Improving immune response

German pharma Phenex joins forces with Janssen Biotech to target autoimmune, chronic inflammatory disorders

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LUDWIGSHAFEN, Germany—Aimed at providing an urgent unmetneed for disorders such as rheumatoid arthritis, psoriasis and inflammatorybowel disease, Janssen Biotech Inc. and Phenex Pharmaceuticals AG have joinedforces to discover compounds that target the nuclear hormone receptor RORγT inthe treatment of chronic autoimmune and inflammatory disorders. 
Under the terms of an agreement announced Dec. 17, Phenexwill receive an upfront payment and milestone payments up to $135 million uponmeeting specific goals. Phenex will also be eligible to receive tieredroyalties and milestones on the global sales of products that arise from thecollaboration.
There is little doubt that a huge market exists for thesedisorders, which seem to come out of nowhere to disarm the body's immunesystem. Autoinflammatory diseases are a relatively new category of diseasesthat are different from autoimmune diseases, according to the U.S. NationalInstitutes of Health. However, autoimmune and autoinflammatory diseases sharecommon characteristics in that both groups of disorders result from the immunesystem attacking the body's own tissues, and also result in increasedinflammation.
The part of the immune system that orchestrates all of thisdevelops as a person grows, and is known as the acquired immune system. It"remembers" foreign antigens, or proteins, so that it can fight them if theycome back. It employs white blood cells called lymphocytes.
In autoinflammatory diseases, the body's more primitiveinnate immune system causes inflammation for unknown reasons. Autoinflammatorydisorders are characterized by intense episodes of inflammation, resulting insuch symptoms as fever, rash or joint swelling. These diseases also carry therisk of amyloidosis, a potentially fatal build-up of a blood protein in vitalorgans.
Researchers from Phenex and Janssen believe the solution isto work collaboratively to identify compounds that are active against RORγT andoptimized for preclinical development. Janssen will then have soleresponsibility for the continued development and worldwide commercialization ofany compounds that arise from the collaboration.
RORgamma(t), or RORγT, is a nuclear receptor that wasrecently identified as a key differentiation factor of Th-17 cells—immune cellsthat produce and secrete Interleukin-17 (IL-17), which is believed to be a keyplayer in chronic autoimmune-related inflammation.
The relevance of the IL-17 pathway has been highlighted bythe fact that antibodies that target key cytokines in this pathway havedemonstrated impressive efficacy in reducing symptoms in patients with plaque psoriasis.
The effectiveness of inhibiting the IL-17 pathway throughsmall-molecule RORγT inhibitors was recently demonstrated in animal models intwo adjacent publications in Nature.
"The upfront payment and near-term milestones that may beachieved through this collaboration are quite important for Phenex, as thefunds received will make it possible for us to both collaborate with Janssen onRORγT and continue the clinical development of our proprietary FXR programthrough the next few years," says Thomas Hoffmann, Phenex's chief financialofficer.
Under the terms of this agreement, "Phenex will be able tofund its operations and does not expect to seek further equity financing," saysHoffman. "Phenex maintains a favorable and exciting position in its ability toboth help the patients who could benefit from RORγT-based therapies and provideour shareholders with a satisfactory return on their investments."
Murray McKinnon, vice president and head of ImmunologyDiscovery at Janssen Research & Development, has been impressed withPhenex's particular expertise.
"We have been aware of Phenex's expertise in the nuclearhormone receptor field for some years and have followed their RORγT programwith interest," McKinnon tells ddn.  "Phenex brings strong expertise andcapabilities in nuclear receptor biology to the collaboration, as well as astrong portfolio of chemical modulators of RORγT function. We believe ourcombined scientific efforts increase our overall probability of success."
Even the latest, most sophisticated drugs do not helpeveryone, he notes.
"Despite the successes of antibody-based therapeutics inrheumatoid arthritis, psoriasis and inflammatory bowel disease (Crohn's diseaseand ulcerative colitis), there remains unmet need in patients who exhibit aninadequate response, or who are non-responsive, to these therapeutics,"McKinnon says. "Orally available molecules may have advantages in patientcompliance for those who cannot tolerate—or are afraid of—injections."
McKinnon defines "success" in this partnership as "a robust,mutually beneficial scientific collaboration founded on rigorous science thatenables Janssen to test the hypothesis in the clinic and ultimately advancenovel therapeutic options for patients."
Successful external collaborations "continue to enhance ourfocus of driving strong science in the Immunology," McKinnon adds.
"Ultimately, novel, new medicines will position the JanssenImmunology Therapeutic area for future success beyond our current portfolio ofbiologics in addressing unmet needs in autoimmune diseases, and satisfy patientand healthcare provider needs—while strengthening our industry-leadingposition," he says.

Janssen, NGM Biopharmaceuticals target diabetes,metabolic diseases
SOUTH SAN FRANCISCO, Calif.—Janssen Pharmaceuticals Inc.also announced last month a worldwide agreement with NGM BiopharmaceuticalsInc. to discover and develop novel therapeutics for the potential treatment oftype 2 diabetes and other metabolic diseases. 
NGM and Janssen will jointly conduct research on selectedprotein factors discovered by NGM using its diabetes discovery platform, withthe goal of advancing drug candidates that mimic the potential glucoregulatoryeffects of bariatric surgery on diabetes patients. Janssen will receive an exclusive worldwide license todevelop, manufacture and commercialize compounds resulting from thecollaboration.
Under the terms of the agreement, NGM will receive anupfront payment and research support for activities conducted in collaborationwith Janssen. In addition, NGM is eligible to receive payments upon theachievement of certain research, development, regulatory and commercialmilestones, as well as royalties on worldwide product sales. 
"NGM's commitment to drug discovery has resulted in a deeppipeline of novel targets that have a potentially profound effect on metabolicdiseases," said Dr. Jin-Long Chen, founder, president and chief scientificofficer of NGM. "We are pleased to be working with Janssen, who will bringworld-class drug discovery and development expertise to the advancement ofNGM's first-in-class therapies for the treatment of patients with diabetes."

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