The following article is from Yaozhi.com, authored by Dr. July Hu
Figure 1 Introduction of drugs related to immune restart therapy
Data source: Yaozhi Data, Yaozhi Consulting collation
On May 7, 2001, CAMPATH® was initially approved for marketing in the United States, and later in Europe, Canada,*** Kong, China and other countries and regions, and was approved as an injectable therapeutic drug for B-cell chronic lymphocytic leukemia (B-CLL). On August 27, 2008, Thymoglobuline® developed by Sanofi-Aventis was approved for marketing. It has currently been approved for the relevant treatments of graft-versus-host disease, aplastic anemia, transplant rejection reactions, as well as the prevention of transplant rejection reactions and graft-versus-host disease. According to the statistics of Yaozhi Database, a total of 259,900 doses of Thymoglobuline® were sold in the Chinese region in 2023, with sales of nearly 620 million yuan. T-Guard is an ADC mixed preparation introduced by Xenikos from Henogen. In March 2023, its phase III clinical study in GvHD was forced to terminate due to safety issues.
Although the above-mentioned drugs can all exert the function of clearing T cells, the clearing methods are not specific, and the clearing effects of CAMPATH® and Thymoglobuline® are incomplete. T-Guard even has safety problems.
02 Multiple indications simultaneously conduct clinical trials,
VG712 may be the most ideal immunotherapy
It can be seen that restarting the function of immune cells is not simply achieved by killing T cells. The drugs that truly "restart" the immune function of cells should have the characteristics of high specificity, strong affinity, complete clearance, short duration of action, and high safety.
Figure 2 Conditions of drugs for restarting immune cell functions
Data source: Yaozhi Data, Yaozhi Consulting collation
In 1994, Dr. David Neville and Dr. HUAIZHONG HU (Hu Huaizhong) began to verify the construction and mechanism of the bivalent toxin protein molecule targeting the CD3 target, opened up and simplified the relevant production process, and pioneered the research in the field of immunotoxins. In 2008, Dr. David Neville, Dr. Yuan-Yi Liu, and Dr. Jung-Hee Woo jointly founded Angimmune Company. The team, in conjunction with Harvard University and the University of Louisville, advanced the research to the stage of indication and safety exploration, and successively completed preclinical/clinical phase I studies in directions such as organ transplantation, cutaneous T-cell lymphoma, and PD-1 solid tumor combination therapy, and applied for relevant invention patents.
In 2014, it obtained the orphan drug qualification from the FDA, and in 2016, it obtained the FDA fast review qualification due to its significant clinical efficacy. In February 2023, the NIH approved the global exclusive commercial development rights of this pipeline to the US and Hong Kong subsidiaries of Chengdu Vigen Bioboat Biomedicine Technology Co., Ltd. (hereinafter referred to as: Vigen Biotech), and the current pipeline is named VG712.
VG712 is a bivalent fusion protein that combines the antibody binding domain fragment targeting the T cell CD3 site with the modified diphtheria toxin. It can be endocytosed by specific binding with T cells and release toxins***, VG712 has become the most promising drug to achieve the restart of immune cell functions.
Relevant existing studies have shown that VG712 can completely clear T cells in the human body in a short period of time, thereby prompting the cellular immune system to restart and produce a large number of new T cells, thereby restoring normal immune function. This method can improve the long-term ability of T cells to recognize and attack tumor cells; induce immune tolerance after organ transplantation and improve the function and survival period of organs; specifically clear T cells in the lymphatic system, maximize the therapeutic effect and safety of CAR-T therapy, and improve the outcome of cancer patients; reduce the attack of T cells on their own organs and improve the progression of T cell-mediated autoimmune diseases; and clear the latent virus reservoir of T cells in AIDS patients and reverse the condition of drug-resistant patients.
According to the public clinical research results, the clinical phase I study of CTCL conducted in the United States has confirmed that VG712 can quickly and effectively clear T cells in patients within 4 days, and T cells recover to the pre-treatment level within 14 days, and the CD8 memory T cells specifically against tumors increase by 20 times compared to before treatment. Moreover, many patients with advanced cutaneous T-cell lymphoma have achieved clinical cure, obtaining dual recognition in terms of mechanism and efficacy for VG712. Animal experiments have shown that compared with the already marketed T cell clearance drugs, VG712 can not only effectively clear T cells in the circulatory system but also effectively clear T cells in organs.
According to Vigen Biotech's development plan for VG712, confirmatory clinical studies of cutaneous T-cell lymphoma (CTCL) in the United States will be conducted in 2024. At the same time, phase I clinical studies for immune tolerance induction after kidney organ transplantation, phase I clinical studies for GvHD after hormone resistance, and phase I clinical studies for lymphodepletion before CAR-T treatment will also be initiated. Research in areas such as AIDS and autoimmune diseases is also looking for partners to jointly promote.
03
Sales are expected to exceed 70 billion US dollars,
Immunotherapy welcomes new hope
VG712 brings new hope for the restart of cellular immune functions, opens up a new direction in the field of immunotherapy, and will achieve major breakthroughs in anti-tumor, induction of immune tolerance, organ transplantation, lymphodepletion before CAR-T treatment, and other aspects.
According to the assessment by Yaozhi Consulting, the fastest-progressing indication, CTCL, is expected to achieve cumulative sales of 539 million US dollars in the global market (the United States, Europe, China, and Southeast Asia) within five years after its launch (2029-2033). Sales are expected to peak in 2038, with an annual sales peak of 268 million US dollars, and cumulative sales of 1.679 billion US dollars can be created in the global market within ten years of launch (2029-2038).
Based on the comprehensive existing clinical indications and the rNPV valuation method, the global market sales of VG712 within ten years of the planned launch (2028-2038) is approximately 73.933 billion US dollars. In areas such as lymphodepletion before CAR-T treatment, induction of immune tolerance after organ transplantation, GvHD after hormone resistance, autoimmune diseases, and AIDS, clinical needs are obvious, and there are many pain points in existing marketed products. Combined with the innovative treatment principle and excellent clinical manifestations of VG712, this pipeline is expected to achieve market sales of more than 300 million US dollars in the year of launch.
A truly autonomous and long-term acting immunotherapy, VG712 may open up the third route of tumor treatment and become an indispensable drug in the field of immunotherapy in the next two or three decades.
Previously, there was a hundred-billion-dollar blockbuster like "Semaglutide". Will VG712 be the next one?
