Climb Bio, Inc. Common Stock Wells Fargo 21st Annual Healthcare Conference

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.

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. We've focused. The first 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 CLYM-116, we can win on all three, every 12-week dosing, clean safety profile, and being deeper than 50% IgA reduction.

Yeah. 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 mgs 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 first-generation assets.

Yeah. We had a concentration of 160 mgs per mil, so we had doses of 320 and 480 that we reported in our data set. But we have a high concentration formulation so that we will have a 400-mg maintenance dose going forward. When you think about the goal, you want to have 90% plus APRIL suppression over that interval because IgA then follows from that a week or two later in terms of the rise. With our 320 dose, knowing that our go forward will be 400, 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.

Yeah. 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.