Equillium, Inc. · NASDAQ:EQ
Equillium — Technical Presentation (November 2025)
58 slides from Equillium's technical presentation, Nov 5, 2025
Slide 1: Virtual KOL Event to Discuss EQ504: A Novel AhR Modulator for Ulcerative Colitis
Virtual KOL Event to Discuss EQ504: A Novel Aryl Hydrocarbon Receptor (AhR) Modulator for Ulcerative Colitis 1 November 5, 2025
Slide 2: Forward-Looking Statements and Other Disclaimers
Forward-Looking Statements and Other Disclaimers 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,” “
Slide 3: Today's Agenda
Today’s Agenda Introduction Bruce Steel, CFA The aryl hydrocarbon receptor: A target for immune modulation Francisco J. Quintana, PhD Emerging Therapies 2025 Brian Feagan, MD, FRCPC EQ504: Targeting AhR to Promote Mucosal Healing In Ulcerative Colitis Stephen Connelly, PhD Q&A Session Management & K
Slide 4: Introduction: Francisco J. Quintana, PhD
Introduction: Francisco J. Quintana, PhD Francisco J. Quintana, PhD holds the Kuchroo Weiner Distinguished Chair in NeuroImmunology at Harvard Medical School and an Associate Member at the Broad Institute of Harvard and MIT. Dr. Quintana’s research investigates signaling pathways that control the im
Slide 5: The aryl hydrocarbon receptor: A target for immune modulation
The aryl hydrocarbon receptor: A target for immune modulation Francisco J. Quintana Harvard Medical School Broad Institute of MIT and Harvard
Slide 6: Fishing for Novel Regulators of the Immune Response
Fishing for Novel Regulators of the Immune Response Circa 2005 6
Slide 7: The Aryl Hydrocarbon Receptor (AHR)
The Aryl Hydrocarbon Receptor (AHR) Initiation of inflammatory cascade Th1 Teff Th17 CD8+ T cells Treg FoxP3+ Tregs Quintana et al, Nature 2008 Tr1 cells Suppression of inflammation Nature (2008); Nat. Immunology (2010); Nat. Immunology (2010); PNAS (2010); PLoS One (2010); PNAS (2012); Nat. Immunol
Slide 8: AHR Signaling
AHR Signaling 8 Polonio and Quintana, Nature Reviews in Drug Discovery 2025
Slide 9: AHR Physiologic Agonists
AHR Physiologic Agonists 9 Gutierrez-Vazquez and Quintana, Immunity 2018
Slide 10: AHR Responsive Cells in the Gut
AHR Responsive Cells in the Gut Immune Cells Non-immune Cells Immune homeostasis & tolerance Maintain Barrier Function • Innate Lymphoid Cells • Intestinal Epithelial Cells • Dendritic Cells & Macrophages • Goblet Cells • Effector T Cells • Paneth Cells • Regulatory T Cells 10
Slide 11: IL-10 and IL-22 in Mucosal Biology
IL-10 and IL-22 in Mucosal Biology IL-10 IL-22 Immuno-modulatory peacekeeper Epithelial protector and healer • Inhibits production of pro-inflammatory • Strengthens epithelial tight junctions to cytokines from macrophages & dendritic cells promote epithelial barrier integrity • Enhances function of
Slide 12: Regulation of Adaptive Immunity by AHR
Regulation of Adaptive Immunity by AHR 12 Polonio and Quintana, Nature Reviews in Drug Discovery 2025
Slide 13: Role of AHR in gut homeostasis
Role of AHR in gut homeostasis 13 Rothhammer and Quintana, Nature Reviews in Immunology 2019
Slide 14: Role of AHR in intestinal Stem Cells
Role of AHR in intestinal Stem Cells 14 Modified from Wisniweski et al, Frontiers in Immunology 2021
Slide 15: Therapeutic gut AHR activation
Therapeutic gut AHR activation 15 Polonio and Quintana, Nature Reviews in Drug Discovery 2025
Slide 16: Summary
Summary • AHR regulates tissue inflammation and pathology through its effects on both immune and non-immune cells • AHR limits pro-inflammatory responses • AHR promotes the reestablishment of barrier integrity • AHR regulates intestinal stem cell function • AHR anti-inflammatory and tissue protectiv
Slide 17: Introduction: Brian G. Feagan, MD, FRCPC
Introduction: Brian G. Feagan, MD, FRCPC Brian G. Feagan, MD, FRCPC is a gastroenterologist, with training in Clinical Epidemiology and Biostatistics. His research focus is the design, conduct and execution of large-scale randomized controlled trials (RCTs) in Crohn’s disease (CD) and ulcerative col
Slide 18: Brian G. Feagan MD
Brian G. Feagan MD Professor of Medicine, Epidemiology and Biostatistics Western University Senior Scientific Director, Alimentiv Inc. London, Ontario, Canada
Slide 19: Disclosures
Disclosures Grant/Research Support Consultant AbbVie, Abivax, Adiso, AgomAB Therapeutics, Akros, Alira Health, Ally Bridge Group, AnaptysBio, Apini Therapeutics, Argenx, Avoro Capital Advisors, Belmore Law, BioFactura, BioJamp, Biora Therapeutics, Blackbird Laboratories, Boehringer-Ingelheim, Boxer
Slide 20: Topics to Be Discussed
Topics to Be Discussed • The Present -2025 a glass half full! • Where are we headed? • Horizon agents • Combination therapy • Horizon indications/strategies • Summary 20
Slide 21: IBD 2025 - A glass half full!
IBD 2025- A glass half full! • The introduction of • Two emergent multiple new treatments MOAs, anti-integrin in the past 25 years has therapy not resulted in (vedolizumab ) and consistently high rates of IL-12/23 are remission. extraordinarily safe. • Personalized medicine has • Surgical rates have
Slide 22: Topics to Be Discussed
Topics to Be Discussed • The Present = 2024 – A glass half full! • Where are we headed? • Horizon agents • Combination therapy • Horizon indications/strategies • Summary 22
Slide 23: Horizon Agents: TL1A monoclonals
Horizon Agents: TL1A monoclonals • TNF-like cytokine 1A, member of the TNF superfamily • Variants in the TL1A-encoding gene (TNFSF15) are associated with increased IBD risk • Expressed in antigen presenting cells, lymphocytes, and Proliferation of non-suppressive Tregs endothelial cells • Transgenic
Slide 24: TL1A Antagonist as Induction Therapy for UC
24 TL1A Antagonist as Induction Therapy for UC Endoscopic & Clinical Endpoints at Week 14 60% • 14 week open-label study 50% in moderately to severely active ulcerative colitis, 40% * 38.2% N=50 Proportion of Patients (%) • propensity matched 30% ** 24.0% artificial control 17/45 12/50 20% • proof o
Slide 25: Primary and Secondary Endpoints at Week 12: Tulisokibart vs. Placebo
Primary and Secondary Endpoints at Week 12 Tulisokibart vs. Placebo 100% Placebo PRA023 43.8% 90% N=67 N=68 Subjects Achieving Endpoint (%) p <0.0001 80% 70% 66.2% 30.8% 60% p <0.0001 25.0% 50% p <0.0001 40% 36.8% 30% 26.5% 22.4% 20% 10% 6.0% 1.5% 0% Clinical Remission Endoscopic Improvement C
Slide 26: Oral Alpha4Beta7 Blockade: Background
Oral Alpha 4 Beta7 Blockade: Background Alpha 4 Beta 7 MAdCAM -1 • Ligand for 47 is MAdCAM ACT -1 • Animal models show that ACT-1 selectively blocks trafficking of 47 positive lymphocytes to the gut • Raises possibility of gut specific immune modulation • Striking benefit in cotton-top tamarin m
Slide 27: Oral Alpha4 Beta7 Antagonists
Oral Alpha4 Beta7 Antagonists • Highly successful MOA • Vedolizumab market leader in UC • Multiple new indications (pouchitis, post-operative CD, GVH) • Potential in combination therapy = the “polypill”
Slide 28: Morphic Data: Patient a4β7 Receptor Occupancy Consistent with Healthy Volunteer RO
Morphic Data: Patient a4β7 Receptor Occupancy (RO) Consistent with Healthy Volunteer RO a4β7 selectivity over a4β1 consistent with Phase 1 results • a4β7 RO achieved early and sustained saturating levels 100 • a4β1 RO remained at low 80 levels 4 7 RO (%) 60 • No lymphocytosis or changes to circula
Slide 29: Anti-p40 Ustekinumab: Background for Oral IL-23
Anti-p40 Ustekinumab: Background for Oral Il-23 • IL-12 & IL-23 are key cytokines in the IL-12 IL-23 pathogenic immune cascade of Crohn’s p40 disease p35 p19 p40 • Ustekinumab is a fully human IgG1k ustekinumab monoclonal antibody binding the p40 subunit of interleukin-12 and -23 • Inhibits IL-12- a
Slide 30: Transformational Efficacy in Psoriasis Therapy
Transformational Efficacy in Psoriasis Therapy Griffiths CE. et al. N Eng J Med. 2010;362(2):118-28 Lebwohl M et al. N Eng J Med. 2015;373(14):1318-28. Papp KA, et al. N Eng J Med. 2017;376(16):1551- 1560.
Slide 31: Risankizumab for CD: Is anti-P19 the Answer?
Risankizumab for CD: Is anti-P19 the Answer? Clinical remission Endoscopic endpoints over time through Week 12 at Week 12 Primary endpoint 40 * 40 * 36.6 36.6 35 35 * * 30.5 31.7 Proportion of subjects (%) 30 30 * 26.8 ** 24.4 24.4 25 25 *** 20.7 * 19.5 19.5 ** 20 * 17.1 20 * 17.1 14.6 15.4 14.6 * 1
Slide 32: Risankizumab Induction: Clinical Remission Week 12
Risankizumab Induction: Clinical Remission Week 12 ADVANCE MOTIVATE Non-Bio-IR & Bio-IR Bio-IR 100% 100% P<0.001 P<0.001 P<0.001 P<0.001 =16.1% =18.8% =20.5% =19.9% 80% 80% P<0.001 P<0.001 P<0.001 P=0.001 =20.2% =21.9% =22.6% =15.2% %Patients 60% 45.2% 41.6% 60% %Patients 43.5% 41.0% 42.5% 4
Slide 33: Oral IL-23 Peptide Therapy for Psoriasis
Oral IL-23 Peptide Therapy for Psoriasis Oral IL 23 Receptor Antagonist Peptide for Plaque Psoriasis 90 80 P<0.001 70 PASI 75 Response 60 50 40 30 100 mg OD 100 mg BID 25 mg OD 50 mg OD 25 mg BID 20 10 0 IL-23 Receptor Placebo
Slide 34: Understanding RNAi: How Does RNAi Work?
UNDERSTANDING = ~~ RNAi, or “RNA Interference,” is a natural ¥ process that occurs in the cells of plants, animals, and people. . s snceirt messes [DEES : HOW DOES RNAi WORK? 4 HA units of life. 1 It begins when a form of RNA made of two strands (double-stranded RNA, or dsRNA) is introduced into the
Slide 35: Obefazimod Induction Therapy for UC
Obefazimod Induction Therapy for UC • Oral, small molecule agonist that stimulates sRNA production • Inhibits pro-inflammatory cytokine production • Excellent safety profile in HIV therapy studies • Previous positive 2a POC • Phase 2 study in UC Vermiere S. et al. Lancet Gastro Hepatology. Sept 2022
Slide 36: Combination Therapy.... Behold HCV treatment
Combination Therapy…. Behold HCV treatment
Slide 37: SONIC Provides a Clue!
SONIC Provides a Clue! 100 p<0.001 80 Proportion of Patients (%) p=0.009 p=0.022 57 60 45 40 30 20 52/170 75/169 96/169 0 AZA + placebo IFX + placebo IFX+ AZA Colombel JF. et al. N Engl J Med. 2010 Apr 15;362(15):1383-95.
Slide 38: Combination Therapy VEGA: Guselkumab + Golimumab in UC
Combination Therapy VEGA: Guselkumab + Golimumab in UC STUDY ▪Phase 2a, randomized, double-blind, placebo-controlled, active-comparator-controlled, parallel-group, proof-of-concept, multicentre study PURPOSE ▪ To evaluate the safety and efficacy of combination therapy with guselkumab and golimumab i
Slide 39: Clinical Response and Remission at Week 12
Clinical Response and Remission at Week 12 Clinical Response (decrease from baseline in the Mayo score ≥30% and ≥3 points with either a decrease in rectal bleeding subscore ≥1 or a rectal bleeding subscore of 0 or 1) Clinical Remission (modified Mayo score: Mayo stool frequency subscore of 0 or Clin
Slide 40: TL1A: First IBD Target That Mediates Inflammation & Fibrosis
TL1A: First IBD Target That Mediates Inflammation & Fibrosis • TNF-like cytokine 1A, member of the TNF superfamily1,2 • Expressed in antigen presenting cells, lymphocytes, and endothelial cells. • Since its first discovery in 2001 delete, TL1A has been linked to multiple autoinflammatory & fibrotic
Slide 41: MoA: TGF-B directly activates fibrogenic genes and EMT/endMT
vA) MoA: TGF-B directly activates fibrogenic genes and EMT/endMT = TGFB directly activates transcription of fibrogenic genes such = TGF recruits but also generates new myofibroblasts from as serpine-1 (PAI-1), IL-11, collagens and fibronectin epithelial and endothelial cells through induction of EMT
Slide 42: Conclusions
Conclusions • Multiple new agents/approaches are on the horizon • TL1A monoclonals, oral alpha 4 beta,7-IL-23s and mRNA silencing are exciting new therapeutic approaches • Combination therapy is the new black! (two competing visions) • Unique opportunities for new MOAs to provide novel combination •
Slide 43: EQ504: Targeting AhR to Promote Mucosal Healing In Ulcerative Colitis
EQ504: Targeting AhR to Promote Mucosal Healing In Ulcerative Colitis 43 October 2025
Slide 44: Modulation of AhR Clinically Validated in Skin and GI Disease
Modulation of AhR Clinically Validated in Skin and GI Disease Indigo Naturalis (botanical medicine containing indirubin) FDA Approved Phase 2 Trials in Ulcerative Colitis in Psoriasis Up to 50% patients achieved clinical remission with total Up to 34% patients Mayo score ≤ 2, no individual subscore
Slide 45: AhR Agonism Leads to High Rates of UC Clinical Remission
AhR Agonism Leads to High Rates of UC Clinical Remission 50% Placebo Adjusted Clinical 42% Placebo Adjusted Clinical 27% Clinical Remission at Week 8 Remission at Week 8 Remission at Week 8 Studies of ulcerative colitis patients treated with indigo naturalis demonstrate on-target engagement of AhR t
Slide 46: EQ504 is a Potent Analog of ITE with Drug-like Properties
EQ504 is a Potent Analog of ITE with Drug-like Properties ITE is a naturally-occurring, endogenous, non-toxic Induction of CYP1A1 in HepG2 AhR modulator synthesized in the gut & lungs (AhR-Lucia) Reporter Cells • Induces Treg cells and IL-10, while reducing Thelper17 cells and inflammatory cytokines
Slide 47: Multi-modal Mechanism of Action in Mucosal Homeostasis
Multi-modal Mechanism of Action in Mucosal Homeostasis Modulates Immune Cell Responses Barrier function & Tissue Repair EQ504 EQ504 EQ504 MAC T CELL Polarization Differentiation Maintain and protect Treg Th1 Th22 barrier function: IL-22Rα M1 M2 Tissue Th17 ▪ Tight junction Regeneration: maintenance
Slide 48: EQ504 Promotes Ex Vivo Intestinal Epithelial Wound Healing
EQ504 Promotes Ex Vivo Intestinal Epithelial Wound Healing T84 Call Scratch Assay Vehicle ✱ CYP1A1 mRNA (fold change) 80 125 Vehicle 2.0 ✱✱ ✱ IL22RA mRNA (fold change) EQ504 10nM 100 1.8 Indirubin 50nM Wound Area (%) 60 1.6 75 40 1.4 EQ504 50 * 1.2 10nM 20 25 1.0 **** **** 0 0 0.8 e 4 n 0 1 2 3 4 5
Slide 49: EQ504 Modulates Treg Cells and Cytokine Expression In Vitro
EQ504 Modulates Treg Cells and Cytokine Expression In Vitro Frequency of Treg Cells IL-10 IL-22 ✱✱✱ Treg 25 ✱✱ 100 20 80 IL-22 (pg/mL) IL-10 (pg/mL) 15 60 10 40 5 20 0 0 Vehicle EQ504 62.5nM Indirubin 62.5nm EQ504 increases the number and function of suppressive Treg cells that inhibit activity of T
Slide 50: EQ504 Demonstrates Activity in Treating Colitis In Vivo
EQ504 Demonstrates Activity in Treating Colitis In Vivo DSS Colitis Animal Model EQ504 Blocks Weight Loss DSS (7days) in DSS Colitis • DSS-induced colitis is the most widely used in vivo model of UC 0 Body Weight Change (%) • CSA is a broad and strong -5 immuno-suppressant, used as a Colon epithelia
Slide 51: EQ504 Induces Anti-Inflammatory Cytokines in Colon Tissue
EQ504 Induces Anti-Inflammatory Cytokines in Colon Tissue CYP1A1 expression IL-22 expression IL-10 expression (demonstrates target engagement) AhR modulators EQ504 and indirubin activate AhR pathways as demonstrated by increased CYP1A1 and anti-inflammatory cytokine expression in mouse colons with D
Slide 52: EQ504 Protects the Intestinal Mucosal Barrier in DSS Colitis
EQ504 Protects the Intestinal Mucosal Barrier in DSS Colitis Vehicle EQ504 1mg/kg CSA 75mg/kg Loss of crypt Preserved structure morphology Hypertrophy Edema Lymphoid Reduced aggregate lymphoid aggregate Immune infiltration Reduced infiltration Mucosal erosion Preserved mucosa Sections taken from dis
Slide 53: Colonic Delivery of EQ504 Reduces Systemic Exposure
Colonic Delivery of EQ504 Reduces Systemic Exposure Routes of Peak Colonic versus Administration Systemic Exposure Oral 40 >25X EQ504 (fold change) 30 20 Colonic 10 0 Oral Colonic In vivo experiments demonstrate localized delivery of EQ504 directly to the colon of rats, results in 25x greater peak e
Slide 54: Targeting the Colon to Treat Ulcerative Colitis
Targeting the Colon to Treat Ulcerative Colitis Conventional, systemically Enterically-coated, available formulation Colon-targeted Formulation • Targeting the colon in UC patients is a clinically and commercially validated approach e.g., 5-ASA’s and steroids • Colon targeting is achieved using ente
Slide 55: High Unmet Medical Need & Large Market Opportunity
High Unmet Medical Need & Large Market Opportunity EQ504 positioned to have significant utility across multiple lines of therapy Disease Severity 1 2 Oral, Pre- Biologic Cyclosporine Surgical 5-ASAs Steroids Biologics Biologics Failures / Tacrolimus Intervention 3 Up to 30% Approx. $6 bn Clinical Re
Slide 56: Potential to Create Value in Early Clinical Development
Potential to Create Value in Early Clinical Development • Multiple clinical studies of indigo naturalis establish strong proof of efficacy of AhR modulation (CYP1A1) • Planning to conduct SAD/MAD proof of mechanism study • Safety, tolerability • Blood and tissue pharmacokinetics and pharmacodynamics
Slide 57: EQ504 Addresses Gaps in the UC Therapeutic Landscape
EQ504 Addresses Gaps in the UC Therapeutic Landscape A differentiated approach to treating UC with clinical validation and clear biomarkers AhR agonism in UC patients yields high rates of clinical remission with clear target engagement Clinical Validation markers in the colon Specific, Selective EQ5
Slide 58: Q&A Session
Q&A Session 58