Pipeline
of Selective Translation Regulators
eFFECTOR retains global rights to all of its programs
Program
(Target)
Discovery
Preclinical
Phase 1
Phase 2
tomivosertib
(MNK1/2)
Combination
Indication | CPI-A: Combination Add-on to Approved Checkpoint Inhibitors
Indication | TNBC: Combination with Pembrolizumab | 
Monotherapy
Indication | CRPC: Monotherapy in PSA Relapse after Hormone Failure
eFT226
(elF4A)
CPI-A: Add-on treatment with approved checkpoint inhibitors
TNBC: Triple-negative breast cancer
CRPC: Castration-resistant prostate cancer
Tomivosertib inhibits MNK1/2,
a central regulator of immune attenuation
1
2
3
4
5
6
7
1
Release of tumor cell antigens
(tumor cell death)
eFT508
Survival Factors
2
Tumor antigen presentation
(dendritic cells/APCs)
eFT508
Antigen Presentation
3
Priming and activation
(APCs & T cells)
eFT508
Activate T cells
APC Trafficking
Anti-CTLA4
4
Trafficking of T cells to tumors
(CTLs)
5
Infiltration of T cells into tumors
(CTLs, endothelial cells)
6
Recognition of tumor cells by T cells
(CTLs, tumor cells)
7
Killing of tumor cells
(Immune & tumor cells)
eFT508
Checkpoint Proteins
Anti-PD-1, PD-L1
Release of
tumor cell antigens
tumor cell antigens
Release of tumor cell antigens
(tumor cell death)
eFT508
Survival Factors
Tumor
antigen presentation
antigen presentation
Tumor antigen presentation
(dendritic cells/APCs)
eFT508
Antigen Presentation
Priming
and activation
and activation
Priming and activation
(APCs & T cells)
eFT508
Activate T cells
APC Trafficking
Anti-CTLA4
Trafficking of
T cells to tumors
T cells to tumors
Trafficking of T cells to tumors
(CTLs)
Infiltration of
T cells into tumors
T cells into tumors
Infiltration of T cells into tumors
(CTLs, endothelial cells)
Recognition of
tumor cells by T cells
tumor cells by T cells
Recognition of tumor cells by T cells
(CTLs, tumor cells)
Killing of
tumor cells
tumor cells
Killing of tumor cells
(Immune & tumor cells)
eFT508
Checkpoint Proteins
Anti-PD-1, PD-L1
Tomivosertib (also known as eFT508) is a novel, potent and highly selective oral small molecule inhibitor of mitogen-activated protein kinase interacting kinases 1 and 2, or collectively, MNK1/2. MNK1/2 play a crucial role in the development of many tumors, including by controlling in a coordinated manner the expression of multiple factors that attenuate an immune response.
The interaction between a patient’s tumor and immune system has been described as a cyclical process referred to as the cancer immunity cycle. Our studies have shown that tomivosertib acts on multiple points in the cancer immunity cycle simultaneously, underscoring its therapeutic potential as both a monotherapy and in combination with existing checkpoint inhibitor treatments. Our preclinical studies suggest combining tomivosertib with a checkpoint inhibitor can overcome mechanisms of resistance to checkpoint inhibitors, resulting in enhanced sensitivity to checkpoint inhibitors and a higher response rate. In addition, our preclinical data demonstrate that tomivosertib as a single agent promotes antitumor immunity that persists after stopping drug treatment.
We have two ongoing Phase 2 trials with tomivosertib. The first is a combination trial adding tomivosertib treatment to patients already receiving checkpoint inhibitors in FDA-approved indications who are experiencing insufficient response to their checkpoint therapy alone (CPI-A). The second is a monotherapy trial in patients with metastatic castration-resistant prostate cancer (mCRPC). We also recently entered into a clinical trial collaboration agreement with Merck to combine tomivosertib and Keytruda (PD-1 checkpoing inhibitor) for the treatment of patients with triple negative breast cancer (TNBC).
eFT226
eFT226 is a highly potent and selective small molecule inhibitor of eIF4A (eukaryotic initiation factor 4A), a strong anti-proliferative target downstream from key oncogenes. We have demonstrated that eIF4A inhibition selectively regulates the translation of a distinct set of target mRNA that include a number of important oncogenes and survival factors, including MYC, β-catenin, Cyclin D, FGFR1, BCL-2, and MCL-1, many of which have been historically intractable as drug targets. Oncogenes are genes that, when altered by mutation, activation or gene amplification, can contribute to the growth of tumors and are known to drive proliferation and avoidance of antiproliferative signals in tumors. Preclinical studies have shown that eFT226 is active in tumor models of triple negative breast cancer, colorectal cancer, non-small cell lung cancer, hepatocellular carcinoma and B cell lymphomas. We anticipate initiating a Phase 1 clinical trial to assess eFT226 in solid tumors in the second half of 2019.
eIF4E
eIF4E (eukaryotic initiation factor 4E) is a highly oncogenic and historically intractable target whose expression is increased, or upregulated, in a variety of human cancers and is linked to poor prognosis and resistance to certain therapies. eIF4E integrates 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. We plan to select an eIF4E product candidate in the first half of 2019 to advance into IND-enabling studies.