Anaptysbio, Inc. · NASDAQ:ANAB
Anaptysbio — Investor Presentation (January 2023)
47 slides from Anaptysbio's investor presentation, Jan 5, 2023
Slide 1: Corporate Overview
Corporate Overview January 2022 Nasdaq: ANAB
Slide 2: Forward-looking statements
2 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 clinical trials, includi
Slide 3: Best-In-Class Immune Cell Modulating Antibodies
3 Best-In-Class Immune Cell Modulating Antibodies Potential to restore immune balance across autoimmune and inflammatory diseases Strong capital position ~4 years of cash with >$575mm as of YE 2022 GSK immuno-oncology financial collaboration Significant royalty potential Research-driven Preclinical
Slide 4: Immune Cell Modulator Development Plan
4 Immune Cell Modulator Development Plan Three phase 2 initiations in 2023 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 Inflammatory Disease ANB032 (BTLA agon
Slide 5: Advantages of Immune Cell Modulation in Treatment of Autoimmune and Inflammatory Diseases
Advantages of Immune Cell Modulation in Treatment of Autoimmune and Inflammatory Diseases
Slide 6: Inflammatory Diseases are Complex, Leading to Shortcomings in SOC Therapies
6 Moderate-to-Severe Inflammatory Diseases are Complex, Leading to Shortcomings in SOC Therapies Breadth of mechanism Cell signaling inhibitors: efficacy ceiling with AEs at most effective doses TYK2 (next gen) • Complex, heterogeneous diseases involve upregulation of multiple cytokines • Treatment
Slide 7: Immune Cell Modulators May Restore Immune Balance
7 JAKi (IC90) JAKi (Approved doses; suboptimal PD) Immune cell modulators: Potential for increased breadth, depth and durable response E ff ic a c y Single Cytokine blockers TYK2 (Sotyktu; suboptimal PD) Breadth of mechanism On-target activity (acceptable tox) Off-target activity (unacceptable tox)
Slide 8: Immune Cell Modulators are a Novel Therapeutic Class
8 ANB033 (CD122 antagonist) ANB032 (BTLA agonist) Rosnilimab (PD-1 agonist) A d ap ti ve Im m u n it y B cells Trm Tcon Treg/Tcon ratio In n at e im m u n it y NK cells ILCs Dendritic cells Potential Mechanisms of Action 1 Bias Treg/Tcon ratio towards tolerance at sites of aberrant inflammation and
Slide 9: Anti-Inflammatory Checkpoint Agonist Antibodies
9 • Checkpoint agonists for PD-1 and BTLA down regulate T cell mediated immune responses - BTLA also present on B cells and dendritic cells • Potential applicability across complex diseases - Dermatology - Gastroenterology - Rheumatology - Respiratory - Neurology • Potential for concomitant or seque
Slide 10: Combination of Characteristics Optimize Agonistic Signaling
10 Phosphatase Kinase Tighter synapse* Looser synapse* • Antigen binding epitope: - Spare natural ligand binding interaction - Bind proximal to the membrane to enhance tight synapse formation • Antigen binding affinity: - Optimal (not maximal affinity) Antigen binding characteristics • Fc receptor b
Slide 11: Rosnilimab (PD-1 agonist mAb) Introduction
Rosnilimab (PD-1 agonist mAb) Introduction
Slide 12: Rosnilimab: Best-in-Class PD-1 Agonist Antibody
Rosnilimab Fc Receptor PD-1 PD-L1 P SHP2 Antigen Presenting Cell T Cell Rosnilimab: Best-in-Class PD-1 Agonist Antibody Suppression of T cell mediated inflammatory diseases • Rosnilimab: IgG1 antibody that binds to PD- 1+ T cells - Membrane proximal binding epitope contributes to differentiated pote
Slide 13: Rosnilimab Significantly Reduces IFNγ in Healthy Donors
• Rosnilimab shows meaningful IFNγ inhibition beginning at low concentrations • Potency differentiation from Lilly’s PD-1 agonist is sustained across clinical concentrations Tetanus toxoid recall stimulation assay measures antigen- specific immune cell response. Prior immunity in majority of populat
Slide 14: Rosnilimab Demonstrates Superior Agonistic Signaling and Depletion of PD-1+ T Cells
Rosnilimab Demonstrates Superior Agonistic Signaling and Depletion of PD-1+ T Cells at Clinically Relevant Concentrations 0.1 1 10 100 0 20 40 60 80 100 120 Antibody (nM) % P ro li fe ra ti n g T c e ll s (n o rm a li z e d t o i s o ty p e ) Lilly PD-1 agonist Rosnilimab 0 0.001 0.01 0.1 1 10 100 0
Slide 15: Rosnilimab Healthy Volunteer Phase 1 Trial Results
Rosnilimab Healthy Volunteer Phase 1 Trial Results Potent and sustained reduction in peripheral PD-1+ T cells for >30 days in SAD -100 -80 -60 -40 -20 0 20 1 5 8 15 22 29 43 85 P e rc e n t C h a n g e F ro m B a s e li n e M e a n ( S E ) Days Treg Tcon PD-1+ Tcon PD-1 high Tcon ✓ Well tolerated wi
Slide 16: Rosnilimab P2a Alopecia Areata Blinded Pooled Interim Data
Rosnilimab 400 mg SC q4w N = 4 5 R an d o m iz ed 2 :1 Placebo Treatment Period Follow-Up Period W e e k 0 W e e k 2 4 W e e k 3 2 W e e k 2 0 Last Dose “Proof of Mechanism” P2a Blinded Pooled Interim Data Peripheral T cell effect • Impact on activated T cells and Tcon / Treg ratio in blood and impl
Slide 17: Rosnilimab P2a Proof-of-Mechanism Blinded Data
-100 -80 -60 -40 -20 0 20 1 2… 8… 1… 1… 2… P e rc e n t C h a n g e F ro m B a s e li n e M e a n ( S E ) Treg Tcon PD-1+ Tcon PD-1 high Tcon 0 (n=51) Week 4 (n=42) Week 12 (n=33) Week 24 (n=22) Week 28 (n=16) Week 32 (n=14) Blinded (pooled treated + placebo 2:1 randomization) Immunophenotyping Data
Slide 18: Rosnilimab (PD-1 agonist mAb) Rheumatoid Arthritis
Rosnilimab (PD-1 agonist mAb) Rheumatoid Arthritis (RA)
Slide 19: PD-1+ T Cells are Clinically Validated Drivers of Disease in RA
19 Initiation of Autoimmunity Pre-symptomatic RA Mild RA Moderate-to-Severe RA CD3+ T cells PD-L1PD-1+ *Adapted from Nature Reviews Disease Primers volume 4, Article number: 18001 (2018) and PLoS One 2018; 13(2): e0192704 PD-1+ T Cells are Clinically Validated Drivers of Disease in RA >80% of T cell
Slide 20: PD-1 Agonists are a Promising Novel Mechanism for RA
20 PD-1 PD-1 Rosnilimab *Adapted from Nature Reviews Disease Primers volume 4, Article number: 18001 (2018), **b/tsDMARD – biologic/targeted synthetic disease modifying antirheumatic drug, LDA – low disease activity PD-1 Agonists are a Promising Novel Mechanism for the Treatment of RA • b/tsDMARDs p
Slide 21: RA is a Substantial Opportunity for a New Class of Biologics
21 • Target population in US generated ~$10 billion in 2021 - Rituxan (typically salvage therapy) achieves well over $1 billion sales in 3L+ RA despite infection risk • No new therapeutic class has launched for RA since JAK inhibitors (Xeljanz) a decade ago (2012) • Lack of established SOC in 2L+ pr
Slide 22: Lilly's PD-1 Agonist Showed Proof of Mechanism in Phase 2a RA Study
22 -40 -30 -20 -10 0 0 2 4 8 12 14 16 20 24 C h a n g e F ro m B a s e li n e Weeks CDAI* Lilly’s PD-1 Agonist Showed Proof of Mechanism and Promising Efficacy in a Phase 2a RA Study • 48% and 61% of patients achieved LDA at week 12 for 300 and 700 mg Q4Q IV doses • Patients achieving LDA at week 12
Slide 23: PD-1 Agonists Potential to Differentiate on ACR50/70
23 63% 71% 62% 60% 65% 51% 71% 74% 29% 45% 32% 32% 36% 26% 42% 57% 13% 25% 10% 17% 18% 10% 20% 35% 0% 25% 50% 75% 100% Adalimumab (TNF) Upadacitinib (JAK) Adalimumab (TNF) Abatacept (CD80/86) Sarilumab*** (IL-6) Rituximab**** (CD20) Peresolimab (700mg Week 12) Peresolimab (700mg Week 14) % R e s p o
Slide 24: Rosnilimab Superior Inhibition of T Cell Proliferation in RA Patient-Derived PBMCs
24 Inhibition of T Cell Proliferation (in RA Patient-Derived PBMCs) • More potent reduction compared to Lilly PD-1 agonist is consistent between healthy PBMCs and RA patient- derived PBMCs Anti-CD3+ anti-CD28 stimulation of PBMCs for proliferation assessment of T cells, representative data from N=3
Slide 25: Rosnilimab P2b Trial in Moderate-to-Severe Rheumatoid Arthritis
25 • Explore broad exposure response and establish efficacious dose • Enable initiation of a registrational phase 3 campaign • Analyze potential predictive baseline characteristics including patient prior therapy and biomarkers • Three dose levels of rosnilimab - High dose is multiple fold higher th
Slide 26: ANB032 (BTLA agonist mAb) Introduction
ANB032 (BTLA agonist mAb) Introduction
Slide 27: ANB032: Best-in-Class BTLA Agonist Antibody
27 • ANB032: IgG4 antibody that binds to BTLA in lymphoid (T and B) cells and dendritic cells - Fc receptor binding profile together with membrane proximal binding epitope contributes to differentiated potency • ANB032 inhibits T cell proliferation and inflammatory cytokine secretion • ANB032 demons
Slide 28: ANB032 Superior Agonistic Signaling vs Lilly BTLA Agonist
28 ANB032 Demonstrates Superior Agonistic Signaling in Healthy PBMCs Compared to Lilly BTLA Agonist 0.1 1 10 100 40 60 80 100 120 140 Antibody (nM) % P ro li fe ra ti n g T c e ll s (n o rm a li z e d t o i s o ty p e ) 0 0.1 1 10 100 40 60 80 100 120 140 Antibody (nM) % I F N -γ S e c re ti o n (n
Slide 29: ANB032 Phase 1 Healthy Volunteer Trial Top-Line Data
29 • 96 healthy volunteers in randomized, double- blind, placebo-controlled SAD and MAD cohorts • ANB032 well-tolerated with no dose limiting tox - Most AEs mild-to-moderate, of short duration, dose independent and resolved without sequelae - No Serious Adverse Events • Favorable PK: ~2-week half-li
Slide 30: ANB032 (BTLA agonist mAb) Atopic Dermatitis Phase 2b
ANB032 (BTLA agonist mAb) Atopic Dermatitis Phase 2b
Slide 31: Atopic Dermatitis is Broader than a Th2 Inflammatory Disease
31 Th1Th2 ILC2 Th2 TRM TRM TRM TRM T T B Th17 Th2 Barrier dysfunction, innate immune activation and Th2-driven inflammation Antigen presentation, Th1 and Th17-driven inflammation Potential for BTLA expression Atopic Dermatitis (AD) is Broader than a Th2 Inflammatory Disease Th2 targeting SOC provide
Slide 32: AD is a Substantial Opportunity for a New Class of Biologics
32 • Dupixent is standard of care in moderate- to-severe AD - >$7 billion projected global sales (2027)** • Significant room to differentiate vs. SOC - Dupixent EASI75 of ~45%-50% leaves substantial opportunity for broader response, including suboptimal responding patients - Dupixent EASI90 of ~35%
Slide 33: ANB032 Inhibits Th1/Th2/Th17 Cytokine Secretion in AD Patient-derived PBMCs
33 0 20000 40000 60000 80000 IF N [p g /m l] CD3/CD28 stimulation **** 0 20 40 60 80 IL -1 3 [ p g /m l] CD3/CD28 stimulation ** 0 250 500 750 1000 1250 1500 IL -1 7 A [ p g /m l] CD3/CD28 stimulation *** p<0.0001 **** p<0.001 *** p<0.01 ** (all at 100 nM) Inhibition of Th1 (IFNγ Cytokine Secretio
Slide 34: ANB032 P2b Trial in Moderate-to-Severe Atopic Dermatitis
• Adult patients with moderate to severe atopic dermatitis • All comer population; includes patients with both Dupixent naïve and Dupixent experience Patient Population • Primary: Mean change from Baseline in EASI at Week 14 • Secondary: EASI75, IGA 0/1, PNRS, DLQI, SCORAD50, Safety • Exploratory: T
Slide 35: ANB033 (anti-CD122 antagonist mAb) Autoimmune and Inflammatory Diseases
ANB033 (anti-CD122 antagonist mAb) Autoimmune and Inflammatory Diseases
Slide 36: ANB033: Anti-CD122 Antagonist mAb Targets Pathogenic TRM Cells
36 CD122 is a shared beta subunit of the receptors for IL-15 and IL-2 • IL-15 mediates survival of TRM cells • Both IL-15 and IL-2 mediate: - Proliferation of T cells - Inflammatory cytokine secretion (IFNγ) during T cell activation • High affinity antagonist antibody induces death in TRM cells by p
Slide 37: ANB033: Durable Survival in GVHD Model
37 0 10 20 30 40 50 60 -20 -10 0 10 20 Average Body Weights (carried) Study Day W e ig h t C h a n g e ( % o f S ta rt ) • 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 driv
Slide 38: Legacy Programs for Outlicense
Legacy Programs for Outlicense Imsidolimab (IL-36r antagonist mAb) Etokimab (IL-33 antagonist mAb)
Slide 39: Generalized Pustular Psoriasis (GPP)
39 • 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 f
Slide 40: Imsidolimab: an Anti-IL-36r Antagonist Antibody
Normal Individuals IL-36 cytokine signaling balanced by functional IL-36 receptor antagonist Disease Patients Uncontrolled signaling due to dysfunctional IL-36 receptor antagonist or elevated IL-36 cytokine levels Treated Patients Anti-IL-36 antagonist antibody has the potential to dampen disease by
Slide 41: Imsidolimab Phase 2 GPP Trial Results
41 • Imsidolimab 750mg IV loading dose + 100mg SC q4w maintenance dose • Rapid and sustained efficacy through week 16 – 6 of 8 (75%) patients achieved primary endpoint of improvement in the clinical global impression scale (CGI) – Early reduction of erythema with skin pustules by week 1; sustained r
Slide 42: Imsidolimab GEMINI-2 Trial Design
42 Patient Population R an d o m iz at io n n =4 5 * W e e 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 se
Slide 43: Etokimab: Phase 2b/3-Ready Anti-IL-33 Antagonist Antibody
• Etokimab: IgG1 antibody that inhibits the activity of the active form of IL-33 • IL-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
Slide 44: GSK Immuno-Oncology Financial Collaboration
GSK Immuno-Oncology Financial Collaboration JEMPERLITM (dostarlimab, anti-PD-1 Antagonist) Cobolimab (GSK4069889, anti-TIM-3 Antagonist) GSK4074386 (TSR-033, anti-LAG-3 Antagonist)
Slide 45: JEMPERLI Royalties and Sagard Monetization
45 JEMPERLI (anti-PD-1 antagonist) GSK anticipates ~$1.2-2.4B peak annual sales for JEMPERLI in currently approved indications and anticipated 1L endometrial/ovarian approvals* • JEMPERLI 12-25% royalties on annual net sales ≥ $1B • JEMPERLI $75mm commercial milestone on annual net sales ≥ $1B In 2H
Slide 46: Dostarlimab: Endometrial, NSCLC and Ovarian Cancer Trials
46 (Anti-PD-1 antagonist) Cobolimab (Anti-TIM-3 antagonist) GSK4074386 (Anti-LAG-3 antagonist) Dostarlimab: 1L Endometrial Cancer • Approved in US and EU for dMMR recurrent or advanced endometrial cancer after progressing a platinum-containing regimen • P3 RUBY trial met primary endpoint in 1L prima
Slide 47: AnaptysBio
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