with Jade Biosciences. With us today is CEO Tom Frohlich and CFO Brad Dahms. Tom, both of you, welcome. Thanks for having us. Tom, to kick off for the investor new to your story, could you give us an overview on what Jade is, and how is your guys' Chinook background, as well as the partnership with Paragon to shape your strategy there? 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. Awesome. Thanks, Tom. Maybe let us stick to the IgA and the 101 for a bit. I guess we all know there is a couple of new IgA drug will be on the market by the end of the year. My question for you guys is why are you guys thinking making IgA as a leading asset, and what do you think at the end of the day, when 101 will be available, how the market and landscape look like? 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. I see. You guys reported positive phase I data early this year. Could you walk the newer investor how the data overview for that? 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. Thanks very much, Brad. You pretty much answered my follow-up question. I guess, let's getting a little bit more active here. We all know JADE101 bio also dropped their data early this month. I guess two questions. What's your overall take on the data? I believe they decided to go taking 800 dose plus 400 maintenance dose forward as a go regimen forward, right? Do you think did that go deep, the IgA reduction for their drug? I think we'll have to see. It's really hard for us to speculate on their go-forward regimen without seeing the data. I think we are looking forward to ASN, where they'll present more follow-up data on the higher doses they had in the phase I. One thing we did notice with the first generation of assets of anti-APRILs, like sibeprenlimab and zigakibart, is when in their single ascending doses, when they increase the dose to very high levels that are kind of multiples of what you see in their phase III and commercial doses, that they weren't really punching through a plateau in IgA reduction. Sibeprenlimab had a 50%-55% reduction in IgA. Even when they went up to 12 mgs per kg IV in the single ascending dose, they weren't breaking through what you kind of see as sort of that plateau. We haven't seen that yet with the Climb data. Their 320 mg dose was quite similar to their 480 or their 2x 320. We didn't see a deepening of effect. But the caveat there was early time points and probably need to see a little bit more. I think what we find extremely encouraging, though, as Brad Dahms was pointing out, is that with JADE101, and we think it's really driven by the potency, is you are seeing those extremely deep reductions in IgA, kind of high 60%, approaching 70% with a 700 mg cohort, where we are getting to these really deep, profound reductions in IgA at early time points, which can be sustained with 12-week dosing, which we think gives us the chance for best-in-disease activity. Sure. Another aspect for their data overview there, they claim this seem like there's no TMDD for their drug. But JADE101 is similar to sibeprenlimab, they still have a little bit of TMDD there. But with a very high potency. So might a high affinity antibody with TMDD versus a relatively low affinity without TMDD. So what's you guys thinking? Yeah, we think that the most important thing in IgA nephropathy, and it sort of says it in the name, is driving down those IgA levels to very profound levels, and doing that in a time course that allows you to see good effects on proteinuria and then eGFR stabilization at fairly early time points that gives that clinician and the patient kind of that really the feeling that the medication is working, and you're going to get to those KDIGO targets, which is below 0.5 grams a day, and understand if you're going to achieve those with a medication in a reasonable timeframe. And we really do think it's the potency that's driving that ability to get to those deep IgA reductions. And so there's a great advantage there. With JADE101, with the dosing format that, or the dosing regimen that we're taking forward, there's a 700 milligram induction dose, which gets you kind of well above that TMDD range. Then you start your maintenance dosing at week 4 with 350 mgs, and then every 12 weeks thereafter. You can really make sure that those IgA reductions are staying down over time. We don't think there's a big penalty to having that potency. I see. I guess the 101 already in the phase II and the guidance for next year for data. For the data readout, what's the expectation we should put on? Yeah. It's a 30-patient open label phase II, pretty consistent with what you've seen with some of the prior IgAN trials. We dosed our first patient in May just before we disclosed the phase I data, enrolling in multiple sites to be pretty representative of a global IgAN population. It is a small study, right? I think it's tough to put exactly what a success looks like. Obviously, you want to be in sort of the zip code of what the first generation agents showed in terms of proteinuria. But we have guided that we'll have data in 2027. As we get closer to that, we'll start narrowing the guidance around what quarter that'll be. But yeah, really excited to have that readout. While that trial's going on, we have also guided that we'll initiate the phase III in the first half of 2027. Really trying to move JADE101 to get to market as quickly as we possibly can. I see. I think you guys take a kind of ready to take a risk, initiate the phase III, before phase II data fully out. Have you guys interacted with the FDA regarding the design of phase III? There was a National Kidney Foundation meeting back in the spring. Basically, the FDA called this consortium that consisted of doctors, regulators, sponsors, including us, patients, to talk about novel designs for phase III trials, acknowledging that it's not ethical to have patients on placebo for 2 years, as has been the case in the first gens. It seemed that they were coming out, leaning to a year or so for a primary endpoint, depending on the mechanism. We know that the B cell modulators have shown to be relatively safe. We feel pretty good that it'll be a much shorter duration trial than the 2-year trial. As we have our own interactions, we'll update the street on those, but feel, again, very good about the initiation in the first half of 2027. Awesome. Another aspect is, you guys decide taking both Q8-week and Q12-week together into the pivotal trial. I guess, maybe help out here a little bit, what's the rationale and what if the Q8-week is really good? What's going to happen for your strategy for the Q12-week? Yeah. I think that would be kind of a big surprise to us, because when we do look at the PK/PD modeling, it does look like the Q12-week dose will maintain the same levels of IgA suppression as the Q8-week dose. Our expectation is actually to have very little differentiation between the doses. Our intention is to commercialize the Q12-week dose and have that as the predominant dose on the market. The reason why we have those 2 doses in the phase III design is, as Brad points out, we're not waiting for the phase II data because it would take actually quite a bit of information to try to differentiate between the 2, if at all. But we do believe because we're moving forward so quickly, there may be a global regulatory expectation that we have some dose range finding in- I see. the studies, which we won't have from the phase II at that point because we're moving so quickly. We're kind of preemptively putting that in there to be able to make sure we're addressing those concerns and allow quick initiation of that study. We don't think there's really a big penalty there either or a cost to including the two dose arms, just because we now know from the first generation of agents kind of what the assumption should be around the placebo group drop in terms of eGFR, and also what the treatment effect size should be from the active groups. We know how to power the study for the number of patients. It's actually probably more powered around a safety database rather than an efficacy size. Including the two dose arms actually isn't that much bigger than just having a single dose arm going forward. I see. That makes sense. Maybe let's shift the gear a little bit here. I know you have another two in the pipeline, 201, 301. Maybe we get 201 first. The data is next year. You guys haven't decided indication yet, right? My question is, what kind of data could give you a very clear guidance to make the pick in terms of indication-wise? Yeah. As mentioned, antibody ianalumab, that is currently at Novartis. They have run six different phase IIIs and have positive Sjögren's data. What was really interesting in that Sjögren's data is they ran two dose arms, a Q4-week and then a Q12-week arm, where the Q4-week was superior in terms of efficacy to the Q12-week. They are moving forward with the Q4. We think the reason that it was more effective was that through that Q4-week dose with ianalumab, they likely had nearly full receptor occupancy for that whole period where they lost it after Q4, and they were just dependent more on B-cell depletion for that Q12-week. We think receptor occupancy is really the thing to focus on. We will be able to look at our phase I, which we are moving forward in rheumatoid arthritis patients, to really understand not only the safety, tolerability, PK, but also what that receptor occupancy time point is and understand are we extending that duration that will give us the opportunity potentially to have a better efficacy because there is more complete receptor occupancy coverage, but then also a longer duration of action, which will obviously be beneficial for patients. I see. For 301, I believe you guys had the presentation at the upcoming EADV. What kind of data we should pay attention from there? Yeah, that will be your typical characterization. Pre-clinical characterization, we will have some non-human primate data. As mentioned in the opening, the introduction, to get an antibody to the muscle, you actually need pretty high Ctrough concentrations because the gradient to get into the muscle is pretty difficult. Yeah. We also know that dazukibart has low bioavailability, so we'll present just a comparison to dazukibart in NHPs looking at pretty standard things like their binding affinity to interferon beta plus half-life. All in the monkey data? Correct. Okay, awesome. I guess I saved the last for the best. Brad, can you remind me the cash position and the runway, what's included, what's not included? Yes, we have $461 million as of our most recent filing, as of June 30th. We've got a runway into Q4 2028, so that supports a really accelerated development timeline for JADE101. For JADE201, as you mentioned, we haven't decided on the exact go forward indications, but we also want to be cognizant of our capital allocation. JADE201 is one of those programs that you could go after half a dozen indications like Novartis is. Obviously, we're not going to do that, so we've embedded a couple of different phase IIs in that assumption for runway. Okay. For JADE301, it assumes, again, let's say an ambitious development plan. As Tom was mentioning, we will go into healthy volunteers in JADE301 in Q4. Then we will have data from that program in 2027 as well as data from JADE101 in phase II and JADE201 in the RA study in phase I. Awesome. Thanks. Thanks, men. Really appreciate it. Thank you, Arthur. Thank you for having me. Appreciate the time.