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

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

TME Pharma Provides Results of Final Exercise of Warrants Y: Additional €854K Raised and Extension of Cash Runway From May Into July 2024 (Businesswire) - "TME Pharma N.V...provides results of the final exercise of Warrants Y and an update on the outstanding number of ordinary shares, Warrants Y and Warrants Z....'We are now looking forward to achieving our next targeted clinical and regulatory milestones, notably approval of the Investigational New Drug application for NOX-A12 in glioblastoma and a response to our Fast Track request targeted by quarter’s end, both of which are important milestones in advancing the development of our lead asset to become the best available therapy for aggressive brain cancer patients.'"

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

TME Pharma Announces Final Median Overall Survival Data Reaching 19.9 Months for NOX-A12 Combination Regimen in GLORIA Brain Cancer Trial and Survival Rate 10-Fold Greater Than Standard of Care (Businesswire) - P1/2 | N=27 | GLORIA (NCT04121455) | Sponsor: TME Pharma AG | "TME Pharma N.V...announces that the final median overall survival (mOS) for newly diagnosed glioblastoma patients receiving NOX-A12, TME Pharma's CXCL12 inhibitor, with the VEGF inhibitor bevacizumab and radiotherapy in the GLORIA expansion arm has reached 19.9 months....The mOS achieved by NOX-A12 in combination with radiotherapy and bevacizumab compares very favorably to the matched standard of care reference cohort, which achieved an mOS of 10.5 months, and exceeds what TME Pharma believes to be all relevant competitor therapy trials in newly diagnosed glioblastoma patients resistant to standard chemotherapy."

P1/2 data • Glioblastoma

TME Pharma Announces Successful Advice Meeting With US Food and Drug Administration on NOX-A12 Development in Brain Cancer (Businesswire) - "TME Pharma N.V...announces that it successfully completed its pre-IND advice meeting with the US regulator, the Food and Drug Administration (FDA), discussing plans for the further clinical development of NOX-A12 as a treatment of aggressive adult brain cancer, glioblastoma. Based on the feedback received, TME Pharma confirms that it is on track with preparations to file its Investigational New Drug (IND) application and the expedited regulatory pathway request on a timeline that will allow successful completion of both by the end of Q1 2024."

FDA event • IND • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

TME Pharma Announces Further Improvement in Median Overall Survival at 19 Months Follow-up in GLORIA Brain Cancer Trial (Yahoo Finance) - P1/2 | N=27 | GLORIA (NCT04121455) | Sponsor: TME Pharma AG | "TME Pharma...announces that with median overall survival (mOS) has now passed 19 months and will improve further in the GLORIA expansion arm for newly diagnosed glioblastoma patients receiving NOX-A12 with the VEGF inhibitor bevacizumab and radiotherapy....'The survival data in the cohort receiving the combination of NOX-A12, bevacizumab and radiotherapy has continued to improve with treatment or follow-up of enrolled brain cancer patients. Passing 19 months suggests a large survival benefit for patients on NOX-A12-based therapy since we are seeing more than an 80% increase in survival over the 10.5 months in the matched standard of care reference cohort of patients with the same profile as those we recruited into the study of NOX-A12'...'We can now say with certainty that median overall survival will be between 19.0 and 19.9 months and plan to provide an update before the end of February 2024'."

P1/2 data • Glioblastoma

TME Pharma Announces Additional Data From NOX-A12 Combination Regimen in Brain Cancer Presented at SNO 2023 Annual Meeting (Businesswire) - P1/2 | N=27 | GLORIA (NCT04121455) | Sponsor: TME Pharma AG | "TME Pharma N.V...announced today investigators from the GLORIA trial have presented a poster featuring a clinical update from the ongoing GLORIA Phase 1/2 trial studying NOX-A12, TME Pharma's CXCL12 inhibitor, in combination with radiotherapy and anti-VEGF (bevacizumab), at the 2023 Society for Neuro-Oncology (SNO) Annual meeting, taking place in Vancouver, Canada, November 15-19, 2023....The presentation...highlights the response, survival and safety data as of October 24, 2023, for patients with the aggressive adult brain cancer, glioblastoma, in the GLORIA expansion arm receiving NOX-A12 with the VEGF inhibitor bevacizumab and radiotherapy. All patients recruited in this expansion arm have residual chemotherapy-refractory tumor detectable after maximal safe surgery."

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

Interim data on dual inhibition of post-radiogenic angio-vasculogenesis by olaptesed pegol (NOX-A12) and bevacizumab in glioblastoma from the first expansion arm of the phase 1/2 GLORIA trial. (SNO 2023) - P1/2 | "Interim data of the ongoing trial confirm the previously established safety profile of NOX-A12 for combinatory treatment with bevacizumab while demonstrating improved efficacy with deeper and longer-lasting responses and a higher ORR compared to treatment with RT and NOX-A12 only."

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