Slide 1: Dual-precision Targeted Protein Degradation
TPD² Approach Dual-precision Targeted Protein Degradation 2026 Q3 1
Slide 2: Disclaimer
Disclaimer Forward-looking Statements This presentation contains forward-looking statements that are based on the current expectations and beliefs of Orum Therapeutics, Inc. (“Orum”). Statements in this presentation regarding matters that are not historical facts, including, but not limited to, stat
Slide 3: Orum is a Leader in Degrader-Antibody Conjugates
Orum is a Leader in Degrader-Antibody Conjugates Daejeon, KR Boston, US Bioconjugation Antibody Oncology Discovery Pharmacology First company to develop a Innovative and proprietary Three FDA IND packages clinical stage DAC platform technologies Bioassay Medicinal Upcoming key events: Our team: Two
Slide 4: Robust CAGR Expected in ADC Market Amid Increasing Demand for Novel MoA Payload
Robust CAGR Expected in ADC Market Amid Increasing Demand for Novel MoA Payload Market expected to reach $28B by 2028 (23% CAGR), with ADCs accounting for 30% of global biopharma licensing agreements Success of maytansinoids, auristatins, and campothecin payload ADC payload types classes has ushered
Slide 5: What is a Degrader-Antibody Conjugate (DAC)?
What is a Degrader-Antibody Conjugate (DAC)? Next generation antibody drug conjugate (ADC) with potential for broad intracellular target diversity Conventional ADC VS Orum TPD2 DAC Antibody Confers selectivity and binding against cell surface antigen, allowing targeted delivery to target cell Linker
Slide 6: TPD2 Dual Precision Mechanism of Action: Targeting for Enhanced Safety & Efficacy
TPD2 Dual Precision Mechanism of Action: Targeting for Enhanced Safety & Efficacy Selective tumor targeting combined with targeted protein degradation drives tumor cell death 1 2 3 4 5 Targeted delivery & Intracellular release of Degrader-mediated Polyubiquitination of Proteasomal internalization de
Slide 7: Orum's TPD2 Presents Potential Improved Efficacy, PK and Safety in Pre-Clinical Studies
Orum’s TPD2 Presents Potential Improved Efficacy, PK and Safety in Pre-Clinical Studies In pre-clinical studies, Orum’s TPD2 approach presented the potential for each of the following: Improved Efficacy Significant Improvement in PK Improved Therapeutic Index (TI) A B C Strong activity in vitro and
Slide 8: Dual-Precision Approach Uniquely Positions Orum Amongst Competitors
Dual-Precision Approach Uniquely Positions Orum Amongst Competitors TPD2 uniquely combines the specificity of antibody-drug conjugation with the robust efficacy potential of targeted protein degradation TPD² Protein degrader conjugated to antibody STRENGTHS STRENGTHS Clinically validated Clinically
Slide 9: Two Deals Completed to Highlight the Value of TPD2 Technology
Two Deals Completed to Highlight the Value of TPD2 Technology Strategic partnerships enabling clinical development and broader application of TPD2 Asset Sale Platform Deal Partner overview Partner overview • Global biopharma leader in oncology, hematology, and • Global biotech leader with approved m
Slide 10: Multiplatform Pipeline to Address High Unmet Medical Need
Multiplatform Pipeline to Address High Unmet Medical Need Dual-precision targeted protein degradation (TPD2) approach technologies Platform Program Target Indication Discovery IND-enabling Phase 1 AML, ORM-1153 CD123 Heme-onc TPD2 GSPT1 ORM-1023 Undisclosed SCLC, NET BMS-986497 CD33 AML, MDS BMS Acq
Slide 11: TPD2 GSPT1 Platform
TPD2 GSPT1 Platform Antibody-enabled Molecular Glues • ORM-1153 • ORM-1023 11
Slide 12: GSPT1 Degraders Are Highly Potent Against a Broad Set of Tumor Types
GSPT1 Degraders Are Highly Potent Against a Broad Set of Tumor Types GSPT1 is a housekeeping protein involved in In vitro screen of GSPT1 degrader translation termination against 250+ cell lines across 20+ tumor types Degradation of GSPT1 → Integrated stress response → Prolonged response Hematologic
Slide 13: ORM-1153: CD123-Targeting GSPT1 DAC
ORM-1153: CD123-Targeting GSPT1 DAC Combining CD123-targeted delivery with GSPT1 degradation Antigen target: Antibody CD123 Orum’s proprietary Fc-silenced Highly expressed in AML, CD123 antibody with enhanced >97% at diagnosis | >98% at relapse internalization and cross-reactivity Low expression in
Slide 14: TPD2 GSPT1: Opportunity in Acute Myeloid Leukemia (AML)
TPD² GSPT1: Opportunity in Acute Myeloid Leukemia (AML) Unmet Needs AML Market Size (global) & Patient Age Trends Market projected to grow from $3.5B in ‘24 to $9.6B Improving efficacy for Significantly lower efficacy in relapsed/refractory patients by ‘34 (10.6% CAGR), with North America making R/R
Slide 15: ORM-1153's Antibody Demonstrates Enhanced Internalization Efficiency
ORM-1153’s Antibody Demonstrates Enhanced Internalization Efficiency Sub-nanomolar CD123 binding enables rapid and efficient internalization, and ORM-1153 shows markedly greater in vivo efficacy vs. talacotuzumab-GSPT1 Internalization efficiency in MV-4-11 (24 hrs) Disseminated MV-4-11-Luc xenograft
Slide 16: ORM-1153 Exhibits CD123-Dependent Activity and Strong Potency in AML Cell Lines
ORM-1153 Exhibits CD123-Dependent Activity and Strong Potency in AML Cell Lines CD123-dependent cytotoxicity in CD123+/- AML cells Comparative potency against SoC agents in MV-4-11 125 125 ORM-1153 ORM-1153 ORM-1153 100 MV-4-11 100 Venetoclax SMol006* CD123+ venetoclax % viability % viability Gemtuz
Slide 17: ORM-1153 Potently Inhibits Growth in AML TP53 Isogenic Cell Lines
ORM-1153 Potently Inhibits Growth in AML TP53 Isogenic Cell Lines Cytotoxicity retained in TP53 KO cells with ORM-1153 indicating potential activity in TP53 mutant AML MV-4-11 TP53 WT/KO cells ORM-1153 Venetoclax Pivekimab sunirine (DecnupazTM) Pivekimab-SMol249* 150 MV-4-11 150 150 150 MV-4-11 tp53
Slide 18: Robust ORM-1153 Activity in AML PDX Models Regardless of Gene Alterations
Robust ORM-1153 Activity in AML PDX Models Regardless of Gene Alterations Consistent efficacy maintained across high-risk profiles including TP53 and FLT3-ITD Ex vivo cytotoxicity and patient sample characteristics (#1 - #7) 1.25 1.25 1.25 Sample Gender Age Diagnosis Treatment Gene Alternation CD123
Slide 19: Robust Tumor Control and Survival Benefit of ORM-1153 in Disseminated AML Model
Robust Tumor Control and Survival Benefit of ORM-1153 in Disseminated AML Model ORM-1153 drives greater reduction in tumor burden and robust survival compared to SoC and benchmark ADC Disseminated MV4-11-Luc xenograft mouse model Greater reduction in AML burden over time 93% tumor reduction at Day 1
Slide 20: Broad Therapeutic Window and Favorable Safety Profile of ORM-1153
Broad Therapeutic Window and Favorable Safety Profile of ORM-1153 Exposure-based preliminary therapeutic window 6 mg/kg (NHP tolerated dose) 0.1 mg/kg (mouse MED) Concentration (ng/ml) ✓ Wide therapeutic margin established between the minimal efficacious dose (MED; 0.1 mg/kg in mice) and the highest
Slide 21: Phase 1 First-in-Human Study of ORM-1153
Phase 1 First-in-Human Study of ORM-1153 Phase 1 Multi-region, First-in-Human Study of ORM-1153 in Patients with R/R AML or Other Hematological Malignancies with CD123 Expression Methodology Phase 1 Dose Escalation (NCT07809906) CD123 expressing R/R AML Open-label, multiregional, Phase 1 dose escala
Slide 22: ORM-1023: GSPT1-DAC for Small Cell Lung Cancer and Neuroendocrine Tumors
ORM-1023: GSPT1-DAC for Small Cell Lung Cancer and Neuroendocrine Tumors Combining targeted delivery with GSPT1 degradation Antigen target: Antibody Undisclosed Orum discovered Fc-silenced antibody against an undisclosed tumor antigen Indication: Small cell lung cancer (SCLC), Neuroendocrine tumors
Slide 23: Limited Diversity of Payloads for SCLC ADCs in Development
Limited Diversity of Payloads for SCLC ADCs in Development Antibody targets vary widely, yet the payload heavily relies on TOPO1 Comparative efficacy landscape of ADCs and TCEs in relapsed small cell lung cancer Distinct clinical profiles derived from Phase I/II trials • 8 of 9 ADCs with reported Ph
Slide 24: Potent Activity of ORM-1023 in SCLC PDX-Derived Models
Potent Activity of ORM-1023 in SCLC PDX-Derived Models ORM-1023 showed sub-nanomolar potency across three PDX-derived lines, including the LU5264 model, where lurbinectedin was inactive (>200 nM) Ex vivo potency of ORM-1023 in SCLC PDX-derived models* LU5217 LU5264 LU5242 150 150 120 ORM-1023 Lurbin
Slide 25: Robust In Vivo Activity of ORM-1023 in SCLC PDX Model
Robust In Vivo Activity of ORM-1023 in SCLC PDX Model Single-dose ORM-1023 demonstrated tumor growth inhibition across multiple SCLC PDX models In vivo activity of ORM-1023 in SCLC PDX model* LU5242 – Tumor Volume LU5242 – Body Weight Vehicle ORM-1023 1 mg/kg 800 ORM-1023 3 mg/kg 40 Tumor volume (mm
Slide 26: TPD2 Novel Degrader Payload Discovery
TPD2 Novel Degrader Payload Discovery Enabled by Orum Know-How and PROTAb Platform 26
Slide 27: Orum DAC Discovery Strategy for 2026 and Beyond
Orum DAC Discovery Strategy for 2026 and Beyond GSPT1 and next-generation payload : Unlocking platform potential across diverse targets • Address limited activity or resistance associated with conventional payloads TPD2 GSPT1 TPD2 New Payloads GSPT1 Payload New Payloads + + Antigen 1 Antigen 2 Antig
Slide 28: Structure-based Discovery Workflow at Orum: From Target to Lead Candidate
Structure-based Discovery Workflow at Orum: From Target to Lead Candidate Protein of interest Co-crystal vs. AI prediction AI-based E3 ternary complex modeling E3 ligase AI prediction ination B. V rm irtu Dete al S Warhead e PROTAC linker screening cr r Electron density map Linker tu ee uc AI or exp
Slide 29: TPD2 PROTAb: Linker Platform to Facilitate the Development of DACs
TPD2 PROTAb: Linker Platform to Facilitate the Development of DACs Adaptor for E3 ligase-based degrader conjugation PROTAb-enabled traceless conjugation process Step 1. PROTAb attachment to ADC linker PROTAb Step 3. Intracellular Linker Step 2. Conjugation to E3-ligase degrader traceless release R A
Slide 30: PROTAb Enables Targeted Degradation with Diverse Hetero-Bifunctional Degraders
PROTAb Enables Targeted Degradation with Diverse Hetero-Bifunctional Degraders Demonstrates effective use of PROTAb with non-GSPT1 targets and hetero-bifunctional degraders POC molecules PROTAb-DACs are BCMA-BRD4 Targeted BRD4 degradation drives cytotoxicity highly effective in vitro Anti-BCMA mAb M
Slide 31: TPD2: Significant Potential to Unlock a Vast Number of Indications
TPD² : Significant Potential to Unlock a Vast Number of Indications Modular platform technology allows for creation of a multitude of targeted therapies ● Orum's strength lies in its ability to develop the antibody and degrader payload separately, tailoring these components to enhance therapeutic be
Slide 32: Expected Timeline for 2026 and Beyond
Expected Timeline for 2026 and Beyond Program 2025 2026 2027 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 DC nomination ASH AACR IND clearance → Phase 1 ORM-1153 DC nomination AACR ORM-1023 DC nomination in 1H ‘27 New Payload Current Partnering • Out-license Orum’s programs and platform technology Focus • Ac
Slide 33: Thank you
Thank you A world where no patients suffer from diseases caused by undruggable targets www.orumrx.com