A Phase 1 trial to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple oral doses of AS-0871 and to evaluate the relative bioavailability and the food effect of new oral formulations of AS-0871 in healthy subjects. - Safety, PK and PD study of AS-0871 in healthy subjects

开始日期2021-12-16

申办/合作机构

Carna Biosciences, Inc.

NL-OMON49497 / CompletedN/A

A single ascending dose trial to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, and food effect of orally administered AS-0871 in healthy subjects - 190388-CS0338

开始日期2020-02-03

申办/合作机构

Carna Biosciences, Inc.

100 项与 Sofnobrutinib 相关的临床结果

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100 项与 Sofnobrutinib 相关的转化医学

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100 项与 Sofnobrutinib 相关的专利（医药）

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项与 Sofnobrutinib 相关的文献（医药）

2024-11-01·CTS-Clinical and Translational Science

Safety, pharmacokinetics, and pharmacodynamics of sofnobrutinib, a novel non‐covalent BTK inhibitor, in healthy subjects: First‐in‐human phase I study

Article

作者: Arimura, Akinori ; Mihara, Katsuhiro ; Oosterhaven, Jart A. F. ; Sawa, Masaaki ; Miller, Robert M. ; Voors‐Pette, Christine ; Geldof, Marian ; van den Dobbelsteen, Marieke ; Sato, Yuji ; Kirita, Shirou ; Matsuda, Naomi ; Miyamoto, Kyoko

Abstract:

Bruton's tyrosine kinase (BTK) is a potential therapeutic target for allergic and autoimmune diseases. This first‐in‐human phase I study evaluated safety, pharmacokinetic, and pharmacodynamic profiles of sofnobrutinib (formerly AS‐0871), a highly selective, orally available, non‐covalent BTK inhibitor, in healthy adult subjects. Single ascending doses (SAD; 5–900 mg) and multiple ascending doses (MAD; 50–300 mg twice daily [b.i.d.] for 14 days [morning dose only on Day 14]) of sofnobrutinib were tested. In the entire study, all adverse events (AEs) were mild or moderate, and no apparent dose‐proportional trend in severity or frequency was observed. No serious treatment‐emergent AEs, cardiac arrythmias, or bleeding‐related AEs were reported. In the SAD part, sofnobrutinib exhibited approximately dose‐dependent systemic exposures up to 900 mg with rapid absorption (median time to maximum concentration of 2.50–4.00 h) and gradual decline (mean half‐lives of 3.7–9.0 h). In the MAD part, sofnobrutinib showed low accumulation after multiple dosing (mean accumulation ratios of ≤1.54) and reached a steady state on ≤Day 7. Single dosing of sofnobrutinib rapidly and dose‐dependently suppressed basophil and B‐cell activations in ex vivo whole blood assays. Multiple dosing of sofnobrutinib achieved 50.8%–79.4%, 67.6%–93.6%, and 90.1%–98.0% inhibition of basophil activation during the dosing interval of 50, 150, and 300 mg b.i.d., respectively. Based on pharmacokinetic‐pharmacodynamic analysis, half‐maximal inhibitory concentration (IC50) of sofnobrutinib for basophil activation was 54.06 and 57.01 ng/mL in the SAD and MAD parts, respectively. Similarly, IC50 for B‐cell activation was 187.21 ng/mL. These data support further investigation of sofnobrutinib in allergic and autoimmune diseases.

项与 Sofnobrutinib 相关的新闻（医药）

2024-04-17

·Pharmaceutical Technology

IGM and Sanofi collaboration will pivot to immunology and inflammation

The IGM and Sanofi collaboration was initially signed in 2022 for the development of IgM agonist antibodies for six indications. Credits: Michael Vi/Shutterstock.com IGM Biosciences has announced that the focus of its exclusive worldwide collaboration agreement with Sanofi will now shift to developing immunoglobin M (IgM) agonist antibodies solely for immunology and inflammation indications. Under the terms of the latest collaboration agreement, IGM will be responsible for leading the research and development of the three immunology and inflammation targets. The Mountain View, California-based biotech will be responsible for the costs of running a Phase I clinical study for up to two constructs directed to each target, after which Sanofi will take over development and commercialisation along with all the related costs of those activities. The terms of the original collaboration agreement, signed in March 2022, saw the two companies utilising IGM’s proprietary IgM technology platform to discover, develop, and commercialise IgM agonists against three targets in oncology and three targets in immunology and inflammation. Pending the achievement of aggregate development, regulatory, and commercial milestones, IGM is eligible to gain up to $1.06bn for each target in addition to “tiered high single-digit to low-teen” royalties on global sales of the candidates. Following the latest shift in focus towards inflammation and immunology, IGM will retain the global rights for its in-house technology associated with the oncology targets that were identified under the partnership. “As we assess next steps with respect to these oncology targets, our top internal priorities remain our clinical-stage oncology and autoimmune programs,” said IGM CEO Fred Schwarzer in the 17 April press release. See Also: TAC-100 by Triumvira Immunologics for Human Epidermal Growth Factor Receptor 2 Positive Breast Cancer (HER2+ Breast Cancer): Likelihood of Approval Sofnobrutinib by Carna Biosciences for Skin Inflammation: Likelihood of Approval In December 2023, IGM fell amongst the wave of pharma companies announcing layoffs, which saw the company jettisoning 22% of its workforce and the discontinuation of operations for all haematologic oncology and targeted cytokine product development. However, the deal with Sanofi remained untouched by the subsequent pipeline shifts.