Hello, everyone, and welcome to this next in the series of fireside chats here at H.C. Wainwright's BioConnect Conference. My name is Ram Selvaraju, and I'm a managing director and senior healthcare equity research analyst here at the firm. Our next company is Climb Bio. Climb is traded on the Nasdaq under the ticker symbol CLYM. We cover Climb Bio with a buy rating and 12-month price target of $20 per share. It is a pleasure to have members of Climb Bio senior management team here with me on the stage. Joining me to represent Climb are Susan Altschuller, Chief Financial Officer, and Perrin Wilson, Chief Business Officer. Thank you so much for joining us.
Thank you for having us.
I think it would be really helpful if you could just give us a brief overview of Climb Bio, two very interesting, rapidly advancing biological drugs aimed at areas of serious unmet medical need within what we colloquially refer to as the I&I space, but certainly with an accent, among other things, on nephrology.
Yes. I'm happy to start, and Perrin, please add. Climb was founded in 2024, built into the shell of Ellume, and was started with budoprutug, our CD19 naked monoclonal antibody. That asset had generated in 5 patients of data some very compelling complete B-cell depletion, autoantibody serum negativity, and proteinuria 60% complete renal response. With that asset, you know, being the basis of forming the company, the initiative was to start trials for budoprutug to fully explore its potential.
I think that there's been a lot of interest in the in the CD19 space, but with much more complex modalities and the naked monoclonal approach that could be dosed in the community we think is, you know, tremendously exciting. We have Budo in a phase II study in PMN, a phase I-B in ITP, and a phase I-B in SLE, and all the ongoing trials will have data for this year. We also have the ability to formulate Budo as subQ.
Our second asset, which is an APRIL-only sweeper monoclonal antibody that has potential to be best in class for IgA nephropathy, that was licensed in January of last year from our partner Mabworks in China, and we presented a really compelling NHP data last September, and we will have data this summer in healthies, and think that this could be potentially again, win on dosing interval, IgA reduction, and safety.
I think, you know, to start off with, maybe we can delve a little bit deeper into budoprutug as a molecule and as a potential commercial franchise. Now, every so often we come across a drug that is a true pipeline and a single product. I think that is clearly the case with Budo, which you are developing on three distinct fronts. I think it would also be helpful if you could give us a sense of what you see as the white space in anti-CD19 and why that is the case, as well as the degree to which there is not only a commercial precedent for a drug like budoprutug with inebilizumab, marketed under the trade name UPLIZNA by Amgen, which acquired it when they bought Horizon. For those who don't know, I personally have had a long history with inebilizumab.
We were covering Viela Bio, which originated that product candidate. It was originally a MedImmune drug, and they successfully brought it through clinical trials and then subsequently were acquired by Horizon, which is now, as I said, owned by Amgen. Clearly that presents a precedent for the anti-CD19 monoclonal space, but also I think it would be helpful to hear how you are thinking about the positioning of budo, not just relative to other anti-CD19 approaches that may be much more involved and onerous to manufacture and deploy, but also building upon the lengthy prior history commercially and biologically in anti-CD20 and what the relative advantage of targeting CD19 versus CD20 is.
Okay. Where should we start? Do you wanna start CD19, CD20, and then I'll talk about UPLIZNA?
Yeah, sure. We think, you know, CD19 is a really emerging as, you know, a really validated target with UPLIZNA sharing, leaning into their experience in neuro diseases in the I&I space. You know, if you look at the expression of CD19 relative to CD20, CD19 is really expressed more broadly across the B-cell lineage from the early precursor B-cells through to the plasmablasts, which are really the autoantibody producing cells, as well as many plasma cells, which also produce those pathogenic autoantibodies. By depleting B-cells through CD19, we really feel that we have the benefit of hitting cells that actually don't express CD20 and really achieving the ability to achieve long-term disease control.
That broad expression really allows you to work not only in, you know, newly diagnosed patients, but perhaps also those patients who might have seen a CD20 and failed.
UPLIZNA is a great analog for us in terms of they started an NMOSD, you know, an ultra-orphan neuro indication. I think that their success and growing success in myasthenia gravis is showing that a CD19 targeted antibody is broadly being adopted in the neurology community, and we see a clear parallel in nephrology and hematology for where we're going with Budo. I would say that when we think about the competition in the class, it's almost like the more complex, more is more approach that CAR Ts and TCEs have taken. We skipped over the more the, you know, antibody approach that is commonly known or more commonly explored.
With an antibody, we don't have the risk of CRS or ICANS like you do with the CARs, CAR Ts, and even some of the TCEs. The safety profile is really compelling. The ability to potentially redose is quite compelling. We just think that there's a much broader adoption versus reserving a treatment for the most severe patients that have to be monitored in an academic setting. We think there's a lot of white space beyond also, you know, I think Amgen is focused in the rare neuro space, but as you said, there's so many different diseases where we see potential, and that's why PMN makes sense because it's IgG4 driven. There's clear precedent with the 5 patients of data we have. ITP is a great disease for us to explore.
You know, there's CD19 positive B cells post rituximab failure, and you get to see the B-cell depletion platelet response. SLE, where we're going, is a little bit different. That's more of a translational experiment because we know if there's real potential for a monoclonal antibody CD19 approach in SLE, that's a much more heterogeneous large population, so that's something that more to come there. We see a lot of white space in additional renal and hematology indications, and so then also with our sub-Q formulation with UPLIZNA does not have a sub-Q formulation.
Once we've generated that data in patients where we're able to fully deplete B cells and see what the profile looks like, that's when we'll talk about additional indications and where we're gonna take Budo to maximize its value with having generated all the data this year to kinda get to the proof of concept.
Drilling down into the first indication, which is primary membranous nephropathy or PMN. You have an ongoing clinical study. Maybe talk us through when you anticipate data from that study and how that is likely to frame your efforts to position Budo for potential pivotal registrational work. Also talk a little bit about the competitive landscape and what you anticipate Budo's unique advantages are likely to be from that perspective, especially when we think about, you know, the ability to ablate or eradicate populations of plasma cells or plasma cell lineage members that an anti-CD20 approach might leave behind.
The 5 patients of data we had were at doses of 100 and 200 mgs. We know we have therapeutic window to go up to 1,000 based on data generated in patients with B-cell malignancies. The data that we'll have in the second half of this year is at 200 mgs, the 15 patients in our phase II study, that first cohort. We have 3 cohorts of dosing. Being able to have 15 patients at 200 and recapitulate those 5 patients of data from the phase I-B is going to be very important and compelling.
In those patients, we were able to have follow-on data for 4 of them, and 3 of the 4 did not need any additional immunosuppression after just the 4, you know, 2 doses, 2 weeks apart, and then 6 months later, 2 doses, 2 weeks apart. The question is, as you dose up, are you able to have more of an immune reset? Are some patients going to need chronic dosing versus some have a treatment-free interval, and we think that's really compelling. On the competitive space, we think really CD19 is the Goldilocks target for PMN. The dosing interval is quite compelling every 6 months, which, you know, rituximab is used off-label there.
The other approaches that are out there, and I'll let Perrin talk about, you know, povetacicept and CD38s in the space, we just really think that the CD19 antibody approach is the best approach in PMN.
I think you alluded to the CD20 and Roche's Gazyva is being studied also in PMN. We will see their phase III data. They've announced that they had a positive study. We'll see details of the data at ERA, where they'll have a late breaker. We anticipate, you know, the obinutuzumab to be incrementally better perhaps than rituximab, and I think that is really based on the evidence that we saw at ASN. There was a Chinese CD20 very similar to Gazyva that showed just that in a phase III study in China, incrementally better results than rituximab.
You know, we think that agent will certainly be perhaps the first approved in PMN, but ultimately have the ability to vastly improve upon that profile with budo and what we were able to see in the phase I-B, where we really got all patients, had complete peripheral B-cell depletion. We saw all the 3 patients that had the autoantibody PLA2R at baseline achieved a serological remission. As Susan alluded to, you know, 3 of the 5 patients achieved a complete renal response. You know, as we go up even higher in dose, can we improve upon that profile? We'll see that from our phase II study. You know, the CD38 is also there, povetacicept, BAFF, APRIL's also there. We see distinct advantages of CD19 over those targeting approaches.
I think, you know, taking BAFF, APRIL to start, you know, that's a continuous dosing paradigm where once you take your foot off the gas there, your, you know, APRIL is going to come back and, you know, ultimately you're going to need continuous dosing. Whereas with budo, we see the potential of those 4 doses, and some patients might achieve long-term disease control. For others who need more continuous dosing, it's really perhaps an every 6 month type paradigm. You know, the early data from povetacicept showed, you know, some benefit there. I think we held ourselves to a higher benchmark in terms of complete renal remission at that UPCR level of 0.3 grams per gram. They looked at 0.5 grams per gram.
You know, on the CD38s, we just think fundamentally it's a very aggressive approach that, you know, might leave you open to safety liabilities, which, you know, we wouldn't anticipate seeing with CD19. I think that evidence is really in the long-term data that we've seen with UPLIZNA where we see, you know, good safety after chronic dosing for long periods of time. You know, we're excited about the budo approach for PMN.
you know, I think two other aspects I wanted to make sure we highlighted are as we shift into potential registrational work with budo, within PMN, you know, how are you thinking about the autoantibody readout relative to what ultimately would be considered a registrational efficacy endpoint, and maybe cite, how those have historically been correlated, to what extent they've been correlated. Also maybe just drop in a hint of what we might expect you folks to be presenting at EHA next month.
In PMN, around 75% of patients, their disease is driven by PLA2R. In the phase I-B study, there were about 3 patients that were PLA2R positive, the rest were negative because the other 25%, it's other autoantibodies, but clearly the CD19 antibody approach will deplete those as well. What we're doing in our phase II study is only enrolling patients that are PLA2R positive because you see B cells deplete, then the autoantibody negativity, the kidneys have to heal slightly, then you're getting to have an impact on proteinuria.
By using PLA2R as a surrogate marker, and Parexel picked it up, it's very well correlated with proteinuria, we'll be able to select a phase III dose based off PLA2R data at the three doses we're studying, rather than waiting for the proteinuria data to select the dose and move. We'll be able to move more rapidly to pivotal, but then also we'll be following those patients from the phase II, so we'll have additional data from that study as we go forward as well.
In the context of immune thrombocytopenia, you know, this is a very different context. You know, now we're talking about platelets. Maybe you can talk through what you expect to be the key efficacy readouts that would be applicable for budo in this context, as well as what the competitive landscape looks like and what you anticipate to be the addressable market opportunity.
Do you want me to take that? Yeah, I'll I know we have 5 minutes, so I'll try to save some room for 116 as well. In ITP, I think, you know, what we are looking at is B-cell depletion and then ultimately platelet response, and there's 2 measures of platelet response. 1 is, you know, looking at just any % of patients that achieve a response, and the second, which is the most meaningful to patients and to physicians, is a durable response. You know, in the pretreated population, which is the population we're assessing in our phase I-B study, you know, the bar that's been set is really by the BTK and Syk inhibitors, where they see about 40%-50% of patients have any level of response, but only about 20% of patients actually have a durable platelet response.
That's really the efficacy bar for that later line, which we hear is the highest unmet need population in ITP. At EHA, we'll have the data from our first cohort, which was a 250 mg dose. It was 6 patients. We'll share the B cell data and the platelet data from that group.
Maybe you can give us a sense of how you are thinking about the third leg of the budo stool, which is systemic lupus erythematosus, or SLE, and the extent to which obviously this represents an area of high unmet medical need, what your hopes are for budo in that context.
Ram, I might reframe this for you. I would say, you know, PMN and ITP are clearly indications if we hit the high bar that we as Climb can execute on our own. Then I think with subQ, that could take us to additional indications, renal and non-renal. I think SLE is a little bit different in that it's a translational experiment for us, if we're able to see an impact that is, you know, an antibody approach, but you're getting that deep B cell depletion and tissue level depletion, that's something that we might consider partnering.
Clearly we don't want to forget about CLYM-116.
IgA nephropathy is another large nephrology indication, which has historically been targeted by several other companies. I think it would be really helpful to talk through the things that make 116 unique, particularly from the perspective of targeting APRIL only versus APRIL-BAFF, and how you think this might ultimately translate into a meaningful competitive advantage. Particularly on the safety side, but not just on the safety side in a disease indication like IgAN.
Stepping back in IgAN, these patients are diagnosed in their 20s or 30s. They're largely asymptomatic, yet in 10 years, they're needing dialysis or a kidney transplant because even low levels of proteinuria are causing damage to the kidneys. This first generation, you know, sibeprenlimab, povetacicept, they're dosed at best once monthly. Table stakes in this indication is to have a single subQ injection. For example, sibeprenlimab didn't bring forth their most efficacious dose from phase II to their pivotal to get into a single subQ injection. There's some safety liabilities on the BAFF side, and I'll let Perrin talk about APRIL-BAFF versus BAFF. With povetacicept hypogamma and infection risk, and then with cibi high molecular weight complex formation.
It's great what they've done for patients, but there's still a lot of room out there. What we have with 116 is potential next generation, and it's a sweeper monoclonal antibody that we think could impart greater potency. What that means is it's pH dependent binding to APRIL. High affinity binding to APRIL extracellularly. It's internalized and in the endosome at the neutral pH, APRIL's released and degraded, FcRn recycles the antibody, you are degrading multiple APRIL molecules with a single antibody approach. We also have an LALA mutation similar to YTE to extend the half-life. What we saw versus sibeprenlimab in NHPs was 2-3 times the half-life and much deeper and more durable IgA suppression.
Now we're in a study in healthies, and I think everybody's anticipating data from the other potential long-acting competitor at ERA, and then our data for 116 will come later in the summer. We see this as a space where patients are gonna be needing lifelong therapy and having better dosing interval, greater efficacy because again, even low levels of proteinuria are imparting kidney damage and having a strong safety profile because young patients don't wanna be open to infection risk. We think we can win on all three legs of the stool and there's a great opportunity for 116.
Susan, from a market perspective, you know, I think you laid it out really nicely. I think, you know, it is expected, Ram, as you said, to be a very big market. I think the KDIGO guidelines are setting that up for us as well. You know, they're the guidelines that just were updated in September really emphasize early diagnosis, really biopsying patients ’cause now there are actual therapeutics that are available and more to come available. Really, aggressive treatment of this disease which historically was thought as more of a benign condition, but I think they're realizing that is not so for all the reasons that Susan laid out. You know, more stringent treatment guidelines really getting patients down to 0.3 grams per gram proteinuria, not just 0.5.
I think, you know, physicians are gonna be looking at those guidelines. I think, you know, those first generation agents which are, you know, a vast improvement on what's available for patients are gonna build that market. Vera, Adzukha, Vertex, you know, really increase all of those aspects of the marketplace and then really set us up to come out with what we think is a best in class agent. I think we believe for many reasons in the APRIL only approach for specifically for IgAN.
You know, just maybe talk through, one aspect of the IgAN opportunity which is, what you see as evolving and emergent pricing paradigms and what implications that may have for 116 assuming it gets to market.
Yeah. I think, you know, looking at it, the historic agents, you know, were in that sort of $150 to $200K range and I think sibeprenlimab came out with, you know, pricing in the $390,000 per year range really recognizing that this was a disease modifying approach that really prevented the sequelae of disease. You know, patients would potentially have this stabilization of eGFR not have, you know, the emergence of kidney disease transplant and I think are priced accordingly.
One other thing that it's not on pricing, but I think is a really important aspect is actually our CEO, Aoife, and our CMO, Edgar, were at a summit in the end of April that NKF sponsored with the FDA to talk about clinical development, particularly for the APRIL-BAFF approaches and given how the data that have been generated thus far, we are positioned to potentially benefit from more efficient clinical trial design and just the recognition that now that we have to meet disease modifying therapies, having a 2-year placebo arm is not ethical for patients.
I think, you know, in the limited time we have left, I wanted to talk through some bigger picture strategic questions. You know, Susan, you know, you previously had stints at Biogen and Alexion, and you talked earlier about the possibility of forward integrating Climb Bio especially in the nephrology space with these two highly complementary assets. Maybe talk through how you see the Climb Bio story developing as we get through not only clinical development but also look beyond that to potential, you know, building of the company into A commercial franchise.
Yes. We're well-capitalized, and we actually just raised an additional $110 million in the end of April, that we, you know, if we have runway into 2028, which is, I think helpful as we turn over these data cards. The clinical proof of concept that you generate in the phase I-B and phase II studies, like looking at the analog of UPLIZNA, once you've established a dose, if we have a dose in renal and we have a dose in non-renal, you can move rapidly into pivotals and additional indications. What we're really balancing is what we can do as an independent, you know, as Climb, as a small independent company and building the capabilities to We can do a pivotal in PMN and IgAN and ITP.
I think that that's, you know, in terms of kind of what we can do, that makes sense. Partner, if it's something much broader and bigger.
I think it's also incumbent upon me to remind our audience that these days it's not enough to be best in class, you have to be best in disease. You know, we've historically seen multiple examples of melt-ups, you know, in the wake of clinical data that positioned the molecule in question as best in disease. You talked earlier, Susan, about, you know, the half-life extending properties, in particular of 116. Maybe you could just frame for us a little bit again, you know, the fact that both Budo and 116 are on the cusp of potentially generating clinical proof of concept that would position them as best in disease. What degree of flexibility, strategic and otherwise, this might confer for Climb as a company.
Yes. That's actually one of the rationales of why we did the relatively small raise because we have the cadence of readouts. We showed our, at our budoprutug spotlight in early May that we have a subcu formulation that's gonna move forward. We have data from our first cohort in ITP at EHA. We'll have our SAD data in healthy that we'll talk about the PK/PD in IgAN later this summer. We'll have the first cohort of PMN data and additional ITP data and SLE data. I think as we turn over those data cards, we're gonna be able to get the fulsome picture of the profile of budoprutug, both as IV and subcu.
By the end of this year, we'll have a much clearer vision of where else we might want to take Budo and what the path forward is. We really like the setup. Also for 116.
I think, you know, just adding to that, Susan, what's important to remember is in IgAN, healthy volunteer data is very translatable to patients. I think we've seen very clearly that the data in non-human primates translate to healthy volunteers, which ultimately translates to the profile seen in patients. You know, whereas in other indications, a healthy volunteer study isn't necessarily informative, I think it's very much so indicative of a target product profile in patients.
I think that's all the time we have today. Really appreciate you walking us through the salient aspects of the Climb Bio story. We obviously look forward with bated breath to the next set of clinical data readouts. Really, it's been a pleasure having you at our conference. Thank you very much to our audience for their attention.
Thanks.