There you go. Hi everyone, thank you so much for attending. My name is Aoife Brennan, I'm the CEO of Climb Bio. I'm going to take you through our corporate deck, and happy to answer any questions at the end of the presentation. We are a public company. I would just guide you to review our SEC filings for risk factors related to some of the forward-looking statements I'll be making today. Climb Bio was really founded around the concept of developing better treatments for the one in seven Americans who suffer from an immune-mediated disease. We believe that there is potential to do much better than currently available therapy for these patients, and our focus is really in addressing that mission. We have broad potential; our two programs have potential to be developed in multiple indications and are both based on clinically validated biology.
These diseases, the diseases we're focusing on, as well as the future opportunity set, are diseases that are growing in prevalence globally and represent a very attractive market opportunity with differentiated treatment potential. We're fortunate to be well-resourced. We're funded through 2027, which will enable us to deliver multiple clinical catalysts within that runway. Since the company started last summer, we've been building a very experienced team who have a track record of delivering value and developing best-in-class assets. This is just some of the team highlights. Most importantly, our pipeline. I mentioned earlier we have two assets currently in development. I'll spend most of my time speaking about Budoprutug, which is an anti-CD19 B-cell depleting monoclonal antibody. We also, earlier this year, licensed a second program that we call CLYM116, which is an anti-APRIL monoclonal antibody in development for IgA nephropathy.
I'll spend some time on that one too. As I mentioned earlier, these B-cell-mediated diseases are a very attractive commercial opportunity. Within our current clinical development plan, we have several indications that together have a prevalence of about 500,000 Americans living with these diseases, many of them with ongoing clinical consequences of uncontrolled disease. B-cell mediated diseases are much bigger than that, and we have potential, as we learn more about these assets, to expand into a broad subset of diseases where B-cells are the leading pathophysiology in those diseases. De-risking in some of these early programs really does enable a much broader application of these both technologies in a number of very important clinical diseases. To touch on Budo, you've probably all seen this B-cell development graphic before, and we really believe at Climb Bio that CD19 is the best target for B-cell-mediated diseases.
Because you can see, in contrast to some of the targets here, CD19 really does achieve that Goldilocks in that it's expressed in cells that matter but not expressed in the long-lived plasma cells that are responsible for maintaining immunity to vaccines and immunity to infectious agents that we've seen in the past. There's really compelling data that demonstrates, with other modalities as well as with a naked monoclonal antibody, that this biology and expression pattern really does translate into very meaningful clinical impacts. If you can deplete the right subset of B-cells, you can really achieve good clinical outcomes in these diseases. That is in contrast to, for instance, CD20, which is expressed in a much narrower subset of B-cells. I think there's increasing recognition now that CD19 is a very, very attractive target, particularly in I&I diseases.
We also believe that a monoclonal antibody is the way to go if you're targeting CD19. It's a well-validated therapeutic modality. We know that we can manufacture this very reproducibly at scale with low cost of goods. It fits within our current supply chain and treatment programs. We have lots of infusion centers that can administer this therapy. We're not requiring special training. It's something that can be rolled out and integrated into current care pathways in a very seamless way. Budo is a very interesting CD19 monoclonal antibody in that it has a very, very high affinity for CD19, which is particularly important for that target, given that CD19 is expressed at low density in some of these B-cells. Getting that high affinity is a really important attribute. We also have this ADCC engineering. Antibodies rely on NK cells to deplete the cells that they engage with.
Our monoclonal antibody has low- fucosylation, which gives it greater than a hundred-fold higher potency compared to an unmodified IgG1. A very important attribute: we've been able to concentrate this molecule. It's very well behaved, and it really puts subcutaneous administration in scope for us. We currently have a concentration at 175 mg per ml with very low viscosity. Those are some of the attributes that are really important if you're thinking about potentially administering a monoclonal through a subcutaneous route of administration. You saw earlier on the pipeline that we're advancing a sub-Q program with Budo currently. As we think about that broad subset of opportunities in B-cell-mediated diseases, we've categorized them into three different opportunity sets, and I'll take you through each one in turn. The first is IgG4-mediated diseases, where our lead indication is primary membranous nephropathy.
The second opportunity set is single-organ rare autoimmune diseases, where immune thrombocytopenia, or ITP, is our lead indication. Finally, we think that there's a very interesting commercial opportunity in complex systemic diseases, albeit with some challenges, given that those development programs are often more complex because of the prevalence and the multiple different organ systems that are frequently involved in diseases like SLE. To touch on PMN, which is our lead indication in the IgG4-mediated disease bucket, we think this indication has very high technical probability of success for several reasons. Number one being that CD19 is expressed on all B-cells that secrete an IgG4 monoclonal antibody. We have potential to be able to deplete all of the B-cells that are secreting the pathogenic antibody.
We also have early clinical data in this indication because we executed a Phase 1b study in a subset of patients with PMN, where we demonstrated a really high complete response rate that exceeds anything that's been reported in this indication before. We also think it's a very interesting opportunity commercially. There is a large number of patients, about 40,000 with PMN in the U.S., and about 40% of them don't respond to currently available therapies, or they're refractory. That gives us a very nice initial population to target if we're able to develop something that meets our bar for efficacy and safety. I mentioned earlier a study that we've executed in this indication, where we enrolled eight patients. We have follow-up data on the five patients who completed all four infusions and had 48 weeks of follow-up.
You can see here in that subset of patients, we had very nice data across all of the endpoints. We were able to demonstrate B-cell depletion that was durable throughout the dosing interval. We got immunological remission, which is defined by PLA2R antibodies that fall below the limit of quantitation in some patients. We also saw very nice resolution of proteinuria along the timeline that you would expect for a highly efficacious therapy. The bar for efficacy in this indication is the complete renal response, which means that the urine protein levels fall below 0.3 g/g. We were able to achieve that in three out of the five patients, with another two that almost just missed that cut point. We had very good safety. You know, we haven't observed any cytokine release or ICANS events like some other modalities targeting CD19.
Eight patients, there were no deaths, there were three SAEs, none were considered related. We think this is a very interesting profile as we think about something that could be broadly applicable to large patient groups. In our second opportunity set, we have immune thrombocytopenia, which is also a disease of high unmet need. There are about 80,000 patients in the U.S. with ITP, and 24,000 of them are refractory to second-line therapy, meaning that they're candidates for additional therapeutic approaches. We believe, based on the pathophysiology of ITP, that CD19 has a very compelling reason to believe, because these patients often respond to rituximab, which is an anti-CD20 monoclonal antibody. In those that fail rituximab or have breakthrough despite rituximab treatment, they'll often go for a splenectomy, where doctors will take out their spleen.
When you look in the spleen of those patients, what you'll see is that rituximab has done a good job. There are no CD20 positive cells there. They're full of CD19 positive B-cells. We believe that CD19 could be a really great therapeutic approach for these patients and is semi-validated by the experience with the CD20 rituximab. We're initiating a study to evaluate this hypothesis right now. We're enrolling patients who've had ITP, where platelet counts at baseline have to be less than 30, and we're giving them budoprutug and following them over 48 weeks to see what happens with their platelet count, antibodies, and B-cells. Our final budoprutug indication is SLE. As I mentioned earlier, it's a really classic example of a complex systemic disease in that these patients often have multi-organ involvement, many antibodies, not just a single antibody like in ITP.
There is really interesting evidence to suggest that B-cell-mediated approaches are going to be efficacious in these patients. I think some of the best evidence comes from the CD19 CAR-T approach. This really drove a lot of excitement in CD19 around this time last year when these data were presented. This is data from Georg Schett's group showing that in these CAR-T patients, you get really big improvements in their SLEDAI, which is a composite endpoint of disease activity in SLE patients. You can see here, you can't almost see the after graphic for each patient because it's right on the axis there, but really remarkable improvements in those post-CAR-T patients. The question we're asking is, can we achieve this with a naked monoclonal antibody so that patients don't have to go through the risks and burdens of a CAR-T procedure?
This is our SLE trial that we're also initiating right now, where we're going to escalate these patients across a number of doses to evaluate that question of whether we can achieve something similar to what's been seen with the cell therapies. This study, we plan to enroll our first patient later this year in this trial. Finally, the new kid on the block is CLYM116, which is an anti-APRIL monoclonal antibody that we licensed earlier this year from Mabworks. It's a really interesting antibody in that APRIL has been very well validated, particularly in IgA nephropathy. We know it's a really important mediator of B-cell and particularly plasma cell function, and it's involved in this class switching between IgM and IgA that's really important in patients with autoimmune disease.
This mAb really has potential to be best in class because it's been modified in two important ways. Number one, the Fc portion has been modified to give it an extension of half-life, reducing burden for patients and potentially allowing less frequent injections. The second important component, it has high affinity but pH-dependent binding of APRIL, meaning that it's able to act like a recycling degrader. It brings APRIL to the cells of the reticuloendothelial system, releases the APRIL intracellularly, and then can circulate back into the circulation to bind more APRIL. These are just some data demonstrating that this mechanism is operational non-clinically. You can see here on the left, this is an ELISA experiment looking at different pH, binding at different pH levels.
Unlike some of the precedent antibodies, you can see that our antibody binds with high affinity at neutral pH 7.4, but at low affinity in the intracellular pH at 5.8. The next question was, does that really result in degradation in vivo? We did some animal experiments looking at what happens when you have this pH-dependent binding antibody on board compared to some of the precedent antibodies. You can see here in the red color that we get much lower APRIL levels because of this degradation compared to just an antibody that binds in the circulation. The next step with this program is to compare it head-to-head with some of the antibodies that are ahead in development in non-human primates, where we'd really be able to get a good assessment of what the differentiation profile for the asset looks like.
We will have more data from those experiments later this year. IgA nephropathy is probably not a new disease to many of you. It's been a very hot area for drug development, and rightly so. It's a relatively high prevalence, rare renal disease, but there's currently really no great treatment options that get a high proportion of patients to their target, which is a proteinuria level of less than 5 g or 0.5 g per 24 hours. This APRIL antibody really could be a great option for these patients, particularly if we can achieve really high potency, a high proportion of patients getting to target, and infrequent home-administered subcutaneous dosing. This disease occurs in midlife. Patients are often in their 30s and 40s when they're diagnosed. They need to remain on treatment for life.
Something that has high compliance is going to be really important in changing the clinical outcomes for this patient group. I'll finally end with our outlook and summary. We're extremely fortunate to be very well funded. We had $212 million, almost $213 million, at the end of 2027. We'll shortly be providing an update with our Q4, Q1 call later this month. We have a number of really important milestones to achieve this year with initiation of clinical trials, first patient dose, and some data from our subcutaneous program, as well as data from our APRIL asset that will come in the second half of 2025. That concludes my remarks. I'm happy to take one or two questions. Great. Thank you so much.
The team is around for a couple of minutes if anyone wants to follow up, but thanks so much for your attention.