We are advancing our pipeline of Selective Translation Regulator Inhibitors (STRIs) with speed and scale.
Our STRIs are designed to overcome cancer’s complex, aggressive nature. They can augment efficacy of existing therapies and those in development, as well as target the oncoproteins, immune suppression factors and resistance mechanisms cancer frequently uses to evade therapeutic intervention.
Tomivosertib
(MNKi)
Zotatifin
(eIF4Ai)
eIF4Ei
Tomivosertib
A POTENT AND HIGHLY SELECTIVE MNK INHIBITOR
Our lead product candidate, tomivosertib, is an oral small molecule inhibitor of MNK. We are developing tomivosertib in combination with inhibitors of checkpoint proteins such as PD-1 and PD-L1 for the treatment of patients with solid tumors. MNK are kinases that phosphorylate eIF4E. Through inhibition of MNK, tomivosertib downregulates production of multiple immune-suppressive proteins and reprograms T cells to delay exhaustion and dysfunction, increasing their ability to combat tumor cells. In preclinical and clinical studies showing target inhibition in patient tumor biopsies, tomivosertib can completely (>90%) block MNK signaling, and in preclinical models enhanced the ability of the immune system to attack tumors.
Based on tomivosertib’s mechanism in immune biology and the encouraging results in our Phase 2a clinical trial, we’ve initiated KICKSTART, a double-blind, randomized, placebo-controlled Phase 2b trial of tomivosertib combined with pembrolizumab in patients with metastatic NSCLC.
Zotatifin
A POTENT AND HIGHLY SELECTIVE eIF4A mRNA HELICASE INHIBITOR
Our second product candidate, zotatifin, is a small molecule inhibitor of eIF4A. eIF4A is a helicase responsible for unwinding complex secondary structures in “onco” mRNAs and enables select tumor cells to overproduce proteins associated with cellular growth, including ER and KRAS. We have initiated multiple Phase 2a expansion cohorts with zotatifin both as a single agent and in combination with targeted agents in ER+ breast cancer and KRAS-mutant NSCLC. In addition, zotatifin is being evaluated in a Phase 1b clinical trial as an antiviral agent in patients with mild to moderate COVID-19 infections. This trial is sponsored by a grant from the Defense Advanced Research Projects Agenda (DARPA) and is being conducted in collaboration with the Quantitative Biosciences Institute (QBI) at the University of California, San Francisco (UCSF).
eIF4E
A GLOBAL COLLABORATION WITH PFIZER
Our third program is focused on developing inhibitors of eIF4E. eIF4E is an oncogenic target involved in the translation of key disease driving proteins. These inhibitors are currently being developed by Pfizer under our research collaboration and license agreement. We have retained an option to co-promote and profit share in the United States.
