Good morning, everyone. Welcome to our first day of our Piper Sandler Healthcare Conference. My name is Yaz Rahimi. I'm a Biotech Analyst here at Piper Sandler. Excited to have Climb Bio with us. I cannot believe 2025 flew by. We're heading into 2026. 2026 is a very big year for Climb Bio. Maybe a good place to start off is just a reminder of the key milestones and inflection points upcoming for the next year before we go through each program.
Of course. It is great to be here, and we're really excited to share the Climb story. This year was fundamental for the company with two clinical-stage monoclonal antibodies for autoimmune diseases. Next year, budoprutug, our CD19 monoclonal antibody, we will have data from the subQ formulation in healthy volunteers in the first half. CLYM 116, our anti-APRIL for IgA nephropathy, we'll have healthy volunteer data mid-year. We have ITP and SLE data for Budo in the second half of the year. We have an abundance of data for these two, we think, potential best-in-class assets for rare autoimmune diseases.
That's wonderful and very exciting. Let's maybe start with your anti-CD19 antibody. I think as you guys started off, help us understand its differentiation as well as how you came about to pick these indications of PMN, ITP, and SLE.
Yeah. CD19 and B-cell mediated disease is an incredibly exciting space, and a lot of really great validation from cell therapy and other approaches targeting CD19. The thesis behind the company was really that we can take these targets that are validated with good clinical data showing that you can really do something that's meaningful for patients, but with the monoclonal antibody modality that will allow much greater scalability and will allow us to reach a much broader population of patients suffering with some really nasty B-cell mediated diseases. That was kind of the thesis behind the program. There's only two monoclonal antibodies targeting CD19 that we know of in clinical development, the first one being UPLIZNA and the second one being Budo. UPLIZNA has been very successful in clinical development, but is really focused on rare neurological diseases.
It's approved for NMOSD, and then it's also peri-approval any day now in myasthenia gravis. Those are great diseases, but there's a huge number of other B-cell mediated diseases where a monoclonal targeting CD19, we believe, could really move the needle for patients and be successful commercially. Our asset is different in that it has high affinity for CD19. CD19 is expressed on B- cells and not as high a density compared to CD20. That high affinity for the receptor is a really important component. The second attribute is the ability to formulate for subcutaneous development. Thinking about broad populations and being able to access patients regardless of whether they're in tertiary referral centers or a community rheumatologist or nephrologist practicing, I think is really important. Having both offerings, I think, is going to be really important for us commercially going forward.
A really exciting space. When we looked at the opportunity set, there are probably 150 diseases where we know that B-cell dysfunction is driving the pathophysiology of that disease. Within that space, really only a tiny wedge has been addressed by the only other CD19 in the INI space being UPLIZNA. When we looked at the opportunity set across all of the other diseases, we realized that, number one, we had a lot of options in terms of where we could develop this. Number two, we really wanted to make sure we were able to generate data within a reasonable framework of time. When we licensed the asset, we already had a small data set in membranous nephropathy. That became kind of our lead asset and lead program. The data demonstrated really excellent efficacy in that indication.
It's a rare renal indication, and we've initiated a phase II study, and we'll be giving guidance around additional milestones coming up over the next couple of months. That was our lead program. It's an important disease, and it's an interesting commercial opportunity. Outside of PMN, we chose two other indications, one being a single organ rare disease in ITP, and the other one being a broader rheumatological disease, systemic lupus erythematosus. All big unmet needs, all interesting commercial opportunities, and all areas where the biology is very supportive of moving forward. I think what you're likely to see from us over the next year, in addition to multiple data readouts, is continuing to kind of focus the indication strategy as we think about preparing to move additional programs into late-phase development.
That will all be based on data that we see from the studies that are ongoing. I would just add that clearly with compelling initial data in PMN patients, that's the lead. With ITP and SLE, we are keeping the bar quite high for us to move forward into further trials, because there's more competition in that space.
No, that's helpful. Maybe for all these two indications, there will be sort of data upcoming. Help us understand across PMN, what do you need to see to moving forward to a larger study? As you alluded to, for ITP and SLE, which are maybe sort of secondary, but also sort of expectation setting.
Yeah. PMN currently has no approved therapy. It's about 70,000 patients. After IgA nephropathy, it's kind of the next most prevalent immune-mediated glomerular disease. It's a very big commercial opportunity with no approved therapies. We know rituximab is used off-label as kind of in patients who are in that moderate to severe category of PMN. Rituximab has had some efficacy, but the bar is fairly low because they show about 12%-14% complete renal response at 12 months and get to about 30% after 24 months. We think that there's kind of a lot of wide open space in terms of being better than the CD20 that's already been used off-label. There's a nice regulatory path as well forward. These patients have symptomatic disease.
Unlike IgA nephropathy, these patients often present with such a high amount of proteinuria that they're disabled, have ankle swelling, shortness of breath. Getting their proteinuria under control is really, really important. To do that quickly with high efficacy, with a higher proportion of responders, I think is going to be very important for prescribers going forward.
Wonderful. Maybe on Budo, just for ITP and SLE, because both of those are also going to be reading out in the back half of 2026, what do you have to see to wanting to commit further development?
Yeah. For ITP, where we're studying right now is a chronic ITP population, and there's a lot of other products in development. ASN is just coming up. I think we'll see more data at ASN. We're kind of following the abstracts very carefully. I think what's really important in the ITP patients, and when you speak to patients and prescribers, what they're looking for is something that fundamentally changed the natural history of this disease in these patients. A lot of the current immunotherapies used in this kind of refractory pay or the chronic population, these are patients who fail steroids. They've often received TPO agonists with mixed success.
It's really something that can change the natural history there so that they don't have to take chronic therapy, so that they're not going through this kind of current cycle of consistent failures of you take steroids, you fail, you take TPOs, you fail, and you go, and it becomes more and more resistant and difficult to treat. I think we're really going to want to see that patients can, that we're actually addressing the underlying pathophysiology, that we're getting these patients into a remission from their ITP, that their platelet counts are increasing and that they're staying high.
If we can do that in a good proportion of patients, we think it's a very compelling opportunity that you can take two or four IV infusions over a year and have your platelets within a safe range, I think would be really important compared to some of these kind of more chronic therapies. That is what we're looking for in ITP. I think if we can achieve that, it's a very interesting development path, very interesting clinical offering for patients, and very interesting commercially. We'll wait and see what the data shows us next year.
Okay. Maybe a few words on the SLE program as well.
Yeah. SLE is a big disease, big indication, very commercially validated, but also requires a lot of heft and cost for late-phase development. Most of the time, it's two phase III studies in contrast to ITP and PMN, where it's often a single phase III. It's this big umbrella of diseases. Often within SLE, there are subtypes. You have predominantly skin, you have predominantly kidney, you have predominantly joints. One of the things we're looking at from our SLE program is, of course, safety number one. These patients are fragile. They're on multiple immunosuppressants. We want to make sure that we have a safe product. I think the second thing is evaluating whether we are seeing a phenotype that suggests we're getting immune reset in some SLE patients, which I think would be very important.
The third thing is looking within that kind of broad group of is there a subset of patients where we think this potential emerging profile would be uniquely positioned, where it's a much more focused development program. Given our focus on renal, maybe that could be part of the story there. I think we're going to learn a tremendous amount from the ongoing study. It's executing really well. We're excited for data next year. I think there's a lot of potential both in the broad SLE, but then also, I think, more appropriate to a smaller company, thinking about some of these smaller subtypes that could be really interesting.
No, that's great. How do you think about the dose selection in the infusion as well as the subQ across these three indications?
Yeah, that's a critical question. I think the short answer is carefully, because we have the benefit of learning from the UPLIZNA development program. Back when they were choosing their dose, it was really just about kind of dampening the fire, but not extinguishing it, right? Getting peripheral B-cell suppression, getting 90% B-cell depletion was considered a huge win. Now, I think what we've learned from some of the more recent programs targeting B-cells is it's not just about the peripheral B-cell suppression. It's actually the deep B-cell depletion. We know that there's a reservoir of B-cells in your lymph nodes, in your spleen, in your tissues. Often the dose that gets you to kind of extinguish or to kind of dampen down the flames is not actually extinguishing the fire, because you have this B-cell reservoir that's not necessarily represented by the peripheral B-cell count.
I think looking at some of the more recently discovered biomarkers around the B-cell dynamics and really looking carefully at the efficacy and asking the question of whether there's a subset of patients where you can really put them into a remission by getting deep B-cell depletion is a really important component for our ongoing studies, which is why we've decided to kind of move slowly and carefully for some of the dose selection studies, because once we've got the dose, we think we can move quickly into phase III. Selecting the right dose, I think, is going to be really critical in the B-cell space for all modalities, not just for us.
Across these three readouts that are in 2026, you'll be in a position to share sort of dose-ranging studies so that post-season inflection points, you would get clarity on what would be the potential dose moving forward to our registrational study, which are pretty clear from that perspective.
100%.
The doses are not necessarily the same from the three indications. They have been optimized based on the pathophysiology of the disease and the B-cell response needed to be there. You will disclose it, I assume, at the time of the data. Right now, there are no doses.
That's one of the additional strategies around ITP is to get a non-renal dosing if we expand into more hematologic indications.
Would the game plan with having a current subQ formulation be that, let's say you move forward with all three indications, the phase III would be ready with the subQ opportunity?
Correct.
Okay. That is moving along that we would be able to do that.
Exactly. Exactly. Having those options, I think, allows us to make sure that at launch, we have the absolute optimal presentation formulation. It's not just a patient component. There's also a market access and how these products are going to be used in the clinic that we need to take into consideration for each indication. Being able to do that in a way that you're really optimizing your late-phase development program, I think, is really important now for all companies, not just for us.
Maybe help us understand what is the half-life of the subQ Budo formulation.
We will tell you that soon.
Yeah. Yeah.
That is ongoing. We will have data in the first half, as Susan mentioned, that will include not just PK, but the PD as well in terms of the B-cell depletion. I think that will be a really important step for us in continuing to develop the subQ formulation.
That's great. You'll get product profile data, you'll get POC data, and now you can plug and play on which the subQ dose will be in phase III, depending on the success. Great. I would love to spend the next 10 minutes, now that we understand Budo and all the different moving parts of the indications, about your anti-APRIL antibody, right, I think, for IgA. I think before we go and understand, just kind of help us understand its differentiation, right? Then we'll go through the phase I study.
I think the IgA nephropathy space has had a real renaissance, and we're really excited about all the progress that's happened in this first generation of anti-APRIL, BAFF-APRIL assets is really going to take the care of patients a step forward. With R-116, this is anti-APRIL, APRIL only, we believe, for IgA nephropathy makes sense. We don't see additional efficacy from BAFF, but potentially some immunologic issues that could arise from that. Not only is there a two- to three-times longer half-life than sibeprenlimab, we also have a sweeper mechanism, which basically it's pH-dependent binding to the antibody. You're recycling the antibody, and then you're also degrading the APRIL. We think the PD effect could be greater.
What you're talking about in this disease space where, yes, it's crowded, but potentially every two to three-month dosing in a chronic disease that's largely asymptomatic, patients are dosed young. We think that with 116, this is potentially best-in-class next generation coming in after this first class of anti-APRIL approaches.
Okay. In this data, just maybe obviously it's higher potency, higher durability, and you're currently in the middle of your phase I study, healthy volunteer study that's ongoing, and the data is mid-2026. Maybe help level set sort of what are the doses that you selected in your SAD, and is the MAT coming at the same time? The design of the study would be good too.
Yeah, absolutely. We have clearance of our CTA. We're on track to share data mid-year next year. It is a very classic phase I study where we're starting off with very low doses, making sure that we have safety first and foremost, and then escalating. The MAD will be kind of interdigitated once we've cleared a dose in the SAD, then we'll be able to think about repeat dosing in healthy volunteers. We'll be able to accumulate a good set of data quite quickly. I think the important thing about the IgA nephropathy and the APRIL targeting mechanisms is that you can see that there's very nice pull-through from non-human primates to healthy volunteers and then to the eventual commercial profile.
I do think given that the biology has been de-risked by sibeprenlimab and some of the first-gen approaches, we'll be able to learn a tremendous amount about the profile from this healthy volunteer study that we have ongoing, where we end up from a dosing at the upper end of the register. It really depends on what we see from the lower cohorts. It is very much kind of a classic start low, escalate, and then continue to build information that can inform what that likely clinical go-forward dose or doses is. Often you may want to take more than one into a patient study. I think it's going to be super informative. We can follow not just PK that will inform the dosing interval. We'll also be able to follow IgA suppression, which is a really important biomarker.
We will be able to follow free and total APRIL to show this kind of degrading of APRIL, not just binding its components. It is going to be a very biomarker-rich data set that will really allow us to move into those late-phase studies with a lot of certainty around the biology, the dosing interval, and the clinical profile. It is super exciting.
That mid-2026 readout includes SAD only at the juncture?
Correct. Yeah. We may be able to, depending on how quickly the study runs, we'll be able to share additional information. As we go through the rest of the year, there'll be additional readouts.
Visibility-wise, probably you could report on the first three SAD doses across these biomarkers and then maybe give color on what the timing of the MAD portion of the study would be.
Exactly. Exactly.
Okay. Do you have to complete all dose ranging of the SAD to start and kick off the MAT study, or can you start concurrently?
They kind of are interwoven. Ideally, you want to have cleared a certain dose that you're giving in a single dose, and then it allows you to both make two decisions. You can escalate to the next dose level in the SAD, and you can initiate dosing in the multi-dose of that dose. That's basically the most efficient way to design a SAD-MAD study, and that's exactly what we're doing.
In order to establish sort of this recycling, what do you need to see in the APRIL component to establish that, and what is the sort of reductions that you need to see?
We've shared some of our non-clinical data showing this really interesting mechanism where a monosibuprenlimab, for instance, which is like a first-gen monoclonal, will just bind to APRIL molecules and bind them tightly and prevent them from interacting with the receptor. It will reduce free APRIL levels, but total APRIL levels stay the same, right? Because all it's doing is binding and preventing that receptor interaction. When you have a recycling monoclonal, what it does is it's binding, but then it's taking the APRIL into the cell where it's being degraded and returning to bind another APRIL. Every molecule of your monoclonal antibody can neutralize multiple APRIL, four, five, six. You're not just limited to two. What you would expect to see in that context is that you're reducing free APRIL, but you're also reducing total APRIL because you're degrading APRIL in the circulation.
Your total APRIL levels should go down as well as your free APRIL concentration. I think that will be important in demonstrating this sweeper mechanism in vivo, which I think will be an important learning from the healthy volunteer study as well.
Okay. Thank you, team. That's going to be very helpful. When you speak with investors, what is sort of the investor interest? Has it mostly been focused on Budo now with 116? What is the?
As someone who joined the company October 1st, and I underwrote joining Climb on Budo alone, the R&D Spotlight 116 data came out right before I joined. There were a lot of investors who are very familiar with the IgA nephropathy space. They were like, "Oh, now I need to take a look at Climb because this profile truly looks very competitive." Now you have to educate them on Budo. The Budo familiar investors that are not familiar with the IgA nephropathy story, they want education. It is actually a great problem to have that we have two potential drugs that are very interesting. In the renal space, there are also some, there is a lot of synergies, and I think that it is a pretty compelling story.
What is the current cash of the company, and what does it entail in terms of?
$176 million at the end of Q3, and we have runway through 2027. More than 12 months beyond all the data coming out in 2026.
Okay. Obviously contingent on the data and deciding which of the three indications you decide moving forward. Maybe help us. It seems like the high unmet need for PMN is very high, which obviously will be a top priority. Let's say fast forward, we get the data, you move forward to a registrational study. What is sort of the size of these studies look like?
They're relatively modest. We know that even though there's no product approved, there is a regulatory path that's been established. The FDA has confirmed that the proportion of patients achieving a complete renal response between an active control and your investigational product is a registrational endpoint, and it's full approval, right? It's not this kind of proteinuria, and then you have to follow GFR. I think that's really important to have that clarity. The size is about 150 patients for PMN, single registrational study with a complete renal response as the endpoint. It makes it a very good choice for a company like ours. As you say, a high unmet need. That one is for sure an area of focus. One other, I think, important point to make about PMN. Seventy thousand patients, sizable market, manageable, pivotal study.
Obinutuzumab, we expect data from that program in PMN next year in the first half. I think that our expectation is it would not be wildly different than rituximab. In talking to clinicians, there is a real recognition of the value and differentiation of CD19 versus CD20. If you are giving generic rituximab, are you going to then choose another CD20 or a CD19? Or would you go with CD19 upfront because you know that it is much more relevant to the disease pathophysiology?
Okay. Perfect. Team, you guys did a great job covering a lot of our questions. We covered a lot of content. Thank you so much for being part of our conference, and very, very excited to see you soon. Let's give a big applause.