전임상 연구 데이터에서 나타나듯이, OX40를 타겟으로 하여 활성화시키는 YH002 단일클론항체는 OX40L과 경쟁적으로 OX40에 결합하여, OX40/OX40L 및 연관된 신호 통로를 활성화시켜, T세포의 증식과 활성화를 촉진합니다. YH002는 또한 독특한 항원결합부위를 갖고 있어, 높은 면역활성화 작용과 안전성을 가지고 있습니다. 또한, YH002는 직접적인 Treg세포의 활성 억제와 ADCC작용을 통한 세포사멸을 통한 간접적인 Treg세포의 활성 억제를 통하여, T세포의 활성효과를 더욱 증대시킴으로서, 다양한 종양을 치료할 수 있도록 합니다. 바이오사이토젠의 OX40 인간화 마우스를 통한 약효실험을 통하여, YH002는 우수한 약효와 병용 투여시의 높은 잠재력을 표출하였습니다.
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.
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.
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.
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 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.
Oct. 18, 2022 | Eucure Biopharma, a Subsidiary of Biocytogen Pharmaceuticals, Licenses OX40 Antibody (YH002) and Multiple Active Ingredients to Syncromune for the Development and Commercialization of Intratumoral Immunotherapy