Thanks for being with us for the Baird Global Healthcare Conference. My name is Colleen Cousy. I'm one of the Senior Analysts covering biotech, and I am pleased to have with us the Climb Bio team, including Aoife Brennan, CEO, and Perrin Wilson, Chief Business Officer. Thanks for being with us today.
Thanks for having us.
Before we dive into some of the Q&A, maybe if you could just start off with a brief company overview of Climb Bio for those that are less familiar.
Yeah, thanks so much for having us. At the end of the day, we're delighted to be hopefully the high point of everyone's conference. Climb Bio is a relatively recent company. We're in existence about a year. We focus on INI. We develop monoclonal antibodies targeting well-validated clinical targets where we believe we can develop best-in-class assets, identified targets against high unmet need indications where there's a well-established path to approval and an identified patient opportunity with a large commercial indication. Our lead program is a CD19 B-cell-depleting drug called Budo, and we have a second indication or a second therapy being developed for IgA nephropathy targeting APRO.
Great. Let's dive into your lead asset, Budoprutug, or Budo for short, target CD19. Talk about why targeting CD19 makes sense in B-cell-mediated diseases.
Yeah, so CD19, there's lots of targets on the surface of B-cells. When you are thinking about the ideal target on the surface of B-cells, what you want is a target that will knock out the pathogenic B-cells but save the B-cells that are responsible for maintaining protective immunity. You're looking for the ideal target there. That's kind of what we call the Goldilocks target, right? That will preserve your vaccine and immunity against infections that you've seen previously in your life, but also knock out those B-cells that are driving your pathogenic response. CD19 checks those boxes, right, in terms of it's involved throughout B-cell development but preserves the long-lived plasma cells. We think that it's the ideal target for INI indications. We were very excited to have the opportunity to develop Budo being a target against that CD19 antigen.
Great. Why do you favor the antibody approach for hitting CD19 versus some of the other approaches out there?
As we kind of think about CD19 being the ideal target, I think the next axis is, what's the right modality, right? If you have lots of people interested in CD19 and targeting it with different classes, be it like CAR-T therapy and K cell therapies, we think fundamentally that something that can be scalable, that we really understand from a manufacturability perspective, that has really good tolerability, that's a very well-known platform, is really the thing that is going to have the biggest impact for the largest number of patients. When we looked across all of those other modalities, we thought, monoclonal antibodies are used in practice. They're very scalable. We understand the safety profile. They can be infused very readily in community-centered settings. We thought a monoclonal antibody targeting CD19 really is something that has a huge amount of potential for like the 100+ different B-cell-mediated diseases.
There was a big opportunity. Oplinza is the first CD19-targeted kind of naked monoclonal antibody that's in development. That's focused really on rare neurological indications, which leaves a huge amount of white space for all of the other B-cell-mediated diseases that could also be applicable for a CD19 monoclonal antibody-based approach.
Yeah, I think it's been surprising to me as I've learned a lot more about your company, just how few CD19 antibodies there are out there. Obviously, you mentioned Amgen's Oplinza that they got through their Horizon acquisition, but it's really Oplinza and Budo for the most part. Why do you think there's been so few in development? Is there something particularly challenging about developing an antibody against CD19?
I think it's for historical reasons. CD19 was really the kind of stepson or stepdaughter or stepchild.
Black sheep. Yeah, that's the right analogy I'm looking for. The black sheep of CD20 was really the kind of the B-cell target that was most of interest because historically, this was an oncology play, right, for B-cell-mediated malignancy. When you think back, that was the rituximab and how rituximab was initially developed. That was a big player in this space. When you have a rapidly dividing oncology, a rapidly dividing clone, CD20 is indeed a better target. We've known that CD19 and CD20 work best on the surface of B cells for a long time. On a given B cell where both are expressed, CD20 is expressed with much higher cell density. It made sense that, you know, both were discovered, one moved ahead in development for oncology, and rituximab was developed. It was initially developed in oncology. Some people started to use it in INI.
It's only been quite recently that we've kind of returned to that. We've known about CD19 for a while, but it's only been quite recently that we've actually come back to it in INI. It's kind of one of these stories, kind of like the DLIP-1s, right? We've known the biology for a long time, but it's kind of coming into its own recently with all of this now opportunity to really impact human biology and disease.
Great. Oplinza is approved in NMOSD and IgG4-related disease. They recently filed in myasthenia gravis as well. How do you think about the comparison of Budo to Oplinza? What are the areas of differentiation, or do you kind of view the antibodies as more similar versus different?
Yeah, I think there are molecular differences. There are differences in terms of how we think about formulation, and there are differences in how both could be developed. From a molecular perspective, they're both different antibodies. There is a higher affinity for CD19, which, given that it's, you know, I just mentioned it's expressed at lower levels on the surface of B-cells, that's important. On the other side of the antibody, on the Fc side, we have a low fucosylation. Oplinza is a fully afucosylated antibody, and there are different characteristics on both of those. From the formulation perspective, we're able to administer IV and subcutaneously, and I think that gives advantages just from a patient segmentation perspective. We may be able to develop the subcutaneous formulation in different indications, for instance, which I think is an advantage that we have for Budo.
In terms of development, we have the opportunity coming behind Oplinza to learn from their program around how to optimize dosing, how to think about different indications, how to really optimize the target patient population as we go forward in development. We're working a lot on selecting the right indications as we move forward. We've initiated some studies, very much learning from their development approach. I think there will be great opportunities for both assets. We're really excited to continue to build on that foundation that they've established.
It's a good place to be. On the differentiated subcutaneous formulation, can you just talk about why Budo should be able to be dosed subcutaneous while to our knowledge Oplinza has so far not been developed as a subcutaneous?
Sure. I think in our most recent earnings, we shared some of the non-human primate data with our subcutaneous formulation where we've showed high bioavailability, which I think is an attractive characteristic as you think about ultimately a subcutaneous formulation. We've been able to tick that bioavailability box. We also have the ability to formulate at a high concentration. Our concentration is 175 mg/mL, which allows us to, in a single injection, have a fairly high concentration of drug. I think the third aspect is the viscosity. We have a low viscosity formulation, which allows for good syringability. As we think about the ideal characteristics for a subcutaneous, we have each of those three parameters encompassed in Budo. Now we're taking on moving from non-human primates into a phase one study in healthy volunteers to really prove out those characteristics and look at that in humans as we continue development.
Great. What benefits would subcutaneous dosing provide to patients? I know you touched on this a little bit before, Aoife, but what benefits to patients in terms of, or maybe for patients and for your development strategy?
Sure. I think it gives us that breadth and optionality in development. There are certainly some indications where patients are very used to a subcutaneous administration. As we think about broader indications with lots of patients, those who are really treated in a community setting, it gives us that breadth of options as we think about what might be important to a patient as they consider their disease treatment. Certainly, there's going to be patients that prefer a subcutaneous treatment at home and patients who honestly prefer to go to the physician's office and get their IV. I think we have both options ahead of us for Budo.
Great. Taking a step back now, thinking about your development strategy, I really like how you guys have really kind of bucketed into three different groups of indications that you're going to go after with Budo. Maybe kind of talk us through those three baskets of disease.
Yeah, so one of the challenges that we had when we started off at the company, when you get this asset, you have this list. You know, the first thing you do is you go and you look up a list of all these, what are all the B-cell-mediated diseases? You get this huge list of like 200 diseases. Like, oh my God, this is daunting. Where do we start? The worst thing is you start throwing pasta at the wall and you've all these studies you start and you don't know how to interpret. What does this tell you in terms of where to go next? We came up with this framework that's very much based on the biology where we said, let's start with a rational approach to how the first set of studies could tell us where to go next.
Very much based on the biology, very much based on different kind of risk profiles and commercial opportunities. We came up with these three pillars that I think really helped us think about how we were going to build a company in advance in a very, you know, data-based decision approach. The first bucket that we identified were these IgG4-mediated diseases. IgG4-mediated B-cell diseases have very particular characteristics from a biology perspective. Now, IgG4 antibodies are a specific type of antibody. The thing that's unique about them is that all of the B cells that produce IgG4 antibodies have CD19 expression on their surface. They respond really well to B-cell depletion with the CD19 monoclonal antibody. PMN is a great example of an IgG4-mediated disease. We already had some data when we acquired the asset. There was already a data set in PMN that showed pretty stunning results.
It really validated the kind of biology that these diseases are a particularly good fit for Budo. These were the diseases that we thought had the very high technical probability of success. That was kind of the first bucket. There were four or five other diseases in that bucket that we could pursue after we had good success in PMN. The middle bucket were these single organ IgG1-3 mediated diseases. These are generally diseases where the B cells and the antibodies have targeted a single organ in your body. It can be platelets that are being destroyed by your B cells in ITP. It can be, for instance, your neuromuscular junction if it's myasthenia gravis. It can be your skin for your hair follicles. There are a number of different diseases where it's a single organ that's impacted.
The final bucket is what we call the complex rheumatological, where it's multiple organ systems that are impacted. Those diseases are often more complex from a development perspective, but more common. They often have very high unmet needs, things like rheumatoid arthritis, systemic sclerosis, SLE. Often there's multiple different antibodies that are impacted. The development path can be complex because often there's composite endpoints that are scoring systems that are involved for approval. There is a huge commercial opportunity associated with those diseases. We chose one indication from each bucket for our initial studies. The idea would be that the data from those initial studies would then guide future development in each area. We've made great progress in initiating studies in all three areas and are really excited to start getting some data sets.
Yeah, I think that makes a lot of sense. Let's start with PMN. You have, as you mentioned, some early data there. Kind of walk us through what those data have shown versus what would be expected otherwise in the standard of care.
Yeah, so PMN, for those who are unfamiliar, is an antibody-mediated renal disease where antibodies essentially attack the glomerular basement membrane in the kidneys. These patients present with nephrotic syndrome where they're just losing a lot of protein in their urine. Usually, they present because they get swelling, shortness of breath, very severely debilitating disease. There's currently no approved treatment for the disease. There was a study that was initiated by the prior sponsor where they enrolled patients who had moderate to severe PMN. They gave them two doses of Budo at baseline and then another two at six months. It was a dose-escalating study. The first four patients got 100 milligrams in the four injections and the next four got 200 milligrams. What we were able to show in that study was that we saw that the Budo was able to deplete the B cells as we expected.
Not only did it deplete the B cells, we saw that the pathogenic antibody, which is called PLA2R, also started to come down. What was most encouraging was that the proteinuria also started to resolve over time. That was a really nice endpoint to see. The approvable endpoint in PMN is what's called a complete renal response. It's the proportion of patients who achieve a proteinuria level of less than 0.3 grams per 24 hours. We got to a rate of 60% at 12 months, which is really the best data set. It was a small data set, but it's the best data set that's ever been put up in PMN as an indication. That was a really kind of early indicator that we were doing something really interesting.
What was the most interesting of all, when we kind of got our hands on the asset, we went back to the investigators. The trial had been discontinued, but we knew who all of the PIs were. We made a few phone calls, went back and called them up and said, "Hey, you know, the patients on the study, how are they doing?" Off they had two, three years since they'd been enrolled in the study and the patients were still doing really well. Despite the fact that they had only received four doses of Budo, a couple of years later, they were still free of their PMN. We were able to kind of induce this long-lived remission of the disease. We thought that was really encouraging and it really encouraged us to initiate the phase two study that we've just gotten going.
We're on track to dose our first patient in the next couple of months. I think it'll be a really great study for us and we're delighted to get some more data.
Yeah, maybe walk us through what that trial design will look like and how many patients you'd enroll.
Sure. The study is really picking up where the last study left off. The prior sponsor had discontinued the study not for any safety or other reasons, but really a strategic reason when the asset changed hands for an acquisition. Our study is 45 patients. It's three doses, 15 patients per dose, and it's dose escalating where we left off in the last study. We'll be looking at B-cell depletion and the PLA2R antibody levels, and ultimately following the patients for proteinuria as well. It's very similar to the prior design and continuing that out, really understanding rapidly what dose we would like to take forward to a pivotal study.
Great. Now let's shift gears to ITP, which falls under your single organ IgG1-3-mediated disease. There are some available treatments in ITP. Could you talk about what the kind of unmet need is and the rationale for CD19 and ITP?
Yeah, so the ITP is a rare disease. There are a number of approved treatments, but about 20,000 patients in the U.S. currently do not respond to the first-line, second-line therapy. There is a good proportion of patients who are still underserved with chronic low platelet counts, fail to respond to first and second-line treatments. It's a B-cell-mediated destruction of your platelets. Patients get recurrent bleeding episodes, easy bruising, you know, very debilitating tiredness. We know that it's a B-cell-driven disease. I think the biology is very interesting in that rituximab works in about 50% of patients. B-cell depletion with CD20 works. The reason that we think Budo could be an interesting opportunity for patients is that when the B-cells are depleted with CD20, often the disease comes back. When you look at what happens biologically in those patients, you'll find that their spleens are full of CD19 positive B-cells.
The theory is that if we can deplete those CD19 positive B-cells, we could have a very nice impact in patients who fail to respond to prior lines of therapy. We're really excited to trial Budo in these patients who've kind of had chronic ITP. We're looking at that kind of second, third line patient population. We've dosed our first patient in the first half, study's enrolling, and we're really excited to generate some data.
Great. What does that phase 1B/2A study, what is the design there, and how many patients would you plan to enroll?
Yeah, so it's a dose escalating study. We're taking patients with chronic ITP, so they have to have responded to at least one prior line of therapy, to have had ITP for some period of time. What we'd be looking for is to see what happens to their B cells, to their antibodies, but most importantly to their platelet count over time. That's going to be the really important endpoint that we'll follow in these patients. We're looking at three dose levels, small, medium, and high, and going to continue to follow those patients for up to a year after they receive a two-dose regimen of Budo.
Okay, great. Now let's shift to the third bucket. Systemic lupus, I actually.
SLE.
Yeah, we'll just call it SLE. The E word is really hard to pronounce. Lupus for sure falls into the complex multi-organ diseases. You know, we're actually seeing CD19 as a target with a few other modalities for SLE, specifically CAR-T, by specifics. How do you view the antibody approach relative to some of those others in SLE?
Yeah, for sure. There's been some really interesting data with CD19 CAR-T, particularly from the Georg Schett Group in Germany, where they took patients who had very, very recalcitrant SLE and had some very stunning data. I think the challenge with CAR-T, CD19 CAR-T in particular, is just it's such an intensive regimen. These patients really have to go through a lot of apheresis, lymphodepletion, reinfusion of the CAR cells. While the data was very interesting, we believe that it will be reserved for a very small subset of patients with SLE. The question we ask is, can a monoclonal antibody targeting CD19 achieve something that's even similar to what we're seeing with CD19 CARs? Nobody's ever asked that question before.
We're pursuing a study taking patients with high CDI scores who have failed, despite current standard of care, and starting at very low doses because you have to be incredibly cautious in these sick SLE patients, but escalating up to therapeutic doses and looking at what happens to their B cells, their immune phenotype, what happens to their antibody levels, what happens to them clinically to look at whether with a treatment that's less intensive, that's less risky, can we get something similar to what we're seeing with CD19 CARs. We think it could be a really important therapy if we can recapitulate what we've seen with some of the CD19 CAR therapy. Again, a really exciting area.
There has been some anecdotal data at least for Oplinza in SLE, right?
Yeah, that's right. We were really intrigued. There were a couple of, you know, two anecdotes, case studies of patients who had NMOSD, who ended up getting SLE that was very difficult to treat, who had really good responses to Oplinza. Just, you know, an N of two, but you're very well informed.
Don't read too much into N of two.
I don't think anything got to do with us. It was a poster at the Toronto Lupus Meeting last year. Yeah, it was definitely very intriguing.
For the phase 1B study that you recently enrolled, what's the trial design? How many patients and what types of patients would you enroll in that study?
Yeah, so we're taking patients who have very similar to all of the SLE phase one studies. Their CDIs are high, eight or above. We're starting at low doses, gradually dose escalating based on safety. They will have, obviously, the CDI can be from a various combination of different organ systems that are impacted. Most important is going to be safety early on. The dose escalation will be based on safety in those initial couple of cohorts. As we start to get up into the higher cohorts, we'll start to look at some of the efficacy parameters in these patients. It's a pretty standard early phase SLE study, but I think will be a very exciting one and a very important one scientifically as we really understand the different modalities targeting CD19. I think it will be an important piece of the puzzle.
Great. As you discussed previously, you're currently looking at these three buckets of indications. Would the strategy be that if Budo works in one of these buckets, you would further expand from there?
Yeah, I think, you know, at the end of the day, we're a business and we're a company. We have to have an indication strategy that makes sense commercially. You look at the space, right, and you think, okay, some of these indications are rare diseases, some are common diseases. We have to have a product that makes sense across all of them. I think it'll be Perrin's job as Chief Business Officer to pull all of the science and the business together and have a strategy that makes sense. We would love to be in a situation to have lots of choice in terms of where to go next. You know, I think do you want to speak to kind of how we've been thinking about things?
We've been actively thinking about that as we initiate all of these studies. As data comes out, we want to be able to quickly move and accelerate development. I think we're obviously very committed in PMN. I think scientifically that CD19 in Budo makes a lot of sense in that indication. We'll identify that dose in phase two that will allow us to initiate and move forward into a pivotal study. I think, as Aoife said, being very data-driven about the data that's generated in the ITP and SLE studies and thinking through where it makes sense. I think renal is obviously a very nice anchor for us in PMN, and the asset, which I think we'll probably chat about next, is our CLYM116 program. It is in IgA nephropathy, so very complementary. I think we're thinking about that.
SLE, there is a subset of patients that is lupus nephritis again, which anchors in renal. I think that's an attractive opportunity for us to consider. The ability to really understand the dose for Budoprutug, the dosing regimen in renal and non-renal indications, I think will give us a lot of information to decide where to best go next.
One thing I don't know that we've really touched on yet, but I think is super interesting about the asset too, is just how infrequently it can be dosed, right? What we see for Oplinza. So far, just talk about kind of the dosing you guys are targeting for.
In the studies now, we give two doses, day one, day 14, and then the next set of doses is at six months. It really gives people an opportunity to have sort of a disease-free interval where we think we can deplete B cells for that entire period of time, keep their disease at bay so they have this disease control and they're not feeling as a patient. We think that's critically important. I think there's optionality as we think about our subcutaneous, how will that be dosed, what indications will we pursue there? Will it be the same as the IV or will it be different where we can potentially address a broader patient subset with that administration?
Perrin, as you mentioned, the next asset that we'll talk about is CLYM116. Your preclinical asset, an anti-APRO antibody for IgA nephropathy, is obviously a crowded mechanism, a crowded space. What makes you excited about this molecule in particular?
Yeah. We licensed the CLYM116 asset earlier this year, and we had a very high bar in terms of a next asset that we wanted to take in. We really had to have a good differentiation story. Knowing that siboprenilumab and some of the other assets were ahead in development, we had a pretty high bar. We really thought that there was very intriguing data on this program, namely the sweeper mechanism of action. Targeting APRO, which is a validated B-cell target, particularly in IgA nephropathy, the sweeper mechanism means that it targets but degrades APRO. It doesn't just bind and prevent it interacting with its receptor.
It actually binds APRO, takes it into the cell, releases it in the cell where it can be degraded, and then the antibody can actually go back out into the circulation and bind an additional molecule of APRO. This is kind of third-generation antibody technology. This is the only one that was in development or that was available that we knew of. When we saw this opportunity come up, we thought it was very synergistic with our platform and particularly with Budo having a renal lead indication, had a really good but early data set supporting a very clear differentiation profile. Importantly, understanding that IgA nephropathy is a chronic disease where patient compliance for life is going to be really important, reducing the burden around the number of injections that a patient might need to take could be really important in terms of market share going forward.
We thought, okay, this could be something really important for us. We brought it in, but we said, okay, let's put it to the test in a really rigorous set of head-to-head studies in non-human primates. We've spent six months and a lot of effort making sure we designed the right set of studies that would give us confidence to further invest in taking the program forward into the clinic. We've just completed those studies and are getting ready to share them externally the end of this month. Depending on what that looks like, making forward the next step to take things into the clinic. We've been really pleased with the progress that we've made there. We think we have an exciting asset on our hands and look forward to sharing the data.
Great. With the sweeper mechanism, what sort of dosing could you expect with CLYM116, or maybe too early to say?
I think we'll show the data later this month. We're not going to preview it here. I think there are good analogies to other areas where sweepers have been developed and some good kind of things I could point to in the complement space. For instance, there have been a number of molecules that have been developed, kind of second and third-gen molecules in complement, and you can look at the impact that has had in terms of being able to reduce the dose, being able to get to better potency with fewer episodes of breakthrough, and then being able to really extend the dosing interval with that kind of second and third-gen molecules. We're hoping to see something similar. That's kind of what we're aiming for.
Stay tuned September 29th, I think, to mark when it happens. All right. Now we're quickly running out of time here. Just in the last minute or so, Climb Bio, as you mentioned, a newer company, but a lot going on at the moment, a lot of exciting programs. Maybe just to finish up, if you can highlight the upcoming catalysts and highlight why investors should be interested in the Climb Bio story for the next year or so.
Yeah, so really 2025 has been a year of execution for us. I think we've gotten now four studies up and running for Budo. We're going to be talking about the data we generated and the CLYM116 program. The guidance we have shared is the Budo subcutaneous healthy volunteer data we expect to have in the first half of next year. I think as we kind of progress the CLYM116 program, you'll hear more later this month on timelines and our development plan there. We've committed to giving guidance on data availability for the ITP and SLE studies later this year. I think that's all forthcoming, but a lot to be excited about and a lot coming, I would say, in the next 12 to 18 months for us.
We've got better cash.
Yeah, we actually do have a nice cash runway through 2027, which allows us to actually get through these multiple clinical inflection points and really learn a lot more about both of our programs.
Fantastic. With that, I think we're just about out of time. Thank you so much for being with us.
Great. Thanks, Colleen.