On July 16, 2021 eFFECTOR Therapeutics, Inc., a leader in the development of selective translation regulation inhibitors ("STRIs") for the treatment of cancer, reported the publication of data highlighting the role of eukaryotic translation initiation factor 4E ("eIF4E"), in the peer-reviewed journal Cell Reports (Press release, eFFECTOR Therapeutics, JUL 16, 2021, View Source [SID1234584905]). eIF4E is a component of the eIF4F complex, which, in conjunction with its activating kinase ("MNK"), triggers an increase in protein synthesis that is critical for cancer growth and immune evasion. The published research, which provides insight into the potential of eIF4E inhibition for the treatment of cancer, was conducted at the University of California, San Francisco in collaboration with eFFECTOR. The eIF4E target is the subject of eFFECTOR’s collaboration with Pfizer.
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"This publication further validates the novel science on which eFFECTOR’s platform is built," said Steve Worland, Ph.D., president and CEO of eFFECTOR. "These findings underscore eIF4E’s role as a key hub for regulating cancer drivers such as mitochondrial stress, and the data showed that jointly inhibiting Bcl-xL while blocking eIF4E activation using our MNK 1/2 inhibitor tomivosertib is a promising approach for treating cancer."
"The results in this paper highlight the numerous genetic interactions with eIF4E that may help inform cancer vulnerabilities," said Davide Ruggero, Ph.D., senior author on the paper; professor at the UCSF Helen Diller Cancer Center; an American Cancer Society Research Professor; and co-founder of eFFECTOR. "Our team is pleased to add to the growing body of scientific research on the interactions between cellular processes that drive cancer and key components of the translation machinery such as eIF4E. We are proud that our contributions have the potential to broaden the treatment landscape for those impacted by cancer."
The Role of eIF4E in Cancer
eIF4E is an oncogene and historically intractable target that is activated in a variety of human cancers and is linked to poor prognosis and resistance to certain therapies. eIF4E is an effector protein integrating signals from multiple important oncogenes and tumor suppressor proteins in the PI3K and RAS oncogenic pathways (including PI3K, AKT, mTOR, PTEN and BRAF), and selectively regulates the translation of a set of target mRNA distinct from those regulated by MNK1/2 and eIF4A. This may expand the potential patient population that may benefit from translation regulation therapy.
About Tomivosertib (eFT508)
Tomivosertib is eFFECTOR’s wholly-owned, highly selective translation regulation inhibitor that targets MNK1 and MNK2 (MNK1/2). The oral, small molecule drug candidate has been shown to enhance killing of tumor cells by T cells, delay T-cell exhaustion/dysfunction and enhance the T-cell central memory pool, in part by down-regulating multiple checkpoint proteins including PD-1, PD-L1, TIM-3 and LAG-3. Tomivosertib is being evaluated in KICKSTART, eFFECTOR’s randomized, double-blind, placebo-controlled Phase 2b study in non-small cell lung cancer ("NSCLC") in combination with pembrolizumab. The KICKSTART trial builds on results obtained in an earlier study of tomivosertib as an extension of checkpoint inhibitor treatment in patients experiencing insufficient response to an FDA-approved checkpoint inhibitor alone.
Please visit www.clinicaltrials.gov for further information on ongoing clinical trials of tomivosertib.