TS-075258 — PROBLEM Chronic heart failure following myocardial infarction (MI) afflicts ~6.7 million US adults and is driven by maladaptive immune activation, particularly persistent activation and proliferation of CD4+ T cells. Existing anti-inflammatory and immunomodulatory approaches have largely failed to …

TS-075254 — Problem Cardiomyopathy weakens the heart muscle and impairs its ability to pump blood effectively, often leading to heart failure or sudden cardiac death. While doxorubicin remains an essential component of many cancer regimens, its use is limited by the risk of causing lethal cardiomyopathy. A maj…

TS-075247 — PROBLEM Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple organ damage, affecting women at a 9:1 rate as compared to men. The etiology of SLE is complex and incompletely understood; however, the susceptibility of women during the years in which estrogen levels ar…

TS-075240 — Problem Dedifferentiated liposarcomas (DDLPS) are aggressive soft tissue sarcomas with limited effective treatment options and a dismal prognosis. Current therapies often fail due to tumor resistance, poor specificity, and toxicity. The aggressive clinical behavior of LPS and its resistance to chem…

TS-075239 — Papaverine is an FDA-approved potent inhibitor of mitochondrial complex I. Papaverine’s mitochondrial complex I inhibition has been shown to be responsible for increased oxygenation and enhanced radiation response. However, papaverine is also a phosphodiesterase 10A (PDE10A) inhibitor with pot…

TS-075232 — Problem Breast cancer (BC) is the most commonly diagnosed malignancy and the second leading cause of cancer-related death among women in the United States. Within its subtypes, triple-negative breast cancer (TNBC) carries the highest mortality, driven in large part by a lack of effective targeted t…

TS-075186 — PROBLEM Exhausted CD8 T cells significantly limit the effectiveness of immunotherapies and cell therapies in cancer and chronic viral infections. Persistent antigen exposure drives durable epigenetic reprogramming that locks T cells into a dysfunctional state, silencing effector and memory-associat…

TS-075181 — PROBLEM Metabolic diseases and peripheral neuropathies represent a major public health burden in the United States, and the risks increase as we age. Metabolic diseases, including diabetes and obesity, and peripheral neuropathy (PN) affect approximately 25-45% and 10-20% of U.S. adults aged 50-70 r…

TS-075141 — THE PROBLEM Current MS treatments typically employ broad immunosuppression rather than targeting specific pathways, resulting in significant side effects and inadequate responses in many patients. The IL-6/STAT3 pathway is critical for balancing inflammatory T effector cells and protective regulato…

TS-066773 — The Need Cardiomyopathy, a disease of the heart muscle, poses significant public health challenges due to its diverse causes, symptoms, and potential complications, including heart failure and arrhythmias. With cardiomyopathy often induced by drugs, such as anthracyclines used in chemotherapy, ther…