Today, a patient of Shanghai Chest Hospital, as the first subject, was administrated with HOT-1030, a recombinant humanized IgG1 type anti-CD137 (also known as 4-1BB) monoclonal antibody agonist developed jointly by Shanghai Huaota Biopharmaceutical Co., Ltd. (aka "Huaota") and Eutilex, Korea. Presently, the patient is in good conditions. By now, Eutilex has been approved by the U.S. Food and Drug Administration (FDA) for Phase I study in the U.S, which is expected to be initiated in May 2021. “

Today, a patient of Shanghai Chest Hospital, as the first subject, was administrated with HOT-1030, a recombinant humanized IgG1 type anti-CD137 (also known as 4-1BB) monoclonal antibody agonist developed jointly by Shanghai Huaota Biopharmaceutical Co., Ltd. (aka "Huaota") and Eutilex, Korea. Presently, the patient is in good conditions. By now, Eutilex has been approved by the U.S. Food and Drug Administration (FDA) for Phase I study in the U.S, which is expected to be initiated in May 2021. “A preclinical study has shown a good balance between safety and efficacy for HOT-1030. The mechanism of its combination with different molecules will be further explored in the future, and our clinical team will continue to accelerate the advancement, so that patients may have more options for treatment as soon as possible” said Dr. Zhu Xiangyang, the CEO of Huaota.

About HOT - 1030:

HOT-1030 is a ligand non-blocking excitatory antibody targeting 4-1BB. Its molecular characteristics are as follows:

1) High target affinity: HOT-1030 may specifically bind to human 4-1BB, with an affinity of 2.25E-10M.

2) Excellent binding epitope: HOT-1030 mainly binds to CRD1 in the extracellular region of human 4-1BB, without blocking the normal 4-1BB binding with its ligand, 4-1BBL. Therefore, HOT-1030 should be better than ligand-blocking antibody in efficacy.

3) Signal remodeling and enhancement: The co-stimulatory signals formed through combination of HOT-1030 with 4-1BB may effectively induce the proliferation and differentiation of tumor infiltrating CD8⁺T cells, enhance the functional activity of cytotoxic T lymphocytes (CTL), regulate the transformation of tumor microenvironment from immunosuppression to immune normalization, and strengthen the antitumor activity of CTL. The antitumor activity of HOT-1030 is similar to or better than that of similar drugs under development from other countries.

4) Low hepatotoxicity risk: Due to the mutation introduced in the Fc segment of its heavy chain, HOT-1030 can weaken its affinity with Fcγ RIIB as eliminating or weakening the effect of ADCC/CDC, thus reducing potential adverse reactions induced by ADCC/CDC and the hepatotoxicity risk for over-activation of 4-1BB signal caused by FcγRIIB cross-linking effectively.

Schematic diagram of action mechanism for HOT-1030

Market Competition:

Currently, drugs with 4-1BB as target are still not marketed. The IgG4 type Urelumab of BMS and IgG2 type Utomilumab of Pfizer are in Phase Ⅱ clinical trial as the fastest ones in research progress. The proposed indications are solid tumor, chronic lymphocytic leukemia, non-Hodgkin's lymphoma, and etc.

Besides the two pharmaceutical giants mentioned above, more and more domestic and foreign research institutions and companies have begun to focus on the target through CD137 monoclonal antibody/bispecific antibody, combination therapy with  monoclonal antibody or chemotherapy of other immune checkpoint inhibitors, and application of cell therapies, e.g., Car T. We believe that the potential of this target will be further revealed in the future.