Good morning, everyone. I am very happy to be here with the management team of Climb Bio. Thank you for joining us on the last day of the Morgan Stanley 24th Annual Global Healthcare Conference. I am joined by CEO Aoife Brennan, CFO Susan Altschuller, and Chief Business Officer Perrin Wilson. Thank you to the three of you for joining us. I am just going to read a quick disclaimer. Please visit morganstanley.com/researchdisclosures for our research disclaimers. Let us jump right in. To begin, maybe Aoife, you can start. Just give us a brief overview of how you are thinking about the opportunity across your two lead programs, CLYM116 and budoprutug. Yeah. For those of you new to the Climb story, Climb was really founded around the thesis that there was a lot of unmet need in B-cell mediated diseases that were validated targets that had not been fully exploited. When we started the company, we set about finding best-in-class assets against validated targets where there was potential to really address an unmet need in a large commercial opportunity. I think the two assets that we have acquired or in-licensed since starting the company really kind of support what we are doing along that axis. The first product that we in-licensed was called budoprutug. It is an anti-CD19 monoclonal antibody that depletes B cells. Then the second asset is called CLYM116. It is an APRIL monoclonal, and we have just recently showed data demonstrating a best-in-class PK/PD profile for that asset as well. I know we will get more into it as the chat continues. But a really exciting time with two very interesting assets where I think the thesis has only strengthened over the past year and a half. So we are really enjoying the opportunity to fully exploit both of those assets now in a lot of ongoing clinical trials. We have a kind of a rich data calendar coming up through this year as well as into next year. So a very exciting time for the company. It definitely is. As you mentioned, let us dig into CLYM116, just given the recency of your R&D spotlight and the phase I data you presented at that event. Maybe if you could give us your interpretation of that data set and what was most important for investors to take away. Yeah. So we in-licensed CLYM116 in January 2025, and at the time, the thesis was really around a couple of pillars. Number one was that IgAN was really emerging as a greenfield opportunity for drug development. It was probably a much larger opportunity than anyone appreciated at the time, and it was a place where we thought could be really interesting for a young company to start establishing a beachhead. I think the second component of that thesis was that APRIL was going to be a very effective target within that space, and I think that has proven out with some of the recent readouts that we've seen. Then if you believe part one and two, the real question was, well, how do you develop an asset with the absolute best profile targeting APRIL? There were a lot of monoclonal antibodies available at the time that bound APRIL, but none of them that really got us excited about having a good differentiation profile. But when we dug into the biology a little bit more around APRIL, we realized that there was going to be a ceiling effect for PK around a phenomenon called target-mediated drug disposition. In that context, we thought a molecule that didn't just bind APRIL, but actually induced APRIL degradation, was the only real mechanism that we found that had potential to break through that ceiling. So we in-licensed the asset based on hypothesis without a huge amount of data. We showed some really nice non-human primate data head-to-head with the first-generation molecules. But it was really the clinical data that we shared just a couple of weeks ago that really proved that thesis to be correct in that we were able to exceed what had previously been achieved in terms of half-life. We were able to see really nice, consistent PK curve. We were able to see best-in-class APRIL suppression. So when you think about a validated target and how do you develop the best possible asset against that target, we really fundamentally believe that PK and PD is where it's at, and that demonstrating best-in-class around both of those will lead to a best-in-class clinical and commercial profile in that space. And we firmly believe that CLYM116 has demonstrated in healthy volunteers something that could be a really important competitor product in the IgAN space. So very exciting time. Very exciting data set to put out. As you mentioned, potentially best-in-class APRIL suppression was demonstrated. But maybe go a little bit further in terms of the evidence that deeper APRIL suppression actually translates into better renal outcomes, greater proteinuria reduction, as opposed to just a PK biomarker. Yeah, for sure. I think there are multiple different pillars of differentiation, if you will. A really important one is efficacy. We know that APRIL now has been pretty well validated. We have seen best-in-class proteinuria, best-in kind of disease proteinuria with sibeprenlimab in their phase III. We have seen it is the only asset that has demonstrated improvement in kidney function over two years based on the eGFR curves. What is really going to become important in this space over time is getting everyone to target. It is not just the average, it is really getting the proportion of patients to target. When we look at the available data set, it is very clear to us that what drives that patient getting to target is full APRIL suppression through the dosing interval. If you look at the sibeprenlimab phase II data that was published in The New England Journal of Medicine, you can clearly see that as dose increases there, you are seeing kind of complete abrogation of APRIL signaling, less breakthrough at the end of the dosing interval, and a higher proportion of patients getting to target. When you think about this disease, it is really a disease that has its first onset in relatively young individuals, so in individuals often in their teens, twenties, early thirties. Preserving their kidneys for 10 years is great, but what you really want is for them to die with their own functioning kidneys, right? It is really about how do you get patients to preserve kidney function over not just 10 years, but it is like a 40-year, 60-year horizon. The way to do that, based on what we know today, is to get the proteinuria to target, to get their eGFR completely stabilized, and to do it in a way with a product presentation that they are going to continue to take. So there is where efficacy and treatment burden become really important. This is a product, if what we have seen in healthy volunteers bears out in patients, that will be given Q12 weekly in an at-home auto-injector format that is super easy and convenient to use, that achieves best-in-class APRIL and proteinuria suppression, and that I think gives young patients the best chance of preserving their kidneys for their kind of natural life based on everything that we know today. So that is really what drives us in developing this product. I think what we have seen so far kind of gives us good evidence that we can achieve that goal. Great. Maybe one for you, Susan. One of the more interesting elements of CLYM116 is the sweeper mechanism that you're pursuing. The antibody's designed to facilitate degradation of APRIL rather than just simply bind it. Can you explain why that matters clinically? Yeah, I think Aoife touched on this with the target-mediated drug disposition. The sweeper technology, as we call it's the technology that I was most familiar with from Soliris to Ultomiris, and it's pH-dependent binding to APRIL. Versus all the first-generation agents or other agents in the space, sweeper is different. High-affinity binding extracellularly, it's internalized in the neutral pH, the APRIL is released, degraded, and the antibody is recycled via FcRn. You can't compare potency to any other molecules because it's high affinity, low affinity internally to actually facilitate that degradation, and we think that is what has overcome this steep decline in drug concentration of the other programs, and that leads to the steep acceleration of APRIL rebounding back to normal. Okay. That's helpful context. Aoife mentioned that you're going to look at every 12-week dosing and maybe, Perrin, when you think about that commercially, what's the importance of that from a differentiation perspective versus some of the other programs? Yeah, I think what Aoife touched on are two elements of the IgAN market that are important. I think patients are diagnosed early in life, some adolescent age, others busy professional-age individuals, and they are going to need to be treated chronically through their lifetime. Once you take the breaks off APRIL will come back, and your disease will come back. We think about every 12 weeks as really fitting into the lifestyle of those patients. It's a much less frequent burden of dosing relative to the first generations, which are either 12 injections a year or 52 injections a year. This would be four. It also fits nicely in the routine of patients seeing their clinicians, so it triggers that memory of making sure that they take their dose. When we think about the need to get as many patients to target as possible, keeping patients on drug is going to be critically important. What we have heard from both physicians and patients themselves is that is a very attractive dosing profile for this disease, which we also remember is asymptomatic. Patients don't wake up and feel that they have IgAN. It allows them this also treatment-free interval where they're not feeling like a patient, which we think from a value proposition is also a really important component. That could be a real game changer in the space. Maybe just turning to the phase II study, the NAVIGATE-2, you're evaluating an 800 mg loading dose followed by 400 mg every eight or 12 weeks. Aoife, why did you choose those doses, and how do you think about the dosing strategy? Yeah. We actually, in order to move fast, it's a competitive space, we initiated our phase II and started to set up sites before we'd seen the full data set from the phase I. We designed the study to enroll patients into two dosing regimens, the 800 mg followed by Q8 week and followed by Q12 weeks. We've become more confident now that we've seen the healthy volunteer data and the Q12-week profile, but we think it's going to be really important to confirm that that is the right regimen before initiating a large phase III study. That's what that study is really designed to do, is to confirm some of the modeling that we've seen around PK and PD to confirm that healthy volunteers really do predict what we're going to see in IgAN patients. Based on how validated this mechanism is, when we've shown our phase I data to some of the KOLs and nephrologists, they're like, "Well, just get on already. Just get on with your phase III." We're absolutely moving with speed on the phase III plan, and we'll be doing multiple things in parallel, reading out the phase II study, as well as engaging with regulators in the first half of next year to make sure we're all buttoned up before going to phase III. Kelly, we will be taking a look at when 10 patients are enrolled in each arm. You need probably 24 weeks of data to confirm that you're fully suppressing APRIL over those 12 weeks. But the beauty of that study is the endpoints are 72 weeks, so we'll have updates on the long-term follow-up while we're starting the execution of the pivotal. Susan, what would you think of as a successful outcome for NAVIGATE-2? Is it a particular magnitude of proteinuria reduction you're targeting or- It's really in patients, are you fully covering APRIL suppression over the 12 weeks, and is that translating into IgA and Gd-IgA1 reductions and that there's no statistical significance. Then you can move when it's confirmed in patients. Okay. I want to hit on safety for a moment in the recent data set. So how much can we learn about the chronic safety from healthy volunteer data versus what really needs to be established in patients? Yeah. I think when you think about safety, there's a couple of components. There's tolerability, injection site reactions, and what we're seeing with that, which I think is going to become an important differentiator commercially. There's no reason why patients would be any different to healthy volunteers when it comes to ISRs. Then I think the second component of safety that we think about is hypogammaglobulinemia. That's particularly been an issue with the past APRIL class. It's something that we hear a lot from prescribers of like make sure that we're not causing risk of infections. I think that's something that we can learn. Obviously, one dose is going to be different to somebody taking this chronically. But you can get an indication of your IgG change from baseline in healthy volunteers. Then there's the unknown unknowns. Like any drug, there are things that may pop up that you just can't de-risk with a short-term study. But the beauty is we'll be following the phase II. As Susan mentioned, we have this early look at 10 per arm at 24 weeks. Our plan is to enroll 30 per arm and to continue to follow those patients, and those patients will contribute to our understanding of safety when combined ultimately with the phase III. So those patients will have potential to be on product for a lot longer than the phase III patients. Like any product, we look at the totality of evidence across both of those data sets to make sure there are no kind of unknown unknowns. There's no reason why there would. We kind of understand, I think, the APRIL class pretty well based on the sibeprenlimab safety data. Like any prudent product, we have to always kind of maintain an open mind around new safety issues that come up. One nuance I would say, because we're APRIL only with CLYM116, not APRIL-BAFF, as Aoife talked about the hypogamma and also infection risk. But sibeprenlimab actually targets a different epitope on APRIL than we do with CLYM116. We've shown at ASN in 2025 that we do not form the high molecular weight complexes that they form because of the epitope that they target. Just wanted to clarify that. I think that's a good segue into the competitive environment you guys are in, because IgAN has, as you would admit, has become a pretty competitive area. We now have approved and late-stage approaches targeting APRIL, BAFF-APRIL, endothelin, complement, and some other pathways. Maybe, Perrin, you can tackle this one, how you think about the ultimate treatment paradigm in IgAN and will it be sequential therapies, will it be combos? How do you see this playing out? Yeah. Just to take a step back, I think IgAN is really an emerging market. I think it's only recently where physicians have actually had approved products other than ACEs and ARBs for their patients. I think we're at the very beginning stages. I think the KDIGO guidelines in 2025, when they came out, were a great shift and really put in place a measure for really biopsying as many patients as possible, which is going to increase diagnosis rates. Really moving to aggressive treatment targets, lowering the bar from that 0.5 proteinuria down to 0.3. I think that will increase treatment. Then also they put out a combination approach where a patient should be on a disease-modifying agent like an anti-APRIL as well as on nephron-protecting agent. I think ultimately we will move to more of a combination-type approach, but I think it will be slow stages. But I think the early uptake that we've seen with sibeprenlimab really shows how physicians are willing and patients are willing to embrace a disease-modifying agent. Then I think coming out next, once some of our friends at big organizations have really started to build that marketplace, people really well understand APRIL biology now, and coming out with a best-in-class agent is really going to aim and allow us to hit the ground running. I think for us now, we're focused on what are those commercial and presentation aspects that are going to be critically important as we enter the market as a small company. I think there is room within IgAN. I think when we were looking at it was a $10 billion marketplace, now might be up to $20 billion. So there's a recognition there. A lot of patients, a lot of unmet need, and now it's really how to define and win. And then, more specifically within the APRIL class, how do you think about positioning CLYM116 versus sibeprenlimab, atacicept, povetacicept, or any other late-stage programs you are kind of directly benchmarking to? Yeah. I think at this point, APRIL has been clinically validated. We know that targeting APRIL allows you to control proteinuria. It allows you to stabilize the eGFR. So I think it goes back to what Aoife mentioned earlier, is getting those patients to target. And I think that is going to be something that we look at within our studies. I think the every 12-week dosing is a real step forward compared to the first generation. And then presentation and ease of an auto-injector, painless, easy to administer for patients themselves or for perhaps a caregiver who is taking care of an adolescent patient. I think aspects like that about the product are going to be critically important, and we are already taking those into our calculations as we plan for both the phase III and the launch. Now, the other thing I would add to that, Kelly, is probably a nerdy comment, but the APRIL versus BAFF-APRIL, I think, are kind of different. Certainly based on the data that we have seen, there is no contribution of the BAFF component to efficacy. There was kind of this theory early on before we had seen the phase III data set that BAFF was actually doing something that might result in better kidney outcomes over time. It is clear that that is not the case now that we have seen atacicept and sibeprenlimab two-year eGFR data. We know BAFF has its baggage from a safety perspective. We know what happens with belimumab with long-term use, you get cytopenias. So I do think over time that will play out, and it is kind of like contribution of components. If there is nothing really being brought to the table by BAFF, but you are having this potential safety issue, I think that will kind of mean that prescribers reach first for the APRIL-only class. So I think that kind of narrows the field a little bit in addition to what Perrin Wilson just outlined. Okay. Very helpful. Climb licensed the CLYM116 asset from Mabworks, which retains greater China rights for the program. How useful is the parallel development that's occurring in China in terms of accelerating your own learning about the asset? I think it's been a huge strategic advantage to us. IgAN is more prevalent in individuals of Asian extraction. If you look at where the phase III trials have been predominantly enrolled, 60% or so of that phase III population are from Asia. So establishing the site network, the KOL relationships, the regulatory path, we already now have parallel phase I's ongoing in China as well as outside of China. We're really moving in lockstep with our partner here to move as quickly as possible with the biggest and broadest data set that supports a global reach for this asset, because we do think it can be very important for patients as well as important commercially. I think being able to move, and I credit the team with establishing that very good working relationship such that we're really moving in lockstep every step of the way, because I think ultimately that will speed our time to the biggest potential pool of patients and the biggest clinical impact that we can have. It's been very important for us strategically to have that good working relationship. It's not necessarily just two independent silos. We really are working collaboratively together and aligning on each step of the way. When you think about the broader CLYM116 opportunity, if it's successful in IgAN, how do you see the opportunity in other APRIL-mediated diseases? Will you go beyond IgAN, or are you focused there? Well, it's a real emerging area of biology. Understanding the role APRIL plays in numerous B-cell mediated diseases, I think, is definitely an emerging space. We're watching carefully. There are a couple of phase II studies ongoing with the first-generation APRIL inhibitors that we learn a lot from that I think will read out in the next 12 months or so here. But certainly the obvious other one, just based on the biology, is Sjögren's disease. There is a study ongoing there in that. I think there's broad potential across both rare and more common rheumatological diseases, and obviously with a best-in-class profile, I think we're in pole position to exploit some of those opportunities as they come up. Certainly an area of ongoing effort within the company to think about the life cycle management and what's there beyond IgA nephropathy. Okay, great. I'm going to switch gears to budoprutug. We'll save some time for that asset. Can you remind us, Aoife, what differentiates targeting CD19 with budoprutug from conventional CD20-directed B-cell depletion? Yeah. CD19 is a super exciting space. We know that CD19 has much broader expression across the life cycle of B-cells, so it starts being expressed earlier in B-cell development, and then it continues to be expressed on the peripherally circulating plasma cells that are actually producing the antibodies. There's been a lot of kind of precedent around CD19 working in indications where CD20 has failed or in patients who have failed CD20. So a really exciting asset. To be able to deplete B-cells with a naked monoclonal, we think has great scalability across patient populations where we're able to avoid some of the CRS ICANS that have been associated with cell therapies. I think recently we've seen a number of kind of bad outcomes and tragedies in the CAR T space in patients with rheumatological diseases. We think CD19, particularly in the context of a monoclonal antibody that can really be administered in care centers, not reliant on those tertiary centers, is going to be really important commercially. We're evaluating it in three different indications now, where MN is our lead indication, which is another rare renal disease, where we'll have some data upcoming at the Kidney Week. And then we'll also have ongoing studies in ITP and SLE. Again, will be data readouts from both of those studies later this year as well. So another very exciting asset. There's kind of a theme coming across, I think, our pipeline with a lead in renal, but then maybe expanding beyond renal where the biology and the commercial opportunity makes sense, and budoprutug absolutely fits that pattern. You bring up a very good point, which is some of the safety concerns that have emerged and actually resulted in trial pauses at Novartis and Bristol Myers Squibb. How does that just affect your overall thesis around CD19. I think what's really important too, there's two different mechanisms you can use to deplete B-cells. Number one is the T-cell based killing or the NK based killing. T-cell based killing or the CAR- T, the T-cell engagers, they're really engaging a mechanism that's prone to a lot of cytokine release. It's aggressive. It results in more rapid B-cell depletion. Makes perfect sense in the context of oncology, where you've a rapidly dividing clone, you really need to hit it very, very hard. I think the question is always, well, that benefit-risk, does that make sense in the context of an autoimmune disease where you don't have that clonal expansion? You can more gradually deplete B cells with the NK cell-based mechanism. It's a very different paradigm. It's the same way that obinutuzumab depletes CD20 cells. We can understand the safety profile. Prescribers are comfortable giving these monoclonals in their clinic, in a chair, in their infusion centers. I think you're looking at a very different risk-benefit profile. You're looking at a very different commercial opportunity. You've the potential to be used earlier lines of therapy compared to maybe something like a CAR- T, where I think there will continue to be a place, but it will be in a small group of patients with very aggressive disease. I think an antibody-based approach has potential to be used in much broader diseases and settings. I think very exciting to have one of two CD19 monoclonal antibodies that are in development, and I think a lot of opportunity for budoprutug. To reference your indications of focus as ITP, MN, and SLE. The early ITP data you presented this summer came from a very heavily pretreated population. How do you think about the strength of the signal that you put out in that data? Yeah, I was kind of joking that we had enrolled patients who had more lines of prior therapy than they had platelets at baseline. It is pretty difficult for these patients, right? They have gone through, some of them were like 10 prior lines of therapy and still have incredibly low platelet counts. They have kind of exhausted everything that is available. It is a great test bed for can your product work in patients who are really out of options for everything else? We showed really nice platelet responses in those patients. Traditionally, those patients have achieved a durable response of in the teens or 20s. We were able to see really nice platelet response in those patients. It is also the commercial opportunity in ITP is those third-line patients. We believe that there is around 15,000-20,000 patients just like that in the U.S. We will continue to share some data about that. A question we often get is, "Well, can you move up the lines of therapy, go to second line and first line?" I think that is something that we are actively thinking about and working with KOLs. Obviously, it all depends on what we see in this third line. If we see something very exciting in third-line patients where we are able to get durable responses, where you are almost achieving that kind of a defined course of therapy, then patients are able to spend six months, a year without any therapy with good platelet counts, I think that could be a very exciting proposition for moving up the lines of therapy. But all to come, the next step, I think, is showing more data later this year, then we will continue to build on the program from there. That is great. Perrin, you have got data across all three indications coming later this year, as Aoife mentioned. If the data are positive across more than one indication, how do you think about the best registrational path for budoprutug? Yeah, I think, just to start, we have chosen indications where there is a really strong biologic rationale for CD19, and that is true across MN with our study that we had, prior sponsor had completed showing compelling proof of concept in that indication. ITP had a very compelling rationale for CD19, and of course, in SLE, we have seen the evidence from the CAR- T and TCE approaches. I think for us, thinking about the profile that best fits what the need is for physicians and patients. We will make very data-driven decisions as we look at the data across all of these studies. MN and ITP are both indications where, as a small company, we could very actively move forward into phase III, about 150, 180 patients in a phase III study. So very doable from a small company perspective, and both indications, as Aoife highlighted, have very high unmet needs, MN, no approved therapies. Obinutuzumab is just the first therapy to file for an approval in this indication, and patients have very severe nephrotic syndrome and are going to require treatment to get to disease control, or they're going to progress to kidney failure. I think on ITP, as we've highlighted, this third-line patient population, incredibly high unmet need, and the existing therapies today are really only getting about 20% of patients to a durable response. So I think we will make decisions based on the commercial need, hitting our TPPs, which we're holding ourselves to high bars, and then ensuring that we can move forward actively as a small company and rapidly develop and get these products to market. Maybe one last question on budoprutug for Perrin Wilson. How important could the subcutaneous administration be for that drug? Yeah, I think that's something that we've spent a lot of time over the last six to nine months, and we'll continue to spend time talking to patients and physicians about what's going to best position budoprutug and what's most attractive from a treatment perspective. I think there's always different schools of patients. Some do prefer an IV and getting that therapy in office. I think the sub-Q, there's two possible bookends. I think we look at the CD20 market as an analog. You have sort of an Ocrevus-like, which is a larger injection at the frequency of an IV, versus Kesimpta, which is really injections at home, more frequently, lower dose. So I think we're evaluating both of those options. We're going to be triggering a study in patients to really understand the PK/PD in patients with a sub-Q administration. But I think we have the possibility to appeal to a patient group with a sub-Q that perhaps wouldn't have chosen an IV. So I think it gives us a lot of optionality in our development program. That's great. Susan, one for you. You now have these two assets that potentially support development across multiple large immune-mediated diseases. How do you organizationally prevent the company from spreading itself too thin, and how do you think of managing costs across the two programs going forward? Great question. We ended Q2 with $239 million. We raised $110 million PIPE at the end of April in order to be able to move with speed. That runway gets us into the second half of 2028, inclusive of all the CMC and pivotal costs associated with a go-forward of CLYM116 in IgAN and budoprutug in pMN. So strong balance sheet there. But as we talked about earlier, lupus is something that pMN, ITP, and IgAN are wholly within our capability and wheelhouse as Climb to execute and deliver on. Something like lupus, we'd be looking to have for a partner because that's just a totally different commercial and development story. Okay, great. Maybe just last word from Aoife. If you can think about the setup into year-end, it's going to be an eventful one. But what are you looking forward to most? What do you want to leave investors with as sort of the next 12 months? What's going to be exciting for Climb? Yeah, I think there's lots of data and updates that will come when I look across the kind of calendar, even looking into next year. There's going to be a lot of clinical data, and that's always kind of the best time, right, as a drug developer, getting that clinical data, evaluating next steps. Was your thesis correct? Do you need to adjust your thesis? It's always an incredibly fun and dynamic time. So, I think it's a really great time to start getting to know Climb as a company and putting time into really understanding some of the programs because a lot of news flow coming up from us. So watch this space. We will stay tuned. We are excited for your budoprutug data later this year and other data updates that are coming. Thank you for joining us. Thanks for making the time, and we will stay tuned for the Climb story. Thank you, Kelly. Great. Thanks for coming.