates over time. Got it. Got it. I mean, I know you are thinking about IgAN. I think that's one area that you are sort of thinking and prioritizing. How would you characterize the unmet need there now that you have more therapies there? Yeah, I think, you know, IgAN, it's exciting to be at ASN, and you know, it really is. I think the renal space is in a bit of a revolution, and you know, having a lot of emerging therapies when these physicians really had nothing a few years ago. You know, even the guidelines which came out in September don't even really speak to some of the even newer agents that are emerging. And so I think, you know, the guidelines are really pointing to the need to diagnose this disease early, to treat aggressively early, and to treat not only just to protect the nephrons that exist today, but also to prevent that pathogenic IgA formation. And so I think what you will see is that as these new agents come to play, that they, you know, I expect them to get good uptake. I expect, you know, Otsuka,, Vera, to really build that market and create that urgency to treat, that I think should exist, given all the parameters that Susan shared of, you know, very young patients ultimately getting to dialysis or needing a transplant within their lifetime. And so I think that bodes well for a market opportunity for then a next-generation agent with a differentiated profile coming to market and filling some of that need. I would say, you know, the newer piece of data that came out of the sibeprenlimab approval is that Sibi also sees some immunogenicity. Yeah. And so, you know, I think that points to the potential for switching in the market over time, as patients may experience ADAs that, you know, may preclude them from achieving the best efficacy level that they could otherwise. I'd say, you know, the other advantage we see with 116 is we don't expect that immunogenicity. There's just something about the binding epitope and the high molecular weight complexes that are formed with sibeprenlimab, which we've seen in our own experiments- Got it ... that we just don't see with CLYM116. Got it. And then in terms of the phase 1 study, so I think the data is gonna come in middle of this year, right? That's what you said. Where are those studies? What exactly are we gonna learn from those studies? ... Yeah, so the, you know, it's a healthy volunteer study, single ascending dose, and so from that study, we'll really understand the PK/PD, and, you know, from there, be able to rapidly move into a patient study, which ultimately will lead us to a pivotal study. You don't need an MAD? Well, sorry, I- Not in healthy volunteers. Okay. Yeah. Okay. Yeah. So one other component that I think is really compelling about our development strategy is our partner, Mabworks, in China. Mm-hmm. They have opened a parallel study in healthies, and they'll go into a cohort of IgAN patients. So what those data, in addition to our data, where we're running the study in healthies in Australia- Yeah This will enable us to more rapidly move to pivotal in IgAN patients. IgAN patients. Yeah. Yeah. Our study does have one MID cohort, but we don't feel that we need that necessarily before moving into a patient study. Got it. Helpful. Then in terms of, obviously, IgAN is one, the first indication you sort of pursue. How are you thinking about indication expansion? Obviously, with the... I mean, there's already a lot going on with just two molecules- ... multiple indication, but just to maximize the, the asset, what about the other indications? Yeah, I think we're going through that exact same exercise as we had done with budoprutug, really mapping where APRIL may play a role in, in potentially other diseases. I think one that, you know, comes to mind is, is Sjögren's- Yeah ... and Otsuka certainly has a study ongoing in Sjögren's as well, and so I think we're actively thinking about where next with this program. Got it. Got it. Okay, I think that's good. With regard to the balance sheet, Susan, how are you sort of situated? Yep. What's the cash for the- So, we runway? Our last disclosure, we had $176 million at the end of Q3, but we just updated our guidance at the beginning of the year that we have runway into 2028. Okay. More than 12 months beyond all the readouts that we've laid out this year. Good. One clarification question: On 116, the studies are IV or subQ? SubQ. SubQ. Yeah, and all of the animal studies were also done subQ. I see. I see. So you already skipped that IV- Yep ... yeah, part. All right, very good. Awesome. Thank you so much. Right. Yeah. This was great. Thank you. Thank you. Appreciate it. Exciting year ahead. Yeah.