AnaptysBio, Inc. · NASDAQ:ANAB
AnaptysBio — Investor Day (October 2025)
56 slides from AnaptysBio's investor day presentation, Oct 14, 2025
Slide 1: ANB033 (CD122 antagonist) Investor Event
ANB033 (CD122 antagonist) Investor Event Oct. 14, 2025
Slide 2: Forward looking statement
Forward looking statement This presentation and any accompanying oral presentation contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to: the timing of the release of data from the
Slide 3: Intention to separate into two independent, publicly traded companies
Intention to separate into two independent, publicly traded companies to unlock and maximize value Biopharma Co Focus on developing and potentially commercializing therapeutics for autoimmune diseases Rosnilimab ANB033 ANB101 (Pathogenic T cell depleter) (CD122 antagonist) (BDCA2 modulator) P2b comp
Slide 4: Targeting CD122 has strong biologic rationale
Targeting CD122 has strong biologic rationale Why target CD122? • Targeting only the IL-15 cytokine addresses inflammation, but may allow pathogenic cell survival through alternative escape mechanisms • CD122 is the shared receptor subunit through which both IL-15 and IL-2 signal • IL-15 and IL-2 ar
Slide 5: ANB033: potential best-in-class CD122 antagonist
ANB033: potential best-in-class CD122 antagonist with optimized dual IL-15 and IL-2 signaling inhibition ANB033 designed for high potency IL-15 IL-2 • Specific binding epitope engineered for high affinity • Inhibit both IL-15 and IL-2 signaling ANB033 Targets pathogenic cells in inflamed tissue X •
Slide 6: Broad therapeutic potential across autoimmune and inflammatory diseases
Broad therapeutic potential across autoimmune and inflammatory diseases Gastroenterology Dermatology Other Areas Celiac Disease Atopic Dermatitis Asthma Crohn’s Disease Alopecia Areata Multiple Sclerosis Eosinophilic Esophagitis (EOE) Hidradenitis Suppurativa Psoriatic Arthritis Ulcerative Colitis L
Slide 7: ANB033 has pipeline-in-a-product potential
ANB033 has pipeline-in-a-product potential ANB033: initiated initial P1b in CeD CeD Market1 • Multiple pathogenic drivers of • >250k diagnosed U.S. disease non-responsive CeD patients • Inflamed cells in CeD respond to • Gluten-free diet highly restrictive; both IL-15 and IL-2 ~50% of patients suffe
Slide 8: Agenda: ANB033 (CD122 Antagonist)
Agenda: ANB033 (CD122 Antagonist) TOPIC SPEAKER Martin Dahl, Ph.D., CD122 biology and preclinical data Senior Vice President, Research John Kwon, M.D., Ph.D. Phase 1a in healthy volunteers Vice President, Clinical Development Joseph Murray, M.D. Professor of Medicine Drug development for CeD Mayo Cl
Slide 9: ANB033 blocks CD122 to inhibit pathogenic immune cells
ANB033 blocks CD122 to inhibit pathogenic immune cells CD122 is the beta subunit (IL-2Rβ) of the receptor for IL-15 and IL-2 • Expressed on subsets of CD8+ and IL-15 IL-2 CD4+ T cells and NK cells CD122 antagonism reduces these ANB033 immune cell subsets • Dependent on IL-15 and/or IL-2 for X mainte
Slide 10: ANB033's optimized epitope and high affinity lead to differentiated inhibition
ANB033’s optimized epitope and high affinity lead to differentiated inhibition of IL-15 and IL-2 signaling 300 ANB033 epitope sits IL-15 stimulation squarely within IL-15 and 125 Clinical 200 IL-2 binding footprint range 100 (% of Stimulated) Proliferating STAT5 Reporter isotype) Proliferating 75 10
Slide 11: ANB033 shows strong survival benefit in aggressive GvHD mouse model
ANB033 shows strong survival benefit and reduced cytolytic gene expression in aggressive GvHD mouse model Survival Survival Body Bodyweight loss (carried) Weight Loss (carried) 10 100 90 End of dosing End of dosing 80 Remaining (%of Start) 70 0 ANB033 Remaining 60 Forte anti-CD122 of Start) 50 Weigh
Slide 12: ANB033 reduces key CD122+ target cells in cynomolgus monkeys
ANB033 reduces key CD122+ target cells in cynomolgus monkeys CD122+ CD8+ T cell impact CD122+ NK cell impact Dosing Recovery Dosing Recovery 40% 40% 20% 20% % Change from baseline % Change from baseline 0% 0% -20% -20% -40% -40% -60% -60% -80% -80% -100% -100% 0 21 42 63 84 105 126 147 0 21 42 63 84
Slide 13: CeD is characterized by dense infiltration of CD122+ immune cells
CeD is characterized by a dense infiltration of inflammatory CD122+ immune cells IFNγ Cell Biopsy scRNAseq CD122 umap2 IL15 CD4+ T cells IFNG Structural cells, myeloid cells, umap1 NK and B cells Granzyme B CD8+ T cells Dense CD122 expression by infiltrating immune cells • IFNγ expression: cytotoxic
Slide 14: ANB033's MOA ideal fit for targeting CeD inflammation
ANB033’s MOA ideal fit for targeting CeD inflammation CeD marked by excessive IL-15 and IL-2 production which perpetuates disease Gliadin from gluten Inhibition of IL-15 signaling Loss of barrier integrity • IL-15 induces proliferation of IELs o Majority of IELs are CD122+ T cells • Inhibiting IL-15
Slide 15: Previous approaches have not addressed multiple pathogenic drivers of CeD
Previous approaches have not addressed multiple pathogenic drivers of CeD However, a CD122 antagonist targets both key pathogenic drivers of CeD Gliadin from gluten Loss of barrier integrity IL-15 antagonists: Clinical PoC P2 ongoing P1b PoC Lacked potency IEL Gliadin IL-15 TG2 IFNγ ANB033 Non-immun
Slide 16: ANB033 prevents gluten-induced villous atrophy
ANB033 prevents key CeD histologic manifestation of gluten-induced villous atrophy Sham Gluten + Gluten + Isotype Control ANB033 ANB033 treatment shows improved histology: preserves villus height and crypt depth (Vh:Cd) in CeD mouse model Note: HuDQ8-Dd-villin-IL-15tg mice on a gluten-free diet are
Slide 17: ANB033 significantly prevents reduction of Vh:Cd ratio
ANB033 significantly prevents reduction of Vh:Cd ratio compared to control Vh:Cd ratio ANB033 impact on Vh:Cd ratio Healthy tissue: * * High villus height, lower crypt depth 3 Vh:Cd Ratio 2 CeD tissue: Reduced villus height, extended 1 crypt depth Sham Isotype ANB033 + Gluten + Gluten ANB033 treatme
Slide 18: ANB033 prevents gluten-induced intestinal inflammation
ANB033 prevents gluten-induced intestinal inflammation Epithelial layer of small intestine No increase in CD8+ IELs 800000 * * Count of CD8+ IELs Count of CD8+ IELs 600000 Lamina propria (LP) 400000 No increase in CD4+ IFNγ + T cells Count of CD4+ IFNγ + cells 6000 * Count of CD4+ IFN-g+ cells 20000
Slide 19: ANB033 differentiated impact in CeD patient-derived PBMCs
ANB033 shows differentiated impact in CeD patient-derived PBMCs compared to competing anti-IL-15s and CD122s Cytotoxic CD8+ T cells CD4+ Th1/Th2 T cells 120 Clinical 120 Clinical range range 100 100 (% of Isotype) (% of Isotype) Proliferating Proliferating 80 80 60 60 40 40 20 20 0 0 10 -3 10 -2 10
Slide 20: Assessing ANB033's potential to treat EoE
Broad therapeutic potential across autoimmune and inflammatory diseases Gastroenterology Dermatology Other Areas Celiac Disease Atopic Dermatitis Asthma Crohn’s Disease Alopecia Areata Multiple Sclerosis Eosinophilic Hidradenitis PsA Esophagitis (EoE) Suppurativa Type 1 Diabetes Ulcerative Colitis L
Slide 21: EoE is characterized by dense infiltration of CD122+ immune cells
EoE is also characterized by a dense infiltration of immune cells presenting CD122+ expression Cell Biopsy scRNAseq CD4+ and ILC2 (dupilumab-sensitive pathway) CD122 IL15 Structural cells, myeloid cells NK umap2 IL13 IL5 CD8+ T cells CD4+ T cells CD8+ and NK and ILC2 Eosinophils (dupilumab-insensiti
Slide 22: ANB033 targets multiple drivers of EoE biology
Similar to CeD, ANB033 targets multiple drivers of EoE biology addressing both dupilumab sensitive and insensitive pathways Allergens, irritants, microbes, reflux, etc. Barrier Dysfunction CD4+ and ILC2 IL-15 IL-15 IL-15 (dupilumab-sensitive) ANB033 ANB033 CD8+ ANB033 • Reduces CD4+ T cell CD4+ prol
Slide 23: Mechanisms targeting only downstream signals have not been successful in EoE
Mechanisms that target only downstream signals of inflammation have not been successful in EoE Allergens, irritants, microbes, reflux, etc. Barrier Dysfunction Tissue Approved damage IL-15 IL-15 IL-15 Dupilumab (anti-IL-4Ra) ANB033 ANB033 CD8+ ANB033 CD4+ Has PoC T cell IL-2 T cell IL-4 ANB033 IL-5
Slide 24: ANB033 reduces CD4+ T cell and ILC2 derived Th2 cytokines
ANB033 reduces CD4+ T cell and ILC2 derived Th2 cytokines, proven drivers of EoE pathology IL-5 secretion IL-13 secretion 125 125 (% of Isotype Control) Clinical Clinical (% of Isotype Control) range range 100 100 PBMC 75 75 IL-5 IL-13 50 50 25 25 0 0 0 0.001 0.01 0.1 1 10 100 0 0.001 0.01 0.1 1 10
Slide 25: ANB033 reduces CD8+ T cell and NK cell derived Th1 cytokines
ANB033 reduces CD8+ T cell and NK cell derived Th1 cytokines and cytolytic markers IFNγ secretion Granzyme B secretion 150 150 Clinical Clinical range (% of Isotype Control) range (% of Isotype Control) 100 100 Granzyme B IFNγ 50 50 0 0 0 0.001 0.01 0.1 1 10 100 0 0.001 0.01 0.1 1 10 100 Antibody (n
Slide 26: ANB033 prevents eosinophilia by targeting upstream inflammation
ANB033 prevents eosinophilia by targeting upstream inflammation Esophageal eosinophils Aspergillus-induced eosinophilia (Lung sample shown) 4×10 -5 Eosinophils (per um2) Isotype Control 3×10 -5 2×10 -5 1×10 -5 0 Saline Isotype ANB033 Control Surrogate Lung eosinophils ANB033 1×10 3 Eosinophils (per
Slide 27: Agenda: ANB033 (CD122 Antagonist)
Agenda: ANB033 (CD122 Antagonist) TOPIC SPEAKER Martin Dahl, Ph.D., CD122 biology and preclinical data Senior Vice President, Research John Kwon, M.D., Ph.D. Phase 1a in healthy volunteers Vice President, Clinical Development Joseph Murray, M.D. Professor of Medicine Drug development for CeD Mayo Cl
Slide 28: ANB033 Phase 1a trial ongoing in healthy volunteers
ANB033 Phase 1a trial ongoing in healthy volunteers Objectives • Safety and tolerability • Evaluate PK and immunogenicity Design • All healthy volunteers have been dosed o ANB033: n=60 o Placebo: n=20 • Administered both IV and SC dosing • 10 cohorts: Four SAD IV, three SAD SC and three MAD SC • Fol
Slide 29: ANB033 favorable safety, tolerability and PK profile in Phase 1a
ANB033 demonstrated favorable safety, tolerability and PK profile in Phase 1a Phase 1a results to date ✓ Safe and well tolerated ✓ No unexpected findings ✓ PK and PD support SC dosing Favorable safety and tolerability Rapid and sustained PK profile • No safety concerns at any dose • Favorable 2 to 3
Slide 30: ANB033 significantly reduces CeD relevant CD8+ T cells and NK cells
ANB033 significantly reduces CeD relevant CD8+ T cells and NK cells after single dose Effect of ANB033 is limited to CD122 expressing cells CD122+ CD8+ T cell impact CD122+ NK cell impact 20% 20% % Change from baseline % Change from baseline 0% 0% 0% -20% -20% -21% -40% -40% -60% -60% -80% -69% -80%
Slide 31: Anti-IL-15 and CD122 therapies show sustained reduction in NK cells
Anti-IL-15 and CD122 therapies have demonstrated sustained reduction in CD122+ NK cells with no observed safety issues ANB033 effect on total NK cells 75% Placebo IV Dose SC Dose % Change from baseline 50% 25% 0% -25% -50% -75% 0 7 13 19 25 31 37 43 49 55 61 67 73 79 85 Time (days) No safety signals
Slide 32: Agenda: ANB033 (CD122 Antagonist)
Agenda: ANB033 (CD122 Antagonist) TOPIC SPEAKER Martin Dahl, Ph.D., CD122 biology and preclinical data Senior Vice President, Research John Kwon, M.D., Ph.D. Phase 1a in healthy volunteers Vice President, Clinical Development Joseph Murray, M.D. Professor of Medicine Drug development for CeD Mayo Cl
Slide 33: KOL discussion
KOL discussion • Co-founder and past president of North American Society for Study of CeD • Contributed to 2013 guidelines and 2019 AGA practice update on diagnosing and monitoring CeD • Published more than 450+ peer- reviewed papers on CeD • Past chair of AGA’s Intestinal Disease Section o Broad ex
Slide 34: Gluten and Celiac Disease (CeD)
Gluten and Celiac Disease (CeD) • Inflammation • Villi destruction • Genetic predisposition • Crypt hyperplasia • Permanent intolerance to gluten • IEL proliferation Gluten Gluten exclusion Normal histology Total villous atrophy (Marsh 0) (Marsh 3) Note: Marsh score -- a histological grading system
Slide 35: Majority of CeD patients desire new treatment options
Majority of CeD patients desire new treatment options Consequences of persistent, chronic active CeD: • GI symptoms: abdominal pain, diarrhea, constipation • Severe malnutrition: vitamin deficiencies, anemia • Reduced quality of life o Reduced social, emotional well being o Diminished physical funct
Slide 36: CeD has a multi-cell pathology
CeD has a multi-cell pathology • Immune scarring is present in treated CeD o Epithelial-stromal- immune impacts / interactions • IL-2, produced by CD4 T cells, elevates following gluten ingestion o Starting 2 hrs. after exposure • Stressed epithelial cells express IL-15 (olmesartan) • Key role of IL
Slide 37: Some mechanisms that have been tried in CeD
Some mechanisms that have been tried in CeD… A Toxic → Non-toxic wheat wheat B C A B Enzymes Gluten + → peptide B Wheat fragments D Protease supplement C (IMGX003), Kumamax (TAK-062), and Allergan E F D Polymeric gluten binder Probiotics (B. E infantis) G H Permeability inhibitor F (larazotide aceta
Slide 38: Rationale in targeting CD8 and CD4 T cells in CeD
Rationale in targeting CD8 and CD4 T cells to broadly impact CeD inflammation • Overactive IL-15 and IL-2 signaling drives pathogenic immune cell expansion and inflammation effects • IL-15 is inflammatory cytokine o Expressed by stressed epithelial cells o Supports T cell and NK cell homeostasis and
Slide 39: Serum IL-2 elevated in CeD patients
Serum IL-2, produced by CD4 T cells, elevated in CeD patients • Increase in IL-2 seen within two hours of gluten ingestion • Magnitude of IL-2 response correlates with severity of symptoms • IL-2 elevation key marker for central role of CD4 T cells • IL-2 elevation is not observed in healthy control
Slide 40: Gluten exposure induces significant serum IL-2 increase vs. sham
Gluten exposure induces significant serum IL-2 increase vs. sham Nexvax2 Placebo NS NS p<0.0001 p<0.0001 Gluten Sham Gluten Gluten Sham Gluten Screening Treatment Period Screening Treatment Period Wk -6 to -8 Wk 12 & 14 Wk -6 to -8 Wk 12 & 14 Immunotherapy aiming to restore tolerance in CD4+ T cells
Slide 41: IL-15 a key driver of IEL expansion
IL-15 a key driver of IEL expansion Three mouse models Mouse model overexpressing IL-15Rα overexpressing IL-15 7 Wild-type IL15R overexpression Lamina propria (LP) IL-15 Epithelial cell (EC) IL-15 LP + EC 6 ** Absolute Expression (x10^6) 5 # IELs/100 IECs 4 3 2 1 0 IEL Intestinal epithelial IL-15 ex
Slide 42: Inhibiting CD122+ CD4+ and CD8+ cells and signaling of IL-15 and IL-2
Inhibiting CD122+ CD4+ and CD8+ cells and signaling of IL-15 and IL-2 • CD122 shared receptor subunit through which both IL-15 and IL-2 signal • Expressed on range of immune cells: CD8+ and CD4+ T cells, NK cells • Inhibiting IL-15 and IL- 2 signaling inhibits A subsets of these cells, A reducing in
Slide 43: Latiglutenase: MOA effective in preventing injury but not healing
Latiglutenase: MOA effective in preventing gluten induced injury in P1b but not in healing established disease Latiglutenase attenuates mucosal Based on means latiglutenase damage by ~80% based on ratio of attenuated abdominal pains for 2g means for IMGX003 vs. placebo arms gluten per day by 93% Thi
Slide 44: Considerations for Phase 1b CeD trial design
Considerations for Phase 1b CeD trial design • Traditional P1b gluten challenge o Controlled symptoms and limited mucosal damage at baseline For drugs with upstream • P2b and P3 population targets symptomatic CeD patients with mucosal damage immunologic MOA, early P1b trial data that • Drugs whose M
Slide 45: Perspectives on FDA guidance for CeD
Perspectives on FDA guidance for CeD • GREAT Conference* o Significant public engagement at advocacy meetings (Beyond Celiac 2024) • Alignment on P2/P3 target population: symptomatic CeD despite a GFD* • Need to prevent symptoms of gluten exposure in CeD patients and improvement of histologic injury
Slide 46: Agenda: ANB033 (CD122 Antagonist)
Agenda: ANB033 (CD122 Antagonist) TOPIC SPEAKER Martin Dahl, Ph.D., CD122 biology and preclinical data Senior Vice President, Research John Kwon, M.D., Ph.D. Phase 1a in healthy volunteers Vice President, Clinical Development Joseph Murray, M.D. Professor of Medicine Drug development for CeD Mayo Cl
Slide 47: Symptomatically controlled CeD patients present with range of histologic activity
Symptomatically controlled CeD patients present with range of histologic activity Histology (Vh:Cd ratio) 3.5 2.5 2.0 1.5 1.0 0.1 Normal Mucosal damage Abnormal Symptoms Asymptomatic Symptom controlled Poorly controlled Symptomatically controlled on GF diet Symptomatic on GF diet Gluten challenge Pe
Slide 48: ANB033 Phase 1b trial in CeD initiated
ANB033 Phase 1b trial in CeD initiated Anticipate top-line data by year-end 2026 Prevention of Mucosal Damage Follow-Up Period Cohort 1 (6 weeks) (n=30) Screening ANB033 SC Dose Q2W (up to 30 days) Gluten Vh:Cd challenge ≥ 2.0 Placebo SC Dose Q2W Primary analysis N=60 Baseline Endoscopy Week 6 Endos
Slide 49: CeD quantitative histology and qualitative symptom assessments
CeD quantitative histology and qualitative symptom assessments Histology (Vh:Cd ratio) 3.5 2.5 2.0 1.5 1.0 0.1 Normal Mucosal damage Abnormal Quantitative histology measures villus height (Vh), Vh:Cd ratio crypt depth (Cd) and intra-epithelial lymphocyte count (IEL per 100 enterocytes) to assess his
Slide 50: Cohort 1 is a gluten-challenge to assess prevention of mucosal damage
Cohort 1 (Vh:Cd ≥ 2.0) is a gluten-challenge to assess prevention of mucosal damage Prevention of Mucosal Damage Follow-Up Period Cohort 1 (6 weeks) (n=30) Screening ANB033 SC Dose Q2W (up to 30 days) Gluten Vh:Cd challenge Placebo SC Dose Q2W ≥ 2.0 Primary analysis Baseline Endoscopy Week 6 Endosco
Slide 51: Cohort 2 assesses ability to heal mucosal damage
Cohort 2 (Vh:Cd < 2.0) assesses ability to heal mucosal damage in symptom-controlled patients Mucosal Healing Follow-Up Period (12 weeks) Cohort 2 (n=30) Screening ANB033 SC Dose Q2W (up to 30 days) Vh:Cd Placebo SC Dose Q2W < 2.0 Primary Analysis Baseline Endoscopy Week 12 Endoscopy Week 0 2 4 6 8
Slide 52: Agenda: ANB033 (CD122 Antagonist)
Agenda: ANB033 (CD122 Antagonist) TOPIC SPEAKER Martin Dahl, Ph.D., CD122 biology and preclinical data Senior Vice President, Research John Kwon, M.D., Ph.D. Phase 1a in healthy volunteers Vice President, Clinical Development Joseph Murray, M.D. Professor of Medicine Drug development for CeD Mayo Cl
Slide 53: Potential blockbuster opportunity for ANB033 in non-responsive CeD
Potential blockbuster opportunity for ANB033 in non-responsive CeD High disease burden • Debilitating symptoms, social isolation 2.1 million U.S. patients1 • Disease awareness driving growth (prevalence) • No approved therapies CD122s differentiated from other Tx in development • HCPs favor MOA that
Slide 54: New therapies in CeD could grow market in responsive and newly diagnosed patients
New therapies in CeD could grow market in responsive and newly diagnosed patients All-Comers Prevention in newly diagnosed ~1M Increasing bar for efficacy Subset of Responsive GF diet liberation ~600K Initial Target Population Non-Responsive Mitigate symptoms As the celiac market evolves, more patie
Slide 55: Assessing potential to treat EoE: significant market
Assessing potential to treat EoE: significant market with increasing prevalence and unmet need 340,000 Significant unmet need with limited diagnosed U.S. patients1 approved therapies • ~50% PPI or steroid non-responsive or intolerant • Dupixent QW approved in 2022 • 20-30% Dupixent non-responsive 17
Slide 56: ANB033 has pipeline-in-a-product potential
ANB033, a potential best-in-class CD122 antagonist, has pipeline-in-a-product potential Development Stage and Anticipated Milestones Antibody Therapeutic IND Phase 1 Phase 2 Phase 3 Program Indication Enabling P2b trial complete Rheumatoid Arthritis ACR late-breaker Rosnilimab on Oct. 29th (Pathogen