Anaptysbio, Inc. · NASDAQ:ANAB
Anaptysbio — Investor Presentation (January 2024)
51 slides from Anaptysbio's investor presentation, Jan 5, 2024
Slide 1: January 2024 Corporate Overview
January 2024 Corporate Overview Nasdaq: ANAB
Slide 2: Forward-looking statements
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
Slide 3: Best-in-class immune cell modulating antibodies
Best-in-class immune cell modulating antibodies 3 Immune Cell Modulators Imsidolimab (IL-36R) Positive P3 data reported in GPP Etokimab (IL-33) P2b/3-ready in epithelial driven diseases ANB033 (CD122 antagonist) ANB101 (BDCA2 modulator) IND-enabling Rosnilimab (PD-1 agonist) P2b in Rheumatoid Arthri
Slide 4: Antibody program pipeline and anticipated milestones
Antibody Program Therapeutic Indication Development Stage and Anticipated Milestones Lead Optimization IND Enabling Phase 1 Phase 2 Phase 3 Rosnilimab (PD-1 agonist) Rheumatoid Arthritis Ulcerative Colitis ANB032 (BTLA agonist) Atopic Dermatitis ANB033 (CD122 antagonist) Inflammatory Diseases ANB101
Slide 5: Checkpoint agonists restore immune balance
Immune cells (e.g., T cells, B cells, dendritic cells) Checkpoint receptors (e.g., PD-1, BTLA) Treat inflammation: Down-regulate immune cells Teff=T effector cells; Tph cells=Peripheral helper cells; Tfh cells=Follicular helper cells. 5 Checkpoint agonists “hit the brakes” to restore immune balance
Slide 6: Structural characteristics and functional outputs of checkpoint agonists
Fc receptor binding affinity Depletion Binding properties Agonism Membrane- proximal epitope 6 S tr u ct u ra l ch a ra ct e ri st ic s Fu n ct io n a l o u tp u ts PD-1 Agonist BTLA Agonist Lilly’s LY-3361237 (IgG4 PAA1) ANB032 (IgG4) Lilly’s Peresolimab (IgG1k) Rosnilimab (IgG1k) Decreased2 Signif
Slide 7: Rosnilimab (PD-1 agonist mAb)
Rosnilimab (PD-1 agonist mAb)
Slide 8: Rosnilimab's differentiated efficacy and safety potential
8 Rosnilimab’s impact in inflamed tissue and periphery has potential to deliver differentiated efficacy and safety 2. Reduce PD-1+ T cell activation 1. Reduce PD-1high Teff cells 3. Reduce PD-1high Tfh/Tph cells Relevant Approved Treatments1 Rosnilimab’s 3 MOAs impact on T cells Immunologic outcomes
Slide 9: Rosnilimab optimizes PD-1+ T cell inhibitory signaling
1. Adapted from Suzuki et al., Sci. Immunol. 8, eadd4947 (2023). 9 Dendritic cell T cell T cell Activation MHCCD80/86 SHP2 TCRCD28 P PD-1 PD-L1 Rosnilimab Fc Receptor # 4 Functional assay of antagonism or agonism1 Lilly epitope Rosnilimab Lilly PD-1 agonist PD-L1 epitope Lilly PD-1 agonistRosnilimab
Slide 10: Potent depletion and agonism at clinically relevant concentrations
1. Healthy donor T cells + NK cells (1:5 ratio) + antibody in in-vitro ADCC assay, representative data from N=5 donors. 2. Healthy donor purified DCs + autologous total T cells stimulated with anti-CD3, cultured for 3 days for assessment of T cell proliferation Two-way ANOVA. Tukey’s multiple compar
Slide 11: Rosnilimab targets only a small proportion of T cells
11 PD-1 expression on both CD4 and CD8 T cells correlates with activation state Rosnilimab targets only a small proportion of T cells In healthy volunteers: ―Deplete PD-1high T cells: ~5-8% of total T cells ―Agonize remaining PD-1int T cells: ~15% of total T cells P D -1 + T c e ll s CD3 PD-1high PD
Slide 12: Sustained reduction in peripheral PD-1+ T cells
1. AA=Alopecia Areata; 2. Results shown from 400mg subcutaneous dose (single dose in healthy and monthly dose in AA). 12 Rosnilimab P2a AA patients Rosnilimab P1 healthy volunteers Consistent PD-1+ T cell effect2 • >90% reduction of PD-1high T cells • >50% reduction of PD-1+ T cells Overall T cell c
Slide 13: Rosnilimab Phase 1 safety and tolerability
SAD=Single ascending dose; MAD=Multiple ascending doses; RO=Receptor occupancy; PK=Pharmakokinetics, SC = subcutaneous. 1. MAD cohort no SAEs; SAD cohorts 2 SAEs unrelated to rosnilimab as follows: Obstructive pancreatitis occurred in a placebo subject and Coronavirus infection occurred in drug 400
Slide 14: Rosnilimab potential in RA and UC
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 14 Rosnilimab has potential to treat wide range of systemic inflammatory diseases, including RA and UC Large comme
Slide 15: PD-1+ T cells prevalent in inflamed tissue in RA and UC
Adapted from Nguyen et al, Human Pathology (2022) 126, 19e27; Guo et al, PLoS One 2018; 13(2): e0192704. Shi et al. (2023), PeerJ, DOI 10.7717/peerj.15481. 1. Murray-Brown et al, RMC Open, 2022, Shi et al. (2023), PeerJ, DOI 10.7717/peerj.15481. 15 PD-1+ T cells are prevalent in inflamed tissue and
Slide 16: Rosnilimab reduces T cell proliferation and cytokines in RA
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. 1. TNFa secretion measured in anti-CD3+ anti-CD28 stimulation of purified
Slide 17: PD-1+ T cells impact drivers of RA pathogenesis
Adapted from Aletaha and Smolen, JAMA, 2018 17 PD-1+ T cells broadly impact multiple 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 patients Naive T Cell IL-17 IFN-y IL-21 CXCL13 APC
Slide 18: PD-1 agonist class clinically validated in RA
Tuttle, J. EULAR 2023, Week 14-Week 24 data estimated from peresolimab (PD-1 agonist) 2022 ACR presentation; CDAI=Clinical disease activity index. Sample size for top two charts: placebo n=24; peresolimab 300mg n=25 and peresolimab 700mg n=49. In bottom graph, placebo n=11, peresolimab 300mg n=12 an
Slide 19: RA approved therapy efficacy comparison
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 (2
Slide 20: Rosnilimab Phase 2b trial design in RA
20 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) Week -5 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 34 38 Visit V1 V2 V3 V4 V5 V6 V7 V8 V9 V10 V11 V12 V13 V14 V15 V16 FUV1 FUV2 FUV3 D
Slide 21: PD-1+ T cells impact drivers of UC pathogenesis
Adapted from Gastroenterology & Hepatology Volume 18, Issue 8 August 2022. 21 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+ B cells IL-23 antagonists αEβ7 Lymph node S1PR modulators TEff MAdCAM-1 Ant
Slide 22: PD-1high Tph cells reduction correlates with remission in UC
PD-1high Tph cells defined by CD3+CD4+CD45RA-PD-1+TIGIT+ICOS+CXCR5-). Long et al, Immunology Letters 233 (2021) 2-10., Rao et al, Nature, 2017. *** p<0.001 22 Reduction of elevated PD-1high Tph cells in both UC colon and periphery correlates with remission PD-1high Tph cells are elevated PD-1high Tp
Slide 23: PD-1 agonists induce remission in murine colitis models
Rosnilimab and HM226 bind to the membrane proximal “epitope 7” of PD-1 that contributes to maximal PD-1 agonism. Rosnilimab formatted to mIgG2a to mediate effector function in mice. Suzuki et al., Sci. Immunol. 8, eadd4947 (2023). 23 Prophylactic or therapeutic dosing of PD-1 agonists induce and mai
Slide 24: Rosnilimab reduces T cell proliferation and cytokines in UC
Anti-CD3+ anti-CD28 stimulation of UC patient PBMCs for assessment of depletion and agonism MOA, representative data from N=6 donors. 24 Rosnilimab’s potent depletion and agonism reduces T cell proliferation and inflammatory cytokines that disrupt barrier function Inhibition of T cell proliferation
Slide 25: UC lacks highly effective treatment options
1. Phase 3 registrational data from product labels; 2 Prometheus Bioscience corp. presentation Mar 2023; 3. Roivant corp presentation Jan 2023: 4. Remission measured using modified Mayo Score, except for Remicade, Humira and Entyvio which used full Mayo Score 25 UC lacks highly effective treatment o
Slide 26: Rosnilimab Phase 2b trial design in UC
26 Rosnilimab Phase 2b in moderate-to-severe UC Initiated Q4 2023; Top-line data H1 2026 Screening Period (up to 35 days) Blinded Placebo-Controlled Treatment Period (12 weeks) Follow-Up Period (10 weeks) Blinded All-Active Treatment Period (12 weeks) Week -5 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28
Slide 27: ANB032 (BTLA agonist mAb)
ANB032 (BTLA agonist mAb)
Slide 28: BTLA is a key node of immune regulation
28 BTLA is key node of immune regulation • B and T lymphocyte attenuator (BTLA) is a potent checkpoint receptor • Expressed only on immune cells and preferentially on activated immune cells • Dysregulation of BTLA pathway accelerates onset and exacerbates disease ANB032: IgG4 antibody (non-depleting
Slide 29: ANB032 best-in-class BTLA agonism
Jurkat BTLA SHP2 Recruitment Assay methodology: BTLA and SHP2 are fused with complementary enzyme fragments, when SHP2 is recruited to activated phosphorylated BTLA, the enzyme donor and enzyme acceptor form active β-gal that is detected by chemiluminescence. 29 10-9 10-8 10 -7 10-6 10-5 10 -4 0 200
Slide 30: ANB032 in-vivo efficacy in GvHD model
30 0 20 40 60 80 100 H um an T c el ls (% T ot al ly m ph oc yt es ) Human T cell expansion (Day 18) 0 10 20 30 40 50 60 70 80 -20 -10 0 10 20 Study Day W ei gh t ( % of S ta rt) Body weight 0 10 20 30 40 50 60 70 80 0 10 20 30 40 50 60 70 80 90 100 Study Day Pe rc en t R em ai ni ng Survival Biweek
Slide 31: ANB032 Phase 1 safety and PK/PD
31 31 ANB032 demonstrated favorable safety and tolerability with rapid and sustained PK/PD activity 96 healthy volunteers in SAD and MAD cohorts in Phase 1 study • Favorable ~2-week half-life with IV and SQ dosing • Full receptor occupancy (RO) within hours and maintained for >30 days Rapid and sust
Slide 32: Opportunity for new biologic class in atopic dermatitis
Opportunity for new biologic class with differentiated outcomes in AD regardless of prior treatment 32 US prevalence2 Target Population Diagnosed Moderate-to-Severe Biologic eligible Moderate-to-Severe Diagnosed5 Million 2 Million 1.2 Million Suboptimal Responders >50% EASI-75 45-50% EASI-90 <35% Si
Slide 33: Immune drivers of atopic dermatitis pathogenesis
33 33 Th1, Th2, Th17, Th22 and dendritic cells in tissue and periphery drive atopic dermatitis pathogenesis Th2 ILC2 Th2 TRM TRM TRM Th2 dupilumab Th22 Potential for BTLA expression (ANB032 impact) TRM Th2 Th22 ILC2 T T Dendritic cell Allergen IL-4 IL-13 IL-5 IL-13 TARC TSLP, IL-33 Th1 Th17 Th17 Th1
Slide 34: AD is highly heterogeneous
34 European-American AD African- American AD Asian AD Th1 Th2 Th17 Th22 AD is highly heterogeneous involving multiple immune cytokines • Immune activation can vary by ethnicity resulting in a highly heterogeneous presentation • Substantial unmet need across all patient populations Expect ANB032 to d
Slide 35: Anaptys leading where the AD landscape is moving
Initial AD clinical efficacy (Dupixent, IL-4/13) (Lebrikuzumab, IL-13) (Amlitelimab, OX-40L) (Ucenprubart, CD200R agonist) (JNJ-67484703, PD-1 agonist) (Rocatinlimab, OX-40) Broadly reduces T cell (Th1, Th2, Th17, Th22) cytokine secretion and modulates dendritic cells inducing Tregs (ANB032, BTLA ag
Slide 36: ANB032 inhibits Th1, Th2, Th17 and Th22 cytokines
Inhibition of Th1 Cytokine Secretion Inhibition of Th17 Cytokine Secretion Inhibition of Th2 Cytokine Secretion Inhibition of Th22 Cytokine Secretion 36 10 100 40 60 80 100 120 Antibody (nM) % IF N γ se cr et io n (n or m al iz ed to is ot yp e) 0 1 Clinical range 10 100 40 60 80 100 120 Antibody (n
Slide 37: ANB032-treated DCs induce functional Tregs
37 Isotype ANB032 Foxp3 C D 2 5 13% Tregs 29% Tregs ANB032-treated DCs induce functional Tregs offering potential to restore immune balance Allogeneic DC-T cell coculture + Isotype or ANB032 treated DCs Naïve CD4+ T cells 5 days Treg
Slide 38: ANB032 Phase 2b trial design in AD
ANB032 Phase 2b in IL-13 mAb naïve and experienced AD patients Initiated Q2 2023; Top-line data YE 2024 38 38 Screening Efficacy: ~3-month treatment Safety/Durability: ~6-month follow up V2 Wk 0 V3 Wk2 V4 Wk4 V5 Wk 6 V6 Wk 8 V7 Wk 10 V8 Wk 12 V9 Wk 14 V10 Wk 16 V15 Wk 36 Patient population • Adults
Slide 39: ANB033 (anti-CD122 antagonist mAb)
ANB033 (anti-CD122 antagonist mAb) Autoimmune and Inflammatory Diseases
Slide 40: ANB033 reduces pathogenic TRM and NK cells
40 CD122 is a shared beta subunit of the receptors for IL-15 and IL-2 Both IL-15 and IL-2 mediate: • Proliferation and survival of NK cells and subsets of T cells • Inflammatory cytokine secretion (IFNγ) during T cell activation IL-15 mediates survival of TRM cells Reduces pathogenic cells by prefer
Slide 41: ANB033 durable survival in GVHD model
• 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 TRM drives more potent and durable response than belatacept - Belatacept (GVHD SOC which only impedes T cell activation) shows mi
Slide 42: ANB101 (BDCA2 modulator mAb)
ANB101 (BDCA2 modulator mAb) Autoimmune and Inflammatory Diseases
Slide 43: ANB101: BDCA2 modulator of pDC function
43 Activated pDCs bridge innate and adaptive immunity • Secrete Type I IFN (1000x increase over other cell types) • Present antigens to adaptive immune system pDCs enriched in tissue in rheumatology and other inflammatory diseases • BDCA2 modulator mechanistic proof-of-concept (Biogen’s litifilimab)
Slide 44: Legacy Programs for Out-license
Imsidolimab (IL-36R antagonist mAb) Etokimab (IL-33 antagonist mAb) Legacy Programs for Out-license
Slide 45: Generalized Pustular Psoriasis (GPP)
GPP is a systemic, life-threatening inflammatory disease characterized by widespread pustules • Associated with unregulated IL-36 signaling • Patients have a high fever and elevated levels of serum CRP and inflammatory cytokines (e.g., IL-8) • Severe GPP patients can die from cardio-pulmonary failur
Slide 46: Imsidolimab GEMINI-1 trial design
46 Patient Population R an do m iz at io n n= 45 1 W ee k 0 Key Endpoints • Male and female subjects 18 to 80 years of age • Clinically confirmed diagnosis of GPP as per ERASPEN definition • Baseline Generalized Pustular Psoriasis Physician Global Assessment (GPPPGA) score of at least moderate sever
Slide 47: Imsidolimab positive GEMINI-1 Phase 3 data
47 • GEMINI-1 trial: registration-enabling trial enrolled 45 patients • First randomized, double-blind, placebo-controlled trial to use the composite endpoint of Generalized Pustular Psoriasis Physician Global Assessment (GPPPGA) at Week 4 as primary assessment • 53.3% of patients who received a sin
Slide 48: Etokimab: IL-33 antagonist
Etokimab: IgG1 antibody that inhibits the active form of IL-33 • The binding affinity of etokimab is <1 pM; best-in- class based on competitor affinities published in patents and literature • Targeting the IL-33 cytokine rather than the IL-33 receptor (ST2) has the potential to not only modify disea
Slide 49: GSK Immuno-Oncology Financial Collaboration
JemperliTM (dostarlimab, anti-PD-1 Antagonist) Cobolimab (GSK4069889, anti-TIM-3 Antagonist) GSK Immuno-Oncology Financial Collaboration
Slide 50: Significant potential royalties from immuno-oncology collaboration
50 Significant potential royalties from immuno-oncology financial collaboration Note: Sale of Zejula (niraparib) royalty interest in September 2022 to wholly-owned subsidiary of DRI Healthcare Trust for $35mm upfront + $10mm potential milestone upon FDA approval of Zejula for the treatment of endome
Slide 51: Dostarlimab women's cancers and lung cancer opportunities
Women’s cancers • 1L endometrial cancer: Approved in US and EU for dMMR/MSI-H primary advanced or recurrent endometrial cancer and dMMR/MSI-H recurrent or advanced endometrial cancer after progressing a platinum-containing regimen • P3 RUBY Part 2 trial (dostarlimab + niraparib) demonstrated signifi