Our lead in house LoF program addresses cancers which are deficient in the tumor suppressor retinoblastoma 1 (RB1) by targeting S-phase kinase-associated protein 2 (SKP2).
The RB1 tumor suppressor gene plays a critical role in coordinating multiple cellular pathways in cancer, including cell proliferation, DNA damage, cell cycle and apoptosis. Loss of RB1 function is a common alteration in several types of solid cancers and frequent in aggressive and metastatic tumors. It is associated with poor patient outcomes.
SKP2 – a highly validated synthetic lethal target for RB1 LoF
SKP2 is the substrate recognition component of an E3 ligase complex which degrades critical cell cycle regulators such as p27 involved in cell cycle progression.
Known as a highly attractive drug target, SKP2 was long considered undruggable. At Tessellate Bio, we believe we have solved this challenge. Using our promising hit series of small molecules, we have demonstrated that the interaction between SKP2 and p27 can be disrupted in RB1 LoF tumors resulting in p27 accumulation and apoptosis.
We are advancing new drug candidates towards preclinical development – view our pipeline.
RB1 LoF – snapshot
Patient population
7% of all tumors display RB1 LoF and are enriched in cancers with a high unmet need.
Two key indications with high unmet need are small cell lung cancer (SCLC) and triple negative breast cancer (TNBC).
Prevalence of RB1 LoF in SCLC is between
80-100%
and in TNBC exceeds
40%
There are no approved targeted therapies for RB1 LoF cancer patients.
RB1 Companion Diagnostic (CDx)
Diagnosis of RB1 loss of function is well established as part of the widely implemented NGS (Next Generation Sequencing) clinical test of panels.
ALT Partnered Program
Therapeutic Strategy
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