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1 November 2025 Leaders in Targeted Treatment of Tissue Inflammation
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2 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” and “ongoing,” or the negative of these terms, or other comparable terminology intended to identify statements about the future. These statements are based on Company management’s current beliefs and expectations . These statements include but are not limited to statements regarding the Company’s business strategy; the Company’s plans to develop and commercialize its product candidates; the safety and efficacy of the Company’s product candidates; the Company’s plans and expected timing with respect to regulatory filings and approvals, size and growth potential of the markets for the Company’s product candidates; the potential for the Company to receive the additional $20 million in the financing upon the clinical trial initiation and the occurrence of the other milestones in the financing agreement ; the Company’s expectation that the net proceeds from the $30 million funded in the financing will fund its operations through 2027, or that the additional $20 million of the financing, if received by the Company, will fund its operations beyond 2027; the Company’s ability to use the proceeds from the financing to advance the development of EQ504; the Company’s ability to initiate or progress a clinical study on the anticipated timelines, if at all; and other statements that are not historical facts. These statements involve known and unknown risks, uncertainties and other factors, many of which are outside the Company’s control, that may cause the Company’s actual results, levels of activity, performance or achievements to be materially different from the information expressed or implied by these forward- looking statements. The Company may not actually achieve the plans, intentions or expectations disclosed in its forward-looking statements, and you should not place undue reliance on the Company’s forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed or implied in the forward-looking statements the Company makes due to the risks and uncertainties inherent in the Company’s business, including without limitation, the risks described in the Company’s filings with the Securities and Exchange Commission (“SEC”). You are cautioned not to place undue reliance on these forward-looking statements, which represent the Company’s views as of the date of this presentation . The Company anticipates that subsequent events and developments will cause its views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company has no obligation or current intention of doing so except to the extent required by applicable law. These and other risks and uncertainties are described more fully under the caption “Risk Factors” and elsewhere in the Company’s filings and reports, which may be accessed for free by visiting EDGAR on the SEC web site at http://www.sec.gov and on the Company’s website under the heading “Investors.” All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the “safe harbor” provisions of Section 21E of the Securities Exchange Act of 1934, as amended. This presentation may contain trademarks, service marks, trade names and copyrights of other companies, which are the property of their respective owners. Solely for convenience, some of the trademarks, service marks, trade names and copyrights referred to in this presentation may be listed without the TM, SM © or ® symbols, but Equillium will assert, to the fullest extent under applicable law, the rights of the applicable owners, if any, to these trademarks, service marks, trade names and copyrights. This presentation discusses product candidates that are under clinical study, and which have not yet been approved for marketing by the US Food and Drug Administration . No representation is made as to the safety or effectiveness of these product candidates for the use for which such product candidates are being studied. Caution should be exercised when comparing data across trials of different products and product candidates, as significant differences may exist between trial designs, patient populations and other study characteristics . Furthermore, the results across such trials may not have interpretative value on our existing or future results. Forward-Looking Statements and Other Disclaimers
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3 Advancing EQ504, A Potential Best-in-Class AhR Modulator for UC UC: ulcerative colitis; AhR: aryl hydrocarbon receptor; V First tranche of $30 million up front, with the potential to receive a second tranche of $20 million at clinical study initiation Validated Approach with Compelling Product Profile • AhR modulation validated through an approved product and multiple clinical studies (VTAMA, indigo naturalis) • Differentiated product profile attractive for both mono and combination therapy approaches • AhR IP Portfolio includes 4 patent families, 9 issued patents, and 5 applications pending Top-Tier Investor Support Fully Funded through Key Milestones • Up to $50MV investment led by ADAR1 and Janus Henderson completed in August 2025; first tranche provides runway through key milestones and EoY 2027 • Phase 1 proof-of-mechanism study expected to initiate mid-2026, with topline data 6-months thereafter UC: Large Growing Market with Significant Unmet Need • ~800,000 patients treated for UC in the U.S. in 2023, with a >$12B global market projected by 2030 • Despite >15 approved therapies, remission rates remain low and mucosal healing is a major clinical priority • Significant opportunity remains for safe and effective locally-acting agents to expand therapeutic options Differentiated, Colon- Targeted Therapy for UC • EQ504 is a potent, selective oral AhR modulator formulated for colon-specific delivery • Offers a multi-modal, non-immunosuppressive mechanism, complementary to existing therapeutics • Strong preclinical activity in barrier function, wound healing, and immune regulation assays and UC models
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4 Pioneering novel drug candidates for severe autoimmune and inflammatory disorders with high unmet medical need Wholly-Owned Development Pipeline of Targeted Therapeutics IND: investigational new drug Indication Discovery IND Enabling Phase 1 Phase 2/3 Status EQ504 AhR Modulator Ulcerative Colitis (oral, colon-targeted) Phase 1 Initiation mid-2026 Lung Inflammation (inhaled, lung-targeted) EQ302 IL-15/21 Inhibitor Celiac Disease (orally delivered peptide) Development Candidate ready for partnering
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5 Unmet Medical Need in Ulcerative Colitis Remains High Le Berre at al., Lancet, 2023; Danese et al., NatRev GastroenterolHepatol, 2025 * Labeled data on placebo placebo-adjusted basis Despite Available Therapies, UC Clinical Remission Rates are Poor Despite >15 approved drugs, therapeutic efficacy remains low, with clinical remission rates below ~30%* Current drugs cause systemic immune suppression and increase potential for infection Poor long-term clinical outcomes driven by lack of mucosal healing There remains a gap therapies that promote mucosal healing and restore gut homeostasis Novel therapeutic approaches or combination therapy may be required to enable improved clinical outcomes
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6 High Unmet Medical Need for New Advanced Therapy Abbreviations: ASA, aminosalicylic acid; MoA, mechanism of action * Estimates based on IQVIA 2023 data analyses of advanced vs conventional therapy consensus data, Evaluate Pharma † Labeled data on placebo placebo-adjusted basis UC Treatment Progression in the U.S. (estimated ~780k treated patients) * Disease Severity 5-ASAs Steroids Biologics Cyclosporine / Tacrolimus Surgical Intervention Biologic Failures Oral, Pre- Biologics 180k patients on advanced therapy 24% are new, while while 27% have sub-optimal response 600k patients on conventional therapy 15% of these remain uncontrolled ≅$6B in US sales Significant opportunity exists for new advanced therapy to improve clinical remission rates ≦ 30% Clinical Remission† Rapidly Advancing EQ504 Towards Value Creation Milestones
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7 The Aryl Hydrocarbon Receptor (AhR) & Signaling Pathway AhR Ligands Cytoplasm Signaling begins when a ligand binds to AhR in the cell cytoplasm, forming an AhR ligand complex The AhR ligand complex then translocates to the nucleus and heterodimerizes with the AhR nuclear translocator (ARNT) The AhR ligand/ARNT complex binds to specific elements on DNA and promotes modulation of AhR responsive genes Genes induced responsible for detoxification, immune modulation, anti- inflammatory cytokines, anti-oxidant proteins, barrier function and repair Nucleus AhR AhR ARNT ARNT AhR 1 2 3 4 Esser & Rannug., Pharmacol Rev., 2015; Rothhammer & Quintana, Nat.Rev. Immunol., 2019; Polonio et al., Nat.Rev.Drug Discov., 2025 7
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8Esser & Rannug, Pharmacol Rev, 2015; Rothhammer & Quintana, NatRev Immunol, 2019; Polonio et al., NatRevDrug Discov, 2025 AhR expression is high in barrier tissues and mucosal epithelia such as skin, gut, lung, and eye AhR in Barrier Tissue Physiology and Immunology Plays a critical role in… o Maintaining and regulating barrier function o Modulating the activity of key immune cells to support gut homeostasis o Inducing the production of anti-inflammatory and barrier-protective cytokines IL-10 and IL-22 o Promoting barrier tissue repair and regeneration
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9 Modulation of AhR Clinically Validated in Skin and GI Disease Week 0 Week 4 Week 12 Week 0 Week 12 Week 0 Week 8 FDA Approved in Psoriasis Up to 34% patients achieved a PGA-Pso score of 0-1 by week 12 Phase 2 Trials in Ulcerative Colitis Up to 50% patients achieved clinical remission with total Mayo score ≤2, no individual subscore > 1 Indigo Naturalis (botanical medicine containing indirubin) Up to 27% patients with treatment refractory disease achieved clinical remission with total Mayo score < 3, no individual subscore > 1 FDA Approved in Atopic Dermatitis Up to 34% patients achieved a vIGA-AD score of 0-1 by week 8 https://vtamahcp.com/ ; Nagmura et al., Gastroenterology, 2018; Ben-Horin et al., Clin Gastroenterol Hepatol., 2024; Saiki et al., BMJ Open Gastro., 2021
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10 AhR Agonism Leads to High Rates of UC Clinical Remission Nagmura et al., Gastroenterology, 2018; Ben-Horin et al., Clin Gastroenterol Hepatol., 2024; Saiki et al., BMJ Open Gastro., 2021 Studies of ulcerative colitis patients treated with indigo naturalis demonstrate on-target engagement of AhR through increased intestinal CYP1A1 and high levels of clinical remission 42% Placebo Adjusted Clinical Remission at Week 8 50% Placebo Adjusted Clinical Remission at Week 8 27% Clinical Remission at Week 8
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11 EC50 = 0.67nM EC50 = 138nM ITE is a naturally-occurring, endogenous, non-toxic AhR modulator synthesized in the gut & lungs • Induces Treg cells and IL-10, while reducing Thelper17 cells and inflammatory cytokines • Induces IL-22 expression leading to improved barrier function and repair EQ504, derived from ITE, is a highly potent and selective modulator of AhR • Water soluble, GI stable with well-defined ADME, PK and PD properties • Key IND enabling studies complete EQ504 is a Potent Analog of ITE with Drug-like Properties Abbreviations: GI, gastrointestinal; ADME, absorption, distribution, metabolism, and excretion; PK, pharmacokinetic; PD, pharmacodynamic; GMP, good manufacturing practices; 16:1 molar ratio of indigo to indirubin in indigo naturalis based on Saiki et al., BMJ Open Gastroenterol, 2021 Induction of CYP1A1 in HepG2 (AhR-Lucia) Reporter Cells
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12 EQ504 Promotes Ex Vivo Intestinal Epithelial Wound Healing ****p<0.00001, **p<0.001, *p<0.005 vs Vehicle by Two-way ANOVA. T84 cells in a standard scratch assay, see Lanis et al., Mucosal Immunol, 2017. In-house data, Marroccoet al., American Association of Immunologists, 2025 0 1 2 3 4 5 0 25 50 75 100 125 Day Wound Area (%) Vehicle EQ504 10nM Indirubin 50nM * ******** Modulation of AhR (CYP1A1) induces IL-22, which leads to increased levels of wound healing T84 Call Scratch Assay Vehicle EQ504 10nM Indirubin 50nM Vehicle EQ504 10nM Indirubin 50nm vehicle EQ504 Indirubin 0 20 40 60 80 CYP1A1 mRNA (fold change) ✱ vehicle EQ504 Indirubin 0.8 1.0 1.2 1.4 1.6 1.8 2.0 IL22RA mRNA (fold change) ✱✱ ✱
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13 EQ504 Modulates Treg Cells and Cytokine Expression In Vitro ****p<0.0001 ,***p<0.001; one-way ANOVA Treg define as CD 4+CD 25hiC D127 lo. Naïve T cells are differentiated under standard Treg differentiating conditions; retinoic acid + TGFB (cocktail) with a low CD3/CD28 stimulation for 7 days. TGIT+ Treg cells selectively inhibit pro-inflammatory Th1 and Th17 cells (Joller et al., 2015), while CD39hi Treg cells have stronger stability and function under inflammatory conditions (Gu et al., 2017). Ampudiaet al., American Association of Immunologists, 2025 (Poster 107) Treg EQ504 increases the number and function of suppressive Treg cells that inhibit activity of Th1 and Th17 cells and promote tissue homeostasis Vehicle EQ504 62.5nM Indirubin 62.5nm 0 5 10 15 20 25 IL-10 (pg/mL) ✱✱ 0 20 40 60 80 100 IL-22 (pg/mL) ✱✱✱ Frequency of Treg Cells IL-10 IL-22
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14 ****p<0.0001 ,***p<0.001; one-way ANOVA Total PBMCs were incubated for 72hrs with CD3/CD28 stimulation. Th17 CXCR6+RORγδ+ Th17 cells migrate to inflamed tissues to mediate further inflammation (Schnell et al., 2021). Abbreviations: AhR, aryl hydrocarbon receptor, IAmpudiaet al., American Association of Immunologists, 2025 EQ504 Modulates Th17 Cells and Cytokine Expression In Vitro Modulation of AhR by EQ504 decreases the number and function of pathogenic Th17 cells Pathogenic Th17 Cells 0 5 10 15 20 25 % pathenogenic Th17 ✱✱✱ ✱✱✱ 0 100 200 300 400 IL-17A pg/ml ✱✱ ✱✱✱ Vehicle EQ504 7.8 nm Indirubin 7.8nm IL-17A Vehicle EQ504 7.8nM Indirubin 7.8nm
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15 EQ504 Demonstrates Activity in Treating Colitis In Vivo Eicheke et al., World J Gastroenterol 2017; Gao et al., Acta Histochemica 2016; DSS: Dextran Sodium Sulfate; IBD: Inflammatory Bowel Disease,; CSA: cyclosporin; In-house data, Chuet al., American Association of Immunologists, 2025 DSS Colitis Animal Model • DSS-induced colitis is the most widely used in vivo model of UC • CSA is a broad and strong immuno-suppressant, used as a positive control • Indirubin is efficacious at 10 mg/kg in the DSS model • EQ504 is efficacious at 1mg/kg in the DSS model • Human equivalent dosing of approximately 5mg total DSS (7days) Colon epithelial breakdown Inflammation and immune infiltration Body Weight Loss EQ504 Blocks Weight Loss in DSS Colitis **p<0.001 vs Vehicle by One-way ANOVA, n=8-10 -25 -20 -15 -10 -5 0 Body Weight Change (%) ** ** **
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16 EQ504 Induces Anti-Inflammatory Cytokines in Colon Tissue ***p<0.0001, **p<0.001 vs Vehicle by One-way ANOVA, n=8-10; In-house data, Chuet al., American Association of Immunologists, 2025 CYP1A1 expression (demonstrates target engagement) IL-22 expression IL-10 expression AhR modulators EQ504 and indirubin activate AhR pathways as demonstrated by increased CYP1A1 and anti-inflammatory cytokine expression in mouse colons with DSS colitis
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17 EQ504 Blocks Inflammatory & Histopathologic Changes in DSS Colitis Histology scoring of distal colon on day 10 in the acute DSS mouse model, **p<0.001, *p<0.05 vs Vehicle by One-way ANOVA, n=8 Mucosal Damage p=0.055p=0.086 Immune Infiltration Lymphoid Aggregates EQ504 reduces inflammatory infiltrates & preserves colonic morphology in mouse DSS colitis
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18 EQ504 Protects the Intestinal Mucosal Barrier in DSS Colitis Sections taken from distal colon at day 10 in acute DSS mice Mucosal erosion Lymphoid aggregate Immune infiltration Vehicle Loss of crypt structure Hypertrophy Edema Reduced lymphoid aggregate Preserved mucosa Reduced infiltration EQ504 1mg/kg CSA 75mg/kg Preserved morphology
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19EQ504 in 2% HPMC and 0.1% Tween-80 and delivered by either oral gavage or via colonic cannula in Male SD rats (n=3 /group). Concentration was measured by LC/MS from colon tissue and blood plasma at 3, 6, 24hrs post dose. Peak exposures were analyzed as a ratio of colonic/systemic concentration and expressed as fold increase in colonic route vs oral route. Colonic Delivery of EQ504 Reduces Systemic Exposure Peak Colonic versus Systemic Exposure Oral Colonic Routes of Administration Oral Colonic 0 10 20 30 40 EQ504 (fold change) >25X In vivo experiments demonstrate localized delivery of EQ504 directly to the colon of rats, results in 25x greater peak exposures in colon tissues versus blood
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20Ben-Horin et al., Clin Gastroenterol Hepatol., 2024. https://www.evonik.com/en/products/hc/pr_52036408.html Targeting the Colon to Treat Ulcerative Colitis • 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 enteric coating systems that dissolve at the start of the colon • Targeted, localized treatment of the colon has several potential therapeutic benefits in UC: ➢ Allows for optimization of dosing to target tissues: higher tissue and lower systemic exposures ➢ Potential to expand therapeutic window with improved safety and tolerability profile • Validated approach for AhR modulation through indigo naturalis administered in EudraGuard®️ capsules Enterically-coated, Colon-targeted Formulation Conventional, systemically available formulation Lower Drug exposures Higher
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21 High Unmet Medical Need & Large Market Opportunity Abbreviations: ASA, aminosalicylic acid; MoA, mechanism of action EQ504 positioned to have significant utility across multiple lines of therapy Disease Severity Pre-biologic: Substantial unmet need for new oral agents in the pre -biologic setting Biologic failures: Robust efficacy may support incremental opportunity in biologic failure patients Combination therapy: Unique MoA is attractive for combination with current immuno-modulatory therapies 1 2 3 3 1 2 5-ASAs Steroids Biologics Cyclosporine / Tacrolimus Surgical Intervention Biologic Failures Oral, Pre- Biologics Up to 30% Clinical Remission† ≅$6B in US sales
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22 • 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 and tolerability • Blood and tissue pharmacokinetics and pharmacodynamics • Target engagement & activity in colon biopsies by CYP1A1, IL-10, IL-22 • Phase 1 study initiation expected mid-2026 • Potential to achieve proof of concept with addition of UC patient cohorts following SAD/MAD Potential to Create Value in Early Clinical Development Nagmura et al., Gastroenterology, 2018; Saiki et al., BMJ Open Gastroenterol, 2021; Ben-Horin et al., Clin. Gastroenterol. Hepatol, 2024 Abbreviations: SAD/MAD, single ascending dose/multiple ascending dose; UC, ulcerative colitis; AhR, aryl hydrocarbon receptor CYP1A1 IL-22 IL-10
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23 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 markers in the colon Oral medication for targeted treatment of inflammation in colon aimed at maximizing tissue exposure and minimizing systemic exposures EQ504 multi-modal MoA modulates AhR signaling pathways to reduce inflammation and promote mucosal healing Application both pre- and post-biologics and potentially well suited for multiple combination approaches Clinical Validation GI-targeted, Locally Delivered Specific, Selective AhR Modulator Broad Positioning
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24 . Executive Leadership with Extensive Industry Experience Bruce Steel, CFA Chief Executive Officer Steve Connelly, PhD President, Chief Scientific Officer Christine Zedelmayer Chief Operating Officer Penny Tom SVP Finance Clinical Advisors Scientific Advisors Professor Francisco J. Quintana, PhD Harvard University & Associate Member, Broad Institute Dr. Thomas Daniel, MD Venture Partner, Entrepreneur & Industry Veteran Professor Vijay K. Kuchroo, DVM, PhD Harvard Medical School & Member of the Broad Institute Dr. Fred Ramsdell, PhD Former CSO & Founder at Sonoma Biotherapeutics Professor Bruce Sands Feinstein IBD Clinical Center, Mt Sinai Hospital Brian Feagan Venture Partner, Entrepreneur & Industry Veteran
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25 Financials and Corporate Overview * August 2025 initial closing of $30M (gross proceeds) included 30,816,705 pre-funded warrants (PFW) included in total above ** Potential second tranche of $20M (gross proceeds) would result in an additional issuance of 35,087,717 shares or PFW As of September 30, 2025 Ticker NASDAQ: EQ Shares & PFW* Outstanding 91.5 M Cash & Equivalents $33.1 M Offices La Jolla, CA In August 2025 Equillium announced a financing of up to $50 Million to Advance EQ504, a Novel Aryl Hydrocarbon Receptor Modulator, into clinical development • $30 million funded at initial closing – provides runway through end of 2027 • Potential to receive an additional $20 million tranche at clinical study initiation and occurrence of other milestones in the financing agreement * * (expected mid-2026) – would extend runway beyond 2027 • Financing led by ADAR1 Capital and Janus Henderson, with participation from Adage Capital, Coastlands Capital, and Woodline
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26 Equillium Intellectual Property Listed IP includes: filed, provisional, and prepared applications, which may or may not issue; potential patent term extensions not modeled 2018 2026 20342022 2030 2038 2042 2046 2050 AhR Modulators - Compositions/Methods AhR Compounds - Compositions/Methods Chiral AhR Compounds - Compositions/Methods EQ504 - Compositions/Methods EQ504 - Formulations AhR Portfolio 4 patent families 9 issued patents 5 applications pending Current EQ Filings Potential EQ Filings
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27 November 2025 Thank you www.equilliumbio.com Contact us at: IR@equilliumbio.com