Zyclara (imiquimod)

In a rat collagen-induced arthritis model, anti-TL1A antibody treatment effectively reduced arthritis severity, with similar efficacy to the TNF antagonist etanercept. In humanized mouse Imiquimod-induced psoriasis and 2,4,6‑trinitrobenzene sulfonic acid colitis models, anti-TL1A demonstrated similar efficacy to anti-IL-23 and anti-TNF antibodies. These findings characterize two novel extended half-life TL1A antibodies and support the ongoing Phase 2 clinical development of SPY002 and SPY072 for immune-mediated diseases such as inflammatory bowel disease and rheumatic diseases.

P3, N=1630, Not yet recruiting, VA Office of Research and Development | Trial completion date: May 2032 --> Aug 2032 | Trial primary completion date: May 2032 --> Aug 2032

P4, N=40, Active, not recruiting, University of Michigan | Recruiting --> Active, not recruiting | Trial completion date: Sep 2027 --> May 2026 | Trial primary completion date: Mar 2027 --> May 2026

Results showed that Khib modification levels at the K42 site of ACTR3 were significantly reduced in lesional tissues from psoriatic patients and imiquimod (IMQ)-induced psoriatic mice...Notably, TAK1 antagonists effectively reversed abnormal keratinocyte proliferation and psoriatic inflammation induced by the ACTR3 K42A mutation. This study elucidates that reduced Khib modification at the ACTR3 K42 locus promotes keratinocyte proliferation via regulation of the TAK1-MK2-HSP27 signalling pathway, offering a previously undescribed molecular insight into psoriasis pathogenesis.

TLR3 and TLR7 agonists induce IFN-driven monocyte activation in PWH, which is effectively modulated by JAK-STAT inhibitors. These findings support their potential as therapeutic agents to mitigate inflammation in chronic HIV infection.

P1, N=25, Recruiting, Northwestern University | Trial completion date: Feb 2026 --> Dec 2027 | Trial primary completion date: Aug 2025 --> Jun 2027

Under acidic conditions, it undergoes structural disassociation, leading to the release of therapeutic components of a near-infrared photosensitizer (FBC) and the Toll-like receptor 7 (TLR7) agonist imiquimod (IMQ)...In vivo experiments demonstrated that FI@PMD increased the infiltration of CD8+ cytotoxic T cells in tumor tissues to 2.85-fold of that in the PBS group while reducing the proportion of Treg cells to 0.86-fold. Collectively, this TAM-targeted reprogramming strategy provides a promising approach to overcome immunosuppressive TME and enhance the efficacy of photodynamic immunotherapy in malignant tumors.

Activation of skin local sympathetic signaling in KCs induces CXCL1 production via the ADRB2-CREB pathway, which contributes to recruiting neutrophils to the skin lesions and fuels psoriatic inflammation.

P1/2, N=50, Not yet recruiting, Centre Leon Berard

P1, N=300, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting | N=117 --> 300

Imiquimod enhances CD47 targeting in phagocytosing and removing OSCC cells by activating macrophage TLR7-NF-κB activation and subsequent M1 polarization, providing a promising approach for treating OSCC.

P1/2, N=18, Not yet recruiting, Amsterdam UMC Stichting