Good morning, everyone. Thank you for joining the 24th Annual Needham Healthcare Conference. My name is Joey Stringer, and I'm one of the biotech analysts at Needham & Company. It's my pleasure to introduce our next presenting company, Climb Bio. Joining us today from the company is CEO Aoife Brennan and CFO Brett Kaplan. For those of you joining on the webcast, if you would like to ask a question, please do so at any time. You can submit a question using the chat box feature at the bottom of your screen. With that, we'll get started. I'll turn it over to Aoife and Brett for the presentation. Great. Thanks so much, Joey, and thanks for the Needham team for inviting us here. A couple of slides we'll go through and then have some time for Q&A at the end. Just before we kick into the formal presentation, I want to make the usual reminders that I will be making some forward-looking statements and that you should review our recent filings with the FSCC for a full list of our risk factors. Climb Bio was really formed around the concept of being able to do something new and different for the one in seven Americans that have immune-mediated diseases. We're really compelled by the unmet need here. There's an increasing prevalence globally of these immunological diseases. What we found was that a lot of the treatments either that are available or that are in development are really working downstream, addressing some of the symptoms and consequences. We felt there was a real opportunity to do something different for patients by tackling really the immune drivers of these diseases and allow patients to have much improved outcomes. That has been our kind of mission statement from day one here, and we're making great progress on realizing some of those ambitions. This snapshot will just give you some of the kind of key takeaway points. I'll share some more data behind each one of these as we go through the presentation today. We're very focused on immune-mediated diseases and our commitment to developing better treatments for patients. Most of our, both of our products that are in development have broad potential and have potential to address multiple diseases with a single investigational product as potential across a broad range of diseases. We believe these represent in totality a very meaningful commercial opportunity because of the current prevalence of immune-mediated diseases, as well as the likely continued increase in prevalence of some of these diseases. In today's world, we're very fortunate to be well-funded through multiple upcoming catalysts. Our cash runway is currently projected to fund the company and all of our operations through 2027. Since the company got going about a year ago, we've really built a very experienced team that have a track record of identifying and developing best-in-class assets, particularly in the I&I space. This is just a snapshot of the team and our board of directors with a lot of very accomplished and experienced biotech executives here. This is our pipeline. You'll see that we have two products. Budo, which is our lead product, budoprutug, is being developed as both an IV as well as a subcutaneous formulation. We have initially targeted three indications for the IV formulation. I'll tell you a little bit about each one of those as we go through the deck. Importantly, we have worldwide rights to develop and commercialize Budo, both the subcu and the IV. A very exciting opportunity here across a broad range of diseases. Our second asset that we just in-licensed earlier this year is an anti-APRIL MAB called CLYM116. I'll tell you a little bit about that as well as the deal later in today's presentation. As I mentioned earlier, one of the really compelling things about these assets is because they work very much upstream in addressing some of these diseases, they have potential across multiple indications ranging from ultra-rare to very common. For both Budo and April, they're really addressing B-cell-mediated diseases. Both target different mechanisms in terms of B-cell maturation, development, and function, but have potential to treat a broad range of diseases. You can see today the indications that we're currently working on in totality address about 500,000 patients living in the U.S., but have potential to expand as part of our lifecycle management and ongoing development into a much broader range of diseases. If we see an opportunity where we can really be differentiated and do something for patients, we have potential to pursue a much broader opportunity set with both of these assets. Just to turn to Budo, which is our lead program for a moment, this is a graphic that's very familiar to a lot of people who follow the B-cell space. It really just gives you a cartoon of how B-cells mature through development to the plasma cell, which is responsible for secreting autoantibodies. You'll see here that there are a number of different targets that could be pursued if you're addressing B-cell-mediated diseases. We believe that CD19 is the best in terms of its expression profile across the B-cell lineage. If you can see compared to CD20 or CD38, it really is the ideal profile in that it's expressed from very early stages, the pro-B cell, the very first step of development into a mature B-cell. It's expressed all the way through the peripherally circulating plasma cells. It spares the long-lived plasma cell in the bone marrow, which is really important for maintaining protective immunity. It really has that kind of Goldilocks expression profile, if you will, addressing all of the cells you would want to and preserving the humoral immunity where the plasma cell is responsible. We believe there are a lot of modalities that are pursuing CD19, but Budo is actually only the second monoclonal that is in development for immune indications, the first one being anebulizumab. We believe that monoclonals have a real advantage over other modalities targeting CD19 in that it is a well-established and validated modality. We know how to make and deliver MABs very well now. As a class, they have 40 years of experience in terms of being used clinically. We believe the high targeting and specificity of a MAB is very important, and it can achieve deep tissue penetration. Unlike other modalities, there is not a known risk of cytokine release in ICAMs. There is no lymphodepletion required. It can really fit within the current kind of therapeutic landscape without a lot of re-engineering how therapeutics are delivered. Because it is a MAB, we have the potential to redose, which is very challenging to do with cell therapies. With the MAB, if a patient has an initial good response but loses that response after a year, 18 months, they can come back in and have a second course of treatment. That is not a huge hurdle. That currently occurs with many MABs that are used commercially. We really do think that CD19 is the best target for B-cells, and then a monoclonal antibody is a really good modality for addressing that target. This is just a cartoon graphic of our antibody, our Budo. It has been differentiated in a number of very important ways. The first one is that it binds CD19 with very high affinity, much higher affinity compared to the other MABs that are ahead in development. We have 18 picomolar affinity here to CD19. That gives us potential to have much better B-cell depletion at lower doses relative to other lower affinity MABs in development. The second important component is that it has this ADCC enhancement that really increases the ability of NK cells to kill those B-cells once they've been bound to Budo. We have about 100% greater potency compared to a wild-type IgG1. This is really important to drive deep and durable B-cell depletion. We have some early evidence to show that we could do just that in humans that I'll show you in a moment. Finally, nobody has a subcutaneous formulation for a CD19 MAB. We've been very successful in formulating to high concentrations with low viscosity. We have a formulation that's currently in non-clinical development at 175 mg/mL. If the non-clinical continues to look good, we plan to move that forward into the clinic later this year. A really exciting asset, I think, for us to continue to develop and move forward. As we thought about this broad potential for CD19 depletion, we categorized our opportunities into three different buckets. Each of them has different profiles. The first being the IgG4-mediated diseases. PMN is a really good example of an IgG4-mediated disease. We believe that the biology there is very conducive to CD19 as the best target, and we have potential for immune reset in these patients with an IgG4-mediated disease. The second bucket is the single organ diseases where we have a monoclonal antibody targeting a single organ. ITP is a really good example of that where you have destruction of your platelets from a platelet antibody-driven disease. The final bucket is what we call complex systemic. These diseases are more complex from a biology perspective, from a development perspective, but represent a really large opportunity if you can do something different for these patients. Even with recent advances, patients with SLE continue to suffer from very poor outcomes. Being able to do something that's differentiated for those patients could be very important and an important opportunity for Budo. I'll tell you in a moment how we're pursuing each of these different buckets of opportunity. You can see here that within each one of these, there's substantial commercial opportunity. PMN, the dark circles are the indications that we have where we have ongoing studies. PMN is about 70,000 patients in the U.S. alone. There are a number of other diseases that also fit there. ITP also has a substantial opportunity. SLE, of course, is probably the most common disease that we're currently pursuing with about 250,000 patients in the U.S. on current active treatment for SLE. Initially, just to touch on PMN, which is our lead indication, it's a rare renal disease. These patients usually present with proteinuria and some of the other consequences of proteinuria. Diagnosis is on the basis of these antibody levels called anti-PLA2R antibodies, which are elevated in the majority of patients who have PMN. There really isn't a lot of approved therapies. There's no approved therapy, in fact. A lot of the therapies that are outlined in the current treatment guidance are actually used off-label. There is a tremendous opportunity to help these patients and do something different, particularly for the 20%-40% of patients in the US that are refractory to currently available lines of therapy and really have no good treatment opportunity. We are very motivated to do something different for these patients. We have some early data from PMN. When we acquired this asset, it already had a data set in PMN. There was a phase I-B study that was conducted in patients with PMN. Most of them had failed currently available therapy. We dosed eight patients at two different dose levels, 100 mg and 200 mg. They received just four injections over the course of about six months or so. We were able to follow these patients over time to look at what were the outcomes in terms of their renal responses and their underlying disease. We saw something very, very interesting that we'll outline on the next slide. You can see here not only were these relatively low doses able to deplete B-cells throughout the dosing interval and out to 48 weeks in the majority of patients here, but we saw this really nice decline in the pathogenic antibodies, which are these PLA2R antibody levels that lagged a little bit. First, the B-cells came down, then the PLA2R antibodies came down. Over about the first year, we saw a really nice improvement in proteinuria in these patients where for 60%, they actually got to the threshold of a complete remission by 48 weeks. There was another patient that just missed that threshold. You can see really very nice responses here that are much greater than the responses that have traditionally been seen with rituximab when it is used off-label in this indication. Usually, you expect only about 14%-20% of patients to get to this complete response level at one year following rituximab. This looked like a really strong early signal that we were doing something that was addressing an unmet need, but also that was differentiated from current therapy. We were very interested in these data and moving forward now with another phase II study in this indication. You can see here a safety profile that was very similar to other MABs. We had no dose-limiting toxicities. We had a number of SAEs, but none were considered related to the investigational product. Importantly, we did not observe any cytokine response or ICAMs in this study. These were patients that were able to kind of go about their business once the infusion was complete, which I think is a very big advantage for a MAB-based treatment. Next steps here is we have just announced that we are starting a dose range finding study, a larger phase II trial in patients with PMN. We are very excited to continue to advance this program into late phase development. The second category that we think about are these single organ IgG1 - 3 mediated diseases, ITP being a great example. There are about 85,000 adults in the U.S. today with ITP, and about 24,000 of them are refractory to currently available therapy. While there are a lot of therapies that have been developed for ITP, there's still a big proportion of patients that go through this kind of they rotate through multiple lines of therapies, but still have refractory disease with low platelet counts and debilitating fatigue. A big unmet need and a substantial commercial opportunity here also. This is the data that kind of gives us reason to believe that we could be able to do something different in these patients. As I mentioned earlier, rituximab is frequently used. If rituximab fails, these patients often go on to have splenectomy. We're able to get some tissue from these patients. You can see that rituximab does a good job, but it leaves behind the CD20, CD19 positive B-cells that continue to produce the pathogenic antibody. We believe that a lot of the reason that these rituximab patients fail or do not actually achieve durable remission following rituximab is because the rituximab leaves behind these CD19 positive cells. Coming along with the CD19 targeted depleter may give these patients a good chance of a durable remission. We're about to do a study to test this hypothesis. This is the design of our phase I-B2a trial in ITP. We're enrolling patients who have had a sufficient response to one prior therapy but have lost that response and have a continued persistent low platelet count. We plan to evaluate three different dose levels and to follow these patients to find out what happens to their B-cells, their antibody levels, and their platelet counts over time. We are really excited to start seeing accruing some data in ITP with the CD19 depleter. Finally, SLE, our complex systemic disease indication. There are about 250,000 patients with lupus in the U.S. alone. A number of therapies are used, belimumab. Rituximab is often used off-label. Despite these, a good proportion of patients continue to be refractory, dependent on chronic steroids with very poor outcomes. Doing something different is very important, I think, for these SLE patients who are refractory. We are inspired by the current B-cell therapies that have really shown promise. If you look across all of the different categories of agents that have been evaluated in SLE, what you'll see is, for the most part, the B-cell targeted agents tend to have the better response rates. If you look across obinutuzumab or belimumab, you see some good responses. Our thesis is that CD19, because of its expression profile, will actually surpass all of these B-cell targeted therapies in terms of its impact on the disease outcomes in SLE. We're doing a study that will evaluate that and test that hypothesis currently. This is some beautiful data from the CAR-T work that's been done in these patients. Obviously, CAR-T is a very high burden treatment, but you can see the results are really beautiful for CD19 targeted CAR-T with almost a complete remission in all patients that have in this small cohort that was published in the New England Journal. You can see that these kind of pre-post SLEDAI disease activity scores really very, very interesting. On the bottom, you can see the biomarkers that were associated with that very dramatic response. These are some of the same biomarkers we're planning to follow in our study. While these data are beautiful, we fundamentally believe that CAR-T therapy is always going to be limited to those very refractory patients at specialist referral centers. If we can achieve something similar to this with the MAB, it would really broaden access for patients because we do not have those barriers of complexity and cost that we are dealing with with the CAR-T administration regimen. This is just a cartoon of the study that we are doing in SLE currently, starting at low doses and then escalating up in these patients to evaluate some of those biomarkers as well as look at disease response by following their SLEDAI scores. This is just a summary of Budo. A lot going on, but I think very exciting times in terms of some of the studies that we are initiating this year and where we will have subsequently some very interesting data. Now, just to turn to our second asset, which is CLIMB-116. This is what is called a sweeper antibody. It's the only sweeper in development for APRIL or the BAFF-APRIL pathway. Sweepers have this ability to both bind the ligand, to bind APRIL, but also to degrade it when it's taken, when it circulates through the cell into the lysosome, which is a very important component that I think gives us a good opportunity to do something really different with this asset. It also has this Fc-engineered increased half-life that we think could be important in terms of achieving our goal, which is to develop a best-in-class APRIL asset that allows patients to have a very good tolerability profile with very infrequent dosing and a very good potency. This is just a cartoon that shows how that sweeper kind of mechanism works. You can see, just like a regular antibody, it binds APRIL with very high affinity in the circulation where the pH is neutral, about 7.4. Once the APRIL bound to the antibody is engulfed in the endosome as part of the endothelial cell, what happens is APRIL actually separates from the antibody. The APRIL can get shuttled to the lysosome for degradation, and the antibody gets recycled back to the surface. These MABs have very high levels of free antibody in circulation and very low levels of the ligand because they cause this degradation of APRIL. That is really a unique feature of this antibody. We have not found another antibody in development targeting APRIL or the BAFF-APRIL pathway that does this. We think it could be very exciting in this space for patients and to be able to do something different for them. We have some early data that demonstrates that differentiation in vitro and in mice that really shows, compared to some of the antibodies that are ahead in development, how this binding mechanism works and how it results in much lower free APRIL concentrations. The next step for this program will be to evaluate in a non-human primate some head studies, and we'll have data later this year. IgA nephropathy is a familiar indication. We think it's a growing market opportunity where an asset that's able to allow a high proportion of patients to achieve their target in terms of urinary protein excretion, and that's dosed infrequently with a good safety profile, could really get a substantial market share of this large and growing opportunity. In summary, we're making great progress with our second program as well. We licensed it earlier this year. It's currently in IND-enabling studies, and we'll be providing additional updates as we go forward in 2025. Maybe I'll hand over to Brett now to talk you through some of our upcoming catalysts and our financial foundation. Thanks, Aoife. Just to summarize where we are from a financial perspective, we're uniquely positioned in that we are well-funded. We had $212 million as of December. This funds us through 2027 and allows us to achieve multiple catalysts. For this year, really a year of execution. Lots going on here at Climb with our two assets. We'll initiate our SLE study with our first patient in the first half, as well as the ITP study is on a similar timeframe. An important asset of ours is our subcutaneous program, and we'll have non-clinical data in the first half and advancing that into clinical studies later this year. We'll advance our PMN program into the phase II studies. Finally, we will initiate, as I mentioned, the subcutaneous program phase one. With respect to 116, we will share in the second half benchmark competitive data from our preclinical non-human primate ongoing studies and look forward to sharing those with you. In summary, very well positioned from a cash perspective and looking forward to continuing the year of execution here. Great. That is our form of presentation, Joey. Happy to answer any questions that you have or anything you'd like to dig deeper into. Fantastic. Thank you, Aoife and Brett, for the excellent presentation. We'll jump right into Q&A. Once again, you can ask a question anonymously using the chat box at the bottom of your screen. A few for me to start off with, Brett and Aoife, if you don't mind. I guess for the phase II PMN trial, can you, the planned trial, can you highlight any key differences in the patient demographics or characteristics relative to the phase I-B in terms of UPCR in particular? It looked like you'd be potentially enrolling more severe patients, if I caught that right, based on UPCR. What's the potential impact there? I guess on some of the key secondaries for that phase II readout, remission rates, you mentioned that you saw 60% complete remission in the phase I-B and I think 100% partial. Just given that data, how should we think about expectations or potentially bar for success on the remission endpoint in the planned phase II? Yeah, two great questions, Joey. The current regulatory path for PMN is that you can achieve full approval based on a complete remission rate if you enroll a nephrotic population at baseline. Unlike a lot of investors who follow the kidney space, you will be familiar with IgA nephropathy, where it is accelerated approval for proteinuria, and you have to follow patients to have stabilization of glomerular filtration rate over time, which is challenging, right? Because keeping patients on study to get those GFR endpoints is often very challenging from an execution perspective. We have the advantage here of being able to get full approval on the basis of the proteinuria endpoint, assuming we enroll patients with bad disease at baseline and nephrotic range proteinuria. That is how the current regulatory piece is set up. If you enroll patients with sub-nephrotic proteinuria, you may have to follow them for eEGFR endpoints over time. That's kind of the trade-off in deciding who you're going to enroll in your phase III study. We have the benefit of being able to review programs that have already gone into phase III and gone through the negotiation with FDA and follow kind of how they've managed to navigate that space. We believe that while we had actually a good cross-section of patients in the phase I-B in terms of their baseline proteinuria, as we move into phase II, we want to move closer to that eventual phase III population so that we're able to determine, is there an impact on exposure in the patients who have higher proteinuria compared to those who have lower and answer some of these really important questions that will allow us to choose the absolute optimal dose to take into phase III testing. That's a really important component of the design here. We'll be able to enroll patients with nephrotic as well as some sub-nephrotic patients to help us from a just getting the study done perspective and in a timely manner to achieve our enrollment goals. There'll be, we've limited the number of patients who can come in on the sub-nephrotic range, which is the urinary protein between two and two to five. We will make sure that we have enough patients in the kind of higher end of the register, if you will,[crosstalk] so that we really understand the impact of proteinuria on some of the important outcomes. That's kind of how we thought about the phase II study as kind of being a stepping stone, if you will, between the data we already have in hand, but also looking forward to what we might need to achieve full approval in a timely manner and not have to mess around with acceleration and trying to follow patients for a subsequent full approval on the eEGFR endpoints. That's kind of how the PMN landscape from a regulatory perspective and how that has informed the study design. To your second question, I think our phase II study is open label, so we'll be able to have data as we go along. Likely the first, the endpoints will fall in sequence, if you will, as like a sequence of dominoes. First one is going to be the B cell levels and looking at what dose gets all patients to the B cell suppression target. After that will come the anti-PLA2R antibody levels. Now, there's a lot of data supporting the importance of anti-PLA2R antibody levels as an endpoint in these PMN patients. It's part of the CADICO guidance in terms of what you need to see for patients to have a good prognosis and outcome on treatment. I do think the anti-PLA2R antibody levels will be very informative in PMN. That would be kind of the second domino to fall, if you will. I think the third domino will be looking at the protein reduction. I think we'll really want to have patients on study for nine months to 12 months because the kidney does take time to heal. It's not something that you see immediately. I think once we have a good number of patients at nine months to 12 months timeframe, we'll be able to start looking at those rates of proteinuria and complete and partial response that I think will be very important for the investment community to think about how we're differentiated, as well as important for us in giving us confidence to move forward with the phase III study, knowing that we can achieve that approvable endpoint, which is the proportion of patients getting to the complete renal response. That is kind of how we thought about the design of the phase II, if that makes sense. Y eah, great. No, very detailed answer and very helpful. I guess my last question is on the subQ program. Can you just remind us what the goal of that program is? Is it essentially same drug, different formulation? Is it just a kind of dosing convenience kind of play here, or are there other factors beyond that subQ version? Yeah, I think there's multiple advantages to the subQ. When you look across other targets in this space, even if you look at the CD20 space, a close relative of ours, and look at how broadly the subcutaneous formulation of the CD20s are used, they actually are one of the few that have gained substantial market share over time. I think that speaks to this element of just choice, of giving prescribers and patients choice around what they—not everyone is set up in a clinic with kind of—when you live in the Boston area, you assume everyone goes to MGH. That's not the reality for the vast majority of clinics. Having something that allows a physician practicing in a solo practice rheumatology clinic to be able to administer a product, I think is very meaningful. It also gives patients choice. I think that's the first element. The second element I think that's really important is thinking about we have a really broad potential opportunity here with CD19. I think it's likely based on the biology that there will be some indications where immune reset is very important and when we can give two IV injections and get long-term durable remission. In those contexts, maybe a subcutaneous formulation is not as impactful as other contexts for patients with bad disease who continue to get recurrence, will continue to receive this product over time. Having a subcutaneous formulation to be able to go where the data is telling you in terms of what might be needed. It gives us then the flexibility to be able to potentially have differential pricing and unlock some of those potential opportunities commercially as well, I think is something that we're working through right now. Certainly having another arrow in the quiver here is important as we see the kind of opportunity set and thinking about how we could target some of those diseases. Great. Aoife and Brett, thank you so much for the excellent presentation and the very informative discussion. Thanks.[crosstalk] Thanks so much, Joey. Thank you, everyone, for joining us on the webcast. Have a good day and a good rest of the conference.