Monte Rosa Therapeutics, Inc. Common Stock Wells Fargo 21st Annual Healthcare Conference

All right, everyone, I think we'll get ready here for our next fireside. My name's Derek Archila. I'm one of the biotech analysts here at Wells. Very excited to have Monte Rosa Therapeutics. From the company, we have Markus Warmuth.

That's about correct. That's all right.

Very close. CEO Markus, thanks so much for joining us.

For sure. Yeah, thanks for inviting us.

Excellent. Well, maybe just to start off, maybe give a high level overview of what you guys are working on at Monte Rosa. We can dig into the questions after.

Yeah, no, happy to. Just sort of high level, company's active in the space of targeted protein degradation. We like to just destroy, take out proteins. We're not inhibiting them. Within that field, we're sort of singularly focused on what's called molecular glue degraders, as opposed to heterobifunctional molecules. How do these work? These are small molecules that bind to the protein destruction complex, or a protein in that complex known as ubiquitin ligase. Reshapes the surface, and then eventually creates affinity for a protein we want to take out. We've applied this now across several dozens of proteins. Obviously, not all of that work is in public domain. Have built a clinical portfolio by now with three assets in the clinic, and actually more to come over the next 12 months or so.

Excellent. So maybe let's talk about the lead program, MRT-8102.

NEK7 program. I guess, why do you like NEK7 as a target, and what utility does it have across broad I&I indications?

Yeah. NEK7 is a protein involved in the NLRP3 inflammasome, so we are in inflammation. Lots of evidence out there that that inflammasome is involved in sterile inflammation mostly, so it is not so much host defense, really sterile inflammation in the human body, across a spectrum of diseases. I am sure we will talk about some of them, like the ones we are focused on for our indications. NEK7 in that complex actually is a scaffolding protein, so we have learned over time that when you take out NEK7, that inflammasome cannot even assemble. Which is really cool because, sure, there are companies that are working on inflammasome NLRP3 inhibitors, like NLRP3 inflammasome inhibitors. That is inhibiting the fully assembled inflammasome. We obviously take the scaffold away, so basically no risk of that inflammasome to become active at any time during the day.

Got it. I guess you guys are working on developing NEK7 in cardiovascular inflammation.

That is kind of the lead indication. We saw some results from the ZEUS trial. I think this is a different target, IL-6, but also kind of trying to target that inflammation cascade. It failed. I guess, what are the key learnings from that trial, and how do you kind of expect to apply this to your program in the future development there?

Yeah, no. Great. How much time do I have?

All the time. I'm ready.

Just kidding. Maybe let's start, like why ASCVD for that asset? The amount of literature, the amount of evidence connecting the NLRP3 inflammasome with ASCVD is overwhelming. That goes from preclinical data to human genetics, to clinical evidence that by interfering in this pathway, you can actually change the outcome of ASCVD cardiovascular disease, more or less in general. That's really the data that convinced us that this is where we should go. Also, really cool, right? It looks like an ASCVD, that is the pathway, right? You don't have 3, 4 different immune pathways all playing together. Atherosclerotic plaques, they're essentially driven by activation of the NLRP3 inflammasome, that's why we believe MRT-8102 will work there. Then comes ZEUS, of course it hits on a Friday, I think we were all like, "Oof.