We currently have 3 areas of focus:
Phase
Discovery
IND-Enabling
Phase 1
Phase 2
Phase 3
4ET1103
Migraine Pain
MNK-elF4E
Acute Pain
GPCR enriched in human DRG neurons
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
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
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
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
Trends in Neurosciences
February 01, 2018
Translational Control Mechanisms in Persistent Pain
The Journal of Neuroscience
January 16, 2019
Nociceptor Translational Profiling Reveals the Ragulator-Rag GTPase Complex as a Critical Generator of Neuropathic Pain
Biological Sciences
September 23, 2019
MNK-eIF4E signalling is a highly conserved mechanism for sensory neuron axonal plasticity: evidence from Aplysia californica
Neuropsychopharmacology
October 07, 2019
Reversal of peripheral nerve injury-induced neuropathic pain and cognitive dysfunction via genetic and tomivosertib targeting of MNK
Pharmacological Reviews
