Tme Pharma N.v. · EURONEXT:ALTME
Tme Pharma — Investor Presentation (June 2025)
48 slides from Tme Pharma's investor presentation, June 2025
Slide 1: Improving Therapeutic Outcomes by Targeting the Tumor Microenvironment
www.tmepharma.com Improving Therapeutic Outcomes by Targeting the Tumor Microenvironment June 2025 June 2025 © TME Pharma
Slide 2: Forward Looking Statements
Forward Looking Statements The information and opinions contained in this presentation officers, employees, direct or indirect shareholders, agents, presentation contains forward looking statements. These and any other information discussed at this presentation are affiliates, advisors or any other
Slide 3: Strong Value Proposition Through Differentiated Pipeline Targeting the Tumor Microenvironment
Strong Value Proposition Through Differentiated Pipeline Targeting the Tumor Microenvironment NOX-A12 VERY FOCUS ON UPCOMING MISSION LEVERAGEABLE PROMISING ORPHAN CANCER CATALYSTS TECHNOLOGY DATA1 INDICATIONS Brain Cancer (1st line GBM) Develop novel therapies Dual MoA leverageable Phase 1/2 clinica
Slide 4: Financial Profile
Financial Profile FINANCIAL OVERVIEW SHAREHOLDING STRUCTURE TME Pharma is listed on Euronext Growth Paris – Public listing 2016 ALTME ISIN Code NL0015000YE1 Cash & equivalents: Ticker ALTME • €3.2 million (31 Dec 2024) Market Euronext Growth Paris • €1.7 million raised in 2025 Market Cap* €7.3 M Sha
Slide 5: Combinations Improve Best Response Rates and Depth of Tumor Shrinkage vs. Standard of Care
NOX-A12 Combinations Improve Best Response Rates and Depth of Tumor Shrinkage vs. Standard of Care Standard of Care Radiotherapy + NOX-A12 Radiotherapy + NOX-A12 Radiotherapy + Chemotherapy + anti-VEGF (Matched reference cohort from center participating in trial: MGMT Unmethylated & incomplete surgi
Slide 6: OS significantly increased for NOX-A12 + anti-VEGF + RT over standard of care and NOX-A12 + RT
NOX-A12 + radiotherapy (N = 10 patients) OS significantly increased for NOX-A12 + anti-VEGF + RT NOX-A12 + radiotherapy + anti-VEGF (N = 6 patients) SOC biomarker (N = 22 patients) over standard of care and NOX-A12 + RT mOS 19.9 months Statistically significant improvement 100 in overall survival fo
Slide 7: Spiegelmer® Platform: Next-Generation RNA Aptamers
Spiegelmer® Platform: Next-Generation RNA Aptamers RNA aptamers made with L-stereoisomer bind their targets with affinity similar or higher than antibodies and come with key benefits: Spiegelmer • Natural resistance to nuclease degradation - no chemical (Blue) modification of backbone needed • Large
Slide 8: Pipeline Assets Complement Anti-Cancer Therapies to Enhance Treatment Efficacy
Pipeline Assets Complement Anti-Cancer Therapies to Enhance Treatment Efficacy Next Inflection Partner/ Therapy & Indication Preclinical Phase 1/2 Phase 2 Phase 3 Point Collaborator NOX-A12 + Radiotherapy ± anti-VEGF Phase 2 protocol Financing and Brain cancer / Glioblastoma approved; Fast Track ini
Slide 9: Experienced Biopharma Team and Board
Experienced Biopharma Team and Board Diede van den Ouden Jarl Ulf Jungnelius, MD Chief Executive Officer Chief Medical Officer - 20+ years professional investor - Oncologist with 25+ years clinical & MANAGEMENT experience research experience - Executive and advisory roles in EU listed - Isofol, Celg
Slide 10: Unique Approach: Modulating Tumor Microenvironment Chemokines to Improve Cancer Therapy
UNIQUE APPROACH: Modulating Tumor Microenvironment Chemokines to Improve Cancer Therapy
Slide 11: The Tumor Microenvironment (TME) is a Key Hurdle to Solid Tumor Treatments
The Tumor Microenvironment (TME) is a Key Hurdle to Solid Tumor Treatments Efficacy of cancer therapy has been limited by the TME of both solid and hematological cancers. Targeting the TME can address key hurdles Sources: Haslam A. & Prasad V., JAMA Network Open. 2019;2(5):e192535. doi:10.1001/jaman
Slide 12: TME Pharma's Drug Candidates Allow the Immune System to Penetrate Solid Tumor Defenses
TME Pharma’s Drug Candidates Allow the Immune System to Penetrate Solid Tumor Defenses and Block Repair of Damaged Tumors NOX-A12 effects Blocks repair of Prevents entry of Enables infiltration of anti-cancer damaged tumors immuno-suppressive cells immune cells into the TME 4 NOX-A12a 3 NOX-A12b & N
Slide 13: Role of CXCL12 Chemokine Axis in Cancer
Role of CXCL12 Chemokine Axis in Cancer NOX-A12 Inhibition of CXCL12 Provides Strong Differentiation Roles of CXCL12 / CXCR4 / CXCR7 Axis MIGRATING CELLS (Immune, Tumor, Endothelial) • Establishment of tumor-promoting microenvironment excluding / sequestering effector T-cells and recruitment of immu
Slide 14: NOX-A12 – Dual Mechanism of Action
NOX-A12 – Dual Mechanism of Action Blockage of Vasculogenesis: Overcome immune exclusion & prevent recruitment of immune-suppressive cells Use in combination with anti-vascular agents such as radiotherapy or anti-VEGF-(R) Combos with CPIs, Bi-Specifics, Cell Therapies RADIOTHERAPY VASCULOGENESIS ANT
Slide 15: TME Pharma at the Forefront of Chemokine Development for Cancer with Limited Direct Competition
TME Pharma at the Forefront of Chemokine Development for Cancer with Limited Direct Competition in Brain & Pancreatic Cancer The CXCL12/CXCR4/CXCR7 axis involved in many cancers and other indications Blocks CXCL12 interaction w/ Developed in CXCR4 CXCR7 Pancreatic Glioblastoma receptor receptor Canc
Slide 16: Brain Cancer is an Area of Active Pharma Interest
Brain Cancer is an Area of Active Pharma Interest • Servier received FDA approval for Voranigo (vorasidenib) in low grade, IDH mutant glioma in Aug 2024 following its $2 billion acquisition of Agios’ oncology business in 20211 • Royalty Pharma, which earlier this year acquired a stake in Agios’ roya
Slide 17: NOX-A12 + Radiotherapy ± Bevacizumab in Chemotherapy Refractory Glioblastoma
NOX-A12 + Radiotherapy ± Bevacizumab in Chemotherapy Refractory Glioblastoma
Slide 18: Glioblastoma is a Devastating Orphan Brain Cancer where the TME Plays a Significant Role
Glioblastoma is a Devastating Orphan Brain Cancer where the TME Plays a Significant Role LACK OF EFFECTIVE THERAPIES & LOW OVERALL SURVIVAL NOX-A12 OFFERS CHEMO-FREE REGIMEN FOR HIGH UNMET NEED PATIENT SEGMENTS CHEMO-RESISTANT 5Y • >50% of GBM patients have unmethylated MGMT promoter leading to no s
Slide 19: NOX-A12's MOA is Relevant to GBM: Attacking Key Survival Mechanisms Following Radiotherapy
NOX-A12’s MOA is Relevant to GBM: Attacking Key Survival Mechanisms Following Radiotherapy RADIOTHERAPY SUPERIOR NOX-A12 VASCULOGENESIS Monocytes PHARMACOLOGY Main driver of new vessel formation after Direct targeting of CXCL12 provides radiotherapy is driven by CXCL12 and more complete inhibition o
Slide 20: NOX-A12 + Radiotherapy Increases Survival and Demonstrates Complete Regression in Animal Models
NOX-A12 + Radiotherapy Increases Survival and Demonstrates Complete Regression of Brain Tumors in Animal Models EFFECTS OF TREATMENTS Autochthonous brain tumor model in rats Radiotherapy at N = 6 animals per group • Spontaneous tumor development in immuno-competent host day 0 • Diversity of tumor ce
Slide 21: GLORIA Phase 1/2 Dose Escalation Study & Expansion Arm
GLORIA Phase 1/2 Dose Escalation Study & Expansion Arm 1st line brain cancer (glioblastoma) with extremely poor prognosis due to: Radiotherapy Wearable pump2 Dose Escalation Cohorts NOX-A12 + RT for 6 weeks • Incomplete surgical Continuous IV NOX-A12 Doses tested: NOX-A12 weekly refill resection or
Slide 22: Combinations Improve Best Response Rates and Depth of Tumor Shrinkage vs. Standard of Care
NOX-A12 Combinations Improve Best Response Rates and Depth of Tumor Shrinkage vs. Standard of Care Standard of Care Radiotherapy + NOX-A12 Radiotherapy + NOX-A12 Radiotherapy + Chemotherapy + anti-VEGF (Matched reference cohort from center participating in trial: MGMT Unmethylated & incomplete surgi
Slide 23: OS significantly increased for NOX-A12 + anti-VEGF + RT over standard of care and NOX-A12 + RT
NOX-A12 + radiotherapy (N = 10 patients) OS significantly increased for NOX-A12 + anti-VEGF + RT NOX-A12 + radiotherapy + anti-VEGF (N = 6 patients) SOC biomarker (N = 22 patients) over standard of care and NOX-A12 + RT mOS 19.9 months Statistically significant improvement 100 in overall survival fo
Slide 24: Key Factors Affecting Glioblastoma Patient Survival when Benchmarking Survival Data
4 Key Factors Affecting Glioblastoma Patient Survival to Consider when Benchmarking Survival Data 1. IDH status • Since 2021 WHO guidelines1, only tumors with wild-type IDH gene are recognized as glioblastoma • For such ‘true’ GBM patients, only 1/3 of median survival time can be expected in compari
Slide 25: Relevant Benchmark Studies in Chemotherapy Resistant Glioblastoma from US and EU
Relevant Benchmark Studies in Chemotherapy Resistant Glioblastoma from US and EU Surgical removal of Overall Median Overall Experimental Agent Patient Response detectable tumor (T=total; Response Rate Survival (mOS) Status Reference (Company) number criteria P=partial; B=biopsy only) (ORR) in months
Slide 26: Higher Survival at 21 Months with NOX-A12 + BEV Than Seen in Benchmark BEV Studies
Higher Survival at 21 Months with NOX-A12 + BEV Than Seen in Benchmark BEV Studies Enrolling Patients with Better Prognosis OS at 21 months: OS at 21 months: Benchmark Phase 2 study with only MGMT Benchmark Phase 3 studies with mixed populations in terms of MGMT unmethylated patients but incl. gross
Slide 27: Approved Phase 2 Study Design in GBM in US and Germany
Approved Phase 2 Study Design in GBM in US and Germany: 5-arm Randomized Controlled Study, 20 Patients / Arm • Newly diagnosed glioblastoma RT - 6 weeks Arm 1 patients with extremely poor NOX-A12 – 200mg/week + bevacizumab prognosis: • Incomplete surgical resection RT - 6 weeks • MGMT promoter Arm 2
Slide 28: The EG12 Score: A Potential Predictive Biomarker for Clinical Outcome
The EG12 Score: A Potential Predictive Biomarker for Clinical Outcome • A predictive biomarker is a measurable biological characteristic that provides information about the likelihood of an individual patient to respond to a specific treatment • Analysis of tumor tissue revealed that the EG12 score
Slide 29: NOX-A12 + RT + Bevacizumab: Near-Complete Response in Exemplary Patient
NOX-A12 + RT + Bevacizumab: Near-Complete Response in Exemplary Patient NOX-A12 + BEV Baseline RT W9 W18 W26 W36 W44 TL A-001 TL 1 Radiographic treatment course of an exemplary patient A-001 with target lesion (TL), non target lesions (NTLs) and MRI volumetric, diffusion (ADC) pPR cPR cPR cPR cPR NT
Slide 30: NOX-A12 Neutralizes the CXCL12 Chemokine on Blood Vessel Walls in GBM Patient
NOX-A12 Neutralizes the CXCL12 Chemokine on Blood Vessel Walls in GBM Patient Baseline Post RT on NOX-A12 CXCL12+ cells Patient C1-001 GLORIA 20 50 C1-001 Out of CD31+ cells (%) Out of total cells (%) 40 DAPI 15 CD31 30 Baseline Post RT/TMZ 10 CXCL12 20 5 Images show 10 areas of pathologist- 0 0 con
Slide 31: NOX-A12 + RT Reduces Tumor Cell Proliferation in GBM Patient
NOX-A12 + RT Reduces Tumor Cell Proliferation in GBM Patient Baseline Post-RT on NOX-A12 GLORIA Proliferating cells Patient C1-001 C1-001 15 Out of total cells (%) DAPI 10 Baseline Post RT/TMZ Ki67 Images show 5 areas of pathologist- confirmed 0 tumor tissue e 12 in Reference A el X- as O Baseline P
Slide 32: NOX-A12 + RT Leads to Extensive Penetration of Immune System in the Tumor of GBM Patient
NOX-A12 + RT Leads to Extensive Penetration of Immune System (Cytotoxic T Cells) in the Tumor of GBM Patient Baseline RT on Post RT NOX-A12 / under OLA Clusters of Granzyme B CD8+ GNZB+ CD8+ positive, cytotoxic T cells Patient C1-001 Patient C1-001 consistent with 2.0 0.8 Out of total cells (%) coor
Slide 33: NOX-A12 + RT = Anti-Cancer Cells + Pro-Cancer Cells
NOX-A12 + RT = Anti-Cancer Cells + Pro-Cancer Cells T cells Macrophages 2.5 C1-001 – +re-surgery on week 13 CD8 – re-surgery on week 13 2.5 Out of total cells (%) CD8+ CD8+/GNZB+ 2.0 Out of total cells (%) 2.0 CD8+/GNZB + + + CD8 /Ki67 1.5 CD8+/Ki67+ 1.5 – re-surgery on week 31 C3-001 –+re-surgery o
Slide 34: Robust Protection Possible Through Foundational Method Claims on NOX-A12
Robust Protection Possible Through Foundational Method Claims on NOX-A12 Method of use patents offer protection nearly identical to that of a composition-of-matter patents for drugs where the first approval is under protection of a method of use patent1: • If using NOX-A12 proves to be therapeutical
Slide 35: Commercial Protection – Minimum Protection is Orphan Drug Exclusivity and Upside into late 2040's
Commercial Protection – Minimum Protection is Orphan Drug Exclusivity and Upside Potential into late 2040’s Patents • Core Method of Use claims on NOX-A12 + Irradiation + Bevacizumab for Glioblastoma will expire in 2043, before any extensions, if granted. • Granted patent covering use of NOX-A12 for
Slide 36: NOX-A12 Combination: Potential for Transformational Activity in GBM
NOX-A12 Combination: Potential for Transformational Activity in GBM • Unprecedented activity in MGMT unmethylated glioblastoma patients with residual tumor after surgery: statistically significant improvement in survival and doubling of mOS1. • High rates of tumor response: 83% mRANO responses durab
Slide 37: NOX-A12 + Immunotherapy in Pancreatic Cancer
NOX-A12 + Immunotherapy in Pancreatic Cancer
Slide 38: Pancreatic Cancer – Extremely Low Overall Survival and Limited Treatment Options
Pancreatic Cancer – Extremely Low Overall Survival and Limited Treatment Options HIGH UNMET NEED IN RELAPSED & REFRACTORY PATIENT LACK OF EFFECTIVE THERAPIES & LOW OVERALL SURVIVAL SETTINGS 5Y • Pancreatic cancer stroma sequesters T cells preventing engagement with tumor cells – many immuno-suppress
Slide 39: NOX-A12 + Immunotherapy: Mode of Action
NOX-A12 + Immunotherapy: Mode of Action CXCL12: - excludes effector immune cells from entering the tumor - attracts bone-marrow derived immuno-suppressive / pro-cancer cells to region of tumor ANTI-CANCER IMMUNE IMMUNO-SUPPRESSIVE / RESPONSE PRO-CANCER Cancer Cells Helper T Cell CXCR4 receptor CXCR7
Slide 40: NOX-A12 + Immunotherapy: Mode of Action
NOX-A12 + Immunotherapy: Mode of Action NOX-A12: - reduces CXCL12 “wall” around solid tumors, which - allows Killer T Cells to enter, eliminates attraction of immuno-suppressive / pro-cancer cells1 ANTI-CANCER IMMUNE IMMUNO-SUPPRESSIVE / RESPONSE PRO-CANCER Cancer Cells Helper T Cell CXCR4 receptor
Slide 41: NOX-A12 + Immunotherapy: Mode of Action
NOX-A12 + Immunotherapy: Mode of Action NOX-A12: - reduces CXCL12 “wall” around solid tumors, which - allows Killer T Cells to enter, eliminates attraction of immuno-suppressive / pro-cancer cells1 ANTI-CANCER IMMUNE IMMUNO-SUPPRESSIVE / RESPONSE PRO-CANCER Cancer Cells Helper T Cell CXCR4 receptor
Slide 42: Phase 1/2 Trial Completed in Pancreatic Cancer and Metastatic Colorectal Cancer Patients
Phase 1/2 Trial Completed in 9 Pancreatic Cancer and 11 Metastatic Colorectal Cancer Patients Baseline tumor 2nd tumor biopsy biopsy Clinical Trial a Scientific Collaboration with: NOX-A12 NOX-A12 + Keytruda® NOX-A12 Patients from Part 1 then transitioned to 1 monotherapy 2 combination treatment of
Slide 43: In PDAC / CRC Patients NOX-A12 Monotherapy Induces Integrated Immune Response and T Cell Clustering
In PDAC / CRC Patients NOX-A12 Monotherapy Induces Integrated Immune Response and T Cell Clustering Cytokine profile Unsupervised clustering of patients based on relative changes in the molecular immune landscape at the end of NOX-A12 monotherapy. Concentrations of the most affected cytokines before
Slide 44: Impressive Survival in Heavily Pre-Treated Patients
Impressive Survival in Heavily Pre-Treated Patients • Pancreatic 4th line of therapy on average 4th line pancreatic cancer patients who lived > 1 year after having no response and rapid progression (2 months) on 3rd line therapy • CRC 6th line of therapy on average 44 Source: Suarez-Carmona M, et al
Slide 45: Overall Survival Longer Than Expected for this Heavily Pre-Treated Population
Overall Survival Longer Than Expected for this Heavily Pre-Treated Population Expected survival Pancreatic cancer patients receiving on average their 4th line of therapy Colorectal cancer Responses to patients receiving on immunotherapy can average their take 6th line of therapy 3-6 months to observ
Slide 46: Status and Next Steps in Development of NOX-A12 in Pancreatic Cancer
Status and Next Steps in Development of NOX-A12 in Pancreatic Cancer • Phase 2 designed to position NOX-A12 + immunotherapy as Standard of Care in 2nd line pancreatic cancer • Design tests 2 arms, each with NOX-A12 + pembrolizumab combined with either gemcitabine/Abraxane® or Onivyde®/5FU/LV • Proto
Slide 47: NOX-A12: Two Orphan Indications with ~$8.5bn Total Addressable Market
NOX-A12: Two Orphan Indications with ~$8.5bn Total Addressable Market NOX-A12 Brain Cancer NOX-A12 Fast Track & Orphan Drug Pancreas Cancer Status Granted Target population US & EU – 69,000 (2nd line) 29,000 New cases per year 107,000 (1st line) Expected duration of treatment >12 months >12 months b
Slide 48: Thank you.
Thank you. Contact us: tme@tmepharma.com