前臨床研究データによると、OX40アゴニストYH002モノクローナル抗体は、OX40Lと競合的にOX40と結合し、OX40/OX40Lと一連のシグナル伝達経路を活性化することで、T細胞の活性化と増殖を大幅に促進することが知られています。YH002は独特なエピトープを持って、免疫反応をさらに強く加速し、高い安全性を持っています。また, 制御性T細胞の活性化を直接的な抑制やADCC依存性細胞除去の媒介などの働きがあり、T細胞の活性化シグナルを拡大して多種多様な腫瘍を治療することができます。バイオサイトジェンのOX40ヒト化マウスにおいて、YH002は優れたin vivo活性を示し、併用薬として巨大な潜在力を引き出しました。
YH002は、アメリカ食品医薬品局（FDA）および中国の国家薬品監督管理局（NMPA）の承認を得、臨床試験に入りました。2020年6月にはYH002のオーストラリアでの第I相臨床研究のための最初の患者のリクルートが行われました。
YH002 is a highly effective recombinant humanized agonistic OX40 IgG1 monoclonal antibody that exhibits potent anti-tumor activity. By mimicking the function of OX40L and binding to OX40, YH002 acts as an excellent immune-activating antibody with a unique antigen-binding epitope and a favorable safety profile.
Clinical Progress
An open-label, single-arm phase I dose escalation study was conducted in Australia to evaluate the efficacy of YH002 alone in patients with advanced solid tumors. The preliminary results from this study, completed in June 2022, demonstrated that YH002 was both safe and effective for treating advanced solid tumors.
Trial #：YH002002
NCT #：NCT04353102
We have received the IND approvals from the NMPA and the U.S. FDA for Phase I clinical trials of YH002 as a single agent in China and the U.S..
This multicenter, open-label phase I dose escalation study aimed to assess the safety, tolerability, and pharmacokinetics of YH002 in combination with YH001 (a CTLA-4 monoclonal antibody) among patients with advanced solid tumors. The study was conducted simultaneously in Australia and China. In July 2022, enrollment for three dose groups of YH002 combined with YH001 was completed in Australia for the YH002004 trial.
Trial #：YH002004
NCT #：NCT05169697
The preclinical studies conducted on YH002 have yielded significant findings:
1. YH002 was found to be non-toxic even at a high dose of 30 mg/kg.
2.In a syngeneic mouse tumor model, YH002 exhibited excellent anti-tumor activity both alone and when combined with PD-1 antibodies.
3.Complete tumor response was observed with YH002 even at low doses (0.1 mg/kg) when used in combination with YH001 (CTLA-4 monoclonal antibody).
4.It was discovered that YH002 binds specifically and with high affinity to OX40 but not other members of TNFRSF.
5. YH002 is an IgG1 subtype with strong ADCC capabilities.
OX40 Target
OX40 is a type I transmembrane glycoprotein belonging to the TNFRSF family and plays an essential role as a costimulator of T cell response by enhancing TCR signaling after engagement. It promotes proliferation and survival while also releasing effector cytokines that prevent T-cell tolerance formation. Additionally, activation of OX40 inhibits the production and secretion of inhibitory cytokines such as IL-10 and TGF-b by Treg cells while contributing significantly to memory T cell formation.
There are currently no marketed OX40 drugs.
News
Poster Downloads
AACR2020: Rapid screening of novel OX40 agonistic antibodies for cancer immunotherapy
AACR2019: Rapid screening of anti-OX40 antibodies for cancer immunotherapy
