With the Jefferies Investment Banking Team, and it is my great pleasure to introduce Tom Frohlich from Jade Biosciences. Great. Thanks so much. Really appreciate it. Thanks to Jefferies for hosting. We're very pleased to present Jade to this audience. Forward-looking statements, as everyone usually has in their presentation. For more formal documentation, please look at our SEC materials online. Jade is a fairly new company. We were actually officially formed in June of last year, so we're less than a year old, but really exciting. We've achieved a lot in our first less than a year of existence. We were founded off of three assets that we've actually got access to from Paragon. Paragon is an antibody discovery shop in Boston. A group of extremely talented protein engineers have a capability of developing extremely high-quality, high-binding affinity antibodies and have an expertise in half-life extension technology. Really have this capability of providing best-in-class monoclonal antibodies. The three assets that we have access to from Paragon are across a number of different autoimmune targets. We really do have the ambition of becoming a best-in-class company across a number of autoimmune indications. Our lead program, which we'll talk a lot about today, is JADE 101, is the development candidate. It's focused on targeting anti-APRIL. We're developing it as the lead indication in IgA nephropathy, where we believe it has a huge opportunity to become a best-in-disease molecule across a large $10 billion+ branded opportunity. We're moving that program forward. Anticipate getting the clinical trial started in the first half or starting the second half of 2025, with a very meaningful data readout in the first half of 2026. It's a healthy volunteer study, but since IgAN is such a biomarker-rich area, it's going to give us a lot of information, not only on safety, PK, but also some key pharmacodynamic markers, where we'll be able to look at reductions in total IgA, which is a direct read on what we expect to see in terms of patient activity, but also look at the depth and duration of free APRIL knockdown, which will give us all the information we need for the dose and dose interval selection to go very quickly into later-stage patient trials. An extremely exciting program. We're not talking too much about the rest of the pipeline right now, but we do have two other assets, JADE-0 02 and JADE-0 03. We're keeping those targets undisclosed for the time being, mainly for competitive reasons. We don't want fast followers coming out of other geographies. What we are disclosing about JADE 201, we have nominated that development candidate earlier this year, and we are on track and anticipate getting that first-in-human trial started in the first half of 2026, only a couple of quarters behind 001. We are very quickly moving to becoming a company with multiple clinical assets. That is not specifically a kidney-focused indication or asset. It really is a B-cell depleting target that has opportunities across multiple systemic autoimmune diseases. We are very quickly moving to becoming a company with multiple products in the clinic. Other big piece of news in the first year of existence is we've completed a reverse merger with concurrent financing that closed at the end of April this year. We are a fairly new public company trading on NASDAQ. In that financing, we did raise enough funding to keep us well-resourced through 2027 to run these three programs. We feel like we're extremely well-capitalized and well-positioned to move quickly and execute on our mission. Turning to JADE 101 and why we believe we have a large opportunity here. Really, to summarize, we believe IgAN is a very appealing commercial opportunity. Up until recently, there were not any approved products for IgAN. Over the last couple of years, there have been a few new entrants that have been approved, but none of the new entrants actually are disease-modifying, and none of them stabilize kidney function as measured by EGFR. It is a large patient population for a rare disease. I know that is a little bit of an oxymoron, but we do believe it is a $10 billion market opportunity that is going to be rapidly emerging. Within the IgAN space, we do have strong conviction that the anti-APRIL mechanism is going to become the predominantly used class of agents. As I mentioned, none of the currently approved therapies are disease-modifying. The anti-APRILs have demonstrated an ability to reduce galactose-deficient IgA, which is the pathogenic driver of disease. They do this in a very targeted way without any unneeded immunosuppression. Within the IgAN class, we do see an opportunity for a straight line to become best-in-class. As we'll talk about through this presentation, there are two assets that are further ahead in clinical trials. We believe that the properties of JADE 101, it's designed to have higher potency. It has half-life extension. We believe it's really positioned well to capture the full efficacy available to this mechanism and do that with a very, very convenient dosing profile, which for patients will be extremely useful, given that they're generally diagnosed in their 20s and 30s, and having something convenient over decades of treatment will be very, very useful for them. Lastly, as I mentioned, a very efficient path to proof of concept. That healthy volunteer study that I mentioned that's reading out in the first half of 2026, very biomarker-rich, will provide full characterization of the program to be able to move quickly into later-stage trials. There is a very efficient pathway to approval with proteinuria as a reasonably likely surrogate marker that does make it eligible for an accelerated approval pathway. Rapid pathway to the market. Quickly, just I won't spend a lot of time on this, but in terms of market size, there are 170,000 patients with IgAN in the U.S., several hundred thousand more in Europe, and then actually several million in Asia. About 60%-75% of those patients remain at high risk of disease progression, as indicated by higher levels of proteinuria, about half a gram a day. Patients are typically diagnosed in their 20s and 30s, which really does call for very safe, very convenient medications to address this large unmet need. This unmet need is actually really well highlighted in the recent updates, the proposed updates to the KDIGO guidelines for IgAN. There are three main things that we call out when we think about these updates to the guidelines. The first one you'll see on the right is expanding the patient population. Up until recently, IgAN has been treated very similarly to every other kidney indication with old blood pressure medications and steroids. Recently, since there are now approved therapies, there is an increased call to diagnose those patients. Any patient that comes in with above 0.5 g of protein a day suspected of IgAN now should get a biopsy so they can get these more specialized treatments. We believe this is really going to increase the market size. The second point that we find really crucial is the guidelines are now calling for much lower proteinuria targets, so much more aggressive treatment of the disease. The new guidelines really spell out that every patient should be below 0.5 g a day, or additional treatment does need to be added. They say preferably, actually, patients should get down to below 0.3 g a day. Really stringent targets calling for very, very efficacious medications to come to the market. Finally, they do redefine the treatment strategies. What they're now really distinctly calling for is for IgAN to be treated as an autoimmune disease, not just with generic treatments that preserve the kidney function. They are calling for every patient to be on medications that have proven to reduce the pathogenic forms of Gd-IgA. That's why we believe the anti-APRIL therapies will move to much earlier lines of treatment and actually become a foundational part of every IgAN patient's treatment right upon diagnosis. The only two classes of agents that have actually shown that they've reduced this pathogenic IgA are the selective anti-APRIL therapies or the TACI receptors. They're the dual receptors that hit both APRIL and BAFF. As I'll describe in the next couple of slides, we believe there's going to be a strong preference for the selective anti-APRIL therapies because all the efficacy in IgAN is being driven by APRIL. We believe BAFF is really only there as a potential liability specifically in IgAN. This is a slide just summarizing a little bit about the pathogenic production of IgA. As you'll see on the right-hand side, there's a four-hit hypothesis in IgAN. The first hit is this production of this pathogenic galactose-deficient IgA. The second hit is the synthesis of autoantibodies to that galactose-deficient IgA, which actually forms immune complexes, which then deposit on the kidney and cause damage. You'll see that in the past, broad B-cell depletion strategies have been tried in IgAN, things like rituximab or even selective BAFF inhibitors, but they had no effect. That's because what's really driving these pathogenic immunoglobulins in IgAN is the plasma cell. It is APRIL that's actually directly involved in the B-cell class switching to IgA-producing plasma cells and the survival of those plasma cells. APRIL is really emerging as the key driver in the pathogenesis of IgA, in IgA nephropathy. We see that with a large body of evidence across genetic models, mechanistic models, IgAN disease models. Most importantly, we're seeing that play out actually in the clinical data. What we're seeing when we look at cross-trial comparisons is that when you plot the efficacy of various agents, looking on the top at reductions in protein and on the bottom at reductions in total IgA, you'll see that in yellow, selective anti-BAFF inhibitor actually had no impact on either proteinuria or on reductions in total IgA. When both the selective anti-APRILs or the dual APRIL/ BAFF inhibitors are plotted, you'll see both effects on proteinuria and on IgA are very similar. You really would expect if BAFF was playing a role that there'd be some additive benefit there. Really, when you look at the data, even in more detail across more parameters like total IgA, galactose-deficient IgA, and urinary protein-creatinine ratio, proteinuria, you'll see that with the selective anti-APRILs on the left and the dual APRIL/ BAFF inhibitors on the right, there's really no difference across all the parameters. Really questioning why would you add BAFF if it is not adding efficacy. What you do introduce with BAFF is a potential long-term liability. When you look at impact on B-cell populations with a selective BAFF inhibitor, BENLYSTA in this case in lupus over longer-term trials, you'll see that there is a large impact on B-cells, up to an 80%-90% reduction in some B-cell populations. Conversely, on the right-hand side, you'll see with a selective anti-APRIL inhibitor, there's actually no impact over a 76-week period on circulating lymphocytes. This really begs the question, if all the efficacy is being driven by APRIL and BAFF is not adding any additional activity, why would you treat patients with a dual BAFF inhibitor? Why would we win within the selective anti-APRILs? There is really good data that selective anti-APRIL inhibitors are providing a lot of benefit for patients in IgA nephropathy. Some of the best data comes actually out of this phase II study from sibeprenlimab in the New England Journal of Medicine, really looking across three different dose levels. You can see that when sibeprenlimab was studied at 2, 4, and 8 mg IV dosed, they are getting good results. In this study, they actually did not see any increased adverse events across the doses, but they did get very good efficacy at the highest dose. You will see that there is a dose-dependent reduction in free APRIL. You will see on the right-hand side that at the high dose, the 8 mg per kilogram, when you do get this complete reduction in free APRIL, you actually are getting a dose-dependent increase in activity. On the bottom here, what you do see when looking at getting patients down into the clinical remission range, so that's below 0.3 g per day, that you get nearly twice as many patients getting to that clinical remission range as you do with the middle dose, that 4 mg per kilogram. When sibeprenlimab actually switched from phase II into phase III, they actually went into a sub-Q formulation, really looking at patient convenience over the long term. They went from an IV body-weight-adjusted dose into a flat 400 mg sub-Q dose. When we looked at it, they seemed to have packed as much drug as they could into a single injection to make it convenient. When you do the calculations, that 400 mg every four weeks, when you look at bioavailability and average body weight, they're probably dosing somewhere around that middle dose, somewhere around 3.5 mg per kilogram. We really do believe that they're leaving some efficacy on the table. Our goal with JADE 101 is to get the equivalent of this 8 mg per kilogram dose, so full inhibition of APRIL throughout the dosing interval, to get those really high levels of proteinuria reduction as seen by this top dose and also more patients into that clinical remission range. We believe that we can get best-in-class efficacy and do that with very convenient dosing with a longer dosing interval. That is the goal, as just mentioned. The profile of JADE 101 is to have this best-in-class efficacy, do it with the longest duration of action. Really aiming for a dosing interval of every eight weeks or longer, so six or less injections a year, and do it by selectively targeting APRIL without hitting BAFF. A little bit about the properties of JADE 101. This was a de novo antibody discovery campaign, so a brand- new antibody with a new epitope. It's built on an IgG1 backbone effector null. The goal was to have ultra-high affinity binding to APRIL and to introduce this half-life extension to provide really long coverage of the target at very convenient dosing intervals. We're very pleased to say that we've really hit this target product profile in preclinical testing. We will actually be presenting a poster this coming Friday at the European Renal Association, providing more characterization of this preclinical profile with some more information. What we are disclosing now is that Jade does have this femtomolar affinity and a very slow off rate, which is actually orders of magnitude more potent than any of the other competitive agents. You'll see here that compared to sibeprenlimab, which we feel is the most advanced product in this field, it's 755-fold more potent. Looking at zigakibart, which is the former Chinook, now Novartis asset, it's nearly 2,000-fold more potent. Looking at the most potent dual inhibitor of APRIL/ BAFF, povatacicept, it's over 20-fold more potent. What's important about this is that APRIL affinity really is predictive of in vivo potency, so allowing to have target coverage at lower concentrations. Really, even when you're getting down to lower concentrations in plasma, you're still going to have that complete coverage of APRIL, allowing for an extended dosing interval, but also for that complete inhibition of APRIL, which we anticipate will translate into higher clinical activity. This was really exhibited in our preclinical non-human primate studies. On the left here, you'll see the pharmacokinetic profile of JADE 101 in teal and light teal compared to sibeprenlimab in blue. On the left, you'll see on the pharmacokinetic on the left-hand side here that sibeprenlimab exhibits a very typical clearance profile that you would see in an antibody get clearance over kind of a 28-day period, which is really associated with the pharmacodynamic effect. You'll see there on the right-hand side that you have this clearance associated with the recovery of IgA. Conversely to that, what you see with JADE 101 when dosed at a similar level in teal, that's the 30 mg/ kg arm in the non-human primates, which is equivalent to how sibeprenlimab was dosed. You can see this linear clearance that really stays in the serum for many, many folds more than sibeprenlimab. This is driven partly by the fact that there is a much longer half-life. JADE 101 has a non-human primate half-life of 27 days, so nearly four-fold higher than sibeprenlimab, but also driven by the potency, which seems to overcome the target-mediated drug disposition, which you see exhibited with sibeprenlimab. What's quite remarkable here is we also show a 4 mg/ kg dose, so nearly 7.5-fold lower concentration or dose than sibeprenlimab. You will see a lower initial concentration with that dose, as you would expect. Then even around the three-week, four-week time frame, you're getting higher exposures than sibeprenlimab because you're not getting that same level of clearance that you get there. This translates on the right-hand side into very encouraging pharmacodynamic results, where you get really deep and durable depletion of IgA for extended periods of time. This profile gets us very encouraged because in IgA nephropathy, historically, what you've seen is excellent translation from non-human primates to healthy volunteers and then from healthy volunteers to patients. This gives us a lot of confidence that we can achieve our profile of best-in-class efficacy with extended dosing, allowing for dosing no more frequently than every eight weeks. We're advancing this quickly. Right now, we're in IND-enabling studies, GLP tox and getting the CMC underway for drug product release. We are on track to get initiation in the second half of this year with our phase I study. As mentioned previously, the readout for this study is in the first half of 2026. Just to say, this is not your typical healthy volunteer study just because you are going to get those very rich biomarkers out of this. We will be looking at PK. We will be looking at reductions in total IgA, which does translate well into what you expect to see in patients and then a good predictor of what you expect to see in terms of proteinuria reduction. We will be measuring reductions in free APRIL. We will be able to see the duration of time that that free APRIL is knocked down, completely suppressed, which will really give us our dose and our dose interval that we are planning to take forward into later stage trials. That will really arm us to move quickly into those patient trials and move towards generating that robust information. This is just a slide just to remind everyone that there is really a high level of translation from what you see in healthy volunteers to patients. You can see that in IgAN patients, you do see a very close correlation to what you see from healthy volunteers. In IgAN patients as well, on the right-hand side, lowering in IgA does have a predictive effect of what you anticipate seeing in terms of proteinuria reduction, which is that surrogate biomarker that can be used for accelerated approval. I did mention we are also developing a pipeline beyond JADE 101. We are looking at a number of indications and targets just beyond IgAN. We are bringing, we do have two other assets, so JADE-0 02 and JADE-0 03 as well. Just to summarize, we're extremely excited. It's been a very, very eventful first year of existence for us as Jade. We're really excited to keep moving forward and continue to drive towards becoming a clinical stage company in the second half of this year. We do believe that the anti-APRIL compound, JADE 101, has a clear line to becoming best in class and best in disease for a large market opportunity. We're extremely excited to present that data in the first half of the year, which we believe is extremely de-risking and eventful. Just a reminder, we are well-funded. When we launched the company, we raised a $95 million convertible note. Then concurrently with the reverse merger that we closed at the end of April, we raised another $205 million. Since inception, we have raised $300 million. That does support operations of these three programs through 2027, through some very meaningful milestones for the company. Maybe I'll leave it there and just say thank you and see if there's any questions. The efficacy profile is the same as the other anti-APRILs in development. Do you think the increased potency and affinity affecting sort of the dosing regimen being easier would be enough to position it superiorly commercially? The short answer to that is yes. We do know that these patients are typically diagnosed between the ages of 15 and 30 or the second and third decades of life. They need decades and decades of treatment. This is a long-term chronic illness that typically proceeds over 10, 20 years to end-stage kidney disease. We do think that the less a patient has to administer, the less a patient has to think about it, the more useful it will be. As mentioned in the presentation, we think with this profile, we have a high degree of confidence that we can get to Q8-week dosing, so roughly six injections a year. There is a possibility that if everything goes our way, it could be even a little bit of a longer dose interval. We do think that is really meaningful for patients and their families as well, so they do not have to think about their disease other than these injections that are not very frequent. That said, we do see a very meaningful opportunity to differentiate on efficacy, which is really the ultimate driver for clinicians and for patients. We do have strong conviction that sibeprenlimab is not optimizing their dosing. We will pick our dose and dose interval to maximize that reduction in free APRIL, which we believe will then translate into better overall levels of proteinuria. As mentioned, we think the most important thing is getting more patients into those target zones, so 0.5 g a day or lower, but ideally into that clinical remission range, into 0.3 g and lower. We do think that there's a really good opportunity to differentiate that way as well. Okay. Quick follow-up with that in mind, do you see yourself doing a direct comparison trial somewhere in your clinical development program, or do you think comparing across studies will get you there? Yeah. Really good question. We have not guided towards that at this point. We have just really guided through providing data in the first half of 2026. At that point, pending positive data, we will look at the data and understand what is possible, have some regulatory interactions, and decide on the future development plan. More to come on that question.