ucenprubart (LY3454738) / Eli Lilly - LARVOL DELTA

Ucenprubart is an agonistic antibody to CD200R with the potential to treat inflammatory skin disease: preclinical development and a phase 1 clinical study. (PubMed, Nat Commun) - P1 | "The primary endpoint is not met; however, overall improvements are observed in EASI-75 and SCORAD through 12 weeks. CD200R may be a promising therapeutic target for treating autoimmune disease, including inflammatory skin diseases."

Journal • P1 data • Preclinical • Atopic Dermatitis • Contact Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Oncology • CD200R1

Ucenprubart is an agonistic antibody to CD200R with the potential to treat inflammatory skin disease: preclinical development and a phase 1 clinical study (Nature) - P1 | N=128 | NCT03750643 | Sponsor: Eli Lilly and Company | "Preclinical studies find ucenprubart inhibiting Fcγ receptor-induced cytokine secretion from myeloid cells in vitro and demonstrating efficacy in a mouse contact hypersensitivity model...Sixty-two healthy participants and 40 patients are enrolled. No serious adverse events or discontinuations due to adverse events is seen with ucenprubart. The primary endpoint is not met; however, overall improvements are observed in EASI-75 and SCORAD through 12 weeks. CD200R may be a promising therapeutic target for treating autoimmune disease, including inflammatory skin diseases...For EASI-75 responders at week 12, 50.0% (n = 5/10) continued to maintain a 75% response in EASI score at week 24. For those with a ≥90% improvement in EASI score at week 12, 57% (n = 4/7) maintained a ≥90% response at week 24."

P1 data • Preclinical • Atopic Dermatitis

UPDATED: Eli Lilly lops...assets from pipeline in Q4 update (FierceBiotech) - "The drugmaker also removed ucenprubart and volenrelaxin from its pipeline. Ucenprubart is a CD200R1 agonist that Lilly was studying as a treatment for eczema. Lilly stopped enrollment in a phase 2 trial of the candidate, which is also known as LY3454738, last month before reaching its recruitment target....Volenrelaxin was in development in heart failure and chronic kidney disease (CKD)."

Discontinued • Enrollment closed • Atopic Dermatitis • Chronic Kidney Disease • Dermatology • Heart Failure

A Study of LY3454738 in the Treatment of Adult Participants With Moderate-to-Severe Atopic Dermatitis (clinicaltrials.gov) - P2 | N=236 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting

Enrollment closed • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

A Study of LY3454738 in the Treatment of Adult Participants With Moderate-to-Severe Atopic Dermatitis (clinicaltrials.gov) - P2 | N=260 | Recruiting | Sponsor: Eli Lilly and Company | Trial completion date: May 2025 ➔ Mar 2026 | Trial primary completion date: Sep 2024 ➔ Jun 2025

Trial completion date • Trial primary completion date • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

A Relative Bioavailability Study of LY3454738 in Healthy Participants (clinicaltrials.gov) - P1 | N=30 | Completed | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Completed

Trial completion

A Relative Bioavailability Study of LY3454738 in Healthy Participants (clinicaltrials.gov) - P1 | N=30 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting

Enrollment closed

A Relative Bioavailability Study of LY3454738 in Healthy Participants (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open

A Relative Bioavailability Study of LY3454738 in Healthy Participants (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P1 trial

A Study of LY3454738 in the Treatment of Adult Participants With Moderate-to-Severe Atopic Dermatitis (clinicaltrials.gov) - P2 | N=260 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Mast cell silencing: A novel therapeutic approach for urticaria and other mast cell-mediated diseases. (PubMed, Allergy) - "MC silencers, such as agonist monoclonal antibodies that engage inhibitory receptors (e.g., sialic acid-binding immunoglobulin-like lectin8 -[Siglec-8] [lirentelimab/AK002], Siglec-6 [AK006], and CD200R [LY3454738]), have reached preclinical and clinical stages of development. In this review, we (1) describe the role of MCs in the pathogenesis of CU, highlighting similarities with other MC diseases in disease mechanisms and response to treatment; (2) explore current therapeutic strategies, categorized by nonspecific immunosuppression, targeted inhibition of MC activation or mediators, and targeted modulation of MC activity; and (3) introduce the concept of MC silencing as an emerging strategy that could selectively block activation of MCs without eliciting or exacerbating on- or off-target, immunosuppressive adverse effects."

Journal • Review • Dermatology • Immunology • Inflammation • Urticaria • CD200 • CD200R1 • SIGLEC8

A Study of LY3454738 in the Treatment of Adult Participants With Moderate-to-Severe Atopic Dermatitis (clinicaltrials.gov) - P2 | N=260 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P2 trial • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Safety and efficacy of LY3454738, a novel CD200R checkpoint inhibitor agonist, in a 12 week phase 1 study in atopic dermatitis (EADV 2022) - No abstract available

Checkpoint inhibition • Clinical • P1 data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Oncology • CD200

A Study of LY3454738 in Healthy Participants and Participants With Atopic Dermatitis (clinicaltrials.gov) - P1; N=128; Completed; Sponsor: Eli Lilly and Company; Active, not recruiting ➔ Completed; N=64 ➔ 128

Clinical • Enrollment change • Trial completion • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

A Study of LY3454738 in Healthy Participants and Participants With Atopic Dermatitis (clinicaltrials.gov) - P1; N=64; Active, not recruiting; Sponsor: Eli Lilly and Company; Trial primary completion date: Jun 2021 ➔ Sep 2021

Clinical • Trial primary completion date • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

A Study of LY3454738 in Adults With Chronic Spontaneous Urticaria (clinicaltrials.gov) - P2; N=52; Terminated; Sponsor: Eli Lilly and Company; Trial completion date: Sep 2021 ➔ Feb 2021; Active, not recruiting ➔ Terminated; The study was terminated for lack of efficacy after an interim analysis was performed

Clinical • Trial completion date • Trial termination • Chronic Spontaneous Urticaria • Dermatology • Urticaria

A Study of LY3454738 in Healthy Participants and Participants With Atopic Dermatitis (clinicaltrials.gov) - P1; N=64; Active, not recruiting; Sponsor: Eli Lilly and Company; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Biologics for the Use in Chronic Spontaneous Urticaria: When and Which. (PubMed, J Allergy Clin Immunol Pract) - "Guidelines for the treatment of chronic spontaneous urticaria (CSU) recommend the use of the IgE-targeted biologic omalizumab in patients with antihistamine-refractory disease...We provide information on the effects of the off-label use, in CSU, of biologics licensed for the treatment of other diseases, including dupilumab, benralizumab, mepolizumab, reslizumab, and secukinumab...These include IgE/ligelizumab, IgE/GI-310, thymic stromal lymphopoietin/tezepelumab, C5a receptor/avdoralimab, sialic acid-binding Ig-like lectin 8/lirentelimab, CD200R/LY3454738, and KIT/CDX-0159. Our aim is to provide updated information and guidance on the use of biologics in the treatment of patients with CSU, now and in the near future."

Journal • Cardiovascular • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

A Study of LY3454738 in Adults With Chronic Spontaneous Urticaria (clinicaltrials.gov) - P2; N=60; Active, not recruiting; Sponsor: Eli Lilly and Company; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Chronic Spontaneous Urticaria • Dermatology • Urticaria

A Study of LY3454738 in Healthy Participants and Participants With Atopic Dermatitis (clinicaltrials.gov) - P1; N=64; Recruiting; Sponsor: Eli Lilly and Company; Trial completion date: Dec 2021 ➔ Aug 2021

Clinical • Trial completion date • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

A Study of LY3454738 in Healthy Participants and Participants With Atopic Dermatitis (clinicaltrials.gov) - P1; N=64; Recruiting; Sponsor: Eli Lilly and Company; Trial primary completion date: Jan 2022 ➔ Sep 2021

Clinical • Trial primary completion date • Atopic Dermatitis • Dermatitis • Dermatology • Dermatopathology • Immunology

[VIRTUAL] Development of LY3454738, an agonistic antibody to human CD200R (SID 2020) - "After demonstrating safety and tolerability in a phase 1 trial in healthy volunteers, LY3454738 is currently being studied in patients with atopic dermatitis and chronic spontaneous urticaria. The poster will describe properties and functional activities of the clinical drug candidate."

Late-breaking abstract • Atopic Dermatitis • Dermatitis • Dermatology • Dermatopathology • Hematological Disorders • Immunology • Urticaria

A Study of LY3454738 in Healthy Participants and Participants With Atopic Dermatitis (clinicaltrials.gov) - P1; N=64; Recruiting; Sponsor: Eli Lilly and Company; Suspended ➔ Recruiting; N=128 ➔ 64

Clinical • Enrollment change • Enrollment open • Atopic Dermatitis • Dermatitis • Dermatology • Dermatopathology • Immunology

A Study of LY3454738 in Adults With Chronic Spontaneous Urticaria (clinicaltrials.gov) - P2; N=60; Recruiting; Sponsor: Eli Lilly and Company; Suspended ➔ Recruiting

Clinical • Enrollment open • Dermatology • Dermatopathology • Immunology • Urticaria

A Study of LY3454738 in Adults With Chronic Spontaneous Urticaria (clinicaltrials.gov) - P2; N=60; Suspended; Sponsor: Eli Lilly and Company; Recruiting ➔ Suspended

Clinical • Trial suspension • Dermatology • Dermatopathology • Immunology • Urticaria