Tme Pharma N.v. · EURONEXT:ALTME
Tme Pharma — Investor Presentation (December 2023)
45 slides from Tme Pharma's investor presentation, December 2023
Slide 1: Improving Therapeutic Outcomes by Targeting the Tumor Microenvironment
www.tmepharma.com Improving Therapeutic Outcomes by Targeting the Tumor Microenvironment December 2023 December 2023 © 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 DATA INDICATIONS Brain Cancer (1st line GBM) Develop novel therapies Dual MoA leverageable Phase 1/2 clinical
Slide 4: 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: MGMT Unmethylated & incomplete surgical resection or biopsy only) Compl
Slide 5: 13-Fold Improvement in 18-month Survival for NOX-A12 + RT + anti-VEGF
13-Fold Improvement in 18-month Survival for NOX-A12 + RT + anti-VEGF vs. Standard of Care Since neither bevacizumab Survival at 18 months (anti-VEGF) alone, nor bevacizumab plus radiotherapy have previously been shown to 67% extend survival 4, the strong increase in survival can be attributed to th
Slide 6: Spiegelmer Platform: Next-Generation L-stereoisomer RNA Aptamers
Spiegelmer® Platform: Next-Generation L-stereoisomer RNA Aptamers • Mirror-image (L-stereoisomer) injectable RNA therapeutics coupled to 40kD PEG for prolonged half-life • NOX-A12 anti-CXCL12 chemokine Spiegelmer • NOX-E36 anti-CCL2 chemokine Spiegelmer • Spiegelmers directly bind and neutralize pro
Slide 7: 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 Pending regulatory Q4 2023: FDA advice Brain cancer / Glioblastoma approvals & & feedback Orpha
Slide 8: Experienced Biopharma Team
Experienced Biopharma Team Aram Mangasarian Ewelina Staniuk Jarl Ulf Jungnelius, MD Chief Executive Officer Sr Director, IR & BD Chief Medical Officer - 20+ years experience in biotech - 10+ years in international projects - Oncologist with 25+ years clinical & - ~€65m raised for TME Pharma - Portfo
Slide 9: Unique Approach: Modulating Tumor Microenvironment Chemokines
UNIQUE APPROACH: Modulating Tumor Microenvironment Chemokines to Improve Cancer Therapy
Slide 10: The Tumor Microenvironment 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 11: TME Pharma's Assets Allow the Immune System to Penetrate Solid Tumor Defenses
TME Pharma’s Assets Allow the Immune System to Penetrate Solid Tumor Defenses NOX-A12 effects Enables infiltration of anti-cancer Prevents entry of Blocks repair of immune cells into the TME immuno-suppressive cells damaged tumors 4 NOX-A12a 3 NOX-A12b & NOX-E36c 5 Increase in trafficking Decrease i
Slide 12: 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 13: 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 14: TME Pharma at the Forefront of Chemokine Development for Cancer
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 15: NOX-A12 + Radiotherapy ± Bevacizumab in Chemotherapy Refractory Glioblastoma
NOX-A12 + Radiotherapy ± Bevacizumab in Chemotherapy Refractory Glioblastoma
Slide 16: Glioblastoma is a Devastating Orphan Brain Cancer
Glioblastoma is a Devastating Orphan Brain Cancer where the TME Plays a Significant Role LACK OF EFFECTIVE THERAPIES & LOW OVERALL SURVIVAL HIGH UNMET NEED PATIENT SEGMENTS • ~50% of patients who will derive no significant benefit 5Y from standard chemotherapy (detectable in advance: MGMT gene promo
Slide 17: NOX-A12's MOA is Relevant to GBM
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 18: NOX-A12 + Radiotherapy Demonstrates Complete Regression of Brain Tumors
NOX-A12 + Radiotherapy Increases Survival and Demonstrates Complete Regression of Brain Tumors EFFECTS OF TREATMENTS Autochthonous brain tumor model in rats Radiotherapy at • Spontaneous tumor development in immuno-competent host day 0 • Diversity of tumor cell types with therapeutic resistance comp
Slide 19: GLORIA Phase 1/2 Dose Escalation Study & Expansion Arms
GLORIA Phase 1/2 Dose Escalation Study & Expansion Arms 1st line brain cancer Radiotherapy Dose Escalation Cohort NOX-A12 + RT for 6 weeks (glioblastoma) with extremely Wearable pump2 NOX-A12 Doses tested: poor prognosis due to: NOX-A12 Continuous IV weekly refill 200, 400 & 600 mg/week • Incomplete
Slide 20: Combinations Improve Best Response Rates and Depth of Tumor Shrinkage
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: MGMT Unmethylated & incomplete surgical resection or biopsy only) Compl
Slide 21: NOX-A12 Demonstrates Superior ORR vs Historical Controls
NOX-A12 Demonstrates Superior ORR vs Historical Controls in More Challenging Brain Cancer Population AVAglio and BIOMARK are two studies where BEV (anti-VEGF) was added on top of Standard of Care – Stupp protocol: surgery and radiochemotherapy with temozolomide (TMZ) Overall Response Rate (ORR) RT+
Slide 22: NOX-A12 + RT + Bevacizumab: Maturing Survival Data
NOX-A12 + RT + Bevacizumab: Maturing Survival Data 67% OS at 18 months Standard of Care1 18 months mOS 10.5 months on study • 67% landmark overall survival at Patient 1 18 months Patient 2 • Median overall survival (mOS) at least 18 months and continuing to increase Patient 3 deceased • 83% of patie
Slide 23: 13-Fold Improvement in 18-month Survival
13-Fold Improvement in 18-month Survival for NOX-A12 + RT + anti-VEGF vs. Standard of Care Since neither bevacizumab Survival at 18 months (anti-VEGF) alone, nor bevacizumab plus radiotherapy have previously been shown to 67% extend survival 4, the strong increase in survival can be attributed to th
Slide 24: Relevant Benchmark Studies in Chemotherapy Resistant Glioblastoma
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 Survival (mOS) in Status Reference (Company) number criteria P=partial; B=biopsy only) Rate (ORR) months
Slide 25: The EG12 Score: A Potential Predictive Biomarker
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 26: 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 27: NOX-A12 + RT Show Neutralization of CXCL12
NOX-A12 + RT Show Neutralization of CXCL12 Post RT / under Baseline 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 confirmed e e 12 12 in in A A tum
Slide 28: NOX-A12 + RT Reduce Tumor Cell Proliferation
NOX-A12 + RT Reduce Tumor Cell Proliferation Post RT / under Baseline 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 Post RT/TMZ/
Slide 29: NOX-A12 + RT Leads to Extensive Penetration of Cytotoxic T Cells
NOX-A12 + RT Leads to Extensive Penetration of Immune System (Cytotoxic T Cells) in the Tumor Baseline Post-RT Post RT on 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 (%) coordinated im
Slide 30: 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 31: Good Safety, Tolerability and Promising Efficacy Data
Good Safety, Tolerability and Promising Efficacy Data in NOX-A12 and NOX-A12 + Bevacizumab Arms • Good safety and tolerability profile of all combinations • Tissue analysis confirms mode(s) of action2,3 • Potential biomarker identified which is predictive for PFS in patients treated with NOX-A12 + R
Slide 32: NOX-A12 + Immunotherapy in Pancreatic Cancer
NOX-A12 + Immunotherapy in Pancreatic Cancer
Slide 33: 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 34: 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 35: 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 36: 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 37: Phase 1/2 Trial in Pancreatic 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 38: 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 39: 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 39 Source: Suarez-Carmona M, et al
Slide 40: 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 41: 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 42: Strong Value Proposition
TME & pharma Strong Value Proposition
Slide 43: NOX-A12: Two Orphan Indications with ~$8.5bn Total Addressable Market
NOX-A12: Two Orphan Indications with ~$8.5bn Total Addressable Market NOX-A12 NOX-A12 Brain Cancer Pancreas Cancer 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 based on median OS $ Total Addressable Ma
Slide 44: Financial Metrics
Financial Metrics FINANCIALS AND SHAREHOLDING STRUCTURE TME Pharma is listed on Euronext Growth Paris – ALTME Public listing 2016 Highly efficient structure with 14 employees and key expertise in-house ISIN Code NL0015000YE1 Cash & equivalents: Ticker ALTME Market Euronext Growth Paris • €3 million
Slide 45: Thank you.
Thank you. Contact us: tme@tmepharma.com