We currently have 3 areas of focus:
Phase
Discovery
IND-Enabling
Phase 1
Phase 2
Phase 3
4ET1103
Migraine Pain
4ET2124
Acute Pain
MNK-eIF4E
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 completed IND-enabling studies and IND application to be submitted Q4 2023.
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
4ET2124
Selected as lead compound
Building upon these discoveries, 4E is developing small molecule MNK inhibitors into next generation drugs for the treatment of migraine. 4ET2124 has been selected as a clinical candidate for the treatment of migraine pain, with 4ET2104 positioned as backup. Both compounds have excellent in vitro safety profiles and are efficacious across multiple animal models of migraine.
4ET2124 and 4ET2104 are ready to begin IND-Enabling studies.
Acute Pain
Peripherally restricted MNK inhibitor
Phase
Discovery
IND-Enabling
Phase 1
Phase 2
Phase 3
MNK-eIF4E Signaling Pathway
Our approach employs non-brain penetrant small molecules to selectively inhibit MNK. 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 2024.
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
