Good afternoon, everybody. Thanks for joining us here on the first day of the Leerink Partners Global Healthcare Conference. My name's Tom Smith, I'm one of the senior biotech analysts here at Leerink, and it's my pleasure to introduce our next company, Climb Bio, and happy to be joined on stage by CEO Aoife Brennan and CFO Susan Altschuller. Thank you both for joining us. Looking forward to the discussion. Aoife, maybe you could kick us off, give a little bit of background for those in the audience who may be less familiar with the Climb story. Walk us through, you know, 2025 important year of execution. 2026, lot of data coming, very excited for the data later this year, but maybe just help set the stage for everybody.
Yes. Yeah, delighted, thanks so much to Leerink for having us and for putting us in a room with AC this year. It's really great to be here. It's becoming a really important event, I think, we're delighted to have an opportunity to tell the story. First off, if you haven't heard of Climb, you're probably not alone because, you know, we're a relatively new and young company. We actually started in business in 2024 as being built within the Eliem Therapeutics ticker, that's kind of how we came about. The real thesis behind the company was that some of the newer modalities had validated or provided more validation around some really important B-cell targets, but that there was more to do from the monoclonal antibody perspective.
Kinda taking almost like a step backwards from the CAR-T and the T cell engager data that was emerging and looking again at monoclonals to see based on the fact that monoclonals are just so much, you have better scalability, better market access criteria, you're thinking again about the monoclonal space in some of these B-cell mediated diseases. We started off with one really important asset, budo, which is a CD19 monoclonal antibody, B-cell depleting antibody, and then we inlicensed our second asset in early 2025.
As Tom alluded to, you know, 25 was very much a year of execution for us, laying the right foundation for both programs, making sure that we had the data, that we had manufacturing, the assays, and the studies set up in the right way, which allows us to now come into 26 with a very rich data year. We will have readouts from both programs. We'll have readouts from all of our studies that are ongoing this year. Really looking forward to an exciting period ahead where we get to turn over some really important data cards that we think will be really interesting and value-creating for investors.
Yep. Awesome. Great. Let's start, kinda high level and just talk about your approach to targeting CD19, why this is a better B-cell depleting approach than targeting CD20 or BCMA or others.
Yes. The CD19 space has different modalities in it, there's a number of modalities focused on CD19. In the antibody-mediated space, there are really only two. There's us and UPLIZNA. CD19 fundamentally is a very interesting target from an I&I perspective because it's expressed in a much broader set of B cells compared to CD20. A lot of our experience with rituximab is based on the CD20 target, which was initially developed in oncology, where it makes perfect sense for CD20 to be the right approach in B-cell malignancies because it's expressed with much greater receptor density on B cells where both CD19 and CD20 are co-expressed. It made a lot of sense that that was the initial path forward.
Now that we're looking at I&I indications, actually the breadth of expression is very important because we're able to target cells from that pro-B cell space to some of the circulating plasma cells in the circulation. We think that targeting that breadth of B cells is going to be very important, both in terms of getting a higher proportion of patients to respond in tackling diseases where CD20 has not been successful, and then in treating patients who've already experienced CD20 and have failed and have recurrence of disease or where they haven't responded at all to CD20. We have evidence that that is truly the case, right? It's not just theoretical basic immunology anymore. We now have clinical data sets, particularly with UPLIZNA, demonstrating that we can address diseases that where CD20 has failed, like myasthenia gravis.
We had a really nice data set from Amgen's MINCH study demonstrating very nice efficacy. They now have approval and are launching that product. Understanding how that performs commercially, I think, will be really important for us. Also importantly in patient populations where the patients have had CD20, haven't respond, and then have gone on to have a very good response to CD19. I think we're beyond the realm of the theoretical now, and we're into the realm of actually being able to underwrite some of that theory with clinical data sets, and we're going to generate some more data supporting that thesis as well.
Awesome. You brought up Amgen's UPLIZNA. Agree with you. Like, I think a lot of eyes are tracking the MG uptake, following the MINT data, but maybe just sort of compare and contrast your product profile versus theirs and your strategy versus Amgen's?
Yeah, Amgen and the UPLIZNA molecule has done a really great job, and we've learned a tremendous amount. Their first indication was NMOSD, and we see that their lifecycle management strategy really is focused on those rare neurological diseases. They have IgG4-RD, they have PMN, all of them very nice placebo-controlled data sets. They've just announced that they're pursuing CIDP. There's kind of a theme here in terms of where they're positioning their monoclonal antibody. You know, our antibody is different molecularly, but I think what's going to be more interesting is thinking about how we develop it. We have now a subcutaneous formulation that gives us an opportunity to really think about diseases where subq may be preferred.
Our initial indications are in disease areas that have not been evaluated with UPLIZNA. There's a tremendous amount of white space in the CD19 monoclonal. We're absolutely targeting diseases and indications where we believe we can be kind of the best in disease profile and do something really meaningful for patients. I think we've plenty of opportunity to do that.
Yep. That's a great segue into the subq data you're generating. I think you've said that's gonna be available in the first half of this year. Maybe just talk about what your bridging strategy is and how important it is for you to get to a viable subq?
Yeah. We had some data showing that we can really concentrate this at high concentrations. We're at 175 mg/mL, which kind of brings subq into an interesting opportunity space. We had some data in non-human primates, really the question that we're aiming to answer with the upcoming dataset is whether we can see B-cell depletion that's consistent with the exposure that we're achieving IV. We're dosing in healthy volunteers lower doses than the full B-cell depletion dose because it's not feasible to completely wipe out B cells in these healthy patients.
We're hoping to see that we can see measurable B-cell depletion, that it's in the range of what we would expect based on our IV experience, and that really demonstrates that we have a feasible path forward when we show those data. I think the next step would be taking it into a patient population at a dose that we expect to fully deplete B cells, and then really providing clarity for investors around where we think that the subq really makes sense from a further development perspective. It's one that people have been watching very closely because of that ability to really unlock new opportunities for the CD19 B-cell space. We're very excited to share that, and that's kind of the first chapter in multiple chapters that we have this year in terms of data readouts.
Yep.
It will kick us off nicely.
Yeah. let's flip over to one of those other chapters, primary membranous nephropathy.
PMN.
I can speak. PMN. You have some data there from kind of historical legacy experience. Maybe just describe the signal that you've seen and maybe like also take a step back and just kind of like frame that opportunity.
Yeah. PMN is one of these really interesting diseases in that it has very high prevalence. It's probably the second biggest immune-mediated glomerular nephropathy behind IgA nephropathy. We estimate there are about 70,000 patients in the U.S. About a third of those patients will have a benign disease course, meaning that they will be very well controlled with ACE or A or Bs. They will sometimes spontaneously remit. We're actually targeting the moderate to severe patient population, so the two-thirds of patients that need immunotherapy, and we can predict who those patients are usually by the degree of proteinuria at baseline and by the level of their antibodies, right? There's established guidance around how to treat these patients, but there is no currently approved therapy.
It's a really interesting space for further development, and I think probably has an underestimated commercial potential because no product has launched into that space. Most of the therapies that are used are used off-label. Very interesting, a priori. We had some early data to show that we could really get nice B-cell depletion, PLA2R, meaning immunological remission in these patients, and we achieved 60% of patients had a complete renal response, meaning their proteinuria fell to less than 0.3 grams per 24 hours. When we acquired the asset, we were able to go back to those sites and investigators and say, "Well, what happened? The study was discontinued. Do you know who you put on the study?
How did they do afterwards after long-term follow-up? We shared some of the data last year at Kidney Week showing that in 3 of the 4 patients where we had data, they required no further immunotherapy over 3 years. It kind of gets to the potential, I think, of CD19 B-cell depletion, particularly in PMN. We had this legacy study. It was kind of abandoned halfway through for various reasons, and when we took over the asset, we decided that we wanted to complete that kind of dose escalation, increase the number of patients, make sure the patients matched the moderate to severe phenotype that we plan to target commercially and in phase 3, and then to really make sure that we were able to complete the dose escalation component. We will have data in the second half of next year.
It will be early data, so we won't have.
This year.
This year. 26th. We won't have 1 year of data even for the first patient enrolled, so it would be relatively early biomarker-based safety, B-cell depletion, PLA2R levels. We'll be able to show trends in proteinuria, but we won't necessarily have the 1-year or 2-year endpoint in terms of CR rate that is important in this patient population.
Yeah. Just remind us of the design of this. It's a dose escalation study, and when we get to the readout in the second half of the year, like, do we have an idea of kind of patient numbers? What's a good readout for you look like in the second half of the year?
Multiples of what we've already shown because I think the reception we get, the data that we inherited, as you characterized it, is really interesting but very small numbers in 5 patients. There can be just, you know, sometimes those small data sets don't necessarily replicate. Replicating in multiples of the 5 we've already shown, and importantly it will be some of the early biomarker data. Those data tend to be more interpretable over a shorter period of follow-up, and then more to come in 2027.
Got it. Okay. Let's turn the page. Another chapter. We have studies ongoing in ITP and SLE. Maybe if we start with ITP and just talk about I guess what you expect the patient population to look like in this particular cohort, like how refractory are these patients and similarly, like, help kinda set expectations for that readout coming later this year.
The, the focus of this initial study is going to be on patients who have ITP, chronic or persistent ITP, who have already failed available therapy. It will be a cross-section of patients, some of whom have received rituximab, some of whom have received TPO, depending on what that patient and physician had kind of sequenced. There's no 1 single sequence that these ITP patients go through. Most of them get steroids initially, what happens after steroid failure is variable depending on patient and physician preference. They will be very treatment experienced. We'll provide their baseline characteristics. Some of them will have received rituximab. Some of them will never have received rituximab, it's going to be very consistent with that kind of 3rd line ITP patient population that has been evaluated by a number of other sponsors.
We look at platelet responses. We look at B cell depletion and look at, you know, what happens around the trajectory of the platelet response. Do we see an increase? Is it maintained over time? I think these are really important endpoints to this patient community. They want something that changes the natural history. They don't want to be cycling through lines of therapy every 3-6 months. I think demonstrating that we can really do something meaningful for these patients with the kind of treatment refractory, let's call them, disease, will be really important for us in terms of determining the next steps.
Yep. objective biomarkers-.
Yes
should give you a very good read on what exactly you're doing. I guess, do we have a sense of number of patients or amount of follow-up?
We are doing 3 different doses, 6 in each cohort, so I think there will be a nice interpretable data set from ITP. It is kind of a drug development nirvana in the placebo rate is low and consistently low in this kind of third line population. Platelet response is the approvable endpoint. Phase 2 generally, you know, translates nicely into phase 3. I think it's gonna be very informative in kind of establishing a go, no go in ITP as a path forward for budoprutug.
Got it. Let's turn to SLE. This one, single dose, a little bit different design. Maybe just talk about, I guess, what you're looking to achieve in SLE and then strategically, like, what, how are we thinking about lupus?
Lupus is a very interesting indication. It's probably one of the more complex B-cell mediated therapy just because of the clinical complexity around all the various manifestations patients can have, as well as immunologically, these patients. Really asking the question, with naked monoclonal, can you achieve the kind of biomarkers of reset that you see with CAR-T and T cell engagers? That's why we did the study. It's not a study that's powered for clinical endpoints. In fact, in these early studies, often the clinical data is difficult to interpret in SLE. Really looking at some of those translational biomarkers and comparing it to what you see in SLE patients with CD19 targeted different modalities is going to be really important for us in terms of seeing next steps. We know that these SLE patients respond to B cell.
You know, the obinutuzumab data was shared in The New England Journal just over the weekend, showing very nice disease control chronically. I think really understanding the path forward in SLE is gonna be very important. Is it going to be episodic or chronic treatment? I think that will really inform what the next steps are.
I guess just building on that, from where you sit, I guess, like, what's the level of confidence or do you think this ends up being more of a chronic therapy, or is there a potential to drive, like, that immune reset, durable drug-free remission that we've seen from cell therapy TCEs?
I think, you know, this is and this is CEO predicting the future, like, this is like one of these, like, major forward-looking statements here. I'm just like, what's gonna happen in the future where we have all these modalities for these autoimmune diseases? My prediction of what's going to happen is within any of these diseases, there's gonna be a proportion of patients that will establish a disease remission for whatever reason. Maybe we get them early enough in their disease course. Maybe they're in the younger end. You know, there's probably biomarkers or predictors that we can develop over time with enough data. Then there will be some patients who need repeat treatment, even in the most intensive regimens of CAR-T, where you're doing full ablation and you're getting them their own cells back.
The proportion in all those indications, I think, is we don't know yet, right? The nice thing about having a monoclonal is it doesn't really matter because patients who opt in to needing repeat dosing can receive that repeat dosing. I mean, that's been established. We can safely chronically deplete B cells. You know, we know that from UPLIZNA and NMOSD. If patient need it, they can come in every six months and get depletion. We even see a world where a patient gets an initial CD19 targeted TCE or CAR-T. They have a good response, the disease comes back very quickly. You know that patient has a very B-cell driven disease phenotype. You know CD19 works in them. Are you gonna give them a CAR-T procedure every six months? Probably not, right?
Even if you post-CAR-T and a patient gets recurrence, that could be a really interesting place to reach for budoprutug. I think that's how the landscape is going to evolve. We'll get better biomarkers to follow patients to predict before a clinical relapse that they need to be redosed. But I think there is a world where there's a sequence, depending on how a patient presents at baseline around some of these CD19s focused approaches. It's certainly not a one size fits all or only one winner type of market in my imaginary future state.
I agree. I don't think it's.
Yeah.
I don't think it's that imaginary. That is also our base expectation.
Yeah.
maybe you could just help us understand kind of like how these chapters are woven together and sort of understand the cadence of these readouts as we get into the second half of the year.
The subq healthy volunteer data for budo, we've said in the first half. Midyear, and we're gonna talk about CLYM116 next, is our APRIL only sweeper antibody, healthy volunteer data. In the second half, we will have initial data from the ITP study of budo, the SLE study of budo, and the PMN study.
Awesome. Okay.
A lot to look forward to.
Yep. A lot of data coming. Okay. Yeah. Let's switch gears and talk about 116, and we in-licensed this last year. Maybe just talk about sort of product attributes, like what drove you towards this as a, like, an optimized half-life extended anti-APRIL. Are there specific aspects to it as we look at this versus some of the other anti-APRIL or APRIL BAFF compounds that are in the clinic?
Yeah. I can talk about kind of the early. It was before Susan Altschuller joined the company. When we looked at the B-cell space, we felt that APRIL and the BAFF-APRILs were very interesting. We set about looking globally at what assets were available. For BAFF-APRIL, our thesis was it had to be better than povetacicept or at least have a good theoretical reason to be better than povetacicept. For the APRIL only, it had to be better for sibeprenlimab. We fundamentally believe that there's the right targets for the BAFF-APRILs. They're the right targets for the APRIL only, and we would have, depending on what was available and where we could get comfort with some of the business terms, pursue development with either asset in indications that we thought it made sense. We found this great asset.
It was in China, very little data available, based on other products that had this sweeper technology, we really thought that it could be interesting and differentiating. We wanted to control the non-human primate study that was done to make sure that before we invested another $1, we had a very good evidence to support what at the time was a theoretical differentiation story. We in-licensed it in January of 2025. I'm getting screwed up on my years. January of 2025, we executed a head-to-head non-human primate study, when we looked at all of the other APRIL assets that had been developed in the BAFF-APRILs, NHP data really does predict nicely what you see in humans. It's kinda like drug development nirvana, where you actually have multiple biomarkers and a translatable animal model.
We thought, "Okay, if the head-to-head, if it really gets separation from a sibeprenlimab at a low dose, this would give us conviction to further invest in the asset and bring it into the clinic." I think what's happened over that time is the interest in APRIL, I think as a target, has increased. The interest in IgAN as a commercial market has increased, and we've put up very nice head-to-head data in NHPs. That was, I think, a day or 2 before you joined the company.
2 days before I joined the NHP study. It was very short. I underwrote joining Climb Bio on budoprutug alone, the NHP data was quite a surprise. When you asked about the differentiation, I really think it's the sweeper mechanism of action. We do have half-life extension, LALA mutation, the sweeper mechanism of action is pH dependent binding to APRIL. Extracellularly, we bind APRIL, it's internalized in the endosome, APRIL's released and degraded, and the antibody's recycled via FcRn. You might have multiple APRIL molecules degraded with one antibody rather than just tightly bound. That's where we think we could get additional potency. Also when we compared in NHPs, we compared to sibeprenlimab, it's 2-3 times the half-life.
We think that in the future treatment paradigm, 4 years from now, being able to dose every 2 months, maybe even 3, with deeper IgA suppression and a good safety profile is going to be very compelling for this patient population.
That makes sense to me. How, you're generating the healthy volunteer data now. Yeah, just help frame expectations for that healthy volunteer readout and, how much, I guess, line of sight will we have into, like, optimal dosing interval based on the healthy volunteer data?
In the healthy volunteer data, it's like NHPs translate to healthy, translate pretty readily to IgAN patients. What we'll be looking at. Now again, they're healthy, so we'll be looking at the IgA depletion and we will look at Gd-IgA1, but these are healthy patients, so it's not there. I think it's really about looking at the PK and what is the dosing interval, and then what is your IgA reduction. What we've seen with the Povi and Sibi is around 50%, and we'll see. We had up to 80% in NHP, so we'll see what we're able to deliver.
I think the third leg of the stool from a differentiation perspective is the immunogenicity piece. These patients are on therapy for the long term. We know that the sibeprenlimab label includes a very decent ADA rate, and patients with ADA had lower efficacy in terms of lower proteinuria reduction. I think that's going to drive switching in this market. We have theoretical support that the 116 asset will not have the same issues with ADA because of the binding epitope on APRIL. I think there's kinda 3 components, and we'll be able to get information about all 3 in the HV study. We're really looking forward to turning over that card.
That's great. Yeah, should be very informative. Okay. I guess longer term in this world where we have APRIL targeted compounds, APRIL BAFF targeted compounds, like how do we think the market dynamics kinda play out in IgAN specifically? Maybe just like high level, like how large of an opportunity we think IgAN's gonna be, but then which of these approaches. Obviously you feel like APRIL mono is gonna win. Why?
You're asking me to predict the future, and of course I will.
Yeah.
I'm willing to do that. I do think it's gonna very much evolve like diabetes evolved, right? We know that you need to do for a young patient who presents with proteinuria is get their protein level less than 0.3 grams per day. You know, get these kind of relative reductions in proteinuria I think become less important over time. They become important for proof of mechanism in biology. What becomes important clinically is your patient achieving their treatment goal, which is they're measured by their proteinuria. Patients will come back every 6 months to look at how they're progressing from proteinuria perspective.
It's gonna be really important for prescribers to get them to that target because we know like if you're seeing a 20-year-old patient just sitting in front of you, they need their kidneys for another 60 years. You want to give them the best opportunity possible to remain off dialysis. I think that's going to be driving to the lowest possible proteinuria reduction in that patient population. It becomes an issue of like, what's your preference? What's first line? What do you escalate to if patients are not doing well? At what point do you escalate therapy? If patients are doing very well on an APRIL, you know, they stay on that. If they're not, then they get to a more highly potent APRIL or next gen APRIL. Do they go from an APRIL to a BAFF/APRIL?
Certainly based on the data we have today, there doesn't appear to be any advantage to the BAFF component and some theoretical safety risks with hypogammaglobulinemia and cytopenia. We need more data, though, you know, from both assets, I think, to really understand how that commercial opportunity is going to evolve over time. We're really looking forward to some data from povetacicept that will come later this year, really understanding as physicians start to get their hands on sibeprenlimab now that it's launched. I think this will be a rapidly evolving market, and we're really excited to be part of it.
Yep. That's awesome. Then for CLYM116, how do you think about indication expansion opportunities-
Mm-hmm.
Like, where this could or should go next?
I mean, I think that for us, IgAN makes the most sense. You know, clearly that's the lead. We'll be thinking about where APRIL-only approach might make most sense. Sjögren's is one disease of interest, but more to come on that when we prove out the product profile.
Got it. Okay. When we think about budoprutug and like CLYM116, and like, it seems like massive kind of opportunity sets across both assets, how do you guys think about capital allocation, I guess, between the two? You have budoprutug that's clearly more advanced at this point in PMN. You've got CLYM116 coming in IgAN. Like, how should we think about, I guess, the split of spend across the two programs going forward?
Well, we have what we've given just to give you our financial status, we ended Q4 with $161 million on the balance sheet and runway into 2028. We feel that we, you know, we can fund all the programs through that, but that does not include a pivotal trial ramp-up for things like PMN or IgAN or any other indications that we might go in. I think that we, you know, right now, there's more trials ongoing, of course, with Vuto, that's going to be where more of our expenses. I think that right now when we look at PMN or ITP, those are smaller pivotal trials, maybe 150 patients. IgAN is larger, again, those trials are also manageable for us.
I would say we're kind of equally excited about both assets right now. Maybe a little more spend on budoprutug, but how that shifts over time will depend on the data that comes this year.
Yeah.
I think the important component just from an organizational perspective is there's a ton of synergy between both assets as well. We're getting to know the kidney space, the sites, very similar assays, very similar infrastructure set up. I think keeping them both together makes a tremendous amount of sense in the short term, and building the capabilities to kind of be successful in those indications, I think is an important focus for us this year.
Yeah. That makes a lot of sense. Maybe last question. I know we're running up against time, but I remember speaking around the CLYM116 acquisition, and this was basically, look, we told people we're going to go out and do business development, and we're still looking. That was 1 year ago. I guess we fast-forward to, you know, March 2026. Like, how are we thinking about potential other business development opportunities? Are we out there looking to in-license additional programs? Are we thinking about that maybe in relation to this, sort of like rare renal vertical that we've built out across Vuto and CLYM116?
Yeah. We're certainly always looking at new opportunities to take something forward. I mean, we can't compete with, you know, big pharma for well-validated assets. We think about what we did with the 116 asset as being the kind of right MO for us, like where we should be looking, not for like phase 2 or phase 3-ready assets, but really taking on a little bit more of the risk by in-licensing assets at an earlier stage of development where we can really use our expertise to guide them, you know, through that kind of IND and early proof of concept.
I think if we do do something, it would be very much like what we've done with the 116 asset, and obviously that gives us a big scope globally to look at some of these kind of late non-clinical stage assets. You know, certainly that's something that we'd like to do, particularly if we can use our current infrastructure and expertise to add value to those assets. We're not gonna go off and do something in oncology or neuroscience or something else. We'll be very disciplined about in-licensing additional opportunities.
Great. Excellent. Well, we're up against time, but thank you Climb team for joining us. Thank you, Susan and Aoife. We'll stay tuned. Big year of data coming in 2026.
Yes.
Looking forward to it.
You'll be hearing more from us.
Thanks so much.
Excellent. Thanks.