Chengdu-Based Chimagen Biosciences Secures $300M Upfront in $850M Deal with GSK for Trispecific Antibody CMG1A46

On October 29, GlaxoSmithKline (GSK) and Chimagen Biosciences announced an agreement to acquire CMG1A46, a trispecific antibody in the clinical stage developed by the latter. GSK plans to develop and commercialize CMG1A46, focusing on its potential in B-cell-driven autoimmune diseases such as systemic lupus erythematosus (SLE) and lupus nephritis (LN), with the possibility of expanding into other autoimmune conditions.

According to the terms of the agreement, GSK will pay an upfront fee of $300 million (approximately 2.139 billion RMB) to obtain full global rights to CMG1A46. In addition, Chimagen Biosciences will be eligible to receive up to $550 million in development and commercial milestone payments for CMG1A46. The total value of this collaboration amounts to $850 million, approximately 6 billion RMB.

According to Qichacha information, Chimagen Biosciences, headquartered in Chengdu, Sichuan, was established in 2016. It focuses on discovering and developing novel multispecific T-cell engagers and NK-cell engagers generated by a proprietary antibody engineering platform, aiming to improve the lives of patients with cancer and autoimmune diseases.

Since its establishment in 2016, Chimagen Biosciences has only raised approximately 100 million RMB. Several industry insiders have commented, "Compared to other Biotechs of the same period, Chimagen Biosciences has raised too little capital and is overly low-profile." In addition to minimal financing, information about Chimagen Biosciences remains extremely scarce in this era of new media. There are only a few articles reporting on pipeline collaborations, with no comprehensive coverage available to satisfy public curiosity.

Although Chimagen Biosciences behaves "low-key," its technology and products are not "low-key."

Since its establishment, Chimagen Biosciences has been deeply engaged in the fields of bispecific and trispecific antibodies. Its patented antibody engineering platform, DICAD/TRIAD, boasts significant technological advantages. The platform can develop various valency ratios such as 1:1:1, 1:2, 2:2, and 1:1, offering high flexibility. Additionally, the platform exhibits low immunogenicity, favorable pharmacokinetic properties, a long half-life, and the CMC of symmetric structure antibodies shows almost no difference compared to traditional monoclonal antibodies. Based on this platform, Chimagen Biosciences has built a robust product pipeline targeting multiple disease areas, including malignant hematological tumors, malignant solid tumors, and autoimmune diseases.

Good technical platforms and products naturally attract public attention. Before this collaboration with GSK, Chimagen Biosciences' pipeline and technology had already gained recognition from institutions and peers.

In December 2021, Chimagen Biosciences received the FDA's SMP (Study May Proceed) letter, officially approving the clinical trial application for its tri-specific antibody CMG1A46 targeting CD3, CD19, and CD20 for the treatment of refractory and relapsed B-cell malignant hematological tumors. In October 2022, the world's first T-cell mediated tri-specific antibody CMG1A46 against malignant B-cell blood tumors completed the dosing of the first subject in a Phase I clinical trial in the United States.

In December 2021, Bright Biology and Chimagen Biosciences announced a strategic partnership. As the exclusive partner, Bright Biology’s IND application for the trispecific antibody BR110 (CMG1A46), developed by Chimagen Biosciences, was approved by the National Medical Products Administration.This is the world's first approved clinical anti-CD3/CD19/CD20 tri-specific antibody product.Bioray Pharmaceutical Obtains Clinical Development, Manufacturing, and Commercialization Rights in China. In November 2022, Bioray Pharmaceutical announced another strategic cooperation agreement with Chimagen Biosciences. Bioray Pharmaceutical obtained the preclinical development, clinical registration, development, manufacturing, and commercialization rights in China for Chimagen Biosciences' tri-specific antibody BR115 (CMG6A19).

The pipeline acquired by GSK this time is also CMG1A46. CMG1A46 is a trispecific antibody developed by Chimagen Biosciences based on its TRIAD platform. It can simultaneously target the CD3 receptor on T cells, as well as two different biomarkers on tumor cells, CD20 and CD19. CMG1A46 is currently undergoing Phase I clinical trials in the United States and China for leukemia and lymphoma. GSK plans to begin Phase I trials in lupus patients in 2025.

Regarding this collaboration, GSK Chief Scientific Officer Tony Wood stated: "Through our work in systemic lupus erythematosus and lupus nephritis, we are gaining an increasing understanding of the underlying drivers of B-cell-driven diseases. CMG 1A46, as a novel therapeutic option targeting deep B-cell depletion, offers exciting potential, and we are thrilled to continue advancing it to address unmet needs in lupus and related autoimmune diseases."

Chimagen Biosciences CEO Zhenhao Zhou stated, "We are excited about the potential of CMG1A46 to improve the lives of patients with autoimmune diseases and thank GSK for accelerating the realization of this vision. This agreement further validates our proprietary T-cell engager platform, and we are eager to continue developing novel multispecific antibody therapies."

Compared with the well-known monoclonal antibodies (mAbs) and bispecific antibodies (bsAbs), some people may wonder what "trispecific antibodies" are?

Trispecific Antibodies (TsAbs) possess three specific antigen-binding sites, enabling simultaneous interaction with target cells and functional cells, thereby enhancing the killing of target cells. TsAbs can not only bind to target cell-related antigens and activate receptors on functional cells like bispecific antibodies, but also bind to another target on the surface of functional cells. This facilitates drug redirection to the tumor site, increases binding specificity, improves the accuracy of drug targeting to tumor cells, reduces off-target toxicity, and enhances anti-tumor capability.

Tri-specific antibodies are generally created using variable domain genes, and compared to bispecific antibodies, they have a broader application space. They can simultaneously bridge and activate immune cells, or bridge immune cells while blocking dual signaling pathways, among other functions. Notably, the mechanism of simultaneously bridging and activating immune cells is closely related to the human immune system and has a strong killing effect on target cells.

Currently, there are no tri-specific antibody products on the market globally. According to data from VCBeat, as of June this year, there are 136 tri-specific antibody drugs in development worldwide, with 41 entering clinical research. The global research and development of tri-specific antibody drugs is still in its early stages, with the most advanced ones currently in Phase II clinical trials (3 drugs).

According to the data from VCBeat, currently, more than 70 institutions or pharmaceutical companies globally are developing trispecific antibody drugs. The number of products under development by major multinational corporations (MNCs) such as Merck (14 drugs), Sanofi (9 drugs), BMS (5 drugs), Pfizer (2 drugs), and Roche (3 drugs) totals 44, accounting for one-third of all trispecific antibody drugs in research. Notably, over half of the companies involved in trispecific antibody development are local Chinese enterprises, including Chimagen Biosciences, Simcere Pharmaceutical, BeiGene, Pumicstone Biomedicine, TianGuangShi Biotechnology, Huihe Bio, TopAlliance Biosciences, Genor Biopharma, and Innovent Biologics.

This heated situation of both domestic and overseas competition for tri-specific antibodies is also reflected in the frequent transactions. Since this year, there have been several significant collaborations regarding tri-specific antibodies.

In March, Gilead announced a research collaboration and licensing agreement with Merus to jointly develop trispecific antibodies targeting novel dual tumor-associated antigens (TAA). According to the terms of the agreement, if Gilead exercises its option, it will be responsible for additional research, development, and commercialization activities for the program. Merus is entitled to receive a $56 million upfront payment and a $25 million equity investment from Gilead. Across all potential programs, Merus is also eligible to receive up to $1.5 billion in payments, including additional near-term and option exercise fees, potential development and commercial milestones, as well as sales royalties. For the third potential program, Merus may opt for a 50/50 profit share with Gilead instead of future milestone and royalty payments.

In May, Merck & Co. and ophthalmic biotechnology company EyeBio announced a definitive acquisition agreement. Under the terms of the agreement, Merck will acquire EyeBio through its subsidiary for up to $3 billion, including $1.3 billion in upfront cash and $1.7 billion in potential development, regulatory, and commercial milestone payments. EyeBio’s lead candidate drug, Restoret (EYE103), is a potential “first-in-class” tetravalent tri-specific antibody expected to enter pivotal Phase 2b/3 clinical trials in the second half of this year.

Although no tri-specific antibody product has been launched yet, with the optimization of technology and the accumulation of research, several biopharmaceutical companies have designed target combination drugs with iterative advantages through tri-specific antibodies. We look forward to CMG1A46, as the world's first CD3/CD19/CD20 tri-specific antibody product approved for clinical trials, demonstrating excellent clinical data in the fierce competition. We also anticipate that, with the support of multinational corporations (MNCs), the tri-specific antibody field will accelerate its development, bringing more accessible therapies to patients.

References:

1. PharmaSmart Headlines, "The Hype Around Mono- and Bispecific Antibodies Hasn't Faded, Are Trispecific Antibodies Already Here?"

2. Drug Hunter Club, "The Rise of Trispecific Antibodies: Chinese Pharmaceutical Companies Hold Up Half the Sky!"