Agreement Enlarges China's Role in Cancer Immunotherapeutics Development

A recent agreement marks the expansion of drug development collaboration between a Chinese biopharmaceutical company and a major international drug corporation.

Eli Lilly (Indianapolis, IN, USA) and Innovent Biologics, Inc. (Suzhou Industrial Park, China) announced that they will undertake a decade long collaborative effort to develop and commercialize up to three anti-PD-1 (programmed cell death protein 1) bispecific antibodies to be used for cancer treatment.

PD-1, functioning as an immune checkpoint, plays an important role in downregulating the immune system by preventing the activation of T-cells, which in turn reduces autoimmunity and promotes self-tolerance. The inhibitory effect of PD-1 is accomplished through a dual mechanism of promoting apoptosis in antigen specific T-cells in lymph nodes while simultaneously reducing apoptosis in regulatory T cells (suppressor T-cells). New classes of drugs that block PD-1, the PD-1 inhibitors, activate the immune system to attack tumors and are therefore used with varying success to treat some types of cancer.

A bispecific monoclonal antibody (BsMAb, BsAb) is an artificial protein that is composed of fragments of two different monoclonal antibodies and consequently binds to two different types of antigen. The most widely used application of this approach is in cancer immunotherapies, where BsMAbs are engineered that simultaneously bind to a cytotoxic cell (using a receptor like CD3) and a target such as a tumor cell to be destroyed. Cancer immunotherapy with ordinary monoclonal antibodies does not activate T-lymphocytes because this type of cell does not possess Fc receptors, so the Fc region cannot bind to them, and the Fab regions are already used for binding the tumor cells. Bispecific antibodies have a higher cytotoxic potential, as they bind to antigens that are expressed relatively weakly.

According to the agreement Eli Lilly will create the three preclinical anti-PD-1 based bispecific antibodies using an antibody sequence contributed by Innovent. Lilly will then exercise its rights to develop, manufacture, and commercialize these potential cancer treatments outside of China. Innovent will have the rights to develop, manufacture, and commercialize these potential cancer treatments in China, subject to a Lilly opt-in right for co-development and commercialization. Under the terms of the expanded agreement, Innovent could receive additional milestone payments totaling more than one billion USD if the products reach certain development, regulatory, and sales milestones, both inside and outside of China.

"We believe that combination therapy in immuno-oncology has the potential to transform the way cancer is treated," said Dr. Greg Plowman, vice president of oncology research at Eli Lilly. "We are pleased to be expanding our collaboration with Innovent to further the development of potential therapies for those fighting cancer in China and around the world."

Dr. Michael Yu, president and CEO of Innovent, said, "We are honored that Lilly is so quickly expanding our relationship and that Lilly is trusting Innovent to develop and manufacture their newly created bispecific antibodies for China. We are excited to be at the forefront of immuno-oncology drug development and to benefit from Lilly's deep experience in bispecific antibodies."

Related Links:
Eli Lilly
Innovent Biologics, Inc.