BMS-986442 (AGEN1777), a TIGIT/CD96 Bispecific Antibody Acquired by BMS for Over $1.5 Billion, to Present Preclinical Data at AACR
Agenus
Cancer Drug Developer
Bristol-Myers Squibb
Biopharmaceutical and Nutritional Product R&D and Sales
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On March 6, 2024, Agenus announced that BMS-986442 (AGEN1777), co-developed by the company and Bristol-Myers Squibb ("BMS"),Preclinical data to be presented at the upcoming AACR meeting.BMS-986442 is a TIGIT and CD96 dual antagonist. Currently,This drug has demonstrated excellent pharmacological activity, enhancing anti-tumor immunity in patients with advanced solid tumors., providing a unique option.
In May 2021, BMS and AgenusWith a $200 million upfront payment, a potential milestone payment of $1.36 billion, and tiered double-digit royalties on net product sales, Obtained the Global Development and Commercialization Rights for Agenus' Bispecific Antibody Pipeline AGEN1777. In November 2023, Agenus announced that withFirst Patient Dosed in the Expansion Portion of Phase 2 CA115-001 Clinical TrialThe company received a cash payment of $25 million from BMS.
1. About BMS-986442
BMS-986442 has an enhanced Fc region that improves tumor-reactive T-cell responses. The Fc enhancement modification helps strengthen the binding of Fc to receptors, further enhancing Fc-mediated effects, including ADCC, thereby achieving better activation of T cells or NK cells. This mechanism is crucial for the efficacy of TIGIT antibodies.
TIGIT is an inhibitory receptor primarily expressed on T cells and NK cells. It suppresses the activation mechanism of CD226 by competitively binding with CD226 to PVR (CD155), thereby inhibiting the activity of T cells. Similar to TIGIT, CD96 can also bind to PVR to transmit immunosuppressive signals.
Therefore, TIGIT and CD96 are a set of complementary targets, and simultaneous blockade of both can further block the immunosuppressive signals mediated by PVR.
The T cell response effect of using BMS-986442 is significantly better than using anti-TIGIT antibody or anti-CD96 antibody alone, and also significantly better than the combination of two single-target antibodies.
Earlier, BMS disclosed at the 2023 R&D Day event that it would terminate the development of the TIGIT antibody and further develop the TIGIT/CD96 bispecific antibody BMS-986442. Currently, the company is developing BMS-986442 for non-small cell lung cancer and gastric cancer. The monotherapy Phase I clinical trial has been completed; the combination therapy (e.g., PD-1±chemotherapy) Phase 1/2 dose escalation trial is expected to report data in 2024.
2. Development of TIGIT Bispecific Antibodies
According to incomplete statistics, there are currently over 80 TIGIT drugs under research, with more than half in the preclinical research stage.
Among these investigational drugs, 22 are bispecific antibodies, with targets for TIGIT-binding bispecific antibodies including PDL1/PD1, CD112R, CTLA4, CCR8, LAG3, CD96, and others.
In the above pipeline, a total of 18 pipelines are participated in research and development by domestic companies, including Huabio Biotech, Henlius, Pumeds, Buchang Pharmaceutical, Innovent, Hengrui, Shenghe, Simcere, Zelgen, etc., and all drugs from the aforementioned companies have entered the clinical stage.
The general view is that the combination of TIGIT monoclonal antibody with PD-1 monoclonal antibody and PD-L1 monoclonal antibody can enhance the effects of PD-1 monoclonal antibody and PD-L1 monoclonal antibody. In 2022, the global PD-(L)1 market size was approximately USD 38.764 billion, increasing by 19% year-on-year. This marks the 8th consecutive year of expansion for the PD-(L)1 market. It is speculated that TIGIT is expected to become the next blockbuster worth tens of billions of dollars.
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