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

Dual inhibition of post-radiogenic revascularization in newly-diagnosed glioblastoma: Final results of the multicentric phase 1/2 GLORIA trial (EANO 2026) - P1/2 | "Subsequently, we expanded the ongoing trial and six additional patients were included that additionally received the VEGF-targeting antibody bevacizumab (BEV) to RT and NOX-A12.The primary endpoint was safety. Our findings establish proof-of-principle that dual inhibition of angio- and vasculogenesis following RT via blockade of VEGF and CXCL12 is a safe and promising targeted strategy for patients with newly-diagnosed GBM."

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

Inhibition of chemokine CXCL12 modulates the tumor microenvironment in glioblastoma and potentiates immune checkpoint inhibitor efficacy in a tissue-specific manner. (PubMed, Neurooncol Adv) - "We treated SB28 tumor-bearing mice with vehicle, ICI, CXCL12 inhibitor (NOX-A12), or a combination of NOX-A12 with ICI...CXCL12 inhibition demonstrates therapeutic potential in facilitating anti-tumor immune response by dual mechanism, including T cell expansion and TAM reduction. The inability to deplete TAMs and improve survival in intracranial GBM underscores the need to address brain-specific mechanisms underlying TAM persistence to advance immunotherapy in GBM."

Biomarker • Checkpoint inhibition • Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CD4 • CD8 • CXCL12

Dual Inhibition of Post-Radiogenic Revascularization in Newly-Diagnosed Glioblastoma - Final results of the multicentric phase 1/2 GLORIA trial. (ESTRO 2026) - P1/2 | "Subsequently, we expanded the ongoing trial and six additional patients were included that additionally received the VEGF-targeting antibody bevacizumab (BEV) to RT and NOX-A12.The primary endpoint was safety. Our findings establish proof-of-principle that dual inhibition of angio- and vasculogenesis following RTvia blockade of VEGF and CXCL12 is a safe and promising targeted strategy for patients with newly-diagnosed GBM."

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

TME Pharma Announces Publication of NOX-A12 'Triple Therapy' Phase 1/2 Expansion Arm A Findings from GLORIA trial in Nature Communications (GlobeNewswire) - "The authors noted that overall survival (OS) of patients receiving NOX-A12 Triple Therapy significantly outperformed two different cohorts of similar patients external to the trial who received standard of care treatment, and further noted that due to the conservative trial design, the study 'likely underestimates survival compared with most contemporary trials'.....The findings described in the publication demonstrate the potential and value of TME Pharma’s NOX-A12 asset."

P1/2 data • Glioblastoma

L-RNA aptamer-based CXCL12 inhibition combined with radiotherapy and bevacizumab in newly-diagnosed glioblastoma: expansion of the phase I/II GLORIA trial. (PubMed, Nat Commun) - P1/2 | "Rapid vascular recovery is a key feature preceding glioblastoma (GBM) recurrence after radiotherapy (RT). Median progression-free (PFS) and overall survival (OS) after RT + BEV + NOX-A12 were 9.1 and 19.9 months, respectively, significantly outperforming RT + NOX-A12 (p = 0.009; p = 0.021) in a post-hoc comparative analysis, with two patients exceeding 2-year OS. These findings establish proof-of-principle for dual inhibition of CXCL12 and VEGF in patients with newly-diagnosed GBM following RT."

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

SDF-1 Inhibition Attenuates VEGF-Driven Retinal Leukostasis and Neovascularization in Ischemic Retinopathy. (PubMed, J Ocul Pharmacol Ther) - "SDF-1 functions as a cooperative mediator of VEGF-driven retinal vascular pathology. Dual targeting of SDF-1 and VEGF enhances suppression of ischemic retinal injury and NV."

Journal • Diabetic Retinopathy • Inflammation • Retinal Disorders • Retinopathy of Prematurity • CDKN1A • CXCL12

Aptamers in cancer therapy: Why has clinical translation lagged behind preclinical promise? (PubMed, Biomed Pharmacother) - "Through analysis of representative clinical programs, including the systemic nucleolin-targeting aptamer AS1411, the microenvironment-modulating CXCL12 inhibitor NOX-A12, and the locally administered personalized platform AM003, this review highlights how delivery strategy, target context, and clinical deployment critically shape therapeutic outcomes. Recurrent translational barriers related to systemic exposure, tumor accessibility, regulatory pathways, and competition with established modalities are identified, together with lessons from both failed and emerging programs. Finally, we discuss practical strategies to improve clinical alignment, including human-relevant selection models, localized or combination therapies, and AI-assisted design, positioning aptamers for context-appropriate roles in future precision oncology."

Journal • Preclinical • Review • Oncology • CXCL12 • NCL

Aptamers targeting immune checkpoints for tumor immunotherapy: a comprehensive review. (PubMed, Front Oncol) - "Although most aptamer-based checkpoint inhibitors remain in preclinical stages, early phase clinical investigations (primarily with C-X-C motif chemokine ligand 12 (CXCL12)-targeting Spiegelmer NOX-A12 in combination settings, as well as earlier programs such as AS1411 targeting nucleolin) have demonstrated effective inhibition of immune checkpoint signaling, reactivation of T-cell function, and synergistic effects when combined with existing immunotherapies. Preclinical and early phase clinical investigations have demonstrated that aptamers can effectively inhibit immune checkpoint signaling, reactivate T-cell function, and potentiate synergistic effects when combined with existing immunotherapies. By critically evaluating current progress and identifying key translational challenges, this review provides strategic insights into the future development of aptamer-based immunotherapeutic platforms, ultimately guiding the advancement of more precise, cost-effective,..."

Journal • Review • Oncology • CXCL12 • NCL • PD-1

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