Our peptides target intracellular or intranuclear protein-protein interactions (PPIs), including oncogenic/immune modulatory signaling cascades and transcription factors (TFs). TFs are proteins that bind DNA at specific sequences to activate or inhibit gene expression. Typically, the formation of a transcription complex composed of two or more TFs is required for the transcription of particular segments of DNA. Dysregulation of transcription complexes may occur in normal cells, resulting in aberrant gene expression that may lead to the formation of cancer (oncogenesis). Inhibition of oncogenic transcriptional activity by disrupting essential PPIs represents a powerful approach to treating cancer. However, these interactions are difficult to target with chemical or protein-based drugs due to limitations of these molecules, rendering transcription complexes undruggable.
By targeting intracellular signaling cascades and TFs, we focus on the discovery and development of peptides that act at the level of transcriptional regulation of oncogenic and immune-modulatory proteins.
ST101 is a peptide inhibitor of C/EBPβ, which is a transcription factor overexpressed in many cancers that regulate cellular differentiation and promote tumor survival and proliferation. ST101 significantly decreases the expression of C/EBPβ target genes/proteins involved in cell survival, proliferation and differentiation including BCL-2, MCL-1, BIRC5/survivin, cyclins and ID family of proteins. ST101 has been demonstrated to induce selective cancer cell cytotoxicity across a variety of tumor types, including but not limited to breast cancer, melanoma, prostate cancer, GBM, lung cancer, and AML. C/EBPβ is expressed and active in cancer cells but not active in normal cells (post-differentiation), providing a therapeutic opportunity.View ST101
β-catenin is a critical member of the canonical WNT signaling pathway; a well-known development stage pathway that has been a desired drug target for decades. Promising data suggests that our β-catenin antagonist demonstrates activity against 3D patient-derived breast cancer tumoroids in vitro and anti-tumor activity in multiple of in vivo diseases.View β-Catenin Antagonist
cJun and cFos form one of the most formidable, yet desired, undruggable targets, the AP-1 complex. Data demonstrates that our cJun antagonist causes in vitro cell killing and in vivo anti-cancer activity.View cJun Antagonist
Myc is a proto-oncogene deregulated in many tumors, estimated at approximately 70% of all cancers, but due to its lack of enzymatic activity, it has historically been viewed as an undruggable. Data demonstrates that our cMyc antagonist causes potent inhibition of Myc-dependent gene transactivation and significant in vitro cell kill against Myc-dependent tumor cell lines.View cMyc Antagonist
FoxP3 functions as a master regulator for the development and function of regulatory T cells (Tregs), a subpopulation of T cells that modulate immune responses by suppressing or downregulating induction and proliferation of effector T cells. Tregs contribute to cancer by suppressing T effector cells, thereby compromising tumor killing and promoting tumor growth. Data suggests that our FoxP3 antagonist peptides (FAPs) have potent inhibition of FoxP3 gene transcription by in vitro reporter assay.View FoxP3 Antagonist
At Sapience we are committed to developing safe and effective therapies for high mortality cancers and making them available to patients as quickly and efficiently as possible by conducting rigorous clinical trials needed to gain regulatory approval. We support expanded access to our investigational medicinal products when there is substantial scientific evidence to assure both safety and efficacy. Early in development the risks of expanded access tend to outweigh the benefits due to limited data. Thus, evaluation of requests will generally require availability of positive Phase 3 data as well as meeting program and patient eligibility criteria.View Expanded Access