emapticap pegol (NOX E36) / 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 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

NOXXON Enters Into Collaboration With US National Cancer Institute to Characterize Effects of Lead Compounds on Brain Tumors (Businesswire) - "NOXXON Pharma N.V...announced today it has entered into a material transfer agreement with the U.S. National Cancer Institute (NCI), of the National Institutes of Health (NIH), to further explore the effects of NOXXON’s lead compounds, the CXCL12 inhibitor NOX-A12 and the CCL2 inhibitor NOX-E36, individually and combined, on brain tumors....Under the agreement, NOXXON will supply NOX-A12 and mNOX-E361 to the NCI, which will conduct preclinical testing in different combinations with immunomodulatory treatments, including immune checkpoint inhibitors. The various combinations will be tested in an array of experiments in three murine brain cancer models, with extensive and detailed characterization of the tumor microenvironment."

Licensing / partnership • Brain Cancer • CNS Tumor • Oncology

NOXXON Reports H1 2021 Financial Results and Provides Business Update (Businesswire) - "NOX-A12 + radiotherapy in Brain Cancer: Completion of the ongoing Phase 1/2 dose escalation trial is planned for Q1 2022....Anticipating that the ongoing Phase 1/2 trial data supports further development, NOXXON plans to initiate in 2022 a pivotal trial of NOX-A12 combined with radiotherapy in first-line MGMT promoter-unmethylated glioblastoma patients vs. standard of care, with first market authorization application and approval targeted for 2025....NOX-E36, is also being readied for the first clinical trial of NOX-E36 in oncology. Manufacturing of clinical supply has been contracted and clinical trial supply is projected to be available in Q1 2022, and trial initiation is targeted for mid-2022."

Enrollment status • New trial • Regulatory • Brain Cancer • Glioblastoma • Oncology

Increased Antiangiogenic Effect by Blocking CCL2-dependent Macrophages in a Rodent Glioblastoma Model: Correlation Study with Dynamic Susceptibility Contrast Perfusion MRI. (PubMed, Sci Rep) - "In this study, we used a CCL2 inhibitor, mNOX-E36, to suppress the recruitment of TAMs in a CCL2-expressing rat GBM model and investigated the effect of combination therapy with bevacizumab using DSC-MR imaging. Our results provide direct evidence that CCL2 expression can increase the resistance to bevacizumab, which can be assessed noninvasively with the DSC-MR imaging technique. This study shows that the suppression of CCL2 can play an important role in increasing the efficacy of anti-angiogenic treatment in GBM by inhibiting the recruitment of CCL2-dependent macrophages."

Journal • Preclinical • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

CCL2/MCP-1 and CXCL12/SDF-1 BLOCKADE BY L-aptamers IMPROVE PANCREATIC ISLET ENGRAFTMENT AND SURVIVAL IN MOUSE. (PubMed, Am J Transplant) - "We evaluated the efficacy of the CCL2-specific mNOX-E36 and the CXCL12-specific NOX-A12 on islet survival in a syngeneic mouse model of intraportal islet transplantation and in a multiple low doses of streptozotocin (MLD-STZ) diabetes induction model. Additionally, both L-aptamers significantly attenuated diabetes progression in the MLD-STZ model. In conclusion, CCL2/MCP-1 and CXCL12/SDF-1 blockade by L-aptamers is an efficient strategy to improve islet engraftment and survival."

Journal • Diabetes • Metabolic Disorders • Transplantation • Type 1 Diabetes Mellitus

CCR2+ monocytes aggravate the early phase of acetaminophen induced acute liver injury. (PubMed) - Hepatology - "Infiltrating monocyte-derived macrophages aggravate APAP hepatotoxicity, and the pharmacological inhibition of either CCL2 or CCR2 might bear therapeutic potential by reducing the inflammatory reaction during the early phase of APAP-induced liver injury."

Journal • Biosimilar

Systemic monocyte chemotactic protein-1 inhibition modifies renal macrophages and restores glomerular endothelial glycocalyx and barrier function in diabetic nephropathy. (PubMed, Am J Pathol) - "Inhibition of monocyte chemotactic protein-1 (MCP)-1 with the Spiegelmer emapticap pegol (NOX-E36) shows long-lasting albuminuria-reducing effects in diabetic nephropathy...Functional analysis of isolated renal macrophages showed increased release of interleukin-10, whereas tumor necrosis factor and cathepsin L release was reduced, further confirming polarization of tissue macrophages toward an anti-inflammatory phenotype during mNOX-E36 treatment. We show that MCP-1 inhibition restores glomerular endothelial glycocalyx and barrier function and reduces tissue inflammation in the presence of ongoing diabetic injury, suggesting a therapeutic potential for NOX-E36 in diabetic nephropathy."

Journal • Biosimilar • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Immunology • Metabolic Disorders • Renal Disease

Reprint of "Dual blockade of the pro-inflammatory chemokine CCL2 and the homeostatic chemokine CXCL12 is as effective as high dose cyclophosphamide in murine proliferative lupus nephritis". (PubMed, Clin Immunol) - "Dual blockade reduced leukocyte counts and renal IL-6, IL-12p40, CCL-5, CCL-2 and CCR-2 mRNA expression. Dual blockade of CCL2 and CXCL12 can be as potent as CYC to suppress the progression of proliferative lupus nephritis probably because the respective chemokine targets mediate different disease pathomechanisms, i.e. systemic autoimmunity and peripheral tissue inflammation."

Journal • Biosimilar • Complement-mediated Rare Disorders • Immunology • Lupus • Rare Diseases • Renal Disease

C-C motif-ligand 2 inhibition with emapticap pegol (NOX-E36) in type 2 diabetic patients with albuminuria. (PubMed) - Nephrol Dial Transplant - "Inhibition of the CCL2/CCL2 receptor axis with emapticap pegol was generally safe and well tolerated. Beneficial effects on ACR and HbA1c were observed in this exploratory study, which were maintained after cessation of treatment. Taken together, emapticap may have disease-modifying effects that warrant further investigation in adequately powered confirmatory studies."

Journal • Biosimilar • Complement-mediated Rare Disorders • Diabetes • Renal Disease

Novel compound shows promise in diabetic nephropathy (Medscape) - P2a, N=72; NCT01547897; "A novel molecule that directly targets inflammation in diabetic nephropathy is safe, well-tolerated, and has significant effects that last for at least 12 weeks after discontinuation of the drug, a phase 2 trial shows. In patients with type 2 diabetes and albuminuria, treatment with emapticap pegol (NOX-E36, NOXXON Pharma) for 12 weeks reduced the mean albumin/creatinine ratio and the level of glycated hemoglobin (HbA1c), report Hermann Haller, MD, director of nephrology and hypertension at Hannover Medical School in Germany, and colleagues."

P2a data • Diabetic Nephropathy • Renal Disease

NOX-E36 in patients with type 2 diabetes mellitus and albuminuria (clinicaltrials.gov) - P2, N=75; Recruiting; New P2 trial

New trial • Renal Disease

Bio 2012 (Noxxon) - Anticipated interim data for P2a trial for diabetic nephropathy in Q4 2012; Anticipated final data for P2a trial for diabetic nephropathy in mid-2013; Anticipated POC data for P2a trial for diabetic nephropathy in 2012

Anticipated P2a data • Diabetes

Pharmacokinetics, pharmacodynamics, safety and tolerability of the CCL2 antagonist NOX-E36, a novel agent being investigated for treatment of diabetic nephropathy (KIDNEY WEEK 2012) - Presentation time: NA; P2, N=NA; NCT01547897; NOX-E36 was safe & well tolerated, no MTD was reached; PK/PD parameters indicate that NOX-E36 effectively antagonizes the CCL2/CCR2 axis; First trends for dose-dependent anti-inflammatory & reno-protective effects were observed

P2 data • Diabetes • Renal Disease

NOXXON: Corporate Fact Sheet (Noxxon) - Anticipated 75 patients efficacy data from P2a trial for diabetic nephropathy in Q4 2013

Anticipated P2a data • Renal Disease

NOXXON presents positive results from emapticap pegol phase IIa diabetic nephropathy study (Noxxon Press release) - P2a, N=75; Sponsor:NOXXON Pharma; NCT01547897; "Results showed relevant, statistically significant reductions in urinary albumin excretion and improved glycemic control. Importantly, these effects were independent of hemodynamic changes and maintained after cessation of treatment, suggesting that emapticap pegol interferes with the underlying pathophysiology of diabetic nephropathy."

P2a data • Diabetic Nephropathy • Renal Disease

BioEurope Spring Conference (Noxxon) - Spiegelmer (NOX-E36) / Noxxon; Initiation of P2a trial in diabetic nephropathy Q4’11; Anticipated P1b study completion in diabetics; Anticipated renal impairment study completion in Q3 ’11

Anticipated P1b study completion • Anticipated P2 enrollment • Renal Disease

Bio 2012 (Noxxon) - P1 & P1b data release

P1 data • Renal Disease

Anti-inflammatory and renoprotective effects of CCL2 inhibition with emapticap pegol (NOX-E36) in type 2 diabetic patients with albuminuria (KIDNEY WEEK 2014) - Abstract #FR-OR120; P2a, N=75; NCT01547897; Sponsor: Noxxon Pharma AG; “Emapticap pegol was safe and well tolerated and resulted in clear benefi cial effects on ACR (-32% at Day 85, P=0.014) and HbA1c (-5% at Day 85, P=0.096) which were maintained even after cessation of dosing (ACR: -39% at Day 141, P=0.010; HbA1c: -7% at Day 113, P=0.036). No change was observed for blood pressure and eGFR. Treatment with emapticap was accompanied by a rapid decrease in the number of peripheral monocytes by approx. 20% and a concomitant decrease in surface marker CCR2.”

P2a data • Diabetic Nephropathy • Renal Disease

A phase I clinical trial to evaluate the effect of renal impairment on pharmacokinetics of NOX-E36 (clinicaltrials.gov) - P1, N=32; Sponsor: Noxxon Pharma AG; Recruiting -> Completed; Completion Date: Dec 2011 -> Oct 2012

Trial completion • Renal Disease

NOXXON Pharma N.V. reports 2019 financial results (Businesswire) - "In September 2019, the company initiated a Phase 1/2 clinical trial testing the combination of radiotherapy and NOX-A12 in newly diagnosed brain cancer patients for up to six months...The DSMB will reconvene at the end of April 2020 to determine whether it is safe to proceed from the low to the middle dose regimen of NOX-A12...NOXXON supplied NOX-A12 to the pharmaceutical company that has funded and been conducting the preclinical studies. The evaluation results are anticipated in Q2‑2020....NOXXON plans to test NOX‑E36 in patients with solid tumors both as a monotherapy and in combination."

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