ApTOLL / aptaTargets - LARVOL DELTA

ApTOLL ameliorates cognitive dysfunction and brain injury in ischemic stroke by regulating the miR-335-5p/IRAK1 axis. (PubMed, Neurotherapeutics) - "ApTOLL effectively mitigates ischemic stroke-induced neuronal damage by modulating the miR-335-5p/IRAK1 axis. These findings reveal a novel mechanistic pathway for ApTOLL's therapeutic effects and highlight its potential as a promising treatment strategy for ischemic stroke."

Journal • Cardiovascular • CNS Disorders • Cognitive Disorders • Inflammation • Ischemic stroke • Vascular Neurology • IRAK1 • MIR335

Clinical trial to compare safety and tolerability between intravenous infusion and bolus intravenous injection of ApTOLL in healthy volunteers. (PubMed, Mol Ther Nucleic Acids) - P1 | "Maximum concentration was detected at the end of the infusion/injection, and mean half-life was 9.5 h for both routes of administration. These results show that safety and pharmacokinetic profiles were comparable between intravenous infusion and bolus injection of ApTOLL, supporting a change of the route of administration for future clinical practice (ClinicalTrials.gov: NCT05569720)."

Journal • Cardiovascular • Inflammation • TLR4

Ischemia/reperfusion injury in acute human and experimental stroke: focus on thrombo-inflammatory mechanisms and treatments. (PubMed, Neurol Res Pract) - "The fact that the significance of I/R injury in AIS has recently been formally established and given the decisive role of platelet-leukocytes interactions herein, new avenues for adjunct stroke treatments emerge. Adjusted study designs to increase the probability of success are of outmost importance and we look forward from what can be learned from the so far unpublished, presumbably negative ACTISAFE and MOST trials."

Journal • Review • Cardiovascular • Inflammation • Ischemic stroke • Reperfusion Injury • TLR4

Cerebroprotective Effects of the TLR4-Binding DNA Aptamer ApTOLL in a Rat Model of Ischemic Stroke and Thrombectomy Recanalization. (PubMed, Pharmaceutics) - "ApTOLL was compared with TAK-242 (a TLR4 inhibitor). These results show the cerebroprotective effects of ApTOLL in ischemic stroke by reducing the infarct/edema volume, neurofunctional impairment, and hemorrhagic risk, as well as the peripheral and local immune response. They provide information about ApTOLL dose effects and its therapeutic time window and target population, as well as its mode of action, which should be considered in the design of pivotal clinical trials."

Journal • Preclinical • Cardiovascular • Hematological Disorders • Immunology • Inflammation • Ischemic stroke • TLR4

EFFECT OF THE PHARMACOLOGICAL INHIBITION/ABSENCE OF TLR4 IN BACTERIAL TRANSLOCATION AFTER EXPERIMENTAL STROKE AND IT'S INFLAMMATORY CONSEQUENCES (ESOC 2024) - "Since our group demonstrated the significant role of TLR4-receptor in this disease, a potential antagonist of these receptor (ApTOLL) has proved to be beneficial experimentally and clinically... Our results show that the inhibition/absence of TLR4 not only reduces the infarct volume, but also the BT process and its inflammatory consequences."

Cardiovascular • TLR4

CEREBROPROTECTIVE EFFECTS OF THE TLR4-BINDING DNA APTAMER APTOLL IN A RAT MODELOF ISCHEMIC STROKE AND THROMBECTOMY RECANALIZATION (ESOC 2024) - "These results show the cerebroprotective effects of ApTOLL in ischemic stroke by reducing infarct/edema volume, neurofunctional impairment, hemorrhagic risk, as well as peripheral and local immune response. They provide information about ApTOLL's dose-effect, therapeutic window and target population, as well as its mode of action, to be onsidered in the design of pivotal clinical trials."

Preclinical • Cardiovascular • Ischemic stroke • TLR4

ApTOLL: A new therapeutic aptamer for cytoprotection and (re)myelination after multiple sclerosis. (PubMed, Br J Pharmacol) - "Our findings reveal a new therapeutic approach for the treatment of inflammatory and demyelinating diseases such as MS. The molecular nature of the aptamer exerts not only an anti-inflammatory effect but also neuroprotective and remyelinating effects. The excellent safety profile demonstrated by ApTOLL in animals and humans opens the door to future clinical trials in MS patients."

Journal • CNS Disorders • Immunology • Inflammation • Multiple Sclerosis • Solid Tumor • TLR4

Targeting Against Inflammation: apTOLL Neuroprotection Research Line (ISC 2024) - "There is no abstract associated with this presentation."

Inflammation

Neuroprotection during Thrombectomy for Acute Ischemic Stroke: A Review of Future Therapies. (PubMed, Int J Mol Sci) - "Advances in multiple neuroprotective therapies, including uric acid, activated protein C, nerinetide, otaplimastat, imatinib, verapamil, butylphthalide, edaravone, nelonemdaz, ApTOLL, regional hypothermia, remote ischemic conditioning, normobaric oxygen, and especially nuclear factor erythroid 2-related factor 2, have promising evidence for improving stroke care. Sedation and blood pressure management in endovascular thrombectomy also play crucial roles in improved stroke outcomes. A hand-in-hand approach with both endovascular therapy and neuroprotection may be the key to targeting disability due to stroke."

Journal • Review • Anesthesia • Cardiovascular • Ischemic stroke • Reperfusion Injury

ApTOLL for the Treatment of COVID-19 (clinicaltrials.gov) - P1 | N=5 | Terminated | Sponsor: Macarena Hernández Jiménez | N=30 ➔ 5 | Recruiting ➔ Terminated; Lack of patients due to reduced incidence in the COVID-19 infected population in Spain

Enrollment change • Trial termination • Infectious Disease • Novel Coronavirus Disease

Safety and Efficacy of ApTOLL in Patients With Ischemic Stroke Undergoing Endovascular Treatment: A Phase 1/2 Randomized Clinical Trial. (PubMed, JAMA Neurol) - P1/2 | "These preliminary findings await confirmation from larger pivotal trials. ClinicalTrials.gov Identifier: NCT04734548."

Clinical • Journal • P1/2 data • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Ischemic stroke • TLR4

IMAGING OUTCOMES IN THE APRIL STUDY: A DOUBLE-BLIND, PLACEBO-CONTROLLED, RANDOMIZED, PHASE IB/IIA CLINICAL STUDY OF APTOLL FOR THE TREATMENT OF ACUTE ISCHEMIC STROKE (ESOC 2023) - "ApTOLL 0.2mg/kg in combination with mechanical thrombectomy significantly reduced lesion volume and cerebral edema at 72h. Further data about the effect of ApTOLL on imaging outcomes will be given at the conference."

Clinical • Late-breaking abstract • P1/2 data • Cardiovascular • Ischemic stroke

Beneficial effect of TLR4 blockade by a specific aptamer antagonist after acute myocardial infarction. (PubMed, Biomed Pharmacother) - "In addition, the expression of anti-inflammatory genes, such as IL-10, and pro-resolution molecules, such as resolvin D1 are enhanced after 4FT administration. These results indicate that targeting TLR4 with 4FT offers new therapeutic opportunities to prevent cardiac dysfunction after infarction."

Journal • Cardiovascular • Coronary Artery Disease • Inflammation • Myocardial Infarction • Myocardial Ischemia • Reperfusion Injury • IL10 • NF-κβ • TLR4

APRIL: A double-blind, placebo-controlled, randomized, Phase Ib/IIa clinical study of ApTOLL for the treatment of acute ischemic stroke. (PubMed, Front Neurol) - P1/2 | "In Phase Ib, 32 patients will be allocated to four dose ascending levels to select, based on safety criteria, the best two doses to be administered in the following Phase IIa in which 119 patients will be randomized to three arms of treatment (dose A, dose B, and placebo). EudraCT: 2020-002059-38 and ClinicalTrials.gov Identifier: NCT04734548 https://clinicaltrials.gov/ct2/show/NCT04734548?term=ApTOLL&cond=Stroke&draw=2&rank=1."

Journal • P1/2 data • Cardiovascular • Inflammation • Ischemic stroke • TLR4

April: A Double-blind, Placebo-controlled, Randomized, Phase Ib/IIa Clinical Study Of Aptoll For The Treatment Of Acute Ischemic Stroke (ISC 2023) - P1/2 | "Regarding efficacy, at 72 hours Dose B reduced mean infarct volume (-29.31cc, 90% CI -49.28, -9.34), and NIHSS (-3.94, 90% CI -6.86, -1.02) and at 90 days the disability ( mRS shift: common OR: 0.41, 90% CI 0.20, 0.85).|Conclusion In acute ischemic stroke, 0.2mg/kg of ApTOLL administered within 6h of onset in combination with EVT was associated with reduced mortality and disability at 90 days and a favorable safety profile compared to placebo. These preliminary findings await confirmation from larger, phase III trials (NCT04734548 / EudraCT:2020-002059-38)"

Clinical • Late-breaking abstract • P1/2 data • Cardiovascular • CNS Disorders • Hematological Disorders • Ischemic stroke • TLR4

Phase Ib/IIa Clinical Study of ApTOLL for the Treatment of Acute Ischemic Stroke (clinicaltrials.gov) - P1/2 | N=151 | Completed | Sponsor: aptaTargets S.L. | Active, not recruiting ➔ Completed

Trial completion • Cardiovascular • Ischemic stroke

APTABOLUS: First in Human Study to Compare Safety Between Intravenous Bolus Versus Infusion of ApTOLL (clinicaltrials.gov) - P1 | N=6 | Completed | Sponsor: aptaTargets S.L.

New P1 trial • Cardiovascular

ApTOLL for the Treatment of COVID-19 (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Macarena Hernández Jiménez | Trial completion date: Jul 2022 ➔ Jan 2023 | Trial primary completion date: Jun 2022 ➔ Jan 2023

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

Phase Ib/IIa Clinical Study of ApTOLL for the Treatment of Acute Ischemic Stroke (clinicaltrials.gov) - P1/2 | N=151 | Active, not recruiting | Sponsor: aptaTargets S.L. | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Ischemic stroke

First-in-human phase I clinical trial of a TLR4-binding DNA aptamer, ApTOLL: Safety and pharmacokinetics in healthy volunteers. (PubMed, Mol Ther Nucleic Acids) - "Consequently, the multiple dose study did not show any accumulation of ApTOLL. These results show an excellent safety and adequate pharmacokinetic profile that, together with the efficacy demonstrated in nonclinical studies, provide the basis to start clinical trials in patients."

Journal • P1 data • PK/PD data • Cardiovascular • Immunology • Inflammation • Ischemic stroke • Myocardial Infarction • TLR4

ApTOLL for the Treatment of COVID-19 (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Macarena Hernández Jiménez

New P1 trial • Infectious Disease • Novel Coronavirus Disease