Helix Biopharma Corp. · TSX:HBP
Helix Biopharma — 16th World ADC London 2026
25 slides from Helix Biopharma's conference presentation, Feb 24, 2026
Slide 1: Next-Generation ADCs: Unlocking the Potential of CEACAM6-Directed Targeted Therapies
Next-Generation ADCs: Unlocking the Potential of CEACAM6-Directed Targeted Therapies Jonathan Davis Director of ADC Discovery, Helix Biopharma 16th World ADC London, 23 February 2026
Slide 2: Disclaimer
Disclaimer This presentation document contains certain forward-looking statements and information (collectively, “forward-looking statements”) within the meaning of applicable securities laws. Forward-looking statements are statements and information that are not historical facts but instead include
Slide 3: De-Risking Biologics Development
De-Risking Biologics Development The biologics pipeline is expensive and risky — most candidates fail. Smart diversification reduces the probability of total failure. Multiple Targets If one antigen is lost or insufficient, a second target provides backup. Bispecific approaches (OR/AND gates) raise
Slide 4: The Target: CEACAM6 (CD66c)
The Target: CEACAM6 (CD66c) A member of the CEACAM family. Interacts with multiple CEACAMs in trans to promote metastasis and suppress the immune system Thomas J, Klebanov A, et al. Genes and Cancer 2023;14:12-26; Cell Membrane https://doi.org/10.18632/genesandcancer.230
Slide 5: Why CEACAM6 Is an Ideal Cancer Target
Onco Targets Ther. 2018;11:3159-3166 https://doi.org/10.2147/OTT.S161807 The Target: CEACAM6 (CD66c) Why CEACAM6 Is an Ideal Cancer Target Osteosarcoma • GPI-anchored IgSF member; V-type – (C-type)2 domain structure patients • Overexpressed in >70% of epithelial malignancies • Higher tumor expressio
Slide 6: CEACAM6 Expression Across Cancer Types
CEACAM6 Expression Across Cancer Types Cancer Type CEACAM6 + Intensity Key Finding Pancreatic (PDAC) >90% Strong Independent prognostic factor Colorectal (CRC) 70-85% Strong Correlates with metastasis Lung (NSCLC) ~50% Moderate-Strong Higher in adenocarcinoma vs SCC Breast 60-75% Moderate-Strong Hig
Slide 7: Immunohistochemistry: CEACAM6 Expression
Immunohistochemistry: CEACAM6 Expression Tumor vs Normal Strong CEACAM6 staining in tumor epithelium with minimal staining in adjacent normal tissue. Membrane and cytoplasmic pattern. Tumor Specificity VHH (AFAIKL2) from llama binds tumor-expressed CEACAM6 preferentially over healthy cell CEACAM6 —
Slide 8: Therapeutic Approaches Targeting CEACAM6
Therapeutic Approaches Targeting CEACAM6 Approach Developer Stage Payload/MOA Efficacy Signal L-DOS47 (ADEPT) Helix BioPharma Phase I/II Urease → pH modulation 41.7% ORR (combo); PFS↑ mono Phase I BAY 1834942 Bayer Anti-CEACAM6 mAb (checkpoint) Terminated Terminated 84-EBET (ADC) Eisai Preclinical B
Slide 9: ADEPT: Antibody-Directed Enzyme Prodrug Therapy
ADEPT: Antibody-Directed Enzyme Prodrug Therapy L-DOS47 — A novel twist on ADC: the drug created on-site The ADC Argument The Checkpoint Argument • Classical ADEPT: Ab delivers enzyme → enzyme activates systemic prodrug • Tumor acidosis is profoundly immunosuppressive • L-DOS47 innovation: the prodr
Slide 10: L-DOS47: Structure and Mechanism
L-DOS47: Structure and Mechanism • Jack Bean Urease is a hexameric enzyme from Jack Beans • Can be isolated and purified from the beans • Production of two NH 3 raises the local pH Conversion of urea to ammonia catalyzed by urease • VHH (AFAIKL2) targeting CEACAM6 fused to Jack Bean urease • SIAB cr
Slide 11: L-DOS47: Preclinical Evidence
How it is done: L-DOS47 INCR L-DOS47: Preclinical Evidence CEST MRI reveals pH increases between 4- In Vitro Cytotoxicity In Vivo Efficacy baseline 72h post-LDOS47 • M Specificity confirmed in 4 cell lines (BxPC-3, A549, MCF7, hu CEACAM6-transfected H23). BxPC-3 (CEACAM6+) was most Intratumoral admi
Slide 12: Clinical Results: L-DOS47 + Pemetrexed/Carboplatin
Clinical Results: L-DOS47 + Pemetrexed/Carboplatin 41.7% 75.0% 187d 0 Objective Clinical Median Duration Dose-Limiting Response Rate Benefit Rate of Response Toxicities Phase I Combination Study (NCT02309892) • 14 patients with Stage IV non-squamous NSCLC; doses 0.59–9.0 μg/kg • Well tolerated: No S
Slide 13: Clinical Results: L-DOS47 Monotherapy (Phase I/II)
Clinical Results: L-DOS47 Monotherapy (Phase I/II) Phase I/II First-in-Human Monotherapy (EudraCT: 2010-020729-42) • Stage IIIB/IV NSCLC patients; Phase I: 3+3 dose escalation (weekly Progression-free Survival dosing); Phase II: twice-weekly • 0.12-13.55 ug/kg for phase I dose escalation, 13.55 ug/k
Slide 14: Clinical Results: L-DOS47 Monotherapy (Phase I/II)
Clinical Results: L-DOS47 Monotherapy (Phase I/II) Phase I/II First-in-Human Monotherapy (EudraCT: 2010-020729-42) • In fact, high ADA was correlated with longer PFS • Why? We are not sure • Suggests that the presence of ADA does not prevent continued efficacy Ramlau et al., Front Oncol 2025 (DOI:10
Slide 15: The Promise of L-DOS47: A Novel "ADC"
The Promise of L-DOS47: A Novel "ADC" Catalytic Payload Unlike stoichiometric ADCs, one enzyme molecule converts thousands of urea molecules per second — amplifying the therapeutic effect far beyond the DAR. No Internalization Needed Works on the cell surface. Avoids resistance mechanisms related to
Slide 16: What Are the Best Ways to Exploit a Clean Target?
What Are the Best Ways to Exploit a Clean Target? Our VHH binds tumor-expressed CEACAM6 preferentially — this cleanliness opens doors to potent killing mechanisms. Direct Cell Killing (The Big 4) Indirect Approaches Fc Effector Functions Death Receptor Activation ADCC, CDC, ADCP via immune cell recr
Slide 17: De-Risking CEACAM6: Multiple Technologies
De-Risking CEACAM6: Multiple Technologies Don't put all hopes into one method — exploit this target through multiple independent technologies. ADEPT / L-DOS47 Radioimmunotherapy Classical ADCs Enzyme delivery → TME pH Radionuclide conjugated Cytotoxic payloads via modulation + immune to anti-CEACAM6
Slide 18: Radioimmunotherapy Approach
Radioimmunotherapy Approach Anti-CEACAM6 VHH–Radionuclide Conjugates • VHH nanobodies (~15 kDa) offer rapid tumor penetration and fast blood clearance — ideal for radiotherapy • Radionuclides deliver DNA-damaging radiation directly to CEACAM6+ cells • Not affected by ABC transporter-mediated drug ef
Slide 19: ADC Strategy: Dual Orthogonal Warheads
ADC Strategy: Dual Orthogonal Warheads Force the tumor to develop two simultaneous resistance systems — making escape exponentially harder. Drug A — Enzymatic Conjugation Drug B — Cysteine Conjugation • Fixed DAR of 2 via sortase/transglutaminase • Higher DAR (4-8) via native or inserted Cys • Site-
Slide 20: Bispecific Antibody Strategies: AND vs OR Gates
Bispecific Antibody Strategies: AND vs OR Gates OR gate: AND gate: Each arm Each arm high low affinity. affinity, one Only binds is enough if avidity to bind. (both X targets Raises present) resistance barrier Raises X specificity Best for REDUCING TOX Best for CLEAN targets
Slide 21: Bispecific Antibodies: Beyond AND/OR Gates
Bispecific Antibodies: Beyond AND/OR Gates OR Gate (Clean Target Advantage) Both arms bind independently to different antigens. Because CEACAM6 is clean, the second target doesn't need to improve specificity — it raises the escape barrier. Tumor must downregulate BOTH antigens to evade the drug. Rap
Slide 22: Risk Assessment: Balancing Innovation and Validation
Risk Assessment: Balancing Innovation and Validation The golden rule: if you choose a novel target or novel format, use well-validated drugs and linkers. Don't multiply risks. Component Validated Options Novel Options Risk When Novel Target CEACAM6 (well-characterized) New epitope / isoform LOW — ex
Slide 23: CEACAM6 Pipeline: De-Risked Through Diversification
CEACAM6 Pipeline: De-Risked Through Diversification L-DOS47 (ADEPT) pH modulation + immune reactivation Phase I/II ✓ Validated Urease × VHH ADC — Drug A Cytotoxic (non-P-gp substrate) Discovery Novel payload, validated target Payload1 (enzymatic DAR 2) ADC — Drug B Cytotoxic (orthogonal MOA) Validat
Slide 24: Summary
Summary CEACAM6 is a validated, high-value cancer target Overexpressed in >70% of epithelial cancers, prognostic of poor outcome, and our VHH shows preferential binding to tumor- expressed CEACAM6. L-DOS47 demonstrates the target's clinical potential A novel ADC/checkpoint hybrid that is safe and sh
Slide 25: Thank You
Thank You