Pipeline

of Selective Translation Regulators
eFFECTOR retains global rights to all of its programs

Program
(Target)

Discovery

Preclinical

Phase 1

Phase 2

eFT508
(MNK1/2)

Combination

Indication | MSS CRC: Combination with Avelumab |

Phase 2

Indication | CPI-A: Combination Add-on to Approved Checkpoint Inhibitors

Phase 2

Indication | TNBC: Combination with Checkpoint Inhibitor

Initiate P2 1H 2019

Monotherapy

Indication | Non-GCB DLBCL: Monotherapy

Phase 2

Indication | mCRPC: Monotherapy in PSA Relapse after Hormone Failure

Initiate P2 2H 2018

eFT226
(elF4A)

Indication | Lymphoma

Preclinical

elF4E

Discovery

MSS CRC: Microsatellite stable colorectal cancer

CPI-A: Add-on treatment with approved checkpoint inhibitors

TNBC: Triple-negative breast cancer

Non-GCB DLBCL: Non germinal center B cell diffuse large B cell lymphoma

mCRPC: Metastatic castration-resistant prostate cancer

eFT508

acts at multiple stages in the cancer immunity cycle

1

2

3

4

5

6

7

Release of
tumor cell antigens

Release of tumor cell antigens
(tumor cell death)

eFT508
Survival Factors

Tumor
antigen presentation

Tumor antigen presentation
(dendritic cells/APCs)

eFT508
Antigen Presentation

Priming
and activation

Priming and activation
(APCs & T cells)

eFT508
Activate T cells
APC Trafficking
Anti-CTLA4

Trafficking of
T cells to tumors

Trafficking of T cells to tumors
(CTLs)

Infiltration of
T cells into tumors

Infiltration of T cells into tumors
(CTLs, endothelial cells)

Recognition of
tumor cells by T cells

Recognition of tumor cells by T cells
(CTLs, tumor cells)

Killing of
tumor cells

Killing of tumor cells
(Immune & tumor cells)

eFT508
Checkpoint Proteins
Anti-PD-1, PD-L1

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 eFT508 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 eFT508 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 eFT508 as a single agent promotes antitumor immunity that persists after stopping drug treatment.

We have initiated a Phase 2 combination trial of eFT508 with avelumab, an anti-PD-L1 checkpoint inhibitor, in patients with microsatellite stable colorectal cancer (MSS CRC), under a clinical collaboration with Pfizer Inc. and Merck KGaA. We plan to expand our Phase 2 clinical program with a combination trial adding eFT508 treatment to patients already receiving checkpoint inhibitors in FDA-approved indications who are experiencing insufficient response to their checkpoint therapy alone, and a separate combination trial in triple negative breast cancer. We have initiated a Phase 2 monotherapy trial in patients with non-germinal center diffuse large B cell lymphoma (non-GCB DLBCL), and we are planning an additional monotherapy trial in patients with metastatic castration-resistant prostate cancer (mCRPC).

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 diffuse large B cell lymphoma, Burkitt’s lymphoma, acute myeloid leukemia, non-small cell lung cancer, hepatocellular carcinoma and triple negative breast cancer. We anticipate initiating a Phase 1 clinical trial to assess eFT226 in lymphoma in the second half of 2018.

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, including KRAS, MYC, mechanistic target of rapamycin, or mTOR, PI3K, AKT and PTEN, 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 second half of 2018 to advance into IND-enabling studies.