Leveraging the power of the immune system to develop first-in-class therapies for autoimmune diseases and cancer.
Our immune systems have an almost infinite capacity to recognize and eliminate threats from invading pathogens and renegade cancer cells. However, the immune system can be outwitted and overpowered by cancer cells; conversely, an overstimulated immune system can cause debilitating autoimmune diseases like lupus. The cGAS/STING pathway plays a critical role in the immune response to tumor cells and in the pathogenesis of lupus. Nudge scientists are dedicated to discovering small molecules that modulate the cGAS/STING pathway, stimulating it to improve tumor immunity and dialing it down for autoimmunity.
Nudge Therapeutics was formed in 2019 to develop BellBrook Labs’ proprietary assets, technologies and biology domain expertise directed towards discovery of small molecule drugs targeting the cGAS/STING pathway.
The company is a wholly owned subsidiary of BellBrook Labs registered as a Delaware C-Corporation; BellBrook is owned by employees and local investors.
Aberrant activation of the immune sensor cyclic GAMP synthase (cGAS) by self-DNA triggers overproduction of type I interferons that play a central role in the pathology of lupus and other autoimmune diseases.
Targeting cGAS is likely to be more effective than attempting to intervene therapeutically in the pleiotropic downstream effects of type I IFN induction.
Nudge Therapeutics has used proprietary assay technology to develop two mechanistically distinct cGAS antagonist chemotypes with nanomolar potency and promising drug-like properties.
Robert Lowery, PhD – CEO, CSO
Bob is co-founder of BellBrook Labs where he has served as President & CEO for over a decade and is the PI on two NIH SBIR grants focused on cGAS assay development and drug discovery. He has more than twenty years of experience working with pharmaceutical and biotech customers on small molecule HTS and hit-to-lead programs.
Dave Maloney: Med Chem/Translational Consultant
Co-Founder & Managing Partner, Nexus Discovery Advisors, LLC; Co-Founder & Chief Science Officer, Veralox Therapeutics, Inc.
Nine years as Group Leader in Chemistry at NIH’s National Center for Advancing Translational Sciences (NCATS). Led lead-identification and late-stage lead optimization for a broad range of therapeutic areas and target classes. Co-author on more than 90 scientific publications and co-inventor on over 10 composition of matter patents.
Matt Boxer: Med Chem/Translational Consultant
Co-Founder & Managing Partner, Nexus Discovery Advisors, LLC; Co-Founder & Chief Operating Officer, Veralox Therapeutics, Inc.
Nine years as Medicinal Chemistry Group Leader at NCATS. Led interdisciplinary teams responsible for small molecule hit-to-lead and lead-optimization for over 25 projects including targets in oncology, rare genetic disorders, infection and lipid disorders. Co-author on more than 50 scientific publications and inventor on over 10 composition of matter patents.
Peter Sausen: Director
Global Vice President, Strategic Development Solutions, Covance Laboratories Inc.
Global scientific leader with more than 25 years of drug development experience in pharmaceutical and contract research organizations (CRO). Provided scientific leadership and strategic guidance to 100’s of small biotechnology and large pharmaceutical clients enabling them to advance their drug development programs into clinical trials and reach their company objectives.
SCIENTIFIC ADVISORY BOARD
Bill Janzen, Ph.D.
Vice President, Lead Discovery and Research Operations, Ribometrix
Formerly Executive Director of Lead Discovery, Epizyme.
More than 25 years small molecule drug discovery experience at Eli Lilly, Amphora Discovery, Chaperone Therapeutics, Epizyme and Ribometrix.
6 years at the University of North Carolina, Chapel Hill
Keith Elkon, MD
Head of Rheumatology, U. Washington, Seattle
Thought leader on the molecular and genetic basis of autoimmune disease biology who has pioneered research on the involvement of cGAS in SLE; over 200 publications.
Cofounder of Resolve Therapeutics, which currently has a biotherapeutic lead molecule in Phase II clinical trials for SLE
Kenneth Kalunian, MD
Associate Director of the Center for Innovative Therapy and a Professor in the Division of Rheumatology, Allergy and Immunology in the School of Medicine at UC San Diego
Extensive experience in SLE clinical trials, with over 50 publications.
Serves on the Medical Scientific Advisory Board of the Lupus Foundation of America and is a founding member of the Systemic Lupus International Collaborating Clinics.
Targeting cGAS for autoimmune diseases driven by type I interferons. The cGAS/STING pathway activates the immune system in response to foreign and/or damage induced self-DNA by inducing a robust type I interferon (IFN) response. It plays a central role in the response to viral and bacterial infection as well as to nucleic acids leaking from damaged cells in the tumor microenvironment. However, in lupus and related diseases, DNA released from damaged cells precipitates a vicious cycle of autoimmunity driven by type I IFNs that circulate throughout the body activating the immune system to attack critical organs and tissues. Cyclic GAMP synthase (cGAS) is the trigger for autoimmunity: it senses DNA released from damaged cells and produces signaling molecules that activate the pathway for production of type I IFN. Multiple lines of evidence, including genetic knockouts of cGAS in mouse models of monogenic lupus, have clearly established that blocking cGAS is a compelling therapeutic strategy for lupus and an increasing number of type I IFN-driven autoimmune diseases.
Development of a first-in-class TREX1 antagonist could have broad impact on cancer immunotherapy. The cGAS/STING pathway is required for induction of tumor immunity, including activation of T cells in the tumor microenvironment as well as adaptive immune responses that provide sustained, systemic protection against relapse and metastasis. TREX1 is the major exonuclease responsible for degrading cytosolic DNA, and it plays an important role in preventing aberrant autoimmune responses in normal cells by acting as a checkpoint for the cGAS/STING pathway. But by dampening cGAS/STING-dependent immune responses in the tumor microenvironment, TREX1 plays a pro-tumorigenic role in cancer. TREX1 is upregulated by therapeutic doses of radiation and some cytotoxic drugs, and this upregulation been shown to dampen the cGAS/STING dependent antitumor immunity in mice. Whether used in combination with downstream checkpoint inhibitors or as monotherapy, blocking TREX1 may stimulate cGAS/STING-driven antitumor immunity sufficiently to eliminate the need for cytotoxic treatments altogether.