[Translation] Safety, tolerability, pharmacokinetics and pharmacodynamics of HT-102 (BM012) injection in healthy subjects and e-antigen-negative patients with chronic hepatitis B virus infection: a randomized, double-blind, placebo-controlled, single and multiple subcutaneous injection, dose-escalation phase I clinical study

研究健康受试者单次皮下注射HT-102（BM012）注射液和慢性乙肝病毒感染患者多次皮下注射HT-102（BM012）注射液的安全性及耐受性

[Translation]

To investigate the safety and tolerability of a single subcutaneous injection of HT-102 (BM012) injection in healthy subjects and multiple subcutaneous injections of HT-102 (BM012) injection in patients with chronic hepatitis B virus infection

Start Date12 Jun 2023

Sponsor / Collaborator

Suzhou Biomissile Pharmaceuticals Co., Ltd.

100 Clinical Results associated with HT-102

100 Translational Medicine associated with HT-102

100 Patents (Medical) associated with HT-102

Literatures (Medical) associated with HT-102

15 Nov 2024·The Journal of Immunology

Immunometabolic Mechanisms of LANCL2 in CD4+ T Cells and Phagocytes Provide Protection from Systemic Lupus Erythematosus

Article

Author: Fitch, Sarah N. ; Leber, Andrew ; Tubau-Juni, Nuria ; Bassaganya-Riera, Josep ; Hontecillas, Raquel

AbstractLanthionine synthetase C–like 2 (LANCL2) is an immunoregulatory therapeutic target for autoimmune diseases. NIM-1324 is an investigational new drug aimed at addressing the unmet clinical needs of patients with systemic lupus erythematosus (SLE) by targeting the LANCL2 immunometabolic pathway. In R848 and bm12 adoptive transfer models of systemic inflammation that share pathologies with SLE, Lancl2−/− mice experienced greater mortality, increased spleen weight, and reduced CD25hi FOXP3+ CD4+ regulatory T cells compared with the wild type. Conversely, treatment with NIM-1324 in the wild type increased CD25hi FOXP3+ regulatory T cells while reducing inflammatory IL-17+ and IL-21+ CD4+ T cell subsets in the spleen. In traditional mouse models of SLE (NZB/W F1 and MRL/lpr), oral treatment with NIM-1324 protected against weight loss and proteinuria, decreased anti-dsDNA titers, and provided similar changes to the CD4+ T cell compartment in the spleen. The pharmacological activation of LANCL2 by NIM-1324 rescued hypocomplementemia, reduced kidney histopathological scores, and decreased blood IFN response genes and inflammatory cytokines. The loss of LANCL2 in phagocytes impairs phagosome processing, leading to increased uptake of material and inflammatory cytokine production, yet decreased markers of endosomal maturation, phagosome turnover, and lysozyme activity. Treatment with NIM-1324 increases metabolic and lysozyme activity in the phagosome, providing support for increased markers of early phagosome function. This efficacy translated to human PBMCs from patients with SLE, because ex vivo treatment with NIM-1324 resulted in reduced levels of IFN-α, IL-6, and IL-8. Consequently, the activation of LANCL2 effectively modulates CD4+ T cell differentiation and phagocyte activation, supporting immune tolerance in SLE.

01 Jun 2024·Lupus Science & Medicine

Inhibition of receptor interacting protein kinase-1 (RIPK1) in the treatment of murine lupus

Article

Author: Qin, Weisong ; Yang, Shuying ; Wang, Pengcheng ; Yang, Fan ; Xia, Hongguang ; Xu, Xiaodong ; Chen, Dacheng ; Peng, Lin ; Liu, Zhi-Hong ; Xu, Feng

ObjectiveSystemic lupus erythematosus (SLE) is a type of autoimmune disease that involves multiple organs involved as well as cytokine dysregulation. The treatment of SLE is still challenging due to the side effects of the different drugs used. Receptor-interacting protein kinase 1 (RIPK1) is a kinase involved in T cell homeostasis and autoinflammation. Although clinical trials have shown that RIPK1 inhibition exhibits significant efficacy in different autoimmune diseases, its role in SLE remains unclear.MethodsMRL/lpr lupus-prone mice received RIPK1 inhibitor ZJU37 or vehicle intraperitoneally for 10 weeks. A BM12-induced chronic graft-versus-host-disease (cGVHD) lupus-like model was introduced in RIPK1 D138N mice or C57BL/6 mice. Nephritis, serum autoantibody levels, dysregulation of adaptive immune response and cytokines were compared in treated and untreated mice.ResultsZJU37 alleviated the clinical features of the MRL/lpr mice including nephritis and anti-dsDNA antibody production. In addition, ZJU37 treatment reduced the proportion of double-negative T cells in the spleen and the cytokines of TNFα, IFN-γ, IL-6, IL-17 and IL-1β in the serum. Moreover, RIPK1 D138N mice were able to prevent the cGVHD lupus-like model from SLE attack, manifesting as anti-dsDNA antibody production, the proliferation of germinal centre B cells, plasma cells, and T follicular helper cells as well as IgG and C3 deposits in kidneys.ConclusionRIPK1 inhibition has a protective effect in the mouse model of SLE and can potentially become a new therapeutic target for SLE in humans.

01 Jan 2009·Journal of Pharmaceutical and Biomedical AnalysisQ3 · MEDICINE

Quantitative solid-state analysis of three solid forms of ranitidine hydrochloride in ternary mixtures using Raman spectroscopy and X-ray powder diffraction

Q3 · MEDICINE

Article

Author: Dorothy Saville ; Jaakko Aaltonen ; Thomas Rades ; Sönke Rehder ; Norman Chieng

The aim of the study was to develop a reliable quantification procedure for mixtures of three solid forms of ranitidine hydrochloride using X-ray powder diffraction (XRPD) and Raman spectroscopy combined with multivariate analysis. The effect of mixing methods of the calibration samples on the calibration model quality was also investigated. Thirteen ternary samples of form 1, form 2 and the amorphous form of ranitidine hydrochloride were prepared in triplicate to build a calibration model. The ternary samples were prepared by three mixing methods (a) manual mixing (MM) and ball mill mixing (BM) using two (b) 5 mm (BM5) or (c) 12 mm (BM12) balls for 1 min. The samples were analyzed with XRPD and Raman spectroscopy. Principal component analysis (PCA) was used to study the effect of mixing method, while partial least squares (PLS) regression was used to build the quantification models. PCA score plots showed that, in general, BM12 resulted in the narrowest sample clustering indicating better sample homogeneity. In the quantification models, the number of PLS factors was determined using cross-validation and the models were validated using independent test samples with known concentrations. Multiplicative scattering correction (MSC) without scaling gave the best PLS regression model for XPRD, and standard normal variate (SNV) transformation with centering gave the best model for Raman spectroscopy. Using PLS regression, the root mean square error of prediction (RMSEP) values of the best models were 5.0-6.9% for XRPD and 2.5-4.5% for Raman spectroscopy. XRPD and Raman spectroscopy in combination with PLS regression can be used to quantify the amount of single components in ternary mixtures of ranitidine hydrochloride solid forms. Raman spectroscopy gave better PLS regression models than XRPD, allowing a more accurate quantification.

100 Deals associated with HT-102

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Indication	Highest Phase	Country/Location	Organization	Date
Hepatitis B, Chronic	Phase 1	-	Suzhou Xingyao Kunze Biopharmaceutical Co., Ltd.	06 Apr 2022
Hepatitis D	Phase 1	CN	Suzhou Xingyao Kunze Biopharmaceutical Co., Ltd.	-

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