olaptesed pegol (NOX-A12) / TME Pharma - LARVOL DELTA

Aptamer-based conjugated molecules in experimental and clinical approaches to treatment of glioblastoma (PubMed, Zh Vopr Neirokhir Im N N Burdenko) - "Important clinical successes include the results of NOX-A12 drug and data on combined drugs based on trastuzumab in patients with metastatic breast cancer. Furthermore, very high control of breast cancer brain metastases in HER-2 positive cases was demonstrated for trastuzumab-emtansine and trastuzumab-deruxtecan. The last finding indicates the perspective for aptamer targeting glioblastoma tumor cells in conjugation with emtansine or deruxtecan."

Journal • Review • Brain Cancer • Breast Cancer • Glioblastoma • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CXCL12 • EGFR • HER-2

TME Pharma continues its active discussions with potential partners for the NOX-A12 program. (The Manila Times) - "TME Pharma has kept the clinical trial for glioblastoma open so that it can be resumed as soon as a suitable partner is found. TME Pharma expects to be able to present a clear update and strategy to the market in the coming weeks."

Trial status • Glioblastoma

Dual inhibition of post-radiogenic revascularization in newly-diagnosed glioblastoma: Final results of the multicentric phase 1/2 GLORIA trial. (SNO 2025) - P1/2 | "Six patients were included that additionally received the VEGF-targeting antibody bevacizumab (BEV) to RT and NOX-A12. Our findings establish proof-of-principle that dual inhibition of angio- and vasculogenesis via blockade of VEGF and CXCL12 is a safe and promising targeted strategy for patients with newly-diagnosed GBM following RT."

Clinical • P1/2 data • Brain Cancer • Glioblastoma • Solid Tumor • CXCL12 • MGMT

Dual inhibition of post-radiogenic revascularization in newly-diagnosed glioblastoma: Final results of the multicentric phase 1/2 GLORIA trial. (WFNOS 2025) - P1/2 | "Six patients were included that additionally received the VEGF-targeting antibody bevacizumab (BEV) to RT and NOX-A12. Our findings establish proof-of-principle that dual inhibition of angio- and vasculogenesis via blockade of VEGF and CXCL12 is a safe and promising targeted strategy for patients with newly-diagnosed GBM following RT."

Clinical • P1/2 data • Brain Cancer • Glioblastoma • Solid Tumor • CXCL12 • MGMT

The brain tissue environment contributes to a unique response of glioblastoma against immunotherapy (SITC 2025) - "However, an increase in T cells by CXCL12 inhibition was not translated into increased survival, suggesting that additional factors in the brain tissue contribute to treatment resistance. Elucidating those factors is imperative for the development of innovative strategies to augment immunotherapy efficacy in GBM.Acknowledgements We acknowledge TME Pharma AG for providing of Nox-A12Ethics Approval All animal experiments and protocols were reviewed and approved by National Cancer Institute"

Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CD4 • CD8 • CXCL12

OPTIMUS: Olaptesed With Pembrolizumab and Nanoliposomal Irinotecan or Gemcitabine/Nab-Paclitaxel in MSS Pancreatic Cancer (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: TME Pharma AG | Trial completion date: Oct 2028 ➔ Mar 2029 | Trial primary completion date: Oct 2027 ➔ Mar 2028

Trial completion date • Trial primary completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

TME Pharma Announces New Strategy (Businesswire) - "TME Pharma N.V...announces today a strategic change to facilitate ongoing efforts to finance the next clinical trial for NOX-A12 through agreements with pharma or financial partners....TME Pharma will continue to pursue all ongoing discussions and opportunities to optimize the value of its NOX-A12 and NOX-E36 assets. Both assets will be maintained to allow rapid advancement of the programs once financing and/or partnerships are in place."

Commercial • Oncology

TME Pharma Announces the Launch of Fully Guaranteed Public Offer for €2.6 Million Open Only to Shareholders to Enable Completion of Strategic Transactions by June 2025 (Businesswire) - "TME Pharma N.V...announces the launch of a €2.6 million financing to be carried out through a public offer without preferential subscription rights for in total 52,000,000 new shares...The net proceeds are expected to extend financial visibility into June 2025. Approximately 1/3 of the net proceeds of the capital increase will be used for research, development and regulatory activities including completion of the ongoing Phase 1/2 part of the NOX-A12 GLORIA trial in glioblastoma. Approximately 1/3 of proceeds will be used for general and administrative corporate purposes. Approximately 1/3 will be used to support pursuing and executing out-licensing, financing, spin-out and/or strategic transactions for both NOX-A12 and NOX-E36."

Financing • Glioblastoma

TME Pharma Announces Corporate Strategy Update and Upcoming €2.6 Million Guaranteed Financing With Intention to Launch Public Offer Open Only to Shareholders to Enable Completion of Transactions Around NOX-A12 and NOX-E36 by June 2025 (Businesswire) - "TME Pharma N.V...announces its intention to launch a €2.6 million financing to be carried out through a public offer without preferential subscription rights for in total 52,000,000 new shares. The public offer will be reserved for the company's shareholders only, determined as at the record date of December 10, 2024...'This planned guaranteed capital injection secures the operations of TME Pharma into June 2025 under its current plans, with the goal of completing ongoing initiatives with regards to licensing, financing, spin-out or a strategic transaction on both NOX-A12 and NOX-E36.'"

Financing • Inflammation • Oncology

TME Pharma Announces Poster Presentation by U.S. National Cancer Institute on CXCL12 Inhibition by NOX-A12 in Glioblastoma at 2024 SNO Annual Meeting (Businesswire) - "The presentation showed that combining CXCL12 inhibition with anti-PD-1/CTLA4 immune checkpoint inhibition increases the presence of anti-cancer immune cells in tumor tissues both inside and outside the brain, including activated cytotoxic ('killer') T cells. Importantly, improved long-term survival and immunological protection from tumor recurrence were seen in models of tumors growing outside but not inside the brain. This suggests that while the combination with anti-PD-1/CTLA4 immune checkpoint inhibitors is a promising therapy for tumors outside the brain, it may not be an optimal approach for treating brain tumors."

Preclinical • Glioblastoma • Solid Tumor

Potentiating the efficacy of immune check-point inhibitors in glioblastoma by inhibition of CXCL12 (SNO 2024) - "We examined the immunomodulatory and therapeutic efficacy of CXCL12 inhibition, using a small molecule NOX-A12, with and without ICIs in pre-clinical murine GBM models... Inhibition of CXCL12 enabled the increase of effector cytotoxic T cells by ICI, improving survival in the s.c. GBM model, but not in i.c. GBM model. This might be due to differences in CXCL12 effect between extra and intra-CNS tumor or due to robust immune response causing excessive brain edema and death. These will be further explored in ongoing and future studies."

Clinical • Brain Cancer • CNS Disorders • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CD4 • CD8 • CXCL12 • PD-L1

Potentiating the efficacy of immune check-point inhibitors in glioblastoma by inhibition of CXCL12 (SITC 2024) - "We examined the immunomodulatory and therapeutic efficacy of CXCL12 inhibition, using the small molecule NOX-A12, with and without ICIs in pre-clinical murine GBM models...These differences between extra and intra-CNS tumor will be further explored in ongoing and future studies. Ethics Approval All animal experiments and protocols were reviewed and approved by National Cancer Institute review board."

Clinical • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CD4 • CD8 • CXCL12 • CXCR4 • PD-L1

TME Pharma Awarded €2.4 Million German Federal Grant to Support NOX-A12 Phase 2 Trial in Brain Cancer (Businesswire) - "TME Pharma N.V...announces that it is awarded a non-refundable grant of €2.4 million from the KMU-innovativ funding program run by the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF)....The non-dilutive non-refundable funding will support TME Pharma’s planned Phase 2 randomized controlled study evaluating its lead asset, the CXCL12 inhibitor NOX-A12, for use in the treatment of aggressive adult brain cancer, glioblastoma. Funds will be disbursed after the relevant costs in the trial have been incurred. This grant complements other non-dilutive support worth approximately €5 million for study aspects that are out of the scope of the BMBF grant."

Financing • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Outlook for the Remainder of 2024 and for 2025 (Businesswire) - "TME Pharma has achieved significant regulatory milestones in advancing the NOX-A12 glioblastoma program to the next phase of clinical development, having received approval for the Phase 2 study protocol from both the FDA in the US and BfArM in Germany. TME Pharma’s next milestones in the clinical development of the NOX-A12 program are financing and initiation of the randomized, controlled Phase 2 clinical trial...The Society for Neuro-Oncology (SNO) Annual Meeting in November 2024 will feature a poster presentation highlighting data from preclinical studies conducted at the U.S. National Cancer Institute (NCI) exploring the effects of inhibition of CXCL12 by NOX-A12 in combination with immune checkpoint inhibition in glioblastoma models."

New P2 trial • Preclinical • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

GLORIA: Glioblastoma Treatment With Irradiation and Olaptesed Pegol (NOX-A12) in MGMT Unmethylated Patients (clinicaltrials.gov) - P1/2 | N=117 | Active, not recruiting | Sponsor: TME Pharma AG | N=27 ➔ 117 | Trial completion date: Dec 2024 ➔ Dec 2028 | Trial primary completion date: Dec 2024 ➔ Dec 2028

Enrollment change • Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • IDH1

TME Pharma Announces Acceptance of the NCI’S Abstract on NOX-A12 in Glioblastoma for Presentation at the SNO 2024 Annual Meeting (Businesswire) - "TME Pharma N.V...announces that an abstract highlighting NOX-A12 data from preclinical studies performed by the U.S. National Cancer Institute (NCI) has been selected for poster presentation at the 2024 Society for Neuro-Oncology (SNO) Annual Meeting, taking place in Houston, Texas, USA, November 21-24, 2024. NCI is part of the National Institutes of Health...The research was conducted at the NCI under the material transfer agreement established with TME Pharma in June 2022 to explore the effects of TME Pharma's CXCL12 inhibitor NOX-A12 in brain tumors....The full abstract will be published in the SNO official journal Neuro-Oncology on Friday, November 11, 2024. Both the abstract and poster presentation will be made available on the TME Pharma website following the conference."

Clinical • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

TME Pharma Announces Oral Presentation at ESMO Congress 2024 With Updated Results From NOX-A12 GLORIA Phase 1/2 Trial in Glioblastoma - P1/2 | N=27 | GLORIA (NCT04121455) | Sponsor: TME Pharma AG | "TME Pharma...announced an oral presentation by Dr.Frank A. Giordano, lead investigator of the NOX-A12 GLORIA Phase 1/2 trial in first-line brain cancer (glioblastoma), taking place on Sunday, September 15, 2024, at the European Society for Medical Oncology (ESMO) Congress in Barcelona, Spain...The research showed a significant decrease in tumor perfusion which supports the suggested mode of action of the combination therapy. The presentation also reveals that the deeper responses to the combination therapy with NOX-A12 and bevacizumab translate to significantly longer median progression free survival (mPFS: 9.1 months, p=0.003) and median overall survival (mOS: 19.9 months, p=0.005) compared to a matched SOC reference cohort (mPFS: 4.0 months; mOS: 9.5 months) or to NOX-A12 alone (mPFS: 5.7 months; mOS: 12.7 months)."

P1/2 data • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

Dual inhibition of post-radiogenic angio-vasculogenesis in glioblastoma: Results of the phase I/II GLORIA trial (ESMO 2024) - P1/2 | "Here, we report data from exploratory tissue analysis and clinical outcomes for dual inhibition of vasculo- (NOX-A12) and angiogenesis (bevacizumab, BEV) in GBM in the first expansion arm. GBM tissue samples were analyzed by spatial omics to explore regulation and cellular sources of CXCL12 and VEGFA expression. Post-radiogenic VEGF-driven angiogenesis and CXCL12-driven vasculogenesis are complementary and non-redundant, spatially distinctive mechanisms facilitating GBM recurrence. Combinatory inhibition by NOX-A12 + BEV is safe and yields promising clinical outcomes."

P1/2 data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CXCL12 • MGMT

TME Pharma Announces Oral Presentation of NOX-A12 GLORIA Phase 1/2 Trial in Glioblastoma at ESMO Congress 2024 (Businesswire) - "TME Pharma N.V...announced today that an abstract featuring results from the NOX-A12 GLORIA Phase 1/2 trial in first-line brain cancer (glioblastoma) has been selected for presentation at the European Society for Medical Oncology (ESMO) Congress taking place in Barcelona, Spain, September 13-17, 2024. The oral presentation will provide further analysis of the dual inhibition of NOX-A12 and bevacizumab in glioblastoma in the expansion arm of the GLORIA Phase 1/2 trial."

P1/2 data • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

OPTIMUS: Olaptesed With Pembrolizumab and Nanoliposomal Irinotecan or Gemcitabine/Nab-Paclitaxel in MSS Pancreatic Cancer (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: TME Pharma AG | Trial completion date: Oct 2027 ➔ Oct 2028 | Trial primary completion date: Oct 2026 ➔ Oct 2027

Metastases • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

TME Pharma Announces a Financing Guarantee Agreement and the Launch of Capital Increase of Minimum 2.2 Million Euros (Businesswire) - "TME Pharma...announced the launch of a capital increase through issuance of new shares for a minimum of €2.2 million gross proceeds. Guaranteed net proceeds will allow the company to reach key strategic partnering and financing milestones in 2024...Approximately 30% of net proceeds from the capital increase will be used on research and development (R&D) activities including ongoing NOX-A12 GLORIA Phase 1/2 trial in brain cancer, regulatory interactions in Europe for the next brain cancer trial and intellectual property activities. Another approximately 30% of net proceeds will be used for outreach to potential industry partners and investors, the pursuit of government or charitable grants and preparation for the targeted monetization of the NOX-E36 program. The remaining 40% of net proceeds will be used for general corporate purposes including accounting, auditing, legal advice and maintenance of the listing."

Financing • Brain Cancer • CNS Tumor • Oncology • Solid Tumor

TME Pharma Announces Publication in Nature Communications of Biomarker Data From NOX-A12 Gloria Phase 1/2 Trial in Glioblastoma (Businesswire) - P1/2 | N=27 | GLORIA (NCT04121455) | Sponsor: TME Pharma AG | "The EG12 score is calculated by analyzing the frequency of positivity for NOX-A12’s target, CXCL12, on two key cell types in the glioblastoma tumor microenvironment: endothelial (E) and glioma (G) cells. The score significantly correlated with the clinical outcome, in terms of progression-free survival (PFS) for patients treated with NOX-A12 and radiotherapy (r = 0.87; p = 0.005), but not for a cohort of reference patients with comparable characteristics treated with standard of care (r = 0.13; p = 0.56). As such, the biomarker appears to be specific for response to NOX-A12-based therapies. When dividing the trial population into two groups in the middle by its EG12 score, GLORIA patients with higher EG12 scores had a significantly longer median PFS than those with lower scores (6.0 vs. 3.0 months; p = 0.031) and also a strong trend towards improved median overall survival (15.8 vs. 11.1 months; p = 0.075)."

P1/2 data • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

L-RNA aptamer-based CXCL12 inhibition combined with radiotherapy in newly-diagnosed glioblastoma: dose escalation of the phase I/II GLORIA trial. (PubMed, Nat Commun) - P1/2 | "In a post-hoc exploratory analysis of tumor tissue, higher frequency of CXCL12+ endothelial and glioma cells was significantly associated with longer PFS under NOX-A12. Our data imply safety of NOX-A12 and its efficacy signal warrants further investigation."

Journal • P1 data • P1/2 data • P2 data • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • CXCL12 • MGMT

TME Pharma Receives US FDA Fast Track Designation for Lead Asset NOX-A12 in Brain Cancer (Businesswire) - "TME Pharma N.V...announces that the US Food and Drug Administration (FDA) has granted Fast Track designation for NOX-A12 (olaptesed pegol), TME Pharma's CXCL12 inhibitor, in combination with radiotherapy and bevacizumab for use in the treatment of the aggressive adult brain cancer, glioblastoma, in the newly diagnosed setting where the tumor is resistant to chemotherapy and measurable tumor remains after surgery....TME Pharma's latest regulatory milestones were supported by recent survival data from the GLORIA Phase 1/2 study..."

Fast track designation • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

TME Pharma Announces FDA Clearance of Investigational New Drug (IND) Application for NOX-A12 Phase 2 Trial in Brain Cancer (Businesswire) - "TME Pharma N.V...announces that the US Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for NOX-A12, TME Pharma's CXCL12 inhibitor, for use in the treatment of aggressive adult brain cancer, glioblastoma.... The study is expected to be initiated later this year, starting first in Europe, once the necessary resources and preparations are in place....Together with the IND submission TME Pharma has also submitted a Fast-Track Designation request to the FDA to secure an expedited regulatory pathway for NOX-A12 in glioblastoma and the company expects to receive the FDA's decision before the end of March 2024."

Fast track designation • IND • New P2 trial • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor