Heidelberg Pharma Ag · XETR:HPHA

Heidelberg Pharma — International Myeloma Society 22nd Annual Meeting & Exhibition 2025

16 slides from Heidelberg Pharma's conference presentation, Sep 20, 2025

  1. Slide 1: HDP-101 anti-BCMA ADC with novel amanitin payload shows promising data in RRMM

    International Myeloma Society 22nd Annual Meeting & Exhibition Toronto, Canada September 20, 2025 THE ANTI-BCMA ANTIBODY-DRUG CONJUGATE HDP-101 WITH A NOVEL AMANITIN PAYLOAD SHOWS PROMISING DATA IN RELAPSED/REFRACTORY MULTIPLE MYELOMA IN A PHASE 1/2A CLINICAL TRIAL AS IT ADVANCES INTO COHORT 9 Prese

  2. Slide 2: Disclosures

    Disclosures Grant/Research Support: Janssen; BMS; GlaxoSmithKline; Pfizer; Beigene; Kite Pharma, Inc.; Amgen; Abbvie; Novartis; Genentech; Fortis Therapeutics, Inc; Takeda; Genmab; Heidelberg Pharma AG; Nexcella, Inc; Poseida Consultant: Sanofi; Sebia; BMS; Ascentage; Genentech 2

  3. Slide 3: HDP-101 – BCMA-ATAC – Innovative ADC with Amanitin Payload

    HDP-101 – BCMA-ATAC - INNOVATIVE ADC WITH AMANITIN PAYLOAD HDP-101 – anti-BCMA ATAC Payload: α-Amanitin a Third-generation ADC • Identified in Amanita phalloides mushroom • Completely novel MOA: • Inhibition of RNA Polymerase II • Kills dormant/non-dividing tumor cells • Circumvents resistance via n

  4. Slide 4: HDP-101 Phase I/IIa Trial Design in RRMM – Dosing Regimen Optimization from Cohort 6

    HDP-101 PHASE I/IIa TRIAL DESIGN IN RRMM - DOSING REGIMEN OPTIMIZATION FROM COHORT 6 CX RP2D tbc Phase I: Dose Escalation Key Eligibility Criteria Q3W intravenous dosing, BLRM Design Split 1st dose & 175 µg/kg C9 premed*, then Q3W Arm C (+ premed) • Prior SCT or transplant ineligible Q1W split • Pri

  5. Slide 5: HDP-101 Phase I/IIa Patient Characteristics

    HPD-101 PHASE I/IIa PATIENT CHARACTERISTICS Demographics Total (N=42) Prior Therapy Total (N=42) Age (years) Number of prior treatments Median 69.5 Median 6 Min, Max 43-90 Range 2-15 Gender Number of patients exposed to BCMA-targeting therapies Female 13 Total anti-BCMA exposed 13 Male 29 Number of

  6. Slide 6: Favorable Safety of HDP-101

    FAVORABLE SAFETY OF HDP-101 MOST COMMON TREATMENT-EMERGENT AES UP TO COHORT 8 Preferred Term (N=42) Any CTCAE grade (%) Grade 3-4 (%) Thrombocytopenia 14 (33,3%) 9 (21,4%) Anaemia 9 (21,4%) 4 (9,5%) Arthralgia 9 (21,4%) 0 (0%) Dose optimization Fatigue 7 (16,7%) 0 (0%) strategies adopted in Aspartat

  7. Slide 7: 100 mcg/kg Dosing Associated with Transient Thrombocytopenia and LFT Elevation

    100 MCG/KG DOSING WAS ASSOCIATED WITH TRANSIENT THROMBOCYTOPENIA AND LFT ELEVATION Cohort 5 - PLATELETS Cohort 5 - AST (100 µg/kg) (100 µg/kg) 350 300 400 350 250 300 200 250 150 Grade 1 200 100 150 Grade 2 100 50 Grade 3 50 Grade 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 4

  8. Slide 8: Dose Optimization Strategies from Cohort 6

    DOSE OPTIMIZATION STRATEGIES FROM COHORT 6 • Post-Cohort 5 Safety review: SRC Dose Optimization recommended study continuation with 90 microgram/kg BW dose level mitigation strategies for transient thrombocytopenia • Mitigation: corticosteroid/antihistamine premed, weekly dosing, split first-cycle d

  9. Slide 9: New Treatment Strategies Had a Positive Effect on Thrombocytopenia

    NEW TREATMENT STRATEGIES HAD A POSITIVE EFFECT ON THROMBOCYTOPENIA Cohort 5 Cohort 7 Cohort 8 (100 µg/kg) (112.5 µg/kg) (140 µg/kg) 600 600 600 500 500 500 400 400 400 300 300 300 G/l 200 200 200 Gr 1 Gr 1 Gr 1 100 Gr 2 100 Gr 2 100 Gr 2 Gr 3 Gr 3 Gr 3 Gr 4 Gr 4 Gr 4 0 0 0 1 2 3 5 8 15 22 24 29 36 4

  10. Slide 10: New Treatment Optimization Strategies Mitigated the Impact on Liver Function

    NEW TREATMENT OPTIMIZATION STRATEGIES MITIGATED THE IMPACT ON LIVER FUNCTION Cohort 5 Cohort 7 Cohort 8 (100 µg/kg) (112.5µg/kg) (140 µg/kg) 400 400 400 350 350 350 300 300 300 250 250 250 AST U/l 200 200 200 150 150 150 100 100 100 50 50 50 0 0 0 1 2 3 5 8 15 22 24 29 36 43 44 45 47 50 58 65 72 79

  11. Slide 11: All Analytes Appear Dose-Linear with Respect to AUC0-21 day and Cmax

    ALL ANALYTES APPEAR DOSE-LINEAR WITH RESPECT TO AUC0-21 DAY AND CMAX Cohort 1-6 Cohort 7 Cohort 8 → Cohort 7 and 8 AUC0-21days and Cmax show no markable differences compared with Cohorts 1-6 → AUC0-21days and Cmax exhibit dose linearity for total Ab → Not shown: AUC0-21days and Cmax also exhibit dos

  12. Slide 12: Dose-Dependent Efficacy of HDP-101 Treatment

    DOSE-DEPENDENT EFFICACY OF HDP-101 TREATMENT 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 10101_P26 B 10101_P21 C

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

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

  14. Slide 14: Objective Response Rates (ORR)

    OBJECTIVE RESPONSE RATES (ORR) 60% 50% PRELIMINARY EFFICACY 50% • Multiple responses were seen (from 90 µg/kg) across different dosing arms 36% 16.7% 40% • In Cohort 6 (90 μg/kg), 2 of 10 patients showed PR (1 patient is still ongoing with PR after 18 treatment cycles) 3.5% 30% 3.5% • In Cohort 5 (1

  15. Slide 15: HDP-101-01 – Summary and Conclusions

    HDP-101-01 – SUMMARY AND CONCLUSIONS FAVORABLE SAFETY AND EFFICACY IN PHASE I/IIa CLINICAL TRIAL FAVORABLE SAFETY PRELIMINARY EFFICACY • Overall mild AEs: no signs of ocular or renal tox, • Multiple responses were seen (from 90 µg/kg) across myelosuppression or liver damage. Transient different dosi

  16. Slide 16: Acknowledgements

    ACKNOWLEDGEMENTS We sincerely thank: • Patients and their families • Investigators, study coordinators, research nurses and site staff • Collaborating institutions and partners 16

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