Great. Welcome, everybody, back to another session here at Oppenheimer's 35th Annual Healthcare Life Sciences Conference. I'm Leland Gershell, one of the analysts on the Biotech Equity Research Team. Really pleased to have with us as our next presenting company, Climb Bio. Climb is a public company. Ticker is CLYM. We have with us the company's CEO, Aoife Brennan, who will be running through a presentation. We'll have some time for questions at the end, so feel free to submit, and I will do my best to ask on your behalf. With that, I will hand the podium over to Aoife.
Great. Thanks so much, Leland. Thanks for the invite. It's a real pleasure to be able to come here today and share a little bit of the background and the exciting programs we're working on at Climb. Before I begin, as Leland mentioned, we are a public company, and I'm obligated to make some forward-looking disclosures here. I would just refer anyone to our SEC filings for a full description of our disclosures and risk factors. At Climb Bio, we were really formed as a company around this opportunity to do something different for patients with immune-mediated diseases.
There are one in seven Americans approximately suffering from an immune-mediated disease. They're increasing in prevalence.
We believe that there's really a lot of unmet need that remains within this patient population to really do something different, focused on giving them as much of a return to normal life as possible. The company was really founded around this mission to become a leader in developing new treatments for patients with immune-mediated diseases. We have a really exciting setup. Our commitment is to focus on programs that have some validation from a clinical perspective, but also have potential to be developed in multiple different indications, where we believe we can identify differentiated products that we can bring to market to really help address this need for patients,
not just to help them symptomatically, but to really give them as much of a normal life and lifestyle as possible. We're really motivated by that mission and that opportunity.
We're very fortunate to be well-resourced. We have funding through 2027, which will enable delivery of key catalysts across multiple programs and clinical trial readouts. Since we got going here last July, we've really been able to assemble a very experienced team with the track record of identifying and developing best-in-class assets. This is some of the team members that we've gathered so far. This is the pipeline that we've pulled together. Our lead program is Budo, Budo prutug. We're calling it Budo for short. That's a really exciting B-cell-depleting CD19 antibody.
I'll tell you a little bit more about that. It's been developed in three indications, where we believe there's both a combination of very exciting commercial opportunity, as well as an opportunity to do something very different for patients and address an unmet medical need.
We're also developing a subcutaneous formulation of Budo, and that's in IND-enabling studies right now. We'll have some more data on that later this year. We have just earlier this year announced that we've enlicensed a second asset, which is a sweeping antibody for IgA nephropathy that targets APRIL. I'll tell you a little bit about that. We have rights to Budo worldwide. For our CLYM116 program, we have the rights to develop and commercialize outside of Greater China and have a partnership with Mab to execute that global development program.
This is what I believe is a really exciting opportunity set for B-cell-mediated diseases. We have a number of indications that are in focus today that together impact about 500,000 patients in the US currently.
You can see here on the right-hand side of the slide that there's potential to expand into multiple different diseases and disease areas that we think continue to allow us to build opportunities within this kind of B-cell-mediated space. Together, all of these diseases impact about 2.5 million Americans. Our understanding of B-cell biology has really advanced to the point now where we can think about doing something very different for these patients, really addressing the underlying driver of the disease, not just the symptoms or some of the downstream cytokines and inflammation,
but really get to that upstream B-cell biology based on some new understanding of regulation of B-cells and how we can really address these diseases at the roots of the pathophysiology. It is really a very exciting time in this B-cell space.
I think that's reflected by a lot of excitement and work in this area. We're hoping to really be part of that story and do something different for these patients. Initially, I'll just tell you a little bit about Budo. It's a CD19-depleting monoclonal antibody. This just shows how B-cells mature and the kind of various phases that B-cells go to in kind of developing into plasma blasts and plasma cells, which are the antibody-secreting B-cells. You can see here that in contrast to some other targets for B-cell-mediated diseases, CD19 is really the optimal target. It has that what I call Goldilocks, in that it is expressed on pro-B cell up to the early plasma cell.
It is not expressed on the long-lived plasma cells that are important for maintaining response to vaccines and for secreting some of the antibodies that are associated with response to infection. We are able to kind of address B-cells but preserve that long-lived immunity that is very, very important for patients. That is in contrast to some of the other targets that are either in development or have been explored, where the expression profile is more narrow. We think that this really gives an interesting opportunity to treat some of these diseases in a new way by targeting this kind of broad subset of B-cells.
This is Budo. It has been engineered to have 100 times greater potency for B-cell depletion based on the low-fucosylated Fc part of the antibody. That causes increased ADCC activity, which is ultimately how B-cells end up being destroyed and eliminated.
It has very, very high affinity for CD19 in the 18 picomolar kind of range. Very importantly, we've succeeded in being able to concentrate this to a concentration that really allows us to be optimistic about our ability to develop a subcutaneous formulation. We've been, since we started as a company, really working on understanding and optimizing Budo as a therapeutic option for patients.
This is the Budo pipeline. We believe these are some of the initial indications that are very exciting, but as I mentioned earlier, have potential to expand beyond this initial set to additional potential indications as we start to understand more about dose and dose range and PK in some of these initial indications.
As we think about an opportunity set that's as broad as the opportunity set that we could pursue with Budo, we have aligned on this kind of three opportunity set strategy for the assets, the first one being in IgG4-mediated diseases. We have an opportunity, I think, in single-organ diseases as well as in complex systemic. We have an indication and a study that we're initiating in each of these three opportunity sets that I think will really help us understand how we can further develop this asset and what the best kind of commercial opportunities are for this program. This is kind of how we're thinking about the focus going forward for the assets.
You can see there's multiple different opportunities within each indication set.
We have one here in dark blue that we've identified as our initial approach in each area. I'll briefly just outline our IgG4-mediated disease opportunity. The first indication there is primary membranous nephropathy, or PMN. This is a disease, for those who are not familiar, where it's caused by autoantibody-mediated destruction of the podocytes, which are very important cells in the kidney that are involved in filtering blood as it passes through the kidney. About 60%-80% of these patients have a pathogenic antibody that's identified called PLA2R. It's a really important biomarker for the disease.
When the antibody levels decrease, often proteinuria reduction follows months later. It's something that we can follow in our early studies as a good indicator that we're doing something interesting for these patients. Proteinuria is the main problem these patients have. Often it causes nephrotic-range proteinuria.
About 20%-40% of patients today are refractory to all available lines of therapy, most of which are used off-label. We know that complete response, complete renal remission, is the provable endpoint in this disease. It has been associated with improvements over time in these patients in terms of preservation of renal function, as well as some of the symptoms of nephrotic syndrome. There are good guidelines available that can help in terms of identifying the right patients for clinical trials, as well as helping to inform how we might think about commercializing the assets. We are very fortunate here in that we have some early clinical data that is very promising.
Prior to enlicensing the asset, a small phase 1B study had been conducted by a prior sponsor evaluating two dose levels.
We had some really interesting data from this early study, particularly in the five patients who received all of the planned four doses in the study. These data are available on this slide, really showing that we were able to, at quite low doses, completely deplete B-cells for the duration of the dosing interval. It was given in a pair of injections six months apart. You can see here that the B-cells remained below the level of detection in almost all patients for the entire duration of that dosing interval. As I mentioned earlier, these PLA2R antibodies, being the real driver of disease, came down very nicely and kind of preceded the improvement in proteinuria that you can see on the far right-hand side panel here.
We had 60% of patients achieve that kind of complete response, complete remission, where their protein excretion fell below the 0.3 grams per day, which is a very important threshold for these patients. We had good safety, as you can see here, very much consistent with the prior experience with Budo in the oncology setting. Very encouraging. I think, importantly, this is not an asset that's associated with cytokine release, which makes us very optimistic that we'll be able to achieve home-based dosing when we develop our subcutaneous formulation here.
Just briefly to touch on the other two opportunities, ITP is a well-known indication, but an indication where there is still a lot of unmet need. In just the chronic ITP population in the U.S., there are about 85,000 adults. These are patients who have not responded to currently available therapy.
A lot of those patients continue to be refractory to a second-line treatment. I think it could be a nice opportunity for an asset like Budo. Rituximab has been used in this indication, and I think it gives us some interesting pointers around the biology of why these patients relapse with the chronic ITP or are not responding. If you look at these patients, what you'll see is rituximab does a great job of depleting the CD20-positive B-cells. Actually, when you do a splenectomy,
what you see is the spleen is chock-full of CD19-positive cells. We believe that a CD19-depleting antibody could really help in these chronic ITP patients, but also potentially in changing the natural history of this disease.
If we're able to move up the lines of treatment and address these patients early following diagnosis, we may be able to do something that rituximab has not been able to do, which is to induce a long-lasting remission in these patients. We have a phase 2 trial that we're initiating currently. This is just an outline of what that study looks like. We'll be targeting patients who've had an insufficient response and continue to have low platelet counts.
We'll be giving them a pair of doses of Budo and then following them over the following 48 weeks to evaluate how they respond from a platelet count perspective, as well as some of the other biomarkers of disease, which I think will be very informative. Finally, our final opportunity set is where we call complex systemic diseases.
SLE is a good kind of lead indication or a good exemplar of that opportunity set. These are often diseases where multiple organ systems are impacted. There are often multiple different pathogenic antibodies in these diseases and are much bigger in terms of prevalence compared to PMN and ITP. You can see here that the burden of SLE in the U.S. is about 250,000 patients. These are patients who have active disease or actively under treatment with currently available immunosuppressants. A big chunk of those are obviously patients with lupus nephritis, which ends up being one of the most devastating consequences of SLE.
Patients can require, in some cases, dialysis when their lupus nephritis continues to be unabated. While there have been some advances recently, you can see here the standard of care has a number of therapies available that do target B-cells, including belimumab and rituximab.
When you look at these treatments, they really don't address the full kind of unmet need. They often result in a delta between placebo and active treatment in their phase 3 studies in the teens. We believe that there's an opportunity moving kind of upstream on the B-cell lineage to do something that's a lot more impactful for these patients with the CD19-targeted antibody. This just outlines where we are from the other B-cell targeted therapies used in SLE. Actually, the lupus nephritis obinutuzumab data just came out over the weekend, which was not all that different to belimumab in terms of the delta between active and placebo.
For the LN indication, it was in the mid-teens in terms of that difference.
It definitely continues to support a B-cell hypothesis in SLE, but also supports the opportunity to do something a lot better for patients, particularly those patients who do not have a good response to some of the other B-cell targeted therapies. Of course, there has been a lot of interest in this. CD19, in particular, has been really, I think, has become a very interesting target as a result of some of the CAR-T experience, where the CD19 CAR-T therapies have been able to do something really dramatic in these often very refractory SLE patients.
You can see here the bar chart on the top just showing a case series of eight patients where all eight were able to achieve almost complete normalization of disease activity, which is really stunning in these very sick SLE patients.
Obviously, I think everyone's aware that CAR-T has challenges and limitations, particularly when it comes to scaling and addressing the large unmet need in a broad disease area like SLE. We are very interested in evaluating whether this is something that we can do with a naked CD19 antibody that obviously we can scale. It can be delivered in a home setting even potentially. It has a lot better generalizability, I think, compared to a cell therapy type approach. We are looking at this.
This is the SLE trial design. We plan to continue to dose escalate in patients with active SLE. We will be starting at low doses because safety is so important in these quite sick patients.
Then escalating, assuming safety looks good in the low-dose cohorts, escalating up, and we have potential to go up to 1,000 milligrams in these patients to evaluate whether we can achieve something similar to the CD19 CAR-Ts in these SLE patients, and then potentially doing an expansion cohort when we identify a dose that looks promising based on the pharmacokinetics and pharmacodynamics. Just briefly to touch on the new kid on the block here, which is a program we're calling CLYM116. It's an APRIL targeted antibody. We enlicensed it earlier this year from China. Really interesting features.
We had a very high bar for a differentiated antibody, given that there are two APRIL targeted monoclonal antibodies already ahead of us in the clinic. We really wanted to make sure that if we did enlicense something, it had a very good potential to be differentiated clinically.
This is a very interesting antibody. It's engineered in two ways. The first is to have this pH-dependent binding of APRIL, which we believe will result in both not just inhibition of APRIL interaction with the receptor, but also enable clearance of APRIL, which will do something very different for patients from an activity perspective. We also have an Fc engineered molecule that increases affinity for FcRM and has potential to extend the dosing interval in patients. We don't know yet where we'll get to from a dose extension perspective, but there are good precedents for these Fc engineered antibodies.
We think that could be very impactful in these patients, particularly with IgA nephropathy, who will likely require treatment indefinitely. It's a disease that's identified often in 30s and 40s.
Something that has a low burden is going to be really important to get optimal compliance in this patient population. This is just a cartoon of our mechanism of action, where you can see this pH-dependent binding and how that results in degradation of the APRIL and recycling of the free antibody back into the circulation where it can do its thing again, which we think will be very interesting to look at clinically and how that impacts activity as well as the pharmacokinetics and pharmacodynamics will be very interesting to study. We are going to have data from this product in non-human primates later this year. If that all looks good, be moving rapidly into clinical studies.
This is just some of the non-clinical data in vitro and in vivo in mice, really demonstrating those attributes I mentioned, the pH-dependent binding, as well as this ability to clear APRIL in the circulation, which we think is very promising for a differentiated clinical profile. This is our lead indication here is IgA nephropathy, very big and interesting opportunity, but also opportunity to evaluate the antibody in other B-cell mediated diseases if the data looks good from some of the early studies.
As I've mentioned, we really believe this is a very interesting market opportunity that will grow over time, particularly as the treatment guidance for both screening, identifying these patients, as well as really tightly controlling the urine protein excretion continue to evolve.
This is a very interesting kind of growing market opportunity that we think could peak at greater than $10 billion annually over the next 5 to 10 years. This is some of our upcoming milestones and readouts. As I mentioned, we're busy initiating two clinical studies with Budo right now. We're advancing the PMN program to late phase development. CLIMB116 will have some initial preclinical data later this year. Very fortunate to be well capitalized. At the end of the year, we had $212 million and runway through 2027, even with executing that enlicensing opportunity I mentioned. I'll pause there, Leland, and happy to answer any questions that you or others may have.
Great. That was terrific. Aoife, thank you for that overview. CLIMB's obviously a sort of a newer entrant onto the public markets here, so people are still becoming familiar.
Clearly, it looks like you've got a pretty good anti-CD19, so really potent bindings. Is it fair to say that maybe low antigen density has been an issue maybe with some of the prior CD19s, the less potent and therefore not able to kind of get what could be the strong activity that you may be looking forward to in the clinic?
Yeah, I think certainly the increased binding affinity is wonderful. It allows us potentially to deplete B-cells at a lower dose, which I think is wonderful. Antigen density is obviously an issue with CD19. As you go further along into the plasma cells, the expression of CD19 on the surface of those cells starts to decrease. We also think, while there's precedent from other CD19s, there's one other CD19 in the clinic. It was developed for NMOSD.
I think the team at Horizon and Viella before them did a really great job pioneering this biology. I think we've come to a precedent. Our understanding of CD19 has kind of evolved since those early studies were done. We're very excited about both the potential to bring a higher potency antibody into the clinic, as well as really taking the time to optimize dosing and evaluate whether with higher dosing, we can actually get to better and deeper depletion of B-cells to give patients the opportunity for disease remission, which I think is one of the most exciting components of the CD19 story.
I think that CD19 CAR-T clearly shows that we can get these, whether it's a complete immune reset or not, we still don't know, right? Early days.
Being able to give patients a long-lasting remission where they can essentially have repletion of their B-cells without the disease coming back, I think is a very, very interesting opportunity for the CD19 space. If we can do that with a simple monoclonal antibody, I think that has potential to be incredibly transformative for treatment of all of these diseases. I think it is both optimizing the dosing as well as the increased potency that gives us a really unique opportunity with Budo.
Membranous nephropathy, obviously, your lead sort of indication here, just maybe give us a sense, is this sort of a chronic progressive disorder? Is it an acute event that puts patients maybe in hospital? Kind of maybe just sort of set the stage for how this may be used. Yeah, absolutely.
Yeah, yeah, for sure. It is a rare renal disease, antibody mediated.
Patients, when they do present, generally tend to present with proteinuria. Obviously, there is kind of a spectrum of disease, right? Patients with mild disease will respond to an ACE inhibitor, an ARB, and they will do fine on that. There is about 50%-60% of patients who have much greater extent of proteinuria. They are losing albumin and antibodies in their urine. They have increased risk of clotting. They have increased cholesterol. They get edema from all of that proteinuria loss. They are really having tremendous proteinuria, often up to the teens in terms of grams per 24 hours. When you get to that stage, you have both an acute problem as well as a chronic problem, right?
Often in the acute stage, when you have proteinuria that's that frank and that magnitude, you have a long-term problem in terms of progression of renal disease, and these patients will progress. You also have this acute problem because it's terrible from a quality of life perspective with the edema, with just losing all of your nutrients and protein in your urine. It is really a disease that's been challenging to treat, particularly in that severe patient population with no real good treatment for them right now. Often it's kind of hodgepodge of treatment with ACE inhibitor and maybe this trial of rituximab or CNI.
Doing something that can really address that severe patient population that don't really do great on currently available therapies, I think, is the first place to go.
But then thinking about, can we expand into other earlier lines and into the less severe patients over time, I think will be a great opportunity, particularly if we can induce some of these long-lasting remissions like we've seen in our phase I B study. I think it's an opportunity set that will grow over time as more and more sponsors start to develop therapies in that disease indication.
Terrific. We look forward to seeing enrollment in those studies. Had you mentioned timelines for subQ development?
Yeah, our guidance currently is to share some non-clinical data this year and then, if that looks good, to initiate clinical trials later in the second half of this year, the second half of 2025. It's very much a year of execution for us with very exciting progress and data to come.
We are very enthused to move these two programs forward.
Yeah, and it looks like Budo has a rather broad opportunity in front of it. Looking forward to seeing the progress. Thank you, Aoife, for sharing the story. Thanks to all of you who tuned in for this session with Climb Bio. Have a great night.
Thanks, Leland. Thanks, Peter.