Slides
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1 November 5,2025 Virtual KOL Event to Discuss EQ504: A Novel Aryl Hydrocarbon Receptor (AhR) Modulator for Ulcerative Colitis
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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 and cash runway. These statements involve known and unknown risks, uncertainties and other factors 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 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 Today’s Agenda Introduction Emerging Therapies 2025 The aryl hydrocarbon receptor: A target for immune modulation EQ504: Targeting AhR to Promote Mucosal Healing In Ulcerative Colitis Bruce Steel, CFA Brian Feagan, MD, FRCPC Francisco J. Quintana, PhD Stephen Connelly, PhD Q&A Session Management & KOLs
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4 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 immune response with the ultimate goal of identifying novel therapeutic targets and biomarkers for immune-mediated disorders. He is well known for his research on the role of the Aryl Hydrocarbon Receptor (AhR) identifying important roles for the transcription factor in the control of inflammation driven. Key contributions include studies on the role of AhR in modulating effector and regulatory T cell functions through IL-10 and IL-22, both play an important role in mucosal immunology. Working with Dermavant, Dr. Quintana was involved in the development of Tapinarof (VTAMA®), the first FDA- approved AhR modulator for the treatment of both psoriasis and atopic dermatitis. Overall, Dr. Quintana's research has on AhR has implications in our understanding of the pathology and treatment of multiple autoimmune and inflammatory disorders. Dr. Quintana has published over 230 peer reviewed articles and book chapters. In addition, Dr. Quintana’s research has resulted in multiple patents which have been the foundation of four companies: ImmunArray Ltd, Alma Bio Therapeutics, AnTolRx Inc, and Violet Therapeutics. Dr. Quintana is the Director of the course Autoimmunity at Harvard Medical School. Dr. Quintana has been the recipient of the Lady Anne Chain Prize for Academic Excellence and Scientific Achievements, the Junior Investigator Award from the National Multiple Sclerosis Society , the Pathway to Independence Award of the National Institute of Allergy and Infectious Diseases, the Award for Outstanding Research Achievements form Nature Biotechnology and the Tecan Award for Innovation, the Harry Weaver Award from the National Multiple Sclerosis Society, the Young Mentor Award from Harvard Medical School, the Milestones in MS research from the National MS Society, the AAI-BD Bioscience Investigator Award, the Barancik Prize for Innovation in MS Research from the National Multiple Sclerosis Society, and the Raices Award from the Republic of Argentina. He has been listed as one the Most Highly Cited researchers by the Institute for Scientific Information (ISI) every year since 2019, and has been the Indirawati Kuchroo and Charlotte Weiner Distinguished Professor of Neuroimmunology at Brigham and Women’s Hospital and Harvard Medical School since 2021. Introduction: Francisco J. Quintana, PhD
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The aryl hydrocarbon receptor: A target for immune modulation Francisco J. Quintana Harvard Medical School Broad Institute of MIT and Harvard
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6 Fishing for Novel Regulators of the Immune Response Circa 2005
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The Aryl Hydrocarbon Receptor (AHR) Quintana et al, Nature 2008 Teff Treg Initiation of inflammatory cascade Th1 Th17 CD8+ T cells FoxP3+ Tregs Tr1 cells Suppression of inflammation Nature (2008); Nat. Immunology (2010); Nat. Immunology (2010) ; PNAS (2010); PLoS One (2010); PNAS (2012); Nat. Immunology (2012); Nat. Immunology (2012); Nat. Immunology (2013) ; Nat. Communications (2014) ; Cell (2015);Nat. Medicine (2015); Cell reports (2016a); Cell reports (2016b); Science Signaling (2016); Nat. Neuroscience (2019); PNAS (2020); Nature Neuroscience (2020); Nature) Communications (2021); PNAS (2021); Nature (2022); Nature Cancer (2023); Nature (2025a); Nature (2025b) 7
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AHR Signaling 8 Polonio and Quintana, Nature Reviews in Drug Discovery 2025
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AHR Physiologic Agonists 9 Gutierrez-Vazquez and Quintana, Immunity 2018
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AHR Responsive Cells in the Gut 10 Non-immune Cells Maintain Barrier Function • Intestinal Epithelial Cells • Goblet Cells • Paneth Cells Immune Cells Immune homeostasis & tolerance • Innate Lymphoid Cells • Dendritic Cells & Macrophages • Effector T Cells • Regulatory T Cells
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IL-10 and IL-22 in Mucosal Biology 11 IL-10 Immuno-modulatory peacekeeper • Inhibits production of pro -inflammatory cytokines from macrophages & dendritic cells • Enhances function of regulatory T cells and prevents uncontrolled activation of Th1/17 cells • Prevents excessive inflammation and protects tissues from immune -mediated damage • Essential for tolerance to commensal gut microbiota, maintaining intestinal homeostasis and preventing colitis IL-22 Epithelial protector and healer • Strengthens epithelial tight junctions to promote epithelial barrier integrity • Stimulates proliferation, survival, and repair of intestinal epithelial cells • Promotes wound healing and regeneration following injury or infection • Induces antimicrobial peptides and strengthens host defense against pathogens at barrier sites “IL-10 and IL-22 act together they maintain the immune -epithelial balance”
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Regulation of Adaptive Immunity by AHR 12 Polonio and Quintana, Nature Reviews in Drug Discovery 2025
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Role of AHR in gut homeostasis 13 Rothhammer and Quintana, Nature Reviews in Immunology 2019
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Role of AHR in intestinal Stem Cells 14 Modified from Wisniweski et al, Frontiers in Immunology 2021
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Therapeutic gut AHR activation 15 Polonio and Quintana, Nature Reviews in Drug Discovery 2025
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Summary 16 • 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 protective functions extend to other tissues beyond the gut. • AHR an attractive therapeutic target with clinical validation fquintana@bwh.harvard.edu Follow us in X: @QuintanalabHMS
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17 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 colitis (UC), and over the past 30 years, has been Principal Investigator in over 140 multi-center RCTs.His research has been devoted to the development, validation and optimization of outcome measures to assess the efficacy of novel therapeutics in CD and UC.Dr. Feagan is Professor of Medicine at the Schulich School of Medicine & Dentistry, a gastroenterologist at London Health Sciences Centre and Senior Scientific Director of Alimentiv Inc (formerly Robarts Clinical Trials Inc). Dr. Feagan completed a medical degree at the University of Western Ontario (UWO) in London, Ontario, Canada. His postdoctoral training included a residency in Internal Medicine and a clinical fellowship in Gastroenterology in the Department of Medicine at UWO, and postgraduate training in the Department of Epidemiology and Biostatistics at McMaster University , Hamilton, Ontario. A Fellow of the Royal College of Physicians and Surgeons of Canada, Dr. Feagan holds membership in the Canadian and American Association of Gastroenterology , the American College of Gastroenterology, the College of Physicians and Surgeons of Ontario, Crohn’s and Colitis Canada (CCC) and European Crohn’s and Colitis Organization (ECCO). He has authored over 480 articles and book chapters and has given over 600 invited presentations at national and international scientific meetings. In 1997, Dr. Feagan became Director of Robarts Clinical Trials at the Robarts Research Institute, University of Western Ontario and in 2020, he became Senior Scientific Director of Alimentiv Inc.(formerly Robarts Clinical Trials) His research efforts focus on the design and implementation of randomized controlled trials of therapy for inflammatory bowel disease. He has been the principal investigator on numerous large-scale randomized clinical trials. Introduction: Brian G. Feagan, MD, FRCPC
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Brian G. Feagan MD Professor of Medicine, Epidemiology and Biostatistics Western University Senior Scientific Director, Alimentiv Inc. London, Ontario, Canada
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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 Capital, Celsius Therapeutics, Celgene/BMS, Celltrion, Clarivate, Connect BioPharma, Disc Medicine, Duality, EcoR1, Eli Lilly, Ensho Therapeutics, Evida, Enveda, Faes Farma,First Wave, Forbion, Galapagos, Galen Atlantica, Genentech/Roche, General Atlantic, Genesis Therapeutics, Gilead, Gossamer Pharma, GSK, Imhotex, ImmiDomics, Immunic Therapeutics, Intercept, Janssen, Japan Tobacco Inc., Klick Health, LifeMine Therapeutics, Mage Biologics, Merck, Mestag, Mirador Therapeutics, Mobius, Monte Rosa Tx, Morphic Therapeutics, Nexys Therapeutics, Nighthawk Therapeutics, Nimbus Therapeutics, Novartis, OncoC4, OrbiMed, Orphagen, Pendopharm, Pfizer, Protagonist,32 Bio, REDX, Roche, Roivant/Televant, Sanofi, Sobi, Sorriso, Spyre Therapeutics, Surrozen Inc., Sun Pharma, Synedgen, Takeda, Teva, Triastek, Trex Bio, TR1X Inc. TVM Lifesciences, Ventyx Biosciences, Versant Ventures, Vida Ventures, Zagbio Speakers Bureau AbbVie, Janssen, Takeda Patent Holder Member, Scientific Advisory Board, DSMB AbbVie, AnaptysBio, Boehringer-Ingelheim, Celgene/BMS Eli Lilly, Genentech/Roche, Janssen, Merck, MiroBio, Origo BioPharma, Pfizer, REDX Pharma, Sanofi, Takeda, Teva, Ecor1Capital, Morphic, GSK Member, Board of Directors Stock Shareholder Connect BioPharma, EnGene Expert Testimony Belmore Law Other Relationship/Affiliation Senior Scientific Director, Alimentiv Inc.
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Topics to Be Discussed • The Present -2025 a glass half full! • Where are we headed? • Horizon agents • Combination therapy • Horizon indications/strategies • Summary 20
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• The introduction of multiple new treatments in the past 25 years has not resulted in consistently high rates of remission. • Personalized medicine has not evolved as a management strategy for IBD • We still do not understand the cause(s) IBD 2025- A glass half full! • Two emergent MOAs, anti-integrin therapy (vedolizumab ) and IL-12/23 are extraordinarily safe. • Surgical rates have fallen dramatically in both UC and CD. • Several new MOAs have been validated
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• The Present = 2024 – A glass half full! • Where are we headed? • Horizon agents • Combination therapy • Horizon indications/strategies • Summary 22 Topics to Be Discussed
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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 endothelial cells • Transgenic mice develop colitis and intestinal fibrosis • Murine anti-TL1A antibody alleviates inflammation and fibrosis 1Ruuls et al. Immunity 2001 2 Yue et al. J Biol Chem 1999. 3Furfaro et al. Curr Drug Targets 2021. 4Xu et al. Front Immunol 2022. Proliferation of non-suppressive Tregs
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24 • 14 week open-label study in moderately to severely active ulcerative colitis, N=50 • propensity matched artificial control • proof of concept achieved • No clinically meaningful safety signal observed TL1A Antagonist as Induction Therapy for UC 38.2% 24.0% 0% 10% 20% 30% 40% 50% 60% Endoscopic Improvement Clinical Remission Proportion of Patients (%) 14/42 20/4217/4 5 Endoscopic & Clinical Endpoints at Week 14 * ** Adapted from ECCO’20 Vienna Congress Presentation – Speaker: Dr. Silvio Danese. Danese et al. Safety, Tolerability and efficacy of anti-TL1A antibody PF-06480605 in treatment of ulcerative colitis: the open -label, multicentre, Phase 2a TUSCANY study. 17/45 12/50
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Primary and Secondary Endpoints at Week 12 Tulisokibart vs. Placebo Sands BE. Et al. New Eng J Med. 2024;391(12):1119-29 1.5% 6.0% 22.4%26.5% 36.8% 66.2% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Clinical Remission Endoscopic Improvement Clinical Response Subjects Achieving Endpoint (%) Placebo N=67 PRA023 N=68 43.8% 30.8% p <0.0001 25.0% p <0.0001 Clinical remission per mMS is defined as endoscopic subscore of 0 or 1, rectal bleeding subscore of 0, and stool frequency subscore of 0 or 1 and not greater than Baseline; Endoscopic improvement is defined as endoscopy subscore ≤ 1 with no friability; Clinical response per mMS is defined as reduction from Baseline ≥ 2 points and ≥ 30% in 3-component Modified Mayo Score, accompanied by a reduction ≥ 1 in rectal bleeding subscore or absolute rectal bleeding subscore ≤ 1. | P-values for testing the treatment difference are based on Cochran- Mantel-Haenszel test adjusted for prior biologic exposure status and CDx status. All endpoints are statistically significant according to multiplicity controlled 2-sided alpha of 0.05. p <0.0001
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Oral Alpha 4 Beta7 Blockade: Background • Ligand for 47 is MAdCAM • 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 model Hesterberg PE et al. Gastroenterology 1996;111:1373-80 Podolsky et al. JCI 1993;92:372-80 Alpha 4 Beta 7MAdCAM -1 ACT -1
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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”
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• a4β7 RO achieved early and sustained saturating levels • a4β1 RO remained at low levels • No lymphocytosis or changes to circulating naïve T-cells were observed • a4β1 projected RO was below the limit of quantitation with mean trough value estimated to be <15% Morphic Data: Patient a4β7 Receptor Occupancy (RO) Consistent with Healthy Volunteer RO a4β7 selectivity over a4β1 consistent with Phase 1 results 1 10 100 0 20 40 60 80 100 500 Concentration (ng/mL) 47 RO (%) Phase 1 EMERALD 1 - RO: Receptor Occupancy; BLQ, Below Limit of Quantification UEGW Congress Abstract 2024
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Anti-p40 Ustekinumab: Background for Oral Il-23 NK or T cell membrane p40p19 IL-23 p40 p35 IL-12 ustekinumab No IL-12 or IL-23 intracellular signal 1 Sandborn W, et al. Oral presentation. CCFA 2015 and Rutgeerts P, et al . Oral presentation. ECCO 2016. 2 Feagan B, et al. Oral presentation. ACG and UEGW 2015. • IL-12 & IL-23 are key cytokines in the pathogenic immune cascade of Crohn’s disease • Ustekinumab is a fully human IgG1k monoclonal antibody binding the p40 subunit of interleukin-12 and -23 • Inhibits IL-12- and IL-23-mediated signaling, cellular activation, and downstream cytokine production • Approved for moderate to severe psoriasis and psoriatic arthritis • Induction efficacy recently demonstrated in a broad CD population in UNITI-11 and UNITI-22 Sandborn W.J., et al. DDW 2016. Presentation 768.
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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. Transformational Efficacy in Psoriasis Therapy
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12.8 2.6 0 26.8 14.6 2.4 36.6 19.5 12.2 31.7 17.1 7.3 0 5 10 15 20 25 30 35 40 Endosc. response Endosc. remission Deep remission Placebo (N=39) 200 mg risankizumab (N=41) 600 mg risankizumab (N=41) Pooled risankizumab (N=82) . Risankizumab for CD: Is anti-P19 the Answer? 7.7 2.6 15.4 9.8 17.1 24.4 19.5 24.4 36.6 14.6 20.7 30.5 0 5 10 15 20 25 30 35 40 Week 4 Week 8 Week 12 Proportion of subjects (%) Endoscopic endpoints at Week 12 Clinical remission over time through Week 12 * ** *** * * Primary endpoint * * * * * ** * * Feagan B, et al. Lancet 2017;389:1699 –1709
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Risankizumab Induction: Clinical Remission Week 12 21.7% 43.5% 41.0% 25.2% 45.2% 41.6% 0% 20% 40% 60% 80% 100% P<0.001 =20.2% 44/175 152/336 141/339 P<0.001 =16.1% 146/336 139/33938/175 SF/APS Clinical Remission2CDAI Clinical Remission1 P<0.001 =21.9% P<0.001 =18.8% %Patients ADVANCE Non-Bio-IR & Bio-IR 19.3% 34.6% 39.3% 19.8% 42.5% 40.3% 0% 20% 40% 60% 80% 100% P<0.001 =22.6% 37/187 81/191 77/191 P<0.001 =20.5% 66/191 75/19136/187 SF/APS Clinical Remission2CDAI Clinical Remission1 P=0.001 =15.2% P<0.001 =19.9% MOTIVATE Bio-IR ■ Placebo ■ RZB 600 mg ■ RZB 1200 mg %Patients Ferrante et al UEGW 2021
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Oral IL-23 Peptide Therapy for Psoriasis 0 10 20 30 40 50 60 70 80 90 Oral IL 23 Receptor Antagonist Peptide for Plaque Psoriasis IL-23 Receptor Placebo 25 mg OD 25 mg BID 50 mg OD 100 mg OD 100 mg BID P<0.001 PASI 75 Response
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• 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 Obefazimod Induction Therapy for UC
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Combination Therapy…. Behold HCV treatment
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SONIC Provides a Clue! 30 45 57 0 20 40 60 80 100 Proportion of Patients (%) AZA + placebo IFX + placebo IFX+ AZA p<0.001 p=0.009 p=0.022 52/170 75/169 96/169 Colombel JF. et al. N Engl J Med. 2010 Apr 15;362(15):1383 -95.
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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 ▪ T o evaluate the safety and efficacy of combination therapy with guselkumab and golimumab in patients with moderately to severely active ulcerative colitis PRIMARY ENDPOINT MAJOR SECONDARY ENDPOINTS ▪ Clinical response at Week 12 defined by Mayo score ▪ Clinical remission at Week 12 defined by Mayo score Feagan BG et al. Lancet Gastroenterol Hepatol.2023;8(4):307-320.
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Clinical Response and Remission at Week 12 Sands BE, Feagan BG, Sandborn WJ, et al. Efficacy and safety of combination induction therapy with guselkumab and golimumab in participants with moderately-to-severely active Ulcerative Colitis: Results through week 12 of a phase 2a randomized, double-blind, active-controlled, parallel-group, multicenter, proof-of-concept study (OP36). J Crohn’s Colitis 2022;16(S1);i042. 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) ECCO 2022 data may include drugs, doses and indications not approved by Health Canada Clinical Remission (Mayo score ≤2 with no individual subscore >1 Clinical Remission (modified Mayo score: Mayo stool frequency subscore of 0 or 1 and not increased from baseline, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy)
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TL1A: First IBD Target That Mediates Inflammation & Fibrosis • Transgenic mice develop colitis and intestinal fibrosis • Murine anti-TL1A antibody alleviates inflammation and fibrosis • Variants in the TL1A-encoding gene (TNFSF15) are associated with increased IBD risk oTL1A likely a differential disease driver in a subgroup of IBD patients oGenetically-based diagnostic test being developed to identify patients with higher likelihood of response • 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 diseases, including IBD3,4 1Ruuls et al. Immunity 2001 2 Yue et al. J Biol Chem 1999. 3Furfaro et al. Curr Drug Targets 2021. 4Xu et al. Front Immunol 2022. Proliferation of non-suppressive Tregs
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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 • Future is bright!
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43 October 2025 EQ504: Targeting AhR to Promote Mucosal Healing In Ulcerative Colitis
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44 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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45 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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46 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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47 Multi-modal Mechanism of Action in Mucosal Homeostasis Modulates Immune Cell Responses IL-22Rα Tissue Regeneration: ▪ Stem cell maintenance and differentiation Maintain and protect barrier function: ▪ Tight junction maintenance ▪ Mucus production EQ504 Barrier function & Tissue Repair Anti-inflammatory and Immune modulation: ▪ Cross-talk with immune cells MAC M1 M2 Polarization Reduced pro- inflammatory cytokines EQ504 Differentiation T CELL Treg Th1 Reduced pro- inflammatory cytokines EQ504 Th22 Th17
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48 vehicle EQ504 Indirubin 0.8 1.0 1.2 1.4 1.6 1.8 2.0 IL22RA mRNA (fold change) ✱✱ ✱ 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 Indirubin 0 20 40 60 80 CYP1A1 mRNA (fold change) ✱ Vehicle EQ504 10nMIndirubin 50nm
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49 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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50 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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51 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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52 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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53EQ504 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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54 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 Enterically-coated, Colon-targeted Formulation Higher Lower Conventional, systemically available formulation Drug exposures
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55 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: MoA affords rationale for combination with current lines of immuno -modulatory therapies 1 2 3 3 1 2 5-ASAs Steroids Biologics Cyclosporine / Tacrolimus Surgical Intervention Biologic Failures Oral, Pre- Biologics Approx. $6 bn in US sales Up to 30% Clinical Remission†
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56 • 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 • 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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57 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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58 Q&A Session