Slides
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January 2025CorporateOverview
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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 Company’s clinical trials, including rosnilimab’s Phase 2b clinical trial in rheumatoid arthritis and Phase 2 clinical trial in ulcerative colitis; the timing of initiation of ANB101’s Phase 1 clinical trial; whether any of the Company’s product candidates will be best in class or optimized; the potential to receive any additional milestones or royalties from the GSK collaboration; the Company’s ability to find a licensing partner for imsidolimab or etokimab and the timing of any such transaction; and the Company’s projected cash runway. Statements including words such as “plan,” “continue,” “expect,” or “ongoing” and statements in the future tense are forward-looking statements. These forward-looking statements involve risks and uncertainties, as well as assumptions, which, if they do not fully materialize or prove incorrect, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Forward-looking statements are subject to risks and uncertainties that may cause the company’s actual activities or results to differ significantly from those expressed in any forward-looking statement, including risks and uncertainties related to the company’s ability to advance its product candidates, obtain regulatory approval of and ultimately commercialize its product candidates, the timing and results of preclinical and clinical trials, the company’s ability to fund development activities and achieve development goals, the company’s ability to protect intellectual property and other risks and uncertainties described under the heading “Risk Factors” in documents the company files from time to time with the Securities and Exchange Commission. These forward-looking statements speak only as of the date of this presentation, and the company undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof.Certain information contained in this presentation may be derived from information provided by industry sources. The Company believes such information is accurate and that the sources from which it has been obtained are reliable. However, the Company cannot guarantee the accuracy of, and has not independently verified, such information.The trademarks included herein are the property of the owners thereof and are used for reference purposes only. Such use should not be construed as an endorsement of such products.2 Safe harbor statement
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Cytokine Antagonists(legacy programs for out-licensing) Cytokine Antagonists(legacy programs for out-licensing)3 Immune Cell ModulatorsImmune Cell ModulatorsANB033(CD122 antagonist)P1 in Healthy VolunteersRosnilimab(PD-1 depleter and agonist)P2b in Rheumatoid ArthritisP2 in Ulcerative ColitisAutoimmune and inflammatory diseases including dermatology, gastroenterology and rheumatology 1. GPP – Generalized pustular psoriasis ANB101(BDCA2 modulator)IND SubmittedImsidolimab (IL-36R)Positive P3 data reported in GPP1Etokimab(IL-33)P2b/3-ready in epithelial driven diseases Research and Capital Research and CapitalStrong capital positionResearch-driven•YE 2024 cash: ~$420MM•Expected cash runway: YE 2027 oExcludes GSK royalty and milestone potential for Jemperliand cobolimaboExcludes GSK $75MM milestone for Jemperli$1B annual WW sales•Preclinical pipeline of immunology targets Best-in-class immune cell modulating antibodies
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Development Stage and Anticipated MilestonesTherapeuticIndicationAntibodyProgramPhase 3Phase 2Phase 1IND EnablingRheumatoid ArthritisRosnilimab(PD-1 depleter and agonist)UlcerativeColitisInflammatory DiseasesANB033(CD122 antagonist)Inflammatory DiseasesANB101(BDCA2 modulator)4 Top-line P2b Week 12data – February 2025Top-line P2b Week 28 data – Q2 2025Top-line P2 data Q1 2026P1 initiatedR&D event in 2025 Immune Cell Modulators Multiple clinical-stage data eventsRosnilimab RA P2b Week 12 data expected in February 2025 P1 initiationQ1 2025
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(PD-1 Depleter and Agonist) Rosnilimab
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RosnilimabBest-in-class antibody•Potent depleter and agonist―Deplete 90% of PD-1highT cells•Safety/Tolerability―Clean tox profile; no DLT reached―Benign AE profile in both Phase 1 (HV) and Phase 2 (Alopecia 6-months of dosing) RA Phase 2b trial Robust and well-controlled PD-1Validated target•PoC in RA via PD-1+ T cell depletion MOA―LLY’s peresolimab in Phase 2a has “modest ADCC activity”1•PD-1 polymorphisms associated with increased risk of developing RA2•Inflammatory arthritis common AE of PD-1 antagonist treatment3 •~420 patient US + EU study (~40% b/tsDMARD-experience)•Patients have high disease activity; RF or α-CCP sero-positive •>80% power for ACR50 composite at Week 12 •CDAI LDA responders treated through Week 28 •CRO with extensive RA experience; no rescue tx6 Rosnilimab RA top-line Phase 2b data: Week 12 – February 2025; Week 28 – Q2 2025Rosnilimab RA top-line Phase 2b data: Week 12 – February 2025; Week 28 – Q2 2025 Rosnilimab: PD-1+ T cell depleter and agonist 1. Eli Lilly patents; WO2024196694A2 and WO2024040206A2 2. Liu et al., Int J Genomics, 2024 3. Canavan et al., BMC Rheumatology, 2021
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1. Expected by 2028 (Evaluate 29 Nov 2022); 2. Market research conducted by Ambit in 2022; 3. Expected by 2028 (Evaluate 21 Aug 2023); 4. Phase 3 registrational data from product labels. Rosnilimab has potential to treat wide range of systemic inflammatory diseases, including RA and UCLarge commercial markets•Biologic experienced patientsSOC is insufficient and fragmented•RA (bio-experienced): ~20–30% ACR50•UC: ~25-30% induction of clinical remission7 Ulcerative colitis:•~100,000 U.S. patients>$6.5bn U.S. sales, excluding TNF, market3•1/3 to 1/2 relapsewithin 1 year following remission on induction therapy4 Ulcerative colitis:•~100,000 U.S. patients>$6.5bn U.S. sales, excluding TNF, market3•1/3 to 1/2 relapsewithin 1 year following remission on induction therapy4Significant room to differentiateDrive deeper responses across broader patient populationRestore immune homeostasis Rheumatoid arthritis:•~500,000 U.S. patients>$10bn U.S. sales in “bio-experienced” market1•20-25% cycle through all treatment classes and do not achieve low disease activity2 Rheumatoid arthritis:•~500,000 U.S. patients>$10bn U.S. sales in “bio-experienced” market1•20-25% cycle through all treatment classes and do not achieve low disease activity2
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8 Dendritic cell T cell T cellActivation MHCCD80/86SHP2TCRCD28PPD-1PD-L1 RosnilimabFcReceptorRapidly engage homeostatic mechanisms to induce clinical response12Rosnilimab aims to:Immunologic OutcomeMechanismImmune Cells Impacteddownstream effect on B cellsPlasma cell generationAutoantibody levelsdepletesPD-1highTfh/TphCytokine secretionT cell migrationT cell proliferationdepletesPD-1highTeffCytokine secretionT cell migrationT cell proliferationagonizesPD-1+ Teff Achieve durable remission through histologic normalizationRosnilimab selectively targets activated PD-1+ T cells in the periphery and inflamed tissue Effector T cells (Teff): activated T cells (cytotoxic, helper, Treg); Follicular/Peripheral Helper T cells (Tfh, Tph): support B cell differentiation and maturation
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9 Pre-treatmentPost RosnilimabRA Synovial Tissue PD-1negPD-1negPD-1intPD-1highRosnilimab is designed to bring the immune system back to homeostasis and modify disease Pre-treatmentPost RosnilimabHealthy Periphery PD-1negPD-1negPD-1negTreg PD-1intTreg PD-1highPD-1negPD-1intPD-1intPD-1high Treg PD-1neg Illustrative T cell composition changePD-1intPD-1high PD-1negPD-1neg Rosnilimab preferentially targets activated T cellsLeverages natural immune regulatory pathway to safelyrestore immune homeostasisIn healthy volunteers:―Deplete PD-1highT cells: ~5-8% of total T cells―Agonize remaining PD-1intT cells: ~15% of total T cells PD-1+ T cellsCD3PD-1highPD-1intPD-1negPre-treatmentRosnilimabDay 15depletionagonismData illustrative; Luu K, et al. ACR 2023. November 2023
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Adapted from Akiyama et al, Ann Rheum Dis, 2023.10 PD-1 is expressed preferentially on activated Teff and Tfh/Tph cells that mediate autoimmune pathology Lymphoid tissuesPeripheryInflamed tissue10B cellPD-1highTfhPlasmacelllglglgPD-1highTfhFDC GenerationCXCL13IL-21PD-1highTfh Type I Interferon CXCL13IL-21 Proliferation &inflammatory cytokine secretion Cytokines (eg, IFN-, IL-6, IL-13)CXCL13IL-21 CXCL13 Plasmacell Tfh (follicular helper)Tph (peripheral helper)•In response to stimulation, become highly activated (PD-1high) or moderately activated (PD-1int)•Secrete inflammatory cytokines, cause tissue damage and perpetuate inflammatory cyclePD-1highTfh/Tph•Secrete CXCL13 and IL-21 which recruit and mature B cells into “autoantibody secreting” plasma cells•Are PD-1highTeff (effector)MigrationTfhdifferentiationto TphPD-1highTphPD-1highTphPD-1highTphPD-1intTeffPD-1intTeffPD-1highTeffPD-1highTeffPD-1highTeffPD-1highTeffPD-1intTeffPD-1intTeffPD-1highTeff
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Adapted from Nguyen et al, Human Pathology (2022) 126, 19e27; Guo et al, PLoS One 2018; 13(2). Roosenboom et al, Scand J of Gastro. 2021; 56(6):671-679. 1. Chen et al, Clinical and Translational Immunology, 2024.11 PD-1+ T cells are prevalent in inflamed tissue and periphery in RA and UC Synovial tissueLamina propriaHair follicle Rheumatoid arthritis:Synovial tissueUlcerative colitis:Lamina propriaCD3+T cellsPD-1+T cells In systemic inflammatory diseases, a multiple fold increase of PD-1+ T cells is observed in periphery compared to healthy controls1~2x in RA~2x in UC In systemic inflammatory diseases, a multiple fold increase of PD-1+ T cells is observed in periphery compared to healthy controls1~2x in RA~2x in UC
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Adapted from Aletaha and Smolen, JAMA, 2018; 1. Chen et al, Clinical and Translational Immunology, 2024.12 Reducing PD-1+ T cells broadly impacts multiple downstream, clinically validated drivers of RA pathogenesis >80% of T cells in RA synovium are PD-1+•Similar findings are observed in treatment naïve and biologic experienced patients2x increase of PD-1+ T cells observed in blood vs. healthy controls1 NaiveT Cell IL-17IFN-yIL-21CXCL13APCPD-1+TfhLymph nodeCD80/CD86blockerJAK inhibitorsSynovium PD-1+TphActivated MacrophageActivated FibroblastTNFIL-1IL-6B cellIL-21CXCL13Plasma cellAutoantibodies(eg, -CCP)ImmunecomplexesRheumatoidfactorB cell depletersIL-6 inhibitorsTNF inhibitorsJAK inhibitorsJAK inhibitorsIL-17IFN-yPD-1+ TeffPD-1+ TeffPD-1+ TeffDeplete and AgonizeDepleteDeplete
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Parmley S, et al. ECCO 2024. February 2024.1. Adapted from Suzuki et al., Sci. Immunol. 8, eadd4947 (2023).13 Dendritic cell T cell T cellActivationMHCCD80/86SHP2TCRCD28PPD-1PD-L1 RosnilimabFcReceptor #3, 4Functional assay ofantagonism or agonism1Lilly epitope PD-L1 epitope Lilly PD-1 agonistRosnilimab Rosnilimabepitope Rosnilimab optimizes PD-1+ T cell inhibitory signaling by enabling tight immune synapse formation “A shared feature of agonist mAbs is recognition of the membrane-proximal extracellular region…” and “…activity depends on Fc receptor–supported crosslinking” Suzuki, et al. 2023“A shared feature of agonist mAbs is recognition of the membrane-proximal extracellular region…” and “…activity depends on Fc receptor–supported crosslinking” Suzuki, et al. 2023
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14 PD-1 Agonist LandscapePD-1 Agonist LandscapeFc receptor binding affinityDepletionAgonismMembrane-proximal epitopeStructural characteristicsFunctional outputs Rosnilimab is a best-in-class PD-1 depleter and agonistLilly’s patent notes peresolimab’s “modest” activity and disclosed more potent PD-1 candidates closer to rosnilimab’s profileLilly Peresolimab(IgG1k)AnaptysRosnilimab(IgG1k)Significantly Decreased2 Lilly Improved1(IgG1 mut. Fc)?2?Insights from Lilly Patent:1 “[peresolimab] demonstrated modest ADCC activity”“FcgRIIB binding alone is not a sufficient driver of IgG1 mediated bioactivity”“Multiple FcgR interactions contribute to PD-1 agonist activity…[and] increased FcgR binding increased inhibition of T cell proliferation”“FcgRs work as a hook in the IS [immune synapse] to allow PD-1 to relocate to a close proximity of the TCR to enable inhibition of TCR signalling”Gilead GS-0151(IgG1 mut. FC3)333Additional LLY PD-1 variants engineered to have greater potency than peresolimab1% Mean T cell Proliferation InhibitionHuman FcBinding Domain56IgG1 (Peresolimab)G240IgG1F193IgG1 S239D + I332EF114 – 16Abatacept1. Eli Lilly patents; WO2024196694A2 and WO2024040206A22. Less potent depletion and significantly weaker agonism from membrane-distal binding epitope results in wider immune synapse and lower clustering of PD-13. Fc binding to FcγRIIb only
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15 Rosnilimab P1 healthy volunteers2 Lilly’s Peresolimab P2a RA patients4 DosingPD-1 Inter CD4+ CellsPD-1highCD4+ Cells1. Healthy donor purified DCs + autologous total T cells stimulated with anti-CD3, cultured for 3 days for assessment of T cell proliferation 2. Luu K, et al. ACR 2023. November 2023; 3. Anti-CD3+ anti-CD28 stimulation of RA patient PBMCs for assessment of depletion and agonism MOA, representative data from N=8 donors. Two-way ANOVA, Tukey’s multiple comparison test. ****P<0.0001, ***p<0.001, **p<0.01, *p<0.05. 4. Benschop, R. ACR 2023, Eli Lilly peresolimab Phase 2a data. More potent depletion compared to peresolimab Comparative data of rosnilimab consistently demonstrates potency of impact on PD-1+ T cells In Vitro H2H Depletion of PD-1highT cells3 DosingTregTotal T cellsPD-1+ T cellsPD-1high T cellsRosnilimabIsotype controlLilly PD-1 agonist% PD-1high T cells(normalized to isotype) 10075502500 0.1 1 10 100 % Proliferating T cells(normalized to isotype) Agonism1(DCs + total T cells; no ADCC) RosnilimabIsotype controlLilly PD-1 agonist % Proliferating T cells(normalized to isotype)10075502500 0.1 1 10 100Antibody nM Antibody nM
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Anti-CD3+ anti-CD28 stimulation of RA patient PBMCs for assessment of depletion and agonism MOA, representative data from N=8 donorsTwo-way ANOVA, Tukey’s multiple comparison test. ****P<0.0001, ***p<0.001, **p<0.01, *p<0.05.1. TNFa secretion measured in anti-CD3+ anti-CD28 stimulation of purified DC+T cells from N=4 healthy donors. 16 Rosnilimab’s potent depletion and agonism reduces T cell proliferation and inflammatory cytokines that cause joint damage Reduction of Tfh/Tph chemokine Reduction of inflammatory cytokine1 Reduction of T cell proliferation Depletion of PD-1highT cells % CXCL13 secretion(normalized to Isotype) % PD-1High T cells(normalized to isotype) % TNFa secretion(normalized to isotype) % ProliferatingPD-1+ T cells(normalized to isotype)
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1. Uniform manifold approximation and projection (UMAP) clusters of T cells from RA patient synovium with arrows identifying Tph and Tfh/Tph cells, T-7 and T-3, respectively and feature plot of PD-1 expression across T cell subtypes; Ren et. al. ACR 2024. November 2024 17 In disease, PD-1+ Tregs exhibit a dysregulated phenotype, which induce proinflammatory cytokines Very low % Tregs (<20%) are PD-1+ in RA synovium, even fewer are PD-1high1Rosnilimab likely depletes PD-1high Tregs and reduces PD-1+ Tregs, resulting in favorable Treg/Teff cell ratio PD-1+ Tregs may be pro-inflammatory and induce IFNγ, IL-17A, TNFα Tfh/TphTphCD4+ MemoryProliferatingCD4+ and CD8+CD4+ Memory(GZMK+)
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1. SAEs unrelated to rosnilimab as follows: Obstructive pancreatitis occurred in a placebo subject and Coronavirus infection occurred in drug 400 mg SC cohort on Day 24 until Day 31; participant recovered and discontinued from the study, and AE was deemed unrelated to rosnilimab. 2. Lilly peresolimab Phase 2 data in RA, published in NEJM (A Phase 2 Trial of Peresolimab for Adults with Rheumatoid Arthritis | NEJM). Rosnilimab, and overall PD-1 agonist class, well-tolerated with no significant safety signals 18 Rosnilimab: Favorable safety and tolerability in P1a and P2a studies•Phase 1a individuals and Phase 2a alopecia areata patients for up to 6 months (400mg Q4W SC)•No SAEs related to rosnilimab1•No malignancies observed•No infection risk signal Competitor PD-1 agonist programs•>100+ RA patients in P2a treated with Lilly PD-1 agonist (highest dose of 700 mg IV over 6 months)2•No public disclosure of any PD-1 agonist to show a malignancy or infection risk signal Rosnilimab: Ongoing RA and UC studies•~420-patient 6 month RA study •~132-patient 1 year UC study•Blinded surveillance: no safety signal to date Abatacept (competing T Cell Modulator)•Broadly impacts all T cells including all Tregs•Decades of commercial use •Have not shown clinically relevant carcinogenic increases
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Black box warnings for increasing SAE incidence of commercial products have not impeded blockbuster sales Black box warning~30% infection rate vs. 28% placebo5~0.7% MACE rate vs. 0.4% placebo5 Black box warning~30% infection rate vs. 28% placebo5~0.7% MACE rate vs. 0.4% placebo5 ~54% infection rate vs. 48% placebo5~0.2% MACE rate vs. 0.5% placebo5 ~54% infection rate vs. 48% placebo5~0.2% MACE rate vs. 0.5% placebo5 Black box warning~20% infection rate vs. 18% placebo5~3.4% MACE rate vs. 2.5% placebo5~4.2% malignancy rate vs. 2.9% placebo5 Black box warning~20% infection rate vs. 18% placebo5~3.4% MACE rate vs. 2.5% placebo5~4.2% malignancy rate vs. 2.9% placebo5 Black box warning~39% infection rate vs. 34% placebo5~1.7% MACE rate vs. 1.3% placebo5 Black box warning~39% infection rate vs. 34% placebo5~1.7% MACE rate vs. 1.3% placebo519 RA patients have significant co-morbidities which are further exacerbated with treatmentIncreased co-morbidity rate in RA patients vs. general population2-3xDVT, PE, and MACE Risk1,22xInfection Rate1 2xMalignancy Rate3 $4.5B RA sales4$3.6B RA sales4$2.3B RA sales4~$1B RA sales1. Avina-Zubieta et al., A&R, 2008, 2. Fazal et al., BMC Rheumatology, 2024, 3. Smitten et al., ART, 2008, 4. Evaluate Pharma 2023 WW RA sales, 5. Phase 3 registrational data from product labels
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1. Phase 3 registrational data from product labels; 15mg dose for upadacitinib in STUDY V 2. Tocilizumab (8mg/kg dose); Smolen J (2008) The Lancet Vol 371: 987-997; Emery, P. (2008) ARD 67(11): 1516-1523; Adalimumab; Keystone E (2004) Arthritis & Rheumatism Vol 50 #5:1400-1411; Rituximab; Cohen S (2006) Arthritis & Rheumatism Vol 54 #9: 2793-2806 3. Tuttle, J. (2023) NEJM;388:1853-62. Note patient population is 63% MTX-IR, 37% b/tsDMARD-IR; Similar efficacy was observed regardless of prior b/tsDMARD use.20 45%31%32%30%34%22%18%23%0%10%20%30%40%50%Upadacitinib(JAK)Tocilizumab(IL-6)Abatacept(CD80/86)Adalimumab(TNF)Upadacitinib(JAK)Tocilizumab(IL-6)Abatacept(CD80/86)Rituximab(CD20) % ACR50Absolute scores at Week 121,2Bio-naive PatientsBio-experienced Patients 25%13%13%11%12%8%6%7%0%10%20%30%40%50%Upadacitinib(JAK)Tocilizumab(IL-6)Abatacept(CD80/86)Adalimumab(TNF)Upadacitinib(JAK)Tocilizumab(IL-6)Abatacept(CD80/86)Rituximab(CD20) % ACR 70Lilly PD-1 ACR70 week 12: 20%3Lilly PD-1 ACR50 week 12: 39%3 Targeting PD-1+ T cells is a clinically validated approach in RA with proof of mechanism 15% PBO8% PBO8% PBO8% PBO12% PBO3% PBO6% PBO8% PBO5% PBO3% PBO3% PBO3% PBO2% PBO5% PBO1% PBO0% PBOPlaceboAdjusted
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CDAI = Clinical Diseases Activity Index; LDA = Low Disease Activity. Rheumatologists seek disease modification―CDAI LDA correlates with slowed radiographic progressionWeek 12: Broad response―Switch patients if not improving (i.e. ACR20)Week 24: Stable or deepening response―ACR50/70 in as many patients as possible―Only modest deepening observed for approved drugs from Week 12 to 2421Week 24(Absolute)Week 12(Absolute)Week 12(Placebo-adjusted)PopulationACR50: ~40%ACR70: ~15%CDAI LDA: ~30%ACR50: ~30%ACR70: ~10%CDAI LDA: ~5-15%ACR50: ~15-20%ACR70: ~5-10%Bio-experiencedACR50: ~50%ACR70: ~25%CDAI LDA: ~35%ACR50: ~40%ACR70: ~20%CDAI LDA: ~10-20%ACR50: ~20-30%ACR70: ~5-15%Bio-naïve Treat-to-target practice in RA results in the importance of multiple efficacy endpoints across both Week 12 and 24 Absolute ACR50 RateWeek 12 Week 24Current BiologicsJAKsIllustrative Response Curves Phase 2 Target Product Profile
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22 Screening Period (up to 35 days)Blinded Placebo-Controlled Treatment Period (12 weeks)Follow-Up Period (10 weeks)Blinded All-Active Treatment Period (16 weeks)3834302826242220181614121086420-5WeekFUV3FUV2FUV1V16 V15V14V13V12V11V10V9V8V7V6V5V4V3V2V1VisitEOSEOTDosingActive Eligibility Visit1Rosnilimab SC Dose 1Rosnilimab SC Dose 2Rosnilimab SC Dose 3Placebo SCRosnilimab SC Dose 1Rosnilimab SC Dose 2Rosnilimab SC Dose 3N = 420Randomize 1:1:1:1Primary Statistical AnalysisFinal Statistical AnalysisDosing SC Q2W or Q4WTop-line Data•Adults with moderate-to-severe rheumatoid arthritis, ≥ 6 TJC and SJC•Positive RF or CCP•Includes both MTX-IR and b/tsDMARD experienced patients (~40% b/tsDMARD experienced)•IR or intolerance to < 3 classes of b/tsDMARDsPatient population•Mean change from Baseline in DAS28-CRP at Week 12PrimaryEndpoints•ACR20/50/70•CDAI ≤ 10 (low disease) and ≤ 2.8 (remission)•DAS28-CRP ≤ 3.2 (low disease); DAS28-CRP ≤ 2.6 (remission)Secondary•Mean change from Baseline in synovial and peripheral biomarkersExploratory endpoints 1Blinded study drug treatment will continue for active treatment group subjects that achieve Clinical Disease Activity Index (CDAI) low disease activity (CDAI ≤10) Rosnilimab Phase 2b in moderate-to-severe RAAnticipate top-line Week 12 data February 2025; Week 28 data Q2 2025 ClinicalTrials.gov: NCT06041269
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23Well-established inclusion/exclusion criteriaTrial design and endpoints CRO and monitoringHigh disease activity•≥ 6 tender and ≥ 6 swollen joints•Seropositive RA - Rheumatoid factor or α-CCP positive•CRP > 3mg/L•Majority CDAI>22 (e.g. severe)Stable background medications•Stable dose of cDMARDs >8 weeks prior to baseline•No changes in prednisone (≤10mg)•No changes in background DMARDs•No rescue medications Large (~420 patient) study•3-active SC arms (Q2W / Q4W) vs. PBO•60% b/tsDMARD naïve •~40% b/tsDMARD experienced (up to 2 prior classes)Standardized composite endpoints•>80% power for ACR50 composite (secondary endpoint) at Week 12 •CDAI LDA (≤ 10) responders at Week 14 treated through Week 28 CRO has extensive RA experience•US and EU countries only•Excluded countries with historically high PBO rates (e.g. Mexico, LatAm) All sites, PIs experienced in RA •Blinded independent joint assessors•Participant eligibility reviewCCP=cyclic citrullinated peptide; CRP=C-reactive protein; SIV=site-initiation visit. Robust and well-controlled Phase 2b RA trial
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Adapted from Gastroenterology & Hepatology Volume 18, Issue 8 August 2022. 1. Chen et al, Clinical and Translational Immunology, 2024.24 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+•2x increase of PD-1+ T cells observed in blood vs. healthy controls1 B cells IL-23antagonistsαEβ7Lymph nodeS1PRmodulatorsTEff MAdCAM-1Anti-integrinsα4β7Circulation Anti-integrinsE-cadherin IFNγ IL-21 T cellsT cells CXCL13IL-21JAK antagonistslgGlgGBarrier disruptionTNFIL-23 TL1ATL1A antagonistsTeffTeffTeffTeffAgonizeDeplete and agonize Deplete and agonizeTphTphLamina Propria
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Distal colon histology and scoring Therapeutic dosing of rosnilimab demonstrated efficacy in a murine model of colitis PD-1highTph cells are reduced with remission1,2 25 Reduction of elevated PD-1highTph cells in both UC colon and periphery correlates with remission % PD-1highTph cells% PD-1highTph cellsActive(before treatment)Stable remission(after treatment)543210Percentages of Tph(%)P<0.001Reduction of Tfh/Tph cells should impact plasma cell generation and autoantibody levels, including anti-microbial IgG antibodies that are contributing to colonic inflammation and barrier disruption4Parmley et. al. UEGW 2024. October 2024 1. PD-1highTph cells defined by CD3+CD4+CD45RA-PD-1+TIGIT+ICOS+CXCR5-. Long et al, Immunology Letters 233 (2021) 2-10.2. Rao et al, Nature, 2017. *** p<0.001, * p<0.053. Rosnilimab formatted to mIgG2a to mediate effector function in mice. Suzuki et al., Sci. Immunol. 8, eadd4947 (2023). 4. Uzzan et al, Nature, 2022 Colitis Induction(Day 0-21)hPD-1 CD4T cell transferbiweekly dosing(4 weeks)Day 21Rosnilimab mIgG2a3Anti IL-12 p40IsotypeDays
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Reduction of Tfh/Tph cytokine Reduction of inflammatory cytokine Agonism of PD-1+ T cells Depletion of PD-1highT Cells Parmley et. al. UEGW 2024. October 2024Anti-CD3+ anti-CD28 stimulation of UC patient PBMCs for assessment of depletion and agonism MOA, representative data from N=6 donors.Rosnilimab IgG1 LALA included to demonstrate importance of Fc effector function26 Rosnilimab’s potent depletion and agonism reduces T cell proliferation and inflammatory cytokines that disrupt barrier function % PD-1High T cells(normalized to isotype) 0.1110 1000255075100Antibody (nM)% ProliferatingPD-1+ T cells(normalized to isotype) 0Clinical range025507510000.1110 100Antibody (nM)CXCL13 & IL-21(% Isotype Control)IL-21CXCL13Clinical range025507510000.1110 100Antibody (nM)IFNγ(% Isotype Control)Clinical range Isotype controlRosnilimab IgG1 LALARosnilimab IgG1
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Following remission on induction therapy, one third to one half of patients relapse within 1 year1 Following remission on induction therapy, one third to one half of patients relapse within 1 year1 1. Phase 3 registrational data from product labels; 2 Prometheus Bioscience corp. presentation Mar 2023; 3. Roivant corp presentation Jan 2023; 4. Teva corp presentation Dec 2024; 5. Remission measured using modified Mayo Score, except for Remicade, Humira and Entyvio which used full Mayo Score.27 UC lacks highly effective treatment options to induce and maintain clinical remission 05101520253035404550Induction of Clinical Remission (%)Week 8 Week 8 Week 6Week 8 Week 10 Week 8Week 14Week 12PRA023(All comers)RVT-3101(All comers) Significant market share in severe patients1st line treatments of choice in moderate patients Induction of Clinical Remission1,2,3,4,5Approved Therapies Placebo Duvakitug(All comers)Week 12Week 12Week 12 Placebo-AdjustedTL1A Therapies (P2)
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[Optional for Responders] Blinded Treatment Extension Period (TEP)(26 weeks)Rosnilimab Phase 2b in moderate-to-severe UCTop-line data anticipated Q1 2026Screening Period (up to 35 days)Blinded Placebo-Controlled Treatment Period (12 weeks)Follow-Up Period (10 weeks)Blinded All-Active Treatment Period (12 weeks)24120-5WeekRosnilimab SC Dose 1Rosnilimab SC Dose 2Placebo SCRosnilimab SC Dose 1Rosnilimab SC Dose 2Placebo RespondersN = 132Randomize 1:1:1Primary Statistical AnalysisFinal Statistical AnalysisDosing:SC Q2W or Q4WTop-line Data•Adults with moderate-to-severe ulcerative colitis•Inadequate response to, loss of response to, or intolerance to as least 1 conventional or advanced UC therapy (~50% advanced UC therapy experienced)Patient population•Mean change from Baseline in modified Mayo Score (mMS) at Week 12PrimaryEndpoints•Clinical remission on mMS•Clinical response on mMS•Endoscopic remission•Mucosal healingSecondary•Mean change from Baseline in colonic tissue and peripheral biomarkersExploratory endpointsActive Eligibility VisitPlacebo Nonresponders ClinicalTrials.gov: NCT06127043Assess placebo pmMS clinical response at Week 12Rosnilimab SC Dose 2Rosnilimab SC Dose 2Placebo Responders605028
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Autoimmune and Inflammatory DiseasesANB033(CD122 antagonist)
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30 CD122 is a shared beta subunit of the receptors for IL-15 and IL-2 CD122 is a shared beta subunit of the receptors for IL-15 and IL-2 CD122 antagonist mAb will potently inhibit IL-15 and IL-2 biology CD122 antagonist mAb will potently inhibit IL-15 and IL-2 biologyBoth IL-15 and IL-2 mediate:•Proliferation and survival of T cell subsets, particularly CD8+ TEMRA, and NK cells•Inflammatory cytokine secretion (IFNγ) during T cell activationANB033 reduces pathogenic T cells•Preferentially inhibits lower affinity dimeric IL-2 receptor complex•Spare Tregs which express higher affinity trimeric IL-2 receptor complexANB033 has targeted reduction of CD122 expressing TRMcells•TRMcells require IL-15 for survival•May potentially drive durable response TregsTEMRA, TRM cellsNK cellsCD122CD122ANB033 ANB033: CD122 high affinity antagonist reduces pathogenic T cells and NK CellsPhase 1 trial initiated in healthy volunteers
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GVHD (severe phenotype) model in human IL-15 transgenic mouse supports T cell and NK cell survival•ANB033 preclinical data suggests targeted elimination of pathogenic T cells and reduction of tissue infiltrating T cells leading to a more potent and durable response than belatacept•Belatacept (GVHD SOC which only impedes T cell activation) shows minimal benefit over control End of dosingNote: ANB033 treated mice dosed twice per week through Day 28. 31 Weight Change (%of Start)Hare E, et al. FOCIS 2023. June 2023.GVHD model is biologically relevant to CD122 antagonist MoA with translation to inflammatory diseases driven by pathogenic TRMand Treg imbalance including rheumatology, dermatology, gastroenterology and respiratoryGVHD model is biologically relevant to CD122 antagonist MoA with translation to inflammatory diseases driven by pathogenic TRMand Treg imbalance including rheumatology, dermatology, gastroenterology and respiratory ANB033: Durable survival in GVHD modelAll mice treated at high-dose survived well beyond end of dosing
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Autoimmune and Inflammatory DiseasesANB101(BDCA2 modulator)
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ANB101 will potently inhibit interferon secretion and immune activation ANB101 will potently inhibit interferon secretion and immune activation 33 Activated pDCs bridge innate and adaptive immunity•Secrete Type I IFN (1000x increase over other cell types)•Present antigens to adaptive immune systempDCs enriched in tissue in rheumatology and other inflammatory diseases •BDCA2 modulator mechanistic proof-of-concept (Biogen’s litifilimab) in SLE / CLEANB101: BDCA2 modulator•Potent and sustained internalization of BDCA2 on pDC cell surface•Profound inhibition of interferon secretion reduces inflammation•Preserves pDCs for potential tolerogenic effects ANB101: BDCA2 modulator of plasmacytoid dendritic cell (pDC) function IND submitted; Phase 1 initiation anticipated Q1 2025 BDCA2 is a molecule specifically expressed on pDCs BDCA2 is a molecule specifically expressed on pDCs Note: ANB101 (formerly known as CBS004) was in-licensed from Centessa Pharmaceuticals. Has completed NHP tox studies and P1 clinical material available.
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JemperliTM(dostarlimab, PD-1 Antagonist) Cobolimab (TIM-3 Antagonist) GSK Immuno-Oncology Financial Collaboration
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“Jemperli– only” capped non-recourse monetization•Jemperlireceivables payable to Sagard until cumulative $600MM paydown by Mar. 31, 20311,2•~$90MM paid to Sagard as of early January 2025•Projected cumulative $600MM paydown by 2029 based on Wall Street Consensus3 Potential royalties and milestones to Anaptys from immuno-oncology financial collaboration 351. The $75MM commercial milestone is excluded from Sagard monetization. The following Jemperli milestones are also still potentially payable from GSK but contribute to Sagard paydown: $15MM on regulatory approvals and $50MM on annual net sales of $750MM.2. If cumulative $600MM not paid to Sagard by Mar. 31, 2031, the cumulative paydown increases to $675MM.3. GSK analyst consensus as of 11/14/2024 converted to USD (1.25 conversion rate), GSK website -https://www.gsk.com/en-gb/investors/analyst-consensus/Note: Anaptys’ capped non-recourse monetizations resulted in $300MM of non-dilutive capital, including $250MM in Oct. 2021 and $50MM in May 2024. Note: Separate sale of Anaptys’ Zejula(niraparib) royalty interest occurred in September 2022 to DRI Healthcare Trust for $35MM upfront + $10MM potential milestone upon FDA approval of Zejulafor the treatment of endometrial cancer, to the extent that such approval occurs on or before 12/31/25. At present, the Jemperliplus Zejulacombination demonstrated significantly improved PFS in primary advanced or recurrent endometrial cancer in the RUBY Phase III trial. (PD-1 antagonist)Cobolimab(TIM-3 antagonist) Royalty rate(annual WWnet sales)Remaining retained milestones8% - $0 to $1 billion12% - $1.0 to $1.5 billion20% - $1.5 to $2.5 billion25% - >$2.5 billion$75mm when annual net sales ≥ $1 billion14% - $0 to $250 million5% - $250 to $500 million6% - $500 to $750 million7% - >$750 to $1.0 billion 8% - >$1.0 billion$5MM clinical development$90MM regulatory$165MM commercialRoyalty rate on cobolimab includes potential cobolimab-portion of combination use with dostarlimab
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Actuals $31$57$73$101$137$170$0$50$100$150$200Q2 2023 Q3 2023 Q4 2023 Q1 2024 Q2 2024 Q3 2024Sales (in USD millions)JemperliQuarterly Performance1Consensus projections of Jemperli imply significant royalty upside to Anaptys post-Sagard paydown 1. GSK earnings presentation, US dollar conversion 2. GSK analyst consensus as of 11/14/2024 converted to USD (1.25 conversion rate), GSK website -https://www.gsk.com/en-gb/investors/analyst-consensus/3. GSK June 2024 Oncology Management IR event converted to USD (1.25x conversion rate) $28$176$578$816$974$1,086$1,163$1,216$1,261$1,276$0$550$1,100$1,650$2,200$2,7502022 2023 2024 2025 2026 2027 2028 2029 2030 2031Sales (in USD millions)JemperliWall Street Consensus1,2Current commercial performancePotential future growth drivers•$170MM Q3 2024 Sales (>100% YoY growth)1•Driven from US all-comers launch and higher new patients starts in 1L dMMR endometrial•Continued growth of EU 2L endometrial sales•Substantial investment in additional indications ongoing•1L “all-comers” endometrial: EU approval expected Q1 20251•1L ovarian: Positive P3 PFS data reported in Dec. 2024 to be shared with regulators•2L+ NSCLC: Phase 3 COSTAR (Jemperli+ TIM-3) data anticipated H1 20251•Locally advanced dMMR/MSI-H rectal cancer: granted FDA Breakthrough Therapy Designation36GSK Peak Revenue Guidance >$2.5 billion3
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Lung cancer2•2L NSCLC: P3 COSTAR trial (docetaxel vsdostarlimab + docetaxel vsdocetaxel + dostarlimab + cobolimab)•Top-line data expected in H1 2025•Significant U.S. market opportunity with 237,000 new NSCLC diagnoses/year1Additional dostarlimab royalty opportunities•P3: LA unHNSCC monotherapy sequentially after chemoradiation (JADE study)•P3: 1L NSCLC in combination with anti-TIGIT (belrestotug) (GALAXIES Lung-301)•P1/2 combinations with anti-CD96 and PVRIG across multiple solid tumors immuno-oncology financial collaboration +Cobolimab(TIM-3 antagonist) Colorectal cancer•Rectal cancer: P2 AZUR-1 trial (dostarlimab monotherapy in dMMR/MSI-H in locally advanced [LA] rectal cancer)•Colon cancer: P3 AZUR-2 trial (perioperative dostarlimab monotherapy vs SoC adjuvant chemotherapy in patients with high-risk early-stage dMMR/MSI-H cancer) 1. NCI SEER data 2. In 1L NSCLC, Phase 2 PERLA trial demonstrated 46% cORR for dostarlimab + chemo vs. 37% cORR for pembrolizumab + chemotherapy (not for registration)37 Women’s cancers•Endometrial Cancer:•1L endometrial cancer: Approved in US for primary advanced or recurrent EC; GSK has received a positive CHMP opinion for this same indication in the EU•2L endometrial cancer: Approved in US and EU for dMMR/MSI-H recurrent or advanced EC after progressing on a platinum-containing regimen•P3 RUBY Part 2: Addition of niraparib to dostarlimab in maintenance setting (dostarlimab + niraparib compared to placebo plus chemotherapy followed by placebo) demonstrated significant improvement in PFS in MMRp/MSS•Significant U.S. market opportunity with 23,000 eligible diagnoses/year1•Ovarian cancer: P3 (FIRST) trial (combination of dostarlimab + niraparib) in 1L ovarian cancer•Demonstrated significant improvement in PFS•Significant U.S. market opportunity with ~20,000 eligible diagnoses/year1 (PD-1 antagonist)
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Imsidolimab (IL-36R antagonist)Etokimab (IL-33 antagonist)Legacy Programs for Out-Licensing
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GEMINI-1: Imsidolimab (750mg and 300mg IV) Effective in Treatment of GPP Flare in GEMINI-1 & in Crossover Placebo Patients in GEMINI-2 (750mg IV) Observational data from placebo non-responders in GEMINI-1 who crossed over to GEMINI-2 rescued with imsidolimab 750mg IV showed similar results to GEMINI-1 53.353.413.355.6Imsidolimab750mgImsidolimab300mgPlacebo Imsidolimab750mg04060Percentage of PatientsPrimary Endpoint GPPPGA 0/1 at Week 4120n=15n=15n=15 n=9Single doses of imsidolimab were highly effective at inducing Generalized Pustular Psoriasis Physician Global Assessment (GPPPGA) response vs. placebo •Imsidolimab (n=8) 0% flared vs. placebo (n=8) 62.5% flared•Imsidolimab maintained GPPPGA 0/1 response regardless of GEMINI-1 dose•Placebo crossover patients who received imsidolimab 750mg IV/200mg SC in GEMINI-2 (n=9): 77.8% maintained remission for at least 24 weeks (observational data)In the placebo group, 3 patients received imsidolimab 300mg IV, 4 received 750mg IV, and 1 received placebo in GEMINI-1In the placebo group, 3 patients lost response at Week 2, 1 at Week 12, 1 at Week 28, and 1 at Week 44Time to Loss of GPPPGA 0/1 Response2 •Treatment-emergent adverse events (TEAE) similar across treatment groups•No SAEs or severe AEs in imsidolimab-treated patients•No cases of DRESS or GBS* •Low incidence and no elevation of infections vs. placebo•1 patient treated with 750 mg (n=30, 3%) had detectable non-neutralizing anti-drug antibodies (ADA)•Similar safety across both GEMINI-1 and -2Safety and Tolerability 1. % of patients achieving GPPPGA 0/1 at Week 4 and PRS 0/1 at Week 1 in GEMINI-1 after a single IV dose of imsidolimab 750mg, 300mg, or placebo 2. Kaplan-Meier curve of time to loss of response with imsidolimab 200mg SC (shown by dose of imsidolimab received in GEMINI-1) and placebo every 4 weeks39GEMINI-2: Imsidolimab (200mg SC) Q4W Maintained Response & Prevented GPP Re-flaring Regardless of GEMINI-1 Imsidolimab Dose *Drug Reaction with Eosinophilia and Systemic Symptoms, Guillain-Barre Syndrome Reich A., et al. EADV 2024. September 2024Full EADV 2024 poster and oral presentations are available on Anaptys website here GEMINI-1 and -2 Imsidolimab positive Phase 3 dataData presented at EADV 2024
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Etokimab: IgG1 antibody that inhibits the active form of IL-33•Binding affinity of etokimab is <1 pM; best-in-class based on competitor affinities published in patents and literature•Targeting IL-33 cytokine rather than IL-33 receptor (ST2) has potential to not only modify disease, but also drive epithelial remodelingIL-33 is genetically associated with asthma•IL-33 loss-of-function mutations protect against asthma, while gain-of-function mutations increase asthma incidence•Translational studies have demonstrated IL-33’s role as a pro-inflammatory cytokine released upon allergen contact with epitheliumIL-33 pathway derisked in COPD (positive Phase 2 data via AZ and REGN/SA)Broad commercial opportunity in additional non-respiratory diseases: allergy, epithelial driven diseases in GI and nephrology TAs40 •IL-33 is active in its reduced form and is quickly oxidized into an inactive form as a mechanism to limit its local activity •The majority of IL-33 in the body is the inactive oxidized formGiven etokimab’s MOA, it specifically inhibits only the IL-33 molecules that are driving activity and not “wasted” by binding to non-active oxidized IL-33Etokimab is Phase 2b/3 Ready(drug supply on hand, preclinical toxicology, P2 data, andcompetitor POC data across respiratory diseases, with AZ POC data in diabetic nephropathy expected this year) Etokimab: Ph 2b/3-ready IL-33 antagonist antibodyIL-33 biology applicable to epithelial driven diseases 40