Jade Biosciences, Inc. Common Stock Wells Fargo 21st Annual Healthcare Conference

Great. Thanks so much, and thanks to you and the whole team for hosting us. It has been a really productive, great to get a chance to get back into the season after an amazing summer. Really pleased to talk a little bit about Jade. We are a fairly new company, just started two years ago, looking to develop best-in-class therapies across a number of different autoimmune diseases. We have three assets that we have licensed in from Paragon, which I am sure many people are familiar with, a protein engineering company that really does discovery across a number of different monoclonal antibodies. Our lead program is JADE 101. It is an anti-APRIL, going after IgA nephropathy. Extremely exciting program. IgA nephropathy is an area of large unmet need.

We believe it is around a $20 billion market opportunity in the U.S. alone, and we believe the anti-APRIL class is really going to become dominant and foundational therapy for patients at risk of disease progression. JADE 101 has a really good opportunity to become the best in disease molecule. We recently reported out some phase I data in June of this year, showing very deep and profound reductions in IgA, the key pathogenic marker of potential disease progression, approaching 70%, the largest ever drop seen with a single dose in healthy volunteers with any agent. Really showing that JADE 101, due to its potency, can capture the maximal activity available to the mechanism. Also, those reductions were sustained for up to 12 weeks, really showing that we can have maintenance of the disease with a single injection just every three months.

An extremely promising profile that we are really excited to move forward. We are currently in a phase II trial with JADE 101, reporting out that data next year in 2027, moving quickly towards that key milestone for us as a company. We are not waiting for that data set to advance a phase III study. We are actually working hard to initiate a phase III. We plan to dose our first patient in a phase III in the first half of 2027, and move very quickly towards a data readout there, and commercialization, so we can try to capture as much of that large market as possible. We also have JADE 201, which is just in a phase I study right now. That is an anti-BAFF-R compound that is a B cell depleting agent that is applicable to a number of different autoimmune diseases.

Really anything where rituximab is standard of care, JADE201 has a chance to improve treatment there. We are following the footsteps of ianalumab, which is an asset at Novartis that is currently in 6 different phase IIIs, reported out positive data in Sjögren's last year, as well as second-line ITP, and has a number of different readouts coming out over the next 12 months that will help inform our strategy there. We are currently in a phase I study in rheumatoid arthritis patients, and planning to read out that data in 2027 as well. Our third program, which we just recently disclosed, is JADE301. It is an anti-interferon beta, and the lead indication there is for dermatomyositis, a very severe disease that affects both the muscle and the skin.

We are just going to go into a phase I healthy volunteer study with that program, and looking forward to reading out some data on that one in 2027 as well. Very active build on the pipeline and the team. We have a great team that we have recruited. A number of us actually worked together at Chinook Therapeutics before. Andrew and I were both there essentially since the founding of that company. We have managed to pull across a number of the best talents, so a lot of development capabilities. We are well-funded as well. We have completed a few financings in the last year, which really funds our entire pipeline through to the fourth quarter in 2028, past all of those milestones that I talked about. Very exciting time for us as a company.

Yeah. It is a great question. We remain very confident that with JADE101, we have the best profile given those large levels of IgA reductions and the ability to sustain that for 12 weeks. Andrew, do you want to talk a little bit about the details and the differentiation there?

Yeah. When we designed JADE 101, our goal was to deliver the full disease-modifying efficacy of B-cell modulation in IgAN with a convenient infrequent dosing schedule. We really wanted to optimize two specific parameters. One was to improve the potency over the first-generation agents, and the second was to half-life extend, to be able to spread out that dosing interval. We feel like our phase I healthy volunteer data really demonstrated both of those attributes, where we had an extended half-life relative to sibeprenlimab by about 2.6-fold, and demonstrated really remarkable in vivo IgA-lowering potency, which reflects the high binding affinity to APRIL that JADE101 was selected for. As a result, we see these rapid, large reductions in IgA really reaching the biological max effect you can see with a single dose of a selective APRIL inhibitor.

Our assessment of the CLIMB data suggests they've also effectively half-life extended their molecule similar to JADE101, but have done so with a compound that has lower binding affinity. They really haven't been able to incorporate that improved potency, which we think is really critical to be able to drive early and rapid IgA reductions to maximum levels, and do so consistently across the broader population. Whereas with a lower binding affinity molecule, there is potential for less complete IgA suppression and more variability, and we think that's played out in the data. As Tom mentioned, really confident about the profile of JADE101, and excited to develop it as a best-in-class asset.

Yeah. I think it's both the depth, the duration, and the consistency of the IgA reduction at the 700 milligram dose of JADE301, which is our planned induction dose, taken forward into phase II and phase III. We saw rapid IgA reductions that reached 70% decrease from baseline and were sustained for 12 weeks following dose before recovery beyond that. We saw highly consistent responses across the healthy volunteer participants included in the study, with very small error bars. With CLIMB, they demonstrated IgA reductions that maxed out in the 55-ish percent range- including at their 320 milligram maintenance dose.

Higher doses of CLIMB, either as two separate 320 milligram doses 2 weeks apart or a single 480 milligram dose, didn't appear to be able to break through that mid-50% floor that they achieved. So more like those first-generation agents with sibeprenlimab that appeared to require repeat dosing over time in IgAN patients to approach the IgA reductions observed with JADE101 with a single dose. We also saw higher variability in the response of IgA with CLIMB across all dose levels, which would be consistent, potentially, with the lower binding affinity not being able to completely neutralize all biologically relevant APRIL present in the tissues, particularly the mucosal immune system, to drive local IgA production and mucosal immunity.