Heidelberg Pharma Ag · XETR:HPHA
Heidelberg Pharma — Investor Presentation (February 2025)
42 slides from Heidelberg Pharma's investor presentation, February 2025
Slide 1: The Leader in Next Generation ADC Payloads
THE LEADER IN NEXT GENERATION ADC PAYLOADS Company Presentation • February 2025
Slide 2: Safe Harbor: Forward Looking Statements
SAFE HARBOR FORWARD LOOKING STATEMENTS This communication contains certain forward-looking statements, competition from other biopharmaceutical, chemical and relating to the Company’s business, which can be identified by the pharmaceutical companies, environmental, health and safety matters, use of
Slide 3: Overview
OVERVIEW © Heidelberg Pharma AG 3
Slide 4: Corporate Highlights
CORPORATE HIGHLIGHTS PROPRIETARY PAYLOADS, WHOLLY-OWNED ASSETS & PARTNERED ADCs Lead ADC Program HDP-101 (BCMA-ATAC) Technology and asset partnerships maximize • Proprietary Amanitin Payload (patent exclusivity) value of pipeline • Overcome resistance due to new MoA • HDP-101 Phase I/IIa ongoing in
Slide 5: Management Team
MANAGEMENT TEAM Professor Andreas Pahl András Strassz, MD Chief Executive Officer Chief Medical Officer @ Heidelberg Pharma since 2012 @ Heidelberg Pharma since 2020 Professor of Pharmacology and Toxicology at the University of Erlangen-Nuremberg (FAU) with 25 years experience in research and higher
Slide 6: Our Mission
OUR MISSION Our mission is to build a world-class ADC pipeline by the use of differentiated ADC technologies. Professor Andreas Pahl, CEO © Heidelberg Pharma AG 6
Slide 7: Strong In-House R&D Capabilities and Expertise
STRONG IN-HOUSE R&D CAPABILITIES AND EXPERTISE Synthetic chemistry Antibody generation & Preclinical testing bioconjugation CMC Bioanalytical sciences Clinical Development Best ADC candidate in the shortest time © Heidelberg Pharma AG 7
Slide 8: Value Creation Through Development of Best-in-Class ADC Assets
VALUE CREATION THROUGH DEVELOPMENT OF BEST-IN-CLASS ADC ASSETS DISCOVERY & DEVELOPMENT ENGINE Partnering at IND- ready, First clinical data, EOP1, Clinical POC Scouting Toolbox of proprietary Multiple targets payloads Partnering In-licensing Co-Development Development Upside: Retain Antibodies Exper
Slide 9: Next Generation ADC Payload Platform
NEXT GENERATION ADC PAYLOAD PLATFORM Developing an ADC toolbox and clinical product pipeline to overcome tumor resistance across cancer types Toolbox of proprietary payloads ATAC technology RNA polymerase II inhibitor Amanitin-based ETAC technology ITAC technology Topoisomerase I TLR7 agonist inhibi
Slide 10: Growing Pipeline of Proprietary Programs
GROWING PIPELINE OF PROPRIETARY PROGRAMS Product Target Indication Research Preclinic Phase I Phase II Phase III Approval Partner Huadong HDP-101 BCMA Multiple Myeloma ------------------------------------------------------------------------------------------ (China+) ATAC pipeline HDP-102 CD37 NHL (
Slide 11: Growing Pipeline of Partnered Programs
GROWING PIPELINE OF PARTNERED PROGRAMS Product Target Indication Research Preclinic Phase I Phase II Phase III Approval Partner Partners ATAC TAK-ATAC n/a Oncology ------------------------------------------------------------------------------------------ Takeda Product Target Indication Research Pre
Slide 12: ADC Technologies
ADC TECHNOLOGIES © Heidelberg Pharma AG 12
Slide 13: Resistance Is One of the Biggest Challenges in Oncology
RESISTANCE IS ONE OF THE BIGGEST CHALLENGES IN ONCOLOGY 1 in 2 > 90% people will be diagnosed with of cancer deaths are caused by cancer in their lifetime drug resistance © Heidelberg Pharma AG 13
Slide 14: The Payload MoA Is What Makes the Difference
THE PAYLOAD MOA IS WHAT MAKES THE DIFFERENCE! Enhertu® Payload: deruxtecan (Topo 1 inhibitor) Kadcyla® Payload: emtansine (Tubulin inhibitor) Source: Cortés, J. et al, N Engl J Med 2022; 386:1143-1154 Same target (HER2), same antibody (Trastuzumab), same patient population © Heidelberg Pharma AG 14
Slide 15: ATACs Are ADCs with Amanitin as a Payload
ATACs ARE ADCs WITH AMANITIN AS A PAYLOAD Antibody • Targeting tumor antigen Payload: α-Amanitin • 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 amani
Slide 16: ATACs Address the Limitations of Current Cancer Therapies
ATACs ADDRESS THE LIMITATIONS OF CURRENT CANCER THERAPIES Cancer Diagnosis Treatment Long Term Response Outcome Tumor Relapse Standard Minimal Survival Therapy Increase CSCs survive CSCs survive Tumor bulk diminished Tumor Regrows Tumor ATAC Eradication Cure? Cancer Cell CSCs killed CSCs Eliminated
Slide 17: ATACs Overcome Resistance
ATACs OVERCOME RESISTANCE BREAST CANCER MODEL (JIMT-1 XENOGRAFT) IS RESISTANT TO KADCYLA® AND ENHERTU® JIMT-1 Same antibody (Trastuzumab), different payload xenograft (amanitin vs. topoisomerase inhibitor) PBS (control) Mean tumor volume [mm3] Enhertu® (20 mg/kg) Control Enhertu® ATAC Trastuzumab AT
Slide 18: HDP-101 Overcomes Resistance in Multiple Myeloma
HDP-101 OVERCOMES RESISTANCE IN MULTIPLE MYELOMA Kills non-dividing tumor cells unlike Effectively kills cells from patients other ADC therapeutics multi-refractory to SOC Elotuzumab/Pom resistant Anti-BCMA-MMAF Daratumumab resistant No resistance From bone marrow of patients obtained primary MM cel
Slide 19: HDP-101 Overcomes Resistance in Multiple Myeloma
HDP-101 OVERCOMES RESISTANCE IN MULTIPLE MYELOMA Kills Non-Dividing Tumor Cells Effectively Kills Cells from Patients Kills cells with ultra-low antigen Multi-Refractory to SOC expression Patients derived Anti-BCMA-MMAF 125 BCMA density primary MM cells Pat 1 2262 Pat 2 3309 100 Pat 3 n.d Pat 4 587
Slide 20: Del(17p): Potential Predictive Biomarker
DEL(17p): POTENTIAL PREDICTIVE BIOMARKER Deletion of TP53 (tumor suppressor) • High incidence • More aggressive tumors resistant to SoC and poor prognosis Del(17p) ΔPOLR2A ΔTP53 Deletion of RNA Polymerase II (POLR2A is co-deleted) • Higher sensitivity to ATAC treatment Intracellular target of Tumor
Slide 21: Del(17p): Potential Predictive Biomarker
DEL(17p): POTENTIAL PREDICTIVE BIOMARKER HER2 1+ PATIENT-DERIVED XENOGRAFT MODELS Patient- Wild type - normal RNA Pol II levels del(17p) - reduced RNA Pol II levels derived cell inoculation Tumor volume [mm3] Tumor volume [mm3] PBS (control) PBS (control) 0.5/2 mg/kg Low-dose ATAC (0.5 mg/kg) Contro
Slide 22: Toxicity Mechanism of α-Amanitin in Humans
TOXICITY MECHANISM OF α-AMANITIN IN HUMANS α- Amanitin Ingestion Small Intestine Enterohepatic Cycle α-Ama OATP1B3 RNAP II inhibition Liver Urinary Excretion Hepatotoxicity Upon mushroom intoxication α-amanitin leads to hepatotoxicity by specific uptake of the toxin into hepatocytes via the OATP1B3
Slide 23: Multiple Myeloma and 17p Deletion
MULTIPLE MYELOMA AND 17p DELETION MULTIPLE MYELOMA (MM) • Malignancy characterized by clonal plasma cell expansion in the bone marrow • Despite substantial improvements in PF and OS, MM patients eventually relapse DEL(17p) IN MM • Deletion identified in app. 10% of newly Source: Source: Source: diag
Slide 24: HDP-101 Phase I/IIa: Summary of Preliminary Data
HDP-101 PHASE I/IIa: SUMMARY OF PRELIMINARY DATA Multiple efficacy endpoints show dose dependent and promising anti-cancer activity with intravenous doses of 20 - 100 µg/kg (median of 6.5, maximum of 15 prior lines of therapy): • 56% (10/18) of patients responded to treatment with SD or PR In a heav
Slide 25: HDP-101 Phase I Preliminary Efficacy Data
HDP-101 – PHASE I PRELIMINARY EFFICACY DATA * Complete Response * * Readout: November 2024 Treatment duration (days) Progressive disease (PD) Partial response (PR) Very good partial remission (VGPR) End of treatment Minimal response (MR) Stable disease (SD) Complete response (CR) * Adverse Event, mo
Slide 26: Case Summary: Cohort 5 Complete Response
CASE SUMMARY: COHORT 5 COMPLETE RESPONSE 70 Year Old Female with Stage II IgG-Ϗ Myeloma Since 2002 20 • 9 prior lines of therapies including transplant, IMiDs, PIs, and M-Protein IgG Daratumumab 15 • Last 3 treatment regimens & response: Levels (g/dL) 7th line: BCMA CAR-T (Aug-2018) VGPR 10 8th line
Slide 27: Dose Optimization Strategies from Cohort 6
DOSE OPTIMIZATION STRATEGIES FROM COHORT 6 After Cohort 5 a detailed safety analysis was performed Dose optimization: The Safety Review Committee (SRC) recommended Arm A Arm B Arm C • to continue the clinical study and 1Q3W 1Q1W Split first dose • mitigate the transient platelet reductions after the
Slide 28: HDP-101 Phase I/IIa Trial Design in Relapsed/Refractory Multiple Myeloma
HDP-101 PHASE I/IIa TRIAL DESIGN IN RELAPSED/REFRACTORY MULTIPLE MYELOMA C8 RP2D Key Eligibility Criteria Phase I: Dose Escalation C7 Q1W split dosing Q3W intravenous dosing, BLRM Design • Prior SCT or transplant ineligible Split 1st dose & C7 premed*, then Q3W • Prior treatment with an Objectives Q
Slide 29: Cohort 6 Summary and Cohort 7 Outlook
COHORT 6 SUMMARY AND COHORT 7 OUTLOOK Cohort 6 has been fully recruited • 10 patients treated (3-4 patients per arm) • No DLT observed • The Safety Review Committee unanimously confirmed that 90µg/kg is safe and recommended to escalate the dose • All three new treatment strategies had a positive eff
Slide 30: HDP-101 Overview
HDP-101 OVERVIEW Unique preclinical features Potential clinical benefit Efficacious against dormant tumor cells Stronger & longer lasting tumor response Efficacious in ultra-low BCMA-expressing tumor cells Deeper responses and higher response rate Novel mechanism to which all patients will be naïve
Slide 31: Strong IP Portfolio – Among Others for MoA
STRONG IP PORTFOLIO – AMONG OTHERS FOR MOA PAYLOAD ATAC Platform Antibodies & Products Patient & Tumor Amatoxin synthesis & derivatives Linker attachment HDP-101 Biomarker WO2014009025 – building block WO2010/115629 – linker attachment WO18115466 – 𝛼-BCMA ATAC WO16141185 – TP53/POLAR2A (DHIle)…
Slide 32: ADCs with TOPO I as a Payload
ADCs WITH TOPO I AS A PAYLOAD Antibody • Targeting tumor antigen Payload: TOPO I inhibitor • Clinically validated mechanism of action: Inhibition of Topoisomerase I • GMP manufacturing via fully synthetic process Site-specific conjugation • Proprietary conjugation sites • Reduced Fcγ-receptor bindin
Slide 33: ADC Candidate with New Payload: HDP-201
ADC CANDIDATE WITH NEW PAYLOAD: HDP-201 HDP-201: ANTI-GCC EXATECAN-BASED ADC • New payload: Exatecan (Topoisomerase Inhibitor I) • Guanylyl cyclase C (GCC) is a transmembrane receptor protein (GUCY2C) for regulation of intestinal electrolyte homeostasis • (Over-) Expressed in > 95% of colorectal can
Slide 34: Financials
FINANCIALS © Heidelberg Pharma AG 34
Slide 35: Finances – As of August 2024
FINANCES – AS OF 31 AUGUST 2024 Total Assets (including cash) €65.8M Healthcare Royalty agreement $75M available upon approval* Equity €35.8M Common shares 46.6M Major Shareholders dievini & affiliated parties 46%, Huadong Medicine 35% Cash as of 31 August 2024 expected to fund operations into mid-2
Slide 36: Financials and Shareholdings
FINANCIALS AND SHAREHOLDINGS In € m Guidance 2024 9M 2024 9M 2023 Sales revenue and other income 10.0 – 12.0 7.6 13.9 Freefloat 19% Operating expenses 30.0 – 33.0 22.8 30.0 dievini* Cost of sales 1.5 3.1 and affiliated R&D costs 15.7 22.1 parties 46% Administrative costs 4.7 3.6 Huadong Medicine Oth
Slide 37: Balance Sheet and Cash as of August 2024
BALANCE SHEET AND CASH AS OF AUGUST 2024 Assets (€ m) 31.08.2024 30.11.2023 Equity and liabilities (€ m) 31.08.2024 30.11.2023 Non-current assets 13.4 13.7 Non-current liabilities 21.2 1.3 Other current assets 15.8 13.3 Current liabilities 8.7 19.8 Cash 36.6 43.4 Equity 35.9 49.3 65.8 70.4 65.8 70.4
Slide 38: Outlook
OUTLOOK © Heidelberg Pharma AG 38
Slide 39: Leading ADC Pipeline in Liquid & Solid Tumor Indications
LEADING ADC PIPELINE IN LIQUID & SOLID TUMOR INDICATIONS HDP-101 HDP-102 HDP-103 HDP-104 HDP-201 BCMA-ATAC for CD37-ATAC for Non- PSMA-ATAC for Guanylyl cyclase C Guanylyl cyclase C Relapsed/Refractory Multiple Hodgkin Lymphoma metastatic & castration (GCC)-ATAC for (GCC)-ETAC for Myeloma • CTA file
Slide 40: Upcoming Catalysts: Multiple Value-Creating Milestones
UPCOMING CATALYSTS: MULTIPLE VALUE-CREATING MILESTONES 2024 2025 2026 2027 Phase I Phase IIa Registrational Trial HDP-101 RP2D* Phase I/IIa HDP-102 CTA Submission First Patient In est. RP2D* Phase I/IIa HDP-103 CTA Submission est. RP2D* Phase I/IIa HDP-201 CTA Submission Partnered programs: *data dr
Slide 41: Good Reasons to Invest in Heidelberg Pharma
GOOD REASONS TO INVEST IN HEIDELBERG PHARMA Highly dynamic ADC HDP-101 with first positive environment with an attractive efficacy data and excellent global market that is expected potential for indication with to grow to USD 19 billion high unmet medical need in 2030 Expansion of partner network So
Slide 42: Thank You for Your Attention!
THANK YOU FOR YOUR Heidelberg Pharma AG Ladenburg, Germany Tel.: +49 6203 10090 ATTENTION! investors@hdpharma.com investors@hdpharma.com www.heidelberg-pharma.com www.heidelberg-pharma.com
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