Equillium, Inc. · NASDAQ:EQ
Equillium — Investor Day (December 2020)
114 slides from Equillium's investor day presentation, Dec 4, 2020
Slide 1: Virtual Investor / Analyst Day December 4, 2020
Virtual Investor / Analyst Day December 4, 2020 www.equilliumbio.com Exhibit 99.1
Slide 2: Safe Harbor Statement
Safe Harbor Statement This presentation contains forward-looking statements about Equillium, Inc. (the “Company”). In some cases, you can identify forward-looking statements by the words “will,” “expect,” “intend,” “plan,” “objective,” “believe,” “estimate,” “potential,” “continue”, “target”, “predi
Slide 3: Today's Agenda and Speakers
Welcome Bruce Steel, CEO Potent Immune Modulation with Itolizumab Steve Connelly, CSO Advancing Itolizumab in Graft-vs-Host Disease (GVHD) Krishna Polu, CMO John Koreth, M.D., Dana-Farber Steve Connelly, CSO Itolizumab – a Promising Therapeutic to Treat Lupus Nephritis Krishna Polu, CMO Steve Connel
Slide 4: Novel Treatments for Severe Immuno-inflammatory Disorders
Our mission is to dramatically improve the lives of patients through the development of novel immunotherapies World leaders in CD6 biology developing itolizumab, a first-in-class anti-CD6 antibody targeting the CD6-ALCAM pathway Itolizumab is a validated therapeutic with differentiated mechanism of
Slide 5: Itolizumab Development Strategy
Highly differentiated mechanism of action with potential broad therapeutic utility Itolizumab Development Strategy uncontrolled asthma acute graft-versus-host disease (aGVHD) Indication Phase 1b Phase 2 / 3 Status systemic lupus erythematosus (SLE) / lupus nephritis (LN) FDA Fast Track and Orphan Dr
Slide 6: T Cell Mediated Immuno-inflammatory Diseases
T Cell Mediated Immuno-inflammatory Diseases
Slide 7: Our Journey to Improve Patient Lives
Strategic partnership with Biocon Limited (Biocon): exclusive rights to develop and commercialize itolizumab in the U.S., Canada, Australia, New Zealand Includes supply of commercial-scale drug product manufacturing Three clinical development programs ongoing; initial data promising Strong cash bala
Slide 8: Potent Immune Modulation with Itolizumab
Potent Immune Modulation with Itolizumab
Slide 9: CD6-ALCAM Pathway Central to Immuno-inflammation
CD6 is a co-stimulatory receptor expressed on T cells, differentially expressed on subsets of innate lymphoid (ILC) and natural killer (NK) cells, but not on T regulatory cells (Treg) Activated leukocyte cell adhesion molecule (ALCAM), is expressed on both antigen-presenting cells and endothelial/ep
Slide 10: CD6 Expression Associated with T Cell Function
CD6 Expression Associated with T Cell Function Highest levels of CD6 are found on activated T effector cells (Teff) and associated with amplification of the auto-reactive cascade Immune Regulatory “Tolerance” Autoreactive “Autoimmunity” CD6Low/- CD6 + CD6High CD6 Th1 Th2 Th17 Garcia et al., Cytometr
Slide 11: CD6High Cells Exhibit Greater Pathogenic Capacity
T eff T reg CD6high High Proliferation Pathogenic Phenotypes Pro-inflammatory cytokines CD6low/- Low proliferation Regulatory phenotype Anti-inflammatory cytokines CD6High Cells Exhibit Greater Pathogenic Capacity Consuegra-Fernandez et al., Cell Mol Immunol 2018; Ma et al., J Crohns & Colitis 2019
Slide 12: CD6-/- Phenotype of Teff & Treg Cells
Increased activation induced cell death Decreased Teff proliferative responses Impaired Th17 differentiation Attenuation of disease in EAE, EAU & Pso EAE: Experimental Autoimmune Encephalomyelitis EAU: Experimental Autoimmune Uveitis Pso: Psoriasis Reduced infiltration of Teff cells into tissues Dec
Slide 13: CD6-ALCAM Pathway Central to Immuno-inflammation
CD6-ALCAM Pathway Central to Immuno-inflammation ACTIVITY TRAFFICKING Increased proinflammatory cytokine secretion Suppression of regulatory pathways Increased trafficking of Teff cells into target tissues Optimal immune synapse formation, activation and proliferation
Slide 14: An Example of the CD6-ALCAM Pathway in Disease
An Example of the CD6-ALCAM Pathway in Disease Ma et al., J Crohns & Colitis 2019
Slide 15: CD6 & ALCAM Increased in Intestine of IBD Patients
CD6 & ALCAM are Increased in Intestine of Inflammatory Bowel Disease (IBD) Patients Ulcerative Colitis Crohn’s Disease Healthy control CD6 ALCAM Ma et al., J Crohns & Colitis 2019
Slide 16: CD6-ALCAM Pathway is Associated with Severity of IBD
CD6-ALCAM Pathway is Associated with Severity of IBD Ma et al., J Crohns Colitis 2019 ***P<0.001 ALCAM CD6 Ulcerative Colitis Crohn’s Disease Ulcerative Colitis Crohn’s Disease
Slide 17: CD6high Cells are Enriched in Inflamed GI Tissues
CD6high Cells are Enriched in Inflamed GI Tissues ALCAM CD6 Increased CD6/ALCAM expression localizes to inflamed tissue of IBD patients Ulcerative Colitis Crohn’s Disease Ulcerative Colitis Crohn’s Disease Ma et al., J Crohns Colitis 2019 ***P<0.001
Slide 18: Increased IFNγ/IL-17 Secretion Associated with CD6high Cells
Increased IFNγ/IL-17 Secretion Associated with CD6high Cells Pathogenic dual IFN-γ / IL-17 expressing Th17 cells implicated in multiple autoimmune and inflammatory diseases are associated with levels of CD6 in IBD patients Ma et al., J Crohns Colitis 2019. **p < 0.01, and ***p < 0.001 versus CD6low/
Slide 19: Itolizumab (EQ001) - A First-in-Class Anti-CD6 Antibody
Itolizumab Humanized IgG1 Kappa Binds to domain 1 of human CD6 with 1.3 nM affinity Inhibits ALCAM binding to CD6 and leads to antigenic modulation Non-depleting, no ADCC, CDC activity Manufacturing and formulation Manufactured in CHO cells at commercial scale Single formulation allows for IV or sub
Slide 20: Antigenic Modulation of Cell Surface CD6
Antigenic Modulation of Cell Surface CD6 CD6 mean fluorescence intensity on itolizumab treated cells normalized to isotype treated cells 3 independent experiments on Donor 1041 (unstimulated PBMCs) CD6hi CD6lo Same pattern of CD6 loss is observed in both naïve and effector/memory subsets Pathogenic
Slide 21: CD6 Blockade Inhibits Teff Activation and Proliferation
CD6 Blockade Inhibits Teff Activation and Proliferation Inhibition of activation and proliferation Nair et al., Clin. Exp. Immunol., 2010 Control Itolizumab *p<0.05
Slide 22: CD6 Blockade Inhibits Pathogenic Teff Activity
CD6 Blockade Inhibits Pathogenic Teff Activity Betelli et al., J. Exp. Med. 2005; Muranski et al., Blood 2013; Banuelos et al., Cytokine Growth Factor Rev. 2016; Ramesh et al., J.Exp. Med. 2014; Bughani et al., PLoS, 2017 Downregulation of pSTAT3 RORγT Decrease in pathogenic Th17 cells Pathogenic Th
Slide 23: CD6 Blockade Inhibits Pathogenic Teff Activity
CD6 Blockade Inhibits Pathogenic Teff Activity Lee et al., 2008; Bughani et al., PLoS, 2017 Decrease in pathogenic, dual IFN-γ / IL-17 expressing T cells Pathogenic dual IFN-γ / IL-17 expressing Th17 cells implicated in multiple autoimmune and inflammatory diseases IL-17A IFN-γ
Slide 24: CD6low Cells are Hyporesponsive to TCR Stimulation
Cell-surface CD6 was removed by incubating peripheral blood mononuclear cells (PBMC) with itolizumab (or isotype) for 24 hours Afterwards, all cell-bound and excess itolizumab was removed PBMCs were then stimulated with anti-CD3 and ALCAM for 24 hours and activation markers were assessed by flow cyt
Slide 25: Preclinical Animal Model Data
Animal Model/ Disease Relevance Method T cell response Key Results Human Tissue Expression CD6 ALCAM TNBS Colitis Inflammatory Bowel Disease TCT 2020 Anti-mCD6 Th1, Th17 Decreased colitis Improved body weight Decreased serum cytokine levels EAE Multiple Sclerosis, NMO Li et al., PNAS. 2018 Anti-mCD6
Slide 26: Preclinical Animal Model Data (continued)
Animal Model/ Disease Relevance Method T cell response Key Results Human Tissue Expression CD6 ALCAM Nephrotoxic Serum Nephritis Antibody-mediated Nephritis ACR 2020 Anti-mCD6 Th1, Th17 Decrease in proteinuria, urinary albumin, BUN Decreased renal infiltration/trafficking by activated T cells and ma
Slide 27: Upstream, Disease Modifying Immuno-inflammatory Mechanism
Upstream, Disease Modifying Immuno-inflammatory Mechanism Restoration of immune regulation without immunosuppression Inhibition of Teff trafficking into key target organs Synergistic inhibition of multiple Teff cells and cytokines* Itolizumab acts upstream and selectively targets autoreactive effect
Slide 28: Advancing Itolizumab in Graft-vs-Host Disease (GVHD)
Advancing Itolizumab in Graft-vs-Host Disease (GVHD)
Slide 29: Acute graft-versus-host disease (aGVHD)
Acute graft-versus-host disease (aGVHD) 8,500 30-70% 53% 0 Allo-HSCT’s performed in 2018 4% procedural growth year-over-year since 2007 Allo-HSCT patients will develop aGVHD Reported 5 year survival rate for responders to first-line treatment with corticosteroids Number of approved treatments for fi
Slide 30: aGVHD: Advancing Toward Late-Stage Development in 2021
aGVHD: Advancing Toward Late-Stage Development in 2021 US Investigational New Drug (IND) Orphan Drug Designations Fast Track Designation EQUATE aGVHD Phase 1b interim results Phase 1b Top Line 1H 2021 FDA interaction in 2021 to define regulatory pathway to approval Late phase development to start mi
Slide 31: Acute Graft-versus-Host Disease: A Primer
Acute Graft-versus-Host Disease: A Primer Equillium Investor Day December 4, 2020 John Koreth, MBBS DPhil Associate Professor of Medicine Dana-Farber Cancer Institute; Brigham and Women’s Hospital; Harvard Medical School Boston, MA
Slide 32: Graft vs. Host Disease Classification
Graft vs. Host Disease Classification Acute GVHD (aGVHD): Rapid Onset Involvement of skin, gut, or liver Onset typically 2-3 weeks after stem cell infusion, or during immunosuppression taper Chronic GVHD (cGVHD): Insidious Onset Progressive in nature Onset often after 3 months Acute GVHD Chronic GVH
Slide 33: Graft vs. Host Disease
Graft vs. Host Disease GVHD Triad Antigenic Differences: “Target” +HLA mismatches -Minor histocompatibility antigens, Graft with Immunocompetent Cells C) © Immunessupressed ) Host “Exceptions” + Autologous GVHD CIBMTR) + Transfusion reactions similar to GVHD &
Slide 34: aGVHD Pathogenesis: Three Step Model
aGVHD Pathogenesis: Three Step Model Ferrara et al. Lancet 2009
Slide 35: Risk Factors for aGVHD
Risk Factors for aGVHD Histocompatibility HLA mismatch > HLA match Age - Older patient and donor age Sex mismatch - Female donor to male recipient Donor allo-sensitization Prior pregnancy Transfusion CMV status - CMV sero-positivity in patient or donor Conditioning regimen - Ablative > RIC Advanced
Slide 36: aGVHD: Clinical Features
aGVHD: Clinical Features Most common cause of morbidity and mortality early after CNI-based allogeneic HSCT Matched related donor = 40-60% Matched unrelated donor = 50-70% Clinicopathologic syndrome affecting 3 main organs: Skin (most common): Rash - mild to blistering Gastrointestinal tract: Nausea
Slide 37: Cutaneous Acute GVHD
Cutaneous Acute GVHD Sparse T cell infiltrate Basal cell vacuolization Apoptosis at dermal-epidermal junction May lead to blistering
Slide 38: Intestinal Acute GVHD
Intestinal Acute GVHD Sparse T cell infiltrate Disorganized epithelial maturation Apoptosis at the base of the crypts (stem cells) Eventual surface denudation
Slide 39: Liver Acute GVHD
Liver Acute GVHD Sparse T cell infiltrate Portal tracts primarily affected Loss of bile duct integrity leads to jaundice/high bilirubin Eventual “vanishing bile duct” syndrome
Slide 40: aGVHD Grade/Severity and Survival
aGVHD Grade/Severity and Survival Cahn et al. Blood 2005
Slide 41: aGVHD Severity: Biomarkers
aGVHD Severity: Biomarkers Biomarkers (BM) have been shown to predict aGVHD outcomes: Organ damage BM: ST2: soluble receptor for IL-33, secreted by GI tract REG3a: antimicrobial peptide secreted by Paneth cells AREG: EGFR ligand required for tissue damage repair Systemic GVHD BM: TNFR1: produced by
Slide 42: aGVHD Severity: Biomarkers and Outcomes
aGVHD Severity: Biomarkers and Outcomes The MAGIC prognostic algorithm, ST2+REG3a measured at GVHD onset, predicts Non-Relapse Mortality (NRM) and has been validated Hartwell JCI Insight 2017
Slide 43: Prevention Strategies for aGVHD
Prevention Strategies for aGVHD Control Reduce total number of T cells Ex vivo T cell depletion In vivo T cell depletion (ATG, Alemtuzumab) Interfere with T cell proliferation Methotrexate Mycophenolate (cellcept) Cyclophosphamide (pTCy) Block T cell activation/function Calcineurin inhibition (Cyclo
Slide 44: aGVHD: Steroids as Initial Therapy
aGVHD: Steroids as Initial Therapy Steroids: 1-2 mg/kg methylprednisolone or equivalent Overall response rate ~40-60% Response correlates with clinical stage Survival correlates with response Martin et al. 1990
Slide 45: aGVHD: Initial Steroid Therapy Outcome
aGVHD: Initial Steroid Therapy Outcome Response correlates with classical Grading Scles More Severe (Gr III-IV aGVHD) less responsive Gr II response heterogeneous (subsets do poorly) MacMillan Risk Score classifies aGVHD as High Risk vs Standard Risk Weisdorf et al. 1990; MacMillan et al 2015
Slide 46: Summary: Initial Steroid Dose in aGVHD
Summary: Initial Steroid Dose in aGVHD Grade I-II: 1 mg/kg/d prednisone (or equivalent) +/- topical therapy, or 2 mg/kg/d prednisone (or equivalent) Grade III-IV 2 mg/kg/d prednisone (or equivalent) Pts not responding to 1mg/kg/d may be escalated to 2mg/kg/d if no response No role for escalating ste
Slide 47: Initial Therapy: Additional Agents
Initial Therapy: Additional Agents Steroids + ATG Steroids + Daclizumab Steroids + MMF (CTN-0802) Steroids + Itacitinib Steroids + F-652 (IL-22 dimer) Steroids + AAT (immune modulator) Steroids + Itolizumab Failed studies Ongoing studies EQUATE study
Slide 48: History at the Dana Farber - Targeting CD6 for GVHD
History at the Dana Farber- Targeting CD6 for GVHD Outcome N (%) Acute GVHD 20 (18%) Graft failure 3 (3%) Remission deaths 20 (18%) Relapse 37 (33%) Continuing remission 55 (49%) Soiffer, et al., demonstrated in 112 consecutive BMT patients treated with ex-vivo CD6+ T cell depletion and no other pos
Slide 49: Summary
Summary aGVHD patients, particularly those with Grade III/IV or a high MAP score, have a high mortality rate T cells play a primary role in the pathogenesis of GVHD Prednisone 1-2mg/kg/d alone remains the standard of care. Addition of non-absorbable steroids (budesonide or oral BDP) may be beneficia
Slide 50: EQUATE Trial Overview and Results
€3 EQUATE Trial Overview and Results .
Slide 51: EQUATE Study for First-line Treatment in aGVHD
EQUATE Study for First-line Treatment in aGVHD Assess the safety and tolerability of IV dosing of itolizumab Determine optimal IV dose level(s) of itolizumab Primary Objectives Secondary Objectives Characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of itolizumab Assess the clinical act
Slide 52: Baseline Characteristics
Baseline Characteristics Cohort 1 (0.4 mg/kg) N=4 Cohort 2 (0.8 mg/kg) N=3 Cohort 3 (1.6 mg/kg) N=3 Total N=10 Age (years) mean (SD) 44 (18.0) 47 (21.5) 55 (7.1) 48 (15.7) Sex (M/F) 4 (100%) /0 2 (67%)/1 (33%) 3 (100%) /0 9 (90%)/1(10%) Race (White/Black/Unknown) 4/0/0 2/1/0 3/0/0 9/1/0 Ethnicity (H
Slide 53: Baseline aGVHD Grading
Baseline aGVHD Grading Cohort 1 (0.4 mg/kg) N=4 Cohort 2 (0.8 mg/kg) N=3 Cohort 3 (1.6 mg/kg) N=3 Total N=10 Organ involvement n (%) Skin Liver UGI LGI 0 1 (25%) 0 3 (75%) 0 0 2 (67%) 3 (100%) 1 (33%) 0 0 3 (100%) 1 (10%) 1 (10%) 2 (20%) 9 (90%) aGVHD Clinical Grade1, n (%) III 3 (75%) 1 (33%) 3 (10
Slide 54: EQUATE: Clinically Meaningful Response at Day 29
CR: complete response VGPR: very good partial response – approximates the clinical benefit of a complete response** PR: partial response ORR: overall response rate Overall Response Rate Cohort 1 0.4 mg/kg (N=4) n (%) Cohort 2 0.8 mg/kg (N=3) n (%) Cohort 3 1.6 mg/kg (N=3) n (%) Total (N=10) n (%) Da
Slide 55: Rapid and Durable Response with Itolizumab Treatment
Rapid and Durable Response with Itolizumab Treatment * Study ongoing – data subject to change
Slide 56: Itolizumab Associated with Dose Reduction in Systemic Steroid Use
Protocol specified steroid use of 2mg/kg of methylprednisolone or equivalent at initiation Steroid tapering was not mandated as part of the protocol; investigators could titrate as clinically indicated and per institutional protocols Data presented as mean (SD); Equivalent prednisone dose was calcul
Slide 57: Interpreting EQUATE: Itolizumab Response Rates in aGVHD
Interpreting EQUATE: Itolizumab Response Rates in aGVHD 80% ORR 61% ORR 27% 16% partial response very good partial response complete response Response Rate at Day 28/29 Note: The Phase 1b EQUATE trial has enrolled aGVHD grades III – IV, most of these subjects are also classified as High Risk using t
Slide 58: Itolizumab Decreases Cell Surface CD6 in GVHD Patients
Levels of cell surface CD6 on T cells decrease in aGVHD patients after first dose 0.8 and 1.6 mg/kg dose permit more consistent reduction of cell surface CD6 Loss of response or progressive disease appears to correlate with increasing levels of CD6 Cohort 1 (0.4 mg/kg) Cohort 2 (0.8 mg/kg) Cohort 3
Slide 59: Dose Responsive Loss of CD6 with Itolizumab Treatment
1st Dose 2nd Dose Dose Responsive Loss of CD6 with Itolizumab Treatment * Study ongoing – data subject to change
Slide 60: Reduced Levels of CD6 Inform Dose Selection
Level of CD6 [CD4, CD8] Itolizumab Concentration Baseline level of CD6 Optimized dose of itolizumab Theoretical lower level of CD6 Additional Factors for Dose Selection Clinical response Safety Cell response markers Markers of inflammation Disease biomarkers Reduced levels of CD6 Inform Dose Selecti
Slide 61: Interim EQUATE Safety Data Summary
Interim EQUATE Safety Data Summary – Cohorts 1 to 3* * Study remains open; safety data reporting/accumulation remains ongoing. Data presented includes data in first ten patients through 11/25/20 Safety Overview All patients (n=10) dosed experienced at least one AE 80% of subjects experienced at last
Slide 62: Case Vignette: Patient History
54-year-old white male with history of Hodgkin's Lymphoma, polycythemia vera and myelofibrosis Received HSCT (matched related peripheral blood stem cells with non-myeloablative chemo) February 2020 Received tacrolimus and methotrexate prophylaxis for GVHD Presented with aGVHD (>100 days) after trans
Slide 63: Case Vignette: Outcomes with Itolizumab
Case Vignette: Outcomes with Itolizumab Dosing Period Follow up Long-Term Follow up D1 D57 D43 D15 D29 D60-64 D71 D85 D169 D253 D337 PR VGPR CR CR CR Cell Counts Systemic Steroid Use Adverse Events of Special Interest: decreased lymphocyte counts (Gr2-4) Gr2 Adverse Events: dental crown reattached,
Slide 64: Clinical Regulatory Strategy and Lifecycle Considerations
Equillium plans to engage with FDA in 1H 2021 with goal to discuss: Dosing proposal for P2/3 studies Registration requirements of itolizumab for the treatment of aGVHD Suitability of conducting a single pivotal trial to support a biologics license application (BLA) submission for an indication of in
Slide 65: aGVHD Program Summary
Preliminary data demonstrates rapid, durable and high overall response rates Current data suggests that therapeutic dose range may fall between 0.8 to 1.6 mg/kg Currently expanding Cohorts 0.8 and 1.6 mg/kg to gather more safety, PK, PD, and efficacy data to inform benefit risk profile and dosing fo
Slide 66: Discussion with Dr. John Koreth and Q&A
Tell us more about the prognosis in patients with Grade III/IV [High Risk] aGVHD. How effective are steroids in this population? Limitations? What excites you about targeting CD6? What is your impression of the overall response data? How should we interpret the current safety findings in the trial r
Slide 67: Itolizumab - a Promising Therapeutic to Treat Lupus Nephritis
Itolizumab - a Promising Therapeutic to Treat Lupus Nephritis
Slide 68: Lupus Nephritis
Lupus nephritis 100,000 50%-75% 40% 0 15 Lupus nephritis patients in the U.S. Of patients do not respond to frontline treatments Of severe, proliferative patients will progress to end-stage renal disease Approved treatments Products in development Product in development that modulates both the activ
Slide 69: Advancing a Personalized Medicine Approach in Lupus Nephritis
Advancing a Personalized Medicine Approach in Lupus Nephritis US Investigational New Drug (IND) Fast Track Designation Partnership with Accelerating Medicines Partnership (AMP) on Biomarker Development in Lupus Nephritis Type A Cohort Top Line Q1 2021 Type B interim results 2H 2021 Urinary biomarker
Slide 70: Multiple Cell Types Underscore LN Immune Pathogenesis
Teff B cell Treg Multiple Cell Types Underscore LN Immune Pathogenesis Complement-mediated destruction Activated APC’s/dendritic cells Tissue-targeting Antibodies Activated effector cells Activated B cells Effector cytokines
Slide 71: Therapies Hitting a Ceiling in Achieving Complete Responses
Therapies Hitting a Ceiling in Achieving Complete Reponses Program Complete Remission Rates (52 weeks) Treatment Placebo Voclosporin (P3) 40.8% 22.5% Belimumab (P3)* 43% 32% Obinutuzumab (P2) 35% 23% Renal Survival by Response Rates – Highlights the Importance of Achieving Complete Remission (CR) *
Slide 72: Approaches to Tackling Disease Heterogeneity
Approaches to Tackling Disease Heterogeneity Identify complimentary therapeutics to increase mechanistic synergy Identify therapeutics with broad mechanistic coverage Identify disease biomarkers to select and monitor patients
Slide 73: Increased Urinary ALCAM in Lupus Nephritis
Increased Urinary ALCAM in Lupus Nephritis “Dr. Mohan examined a protein called ALCAM, which is important for activating T cells. ALCAM is also present in several kidney diseases and in the urine of patients with lupus kidney disease. He likens it to a bad guy being caught at the scene of several cr
Slide 74: Accelerating Medicines Partnership (AMP)
The Accelerating Medicines Partnership (AMP) is a partnership between NIH, FDA, NGO and biopharmaceutical industry Goal: to develop new diagnostics and treatments for Alzheimer’s, Type II DM, RA, SLE/LN. Budget for RA and SLE is $53.2 million Equillium is working with AMP investigators to analyze SL
Slide 75: CD6 & ALCAM-expressing Cells are Elevated in LN Patients
CD6 & ALCAM-expressing Cells are Elevated in LN Patients Renal Epithelial Renal Leukocytes Urine Leukocytes CD6 ALCAM 9x 16x 11x Renal cell population Expression level CD6 ALCAM Leukocytes T cells +++ + APCs - ++ B cells + + Plasmablasts - + Structural cells Loop of Henle - +++ Proximal tubule - +++
Slide 76: Efficacy of CD6 Blockade in Murine Models of SLE/LN
Nephrotoxic serum nephritis (NTN) Efficacy of CD6 Blockade in Murine Models of SLE/LN Model of LN commonly used as a translational model to test drug targets. Key Readouts Anti-CD6 treatment ameliorates the nephritis associated with nephrotoxic antibody administration by decreasing: Proteinuria Albu
Slide 77: CD6 & ALCAM are Over-Expressed in MRL Model of SLE/LN
CD6 & ALCAM are Over-Expressed in MRL Model of SLE/LN CD6 expression on renal T cells and ALCAM expression on renal antigen-presenting cells from diseased MRL/lpr mice is significantly higher than on cells from C57BL/6J non-disease controls **** p<0.0001; *** p<0.001; ** p<0.01; * p<0.05
Slide 78: Role of CD6 in T Cell-driven Systemic Autoimmunity
Role of CD6 in T Cell-driven Systemic Autoimmunity MRL/MpJ-Faslpr/J mice are a well-characterized, spontaneous model of SLE Genetic mutation prevents apoptosis, causing uncontrolled lymphocyte proliferation Characterized by SLE-like autoantibodies and manifestations including arthritis, inflammatory
Slide 79: Treatment with Anti-CD6 mAb Ameliorates Renal Disease
Treatment with Anti-CD6 mAb Ameliorates Renal Disease *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001, Presented by Equillium at ACR 2019 & ACR 2020 Reduced terminal ACR, BUN and kidney weight Reduced in-life proteinuria
Slide 80: CD6 Blockade Ameliorates Renal Inflammation
CD6 Blockade Ameliorates Renal Inflammation Decreased immune deposition Reduction of Teff in kidney *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001, Presented by Equillium at ACR 2019 & ACR 2020
Slide 81: CD6 Blockade Improves Extra-Renal Disease and Survival
CD6 Blockade Improves Extra-Renal Disease and Survival *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001, Presented by Equillium at ACR 2019 & ACR 2020 Improved survival Reduced lymph node weight Improved skin scores
Slide 82: Soluble ALCAM as a Biomarker of Activity in Lupus Nephritis
Soluble ALCAM as a Biomarker of Activity in Lupus Nephritis Parodis et al., 2019; Stanley et al., 2020; Ding et al., 2020
Slide 83: ALCAM a Predictive Biomarker in Patients with Active LN
Stanley et al., 2016. Comprehensive Aptamer-Based Screening of 1129 Proteins Reveals Novel Urinary Biomarkers of Lupus Nephritis. ACR/ARHP Annual Meeting. ALCAM a Predictive Biomarker in Patients with Active LN Unbiased screening of >1,100 urinary proteins identified urinary ALCAM as a strong predic
Slide 84: ALCAM Correlates with Disease Across Multiple Ethnicities
ALCAM Correlates with Disease Across Multiple Ethnicities African-American Caucasian Hispanic Asian Parodis et al., 2019; Stanley et al., 2020; Ding et al., 2020
Slide 85: Urine Proteome Analysis of Responders vs Non-responders
CHST4 Siglec-11 Dectin-1 Siglec-6 RANK ALCAM BMPR-IA L-Selectin TMEFF1 IFNab R2 IL-15 Activin A FSH FOLR2 DDR1 LAMP2 TNF RII SREC-I DPPIV CEACAM-1 Serpin A4 MCSF R Desmoglein 2 EGF R Cathepsin H TPP1 uPAR Non responders Responders p = .05 Urine from AMP network patients Response defined as pr/cr <0.
Slide 86: Treating Lupus Nephritis Tomorrow – Individualized Therapy
Treating Lupus Nephritis Tomorrow – Individualized Therapy Biomarker driven diagnostics Informs patient selection for guiding treatment Maximize benefit-to-risk for patients Use of ineffective treatments minimized – lower overall cost to health care system Equillium has developed proprietary high se
Slide 87: EQUALISE Trial Overview and Results
» By covoise y) Trial Overview and Results -
Slide 88: Type A Cohort and B Cohorts
Type A Cohort and B Cohorts Assess the safety and tolerability of itolizumab in subjects with SLE with and without active proliferative lupus nephritis Determine optimal subcutaneous dose level(s) of itolizumab Secondary Objectives Type A Cohort and B Cohorts Characterize the pharmacokinetics (PK) a
Slide 89: Study in Lupus / Lupus Nephritis
Type A Cohort: Subjects without apLN Type B Cohort: Subjects with apLN 0.8 mg/kg (N=6) 1.6 mg/kg (N=6) 2.4 mg/kg (N=6) 1.6 mg/kg (N=7) 0.8 mg/kg (N=7) 0.4 mg/kg (N=6) Subjects will receive a dose Q2W x 2 doses Subjects will receive a dose Q2W x 13 doses Estimated Data: Topline:1Q 2021 for Type A coh
Slide 90: Baseline Characteristics
Baseline 0.4 mg/kg N=6 0.8 mg/kg N=7 1.6 mg/kg N=7 2.4 mg/kg N=6 Total N=26 Age in years- mean (SD) 59.5 (12.9) 44.6 (16.2) 47.1 (6.8) 48.2 (11.6) 49.5 (12.9) Sex (F/M) 6/0 7/0 6/1 6/0 25/1 Race (White/Black or African American) 3/3 5/2 6/1 5/1 19/7 Ethnicity: Hispanic or Latino (Y/N) 4/2 5/2 3/4 4/
Slide 91: Interim Safety Data Summary - Type A Cohorts 1–4
Safety Overview 35% of subjects experienced at last one adverse event No SAE’s or deaths Safety monitored by independent Data Monitoring Committee Drug Discontinuation Dose Limiting Toxicity AEs of Special Interest – Drug Related Two subjects experienced AEs that lead to drug discontinuation due to:
Slide 92: Absolute Lymphocyte Counts with Itolizumab Treatment
Absolute Lymphocyte Counts with Itolizumab Treatment Cohort 3 (1.6 mg/kg) Screening N=7 Day 1 N=7 Day 4 N=7 Day 15 N=6 Day 29 N=4 FU1 N=6 FU2 N=6 Lymphocytes [109/L] Lymphocytes [109/L] Screening N=6 Day 1 N=6 Day 4 N=6 Day 15 N=6 Day 29 N=6 FU1 N=6 FU2 N=6 Lymphocytes [109/L] Cohort 1 (0.4 mg/kg) C
Slide 93: Lupus Nephritis Program Summary
Human tissue analysis in LN patients and mouse clinical trials support the potential benefit of targeting CD6 for the treatment of Lupus Nephritis The EQUALISE study indicates safe to push dosing past 1.6 mg/kg SC dosing of Itolizumab has been well tolerated through dosing of 2.4 mg/kg Type A final
Slide 94: Itolizumab - a Differentiated Approach to Treat Uncontrolled Asthma
Itolizumab - a Differentiated Approach to Treat Uncontrolled Asthma
Slide 95: Uncontrolled moderate to severe asthma
Uncontrolled moderate to severe asthma 2.6M 1.3M ~50% 0 Severe asthma patients in the U.S. Patients uncontrolled by standard-of-care treatments (long-acting beta-agonists, inhaled corticosteroids, oral corticosteroids) Of uncontrolled patients do not respond to existing biologic treatments Approved
Slide 96: CD6-ALCAM Implicated Broadly in the Pathogenesis of Asthma
B cell Eosinophil CD6-ALCAM Implicated Broadly in the Pathogenesis of Asthma Allergens Figure Legend: CD6 is expressed on Th1, Th2, Th17 and ILC2 effector cells that secrete multiple proinflammatory cytokines implicated in asthma pathogenesis. ALCAM is expressed on antigen presentation cells that ac
Slide 97: Potential to Address the Full Spectrum of Uncontrolled Asthma
Potential to Address the Full Spectrum of Uncontrolled Asthma Current therapies target downstream signaling of Th2-associated inflammation Current downstream therapies ineffective in patients with low levels of eosinophils No approved therapies anti-TSLP anti-IgE anti-IL-5 DP2 Antagonists CINQAIR® a
Slide 98: Upregulation of CD6 & ALCAM in Severe Asthma Patients
Upregulation of CD6 & ALCAM in Severe Asthma Patients ***p<0.001, *p<0.05. Examination of gene expression datasets support the presence of increased CD6, CD4 T cells, and ALCAM in the lungs of severe asthma patients Study of the Mechanisms of Asthma (MAST; NCT00595153); Bronchoscopic Exploratory Res
Slide 99: Upregulation of CD6 & ALCAM in Severe Asthma Patients
Upregulation of CD6 & ALCAM in Severe Asthma Patients Fatal asthma Non-asthma ALCAM CD6 overlay epithelium Lamina propria Lamina propria epithelium Examination of lung tissue demonstrates the presence of increased CD6, T cells, and ALCAM in the lungs of severe asthma patients Fatal asthma patients –
Slide 100: CD6-ALCAM in Lung Inflammation & Bronchomotor Tone
CD6-ALCAM in Lung inflammation & Bronchomotor Tone Proliferation & Cytokine production Hyperplasia/ hypertrophy Inflammation + ASM remodeling Teff or ILC2 Airway Smooth Muscle Cells Th1 Th2 Th17 Tn DC IL-4, IL-5, IL-13 IFNγ, TNFα IL-17, IL-6, IL-8 Lung Inflammation Tissue Remodeling
Slide 101: Translational Data Presented at Key Congress
Presentation CD6-ALCAM Pathway is Elevated in Patients with Severe Asthma (Mukherjee et al.) Posters CD6 Is Highly Expressed In Fatal Asthma Patients and May Modulate Bronchomotor Tone (Koziol-White et al.) CD6 Is Expressed On Human Airway and Blood ILCs and Is Upregulated by Epithelial Alarmins IL-
Slide 102: Key Cytokines in Asthma Upregulate CD6 on ILC2s
Key Cytokines in Asthma Upregulate CD6 on ILC2s Day 0 Media only IL-2 IL-2 + IL33 IL-2 + TSLP Day 3 PBMCs incubated with combinations of IL-2, IL33 and TSLP for 72 hours and then analyzed by flow cytometry for CD6 expression on ILC2 population CD6 Data courtesy of Taylor A Doherty, University of Cal
Slide 103: CD6 Enhances Contraction of Asthmatic Airways
48 PCLS on d4 12 - Vehicle Control 12 - 100ng/m IL13 + 100ng/ml TGFb1 (Panettieri, Rutgers) 12 - 100ng/ml CD6 Fc (T Doherty, UCSD) Tx 10m 40m 4h 24h CCh ISO FSK CD6 Enhances Contraction of Asthmatic Airways %Airway contraction CCh dose (nM) Data courtesy of Taylor A Doherty, University of California
Slide 104: EQUIP Trial Overview and Results
J Q EQUIP Trial Overview and Results -
Slide 105: EQUIP Study in Uncontrolled Asthma
EQUIP Study in Uncontrolled Asthma Assess the safety and tolerability of subcutaneous dosing of itolizumab Determine optimal subcutaneous dose level(s) of itolizumab Primary Objectives Secondary Objectives Characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of itolizumab Assess the clin
Slide 106: Asthma Program Summary
Translational data supports the role of the CD6-ALCAM pathway in the pathogenesis of severe asthma CD6 may be implicated in both inflammation and airway remodeling Targeting the CD6-ALCAM pathway may provide a novel approach to target non-T2 based mechanisms in severe asthma The EQUIP trial is curre
Slide 107: Financial and Corporate Update
Financial and Corporate Update
Slide 108: Biocon License Agreement Highlights
Biocon License Agreement Highlights Key rights to itolizumab acquired by Equillium through in-license agreement with Biocon Exclusive rights for the United States, Canada, Australia and New Zealand Exclusive rights to negotiate licensing for select additional major markets, e.g. EU / Japan Equillium
Slide 109: U.S. Intellectual Property Portfolio and Regulatory Exclusivity
U.S. Intellectual Property Portfolio and Regulatory Exclusivity
Slide 110: Equillium Financial Overview
Total Cash and Investments $90.5 million Year-to-Date Operating Cash Burn $16.4 million Outstanding Debt $10.0 million Shares Outstanding 24.7 million Market Cap (as of close 12/03/20) $121.9 million Equillium Financial Overview Lean operating model and disciplined control of spending Sufficiently c
Slide 111: Closing Remarks
Closing Remarks a —— ”
Slide 112: Multiple Catalysts in 2021 Provide Opportunity for Value Creation
Multiple Catalysts in 2021 Provide Opportunity for Value Creation Catalysts & Milestones Timing Topline data from EQUATE Phase 1b study in aGVHD 1H 2021 Initiate Phase 2/3 in first-line aGVHD Mid 2021 Data from EQUALISE Phase 1b study in Lupus / Lupus Nephritis Type A (SLE) topline data Type B (lupu
Slide 113: Q&A
Q&A
Slide 114: For More Information
For More Information Michael Moore VP of Investor Relations & Corporate Communications 619-302-4431 Equillium, Inc. 2223 Avenida de la Playa / Suite 105 La Jolla, CA 92037 www.equilliumbio.com ir@equilliumbio.com