Our RB1 loss-of-function (LoF) program addresses cancers which are deficient in the retinoblastoma 1 (RB1) tumor suppressor protein by targeting S-phase kinase-associated protein 2 (SKP2)
RB1 – a major driver of many cancers
The RB1 tumor suppressor plays a critical role in coordinating multiple cellular pathways in cancer, including cell proliferation, DNA damage, cell cycle and apoptosis. Loss of RB1 is common in several types of solid cancers and frequent in aggressive and metastatic tumors. It is associated with poor patient outcomes. Because RB1 mutations lead to the loss of a functional protein, its direct targeting is not possible.
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.
SKP2 has long been regarded a highly attractive drug target due to its synthetic lethal interaction with RB1 LoF. However, SKP2 has also been considered undruggable. At Tessellate Bio, we believe we have successfully overcome this challenge. Using our promising hit series of small molecules, we have pharmacologically demonstrated synthetic lethality in tumors with loss of RB1.
We are advancing new drug candidates towards preclinical development
RB1 LoF patient population – snapshot
7% of all tumors display RB1 LoF and RB1 LoF is enriched in cancers with a high unmet need.
A key indication with high unmet need is small cell lung cancer (SCLC).
RB1 LoF is considered to be an early and foundational event in SCLC as the prevalence of genetic RB1 loss alone is greater than 80%.
There are no approved targeted therapies for RB1 LoF cancer patients and most new drugs in development for SCLC are large molecules with limited CNS activity expected.
Approximately 250,000 patients are diagnosed annually in the eight major markets.
70% of patients present with advanced disease at diagnosis
60% of patients develop brain metastases
<9% 5 (five) year survival rate
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 Program
Therapeutic Strategy
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