Slides
Page 1
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved OD-001 Phase 2a Monotherapy Trial Update October 20, 2026 Investor and Analyst Webcast
Page 2
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Forward-looking statements and third-party information This presentation contains forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. All statements other than statements of historical facts are forward-looking statements, including, but not limited to, statements regarding our business strategy; the future clinical development, efficacy, safety, and therapeutic potential of our product candidates; expectations regarding the initiation, design, and reporting of data from our preclinical studies and clinical trials; future financial results; anticipated manufacturing plans; expectations regarding regulatory approval of any of our product candidates; and plans for future operations or other characterizations of future events. In some cases, you can identify forward-looking statements through the use of words such as “may,” “will,” “should,” “expects,” “plans,” “anticipates,” “could,” “intends,” “target,” “projects,” “contemplates,” “believes,” “estimates,” “predicts,” “potential,” or “continue,” or the negatives of these words or other similar terms or expressions that concern our expectations, strategy, plans, or intentions. These statements are not guarantees of future performance and involve risks and uncertainties, some of which are beyond our control, and you are cautioned not to place undue reliance on any forward-looking statements. Among the factors that could cause actual results to differ materially from those suggested by forward-looking statements are: our current and future research and development activities and expenses; sufficiency of our capital resources; our anticipated regulatory activities and our ability to obtain regulatory approval for any of our product candidates; our ability to commercialize future products, if approved; our ability to enroll patients in clinical trials; possible safety and efficacy concerns; the timing and results of our preclinical studies and clinical trials; and risks facing our operations and intellectual property. Although the Company believes the information contained in this presentation related to the Company is accurate in all material respects, neither the Company nor any other person assumes responsibility for the accuracy and completeness of the information contained in this presentation except to the extent required by law. The information contained in this presentation is provided for discussion purposes only as of the date hereof, and the Company undertakes no obligation to update or revise such information, including any forward-looking statements, whether as a result of new information, future events or circumstances, or otherwise, except to the extent required by law. Certain information contained in this presentation and statements made orally during this presentation may relate to or be based on studies, publications, estimates, projections, and other data obtained from third-party sources as well as our own internal estimates and research. While we believe these third-party sources to be reliable as of the date of this presentation, we have not independently verified, and make no representation as to the adequacy, fairness, accuracy, or completeness of any information obtained from third-party sources. Intellectual property This presentation contains references to our trademarks and service marks and to those belonging to other entities. Solely for convenience, trademarks and trade names referred to in this presentation, including logos, artwork, and other visual displays, may appear without the ® or TM symbols, but such references are not intended to indicate in any way that we will not assert, to the fullest extent under applicable law, our rights or the rights of the applicable licensor to these trademarks and trade names. This presentation may also contain trademarks, service marks, and trade names of third parties, which are the property of their respective owners. We do not intend our use or display of other entities’ trade names, trademarks, or service marks to imply a relationship with, or endorsement or sponsorship of us by, any other entity. Disclaimers 2
Page 3
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Overview of Presenters Gary D. Glick, Ph.D. Founder and Chief Executive Officer 3 Anthony Opipari, M.D., Ph.D. Chief Medical Officer Collin Todd Senior Vice President, Strategy and Business Development
Page 4
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Today’s Presentation – OD-001 Phase 2a Monotherapy Trial in UC Notes: UC = ulcerative colitis; BID = twice daily; RIPK2 = receptor-interacting protein kinase 2; SAE = serious adverse event; T EAE = treatment-emergent adverse event; AT = advanced therapy. 4 New information today • Shows evidence of a dose response • Confirms that 20 mg BID is the lowest maximally efficacious dose Full 10 mg BID dataset • Systemic and colonic biomarker analyses • Efficacy by patient segments and across time points • Transcriptomic assessments • Comparison by dose Additional analyses Totality of phase 2a data Converging lines of evidence support clinical efficacy of OD-001, a first-in-class RIPK2 scaffolding inhibitor • Robust separation vs. historic placebo rates across numerous efficacy endpoints • Strong correlation between clinical outcomes with OD-001 and inflammatory biomarkers, mucosal transcriptomics, and histologic improvement Corroborates that 20 mg BID is the lowest maximally efficacious dose • Dose was expected to maximally inhibit RIPK2 signaling based on phase 1 ex vivo stimulation assays; dose phenocopies the effect of RIPK2 knockout cells Supports a potentially competitive profile of OD-001 vis-à-vis approved and investigational ulcerative colitis therapies • Well tolerated with no SAEs and no discontinuations due to TEAEs • Efficacy across patient subsets: moderate and severe, AT-experienced, and AT-naïve • Competitive monotherapy efficacy and tolerability profile
Page 5
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Copyright 2026 | Odyssey Therapeutics | All Rights Reserved In search of extraordinary for patients Inflammatory Bowel Disease and RIPK2 5
Page 6
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved 6 IBD encompasses two serious and prevalent diseases, ulcerative colitis (UC) and Crohn’s disease (CD) • Despite multiple approved therapies, placebo-adjusted induction remission in UC remains < 30% • New therapies and combination approaches are needed to address the substantial proportion of patients who fail to respond to current agents and the progressive loss of response over time Ulcerative colitis* Crohn’s disease UC and CD differ in anatomical distribution and natural history but share pathogenic mechanisms: • Intestinal barrier disruption • Microbial translocation • Dysregulated innate and adaptive immunity * Drug development typically begins in UC because it is confined to the colon and mucosal pathology can be effectively scored by endoscopy, allowing more efficient trials than in CD, which is characterized by patchy, transmural disease Despite Multiple Approved Drugs, Significant Unmet Need Remains in IBD
Page 7
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved RIPK2 Plays a Central Role in the Pathogenesis of IBD 7 STEP 1: Loss of epithelial integrity; microbes breach gut barrier STEP 2: Innate immune cell activation (e.g., monocytes, neutrophils, and macrophages) STEP 3: Recruitment and activation of adaptive immune cells (e.g., T cells) Innate Adaptive Lamina propria TLRs NOD1/2 T cells in gut Lymph node egress IL-23 TNF Bacteria Gut lumen RIPK2 transduces NOD1/2 inflammatory signaling… … and RIPK2 activation amplifies TLR inflammatory signaling Neutrophils activated by RIPK2 continue breakdown of epithelial barrier Neutrophil RIPK2 OD-001 Epithelium Blood vessel Tulisokibart Duvakitug Fibroblasts/ fibrosis TL1A
Page 8
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved RIPK2 Is a Validated Target to Treat IBD 8 Animal data Human data RIPK2 knockout mice are developmentally normal Pharmacologic validation of RIPK2: Clinical efficacy with OD-001 provides target validation in UC RIPK2 knockout reduces inflammatory cytokines and improves intestinal histology in animal models of IBD RIPK2 ubiquitination is observed across all UC patients, including those with NOD2 LoF variants Microbes are required for spontaneous colitis in rodent models RIPK2 pathway activation is increased in intestinal tissue from patients with both UC and CD Blocking RIPK2 signaling reduces inflammatory cytokines and intestinal disease in mouse models Genetic validation of RIPK2: ATG16L1 and CARD9 variants are linked to increased IBD risk; protective CARD9 variants to reduced risk Sources: Inflamm Bowel Dis 2015;21(4):862; J Med Chem 2022;65(13):9312; J Med Chem 2019;62(14):6482; Proc Natl Acad Sci U S A 2014;111(25):E25 59; Am J Physiol Gastrointest Liver Physiol 2021;321(5):G500; Mucosal Immunol 2017;10(4):971; J Biol Chem 2014;289(43):29651; Commun Biol 2020;3(1):140; J Med Chem 2016;59(10):4867; Int Immunol 2019;31(1 0):669; Sci Signal 2024;17(819):eabn1101; Immunity 2013;39(5):858; Gut 2011;60(9):1229; Nat Immunol 2007;8(2):198; Nature 2012;491(7422):119; United Eur Gastroenterol J 2023;12(1):103; Front Immunol 2019;10:419.
Page 9
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Increased expression of RIPK2-responsive gene signature in IBD patient biopsies RIPK2 Is Activated in UC and CD and Correlates With Severity Notes: *** p < 0.001; GSVA = gene set variation analysis; GSVA cutoff for % of UC patients with RIPK2 pathway activity is 0.46. Sources: EMBO J 2018;37(17):e99372; Sci Signal 2024;17(819):eabn1101; g ene expression dataset: GSE193677. 9 Increased levels of activated (ubiquitinated) RIPK2 in patients with UC and CD Relative intensity of RIPK2-Ub Non-IBD UC CD 12 10 8 6 4 2 0 *** *** RIPK2 Inflammatory cytokines NF-kB MAPK TAK1 XIAP Active RIPK2 NOD1/2 Peptidoglycan (PGN) XIAP XIAP RIPK2 scaffolding with XIAP is necessary for activation and inflammatory signaling
Page 10
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved RIPK2 Drugs Must Block Scaffolding to Fully Inhibit NOD2 Signaling 10 Mol Cell 2018;69(4):551–565 EMBO J 2018;37(17):e99372
Page 11
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Blocking RIPK2 Scaffolding With OD-001 Achieves Maximal Inhibition 11 Notes: Binding to RIPK2 was measured by competition with a fluorescent ATP-site tracer in cells. XIAP binding to RIPK2 using recombinant protein was measured by HTRF. Cytokine production was assessed after 24 hours by MSD/ELISA in macrophages treated with compound for 1 hour and then stimulated with PGN. Sources: EMBO J 2018;37(17):e99372; Mol Cell 2018;69(4):551–565. OD-001 blocks cytokine production from macrophages stimulated with PGN 0.010.1110100 0 20 40 60 80 100 TNF TL1A IL-23 % Inhibition OD-001, nM0.010.1110100 020406080100 % Binding to RIPK2 % XIAP binding to RIPK2 OD-001, nM IL-23TNFTL1A Relationship between OD-001 and XIAP binding to RIPK2 RIPK2 binding to XIAP OD-001 binding to RIPK2 0.010.11101000 100 50 0 100 50 OD-001 is an allosteric scaffolding inhibitor that reduces the affinity for XIAP Displacement of XIAP OD-001 (RIPK2 scaffolding inhibitor) RIPK2 No inflammatory cytokines
Page 12
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Not All RIPK2 Scaffolding Inhibitors Are the Same 12 OD-001 blocks TL1A production in response to microbial stimulation (PGN) in human macrophages Pharmacology of noncompetitive allosteric inhibitors • Inhibitor and XIAP can bind simultaneously to RIPK2 to form a ternary complex • Inhibitor binding to RIPK2 potentially alters the affinity for XIAP • Extent of scaffolding inhibition depends on KD, which can vary depending on XIAP concentration RIPK2 RIPK2:XIAP RIPK2:I + XIAP + I RIPK2:I:XIAP + XIAP + I KD Scaffolding Kd OD-001 Comparator B1 Comparator A Comparator B2 % TL1A production Concentration, nM 10001000.1 1 10 100 0 50 Notes: Human macrophages were treated with compounds for 1 hour and then stimulated with PGN. Cytokine production was assesse d after 24 hours by ELISA. Sources: Comparator A WO2022192760 Example A6; Comparator B1 WO2024254539 Example 253; Comparator B2 WO2024254539 Example 52.
Page 13
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Copyright 2026 | Odyssey Therapeutics | All Rights Reserved In search of extraordinary for patients Phase 2a Monotherapy Trial NCT06850727 13
Page 14
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Rationale and Dose Selection for Proof-of-Concept Phase 2a Trial • OD-001 is the first innate immune-targeted therapy and the first RIPK2 scaffolding inhibitor to enter UC clinical development • Trial was designed to assess safety and efficacy of OD-001 and determine whether to advance the program - Partnered with Alimentiv, a leading IBD-specialized CRO with deep investigator experience - Primary endpoint: Change from baseline in 3-component mMS at week 12 (90% power at a two-sided 5% significance to detect a 2-point change) - Secondary endpoint: Remission rate (≥ 15% placebo-adjusted compared with a historic placebo rate of 10%; 82% power at a two-sided 10% significance) • Doses selected based on an ex vivo blood assay in the phase 1; 20 mg BID is the lowest dose projected to be maximally effective - Level of inhibition with 20 mg BID approximates that observed with RIPK2 knockout cells 14 IC90 Time post dose on day 14, hours 1000 100 10 0 4 8 12 OD-001 PK vs. human whole blood IC90 10 mg BID 20 mg BID Inhibition of PGN-stimulated TNF following OD-001 BID dosing (AUC) Day 1 Day 14 Placebo 10 mg 20 mg 30 mg 50 mg 10 30 100 300 Mean human whole blood OD-001, ng/mL ~70% reduction ~90% reduction PGN-stimulated TNF, AUC 0–12 hours Notes: 3-component modified Mayo Clinical score (mMS) includes endoscopic severity (0–3), stool frequency (0–3), and rectal bleeding (0–3).
Page 15
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Vedolizumab 300 mg Q8W Vedolizumab 300 mg (weeks 12, 14, 18) Day 1 OD-001 start Week 12 OD-001 stop / Vedolizumab start Week 26 Week 52 10 mg BID 20 mg BID Part 1 (n = 16) Part 2 Randomized 1:4 (n = 45) Phase 2a Monotherapy Trial Overview 15 10 mg BID (2 weeks) then 20 mg BID (10 weeks) • Patients with moderately to severely active UC and an mMS of 5–9 were enrolled from 18 sites across seven countries; up to three prior advanced therapies were permitted • Dosing strategy: - Part 1: Initial evaluation at 10 mg BID to ensure safety in UC patients with submaximal RIPK2 inhibition before testing a higher dose with maximal inhibition - Part 2: Evaluated 20 mg BID to assess safety and efficacy of maximal RIPK2 inhibition; included a subgroup with step-up dosing from 10 to 20 mg BID • Design features to minimize placebo effect: - Required Mayo endoscopic subscore (MES) ≥ 2 and rectal bleeding subscore ≥ 1 - Centralized and blinded endoscopy reads - Limited concomitant steroid dose to maximum of 20 mg prednisone
Page 16
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Participant Characteristics Are Similar to Other Contemporary UC Trials Notes: (1) Includes both approved advanced therapies and investigational agents; includes golimumab, etrasimod, ustekinumab, rosnilimab, MORF-057, PN-943, infliximab, icotrokinra, TYK2 inhibitor, adalimumab, and etrolizumab. Sources: Lancet Gastroenterol Hepatol 2022;7(11):1024 –1035; Abivax corporate presentation, March 2023; Abivax phase 3 topline readout, July 2025; obefazimod UEG Week presentation, October 2025; Clin Gastroenterol Hepatol 2026;24(2):525–534; Spyre SKYLINE Part A induction results, April 2026; icotrokinra UEG Week presentation, October 2025; Prometheus Biosciences corporate presentation, March 2023; duvakitug phase 2 investor call, February 2025; Lancet Gastroenterol Hepatol 2025;10(10):882–895. 16 OD-001 RIPK2 Obefazimod miR-124 SPY001 a4b7 Icotrokinra IL-23 Tulisokibart TL1A Duvakitug TL1A Afimkibart TL1A Phase Phase 2a Phase 2b Phase 3 Phase 2, Part A Phase 2b Phase 2 Phase 2b Phase 2b Age, mean 40 41 42 44 42 41 41 39 Sex, male 49% 59% - 72% 58% 53% 63% 60% Advanced therapy- experienced (1) 30% 49% 47% 19% 43% 47% 39% 39% Modified Mayo score, mean 6.5 7.1 6.9 6.8 6.6 7.0 6.8 7.0 (median) MES = 3 51% 71% 60% 56% 59% 73% 56% 52% Median fecal calprotectin, µg/g 1,752 1,647 1,666 - 1,523 1,307 - 1,511 Duration of disease, mean, years 7 8 8 5 8 7 8 7 Concomitant corticosteroid use 23% 52% 40% 42% 37% 55% 42% 42%
Page 17
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Copyright 2026 | Odyssey Therapeutics | All Rights Reserved In search of extraordinary for patients Biomarker, Efficacy, and Safety Assessments 17
Page 18
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved 18 New clinical data presented today • Previously, Odyssey reported results from 49 evaluable patients: 8 treated with 10 mg BID and 41 with 20 mg BID • After the 8 patients treated with 10 mg BID (~70% target coverage) showed strong efficacy, more patients were enrolled at 10 mg BID to evaluate the signal Total of 56 evaluable patients • Clinical efficacy by patient segments and time points: endoscopic severity and symptomatic remission • Blood- and stool-based biomarkers of colonic and systemic inflammation First release today: Key implications Greatest efficacy observed at the dose that maximally inhibits RIPK2 • 20 mg BID phenocopies cytokine inhibition from RIPK2 knockout cells • Consistent benefit across week 12 endpoints and subgroups by endoscopic severity and AT-experience status, with rapid onset of symptomatic remission Dose response in colonic and systemic inflammatory markers consistent with clinical efficacy being driven by OD-001 • Blood- and stool-based biomarkers provide an unbiased measure of clinical effect Favorable tolerability profile with no discontinuations due to OD-001 • In total, 5 patients were not evaluable, all for reasons unrelated to OD-001 (3 discontinued early, 1 relocated, and 1 failed to report study data) • Competitive monotherapy safety profile could enable backbone use in combinations Induction Portion of the OD-001 Phase 2a Trial Is Complete
Page 19
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved hsCRP, mg/L Markers of systemic and local inflammation suggest 20 mg BID inhibits colonic and systemic inflammation Markers of Systemic and Local Inflammation Are Reduced After OD-001 Treatment Notes: * p < 0.05; ** p < 0.01; nominal, unadjusted p values from paired Wilcoxon signed -rank tests comparing baseline and week 12 within each dose group; pati ents with hsCRP > 5 mg/L: 10 mg, baseline n = 9 and week 12 n = 7; 20 mg, baseline n = 24 and week 12 n = 18. 20 mg n varies by sample availability. Analyses across fecal calprotectin, hsCRP, albumin , and neutrophils include one patient who was not efficacy -evaluable at week 12. 19 Baseline Week 12 • 20 mg BID dosing results in reduced fecal calprotectin across treated patients • 20 mg BID results in reduced serum C-reactive protein • 10 mg and 20 mg BID result in increased serum albumin - Serum albumin may increase due to increased hepatic synthesis as systemic inflammation declines and reduced rectal bleeding as the colonic mucosa heals • 20 mg BID reduces neutrophils, a cell type that expresses RIPK2 and is involved in epithelial barrier breakdown in IBD **** Fecal calprotectin, µg/g Albumin, g/L Neutrophil counts (billion cells/L) OD-001 10 mg OD-001 20 mg OD-001 10 mg OD-001 20 mg OD-001 10 mg OD-001 20 mg OD-001 10 mg OD-001 20 mg (n = 15) (n = 39)(n = 15) (n = 42)(n = 15) (n = 40) (n = 15) (n = 42) * **
Page 20
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Disclaimer: Data presented are from ongoing studies, which will not be finalized until database lock. Thus, these data are subject to change prior to release of the CSR. Future results may differ from those shown here. Notes: OD-001 results represent all patients who completed 12 weeks of treatment per protocol (n = 56); histologic-endoscopic mucosal improvement (HEMI) is defined as MES of 0 or 1 and Geboes index score ≤ 3.1. (1) Historic placebo benchmarks are derived from contemporary post-PoC UC studies (2020–2025); benchmark rates and supporting datasets are as follows: clinical remission 10% (average from 11 trials; n = 3,012 total; 820 placebo-treated patients); endoscopic improvement 15% (average from 10 trials; n = 2,920 total; 789 placebo-treated patients); symptomatic remission 18% (average from 5 trials; n = 1,872 total; 517 placebo-treated patients); HEMI 10% (average from 8 trials; n = 2,565 total; 676 placebo-treated patients); clinical response 37% (average from 9 trials; n = 2,633 total; 726 placebo-treated patients). Internal assessment of historic placebo rate is supported by third-party publications assessing placebo rates using individual patient data (J Crohns Colitis 2025;19(10):jjaf191). 20 OD-001 (20 mg), n = 41 Historic placebo (1)OD-001 (10 mg), n = 15 Clinical remission Endoscopic improvement Symptomatic remission Clinical response HEMI 70% 60% 50% 40% 30% 20% 10% 0% % Trial participants Regulatory endpoints Other endpoints Efficacy Across Prespecified Week 12 Endpoints vs. Historic Placebo • Trial met the primary endpoint of change in mMS from baseline in both parts and on a consolidated basis (-2.4, p < 0.001) • Stronger efficacy observed with 20 mg BID
Page 21
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved 10 mg n = 8 25 mg n = 194 50 mg n = 378 Placebo 20 mg n = 19 ABTECT-1 + ABTECT-2OD-001 trial % Trial participants Obefazimod - n = 189 Similar activity between OD-001 doses in patients with moderate disease (MES = 2) Higher Remission Rate With 20 mg BID Dose in Severe Patients (MES = 3) Disclaimer: Cross-trial comparisons are for context only, and no head -to-head study was conducted; differences in study design, patient populations, and other factors should be considered when interpreting results. OD -001 and a comparator have not been approved and may never be approved by any regulatory authority. Source: Obefazimod ECCO 2026 presentation (P0952). 21 Dose-dependent activity in patients with severe disease (MES = 3) • Greater barrier disruption may increase microbial exposure, requiring greater RIPK2 inhibition for efficacy • Clinical remission rates in patients with moderate endoscopic disease are comparable at both doses 10 mg n = 7 25 mg n = 125 50 mg n = 258 Placebo 20 mg n = 22 ABTECT-1 + ABTECT-2OD-001 trial 43% 36% 9% 30% 31% 0% 16% 1% 9% 14% % Trial participants Obefazimod - n = 128
Page 22
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved 3% 23% 1% 12% 5% 11% 1% 24% 11% 29% 3% 31% 8% 24% 7% 37% 0% 10% 20% 30% 40% 50% Clinical Remission Rate at 20 mg BID Is Similar in AT-Naïve and AT-Experienced Patients Disclaimer: Cross-trial comparisons are for context only, and no head -to-head study was conducted; differences in study design, patient populations, and other factors should be considered when interpreting results. OD -001 and a comparator have not been approved and may never be approved by any regulatory authority. Notes: (1) Historic placebo benchmarks are derived from contemporary post -PoC UC studies (2020–2025) and Rinvoq phase 3 studies; dataset represents 1,819 AT -naïve and 1,475 AT-experienced patients treated with active agent or placebo. 22 Obefazimod (Ph3, ABTECT -1) Obefazimod (Ph3, ABTECT -2) Rinvoq (Ph3, consolidated) Historic placebo (1) OD -001 (20 mg) Placebo group Treatment group Obefazimod (Ph3, ABTECT -1) Obefazimod (Ph3, ABTECT -2) Rinvoq (Ph3, consolidated) Historic placebo (1) OD -001 (20 mg) Advanced therapy experienced (n = 13)Advanced therapy naïve (n = 28) • Existing therapies often show reduced activity in AT-experienced patients, whereas OD-001 shows similar activity in both populations % of patients in clinical remission
Page 23
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved OD-001 Is Competitive With Other Oral Agents on Early Symptomatic Remission, With Increases Through Week 12 23 100 mg QD 200 mg QD Placebo 400 mg QD 25 mg QD 50 mg QDPlacebo Icotrokinra (IL-23)OD-001 (20 mg BID) Obefazimod (miR-124) n=41n=33(1) n=41 n=40 Notes: (1) Part 2 patients were randomized 1:4 to either 10 mg BID for the first two weeks followed by escalation to 20 mg BI D for weeks 3–12, or 20 mg BID from week 1 through week 12. This staggered dosing design accounts for the difference in n at the week 2 time point. Sources: Obefazimod ECCO 2026 presentation (P0923); Icotrokinra UEG Week 2025 presentation (OP206). Proportion in symptomatic remission (%) Proportion in symptomatic remission (%) Patients achieving symptomatic remission (%)
Page 24
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved OD-001 Is Safe and Well Tolerated Across Doses Part 1 Part 2 10 mg BID, n = 16 Group 1 10 then 20 mg BID, n = 9 Group 2 20 mg BID, n = 36 Total n = 45 Total number of TEAEs 11 20 20 40 Severe (grade ≥ 3) TEAE 1 (anemia) (1) 0 0 0 Drug-related TEAE 0 0 3 3 Liver function abnormality identified as a TEAE 0 0 0 0 Drug-related TEAEs leading to trial drug discontinuation 0 0 0 0 SAE 0 0 0 0 TEAEs of special interest: Elevated body temperature that meets specific criteria 0 0 0 0 Elevated hsCRP that meets specific criteria 0 0 0 0 Serious infection 0 0 0 0 Drug-related TEAEs: Fever 0 0 2 2 Headache 0 0 1 1 Disclaimer: Data presented are from ongoing studies, which will not be finalized until database lock. Thus, these data are su bject to change prior to release of the CSR. Future results may differ from those shown here. Notes: One participant in Part 1 and three participants in Part 2 discontinued treatment for reasons unrelated to the trial d rug. One participant in Part 2 was not evaluable for efficacy. Total of 56 patients between Part 1 and Part 2 completed 12 weeks of induction treatment per protocol. (1) Patient had medical history of anemia with mild anemia at time of enrollment; OD-001 treatment was not discontinued and grade 3 anemia resolved with iron supplementation; TEAE was deemed not related to OD-001 treatment. hsCRP = high-sensitivity C-reactive protein. 24
Page 25
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Summary and Conclusions 25 OD-001 20 mg BID has a competitive efficacy profile vs. approved or leading investigational therapies • 27% absolute clinical remission rate with rapid onset of symptomatic benefit • Efficacy across patient subgroups (e.g., AT experience and endoscopic severity) supports potential for broad use Strong correlation between clinical efficacy and biomarkers supports OD-001 therapeutic conclusions • Greater reductions in colonic and systemic inflammatory markers observed at 20 mg BID, the dose projected to maximally inhibit RIPK2 • Objective endpoints (endoscopy and biomarkers) are concordant and align with symptomatic benefit Oral profile with favorable monotherapy safety and tolerability • No SAEs and no discontinuations due to OD-001 at either dose • Well-tolerated oral profile meets patient and prescriber preferences and can potentially enable a broad number of combinations
Page 26
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Copyright 2026 | Odyssey Therapeutics | All Rights Reserved In search of extraordinary for patients Transcriptomic Analyses 26
Page 27
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved • Initial analyses conducted to support target engagement/mechanism of action and to support clinical efficacy endpoints - Biopsy timing is not uniform, so analyses reflect sustained treatment-associated biology vs. immediate drug concentration-dependent effects - Patient-level analyses ongoing to inform potential patient selection/stratification strategy Transcriptomic Analysis of Mucosal Biopsies From Baseline and Week 12 27 OVERVIEW OF MUCOSAL BIOPSY ASSESSMENTS Unbiased assessment of ~20,000 genes across the whole transcriptome to probe mechanism of action Identification of OD-001-specific effects and comparison to public datasets Correlation between clinical outcome, histology, and biomarkers with transcriptional response • Transcriptional response identified decreases in RIPK2-responsive genes, genes encoding inflammatory cytokines, and gene signatures of specific T cell subsets and fibrosis • Increased expression of genes associated with epithelial homeostasis and mucosal healing • Patients with clinical remission or response show concordant improvement across biomarkers and reductions in inflammatory and fibrotic transcriptional profiles • Transcriptional response to OD-001 overlaps with response to anti-IL-23 antibodies (consistent with RIPK2 inhibition significantly controlling IL-23-based inflammatory signaling) • OD-001 treatment reduces inflammatory AP-1 gene transcription that is implicated in IBD, an effect not observed in response to approved therapies
Page 28
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved OD-001 reduces RIPK2 and microbial signatures OD-001 reduces cytokine expression and signaling OD-001 reduces T cell activity OD-001 reduces fibrotic signaling and increases epithelial homeostasis signaling OD-001 Reduces Inflammatory and Fibrotic Gene Expression in IBD • Transcriptomic analysis on mucosal biopsies from patients treated with 20 mg BID (n = 40) at baseline and week 12 were compared to detect differentially expressed genes - Colored dots represent differentially regulated genes with ≥ 1.5-fold change and nominal p < 0.05 • Gene set enrichment analysis was performed on the set of differentially regulated genes to identify biological processes changed following OD-001 treatment • RIPK2-regulated genes, cytokines, T cell signaling, and fibrosis gene pathways were downregulated after treatment • Gene signatures of mucosal healing were upregulated after treatment Notes: DESeq2 volcano plot of week 12–baseline change in the 20 mg cohort (n = 40 paired mucosal samples); two additional samples fail ed RNA-seq QC. Pathway enrichment used hypergeometric testing with FDR adjustment; (1) p values reflect week 12 vs. baseline for only responder/remitter patients (n = 25); all other comparisons are week 12 vs. baseline fo r the full cohort, including one patient not evaluable for efficacy (n = 40); gene sets from MSigDB: Reactome Antimicrobial Peptides, PID AP-1 pathway, PID IL-23 pathway, Hallmark TNF/NF-κB; Internal: RIPK2 Pathway, cited studies: TL1A, Th17, Th1, Inflammatory Fibroblasts, Penetrating Fibrosis, Epithelial Homeos tasis. Sources: Cell Syst 2015;1(6):417–425; Am J Gastroenterol 2011;106(7):1272 –1280; J Leukoc Biol 2017;101(3):727–737; Nat Genet 2025;57(7):1742–1753; Gut 2022;71(7):1289–1301; Sci Rep 2021;11(1):9010. 28 Gene set Effect padj RIPK2 signaling 9E-12 Innate host defense response 9E-5 AP-1 6E-4 p value (-log10) p = 0.05 Gene set Effect padj IL-23 signaling 1E-7 TNF/NF-kB signaling 1E-8 TL1A signaling 7E-4 Gene set Effect padj Th17 signaling 6E-26 Th1 signaling (1) 7E-9 Gene set Effect padj Inflammatory fibroblasts 2E-4 Penetrating fibrosis (1) 7E-3 Epithelial homeostasis 2E-10 log2 fold change (week 12 – baseline) Downregulated Upregulated
Page 29
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Reductions in RIPK2 Gene Signature and Cytokine Gene Responses Following OD-001 Treatment Track With Clinical Outcomes Notes: GSVA scores were calculated for prespecified RIPK2 gene signature (internal), TL1A -Th17 gene signature (J Leukoc Biol 2017;101(3):727-737), PID IL-23, and Hallmark TNFα/NF-κB gene sets from MSigDB. Nominal, unadjusted p values are from paired Wilcoxon signed-rank tests. Analysis includes n = 39 paired baseline/week 12 samples from the 20 mg coh ort; one patient was not efficacy-evaluable and two non-responder samples failed RNA-seq QC. Clinical remission: mMS ≤ 2, SFS ≤ 1, RBS = 0, and MES ≤ 1 at week 12. Clinical response: ≥ 2 -point and > 30% decrease in mMS, with either ≥ 1-point decrease in RBS or absolute RBS 0 or 1 at week 12. * p < 0.05; ** p < 0.01. Source: Cell Syst 2015;1(6):417–425. 29 Baseline 12 weeks RIPK2 IL-23 TNF Clinical remission (n = 11) No response (n = 14) Clinical response (n = 14) Clinical remission (n = 11) No response (n = 14) Clinical response (n = 14) Clinical remission (n = 11) No response (n = 14) Clinical response (n = 14) ** * ** RIPK2 gene signature, GSVA IL-23 signaling, GSVA TNF/NF-kB signaling, GSVA TL1A Clinical remission (n = 11) No response (n = 14) Clinical response (n = 14) * TL1A signaling, GSVA
Page 30
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Baseline 12 weeks Reduction in T Effector Activation Signatures Following OD-001 Treatment Notes: GSVA scores were calculated for prespecified Th17 - and Th1-associated gene sets derived from the ACT1 infliximab mucosal transcriptomic analysis. Nominal, unadjusted p values are from paired Wilcoxon signed -rank tests. Analysis includes n = 39 paired baseline/week 12 samples from the 20 mg cohort; one patient was not efficacy -evaluable and two non-responder samples failed RNA-seq QC. Clinical remission: mMS ≤ 2, SFS ≤ 1, RBS = 0, and MES ≤ 1 at week 12. Clinical response: ≥ 2-point and > 30% decrease in mMS, with either ≥ 1-point decrease in RBS or absolute RBS 0 or 1 at week 12; ** p < 0.01. Source: Am J Gastroenterol 2011;106(7):1 272–1280. 30 Th17 gene signature (RORγ+ T cell subset) Th1 gene signature (T-bet+ T cell subset) Clinical remission (n = 11) No response (n = 14) Clinical response (n = 14) Clinical remission (n = 11) No response (n = 14) Clinical response (n = 14) ** ** Th17-associated genes, GSVA Th1-associated genes, GSVA
Page 31
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved OD-001 Modulates a Distinct Set of Inflammatory Genes Not Addressed With Existing Therapies Notes: Endoscopic responders only. Downregulation: fold -change < 0, FDR q < 0.05. OD-001, n = 13 (20 mg); infliximab, n = 8; vedolizumab, n = 12. Response was MES 0 or 1 at week 12, weeks 4 -6, and week 52, respectively. PID AP-1 genes were from MSigDB; enrichment used hypergeometric testing with FDR adjustment. IEG = immediate early genes. Sources: Gut 2018;67(1):43–52; J Biol Chem 1999;274:33684–33690. OD-001 blocks direct activation of the MAPK pathway from gut bacteria, addressing redundancy missed by existing anti-cytokine therapies AP-1 signature downregulation similar to OD-001 is not observed in published anti-TNF and anti-integrin datasets Fold change (mean, response time point – baseline) 31 2E-8 1E-4 0.79 1 0.88 1 p padj p padj p padj OD -001 Infliximab Vedolizumab • Comparison of OD-001 responders with responder cohorts from competitor datasets suggests OD-001 effects are not attributable to general mucosal improvement AP-1 subunits AP-1/ IEG targets AP-1-related genes are increased in inflamed tissue across IBD, rheumatoid arthritis, psoriasis, multiple sclerosis, and asthma patients Gut bacteria NOD1/2 RIPK2 MAPK TNF, TL1A, IL-23 AP-1 Anti-cytokine (e.g., infliximab) OD-001 Circulating T cells Activated T cells in gut Tissue damage a4b7 inhibitor (e.g., vedolizumab)OD-001
Page 32
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Reduction in Fibrosis-Related Genes and Upregulation of Genes Associated With Healing Align With Clinical Outcomes Notes: GSVA scores were calculated for prespecified Inflammatory Fibroblast, Penetrating Fibrosis, and Epithelial Homeostasis gene sets. Inflammatory Fibroblast was an internal set informed by Nat Genet 2025;57(7):1742 –1753; Penetrating Fibrosis was derived from Gut 2022;71(7):1289 –1301; Epithelial Homeostasis used the UC100 gene set downregulated in UC from Sci Rep 2021;11(1):9010. Nominal, unadjusted p values are from paired Wilcoxon signed -rank tests. Analysis includes n = 39 paired baseline/week 12 samples from the 20 mg cohort; one patient was not efficacy -evaluable and two non-responder samples failed RNA-seq QC. Clinical remission: mMS ≤ 2, SFS ≤ 1, RBS = 0, and MES ≤ 1 at week 12. Clinical response: ≥ 2-point and > 30% decrease in mMS, with either ≥ 1-point decrease in RBS or absolute RBS 0 or 1 at week 12. * p < 0.05; ** p < 0.01. Sources: Nat Genet 2025;57(7):1742–1753; Gut 2022;71(7):1289–1301; Sci Rep 2021;11(1):9010. 32 Inflammatory fibroblast Penetrating fibrosis Epithelial homeostasis Clinical remission (n = 11) No response (n = 14) Clinical response (n = 14) Clinical remission (n = 11) No response (n = 14) Clinical response (n = 14) Clinical remission (n = 11) No response (n = 14) Clinical response (n = 14) ** ** ** Inflammatory fibrosis specific, GSVA Penetrating fibrosis signature, GSVA Epithelial homeostasis, GSVA * Baseline 12 weeks
Page 33
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Depth of Reduction in the Penetrating Fibrosis Signature May Differentiate Responders From Effective Treatments Versus Placebo Notes: GSVA scores were calculated using the prespecified Penetrating Fibrosis Signature from Gut 2022;71(7):1289 –1301. Nominal, unadjusted p values are from paired Wilcoxon signed -rank tests. OD-001 analysis includes n = 39 paired baseline/week 12 samples from the 20 mg cohort; one patient was not efficacy -evaluable and two non-responder samples failed RNA-seq QC. Golimumab (n = 42) and placebo (n = 23) mucosal samples were profiled by microarray at screening and week 6; end of induction therefore represents week 12 for OD -001 and week 6 for golimumab/placebo. OD-001 clinical response includes n = 25 responders/remitters. OD-001 clinical remission: mMS ≤ 2, SFS ≤ 1, RBS = 0, and MES ≤ 1 at week 12. OD-001 clinical response: ≥ 2-point and > 30% decrease in mMS, with either ≥ 1-point decrease in RBS or absolute RBS 0 or 1 at week 12. Cross -study comparisons are exploratory and subject to differences in population, response definitions, timing, platform, and sample size. *** p < 0.001. Sources: Gut 2022;71(7):1289 –1301; Gastroenterology 2014;146(1):8 5–95. 33 Golimumab Placebo OD-001 No response (n = 18) Clinical response (n = 24) No response (n = 15) Clinical response (n = 8) No response (n = 14) Clinical response (n = 25) *** ** *** Penetrating fibrosis signature, GSVA Penetrating fibrosis signature, GSVA Penetrating fibrosis signature, GSVA Baseline End of induction *** Penetrating fibrosis signature, GSVA Penetrating fibrosis signature, GSVA Penetrating fibrosis signature, GSVA
Page 34
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Transcriptomic Changes, Histology, and Fecal Calprotectin Show Concordant Effects in Clinical Remitters Notes: Values were standardized by dividing by the standard deviation; clinical remission, n = 11; no response, n = 14; clini cal remission: mMS ≤ 2 (SFS ≤ 1, RBS = 0, MES ≤ 1) at week 12; one patient treated with 20 mg OD -001 was not evaluable for efficacy and two non-responder patient samples failed QC on RNA-seq and are not included in the analysis. 34 RIPK2 signaling Penetrating fibrosis signature Inflammatory fibrosis signature Geboes score Fecal calprotectin Clinical remission No response Week 12 – baseline, standardized score Pro-inflammatory signaling Fibrotic remodeling Histologic disease activity Mucosal inflammation No change relative to baseline 2 1 2 1 Th17 signaling Patient 1 (AT - experienced) Histologic response Patient 2 (AT - experienced) Histologic - endoscopic mucosal improvement (HEMI)
Page 35
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Differential Expression of Genes Following OD-001 Treatment Correlates With Efficacy Measures and Overlaps With the Response to Anti-IL-23 Notes: OD-001 analysis includes n = 40 paired baseline/week 12 mucosal samples from the full 20 mg cohort. Partial Pearson corre lations assessed gene-expression changes versus Geboes, mMS, and MES, adjusting for baseline value, age, sex, and study site. Positive correlations indicate genes that decrease as disease improves; negative correlations indic ate genes that increase. Dashed line denotes FDR q = 0.10. Two samples failed RNA -seq QC. Mirikizumab data are published summary-level associations with mMS, RHI, and UCEIS. RHI = Robarts Histopathology Index; UCEIS = UC Endoscopic Index of Severity. Source: Clin Transl Gastroenterol 2023;14(7):e00578. 35 Genes most highly correlated with efficacy measures include IL-1β, IL-23, and IL-17, all of which are associated with inflammation Mirikizumab Pearson correlation of published correlations of mirikizumab-regulated genes with disease activity scores -log10 (q-value of correlation coefficient) Correlation coefficient -0.4 -0.3 -0.2 -0.1 0 0.1 0.2 0.3 0.4 0.5 0 1 2 3 4 5 6 7 8 REG1P REG3A PI3 IL1B IGHD2-2 MMP3 S100A8 △ mMS △ RHI score △ UCEIS total score DUOXA2 IGKV2D-40 SLC6A14 MMP1 REG1B DMBT1 AQP8 ABCG2 GUCA2A HMGCS2 TMIGD1 SLC26A2 LOC101928405 OD-001 Pearson correlation of baseline-to-week 12 transcript changes with disease activity scores; selected high-ranking IBD inflammatory/myeloid and epithelial genes are labeled ABCG2 ABCB1 AQP8 SLC26A2 TMIGD1 GUCA2A HMGCS2 -log10 (q-value of correlation coefficient) Correlation coefficient IL1B REG1B PI3 DMBT1 REG3A MMP3 DUOXA2 IGKV2D-40 S100A8 SLC6A14 CXCL8 IL23A CSF2 IL17A OSM TREM1 MMP1 CXCL6△ mMS △ Geboes score △ MES
Page 36
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Patient-Level Analyses of Transcriptional Changes With OD-001 Compared With Publicly Available Datasets Sources: Cell 2019;178(3):714–730; Gut 2018;67(1):43–52; Clin Transl Gastroenterol 2023;14(7):e00578. 36 • Three public UC transcriptomic datasets were identified that included patient-level data suitable for direct responder-based comparisons with OD-001 • OD-001 downregulates a majority of a published 34-gene mucosal signature that is associated with poor response to anti-TNF therapy, providing mechanistic support for the clinical activity observed in AT- experienced patients • Patient-level data for a TNF inhibitor (infliximab) and an a4b7 inhibitor (vedolizumab) enable evaluation of similarities and differences in mucosal effects between OD-001 and two distinct approved mechanisms • Effects of mirikizumab, an approved IL-23 inhibitor, have been presented in summary form, with effects comparable to OD-001, but patient-level data similar to the vedolizumab and infliximab datasets are not publicly available
Page 37
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Biological Processes Modulated in Responders to OD-001 Are Similar to Other Effective Treatments 37 COMPARISON KEY BIOLOGY IMPLICATION Shared among all therapies OD-001, infliximab, vedolizumab ↓ Inflammatory monocytes ↓ TNF / NF-κB, Th17, and IL-6 signaling ↑ Epithelial homeostasis Common features associated with effective UC therapies Shared with infliximab OD-001 + infliximab ↓ Inflammatory cytokine programs ↓ IL-23 / Th17 pathway activity Downregulation of inflammatory cytokines is due to OD-001 rather than reduced disease process Shared with vedolizumab OD-001 + vedolizumab ↓ Fibrosis / collagen remodeling pathways Downregulation of fibrosis genes reflects OD-001 effects independent of TNF inhibition Mechanism-specific overlap with infliximab or vedolizumab responders that is absent in responders to the other agent suggests a drug effect of OD-001 beyond general mucosal improvements expected with a placebo response
Page 38
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Copyright 2026 | Odyssey Therapeutics | All Rights Reserved In search of extraordinary for patients Concluding Remarks 38
Page 39
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Summary of Key Findings • Phase 2a trial provides clinical proof of concept for a first-in-class oral therapy targeting RIPK2 with a compelling efficacy and safety profile - Biomarkers and transcriptomics link RIPK2 scaffolding inhibition with clinical efficacy • Efficacy, biomarker, and transcriptomic data support 20 mg BID as projected therapeutic dose - Differences observed in inflammatory biomarkers by dose support therapeutic effect • Similar clinical remission rates irrespective of AT experience at the 20 mg BID dose • Symptomatic remission as early as week 2 with increased remission rate through week 12 of induction therapy • No serious infections and no discontinuations due to TEAEs - Profile could position OD-001 as a backbone for combinations and long-term oral maintenance therapy • Transcriptomic analyses show decreases across multiple independent and objective measures of inflammation and fibrosis - Differences between the transcriptional response following OD-001 vs. vedolizumab are consistent with complementary therapeutic mechanisms and the potential for additive or synergistic effects of both drugs in combination 39
Page 40
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Next Steps for OD-001 • Advance OD-001 in parallel as a monotherapy and in combination for ulcerative colitis • Establish OD-001 in ulcerative colitis before expanding into Crohn’s disease or other inflammatory indications (e.g., spondyloarthritis, a common comorbidity in IBD) • Placebo-controlled monotherapy and active-controlled combination induction readouts remain on track for H2 2027 40 Phase 2a combination trial with vedolizumab Phase 2b monotherapy trial • Orthogonal combination designed to address upstream activation and downstream immune cell trafficking to the gut • Randomized, double-blind trial will assess the efficacy and safety of combination induction vs. vedolizumab plus placebo • After induction, all patients enter OD-001 monotherapy maintenance (results expected in 2028) • Trial design was presented at ACG 2026 (October) • Designed to support advancement into phase 3 trials • Phase 2b will be a randomized, double-blind trial testing multiple OD-001 doses versus placebo • Further trial design details to be disclosed in the future
Page 41
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Upcoming Milestones for Lead Programs Through 2028 41 • In addition to advancing RIPK2, Odyssey expects to file a CTA for OD-002, an SLC15A4 inhibitor, in H2 2026, with phase 1/2a trial initiation expected in H1 2027 - Phase 1 healthy-volunteer trial will use a validated ex vivo stimulation assay that has translated to efficacy with TLR7/8 antagonists - Phase 2 trial will enroll patients with multiple inflammatory diseases, including one cohort of cutaneous lupus patients • OD-003, a TNFR2 agonist, is currently in IND-enabling studies with projected completion in Q1 2027 2026 2027 2028 H2 H1 H2 H1 H2 OD-001 Ph2b monotherapy trial initiation OD-002 File CTA OD-002 Initiate healthy participant dosing in Ph1/2 trial OD-002 Ph1 results, including ex vivo stimulation assay OD-002 Ph2a readouts in multiple indications OD-001 First maintenance readout OD-001 Ph2a vedolizumab combo trial initiation OD-001 Ph2b monotherapy induction readout OD-001 Ph2a vedolizumab combo induction readout OD-003 IND-enabling study completion
Page 42
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Copyright 2026 | Odyssey Therapeutics | All Rights Reserved In search of extraordinary for patients Appendix 42
Page 43
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Efficacy Analysis of Complete 10 mg BID Cohort 43 May 2026 (n = 8) October 2026 (n = 15) Clinical remission Endoscopic improvement Symptomatic remission Clinical response HEMI 25% 20% 38% 33% 38% 27% 38% 27% 63% 40% 70% 60% 50% 40% 30% 20% 10% 0% % Trial participants • Among the seven additional evaluable patients, one reached clinical remission, one had endoscopic improvement, and five had no response - All additional patients were enrolled at existing phase 2a clinical trial sites and were naïve to advanced therapy
Page 44
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved Notes: Meta-analysis included 12 approved, 2 discontinued, and 9 in-development UC therapies across 38 trials; placebo benchmarks were derived from contemporary post-PoC UC studies (2020–2025) to account for time-dependent placebo effects; endpoint availability among post-PoC trials (11 trials; n = 3,012): clinical remission reported in 11/11 trials; endoscopic improvement reported in 10/11 trials; symptomatic remission reported in 5/11 trials; HEMI reported in 8/11 trials; clinical response reported in 9/11 trials; for comparability, placebo rates were also calculated using the full contemporary dataset (21 trials; n = 9,776), yielding a clinical remission rate of 10%, endoscopic improvement rate of 14%, and clinical response rate of 35%; internal assessment of historic placebo rate is supported by third-party publications assessing placebo rates using individual patient data (J Crohns Colitis 2025;19(10):jjaf191). Historic Placebo Rates Derived From UC Trial Meta-Analysis 44 EMA co-primary endpoints FDA endpoint 38 Phase 2 and 3 trials 2005–2025 data readouts n = 14,881 11 Phase 2/3 trials Total = 3,012, placebo group = 820 Clinical remission = 10% 9 Phase 2/3 trials Total = 2,633, placebo group = 726 Clinical response = 37% Symptomatic remission = 18% Endoscopic improvement = 15% 5 Phase 2/3 trials Total = 1,872, placebo group = 517 10 Phase 2/3 trials Total = 2,920, placebo group = 789 11 Phase 2 and 3 trials 2020–2025 readouts n = 3,012 AVERAGE HISTORIC PLACEBO 21 Phase 2 and 3 trials 2020–2025 data readouts n = 9,776 Includes approved, in development, and discontinued drugs Includes only contemporary post-PoC drugs (not approved) Includes only trials since 2020 8 Phase 2/3 trials Total = 2,565, placebo group = 676 HEMI = 10%
Page 45
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved … stool frequency also showed rapid reduction, but rate of improvement appears slower Patients with clinical response showed rapid reductions in rectal bleeding, similar to patients with clinical remission… Clinical Responders at 12 Weeks May Benefit From Continued Treatment 45 Rectal bleeding score by clinical remission (orange) or clinical response (teal) Stool frequency score by clinical remission (orange) or clinical response (teal) Clinical remission n = 14 Clinical response n = 17 Clinical remission n = 14 Clinical response n = 17 Average rectal bleeding score Average stool frequency score
Page 46
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved OD-001 Treatment Downregulates Genes Associated With Poor Response to Anti-TNF Therapy • A published 34-gene mucosal signature that is predictive at baseline for patients with non-response to anti-TNF therapy • OD-001 treatment significantly downregulated 29 of these 34 genes in clinical responders and remitters (n = 25) • The mucosal signature includes multiple genes linked to myeloid and neutrophil biology, providing mechanistic link to NOD1/2–RIPK2 biology and RIPK2 inhibition Notes: Volcano plot shows week 12–baseline log2 fold change and nominal significance, calculated with DESeq2 for n = 25 responde r/remitter patients. Anti-TNF resistance-associated baseline gene signature: 34 selected genes previously associated with higher pretreatment mucosal expression in anti -TNF non-responders in UC (Cell 2019;178(3):714–730). One patient treated with 20 mg OD-001 is not evaluable for efficacy and two non-responder patient samples failed QC on RNA-seq and are not included in the analysis. Clinical remission: mMS ≤ 2, SFS ≤ 1, RBS = 0, and MES ≤ 1 at week 12. Clinical response: ≥ 2 -point and > 30% decrease in mMS, with either ≥ 1-point decrease in RBS or absolute RBS 0 or 1 at week 12. 46 FCGR3A FCGR3B OSM TREM1 FPR1 S100A8 IL6 CXCL6 FCGR2A p value (-log10) log2 fold change (week 12 – baseline) p = 0.05
Page 47
In search of extraordinary for patientsCopyright 2026 | Odyssey Therapeutics | All Rights Reserved OD-001 responders show concordant mucosal gene changes with infliximab or vedolizumab responders Transcriptional Response to OD-001 Overlaps With Gene Changes From Approved Anti-TNF or Anti-⍺4β7 Therapies 47 Notes: Volcano plot shows week 12–baseline log2 fold change and nominal significance, calculated with DESeq2 for n = 25 responde r/remitter patients. Blue and red points identify top 20 genes decreasing and increasing in responders to infliximab and vedolizumab. Shared genes are labeled. One patient treated with 20 mg OD -001 is not evaluable for efficacy and two non-responder patient samples failed QC on RNA-seq and are not included in the analysis. Non -responders to all three agents show no-to-minimal changes. Clinical remission: mMS ≤ 2 (SFS ≤ 1, RBS = 0, MES ≤ 1) at week 12. Clinical response: decrease in mMS ≥ 2 and > 30% reduction and either a decrease in RBS ≥ 1 point or an absolute RBS = 0 or 1. Sources: Gut 2018;67(1):43–52. log2 fold change (week 12 – baseline) AQP8 PCK1 CDHR1 DUOXA2 C4BPA TNIP3 IDO1 CHI3L1 S100A8 MMP3 SERPINB3 p value (-log10) PADI2 HMGCS2 log2 fold change (week 12 – baseline) p value (-log10) DUOXA2 IDO1 MMP3 C4BPA TNIP3 SERPINB3 CHI3L1 S100A8 AQP8 PADI2 HMGCS2 CDHR1 TCN1 TCN1 KYNU MMP7 KYNU MMP7 ANXA1 ANXA1 VSIG1 VSIG1 SLC26A2 TRPM6 SLC26A2 TRPM6 PCK1 CAPN13 CAPN13 NTRK2NTRK2 GLRA2 GLRA2 SLC13A2 SLC13A2 CWH43 CWH43 ACSF2 ACSF2 Infliximab Vedolizumab Upregulated in comparator dataset Downregulated in comparator dataset OD-001-responder dataset