Nearly 80 domestic dual-resistance models flooded into the market of over 50 billion!

Entering 2022, the field of double antibody research and development has ushered in good news one after another
.

On January 5, Pharmaco announced that its self-developed Kadeninumab (AK104) combined with AK112 double antibody phase Ib/II clinical trial application was approved by NMPA, with or without chemotherapy for the treatment of advanced non-small cell lung cancer.

Only 4 models are listed in the world, and the double antibody field has broad prospects

Only 4 models are listed in the world, and the double antibody field has broad prospects

Double-antibody drugs mainly refer to artificial antibodies containing two specific antigen-binding sites, which can interact with target cells and T cells at the same time to mediate a series of immune responses
.

Compared with traditional monoclonal antibody, the advantage of double antibody is that it has more precise targeting and stronger therapeutic effect.

On May 21, 2021, Johnson & Johnson's Amivantamab, the world's fourth dual-antibody drug, was approved by the U.
S.
FDA for the treatment of EGFR-mutated non-small cell lung cancer.
10 years
.

In more than 10 years, only 4 double-antibody drugs have been launched in the world, in addition to Johnson & Johnson's Amivantamab, there are also TrionPharma's catumumab, Amgen's belintuzumab, and Roche's emerizumab

Table 1: Globally marketed dual anti-drugs

80 domestic models are in the clinical stage, with Cinda, BeiGene, Hengrui, etc.

80 domestic models are in the clinical stage, with Cinda, BeiGene, Hengrui, etc.

Focusing on the domestic double antibody field, the research and development upsurge of double antibody continued
.

According to statistics, nearly 80 double-antibody drugs are currently in the R&D state of clinical application and above, and more than 44 domestic pharmaceutical companies have participated in the layout

In terms of quantity, Innovent Bio is a "big player" in the field of double-antibody, with 7 double-antibody drugs in clinical stage, and is the pharmaceutical company with the most double-antibody drugs under research in China
.

BeiGene has 6 double-antibodies in the clinical stage, 1 was obtained in cooperation with Zymeworks, and the remaining 5 were introduced in cooperation with Amgen

Figure 1: Domestic pharmaceutical companies with more than 3 dual-resistant varieties in clinical stage

From the perspective of research and development progress, Pharmacobio's candeninumab (AK104) is making the fastest progress.
In September 2021, CDE approved the application of PD-1/CTLA4 dual-antibody candeninumab (AK104) for the treatment of relapse.
or metastatic cervical cancer, and given priority review status
.

Hengrui's PD-L1/TGFB double-antibody SHR-1701, Corning Jereh's PD-L1/CTLA4 double-antibody recombinant humanized PDL1/CTLA-4 double-specific single-domain antibody Fc fusion protein (KN046), Kangfang Biotechnology Another dual-antibody AK112, BeiGene’s anti-HER2 multi-site dual-antibody ZW25, and the EpCAM/CD3 dual-antibody catulumumab introduced by Guangdong Lingteng are all in clinical phase III

Table 2: Research status of double antibody in China

Note: Only the application clinical stage and above will be counted; the statistical date will end in early January 2022

In terms of the research and development of the target, PD-L1/TGFB is the most popular combination of dual antibody research and development in China.
By blocking the two signaling pathways of PDL1 and TGFB, PD-L1/TGFB dual antibody not only relieves the immune suppression in the body, It also restores the body's immune killing ability, and theoretically the curative effect can be greater than "1+1"
.

At present, there are 8 PD-L1/TGFB dual antibodies in the clinical stage in China, among which the fastest progress is Hengrui's SHR-1701, which is in clinical phase III
.

According to the China Drug Clinical Trials Publicity Database, 15 related clinical studies have been initiated so far, and indications such as non-squamous non-small cell lung cancer, gastric cancer, and cervical cancer are in Phase III clinical trials

From the statistics of the research and development of a single target, PD-(L)1 is a well-deserved target "social expert" in the field of double antibodies
.

Among the 78 double-antibody drugs included in the statistics, 16 are based on the PD-1 target, and 32 are based on the PD-L1 target.

Figure 2: Target heatmap

Multi-faceted layout, 5 billion double antibodies will be listed soon

Multi-faceted layout, 5 billion double antibodies will be listed soon

Kadeninumab (AK104) is a novel and potentially next-generation first-in-class PD-1/CTLA4 bispecific tumor immunotherapy drug independently developed by Kangfang Bio, which can simultaneously target two validated immune checkpoint molecules: program Sexual cell death protein 1 (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA4), so the clinical efficacy of PD-1 and CTLA4 monoclonal antibody combination therapy and PD-1 and CTLA4 monoclonal antibody combination therapy have not been shown.
Good security provided
.

According to the data of the new version of the global new drug research and development database of Minet.
com, the research and development of candeninumab is not limited to China, and a number of clinical trials have also been carried out in the United States, Australia, and New Zealand.
The indications under development involve a variety of tumor types, including cervical cancer, Gastric cancer, esophageal cancer, renal cell carcinoma, non-small cell lung cancer, adenocarcinoma, lymphoma, solid tumor, breast cancer, squamous cell carcinoma, melanoma, hepatocellular carcinoma, nasopharyngeal carcinoma,
etc.
In China, more than 13 clinical trials of candeninumab have been carried out, among which the clinical trial results of candenizumab in the treatment of recurrent or metastatic cervical cancer were disclosed at the 2020 China Cancer Immunology Conference, showing that the objective response rate (ORR) Compared with PD-1 monotherapy or CTLA4 combination therapy, the efficacy was significantly improved
.

Based on the excellent performance of its clinical trials, on September 26, 2021, CDE has agreed to Acumen Biopharma's submission of a new drug marketing application for cdenimumab for the treatment of recurrent or metastatic cervical cancer, and granted priority review qualification
.
Kadenimumab is expected to be approved in 2022, and has won a series of heavy titles such as "first-in-class", the world's first PD-1/CTLA4 double antibody, and the first domestic double antibody
.
According to brokerage estimates, the peak sales of Kadeninumab are expected to reach 5 billion yuan
.

Figure 3: The specific layout of Kadenin

Source: New version of the Global New Drug Research and Development Library

Epilogue

Epilogue

Data forecasts show that with the entry of new double antibodies into the market and the approval of more indications for double antibodies on the market, the global market size of double antibodies will exceed 50 billion yuan in 2025
.
In recent years, the research and development of innovative drugs in China has ushered in a new climax.
Under the leadership of leading companies such as Kangfang Biotechnology, Corning Jereh, and Hengrui Medicine, the research and development of double-antibody drugs has shown a lively scene of thousands of sails and hundreds of competitors
.
The first domestic double-antibody drug will be launched soon, but the commercialization risks that come with it cannot be underestimated
.
Later players on the double-antibody track should pay more attention to reducing homogeneous competition and seeking product differentiation, so as to have a chance to catch up with the former
.