Immunic, Inc. · NASDAQ:IMUX
Immunic — EFMC-ACSMEDI MedChem Frontiers 2026
18 slides from Immunic's conference presentation, Jun 25, 2026
Slide 1: Discovery of IMU-856, a Selective Sirtuin 6 Modulator
Discovery of IMU-856, a Selective Sirtuin 6 Modulator with Novel Binding Characteristics for Gastrointestinal Disease Treatment Dr. Christian Gege NASDAQ: IMUX | June/25/2026 | EFMC-ACSMEDI MedChem Frontiers 2026 - Dublin
Slide 2: Cautionary Note Regarding Forward-Looking Statements
Cautionary Note Regarding Forward-Looking Statements This presentation contains “forward-looking statements” that involve substantial risks and uncertainties for purposes of the safe harbor within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities
Slide 3: SIRT6 Modulation – Rationale for Gut Barrier Therapeutics
SIRT6 Modulation – Rationale for Gut Barrier Therapeutics Sirtuins are NAD⁺-dependent enzymes regulating histone and non-histone protein modification SIRT6 controls transcription, genome stability, inflammation, metabolism and epithelial homeostasis through deacetylase/deacylase and ADP-ribosyltrans
Slide 4: Hit Identification Strategy for SIRT6 Modulators
Hit Identification Strategy for SIRT6 Modulators Broad screening via HTS campaign of ~500000 compounds from the in-house library of Daiichi Sankyo § Thermal shift assay (TSA) used as primary screen § Goal: identify compounds that bind and stabilize human SIRT6 Functional validation § AlphaLISA-based
Slide 5: Hit Characterization
Hit Characterization TSA Tm (dTm) [degC] 62,2 70 (19.5) 60 43,4 50 (0.7) 42,7 40 30 § TSA: addition of NAD+ resulted in a substantially more pronounced 20 thermal shift (19.5°C) 10 § Deacetylase activity assay (AlphaLISA): 0 100 uM 100 uM IC50 = 37 nM for SIRT6 DMSO 1 1 +NAD 250uM § Surface plasmon
Slide 6: Hit Optimization I
Hit Optimization I [1] à Thioether replacement and increased sp³ character retained SIRT6 potency while improving key developability properties: microsomal stability, free fraction and permeability [1] WO2019/054430 (Daiichi Sankyo) 6 | © Immunic, Inc. | June/25/2026
Slide 7: Hit Optimization II
Hit Optimization II § 2 → 3: Amide-to-pyrazole exchange rigidified the linker and boosted SIRT6 potency § 3 → IMU-856: Spiro-oxetane introduction lowered basicity, improving clearance and oral exposure à MedChem optimization balanced potency and developability through thioether replacement, increase
Slide 8: Synthesis – MedChem Route
Synthesis – MedChem Route § The IMU-856 route uses a convergent synthesis strategy, preparing three key building blocks that are assembled through triazole-core formation and late-stage pyrazole construction[2] § Stable epoxyaldehyde 5f served as a key intermediate, enabling efficient pyrazole forma
Slide 9: Binding Characteristics (X-ray)
Binding Characteristics (X-ray) § X-ray structure confirmed NAD⁺-dependent SIRT6 target engagement § IMU-856 forms a covalent ADP-ribose conjugate in the active site § The adduct spans the NAD⁺ and substrate-binding pockets, explaining tight binding and stabilization à The X-ray structure supports a
Slide 10: SIRT6 Selectivity
SIRT6 Selectivity § IMU-856 potently inhibits SIRT6 across species while sparing other human sirtuins, with no meaningful inhibition of SIRT1/2/3/5/7 at 1 µM § Selectivity extends beyond the sirtuin family, with no inhibition of HDAC1-9 and -11, or nuclear extract at 1 µM, supporting a differentiate
Slide 11: In vitro Pharmacology Profiling
In vitro Pharmacology Profiling § Favorable ADME profile: high metabolic stability, high Caco-2 permeability, and minimal efflux § Clean safety pharmacology: no CEREP off-target hits and no hERG inhibition up to 10 µM § Low DDI/genotox risk: weak CYP/transporter liability and negative Ames/micronucl
Slide 12: Pharmacokinetic Properties
Pharmacokinetic Properties § Low-to-moderate clearance and sustained half-lives across species support durable systemic exposure § Oral dosing achieved quantifiable exposure with moderate-to-high bioavailability across mouse, rat, dog, and cynomolgus monkey à Cross-species PK supports sustained oral
Slide 13: In vivo Efficacy in Chronic Murine DSS-Induced Colitis Models
In vivo Efficacy in Chronic Murine DSS-Induced Colitis Models § Oral IMU-856 reduced DSS-induced colitis severity, preserving colon length in acute and chronic mouse models § Dose-dependent efficacy was observed during injury and recovery phases, supporting effects on mucosal protection and regenera
Slide 14: Celiac Disease is a Major Public Health Problem Worldwide
Celiac Disease is a Major Public Health Problem Worldwide § ~1% prevalence; major global health burden § Rising incidence and substantial underdiagnosis worldwide § Many patients symptomatic despite gluten-free diet § Gluten-free diet insufficient and difficult to maintain § No approved drug therapi
Slide 15: Clinical Phase 1 Results
Clinical Phase 1 Results § Proof-of-concept Phase 1b study in celiac disease patients (80/160 mg once-daily) looking for histological changes, blood biomarkers, nutrient uptake and patient-reported symptoms à well-tolerated, dose-linear PK and steady-state trough levels achieved within first week of
Slide 16: Summary and Outlook
Summary and Outlook § IMU-856: first-in-class, orally available SIRT6 modulator with a novel binding mode driving epithelial regeneration and barrier restoration IMU-856 § Clinical PoC in Phase 1b (celiac disease): improvements observed in villous structure, symptoms, biomarkers and nutrient absorpt
Slide 17: Acknowledgements
Acknowledgements Martina Wirth Toru Taniguchi (MedChem lead) Juliano Fonseca Nobuya Kurikawa (Pharmacology lead) Evelyn Peelen Osamu Iwamoto Sara Elhag Katsuyoshi Nakajima Andreas Muehler Shinji Tanaka Hella Kohlhof Mizuki Takahashi Daniel Vitt Seiko Nagata Isao Yasumatsu Tomoki Imaoka Eriko Michish
Slide 18: Thank you for your attention!
Thank you for your attention! Immunic, Inc. Immunic AG 1200 Avenue of the Americas Lochhamer Schlag 21 New York City, NY 10036 82166 Gräfelfing (Munich) USA Germany Christian Gege Global Head of Intellectual Property Email: christian.gege@imux.com Immunic Australia Pty. Ltd. Melbourne Web: www.imux.