A window into VISTA

Partnership aims to develop immunotherapies for cancer based on new negative checkpoint regulator

Jim Cirigliano
LEBANON, N.H.—Immunology researchersat ImmuNext and Janssen Biotech Inc. have announced a partnership indeveloping novel immunotherapies for cancer.
 
ImmuNext will grant Janssen aworldwide, exclusive license to develop and commercializetherapeutics that antagonize the V-region immunoglobulin-containingsuppressor of T-cell activation (VISTA) signaling pathway. Inexchange, Janssen will provide ImmuNext with an upfront payment, pluspayments for reaching development and commercial milestones. Thetotal payments to ImmuNext could total more than $150 million, plusroyalties on product sales and sponsored research support.

VISTA is a newly identified negativecheckpoint regulator. Through this partnership, ImmuNext and Janssenwill collaborate to research and develop novel cancer therapeuticsthat antagonize the VISTA signaling pathway.

ImmuNext brings into the partnershipits expertise at immunology, and it will pursue the basic research tobetter understand the VISTA pathway with the help of Janssen'ssponsorship. This research will facilitate Janssen in its developmentand potential commercialization of antibodies specific to the VISTAligand.

Recent approaches to immunotherapy forcancer have focused on checkpoint regulators, of which VISTA is one.Checkpoint regulators involve the signal pathways that the body usesto shut down the immune system's response when it is no longerneeded—for example, allowing swelling to subside after a woundheals or returning mucus production to normal levels after a coldvirus runs its course. It is hypothesized that tumors may circumventthe body's natural defenses by "turning off" the local immuneresponse in the tumor microenvironment. A successful VISTA antagonistcompound would disrupt this turning-off process, unleashing thebody's natural immune responses to a foreign presence such as atumor.

Immunotherapy approaches to cancertreatment have not been without skeptics and some early failures. Thefirst attempts at developing cancer immunotherapies were abysmallyunsuccessful, resulting in limited patient responses, and in somecases caused fatal side effects.

"Investors started running away fromthe idea of using the immune system to treat cancer," says ImmuNextCEO David DeLucia. "But in the past year or two, new approaches toimmunotherapy have been helping around 35 percent of patients in somecases, so we're seeing a warming to immunotherapy. Investors arepaying attention again."

Recent successes in the field—includingencouraging trial results shared by Bristol-Meyers Squibb Co.surrounding their immunotherapeutic product Yervoy (ipilimumab), andsubsequent U.S. Food and Drug Administration approval thereof—havelegitimized 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 targetfor enhancing immunity to solid and liquid cancers," ImmuNext'schief scientific officer, Dr. Randolph Noelle, said in a mediastatement.

"Because this approach is focused onthe immune system as a whole, it should work on just about any solidtumor," says DeLucia.

This collaboration is one of a host ofprojects currently in the works for Janssen, one of the JanssenPharmaceutical companies of Johnson & Johnson. Janssen Biotechrecently announced an agreement with GenMab on a late-stage compoundcalled daratumumab, a human CD38 monoclonal antibody currently inclinical development for multiple myeloma. This is in addition to itslate-stage development of abiraterone acetate (Zytiga), a treatmentfor metastatic castration-resistant prostate cancer. Several otherproducts are in the works at various levels of progression.

"One of the goals of the agreement isto generate a therapeutic antibody and to start to understand whattumor types it's best applicable to," says Kellie McLaughlin,oncology therapeutics area communications lead for Johnson &Johnson.

DeLucia co-founded ImmuNext in 2011alongside Noelle, whose laboratory discovered the natural CD40 ligandCD154 and has produced therapeutic antibodies for the treatment of awide spectrum of autoimmune diseases. The company developstherapeutics that modulate the immune system to combat cancer andautoimmune diseases, and actively seeks partnerships in drugdevelopment where such collaborations make sense.

Next in the pipeline for ImmuNext is aVISTA agonist, which will attempt to exploit the same pathway toinstead purposefully suppress immune responses. This has numerouspotential applications in autoimmune and inflammatory diseases suchas lupus, multiple sclerosis and Crohn's disease.



Jim Cirigliano

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