Hi. Good afternoon, everyone. Thanks for joining us. My name is Simone Nasroodin, and I am one of the biotech associates here at Wells Fargo. It is my pleasure to introduce our next company, Climb Bio, and their management team, Dr. Altschuller. I think it will be helpful if you can start with an overview of Climb Bio first.
Yes, of course. Happy to. Climb Bio, we are focused on developing antibodies for immune-mediated diseases. We have two assets. They are kind of co-lead programs. The company started with budoprutug, our monoclonal antibody targeting CD19. While the CD19 space in complex modalities like CAR T and TCEs is quite crowded, there is really only UPLIZNA and budoprutug as naked monoclonals to CD19. And we have a small data set from the phase I-B study in pMN, and now we are in a phase II study in pMN, and then a phase I-B in ITP and SLE. And we think there is broad potential for budoprutug across immune-mediated diseases. And the targeting of CD19, you are getting across the B cell lineage from the pro-B cells, and then you are getting plasmablasts, which are responsible for the pathogenic autoantibody production. So we feel that that is a pipeline and a product.
And then we in-licensed our APRIL-only antibody with a sweeper mechanism of action, which I will explain, from Mabworks in China. That came in off of one monkey of data, and we generated the NHP data that was presented at ASN last year. And we just last Thursday presented our healthy volunteer data showing a best-in-class 12-week profile for IgA nephropathy with the APRIL asset. So we are moving quickly. We are in a phase II study in IgAN patients and working to move to a pivotal, hopefully next year. So a lot of activity, and I am happy to go through, as we go through the program, talk about the catalyst. We have numerous additional data readouts this year and into next.
You guys have a lot going on. So I am going to dive into CLYM116 and its opportunity in IgAN disease. Do you want to start with the mechanism, the sweeper mechanism before we get into the data?
When the company set out to get an asset in the IgAN space, we were APRIL-only believers. We didn't believe that BAFF was adding to the efficacy profile, but also opened you up to safety liability. The sweeper mechanism of action for an abundant soluble ligand like APRIL makes a lot of sense. It's pH-dependent binding to APRIL. It's Chugai technology. It's from back in my day at Alexion, it's the SOLIRIS to ULTOMIRIS. You have high affinity binding to APRIL extracellularly. It's internalized, and then the APRIL is released and degraded, and the antibody is recycled. What that does is it's a potentiating effect. You're actually degrading the APRIL, recycling the antibody. What we're not seeing is TMDD that you see with all the other products in the space, like sibeprenlimab, et cetera.
That is allowing us to have a drug concentration, a nice linear PK profile, free APRIL suppressed over that 12-week dosing interval. Ultimately, the way the biology works is if you're inhibiting APRIL, then you're inhibiting IgA, Gd-IgA1, and that ultimately leads to proteinuria reduction and ultimately eGFR stabilization. The 1st- generations in IgAN at best are dosed monthly. They have different safety liabilities, and you're getting to 50% IgA reduction. We think that with CLYM116, we can win on all three, every 12-week dosing, clean safety profile, and being deeper than 50% IgA reduction.
Getting into the data, did the PK and PD data perform as expected? How should we think about the translation to IgAN patients with higher APRIL burden at baseline?
It did, it met all our expectations in terms of being able to have a profile where we see that free APRIL suppression over the dosing interval. I think that the PK profile is nice linear curves, especially when we are for doses at 160 mg and above, we are not seeing any of that deep drop-off that you see with TMDD and others. I would say that the PD profile as well, with the sweeper, you are seeing deep IgA reduction and a Gd-IgA1 reduction, which are better than what we saw with the 1st-generation assets.
What level of free APRIL suppression do you need at the end of that 12-week interval? How do you expect coverage to look like with the every 12-week dosing?
We had a concentration of 160 mg/ mL, so we had doses of 320 mg/mL and 480mg/mL that we reported in our data set. But we have a high concentration formulation so that we will have a 400-mg/mL maintenance dose going forward. When you think about the goal, you want to have 90%+ APRIL suppression over that interval because IgA then follows from that a week or two later in terms of the rise. With our 320 mg/mL dose, knowing that our go forward will be 400 mg/mL, you had 90% free APRIL suppression through 10 weeks and just at like 75% at week 12. We know with repeat dosing, we will have complete suppression over that 12-week interval.
Looking into the ADA data, immunogenicity data, how important is it to evaluate the durability of that during the 12-week regimen, and when can we expect an update on that data?
We don't have those data yet. We're developing the assay with our partner, Mabworks, to make sure we have that aligned for the phase III trial. I will say that when we look at all our data in the individual patient data, we are not seeing any ADA impact. Also, one of the things with ADAs, the reason that people are focused on them, is sibeprenlimab targets an epitope on APRIL that causes daisy chaining and high molecular weight complex formation that leads to the ADA formation neutralizing antibodies. We showed in ASN 2025 that we're targeting a different epitope on APRIL, and we don't have that high molecular weight complex formation. So we don't think that should be an issue going forward. But, w e're developing the assay. Once we have the data, we will share it.
And you mentioned that you guys are going with a higher dose for the phase II and phase III. Did you see any tolerability differences with the higher concentration dosing?
No. From 160 mg/ mL- 200 mg/mL, we are not concerned. It was very minimal injection site reactions. We do not see any difference moving up. We just are maximizing the concentration that we can deliver in a single 2-mL injection, because formulation matters in IgAN.
When we are thinking about the relationship between the depth of IgA and Gd-IgA1 suppression and the level of proteinuria reduction achieved from the phase II, how should we think about that? Also, how should we think about the phase III that you guys are already pursuing too, and the proteinuria reduction there?
What we have seen, and we have gone back and looked at, again, the data from 1st-generations. As you are increasing Gd-IgA1 reduction, you are also increasing proteinuria reduction. There is a real correlation there. The KDIGO guidelines changed to, you are trying to get patients to 0.3 g/ day versus 0.5 g/ day, because even low levels of proteinuria are causing kidney damage over time. That is what the RaDaR study showed. We see that there is going to be a real desire to manage patients, to keep the proteinuria levels low, and you get there by having full APRIL suppression over that dosing interval.
How are you guys thinking about long-term immunoglobulin monitoring and infection risk under chronic APRIL inhibition?
Again, we do not have the BAFF component. We saw no hypogammaglobulinemia or even any levels below normal in our study. Again, as we mentioned, we do not have the high molecular weight complex formation. We think that the profile over the long term, with an APRIL-only approach, what we have seen is a very safe profile and no concerns there.
I know you guys are starting the phase III soon. What feedback are you seeking from the FDA on the registrational strategy?
Stepping back, we had our SAD/MAD study in healthy volunteers in Australia, and that's our data set. Our partner, Mabworks in China, had a parallel healthy volunteer SAD study, and then we are jointly doing a phase II study in IgAN patients.
I think that the totality of those data, and especially given in the IgAN space, how readily healthy volunteer data translates into patients, et cetera. With our data sets together, we think that that should really provide confirmatory support to bring one regimen into a pivotal trial, and again, pending regulatory feedback, that could be next year. The phase II study that we are doing jointly, we designed it before we had these data. It's very likely that we're heading to full approval with one-year eGFR/UPCR endpoints. To make sure that we're getting more patients to target more rapidly and optimizing for that, we decided to have one loading dose, so 800- mg/mL loading dose, so two injections, and then 12 weeks later, the maintenance dose of 400 mg/mL .
When we designed the trial, we didn't know yet what the data would be, so we have a loading dose, and then an eight-week regimen, and then a 12-week regimen. We had an optional additional cohort that we will not be going forward with. I think that with the data that we have, we're looking to confirm the 12-week profile that we have in healthies and patients, and then move rapidly to a pivotal.
Makes sense. My last question on the IgAN opportunity. From a commercial perspective, is the larger opportunity in treatment-naïve patients or patients who are inaccurately controlled on the 1st-generation agents?
I think that it's both. This is a space where nephrologists have had nothing to give their patients, and now there's recognition that these disease-modifying therapies are really going to be game-changing for patients in the space. We think there's around 200,000 IgAN patients in the U.S. alone. This is a $20+ billion market. The 1st-generations, at best, are monthly dosing. They have some safety liability, and they're at 50% IgA reduction. Yes, you're seeing eGFR stabilization, but there are subsets of patients that are not getting to target. Our goal is to get more patients to target and have that safe profile with 12-week dosing. We see that as patients are going to be monitored based on their UPCR, i f they are not responding, they're going to switch.
But if you're a new patient, the biology of APRIL is very established and validated, and we expect switching to a best-in-class or starting with a best-in-class profile after the 1st-generation have established the market and grown it.
Commenting on the best-in-class profile, outside of dosing advantages and I guess the deeper APRIL suppression that you guys are pursuing, are there any other attributes that you think you can differentiate here from the 1st- gens?
I think that the focus is the safety aspect. No hypogammaglobulinemia. Long-term infection risk, especially patients that are in their 20s and 30s when they're diagnosed. The BAFF infection liability is a question over the long term. For us, it's really about the full APRIL suppression gets you that deeper IgA and Gd-IgA1 reduction. I think that the results that we showed both on IgA and Gd-IgA1 were really compelling to KOLs. If we replicate this profile, that's very differentiated across those three pillars of safety, efficacy, and convenience.
With the lack of efficacy seen with the dual BAFF and APRIL inhibition in IgAN, does this influence where you see the greatest expansion opportunities for CLYM116?
Well, with a best-in-class APRIL asset, we are now making sure that we explore where else we might bring this. I know people have talked about sibeprenlimab going into Sjögren's disease, and we're looking at which disease states and areas would we want to move forward with. Once we confirm the profile in patients, want to make sure that there's lots of diseases where an APRIL asset is going to have potential. So we're exploring that now. We want to move quickly.
Makes sense. I guess switching gears to budoprutug now, which component of the profile is most important for driving deep and durable B cell depletion, and how relevant is that differentiation in tissue components where traditional anti-CD20 therapies may underperform?
So, maybe just stepping back, when we think about our portfolio, there's really nice synergies across APRIL and where we're at in IgAN. And then with CD19, we really think it's the Goldilocks target for pMN. And so we've got the renal disease across both. And the reason I bring that up is that povetacicept is being studied in pMN.
We don't think that that is the best approach or profile in pMN versus a CD19 approach. CD19 is IgG4-mediated disease. The plasmablasts are what is responsible for the pathogenic autoantibody production. In 75% of patients, it's PLA2R. With CD19, you're getting across the B cell lineage, through the plasmablasts, a little bit of the plasma cells, but you are not depleting the long-lived plasma cells that are required for vaccine-based immunity. With the CD20s, they are not getting the plasmablasts, and they're bringing things down, but they're dosed every six months.
At best in pMN, the complete renal response. Obinutuzumab just had their data at ERA in June, and at 18 months and two years, it looked just the same as rituximab, 36% complete renal response. What we had in our five patients of phase I-B data was a 60% complete renal response, full B cell depletion, PLA2R seronegativity, and the complete renal response in three of the five patients. We think that profile is incredibly compelling and in line with current standard of care, which is rituximab.
If you were given a CD20 and you haven't responded, are you going to go with another CD20, or are you going to go with a CD19 approach, which fundamentally is getting to the underlying disease pathophysiology? That's the approach with pMN. Now, when talking about the APRIL/BAFFs there, you're damping things down, and you're going to have chronic dosing, and it's monthly at best. In our phase I-B study, we had follow-up data for four of those patients, and three of the four didn't need any additional immunosuppression after just two doses of budoprutug two weeks apart, and then six months later. They didn't need any additional immunosuppression for three years. The question is, as we dose up, are you getting more patients to getting to target and having a treatment-free interval?
That's the approach there and how we think to maximize. With budoprutug, the approach was, again, pMN makes a lot of sense, and we had the original data. We're in phase II there. We wanted to say, this is potential pipeline in a drug . You see with UPLIZNA, once you know the dose, you can go right into pivotal trials. pMN gives us our renal dose. There's a very strong rationale. We also then started a phase I-B in ITP to get a non-renal dose, and it's a great disease to assess because you see the B cell depletion and platelet response.
We've said that we wouldn't go forward in ITP with a pivotal unless we were really seeing a substantial differentiation and durable platelet response, which right now, with all the current therapies available, is around 20%. We'd need to see something far above that. We did see that in the 250- mg cohort that we presented at EHA. By year-end, we'll have the data in ITP at the 500-mg and 1,000- mg cohorts.
I guess piggybacking off the ITP comment there, the 20% is what you need to see to advance?
No, 20% is what all the agents in the space, the BTK, the SYK inhibitors, you are only getting about a 20% durable platelet response. We saw well over 50% durable platelet response in that small N 250- mg cohort, which is why we are looking forward to putting forth the 500 mg and 1,000 mg data by year end.
With that data by year end, I guess what exactly are you looking for, beyond what you already showed, to advance the program forward? How do you envision the chronic maintenance dosing or periodic disease resets?
Again, small Ns in the Phase I-B study, we want to see. Those data were incredibly compelling. Do they hold up as we have a larger N, more heterogeneous population of patients? But seeing something like we saw, much greater than 50%, is really compelling. I think that, again, with the Phase I-B trial, we were dosing patients, and we had an option to redose. I think that's where the pivotal would end up if we ended up justifying going there. You'd want to make sure that we'd see, is it chronic dosing or are you, again, getting that reset for some patients over time, depending on the data.
I know you've already touched upon pMN, but can you elaborate more on that opportunity? How should we think about the expected remission rates as you move into a broader, more severe patient population?
It is around 75,000 patients in the U.S. There is nothing approved. We do think that with the GAZYVA data and Roche going forward in the market, there is going to be more and more awareness and rising interest. pMN, it is not like IgAN, where patients are largely asymptomatic and diagnosed young. They are heavily proteinuria. They have a lot of water on them. We think that this is a disease that really needs disease-modifying treatment. Again, complete renal response is the aligned endpoint that FDA is looking for. If we are able to recapitulate what we showed, which was obinutuzumab was around 36%, and we had 60% in that phase I-B data. What we will do in a larger patient population is characterize baseline characteristics, how much proteinuria is on. The five patients of data we had three were at 100 mg, two were at 200 mg. Incredibly compelling, but again, we want to see, do we dose up in a more heterogeneous population where there might be some more patients that start out with a higher level of proteinuria?
I guess what would be the ideal baseline populations and how many?
I think that the goal is to have a broad range of the refractory patient population. I think that this is not a subset, really. Around 30% of patients will spontaneously go into remission within six months. But the rest of the patients, we think, would be eligible for a disease-modifying therapy like budoprutug.
Moving on to the SLE opportunity now, what can we expect to learn from that upcoming data set? You can talk more about the opportunity there as well in your plans. When will the program reach clearly therapeutic exposure levels?
That's a great question. When we were designing the strategy to characterize budoprutug, pMN makes sense, renal disease, ITP, hematologic disease. Lupus, there's a strong rationale there. But we think of our two studies as more as a translational experiment. Just knowing that it's a very different beast to go into a pivotal trial in SLE, more heterogeneous population, probably 2,000-patient study, and more subjective endpoints. We started a global study, but FDA requires you to start at MABEL doses in SLE. The data we'll have for budoprutug and SLE this year will be a single dose at 100 mg. We'll be looking at B cell depletion, et cetera, there. I think that's interesting. More, we have a parallel study in SLE in China that we started, where you can start at therapeutic doses.
That will come next year. If we see real potential in SLE, that's something we think of that's more of a partnership opportunity versus something that we as Climb Bio can execute on our own. I think that there's clear potential there, but we just recognize the cost and challenges associated in such a broader indication, and so would need to see really strong data to underwrite a pivotal there.
What are some of the benchmarks, I guess, for the data?
Well, with the data that we have this year, j ust looking at the B cell depletion, I think that the focus for us, I think, in the space is really the pMN dataset that we will have in the fourth quarter and the ITP dataset. I think it's next year, we're at the therapeutic doses where you can look at additional endpoints other than just the B cell depletion.
I know you guys are working on the sub-Q formulation for budoprutug. Can you talk more about your progress there? I guess what indication would be the most likely initial opportunity for that formulation? Do you think the sub-Q administration would help you meaningfully expand use beyond academic centers?
The differentiation we have versus UPLIZNA, we have higher affinity to CD19, enhanced ADCC, and we showed in May at our Budoprutug R&D Spotlight event that we were able to equivalently deplete B cells with a sub-Q formulation and an IV. In healthy volunteers, you can't fully deplete the volunteers of B cells. Now, we need to go into a patient study, likely a basket study, to further characterize what that profile looks like. Is it more Ocrevus-like or Kesimpta-like? We would not wait for the sub-Q formulation to move into a pivotal in any indication. If we were justified to go forward in pMN or ITP, we know that we could do a bridging study for that with launch. We think that the sub-Q formulation is just going to provide a lot of additional optionality for us, not a differentiated indication strategy.
I guess stepping back now on just budoprutug in general, compared to the other B cell diseases and opportunities there, where do you expect the biggest advantage to emerge between budoprutug and rituximab in B cell mediated diseases?
I think that again, it's about targeting the plasma blasts and having the broader coverage across B cells. Another thing that we talk about in dosing up is like obinutuzumab, they've been able to show you are able to deplete B cells in the tissue as well as in the periphery. That's another aspect of budoprutug as we dose up, are you able to see more of that reset? I think that one of the tailwinds for budoprutug and that aha moment is that there's just UPLIZNA and budoprutug in the naked monoclonal, and you're not worried about the CRS risk that a TCE or a CAR T would have. You think about the community nephrologist being much more comfortable prescribing a naked monoclonal antibody approach to the broad swath of patients where you'd be reserving the higher-risk modalities for only the most severe patients.
Is there a specific patient population where you think budoprutug could become the preferred anti-CD19 therapy?
Well, we think in pMN, definitely. I think that, again, the CD19 had been overlooked because CD20 is just expressed in greater abundance. I think that now the UPLIZNA uptake and kind of really seeing where there's potential, we think that the CD19 naked monoclonal in these B cell mediated disease is going to be a preferred mechanism. That's why we have the coverage across the different indications for budoprutug, because we know that we can go into additional indications once we've got that right dose.
Speaking on the pMN opportunity, what's the biggest remaining clinical risk there? Do you think that, years later, if it works out, would it primarily be used in patients with persistent disease ?
As I said, I think there's the spontaneous remission, but then you've got 70% of patients that are going to need a chronic treatment to control their disease. In pMN, there is, again, just rituximab and obinutuzumab, the CD20s. There are other approaches, but we do think that the CD19 monoclonal approach, where you're dosed every six months and there may be an opportunity for a treatment-free disease window is the approach.
I think in terms of the risk, the data that we will present in the fourth quarter, where we have the 200 mg, 15 patients from that first cohort , if we can recapitulate the original data, I think that will be very de-risking. People seeing that we have a drug here, and same with the ITP data later in the year. I don't think that there's any one watch-out. It's just are we able to see and replicate what we did in a smaller patient population and a broader, more heterogeneous population? The biology is very well understood and validated for both these assets.
How much of budoprutug 's potential value depends on demonstrating superiority versus existing B cell depletion, versus simply just offering a more convenient durable alternative?
Well, I think that, again, with what you're seeing, like in pMN, is at 18 months, two years. Obinutuzumab had 36%. That's not a great response rate, and so I don't think you have to be better because it's just if you aren't responding and you have a different mechanism, patients will switch to that. But we do think that the CD19 approach should also provide better efficacy.
Just piggybacking off your prior comments on the dosing, I guess what are the key dose response questions you're trying to answer when you go from a phase II to phase III?
For our phase II study in pMN, we designed it so that we're enrolling patients that are PLA2R positive, because again, that's like 75% of the patients. The reason we're doing that is we have 15 patient cohorts at 200 mg, at 600 mg, and 1,000 mg. We don't want to have to wait for the proteinuria data from the highest dose cohort to make a go-forward decision and go into the pivotal. We can base that off the PLA2R data. We will have all comers for the pivotal trial.
Speaking of the PLA2R data, how are you thinking about the relationship between the anti-PLA2R reduction and the eventual clinical remission in pMN?
It is very correlated. Actually, the PARASOL group is exploring PLA2R as a surrogate endpoint. The complete renal response at either 52 or 72 weeks is the approved endpoint now, and we will be looking at PLA2R levels, of course. I think that it is an interesting approach, and it will be helpful in surrogate and measuring. But again, 25% of patients, their pMN is driven by a different autoantibody, which again, CD19 will address. But using that as the surrogate for all pMN trials going forward, not sure.
It seems like you guys have pMN pretty planned out. I am thinking, given the complexity of SLE, how are you guys thinking about the eventual positioning there with position budoprutug against the CD20-directed therapies and other targeted biologics?
That is why we say it is more of a translational experiment right now. We really would have to see quite compelling data from that China study to say, okay, we are going to partner this and go into a much broader population. I think that the totality of the data we have for budoprutug next year will really let us know where else we want to take it . Like the pMN pivotal, ITP pivotal, less than 150 patients. That's completely within our capability to execute and deliver. SLE is just a totally different ballgame.
Makes sense. Going into more corporate questions now. With multiple datasets expected by year end, how are you guys thinking about capital allocation across CLYM116 and budoprutug as both programs mature?
That's a great question. We ended Q2 with $239 million, and our runway goes into the second half of 2028. We raised $110 million in a pipe at the end of April, and the reason we did that is we wanted to be able to move with expediency, and I'll talk through the catalysts that we have next.
The funding through the first half of 2028 is inclusive of CMC and pivotal startup and execution spend for CLYM116 in IgAN and for budoprutug in pMN. We wanted to make sure that we could move expediently no matter what. Yes, to run a pivotal in IgAN, we would want to bolster the balance sheet to get through full approval. I think we are in a very strong position. Talking through the catalyst, in May, we had our Budoprutug R&D Spotlight, where we announced the sub-Q data. Last Thursday, we announced the top-line data from our healthy volunteer study for CLYM116. Then in the fourth quarter at a medical meeting, we and our partner, Mabworks, will have additional data from our healthy volunteer studies, and we will also have our 200mg cohort of budoprutug and pMN.
Then will be SLE, and then by year end, the ITP data. Then our ongoing IgAN phase II study, we will have data coming out from that at probably every two to three months. With regulatory feedback, we could be in a pivotal next year. We have said the phase II IgAN data will be in the first half of next year. Also the budoprutug 600- mg and 1,000- mg cohorts and more SLE data. It does not stop in 2026. It keeps going into 2027. It is really a joy to have two assets being explored in so many indications.
What would a global IgAN phase III program cost, and at what point would you guys consider partnering?
I don't think that that's something that we would need to partner. That is a $150 million or so study. Something that we, with our partner Mabworks in China, can readily execute, and we think that that's a real asset to our partnership. In China, the standard of care in IgAN is very similar to that in the U.S. There's not a genetic reason that you'd see variability. So we feel very confident about our ability to execute a pivotal in IgAN. It's only 300 or 400 patients. It's not the 2,000 patients SLE study.
Makes sense. I guess my last question with the minute we have left, what is the biggest thing that you think investors are missing about Climb Bio today, and what's the success look like three to five years from now?
There's a lot of things. I think that when you look at where our valuation is relative to competitors, and we have two phase II assets, I think that there's just been a disconnect. We have so much going on. We have two antibodies, multiple indications. Really just getting the story out and the clarity about the potential in each is really the piece for us. Five years from now, we think that we're going to be experts in the renal space and broader autoimmune disease, and we think we have that potential pipeline and a product with both of our assets.
Sounds good. Thank you so much.
Thanks so much.