E2511 / Eisai - LARVOL DELTA

Developing Topics. (PubMed, Alzheimers Dement) - "The mechanism of modulating novel candidate PD biomarkers in human CSF by E2511 was clarified by non-clinical study using rats. The convergence of clinical global proteomics data and non-clinical data have identified PD biomarkers for E2511 consistent with the proposed mechanism of action. Results are supportive of continued development of a E2511-specific biomarker panel and suggestive of pathway activation in healthy volunteers."

Biomarker • Journal • Alzheimer's Disease • CNS Disorders

Positive Allosteric Modulators of Trk Receptors for the Treatment of Alzheimer's Disease. (PubMed, Pharmaceuticals (Basel)) - "Two examples of successful discovery and development of PAMs are the TrkA-PAM E2511 and the pan-Trk PAM ACD856. This review aims to present the concept of positive allosteric modulators of the Trk receptors as a novel future treatment option for Alzheimer's disease and other neurodegenerative and cognitive disorders, and the current preclinical and clinical data supporting this new concept. Preclinical data indicate dual mechanisms, not only as cognitive enhancers, but also a tentative neurorestorative function."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Developmental Disorders

Non-clinical evidence for modulating synaptic CSF biomarkers by E2511, a novel small molecule TrkA biased positive allosteric modulator (AAIC 2024) - "The effect of cholinesterase inhibitor (ChEI) on gene expression was also investigated in rats treated with TID oral donepezil for 4 days. The mechanism of modulating novel candidate PD biomarkers in human CSF by E2511 was clarified by non-clinical study using rats. The convergence of clinical global proteomics data and non-clinical data have identified PD biomarkers for E2511 consistent with the proposed mechanism of action. Results are supportive of continued development of a E2511-specific biomarker panel and suggestive of pathway activation in healthy volunteers."

Biomarker • Clinical • Alzheimer's Disease • CNS Disorders

NETWORK-INFORMED UNBIASED GLOBAL PROTEOMICS STRATEGY TO DISCOVER BIOMARKERS FOR E2511, A NOVEL TRKA MODULATOR (ADPD 2024) - "Human brain network-informed proteomic-profiling of CSF provided a powerful and unique tool to identify hubs within protein co-expression modules related to E2511 MoA. This biomarker discovery strategy helped to corroborate the mechanism of action (MoA) and target engagement of E2511 in regulating axonal and synaptic biology. Further studies to confirm E2511 proof-of-mechanism and support dose-selection are planned."

Biomarker • Clinical

E2511, a Novel TrkA Modulator, Engages its CNS Cholinergic Target in a Phase 1 Clinical Study (CTAD 2023) - "In a phase1 clinical trial of a novel TrkA modulator (E2511), ultra-deep global proteomics profiling of CSF enabled the identification of proteins potentially linked to E2511 MoA. Pathway enrichment analysis and mapping of unbiased ultra-deep CSF proteomes to groups or “modules” of co-expressed brain proteins that reflect various biological functions corroborated the mechanism of action and target engagement of E2511 in regulating axonal and synaptic biology. Further confirmatory studies using targeted assays are warranted to confirm E2511 proof-of-mechanism and to support dose selection for the pivotal clinical trials."

Clinical • P1 data • Alzheimer's Disease • CNS Disorders

Safety and pharmacokinetics of multiple ascending doses of E2511, a novel TrkA allosteric modulator, in healthy volunteers (CTAD 2023) - P1 | "Safety and PK profile of E2511 after multiple doses was favorable supporting further progression of E2511 into clinical development. ."

Clinical • PK/PD data • ADHD (Impulsive Aggression) • Alzheimer's Disease • Attention Deficit Hyperactivity Disorder • Back Pain • Bipolar Disorder • CNS Disorders • Cognitive Disorders • Constipation • Contact Dermatitis • Dermatitis • Dermatology • Gastroenterology • Gastrointestinal Disorder • Immunology • Mood Disorders • Musculoskeletal Pain • Pain • Psychiatry

EISAI TO PRESENT NEW DATA FROM LEQEMBI (LECANEMAB-IRMB) PHASE 3 CLARITY AD STUDY AND OTHER ALZHEIMER’S DISEASE PIPELINE RESEARCH AT THE CLINICAL TRIALS ON ALZHEIMER’S DISEASE (CTAD) CONFERENCE (PRNewswire) - "In addition to the data presented on Eisai's anti-amyloid beta (Aβ) protofibril antibody LEQEMBI, phase 1 data for E2511, an investigational tropomyosin receptor Kinase A (TrkA) positive allosteric modulator (PAM), will be presented as well as other research from the company's AD pipeline. At the conference, Eisai will present data and research in five oral and ten poster presentations. BioArctic will give an oral presentation on lecanemab."

Clinical data • P1 data • Alzheimer's Disease • CNS Disorders

A Study to Assess the Safety and Tolerability of E2511 in Healthy Adult and Elderly Participants (clinicaltrials.gov) - P1 | N=47 | Completed | Sponsor: Eisai Inc. | Recruiting ➔ Completed

Trial completion

First-in-Human (FIH), Single- and Multiple-Ascending-Dose (SAD/MAD) Studies in Healthy Subjects of E2511, a Novel Tropomyosin receptor kinase A (TrkA) Positive Allosteric Modulator (PAM) (AAIC 2022) - No abstract available

Clinical • P1 data

E2511, a novel small compound TrkA biased positive allosteric modulator, reinnervates cholinergic neuron and activates cholinergic functions in non-clinical studies (AAIC 2022) - No abstract available

Clinical

E2511, A NOVEL SMALL COMPOUND TRKA BIASED POSITIVE ALLOSTERIC MODULATOR, REINNERVATES CHOLINERGIC NEURON VIA ENHANCEMENT OF SPECIFIC TROPHIC SIGNALING OF TRKA IN NON-CLINICAL STUDIES (ADPD 2022) - "E2511 enhances cholinergic function by increasing TrkA signaling as biased positive allosteric modulator, and E2511 functionally reinnervates cholinergic neuronal network in Tau tg mice."

Clinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Pain • NGF

A Study to Assess the Safety and Tolerability of E2511 in Healthy Adult and Elderly Participants (clinicaltrials.gov) - P1; N=55; Recruiting; Sponsor: Eisai Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

A Study to Assess the Safety and Tolerability of E2511 in Healthy Adult and Elderly Participants (clinicaltrials.gov) - P1; N=55; Not yet recruiting; Sponsor: Eisai Inc.

Clinical • New P1 trial

[VIRTUAL] E2511, a novel small compound TrkA allosteric modulator, induces a specific trophic signaling via direct binding to TrkA, and can reverse the loss of choline acetyltransferase (ChAT) positive neurons in transgenic models of AD (AAIC 2021) - "E2511 enhances specific trophic signaling by altering TrkA signaling as specific allosteric modulator via direct binding to TrkA, and E2511 shows the reinnervative effect on cholinergic neurons through activation of TrkA signaling without induction of NGF-like adverse effect."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Pain • NGF

"E-2511 reverses the loss of choline acetyltransferase in AD models #AAIC21" (@Cortellis)

Eisai Alzheimer’s Disease Pipeline Research, Including New Lecanemab (BAN2401) Data, to be Presented at 2021 Alzheimer’s Association International Conference (AAIC) (PRNewswire) - "Data and research from Eisai's rich dementia pipeline, including joint assets with Biogen, will be featured in 18 oral and poster presentations at the 2021 Alzheimer's Association International Conference (AAIC)...An oral presentation regarding the clinical study design of the Dominantly Inherited AD (DIAD) Trial of Eisai's investigational MTBR (microtubule binding region) targeted anti-tau antibody E2814 will be given....A poster presentation will be given on the results of in vivo study of E2511…Biogen Inc. will make five presentations about our joint asset ADUHELM™ (aducanumab-avwa) 100 mg/mL solution for injection..."

Clinical data • Clinical protocol • P3 data • Preclinical • Alzheimer's Disease • CNS Disorders • Dementia • Sleep Disorder

A Study to Assess the Safety and Tolerability of E2511 in Healthy Participants (clinicaltrials.gov) - P1; N=45; Completed; Sponsor: Eisai Inc.; Recruiting ➔ Completed

Clinical • Trial completion

A Study to Assess the Safety and Tolerability of E2511 in Healthy Participants (clinicaltrials.gov) - P1; N=56; Recruiting; Sponsor: Eisai Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open