Heidelberg Pharma Ag · XETR:HPHA

Heidelberg Pharma — 16th World ADC Conference San Diego (November 2025)

25 slides from Heidelberg Pharma's conference presentation, November 2025

  1. Slide 1: From Bench to Breakthrough: The Evolution of Amanitin ADCs

    FROM BENCH TO BREAKTHROUGH: THE EVOLUTION OF AMANITIN ADCS – INSIGHTS FROM HDP-101 PHASE I/II & THE FUTURE OF PAYLOAD DIFFERENTIATION Andreas Pahl, CEO Heidelberg Pharma 16th World ADC Conference – San Diego

  2. Slide 2: Safe Harbor

    Safe Harbor FORWARD LOOKING STATEMENTS This communication contains certain forward-looking statements, product liability and limitations of insurance, limitations of supplies, relating to the Company’s business, which can be identified by the competition from other biopharmaceutical, chemical and us

  3. Slide 3: The ADC Payload MOA Dramatically Impacts Tumor Response

    The ADC Payload MOA Dramatically Impacts Tumor Response Enhertu® Payload: deruxtecan (Topo 1 inhibitor) Kadcyla® Payload: emtansine (Tubulin inhibitor) Cortés, J. et al, N Engl J Med 2022; 386:1143-1154 Same target (Her2), same antibody (Trastuzumab), in the same patient population * MOA = mode of a

  4. Slide 4: Heidelberg Pharma's Proprietary Amanitin Payload Technology to Generate a Disruptive New Class of ADCs

    Heidelberg Pharma's Proprietary Amanitin Payload Technology to Generate a Disruptive New Class of ADCs Novel MoA Biomarker for Stratification Single Player Overcoming resistance of High-risk Patients M-Protein & IgG Change Over Standard Risk OS - 110 months 20 11 Cycles of HDP-101 Levels (g/dL) 15 C

  5. Slide 5: ATAC - Innovative ADCs With Amanitin Payload

    ATAC - Innovative ADCs With Amanitin Payload Payload: α-Amanitin HDP-101 – anti-BCMA • Identified in Amanita phalloides mushroom • Completely novel MOA: • Inhibition of RNA Polymerase II • Kills dormant/non-dividing tumor cells • Circumvents resistance via new mechanism • Synthetic amanitin derivati

  6. Slide 6: The Payload Makes the Difference

    The Payload Makes the Difference Breast Cancer Model (JIMT-1 Xenograft) is resistant to Kadcyla® and Enhertu® Same antibody (Trastuzumab), different payload JIMT-1 (amanitin vs. topoisomerase inhibitor) xenograft PBS (control) Mean tumor volume [mm3] Enhertu® (20 mg/kg) Control Enhertu® treatment Tr

  7. Slide 7: HDP-101-01 – Phase I Preliminary Efficacy Data (Cohort 1-5)

    HDP-101-01 – Phase I Preliminary Efficacy Data (Cohort 1-5) Cohort 5 (100 µg/kg) Cohort 4 (80 µg/kg) Cohort 3 (60 µg/kg) Cohort 2 (30 µg/kg) Cohort 1 (20 µg/kg) Readout: November 2024 Treatment duration (days) Progressive disease (PD) Minimal response (MR) Very good partial remission (VGPR) End of t

  8. Slide 8: Study Case: Cohort 5 Stringent Complete Response

    Study Case: Cohort 5 Stringent Complete Response M-protein (g/l) and IgG (g/l) 70 Year Old Patient with Stage II IgG-Ϗ Myeloma Since 2002 • 9 prior lines of therapies including transplant, IMiDs, PIs, and 25 Daratumumab 20 IgG M-protein • Last 3 treatment regimens & response: g/l 15 7th line: BCMA C

  9. Slide 9: 100 µg/kg Dosing Was Associated with Transient Thrombocytopenia and Liver Enzyme Elevation

    100 µg/kg Dosing Was Associated with Transient Thrombocytopenia and Liver Enzyme Elevation Cohort 5 (100 µg/kg) 350 Platelets 400 AST 300 350 250 300 250 200 U/l 200 G/l 150 Gr 1 150 100 Gr 2 100 50 Gr 3 50 Gr 4 0 0 1 2 3 5 8 15 22 24 29 36 43 44 45 47 1 2 3 5 8 15 22 24 29 36 43 44 45 47 50 58 65 7

  10. Slide 10: Dose Optimization Strategies from Cohort 6

    Dose Optimization Strategies from Cohort 6 Dose Optimization • Post-Cohort 5 Safety review: SRC 90 µg/kg BW dose level recommended study continuation with mitigation strategies for transient thrombocytopenia • Mitigation: corticosteroid/antihistamine premed, weekly dosing, split first-cycle dose, ad

  11. Slide 11: HDP-101 Phase I/IIa Trial Design in Relapsed/Refractory Multiple Myeloma

    HDP-101 Phase I/IIa Trial Design in Relapsed/Refractory Multiple Myeloma Q1W split Phase I: Dose Escalation C7 dosing Arm B 112.5 µg/kg Q3W intravenous dosing, BLRM Design Split 1st dose & C7 premed*, then Q3W Arm C (+ premed) Q3W dosing & C6 Arm A Objectives premed* Dosing Regimen Q1W split Primary

  12. Slide 12: New Treatment Strategies Had a Positive Effect on Thrombocytopenia

    New Treatment Strategies Had a Positive Effect on Thrombocytopenia Cohort 5 Cohort 7 (100 µg/kg) (112.5 µg/kg) 350 350 300 300 250 250 Platelets G/l 200 Platelets G/l 200 150 150 Gr 1 Gr 1 100 100 Gr 2 Gr 2 50 50 Gr 3 Gr 3 Gr 4 Gr 4 0 0 1 2 3 5 8 15 22 24 29 36 43 44 45 47 1 2 3 5 8 12 15 19 22 26 2

  13. Slide 13: HDP-101 – Phase I Efficacy Data Cohort 5-7

    HDP-101 – Phase I Efficacy Data Cohort 5-7 Progressive disease (PD) (112.5 µg/kg) 10101_P30 B * Stable disease (SD) Cohort 7 10101_P29 C Minimal response (MR) 10101_P32 B 10101_P33 C * Partial response (PR) Very good partial response (VGPR) 10101_P34 C 10101_P31 B * Stringent complete response (CR)

  14. Slide 14: Changes in the Dose Distribution Maintained the Anti-Tumor Effect

    Changes in the Dose Distribution Maintained the Anti- Tumor Effect M-protein Relative Change from Baseline M-protein % Change from Baseline 10101_P19 A 10101_P30 B 10101_P13 10101_P22 A 10101_P25 B 10101_P32 B 10101_P24 C 10101_P29 C 10101_P10 10101_P01 10101_P08 10101_P02 10101_P28 A 10101_P27 A 10

  15. Slide 15: HDP-101 Phase I/IIa Trial Design in Relapsed/Refractory Multiple Myeloma

    HDP-101 Phase I/IIa Trial Design in Relapsed/Refractory Multiple Myeloma CX RP2D tbc Phase I: Dose Escalation Q3W intravenous dosing, BLRM Design 175 µg/kg Split 1st dose & Ongoing C9 premed*, then Q3W Arm C (+ premed) Q1W split C8 dosing Arm B Objectives 140 µg/kg Split 1st dose & C8 premed*, then

  16. Slide 16: HDP-101 – Phase I Preliminary Efficacy Data (Cohort 8)

    HDP-101 – Phase I Preliminary Efficacy Data (Cohort 8) Cohort 8 Progressive disease (PD) (140 µg/kg) Stable disease (SD) Minimal response (MR) Partial response (PR) Very good partial response (VGPR) Stringent complete response (CR) 10101_P40 C Ongoing treatment 10101_P37 C * n.e. not evaluated 10101

  17. Slide 17: No Signs of Thrombocytopenia or Liver Damage

    No Signs of Thrombocytopenia or Liver Damage Cohort 8 (140 µg/kg) Platelets AST ALT 550 400 400 500 350 350 450 300 300 400 350 250 250 300 U/l U/l 200 G/l 200 250 200 150 150 150 Gr 1 100 100 100 Gr 2 50 50 50 Gr 3 Gr 4 0 0 0 1 3 8 15 22 29 43 45 50 60 71 85 99 1 3 8 15 22 29 43 45 50 64 78 92 1 3

  18. Slide 18: Most Common Treatment-Emergent AEs - Cohort 8 only

    Most Common Treatment-Emergent AEs - Cohort 8 only Preferred Term (N=8) Any CTCAE Grade 3-4 Thrombocytopenia 2 0 FAVORABLE SAFETY OF HDP-101 Anaemia 1 0 Arthralgia 0 0 • Overall mild AEs: no signs of ocular or renal tox, Fatigue 1 0 myelosuppression or liver damage Nausea 1 0 • The implementation of

  19. Slide 19: Objective Response Rates (ORR)

    Objective Response Rates (ORR) 70% PRELIMINARY EFFICACY 60% 57% • Multiple responses were seen (from 90 µg/kg) across 50% different dosing arms, confirming that changes in the dose distribution maintained the anti-tumor effect while 40% 38% 29% improving drug tolerability • We observed 38% ORR in Co

  20. Slide 20: HDP-101 Phase I/IIa Trial Design in Relapsed/Refractory Multiple Myeloma

    HDP-101 Phase I/IIa Trial Design in Relapsed/Refractory Multiple Myeloma CX RP2D tbc Phase I: Dose Escalation Q3W intravenous dosing, BLRM Design 175 µg/kg Split 1st dose & Ongoing C9 premed*, then Q3W Arm C (+ premed) Q1W split C8 dosing Arm B Objectives 140 µg/kg Split 1st dose & C8 premed*, then

  21. Slide 21: High Tolerability and Good Efficacy at Doses below MTD

    High Tolerability and Good Efficacy at Doses below MTD A Comparative Analysis with Multiple Myeloma Approved Therapies HDP-101 Blenrep Tecvayli Carvykti ORR 57% 30-35% 63% 90% Dose 0.140 mg/kg Q3W 2.5/3.4 mg/kg Q3W 1.5 mg/kg QW (opt. Q2W) 2.5/3.4 mg/kg TEAEs Cohort 8 – Phase I DREAMM-21 MajesTEC-12

  22. Slide 22: HDP-101 Relevant Throughout the Spectrum of Treatment in Early Relapse with Combination Regimens

    HDP-101 Relevant Throughout the Spectrum of Treatment in Early Relapse with Combination Regimens Potential Study Populations HDP-101 Regimens Near Term Priority Establish Post-BCMA Monotherapy Monotherapy in Late-line Setting Len-exposed (similar to DREAMM-8) Combination (IMiD + dex) Compete with Bl

  23. Slide 23: Planned Studies Tap into Large, Growing Patient Populations

    Planned Studies Tap into Large, Growing Patient Populations, with High Unmet Need to Prolong Survival Treatment Total Addressab. Range of Annual Peak 2026 2027 2028 2029 2030 2031 2032 2033 2034 2035 Duration Population Size Analog Shares Addressab. (U.S.) (%, WW) US Market1 Accelerated approval Ful

  24. Slide 24: Amanitin-ADC Shows Deep Responses Below MTD

    Amanitin-ADC Shows Deep Responses Below MTD • Phase I dose escalation data demonstrates therapeutic window in patients • HDP-101 data provide clinical validation for the Amanitin platform • Promising safety profile: no ocular tox, no renal tox, no myelosuppression, no liver damage • Overcome resista

  25. Slide 25: Thank You

    Heidelberg Pharma AG Ladenburg, Germany THANK YOU Tel.: +49 6203 10090 investors@hdpharma.com www.heidelberg-pharma.com

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