Climb Bio 3rd Annual Guggenheim Healthcare Innovation Conference

Yeah, delighted, and thanks so much for being here. We're a local Boston company, so it's always a highlight conference for us where we don't have to get on an airplane, so it's wonderful to be back again. Climb Bio, for those of you who don't know us, we're a public biotech company focused on developing B-cell targeted therapies for autoimmune indications. We believe that there's tremendous opportunity to continue to advance on some of the science around specific B-cell targets, particularly in diseases that are undertreated or haven't had very many therapeutic approaches. That's kind of our overarching strategy. Underlying that, we have two assets. The first asset is a CD19 targeted monoclonal antibody, and then the second asset targets APRIL, which is a circulating cytokine that's an important mediator of B-cell differentiation and maintenance. So two clinical stage assets that are advancing very rapidly.

Yatin referenced a busy year, and we've literally been going from one data readout to the next. We haven't had a break pretty much for the last six months. So just a very active pipeline, a very active portfolio of studies that are now starting to yield some really interesting data that helps us to understand the potential of both assets, and helps us to really understand dosing as we think about advancing to one or more assets to phase III development over the next 12 months.

PMN is a rare renal disease mediated by autoantibodies. There is currently no approved therapy. There is a therapy that is under regulatory review, which, if successful, would become the first therapy that has been approved for PMN. It is a very difficult disease for patients who are diagnosed with the disease because we are used to talking about proteinuria for IgA nephropathy, but these patients actually develop nephrotic range proteinuria, so they are having proteinuria excretion of like 5-10 grams per day. When you have that amount of proteinuria, you end up with lots of secondary impacts, like they get swelling, you are predisposed to clots because you are losing your protective clotting factors in your urine, you are losing a lot of your immunoglobulins in your urine, so you are going to get infections.

These patients are often in disability, so it really is a life-altering kidney diagnosis, and that can be very, very challenging to treat. When we in-licensed budoprutug, there was a study that had been started but had not been finished by the prior sponsor. It was just discontinued for business reasons. There was no study report written, but we kind of gathered the data that had been collected up until the point that we in-licensed the asset, and we saw a really interesting signal. This was a phase I-B study that was performed in patients with PMN. Eight patients had been enrolled. We had follow-up data on five of the eight, and what we saw was a 60% complete renal response at 12 months in this small dataset. That was really best in class of any product that had been studied in PMN before.

This was a really transformational efficacy signal. We thought, "Oh, that is really intriguing, but we want to finish the study. We want to get higher N. We want to be able to really explore the range of doses in this population." But we had this really encouraging early signal. We went back to the sites that had enrolled those five patients, and we asked, "Hey, how is the patient doing now?" It turned out that three of the four patients where we were actually able to kind of get anecdotal follow-up had continued to be in remission even though they were not continuing to get dosed with the monoclonal antibody. That was very intriguing to us, but obviously, we wanted to replicate the data and bigger N, make sure it was truly representative of the phase III population.

The data that you are referencing that we shared at ASN was really the first look at the data from the kind of continuation of that study, if you will. We restarted a study, a phase II study called PrisMN. It was evaluating three different doses. The first dose was 200 milligrams. That was really the only dose group that we had sufficient follow-up to look at some of the endpoints that are important in those patients. What we saw was that we enrolled a severe population of patients. They had very high mean proteinuria with 6 grams per 24 hours at baseline, very high PLA2R levels. These were patients who were very resistant to treatment, unlikely to remit, and we were able to get a nice proportion of them to an immunological remission. We saw about a 73% reduction in PLA2R levels at 12 weeks.

These patients continued to be followed, but really encouraging early signal. When we went back and compared how these patients looked to the patients in the phase I-B at the 12-week endpoint, it looks like it is exactly in line with the early kind of looks at those data. So, it is really nice when you are doing clinical development that you can replicate data again in an independent study. It kind of makes you feel like, okay, there really is something real going on here. We are really encouraged and are continuing to follow the first cohort Yeah as well as continuing to dose escalate.

We have completed enrollment in the 600. We are enrolling in the 1,000. We will continue to provide updates from those patients as we go into next year, but certainly off to a good start in terms of being on a solid foundation for the program.

Got it. One additional piece of info I would add is that in the 600 mg dose, while it was less follow-up, you were really seeing silencing of B-cells.

Yeah. There was a dose response.

In a renal population where patients have baseline proteinuria of 6 grams, you are losing drug in the urine.