4E Therapeutics is developing a pipeline of non-opioid therapeutic assets to target pain.

We currently have 3 areas of focus:

Phase

Discovery

IND-Enabling

Phase 1

Phase 2

Phase 3

Neuropathic Pain
4ET1103

IND-Enabling

30%
Migraine Pain
MNK-elF4E

Discovery

11%
Acute Pain
GPCR enriched in human DRG neurons

Discovery

11%
Neuropathic Pain

4E Therapeutics has completed our medicinal chemistry optimization program in which over 150 proprietary, small molecule MNK inhibitors were synthesized and evaluated, leading to the discovery of a cohort of peripherally-restricted, orally-bioavailable compounds.

Phase

Discovery

IND-Enabling

Phase 1

Phase 2

Phase 3

4ET1103

Selected as lead compound

IND-Enabling

30%

Having met our stringent preclinical safety and efficacy criteria, 4ET1103 is highly efficacious in multiple animal models of pain and is well-tolerated in rodents and dogs. Significantly, 4ET1103 blocks evoked MNK activity in human dorsal root ganglion neurons from organ donors, underscoring its translational potential.

4ET1103 has entered IND-enabling studies and is expected to be ready for clinical trials in 2024.
Migraine Pain

4E Therapeutics research shows that the MNK-eIF4E signaling pathway is implicated in migraine, and that disrupting this pathway is a promising strategy for inhibiting migraine pain.

Phase

Discovery

IND-Enabling

Phase 1

Phase 2

Phase 3

MNK-elF4E

Signaling pathway

Discovery

11%

Building upon these discoveries, 4E is developing small molecule MNK inhibitors into next-generation drugs for the treatment of migraine. We are currently evaluating our MNK inhibitors in animal models of migraine.

A development candidate will be selected in 2022.
Acute Pain
Peripherally restricted GPCR agonist

Phase

Discovery

IND-Enabling

Phase 1

Phase 2

Phase 3

GPCR enriched in human DRG neurons

Discovery

11%

Our approach employs non-brain penetrant small molecules to selectively engage a receptor that is highly expressed in human nociceptors. Peripherally-restricted therapeutics are advantageous because they are devoid of central-nervous-system side effects, such as impaired cognitive function and physical dependence.

A lead compound will be selected in 2023.

Publications

The Journal of Neuroscience

August 2, 2017
The MNK–eIF4E Signaling Axis Contributes to Injury-Induced Nociceptive Plasticity and the Development of Chronic Pain
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Trends in Neurosciences

February 01, 2018

Translational Control Mechanisms in Persistent Pain

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The Journal of Neuroscience

January 16, 2019
Nociceptor Translational Profiling Reveals the Ragulator-Rag GTPase Complex as a Critical Generator of Neuropathic Pain
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Biological Sciences

September 23, 2019
MNK-eIF4E signalling is a highly conserved mechanism for sensory neuron axonal plasticity: evidence from Aplysia californica
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Neuropsychopharmacology

October 07, 2019
Reversal of peripheral nerve injury-induced neuropathic pain and cognitive dysfunction via genetic and tomivosertib targeting of MNK
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Pharmacological Reviews

January, 2021
Pharmacological Manipulation of Translation as a Therapeutic Target for Chronic Pain
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