Slide 1: PD-1 Agonist (Rosnilimab) R&D Event
PD-1 Agonist (Rosnilimab) R&D Event Wednesday, Oct. 25, 2023 1:15pm PT/4:15pm ET AnaptysBioW
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 initiation of the Company's
Slide 3: Agenda: MOA and differentiation
MOA and differentiation Rosnilimab in RA Unmet patient needs and opportunity for PD-1 agonists Targeting RA with rosnilimab and translational data Rosnilimab in UC Unmet patient needs, disease biology, and rationale for PD-1 agonist in UC Targeting UC with rosnilimab and translational data PD-1 safe
Slide 4: Developing best-in-class immune cell modulators to restore immune balance
Developing best-in-class immune cell modulators to restore immune balance across autoimmune & inflammatory diseases Cytokine Antagonists Immune Cell Modulators (legacy programs for out-licensing) Rosnilimab ANBO32 ANBO33 (PD-1 agonist) (BTLA agonist) (D122 antagonist) Imsidolimab (IL-36R) P2b in P2b
Slide 5: Immune cell modulator development plan: initiation of three P2 trials
Immune cell modulator development plan: initiation of three P2 trials across three therapeutic areas Development Stage and Anticipated Milestones Antibody Therapeutic Program Indication Lead IND Optimization Enabling Phase 1 iso (ES P2b initiated Q3 2023 Rheumatoid Arthritis Top-line data en mid 202
Slide 6: PD-1+ T cells are prevalent in inflamed tissue and periphery in RA and UC
PD-1+ T cells are prevalent in inflamed tissue and periphery in RA and UC 100 eo Rheumatoid = 3 75 arthri $2 Synovial eS tissue +2 50 TE as a: xe 25 Ulcerative Ss Lamina 0 propria RA uc Synovial — Lamina tissue propria In systemic inflammatory diseases, a multiple fold increase of PD-1+ T cells is o
Slide 7: PD-1+ T cells prevalent in RA and UC, but lacking in AA
PD-1+ T cells are prevalent in inflamed tissue and periphery in RA and UC, but lacking in AA 100 o® Rheumatoid =3 75 re Do arthritis: $2 Synovial eS tissue +2 50 we as a: xe 25 Ulcerative Ss o Lamina 0 T propria RA uc AA Synovial — Lamina Hair tissue propria _ follicle In systemic inflammatory disea
Slide 8: Checkpoint agonists “hit the brakes” to restore immune balance
Checkpoint agonists “hit the brakes” to restore immune balance Checkpoint receptors (e.g., PD-1) Rosnilimab targets PD-1+ T cells through 3 MOAs: Treat inflammation: Immune cells (e.g., T cells) 1. Deplete PD-1" Teff cells Down-regulate immune cells 2. Deplete PD-1''* Tfh/Tph cells 3. Agonize PD-1'"
Slide 9: Rosnilimab’s impact in inflamed tissue and periphery
Rosnilimab’s impact in inflamed tissue and periphery has potential to deliver differentiated efficacy and safety ee Reduce Reduce Reduce on Teells PD-1hi9h Teff cells PD-1+ Tcell activation PD-1"'9 Tfh/Tph cells Immunologic outcomes C*ACTEMRA Eni Relevant eG Ta ee Approved oS HUMIRA’ a ZEPOSIA. Trea
Slide 10: Rosnilimab has potential to treat wide range of systemic inflammatory diseases
Ros ab has potential to treat wide range of systemic inflammatory diseases, including RA and UC Rheumatoid arthritis: Large commercial markets ~500,000 patients >$10bn U.S. sales in “post TNF” market? * biologie experienced patients 20-25% cycle Standard of care is insufficient all treatment classes
Slide 11: Rosnilimab targets PD-1+ T cells broadly impacting pathogenic drivers
Rosnilimab targets PD-1+ T cells broadly impacting pathogenic drivers of autoimmune & inflammatory eases PD-1 agonists deplete and agonize PD-1+ T cells, in both inflamed tissue and the periphery Rosnilimab, a best-in-class PD-1 agonist, reduces T cell migration, proliferation & cytokine secretion a
Slide 12: Agenda
Agenda Rosnilimab: a best-in-class PD-1 agonist Rosnilimab in RA Unmet patient needs and opportunity for PD-1 agonists Targeting RA with rosnilimab and translational data Rosnilimab in UC Unmet patient needs, disease biology, and rationale for PD-1 agonist in UC Targeting UC with rosnilimab and tran
Slide 13: PD-1 expressed preferentially on activated Teff and Tfh/Tph cells
PD-1 expressed preferentially on activated Teff and Tfh/Tph cells mediating autoimmune pathology Teff (effector) In response to stimulation, become highly activated (PD-1h9h) or moderately activated (PD-1""*) Secrete inflammatory cytokines, cause tissue damage and perpetuate inflammatory cycle Tfh (
Slide 14: Rosnilimab depletes and agonizes PD-1+ T cells
Rosnilimab depletes and agonizes PD-1+ T cells targeting multiple drivers of disease pathogenesis Pathogenic driver MoA ——— high PD-1hish Teff pepe PD inah Teff PD-1i* Teff Agonize PD-1+ inhibitory receptor — Immunologic Outcome Impact on T cells —————— Reduce T cell migration, proliferation and cyt
Slide 15: Rosnilimab restores immune balance bringing T cell composition to a less activated state
Rosnilimab restores immune balance bringing T cell composition to a less activated state PD-1 expression on both CD4 and CD8& T cells correlates with activation state Pre-treatment Rosnilimab targets only a small proportion of T cells Ea In healthy volunteers: a - Deplete PD-1hish T cells: ~5-8% of
Slide 16: Rosnilimab optimizes PD-1+ T cell inhibitory signaling
Rosnilimab optimizes PD-1+ T cell inhibitory signaling by enabling tight immune synapse formation Functional assay of Lilly antagonism or agonism? Rosnilimab PD-1 agonist Dendritic cell Blocking activity ‘Agonist activity . om on ae] & a oh a a fh Rosnilimab epitope FART Siren Activation ie Tcell Te
Slide 17: Membrane-proximal binding epitope results in best-in-class potency vs. Lilly’s PD-1 agonist
ab’s membrane-proximal binding epitope results in n-class potency vs. Lilly’s PD-1 agonist Rosnilimab (IgGik Fc) Membrane- proximal epitope Structural PD- characteristics binding properties Fc receptor binding affinity v v Decreased Functional outputs Agonism Go) Decreased KISS ISS
Slide 18: Rosnilimab demonstrates potent depletion and agonism at clinically relevant concentrations
Rosnilimab demonstrates potent depletion and agonism at clinically relevant concentrations Depletion Agonism (NK cell-mediated ADCC)! (DCs + total T cells; no ADCC)? a Isotype z aie > contro! 2 Sos Lilly PD-A 32 22 agonist 53 33 és Be 5 -®& Rosnilimab fs £5 3 #e BE os ~ inical range w& Cina an 5 0 o
Slide 19: Rosnilimab is optimized for two MOAs: depletion and agonism
Rosnilimab is optimized for two MOAs: depletion and agonism of PD-1+ T cells in both inflamed tissue and periphery PD-1 expressed preferentially on activated Teff and Tfh/Tph cells mediating autoimmune and inflammatory pathology Rosnilimab restores immune balance bringing T cell composition to a les
Slide 20: Agenda
Agenda Rosnilimab: a best-in-class PD-1 agonist MOA and differentiation Rosnilimab in RA Unmet patient needs and opportunity for PD-1 agonists Targeting RA with rosnilimab and translational data Rosnilimab in UC Unmet patient needs, disease biology, and rationale for PD-1 agonist in UC Targeting UC
Slide 21: RA Treatment Landscape 2023
RA Treatment Landscape 2023 JONATHAN GRAF, M.D. PROFESSOR OF MEDICINE, UCSF DIRECTOR, UCSF RA COHORT DIVISION OF RHEUMATOLOGY, ZUCKERBERG SAN FRANCISCO GENERAL
Slide 22: Treat to target approach for early RA: 2023
Treat to target approach for early RA: 2023 Start methotrexate Initiate long term therapy with an agent shown to retard radiographic progression If low disease activity target is not achieved, add an b-DMARD (usually anti-TNF agent) or a combination of cs-DMARDs If disease remains active, ascend the
Slide 23: Choice of RA therapy: Not always obvious
Choice of RA therapy: Not always obvious ‘THE RA WHEEL OF EMPIRIC THERAPY* RA is a heterogeneous disease No standard biomarker to predict which therapy best for which patient RA therapeutic landscape is often riddled with trial and error Costly in terms of money, toxicity and delay in reaching T2T g
Slide 24: Rheumatoid Arthritis: The ideal treatment landscape
Rheumatoid Arthritis: The ideal treatment landscape > Cs-DMARDs: a B-DMARDs: MTX; LEFL B-cell depleting therapies B-DMARDs: Anti-TNFs T-cellco-stim i Ts-DMARDs: blockade JAKibs Anti-IL6R 24
Slide 25: Actual treatment landscape: State of RA treatment in real-world cohort
Actual treatment landscape: State of RA treatment in real-world cohort: Poitiers, France 2007-2015 Larid et Objective: to ‘ evaluate the Inclusion 2009 2015 remission rate 47 PATIENTS 54 PATIENTS and the (68.1%) (76.1%) REMISSION maintenance of 69 PATIENTS 71 PATIENTS aAParENTS remission in (32.1%)
Slide 26: Real world 8-year survival rates: Anti-TNF therapy
Real world 8-year survival rates: Anti-TNF therapy 2000-2015 Papadopoulos et al. Rheumatology noes in Pra: me 3, Issue 1, 2019 ‘ACR 20 in RA patients ‘ACR70 in RA patients infliximab Ml adolimumab lll etanercept ‘Survival Addlimumab op} Ys! 2nd Sed ath Sth 6th 7H tH Time in years, Real world is not
Slide 27: Current B-DMARDs do not cure RA
Current B-DMARDs do not cure RA: Attempting to taper TNFis: The ARCTIC REWIND TNFi Trial Liles ‘A Cumulative flares. 260 s 840 3. En é ° raesncn26) o a é % Months No. are Tapering INF 434208381818 SabeTNFi 41 41 tata tat 27
Slide 28: PD-L1 is a central nodal point regulating T cell activity
PD-L1 is a central nodal point regulating T cell activity PD-1*2"Tth/Tph Genetic Factors "Environmental Factors "Smoking, Bacteria and Virus “Autophagy Peptide Citrullination 28
Slide 29: Resetting the immunologic thermostat
Resetting the immunologic thermostat: Potential to down-regulate multiple pathways Known targets of current therapeutics TNF-a IL-1 IL-6 B-cell activation Plasma cell development Other cytokines (GM-CSF) that use JAK-STAT signaling pathways PD-1 agonist class has shown compelling POC 29
Slide 30: What are the unmet needs in RA?
What are the unmet needs in RA? » Sizeable number of patients not at RA disease activity targets » Especially targets that achieve remission (or better) » Need to reset the immune system environment so that: » Treatment efficacy doesn't wane » Therapy will workin ALL RA patients regardless of diseas
Slide 31: Agenda
Agenda Rosnilimab: a best-in-class PD-1 agonist MOA and differentiation Rosnilimab in RA Unmet patient needs and opportunity for PD-1 agonists Targeting RA with rosnilimab and transl Rosnilimab in UC Unmet patient needs, disease biology, and rationale for PD-1 agonist in UC ional data Targeting UC w
Slide 32: PD-1+ T cells broadly impact multiple clinically validated drivers of RA pathogenesis
PD-1+ T cells broadly impact multiple clinically validated drivers of RA pathogenesis —" lee - -- ~ wee ] ary cai Agonize and Deplete Lymph node Synovium S, Activated Fibroblast : ’ 2% GAK inhibitors >) Gi (Caister) TNF inhibitors IL-6 inhibitors Deplete = B cell depleters Autoantibodies ea a-CCP) y
Slide 33: PD-1hi Tph cells are elevated in RA synovium
PD-1hish Tph cells are elevated in RA synovium and secrete cytokines driving autoantibody production Peripheral blood! Cytokine gene expression from 10 synovial cells? Hy IL-21 cXcL13 fa f , 2 , 2 As Ze oe oO §a ga 2° = SS 25 S& 54 go go 2 es $2 os es oe 20 oe . 38 38 28 é De! 33 a3 “e B22 BS pu PD-
Slide 34: PD-1 agonism overcomes synovial heterogeneity challenges
PD-1 agonism overcomes synovial heterogeneity challenges given broad overlap with key disease subtypes RA immune cells cluster Individual patients differ in their into 18 different subtypes composition of each cellular cluster Single cell RNA-Seq data from synovium Leukocyte-rich RA Donors, Therapeu
Slide 35: PD-1 agonist class is clinically validated in RA
PD-1 agonist class is clinically validated in RA with compelling proof of mechanism CDAI - b/tsDMARD-Naive CDAI - b/tsDMARD-Experienced o 0 o 8 8 5 5 2 26 ie) 6 6 = = G30 gi CDAI response (naive + experience) sustained through ~6 months “10 controlled P2a study —, — No safety signal - Consistent eff
Slide 36: Rosnilimab’s potent depletion and agonism reduces T cell proliferation and cytokines
Rosnilimab’s potent depletion and agonism reduces T cell proliferation and inflammatory cytokines that cause joint damage 2 Depletion of PD-1'2'T cells ion of Tfh/Tph chemokine 2 2 10 § 8 100. 32 gs Bs 52 Pear 245. £5 oe TH 5 ae 50 ee 35s 2B 2 . = ee Clinical range “+ Isotype control ‘ Lily PD-+ ago
Slide 37: Rosnilimab depletes and agonizes PD-1+ T cells broadly impacting RA drivers
Rosnilimab depletes and agonizes PD-1+ T cells broadly impacting multiple drivers of RA pathogenesis PD-1 agonism overcomes synovial heterogeneity challenges given broad overlap with key disease subtypes >80% of T cells in RA synovium are PD-1+, including PD-1i9" Tph cells which secrete cytokines dr
Slide 38: Agenda
Agenda Rosnilimab: a best-in-class PD-1 agonist Dan Faga Chief Executive Officer MOA and differentiation Martin Dahl, Ph.D. Senior Vice President, Research Rosnilimab in RA Jonathan Graf, M.D. Unmet patient needs and opportunity for PD-1 agonists Professor, Medicine University of California, San Fra
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Slide 40: Disclosure of potential conflicts of interest
Disclosure of potential conflicts of interest | support for research Janssen Abbvie, Abivax, Aclaris Therapeutics, Adiso Therapeutics, Agomab Therapeutics, Alfasigma, Alimentiv, Amgen, AMT, AnaptysBio, Arena Pharmaceuticals, Artizan Biosciences, Artugen Therapeutics, AstraZeneca, Bacainn Therapeutic
Slide 41: Endoscopy findings of ulcerative colitis
Endoscopy findings of ulcerative colitis Total Mayo ClinicScore = SF + RB + MES+ PGA Stool Frequency (SF) Mayo Endoscopic Subscore 0 =Normal for the patient MES) 1=1-2 stools/day in ad 0 =Normal/inactive the usual 1 = Mild disease (erythema, 2.=3-4 stools/day in ad decreased vascular pattern) the us
Slide 42: UC has high impact on patient lives in U.S.
UC has high impact on patient lives in U.S. “1.5 million with UC in the U.S. Proportion of patients who feel their Psychological Impact of UC condition was controlling their lives _— 400 -) ago, uc rc] 84%" 82% (n=451) 2 £75 - Asthma s (n=305) g 250 - 6 Migraine 5 (n=305) go5 RA 3 (n=309) 2 oa 07 oO
Slide 43: UC clinical presentation driven by activation of T effector cells
UC clinical presentation driven by activation of T effector cells, inflammatory cytokines and failure of regulatory mechanisms Phase I: pre-disease stage Phase Il: acute intestinal inflammation Fibrosis, stenosis, abscess, fistula, cancer: and extra-intestinal manifestations 4B
Slide 44: Increased understanding of IBD pathogenesis has led to biologics and advanced therapies
Increased understanding of IBD pathogenesis has led to the emergence of biologics and advanced therapies: Vedolizumab (IV; ‘SC approved in 2020) Infliximab (IV) ‘Adalimumab (SC) Anticintegrin Ustekinumab (Iv/Sc’) __Risankizumab (IV/SC’) Anti-it-12/23 Antiil-23 p19 ep @ 6 oo > @- 199 199 200 200 200
Slide 45: Anti-TNFs are cornerstone of IBD treatment, but not all patients respond
Anti-TNFs are considered the cornerstone of IBD treatment, including UC, but not all patients respond to treatment and many others lose response over time Treatment response rates with 100 Up to ~30% of patients do not Primary Data more limited respond to induction therapy non-response | for UC. how
Slide 46: Targeting multiple mechanisms provides opportunity to break through efficacy ceiling
Targeting multiple mechanisms provides opportunity to break through efficacy ceiling in moderate to severe UC VEGA: Golimumab vs Guselkumab vs Combination Clinical remission at Week 12 Mayo Stool Frequency Subscore of 0 or 1 and Not Increased from Baseline, a Rectal Bleeding Subscore of 0, and an En
Slide 47: PD-1 mediated T cell exhaustion is associated with reduced flares
PD-1 mediated T cell exhaustion is associated with reduced flares in numerous autoimmune diseases AA Mesinney etal Nature 2035 MM Reduced gene expression from baseline MI Elevated gene expression from baseline Exhaustion can be induced through agonism of PD-1 inhibitory receptor gion, P7007 3 — a 50
Slide 48: Novel subset of T cells (Tfh) expanded in UC
Novel subset of T cells (T follicular helper cells) expanded in UC that may direct the B cell response Fie <cTT + Tfh/Tph cells significantly increased in active UC Ulcerative colitis is characterized by a plasmablast- vr ly 5 me sae skewed humoral response associated with patients compared with sta
Slide 49: Summary: Ulcerative Colitis
Summary: Ulcerative Colitis High impact disease - High personal and economic impacts - Risingrates, globally + Significant therapeutic limitations - Safety (anti-TNFs, JAK inhibitors) - Limited efficacy in achieving and maintaining remission + Targeting multiple mechanisms provides opportunity to br
Slide 50: Agenda
Agenda Rosnilimab: a best-in-class PD-1 agonist MOA and differentiation Rosnilimab in RA Unmet patient needs and opportunity for PD-1 agonists Targeting RA with rosnilimab and translational data Rosnilimab in UC Unmet patient needs, disease biology, and rationale for PD-1 agonist in UC Targeting UC
Slide 51: PD-1+ T cell activation broadly impacts drivers of UC pathogenesis
PD-1+ T cell activation broadly impacts multiple clinically validated drivers of UC pathogenesis >40% of T cells in lamina propria in UC are PD-1+ Deplete and agonize ‘ a Barrier disruption Lamina Propria Adapted from Gastroenterology & Hepatology Volume 18, Issue 8 August 2022. Agonize Deplete and
Slide 52: PD-1+ T cells are elevated and dysregulated in UC
PD-1+ T cells are elevated and dysregulated in UC ~40% of T cells are PD-1+ in Similar dysregulation of PD-1 pathway UC lamina propria genes between RA and UC T cells (CD3+) PD-1+ Nivolumab-induced genes 5 ‘4 a * 3 £ is & ¢ . 2 Lamina 2 5 propria £ E ‘0.0 Bs a se = Fa ks: 2 Healthy 2 S| ee oO * > §
Slide 53: Reduction of elevated PD-1hi Tph cells correlates with remission
Reduction of elevated PD-1is Tph cells in both UC colon and periphery correlates with remission PD-1sh Tph cells PD-1h9h Tph cells are elevated are reduced with remission 40 a P<0.001 2 o> —P<0.002 2 30 8 a Ee E a st < F BS: £2 3 53 £ = B 82 2 oy ne = a 3 2 A a $1 a 10 - ae cy § . 2 8 8 4 HC ONonint
Slide 54: PD-1 agonists induce and maintain remission in murine models
Prophylactic or therapeutic sosing of PD-1 agonists induce and maintain remission in murine models Prophylactic dosing of HM226 PD-1 agonist Therapeutic dosing of rosnilimab induce and maintain remission from colitis induce and maintain remission from colitis Biweekly dosing Biweekly dosing 420 from
Slide 55: Rosnilimab reduces T cell proliferation and inflammatory cytokines
Rosnilimab’s potent depletion and agonism reduces T cell proliferation and inflammatory cytokines that disrupt barrier function Depletion of PD-1'2'T cells Inhibition of Tfh/Tph cytokine 100. BE 100. 38 we : -e sotype control BS 54 82 75. : “= Rosnilimab fe a oe i ’ (wesuc £8 oof HE oo sien) ee Be x
Slide 56: Rosnilimab depletes and agonizes PD-1+ T cells impacting UC drivers
Rosnilimab depletes and agonizes PD-1+ T cells broadly impacting multiple drivers of UC pathogenesis >40% of T cells in UC lamina propria are PD-1+, including PD-1'9) Tph cells which inversely correlate with disease remission PD-1 agonists induce and maintain remission from colitis in murine models
Slide 57: Agenda
Agenda Rosnilimab: a best-in-class PD-1 agonist MOA and differentiation Rosnilimab in RA Unmet patient needs and opportunity for PD-1 agonists Targeting RA with rosnilimab and translational data Rosnilimab in UC Unmet patient needs, disease biology, and rationale for PD-1 agonist in UC Targeting UC
Slide 58: Rosnilimab and PD-1 agonist class well-tolerated with no dose limiting tox
Rosnilimab, and overall PD-1 agonist class, well-tolerated with no dose limiting tox observed to date Rosnilimab Phase 1: 144 healthy volunteers (HV) in SAD and MAD cohorts — Supports monthly SC dosing - Favorable safety and tolerability + No SAEs related to rosnilimab? + No carcinogenic events obse
Slide 59: Rosnilimab P2a in alopecia areata well tolerated
Rosnilimab P2a in alopecia areata (AA) for Q4W SC dosing for 6 months was well tolerated with no significant safety signals Rosnilimab 400 mg Placebo All participants Tee, (N=33) (N=18) (N=51) Participant with at least one TEAE 21 (63.6) 12 (66.7) 33 (64.7) Related 6 (18.2) 3 (16.7) 9 (17.6) Partici
Slide 60: Sustained reduction in peripheral PD-1+ T cells across P1 and P2a studies
Potent and sustained reduction in peripheral PD-1+ T cells for >30 days across P1 HV and P2a AA studies Rosnilimab P1 healthy volunteers Consistent PD-1+ T cell effect —— + >90% reduction of PD-Ahsh T cells + >50% reduction of PD-1+ T cells ‘ LS Overall T cell composition in less activated state = +
Slide 61: PD-1 agonist MOA is not the right approach to treat AA
PD-1 agonist MOA is not the right approach to treat AA given essentially undetectable PD-1+ cells at hair follicle Representative IHC staining of scalp biopsy samples at baseline* ~ Only ~10-15% of T cells were PD-1+ in skin overall ~ Non-localized and scattered throughout layers of skin CD3+ T cell
Slide 62: Rosnilimab Phase 2b in moderate-to-severe RA
Rosnilimab Phase 2b in moderate-to-severe RA Initiated Q3 2023; Top-line data mid-2025 ‘Sereer ea Blinded Placebo-Controlled Blinded All-Active Treatment Period Follow-Up Period Kentaactdeyey ‘Treatment Period (12 weeks) (16 weeks) (10 weeks) Primary Final statatical seatatical ‘analysis ‘analysis R
Slide 63: Rosnilimab Phase 2 in moderate-to-severe UC
Rosnilimab Phase 2 in moderate-to-severe UC Initiating Q4 2023; Top-line data H1 2026 ‘Sereer Blinded Placebo-Controlled Blinded |-Active Treatment Follow-Up Period Period (op ere Saysy Treatment Period (12 weeks) Period (12 weeks) (G0 weeks) oop Final Saat scat Boalysie pacabo Nonreepondere Sin Ros
Slide 64: Robust translational plans explore predictive markers of treatment response
Robust translational plans explore predictive markers of treatment response in RA and UC and inform future indications + Profile agonism and depletion mechanisms + Tissue vs peripheral PD-1+ T cell depletion Peripheral and tissue PD * Precision medicine approaches Breakthrough results and innovative
Slide 65: Rosnilimab is potential best-in-class in RA and first-in-class in UC
Rosnilimab is potential best-in-class in RA and first-in-class in UC Rosnilimab was well tolerated in clinical studies with no significant safety signals while demonstrating potent and sustained reduction in peripheral PD-1+ T cells for >30 days Global Phase 2b trial initiated in moderate-to-severe
Slide 66: Agenda
Agenda Rosnilimab: a best-in-class PD-1 agonist MOA and differentiation Rosnilimab in RA Unmet patient needs and opportunity for PD-1 agonists Targeting RA with rosnilimab and translational data Rosnilimab in UC Unmet patient needs, disease biology, and rationale for PD-1 agonist in UC Targeting UC
Slide 67: Substantial opportunity for new class of biologics in RA
Substantial Opportunity for new class of biologics with differentiate U.S. “biologic experienced” RA prevalence!?+ 1 million Treated with biologics and JAKs (b/tsDMARDs) ~500,000 Pibg (e.g. TNF-class insufficient responders) outcomes in RA >$10bn U.S. sales in “post TNF” market (2021)2 Fragmented ma
Slide 68: PD-1 agonist class has shown commercially meaningful outcomes
PD-1 agonist class has shown commercially meaningful outcomes (ACR50 and ACR70) regardless of prior treatment TNF-IR Patients Lee eee RINVOG C*ACTEMRA Stony Rituxan 1 agonist ACR70 week 14: 35%?) |= = = = = oo Absolute scores at Week 1217 Qatvoa GsACTEMRA Sonny Fina Canvea *ACTEMRA Soucy ituxan 1. P
Slide 69: Substantial opportunity for new class of biologics in moderate and severe UC
Substantial Opportunity for new class of biologics with differentiated outcomes in moderate and severe UC U.S. moderate-to-severe UC prevalence >$6.5bn US sales in “non-TNF” market (2028)2 - UC prevalence growing faster than population ctory; ted therapies Fragmented market — Severe: No clear choice
Slide 70: UC lacks highly effective treatment options to induce and maintain clinical remission
UC lacks highly effective treatment options to induce and maintain clinical remission Following remission on induction therapy, one third to one half of patients relapse within 1 year Induction of Clinical Remission+23+ MmDrug Hi Placebo Lt F Ist line treatment of choice in severe patients Ast line
Slide 71: Rosnilimab targets PD-1+ T cells broadly impacting pathogenic drivers
Rosnilimab targets PD-1+ T cells broadly impacting pathogenic drivers of autoimmune & inflammatory eases PD-1 agonists deplete and agonize PD-1+ T cells, in both inflamed tissue and the periphery Rosnilimab, a best-in-class PD-1 agonist, reduces T cell migration, proliferation & cytokine secretion a