Tme Pharma N.v. · EURONEXT:ALTME
Tme Pharma — KOL Webinar with Dr Frank Giordano (November 2022)
25 slides from Tme Pharma's conference presentation, Nov 22, 2022
Slide 1: KOL Webinar with Dr Frank Giordano
KOL Webinar with Dr Frank Giordano NOX-A12 Combination Therapies in First-Line Glioblastoma – The Key to the Tumor Microenvironment? Analysis of Maturing Data from the Ongoing GLORIA Trial November 22, 2022 | 12 PM ET / 6 PM CET
Slide 2: Webinar Presenters
WEBINAR PRESENTERS Dr. Frank Giordano Professor and Chair of the Dept. of Radiation Oncology at the Aram Mangasarian University Medical Center CEO Mannheim TME Pharma and Lead Investigator of NOX- A12 GLORIA Phase 1/2 Study Webinar moderated by: Guillaume van Renterghem, Managing Director at LifeSci
Slide 3: 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 HIGH UNMET NEED PATIENT SEGMENTS 5Y • MGMT unmethylated promoter – chemotherapy ineffective Orphan • NOX-A12 to focus on MGMT unmethylated patients Status • Inc
Slide 4: 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 5: NOX-A12 + Radiotherapy Significantly Increases Survival and Demonstrates Complete Regression of Brain Tumors
NOX-A12 + Radiotherapy Significantly 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 r
Slide 6: GLORIA Phase 1/2 Dose Escalation Study & Expansion Arms
GLORIA Phase 1/2 Dose Escalation Study & Expansion Arms Dose Escalation Cohort NOX-A12 + RT Expansion Arms NOX-A12 Doses tested: NOX-A12 at 600 mg/week + Radiotherapy + 200, 400 & 600 mg/week anti-VEGF or anti-PD-1 1st line brain cancer (glioblastoma) with extremely poor prognosis due to: • Incomple
Slide 7: Best Response Under NOX-A12 + Radiotherapy vs. Matched Reference Cohort
Best Response Under NOX-A12 + Radiotherapy (RT) vs. Matched Reference Cohort GLORIA MRI Assessment NOX-A12 + RT by MRI Assessment of Standard of Care Independent Central Reader Matched Reference Cohort (n=10) (n=20) SPDP [mm²] SPDP [mm²] 300 NOX-A12 patients 300 Standard of Care patients - 90% w/ tu
Slide 8: Multiplex-IF in On-therapy GBM Patient vs. References: Shows Extensive Infiltration of Activated Cytotoxic T Cells
Multiplex-IF in On-therapy GBM Patient vs. References: Shows Extensive Infiltration of Activated Cytotoxic T Cells Baseline Post-RT Post RT on NOX-A12 / under OLA Clusters of Granzyme B CD8+ GNZB+ CD8+ Patient C1-001 Patient C1-001 positive, cytotoxic T cells 2.0 0.8 consistent with Out of total cel
Slide 9: GLORIA Dose-Escalation Cohorts – Results
GLORIA Dose-Escalation Cohorts – Results Toxicity • Treatment was safe with no dose-limiting toxicity Clinical Efficacy • 9/10 patients achieved SD or better • 4/10 patients achieved PR • 3/4 of the responses occurred after completion of RT • Signs of clinical efficacy despite 3+3 design with escala
Slide 10: GLORIA Phase 1/2 Dose Escalation Study & Expansion Arms
GLORIA Phase 1/2 Dose Escalation Study & Expansion Arms Dose Escalation Cohort NOX-A12 + RT Expansion Arms NOX-A12 Doses tested: NOX-A12 at 600 mg/week + Radiotherapy + 200, 400 & 600 mg/week anti-VEGF or anti-PD-1 1st line brain cancer (glioblastoma) with extremely poor prognosis due to: • Incomple
Slide 11: Dr. Frank A. Giordano
Dr. Frank A. Giordano Professor and Chair of the Dept. of Radiation Oncology at the University Medical Center Mannheim Lead Investigator of NOX-A12 GLORIA Phase 1/2 Study
Slide 12: Data from the GLORIA trial presented at the SNO on November 18 and further updates
Data from the GLORIA trial presented at the SNO on November 18 and further updates
Slide 13: Dual Inhibition of Post-Radiogenic Angio-Vasculogenesis by Olaptesed Pegol (NOX-A12) and Bevacizumab
DUAL INHIBITION OF POST-RADIOGENIC ANGIO- VASCULOGENESIS BY OLAPTESED PEGOL (NOX-A12) AND BEVACIZUMAB IN GLIOBLASTOMA - INTERIM DATA FROM THE FIRST EXPANSION ARM OF THE GERMAN PHASE 1/2 GLORIA TRIAL. Frank A. Giordanot, Julian P. Layer'2, Sonia Leonardelli?, Lea L. Friker®, Christina Schaub, Roberta
Slide 14: Rationale & Study Design
1 RATIONALE & STUDY DESIGN Dual inhibition of the CXCL12- and VEGF-axes after radiotherapy (RT) of glioblastoma (GBM) ➢ abrogates CXCL12-dependent recruitment of pro-vasculogenic/tumorigenic bone marrow-derived cells (BMDC) ➢ prevents VEGF-driven angiogenesis within the tumor compartments Tumor marg
Slide 15: Rationale & Study Design
1 RATIONALE & STUDY DESIGN Primary Endpoint: Safety as per # of patients with treatment-related CTCAE Secondary Endpoints: NOX-A12 plasma levels, tumor vascularization/perfusion as per advanced MRI, PFS-6, mPFS, OS, QoL (Quality of Life), NANO (Neurologic Assessment in Neuro-Oncology) Exploratory En
Slide 16: Safety
2 SAFETY • Triple treatment well-tolerated and safe • Of all G≥2 AEs (n = 66), 3 (4.5%) NOX-A12-related (all G2) • No dose limiting toxicities (DLT) and no treatment-related deaths *NOX-A12-only related AE Extravasation G2 Infusion site reaction G2 Peripheral edema G2
Slide 17: Treatment Course
3 BL W9 TREATMENT COURSE W18 W27 W36 W44 W52 A-001 PR mRANO +/- 0 NANO A-002 PR mRANO +/- 0 NANO A-003 PR mRANO +/- 0 NANO A-004 PR mRANO +/- 0 NANO A-005 PR mRANO -1 -2 NANO A-006 SD PD mRANO NANO: +/- 0 PD NANO decrease in score • 5/6 patients achieved partial responses (PRs) as per mRANO in week
Slide 18: Exemplary Patient
4 TL Baseline NOX-A12 + BEV RT W9 W18 EXEMPLARY PATIENT W26 W36 W44 A-001 TL 1 Radiographic treatment course of patient A-001 with target lesion (TL), non target mRANO pPR cPR cPR cPR cPR lesions (NTLs) and MRI NTL volumetric, diffusion (ADC) A-001 NTL 1 disappeared disappeared disappeared disappear
Slide 19: Exemplary Patient
4 EXEMPLARY PATIENT Multiplexed immuno-fluorescence (CODEX®) analysis of pretherapeutic tumor tissue of the same patient confirms distinct spatial distribution of CXCL12 and VEGFB in tumor compartments CD31 CXCL12 DAPI CD31 CXCL12 VEGFB VEGFB
Slide 20: Target Lesion Response
5 TARGET LESION RESPONSE Data cut-off Oct 27, 2022 • Trial results (left) were compared to the previously reported dose escalation cohorts (center) and a matched imaging reference cohort (right) treated with standard of care (SOC) • The mean best sum of perpendicular diameters (SPD) response was -74
Slide 21: Update: Target Lesion Response
UPDATE: TARGET LESION RESPONSE RT + NOX-A12 + BEV 200 Max. change from baseline [%] 100 PR 6/6 0 Data cut-off Nov 1, 2022 -100 • Trial results (left) were compared to the previously reported dose escalation cohorts (center) and a matched imaging reference cohort (right) treated with standard of care
Slide 22: Advanced Imaging & QoL
6 ADVANCED IMAGING & QoL Mean best changes from baseline Advanced imaging: • Apparent Diffusion Coefficient (ADC) 20.6% (-24.5% to 59.1%) • relative Cerebral Blood Volume (rCBV) -77.9% (-50 to -100%) • Highly perfused-tumor fraction (FTBhigh) -87.2% (-61.3% to -100%) • SPD response of NTL sums -93.8
Slide 23: Conclusions
Conclusions: • Radiotherapy + NOX-A12 + Bevacizumab in chemotherapy refractory GBM is safe • No DLT • Encouraging efficacy of dual inhibition of angio- vasculogenesis • Treatment and follow up ongoing
Slide 24: Q&A Session
Q&A SESSION
Slide 25: Thank you.
Thank you. Contact us: tme@tmepharma.com
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