A window into VISTA
LEBANON, N.H.—Immunology researchers at ImmuNext and Janssen Biotech Inc. have announced a partnership in developing novel immunotherapies for cancer.
ImmuNext will grant Janssen a worldwide, exclusive license to develop and commercialize therapeutics that antagonize the V-region immunoglobulin-containing suppressor of T-cell activation (VISTA) signaling pathway. In exchange, Janssen will provide ImmuNext with an upfront payment, plus payments for reaching development and commercial milestones. The total payments to ImmuNext could total more than $150 million, plus royalties on product sales and sponsored research support.
VISTA is a newly identified negative checkpoint regulator. Through this partnership, ImmuNext and Janssen will collaborate to research and develop novel cancer therapeutics that antagonize the VISTA signaling pathway.
ImmuNext brings into the partnership its expertise at immunology, and it will pursue the basic research to better understand the VISTA pathway with the help of Janssen's sponsorship. This research will facilitate Janssen in its development and potential commercialization of antibodies specific to the VISTA ligand.
Recent approaches to immunotherapy for cancer have focused on checkpoint regulators, of which VISTA is one. Checkpoint regulators involve the signal pathways that the body uses to shut down the immune system's response when it is no longer needed—for example, allowing swelling to subside after a wound heals or returning mucus production to normal levels after a cold virus runs its course. It is hypothesized that tumors may circumvent the body's natural defenses by "turning off" the local immune response in the tumor microenvironment. A successful VISTA antagonist compound would disrupt this turning-off process, unleashing the body's natural immune responses to a foreign presence such as a tumor.
Immunotherapy approaches to cancer treatment have not been without skeptics and some early failures. The first attempts at developing cancer immunotherapies were abysmally unsuccessful, resulting in limited patient responses, and in some cases caused fatal side effects.
"Investors started running away from the idea of using the immune system to treat cancer," says ImmuNext CEO David DeLucia. "But in the past year or two, new approaches to immunotherapy have been helping around 35 percent of patients in some cases, so we're seeing a warming to immunotherapy. Investors are paying attention again."
Recent successes in the field— including encouraging trial results shared by Bristol- Meyers Squibb Co. surrounding their immunotherapeutic product Yervoy (ipilimumab), and subsequent U.S. Food and Drug Administration approval thereof—have legitimized the concept of using the immune system to battle cancer, which has reenergized immunotherapy advocates and investors alike.
"VISTA is an exciting, novel, negative checkpoint regulator that we anticipate will be a key target for enhancing immunity to solid and liquid cancers," ImmuNext's chief scientific officer, Dr. Randolph Noelle, said in a media statement.
"Because this approach is focused on the immune system as a whole, it should work on just about any solid tumor," says DeLucia.
This collaboration is one of a host of projects currently in the works for Janssen, one of the Janssen Pharmaceutical companies of Johnson & Johnson. Janssen Biotech recently announced an agreement with GenMab on a late-stage compound called daratumumab, a human CD38 monoclonal antibody currently in clinical development for multiple myeloma. This is in addition to its late-stage development of abiraterone acetate (Zytiga), a treatment for metastatic castration-resistant prostate cancer. Several other products are in the works at various levels of progression.
"One of the goals of the agreement is to generate a therapeutic antibody and to start to understand what tumor types it 's best applicable to," says Kellie McLaughlin, oncology therapeutics area communications lead for Johnson & Johnson.
DeLucia co-founded ImmuNext in 2011 alongside Noelle, whose laboratory discovered the natural CD40 ligand CD154 and has produced therapeutic antibodies for the treatment of a wide spectrum of autoimmune diseases. The company develops therapeutics that modulate the immune system to combat cancer and autoimmune diseases, and actively seeks partnerships in drug development where such collaborations make sense.
Next in the pipeline for ImmuNext is a VISTA agonist, which will attempt to exploit the same pathway to instead purposefully suppress immune responses. This has numerous potential applications in autoimmune and inflammatory diseases such as lupus, multiple sclerosis and Crohn's disease.