Climb Bio, Inc. Common Stock Morgan Stanley 24th Annual Global Healthcare Conference

Yeah. For those of you new to the Climb story, Climb was really founded around the thesis that there was a lot of unmet need in B-cell mediated diseases that were validated targets that had not been fully exploited. When we started the company, we set about finding best-in-class assets against validated targets where there was potential to really address an unmet need in a large commercial opportunity. I think the two assets that we have acquired or in-licensed since starting the company really kind of support what we are doing along that axis. The first product that we in-licensed was called budoprutug. It is an anti-CD19 monoclonal antibody that depletes B cells. Then the second asset is called CLYM116. It is an APRIL monoclonal, and we have just recently showed data demonstrating a best-in-class PK/PD profile for that asset as well.

I know we will get more into it as the chat continues. But a really exciting time with two very interesting assets where I think the thesis has only strengthened over the past year and a half. So we are really enjoying the opportunity to fully exploit both of those assets now in a lot of ongoing clinical trials. We have a kind of a rich data calendar coming up through this year as well as into next year. So a very exciting time for the company.

Yeah. So we in-licensed CLYM116 in January 2025, and at the time, the thesis was really around a couple of pillars. Number one was that IgAN was really emerging as a greenfield opportunity for drug development. It was probably a much larger opportunity than anyone appreciated at the time, and it was a place where we thought could be really interesting for a young company to start establishing a beachhead. I think the second component of that thesis was that APRIL was going to be a very effective target within that space, and I think that has proven out with some of the recent readouts that we've seen. Then if you believe part one and two, the real question was, well, how do you develop an asset with the absolute best profile targeting APRIL?

There were a lot of monoclonal antibodies available at the time that bound APRIL, but none of them that really got us excited about having a good differentiation profile. But when we dug into the biology a little bit more around APRIL, we realized that there was going to be a ceiling effect for PK around a phenomenon called target-mediated drug disposition. In that context, we thought a molecule that didn't just bind APRIL, but actually induced APRIL degradation, was the only real mechanism that we found that had potential to break through that ceiling. So we in-licensed the asset based on hypothesis without a huge amount of data. We showed some really nice non-human primate data head-to-head with the first-generation molecules.

But it was really the clinical data that we shared just a couple of weeks ago that really proved that thesis to be correct in that we were able to exceed what had previously been achieved in terms of half-life. We were able to see really nice, consistent PK curve. We were able to see best-in-class APRIL suppression. So when you think about a validated target and how do you develop the best possible asset against that target, we really fundamentally believe that PK and PD is where it's at, and that demonstrating best-in-class around both of those will lead to a best-in-class clinical and commercial profile in that space. And we firmly believe that 116 has demonstrated in healthy volunteers something that could be a really important competitor product in the IgAN space.

Yeah, for sure. I think there are multiple different pillars of differentiation, if you will. A really important one is efficacy. We know that APRIL now has been pretty well validated. We have seen best-in-class proteinuria, best-in kind of disease proteinuria with sibeprenlimab in their phase III. We have seen it is the only asset that has demonstrated improvement in kidney function over 2 years based on the eGFR curves. What is really going to become important in this space over time is getting everyone to target. It is not just the average, it is really getting the proportion of patients to target. When we look at the available data set, it is very clear to us that what drives that patient getting to target is full APRIL suppression through the dosing interval.

If you look at the sibeprenlimab phase II data that was published in The New England Journal of Medicine, you can clearly see that as dose increases there, you are seeing kind of complete abrogation of APRIL signaling, less breakthrough at the end of the dosing interval, and a higher proportion of patients getting to target. When you think about this disease, it is really a disease that has its first onset in relatively young individuals, so in individuals often in their teens, twenties, early thirties. Preserving their kidneys for 10 years is great, but what you really want is for them to die with their own functioning kidneys, right? It is really about how do you get patients to preserve kidney function over not just 10 years, but it is like a 40-year, 60-year horizon.

The way to do that, based on what we know today, is to get the proteinuria to target, to get their eGFR completely stabilized, and to do it in a way with a product presentation that they are going to continue to take. So there is where efficacy and treatment burden become really important. This is a product, if what we have seen in healthy volunteers bears out in patients, that will be given Q12 weekly in an at-home auto-injector format that is super easy and convenient to use, that achieves best-in-class APRIL and proteinuria suppression, and that I think gives young patients the best chance of preserving their kidneys for their kind of natural life based on everything that we know today. So that is really what drives us in developing this product.

I think what we have seen so far kind of gives us good evidence that we can achieve that goal.