| PROGRAM | Target | PRECLINICAL | PHASE 1 | PHASE 2 | PHASE 3 |
|---|---|---|---|---|---|
|
VTX958
|
TYK2
|
Potential indications include psoriasis, psoriatic arthritis, Crohn’s disease and others
|
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|
VTX002
|
S1P1R
|
Ulcerative Colitis
|
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|
VTX2735
|
NLRP3
Peripheral
|
Potential indications include cardiovascular, metabolic, hepatic, renal, and rheumatologic diseases
|
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|
VTX3232
|
NLRP3
CNS-penetrant
|
Neuroinflammatory diseases
|
|||
VTX958 is an oral, selective allosteric inhibitor of tyrosine kinase 2 (TYK2) with the potential to address a broad range of immune-mediated diseases such as psoriasis, psoriatic arthritis, Crohn’s disease and lupus.
TYK2 inhibits type I interferon and the Th1/Th17 axis for the treatment of psoriasis and other autoimmune diseases
TYK2 regulates both innate and adaptive immunity by mediating type I interferon, IL-12 and IL-23 signaling. Selectively targeting inhibition of TYK2 without inhibition of other JAK family enzymes provides an optimal balance between reducing inflammation and preserving immune protection.
In autoimmune diseases such as psoriasis, lupus, Crohn’s disease and others, overactive cytokine pathways drive the disease pathology. The essential role of TYK2 signaling in these diseases has been shown in studies of naturally occurring genetic mutations in humans and in genetic deletion/knockout animal disease models. An oral, highly selective TYK2 inhibitor could play a critical role in offering a well-balanced therapy that dampens harmful immune responses in these diseases while preserving protective immunity against pathogens.
VTX002 is an oral, selective sphingosine 1 phosphate receptor 1 (S1P1R) modulator in development for ulcerative colitis (UC).
S1P1R dampens the inflammatory response in UC by sequestering lymphocytes in the lymph nodes
S1P receptors are G-protein–coupled receptors involved in the modulation of numerous biological responses, including lymphocyte trafficking from lymph nodes to the peripheral blood. S1P1R modulators sequester lymphocytes in the lymph nodes, resulting in fewer immune cells in the circulating blood to exacerbate inflammation.
UC is an inflammatory bowel disease that affects ~1 million Americans. It can cause irritation, inflammation and ulcers in the large intestine and colon. While some treatments are available, unmet needs still exist. An oral, selective S1P1R modulator could play a critical role in offering a well-tolerated alternative to existing therapies for UC, thus improving patient care.
VTX2735 is an oral, selective inhibitor of NLRP3 that is designed for the treatment of systemic inflammatory diseases.
NLRP3 targets the inflammasome/IL-1β axis to break the inflammation feed-forward loop in autoinflammatory and autoimmune diseases
Inflammasome inhibition offers a compelling therapeutic pathway for inflammatory disorders with high unmet need. Inflammasomes are multi-protein complexes that sense molecular hallmarks of infection or cellular injury and initiate an appropriate immune response. NLRP3, the best-characterized inflammasome, is known to be activated by a range of non-infectious tissue damage signals associated with aging, physical inactivity and obesity. Activated NLRP3 initiates immune responses, stimulating the production of inflammatory cytokines (IL-1β and IL-18) as well as a type of cell death called pyroptosis and further tissue damage.
The role of IL-1β signaling, downstream of inflammasome activation, has been validated in a broad range of chronic inflammatory disorders with the clinical use of biologics targeting this pathway. NLRP3 activation has been linked via preclinical data with over 20 indications underpinned by aberrant inflammation and subsequent fibrogenic responses. An oral, selective NLRP3 inhibitor could play a critical role in offering a well-tolerated therapy to break the cycle of aberrant inflammatory progression.
VTX3232 is an oral, selective, CNS-penetrant NLRP3 inhibitor with potential therapeutic utility for a range of neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). In preclinical assays, VTX3232 exhibited high selectivity and CNS bioavailability. We are currently conducting IND-enabling studies for VTX3232 and expect to file an IND for the program in the fourth quarter of 2022.