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potential of JADE-001, JADE-002 and JADE-003 to become best-in-class drugs and the timing of the combined company's trading on The Nasdaq Capital Market. The words opportunity, potential, milestones, pipeline, can, goal, strategy, target,
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Jade Biosciences is advancing potentially best-in-class therapies for
autoimmune diseases Current funding through 2027, well-beyond biomarker-rich JADE-001 healthy volunteer data Planned Planned Interim FIH Potential MOA Program Discovery IND-enabling Clinical FIH Data Indications anti-APRIL JADE-001 2H25 1H26 IgAN
Multiple Undisclosed JADE-002 1H26 systemic AI diseases Undisclosed JADE-003 1H27 Undisclosed Development candidates licensed from Paragon Assets designed to maximize clinical responses Patient friendly, infrequent dosing Notes: Jade has entered
into an exclusive JADE-001 license agreement with Paragon Therapeutics. Jade holds an exclusive option to license JADE-002 and JADE-003 from Paragon. Jade has not yet entered into a license agreement with respect to JADE-002 or JADE-003. 3 MOA
- mechanism of action; FIH - First-In-Human; IgAN - IgA nephropathy; AI - autoimmune
JADE-001: a potentially best-in-class anti-APRIL mAb for IgAN
Jade is developing a potentially best-in-class anti-APRIL mAb Current
treatments Mechanism has Estimated Anti-APRIL do not adequately potential to be disease class poised to be address the need for modifying, reducing $10B+ long-term disease- frontline treatment pathogenic IgA and modifying therapy in branded for IgAN
proteinuria, stabilizing a typically young IgAN kidney function market patient population JADE-001 is designed Biomarker-rich and Potentially Efficient to have superior highly translational potency and an HV data expected path to PoC best-in-
extended half-life for in 1H26; surrogate maximal efficacy & and market endpoints class convenient dosing expected to support potential profile IgAN approval HV - healthy volunteer, mAb - monoclonal antibody 5 5
~169K+ IgAN patients in the U.S. with majority requiring treatment*,
representing potential $10B+ market IgAN patients with persistent proteinuria are ~1M+ global patients, at risk of kidney failure significant potential ex-U.S. market potential IgAN is an autoimmune kidney disease, typically diagnosed 0 100 200 300
400 1,300 US in 20- to 30-year-olds, requiring life-long therapy. '000 Patients EU Japan China 169 205 103 783 1,260 ~169K+ patients with IgAN in the U.S., with 60-75% requiring treatment per international guidelines There is a high unmet need
for disease-modifying treatments that are safe, well-tolerated, and convenient particularly considering that IgAN is often diagnosed in young adults and requires lifelong care *Per KDIGO guidelines, treatment should be initiated in all cases where
patients have proteinuria 0.5 g/day. Notes: U.S. prevalence estimate from FDA; EU prevalence estimate from EMA; Japan / China prevalence estimates from a Novartis presentation. Estimated pricing of ~$120K-$150K per year based 6 on Filspari
and Tarpeyo. Sources: 2023 Pitcher (CJASN); FDA Reviews for Filspari / Tarpeyo; EMA; Novartis; 2018 Schena (Seminars in Nephrology); Reuters IgAN est. prevalence
Proposed updates to KDIGO guidelines support the frontline therapeutic
potential of the anti-APRIL class in IgAN Expanding Patient Population IgAN patients at risk of progressive kidney Kidney biopsy recommended in all adults function loss with proteinuria 0.5 g/d where IgAN is a possible diagnosis In
all patients these Recommends additional treatment should Drivers of Manage the generic Manage the IgAN-specific should be addressed response to IgAN-induced nephron be initiated in all cases where patients drivers for nephron loss
simultaneously nephron loss loss have proteinuria 0.5 g/d Lower Proteinuria Targets Establishes new treatment goal: proteinuria maintained at <0.5 g/day, preferably <0.3 Reduce pathogenic Reduce glomerular g/day Cardio- forms of
IgA and Blood Reduce hyperfiltration and vascular Treatment pressure IgA immune glomerular the impact of risk strategies control complex inflammation proteinuria on the Redefining Treatment Strategies reduction formation tubulointerstitium
New guidelines direct the use of treatments that have been proven to reduce pathogenic forms of IgA KDIGO updates anticipated to increase IgAN diagnosis, expand at-risk patient population requiring treatment, lower proteinuria target to clinical
remission, and require targeted therapies that reduce pathogenic IgA. Sources: KDIGO Guidelines Public Review Draft; 2023 Mathur (NEJM); Jade analysis 7 KDIGO - Kidney Disease Improving Global Outcomes
Reducing pathogenic IgA production by plasma cells is a potentially
disease-modifying approach for IgAN Broad B-cell depletion is ineffective in IgAN while targeted plasma cell modulation is highly effective. B-cell depletion with rituximab (anti-CD20) failed to reduce Gd- APRIL and
dual APRIL/BAFF neutralization result in significant and sustained IgA1, anti-Gd-IgA1 autoantibody, or proteinuria and did not depletion of Gd-IgA1, reduction in proteinuria, and eGFR stabilization. impact eGFR. BAFF neutralization
(blisibimod) did not reduce IgA or proteinuria. HIT 1 Plasma cell Mucosa & Production of galactose-deficient Bone marrow Mucosa differentiation bone marrow IgA1 (Gd-IgA1) APRIL blocking HIT 2 therapy Synthesis of anti-Gd-IgA1 autoantibodies HSC
Pro B cell Large Small Immature Mature Na ve Plasma cell pre-B cell pre-B cell B cell B cell HIT 3 Autoantibodies bind Gd-IgA1 to form pathogenic immune Memory B cell complexes APRIL CD20 expression HIT 4 Deposition of immune complexes Antibody
in the mesangium and initiation of BAFF dependency class-switching kidney injury APRIL dependency *Gradient indicates level of receptor expression Neutralizing APRIL depletes Gd-IgA1, reduces proteinuria, and preserves eGFR, providing a
disease-modifying treatment of IgAN without impacting B-cell development and maturation. Sources: 2024 Cheung (Front Nephrol); 2023 Mathur (J Clin Med) 8
Selectively targeting APRIL potentially provides disease modification
without added immunosuppression of BAFF inhibition APRIL is the plasma cell survival factor critically linked Targeting APRIL selectively modulates plasma to IgAN pathogenesis and disease activity cells, maintaining pool of mature B cells APRIL BAFF
Risk variant in IgAN GWAS Elevated in IgAN patients and associated / with disease severity Promotes excess secretion of Gd-IgA1 in IgAN No data patient lymphocytes ex vivo Drives IgA class switching
via TACI in vivo Overexpression in mouse model leads to glomerular IgA deposition KO mouse model decreases IgA levels / IgA+ plasma cells in small intestine Selective inhibition demonstrates
preclinical / clinical efficacy in IgAN Existing genomic, mechanistic, IgAN model, and clinical data support the importance of APRIL over BAFF in IgAN, and APRIL-only blockade avoids the potential for unnecessary immunosuppression
Sources: 2024 Cheung (Front Nephrol); Chinook 2022 CKD3 Presentation; 2004 Castigli (PNAS); 2001 Schiemann (Science) 9
Reductions in proteinuria and IgA in IgAN clinical studies indicate
APRIL inhibition is the driving force behind TACI-Fc efficacy 10 0 Weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 52 -10 Blisibimod (anti-BAFF) -20 Sibeprenlimab (anti-APRIL, 8 mg/kg) Sibeprenlimab (anti-APRIL, 4 mg/kg) -30 Zigakibart (anti-APRIL) -40
Atacicept (TACI-Fc, 150 mg) -50 Atacicept (TACI-Fc, 75 mg) -60 Povetacicept (Eng. TACI-Fc, 240 mg) -70% Povetacicept (Eng. TACI-Fc, 80 mg) 0 4 8 12 16 20 24 28 32 36 40 44 48 52 0 Weeks -10 -20 -30 TACI-Fc fusion proteins inhibit APRIL & BAFF
-40 -50 -60 -70 -80% Notes: Cross-trial comparisons are inherently limited and presented for hypothesis-generating purposes only. Data digitized from graphs where publications did not provide specific values. Values only included if N > 5.
Blisibimod W52 data is from W60. 10 Sources: Anthera 2017 10-K; 2023 Mathur (NEJM); 2023 Barratt (ERA Poster); 2024 Lafayette (KI Reports); 2024 Tumlin (WCN Presentation); 2024 Madan (ASN Presentation) IgA 24h UPCR from Baseline (%)
No clinical evidence that inhibiting BAFF provides additional efficacy
beyond APRIL alone in IgAN Sibeprenlimab Zigakibart Atacicept Povetacicept MoA anti-APRIL anti-APRIL TACI-Fc Engineered TACI-Fc Status P3 P3 P3 P3 IgA Gd-IgA1 UPCR IgA Gd-IgA1 UPCR IgA Gd-IgA1 UPCR IgA Gd-IgA1 UPCR from baseline in critical
disease markers 33% (W36 timepoint*) 53% 59% 60% 60% 64% 63% 64% 67% 65% 69% 69% N=79 (4/8 mg/kg pooled) N=35 (600 mg) N=32 (150 mg) N=9 (80 mg) GFR stabilization (12 months) (18 months) (24 months) (12 months)
Hematuria No data resolution Safety Well tolerated, no overall infections, Well tolerated (no pbo), no drug Well-tolerated, slight in infections (& Well-tolerated (no
pbo) slight in URTIs vs. pbo discontinuations URTIs) vs. pbo 240 mg infections P3 Dosing 400 mg SC, Q4W 600 mg SC, Q2W 150 mg SC, QW 80 mg SC, Q4W Notes: Cross-trial comparisons are inherently limited and presented for
hypothesis-generating purposes only. Zigakibart IgA / Gd-IgA data at W40; UPCR data at W52 (only timepoint available); change from baseline is not pbo-controlled; N represents patients on dose(s) for which data is shown. Atacicept infections/URTIs
placebo - (32%/0%), 25 mg (38%/0%), 75 mg (49%/9%), 150 mg 11 (39%/6%). Povetacicept infection rates: Grade 1/2/ 3 - 80 mg 10%/5%/0%, 240 mg 18%/27%/3%. Sibeprenlimab infections/URTIs placebo - (55%/0%), 2 mg/kg (39.5%/8%), 4 mg/kg
(56%/12%), 8 mg /kg (53%/5%). Sources: 2023 Mathur (NEJM); 2024 Barratt (ERA Presentation); VERA January 2024 R&D Day; ALPN 2024 WCN Investor Update; 2024 Madan (ASN Presentation)
BAFF inhibition is accompanied by the potential for significant
long-term B cell depletion Long-term BAFF inhibition significantly depletes whereas chronic APRIL inhibition does not impact all B cell populations circulating lymphocytes 9 10 /L ~7-year belimumab data in SLE shows continuous BAFF
inhibition lowers B cell populations from ~50% to ~99%, with most populations decreasing >80%. Long-term BAFF suppression, in an otherwise young and healthy patient population, is unnecessary given equivalent efficacy in IgAN from anti-APRILs and
TACI-Fcs observed to date. 12 Sources: 2022 Struemper (Lupus Sci Med); Barratt ASN 2024
Deeper APRIL suppression drives superior clinical efficacy
Highest rates of clinical remission (proteinuria <0.3 g/day) for sibeprenlimab was accompanied by the deepest levels of APRIL suppression. Safety profile consistent across dose levels, with no increase in overall infections.
Potential for anti-APRILs with higher affinity and increased systemic exposure to provide more complete APRIL neutralization throughout the dosing interval and maximize clinical remission rates. Est. P3 AVG equivalent dose JADE-001 has potential to
demonstrate (3.5 mg/kg IV) superior clinical activity by maximizing remission rates in significantly more patients than other anti-APRIL programs in development. Proteinuria < 0.3 g/day (% patients @12 mths) Note: Estimated sibeprenlimab P3 dose
(400 mg SC) based on average 85 kg IgAN patient (95% CI ~50-120 kg) and 75% bioavailability. 13 Source: 2023 Mathur (NEJM) fAPRIL
Sibeprenlimab is potentially under-dosed in ongoing Phase 3 trial Other
anti-APRILs do not inhibit APRIL fully through the dosing interval Sibeprenlimab dosed as a single 400mg SC injection Q4W in ongoing global Phase 3 VISIONARY trial. 400 mg SC Q4W equates to ~3.5 mg/kg IV for average Placebo 2 mg/kg
IV 4 mg/kg IV 8 mg/kg IV IgAN patient (2.5-6 mg/kg). Annualized eGFR slope 2 (mL/min/1.73m , baseline Estimated Phase 3 equivalent dose range demonstrated to W52) lower efficacy on key UPCR endpoints in Phase 2 UPCR from ENVISION
trial. baseline (%, W36) 0.1 ~50% of HV in P1 SAD showed positive antidrug antibody 2 mg/kg dose -0.8 activity following single SC dose, which may further did not 13 stabilize eGFR impact PK, efficacy, and safety profile in Phase 3. at 1
year, while higher doses did -4.1 Potential under-dosing of sibeprenlimab 50 -5.9 creates additional opportunity for JADE-001 57 63 to demonstrate potentially best-in-class clinical Est. P3 AVG Est. P3 AVG activity for patients. equivalent dose
equivalent dose (3.5 mg/kg IV) (3.5 mg/kg IV) Notes: Estimated sibeprenlimab P3 dose based on average 85 kg IgAN patient (95% CI ~50-120 kg) and 75% bioavailability. Sources: 2023 Mathur (NEJM); 2023 Zhang (Clin Pharm) 14 HV - healthy
volunteers; ADA+ - antidrug antibody positive
Potentially best-in-class profile of JADE-001 Femtomolar APRIL Affinity
+ Half Life Extension Potentially best-in-class Infrequent Q8W+ dosing Avoids unnecessary efficacy immunosuppression Minimizes burden in a typically APRIL inhibitors demonstrate Selectively targeting APRIL provides greater proteinuria reduction and
young IgAN patient population disease modifying impact while increased clinical remission rates avoiding B-cell depletion associated potentially requiring life-long therapy with higher exposures and more with BAFF inhibition ( 6
injections/year) complete APRIL suppression 15
Potentially best-in-class properties of JADE-001 Ultra-high (fM) APRIL
binding Novel IP for composition affinity Binds APRIL to neutralize activity of matter into mid-2040s Greater APRIL binding affinity than sibeprenlimab, zigakibart, povetacicept and atacicept De novo antibody discovery Half-life
extension through campaign pursued to achieve fully- validated YTE Fc human, potentially best-in-class modification mAb Longer exposure intended to maximize efficacy and reduce dosing frequency Effector-null human IgG1 Fc Notes; Paragon has
filed provisional patent applications covering the subject matter of JADE-001, which we have exclusively licensed from Paragon. No head-to-head clinical trials have been conducted between JADE-001 and the referenced drug candidates. Cross-trial
comparisons are inherently limited and presented for hypothesis-generating purposes only. 16 16 fM - femtomolar
JADE-001 has femtomolar affinity and a slow off-rate that is superior
to other anti-APRILs currently in development APRIL affinity by SPR is highly predictive of in vivo APRIL affinity by SPR is highly predictive of potency to lower serum IgA in humans in vivo potency to lower serum IgA in humans 1000 Ataci Ziga 100
Sibe 2 R = 0.9987 10 Pove 1 0.1 1 10 100 1000 EC ( M) 50 Source: Internal data; Benchmarks manufactured based on publicly available sequences. Atacicept APRIL KD 672 pM (Vera internal data). IgA EC estimates calculated using compartmental PK
models 50 linked to indirect response models to describe IgA kinetics built using published PK and IgA concentration-time profiles for each molecule. Sibeprenlimab: Mathur, 2022 and Zhang, 2023; Ziga: ASN, 17 2021/2022 and WCN, 2021; Povetacicept:
Davies, 2024; Ataci: Willen, 2020, Nestorov, 2008/2010, Munafo, 2007). These data are derived from different trials at different points in time, with differences in trial design and populations. As a result, cross-trial comparisons cannot be made,
and no head-to-head clinical trials of JADE-001 and other agents have been conducted. KD(pM)