YH001 is a promising recombinant humanized CTLA-4 IgG1 monoclonal antibody that has shown preliminary anti-tumor activity and a good safety profile in combination with PD-1 monoclonal antibodies.
We have reached an agreement with Tracon in the United States to explore indications such as sarcoma and other indications. The Phase I/II clinical trial of YH001 in combination with envafolimab (PD-L1 mAb) and doxorubicin for the treatment of soft tissue sarcoma patients was approved by FDA in August 2022, and dosed the first patient in November 2022.
YH001, in combination with the anti-PD-1 mAb Tuoyi (Toripalimab) from Junshi Biosciences, demonstrated promising safety and efficacy in a phase I clinical trial conducted in Australia. The trial involved dose escalation ranging from 0.05 mg/kg to 6.0 mg/kg. As of the data as cut-off date of December 31, 2022, Among 26 evaluable patients out of 29 enrolled patients, 5 showed partial response (PR) while 11 had stable disease (SD). The study achieved its primary endpoint, and the maximum tolerated dose (MTD) of YH001 in combination therapy was determined to be 4.0 mg/kg.
A phase I/II dose escalation trial of YH001 for subjects with advanced solid tumors was conducted in China. Based on the results of the phase I study in Australia, the dose was modified to escalate from 0.3 mg/kg to 6.0 mg/kg. As of May 2022, 14 patients had been evaluated, with four showing stable disease (SD). The primary study endpoint was achieved, and the highest dose of 6.0 mg/kg for YH001 as a single-agent escalation remained safe and tolerable.
We received the U.S. FDA approval in June 2021, the Taiwan FDA approval in October 2021 and the NMPA approval in November 2021 for the Phase II clinical trial.
Several preclinical studies have demonstrated the effectiveness and safety of YH001:
1.In an in vivo pharmacodynamic tumor model, YH001 showed superior anti-tumor activity when used in combination with the PD-1 mAb pembrolizumab (Keytruda) compared to ipilimumab (Yervoy).
2.In vitro tests showed that YH001 exhibited better blocking activity and stronger antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) effects than ipilimumab.
3. In a mouse model, YH001 significantly reduced the proportion of Tregs in tumor-infiltrating lymphocytes.
4.YH001 displayed a more favorable in vivo safety profile compared to ipilimumab.
Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), also known as CD152, plays a crucial regulatory role in T cell activation. CTLA-4 is expressed on the surface of regulatory T cells (Tregs), and it competitively inhibits the binding of B7 to CD28 on the surface of effector T cells when bound to B7-1 (CD80) and B7-2 (CD86) on the surface of antigen-presenting cells (APCs). Consequently, T cell activation is inhibited. Inhibitory antibodies that target CTLA-4 can block this mechanism and enhance T cell activity, thus improving the patient’s immune response to tumors.
Blocking the inhibitory signal of the human anti-tumor response is currently considered the most promising tumor immunotherapy. CTLA-4 and PD-1 are critical checkpoints of the immune system and are thus key targets of tumor immunotherapy. By blocking them, different types of T cells can be affected, leading to the initiation of anti-tumor immune attack.
Currently, marketed antibody drugs targeting CTLA-4 include the CTLA-4 mAb ipilimumab (Yervoy) from BMS and the PD-1/CTLA-4 bispecific antibody cadonilimab (trade name: Kaitanni; AK104) from Akeso.
Contact us for partnership: [email protected]
November 22, 2022 | First Patient Dosed in Phase 1/2 Trial Evaluating YH001 in Combination with Envafolimab and Doxorubicin in Front Line Sarcoma Patients
August 29, 2022 | US FDA Approval of IND for CTLA-4 Antibody YH001 for the Treatment of Front-line Sarcoma Patients in Combination with Envafolimab
November 9, 2021 | Biocytogen/Eucure Biopharma’s YH001 (Anti-CTLA-4 Monoclonal Antibody) Approved for Phase II Multi-Regional Clinical Trial by China National Medical Products Administration
October 11, 2021 | Eucure Biopharma, a Subsidiary of Biocytogen, and TRACON Pharmaceuticals Announce Partnership for Development of Clinical Stage CTLA-4 Antibody YH001