zagotenemab (LY3303560) / Eli Lilly - LARVOL DELTA

Facile generation of drug-like conformational antibodies specific for amyloid fibrils. (PubMed, Nat Chem Biol) - "Notably, this approach enables the isolation of conformation-specific antibodies against tau fibrils (Alzheimer's disease) and α-synuclein fibrils (Parkinson's disease) with combinations of high affinity, high conformational specificity and, in some cases, low off-target binding that rival or exceed those of clinical-stage antibodies specific for tau (zagotenemab) and α-synuclein (cinpanemab). This approach is expected to simplify the generation of conformation-specific antibodies against diverse protein aggregates and other insoluble antigens."

Journal • Alzheimer's Disease • CNS Disorders • Movement Disorders • Parkinson's Disease

Comparative the efficacy and safety of Gosuranemab, Semorinemab, Tilavonemab, and Zagotenemab in patients with Alzheimer's disease: a systematic review and network meta-analysis of randomized controlled trials. (PubMed, Front Aging Neurosci) - "Further studies are needed to confirm these findings, assess long-term effects, and refine treatment protocols. https://www.crd.york.ac.uk/prospero/#myprospero, CRD42024583388."

Journal • Retrospective data • Review • Alzheimer's Disease • CNS Disorders • Dementia • Infectious Disease • Nephrology

Assessment of Efficacy and Safety of Zagotenemab: Results From PERISCOPE-ALZ, a Phase 2 Study in Early Symptomatic Alzheimer Disease. (PubMed, Neurology) - P2 | "In participants with early symptomatic AD, zagotenemab failed to achieve significant slowing of clinical disease progression compared with placebo. Imaging biomarker and plasma NfL findings did not show evidence of pharmacodynamic activity or disease modification."

Journal • P2 data • Alzheimer's Disease • CNS Disorders • NEFL • Plasma NfL

Safety, Tolerability, and Pharmacokinetics of Zagotenemab in Participants with Symptomatic Alzheimer's Disease: A Phase I Clinical Trial. (PubMed, J Alzheimers Dis Rep) - P1 | "Pharmacokinetics of zagotenemab were typical for a monoclonal antibody. Meaningful pharmacodynamic differences were not observed.Clinicaltrials.gov: NCT03019536."

Journal • P1 data • PK/PD data • Alzheimer's Disease • Cardiovascular • CNS Disorders • Cognitive Disorders • Pain • Pulmonary Disease • Respiratory Diseases

PRE-RECORDED: ASSESSMENT OF SAFETY, TOLERABILITY, AND EFFICACY OF ZAGOTENEMAB: RESULTS FROM PERISCOPE-ALZ, A PHASE 2 STUDY IN EARLY SYMPTOMATIC ALZHEIMER’S DISEASE (ADPD 2022) - P2 | "Conclusions In participants with early symptomatic AD, zagotenemab failed to achieve significant slowing of clinical disease progression. Imaging biomarker and NfL findings did not show evidence of pharmacodynamic activity or disease modification."

Clinical • P2 data • Alzheimer's Disease • CNS Disorders

Comparative Analysis of Aducanumab, Zagotenemab and Pioglitazone as Targeted Treatment Strategies for Alzheimer's Disease. (PubMed, Aging Dis) - "These have shown mixed results so far and the next few years will be critical to elucidate and interpret their broad long-term protective effects. A concerted effort is required to understand and strengthen the translation of pre-clinical findings from these drugs to routine clinical practice."

Journal • Review • Alzheimer's Disease • CNS Disorders • Dementia

A Study of LY3303560 in Participants With Early Symptomatic Alzheimer's Disease (clinicaltrials.gov) - P2; N=360; Completed; Sponsor: Eli Lilly and Company; Active, not recruiting ➔ Completed

Clinical • Trial completion • Alzheimer's Disease • CNS Disorders • MRI

Eli Lilly kick-starts speedy FDA review for Alzheimer’s hopeful donanemab—and a one-on-one test against Aduhelm (FierceBiotech) - "Lilly is also terminating a phase 2 Alzheimer's asset called zagotenemab after the drug failed a phase 2 clinical trial....Lilly now says the drug 'failed to meet the primary endpoint in a Phase 2 study.'"

Discontinued • Alzheimer's Disease • CNS Disorders

[VIRTUAL] Novel use of tau imaging to enrich for pathological homogeneity within the PERISCOPE-ALZ study of zagotenemab (AAIC 2021) - P2 | "PERISCOPE-ALZ successfully implemented flortaucipir PET imaging as the key inclusion criterion to enroll a pathological homogeneous cohort based on level of tau accumulation. As tau-targeted therapies for AD advance into clinical research, staged tau pathology as eligibility criterion may be useful in phase 2 proof-of-concept trials to test disease modifying therapies. Topline trial results are anticipated in late 2021."

Alzheimer's Disease • CNS Disorders • Tau PET

Eli Lilly & Co (LLY) Q4 2020 Earnings Call Transcript (The Motley Fool) - "We look forward to sharing the full results of TRAILBLAZER-ALZ at AD/PD 2021 Virtual Meeting on March 13, and we plan to have an investor call at 11:00 AM on March 15. We hope to reproduce and extend these exciting findings in our second pivotal donanemab trial, TRAILBLAZER-ALZ 2...This study is expected to complete enrollment later this year with nearly twice as many patients as the first to TRAILBLAZER trial. We'll be engaging regulators to finalize the patient numbers and statistical plans for TRAILBLAZER 2...We look forward to sharing the TRAILBLAZER-ALZ data and discussing next step for donanemab with regulators....The Phase 2 readout for zagotenemab, our anti-tau antibody for early Alzheimer's in a trial similar in design to the TRAILBLAZER trial that just read out....We're quite looking forward to getting that data later this year."

Enrollment status • P2 data • Alzheimer's Disease • CNS Disorders

[VIRTUAL] KEY BASELINE CHARACTERISTICS OF PARTICIPANTS ENROLLED USING TAU PET SCREENING IN TWO PHASE 2 TRIALS (CTAD 2020) - P2 | " TRAILBLAZER-ALZ phase 2 therapeutic trial with anti-N3pG antibody donanemab (LY3002813; NCT03367403) and PERISCOPE-ALZ phase 2 therapeutic trial with anti-tau antibody zagotenemab (LY3303560; NCT03518073) implemented National Institute about clinical trial participation and experiences with the US on Aging and Alzheimer’s Association (NIA-AA) guidelines for AD classification based on biomarker-defined pathological stage (Jack et al, Alzheimer’s and Dementia, 2018, 14, 535- 562) with a focus on identifying an early symptomatic AD population. Our findings provide initial insight on using tau PET-quantification to address AD clinical trial population pathologic and clinical heterogeneity."

P2 data • Alzheimer's Disease • CNS Disorders • Dementia • Amyloid PET • Tau PET

Alzheimer's disease: Recent treatment strategies. (PubMed, Eur J Pharmacol) - "Current treatment for AD (donepezil, galantamine, rivastigmine and memantine) is only symptomatic and has modest benefits...Even the positive findings presented by Biogen on Aducanumab are not entirely clear and further data is necessary to confirm its validity...Four monoclonal antibodies anti-tau (Gosuranemab, Tilavonemab, Semorinemab and Zagotenemab) and one anti-tau vaccine (AADvac1) have reached phase II, so far. In this review, we discuss the potential disease-modifying agents tested in clinical trials and update the information of drugs that are still under clinical evaluation."

Journal • Review • Alzheimer's Disease • CNS Disorders

A Study of LY3303560 in Participants With Early Symptomatic Alzheimer's Disease (clinicaltrials.gov) - P2; N=285; Recruiting; Sponsor: Eli Lilly and Company; Active, not recruiting ➔ Recruiting

Clinical • Enrollment open • Alzheimer's Disease • CNS Disorders

A Study of LY3303560 in Participants With Mild Cognitive Impairment or Alzheimer's Disease (clinicaltrials.gov) - P1; N=132; Recruiting; Sponsor: Eli Lilly and Company; Trial primary completion date: May 2020 ➔ Feb 2020

Trial primary completion date • Alzheimer's Disease • Biosimilar

Zagotenemab: Primary completion of P2 trial (NCT03518073) for early symptomatic Alzheimer’s disease in Aug 2021 (Eli Lilly) - Q1 2020 Results: Completion of P2 trial for early symptomatic Alzheimer’s disease in Oct 2021

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Tauopathies And Synucleinopathies

Zagotenemab: Data from P2 trial (NCT03518073) for Alzheimer's disease in mid-2021 (38th Annual J.P. Morgan Healthcare Conference, Eli Lilly)

P2 data

Zagotenemab: Data from P2 trial (NCT03518073) for Alzheimer's disease in mid-2021 (38th Annual J.P. Morgan Healthcare Conference, Eli Lilly)

P2 data

Zagotenemab: Primary completion of P2 trial (NCT03518073) for early symptomatic Alzheimer’s disease in Aug 2021 (Eli Lilly) - Q3 2019 Results: Completion of P2 trial for early symptomatic Alzheimer’s disease in Oct 2021

Trial completion date • Trial primary completion date

A Study of LY3303560 in Participants With Early Symptomatic Alzheimer's Disease (clinicaltrials.gov) - P2; N=285; Active, not recruiting; Sponsor: Eli Lilly and Company; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

A Study of LY3303560 in Participants With Early Symptomatic Alzheimer's Disease (clinicaltrials.gov) - P2; N=285; Recruiting; Sponsor: Eli Lilly and Company; Trial primary completion date: Jan 2021 ➔ Aug 2021

Clinical • Trial primary completion date

Eli Lilly and Company Q2 2019 Earnings Call Transcript (Yahoo Finance) - "...Zagotenemab is our anti-tau antibody currently in a placebo-controlled study of nearly 300 patients...We look forward to seeing the data in 2021...and we're now studying this molecule in phase two in the symptomatic treatment of Lewy body dementia, which includes patients with both dementia with Lewy bodies and Parkinson's disease dementia, focusing on improving attention and cognition...Based on enrollment, we expect data in early 2020."

P2 data

LY3303560: Data from P2 trial (NCT03518073) in early symptomatic Alzheimer's disease in 2021 (Eli Lilly) - Q2 2019 Results

P2 data

A Study of LY3303560 in Participants With Mild Cognitive Impairment or Alzheimer's Disease (clinicaltrials.gov) - P1; N=24; Completed; Sponsor: Eli Lilly and Company; Active, not recruiting ➔ Completed; Trial completion date: Jun 2020 ➔ Jun 2019

Clinical • Trial completion • Trial completion date