Jade Biosciences, Inc. Common Stock H.C. Wainwright 28th Annual Global Investment Conference

Yeah, absolutely. First of all, just thanks, Arthur, for hosting us here at the conference. It's been a great couple of days, so thanks to you and the whole H.C. Wainwright team. Yeah, so at Jade, we're a company focused on developing best-in-class therapeutics for autoimmune disease. We have three assets in our pipeline that, as you mentioned, we have licensed from Paragon and worked with them on the discovery process there. I'm sure everyone's familiar with Paragon. They're able to develop extremely high affinity binding antibodies, and have a particular expertise in half-life extension. It's cutting out. Okay, I'll just use this. Half-life extension technology, and the difference between the or the combination of that potency and the half-life extension just allow it to have really best-in-class therapeutics. Our lead program is JADE101. It's an anti-APRIL in development for IgA nephropathy.

We reported out positive phase I data a few months ago, showing very deep and pronounced reductions in IgA, which is the key biomarker that would predict clinical activity. Feel very confident about having best-in-class clinical activity with the asset. Those IgA reductions were suppressed for 12 weeks, which gives us confidence in getting a Q12 week dosing interval for maintenance. Really moving forward with that asset. Currently in phase II, looking to read out that phase II study in 2027. We are also moving very quickly towards initiating a pivotal trial, anticipate initiating that study in the first half of 2027. JADE201 is an anti-BAFF receptor. That is an Afucosylated effector function enhanced BAFF-R. Very exciting, because it has a dual mechanism action in B cell depletion.

One, it can drop B cells in circulation very quickly, but it also blocks BAFF signaling to starve those B cells from that pro-stimulatory signal. We are very excited by that. Has applicability across a number of different autoimmune diseases. That agent is currently in a phase I study in rheumatoid arthritis patients, and reading out next year as well in 2027. The third program is JADE301, which we recently disclosed. It is going after dermatomyositis. It is an interferon beta antibody, anti-Mi, with symptoms in the neuromuscular, and also skin components. We are following in the footsteps of a compound called dazukibart, which is currently at Pfizer. It is another interferon beta asset, showing very promising phase II data, showing good activity not only on the total improvement score, which is the primary endpoint, but also on skin. Really best in disease activity on skin.

They are currently in a phase III study reading out next year. We believe we have the opportunity to positively differentiate from dazukibart because it has low bioavailability and is dosed IV, with JADE301 we can capture the activity, but go sub-Q to have a big advantage. Super exciting pipeline underpinned by a strong financial position. As you mentioned as well, a lot of our team actually come from Chinook, where we all worked together. Have a lot of experience developing drugs together, particularly in IgA nephropathy, and really have great capabilities to push these programs forward at speed.

Yeah. We were working on IgA nephropathy at Chinook, as you mentioned. But we had a couple of long-held beliefs and thought there was actually some unfinished business there. The long-held beliefs were, one, IgA nephropathy is a very large market opportunity. Almost 170,000 patients diagnosed in the U.S. More than half of those, 60%-75%, are at high risk of disease progression as defined by higher levels of proteinuria. And really believe that they need therapy. About 50% of them will progress to end-stage disease within 10 years of diagnosis. So a huge unmet need there. We've also had a long-held belief that the anti-APRIL, the selective anti-APRIL mechanism of action, will be the dominant class, because it does reduce pathogenic IgA, reduces proteinuria, and can stabilize kidney disease function. We believe that's going to be the predominant foundational therapy for patients.

And then within the class, we think there's room for improvement. That's why we developed JADE101 to be extremely potent and long-acting, to be able to fully capture all of the efficacy available to the mechanism, and do that in the most convenient format for patients. These patients are typically diagnosed very young, in their second or third decade of life, but have a high lifetime risk of progression, so need lifelong therapy. So giving them something that is going to be convenient and have a low treatment burden is going to be very important.

Yeah. Happy to talk through that, Arthur. Yeah. I think if you take a step back, Tom was mentioning there's really two things that we were trying to solve for with JADE101 when the drug was initially invented. One, you want to have really high binding affinity to APRIL, and then two, you want to have an extended half-life. That's why we have the YTE modification in the Fc. But on point one, we have a novel epitope that was designed for ultra-high binding affinity to APRIL. So it's a femtomolar binder. It's about 750-fold more potent than sibeprenlimab in terms of its binding affinity to APRIL, about 2,000-fold more potent than zigakibart. And what we wanted to show in the phase I data set was deep IgA reduction.

Our target was to get to what the initial, so let's call them the first-gen B-cell modulators such as sibeprenlimab and povetacicept, show that there are higher doses that they weren't able to take forward for various reasons, which was roughly in the high 50s to 60% range of IgA reductions. We're very encouraged to see that we're actually able to get to 70% IgA reductions in our 700 milligram dose, which is our induction dose. In our pharmacodynamic modeling, where we basically created a virtual IgAN patient population leveraged off of primarily the sibeprenlimab integrated review.

Taking JADE101 attributes, such as its pharmacokinetic profile, across all doses, and then taking all the geographic disposition from IgAN patients, different body weights, showing 500 simulated clinical trials that we can sustain those IgA reductions at deeper than 70% with a single sub-Q maintenance dose of 350 milligrams. We're able to get to a Q12-week maintenance dose based on our phase I healthy volunteer data. Because this mechanism is so well-behaved, IgA reductions at early time points are very well correlated with UPCR reductions at week 36, which as you know, has been historically the accelerated approval endpoints. Really encouraged by that overall. From a half-life extension standpoint, we were able to show almost a threefold increase from the first-gen sibeprenlimab human half-life, and then almost a ninefold increase over povetacicept in terms of its half-life.

Tom was talking about the selective anti-APRIL MOA. We feel very strongly that that is leading to all of the efficacy in IgAN. After all, it's a plasma cell-mediated disease. Importantly, we were able to show a very clean safety profile consistent with the selective anti-APRIL MOA at doses all the way up to 1,400 milligrams. Really encouraged by the overall data set in terms of getting best-in-class IgA reductions, showing that we're able to do that for a Q12 extended dosing interval, and then showing the clean safety profile of the APRIL MOA.