Pipeline

Introduction

We have a broad clinical and preclinical pipeline focused on neuronal excitability conditions of the central and peripheral nervous system. Each program targets a clinically validated mechanism of action for the diseases it is addressing. Our two lead drug candidates are ETX-810 for chronic pain and ETX-155 for major depressive disorder (MDD), perimenopausal depression (PMD) and focal onset seizures (FOS).

Product Candidates (Mechanism of Action) Target
Indications
Preclinical Phase 1 Phase 2 Phase 3 Anticipated Milestones
ETX-810
(PEA prodrug)
Diabetic
neuropathic pain
Lumbosacral radicular pain
(sciatica)
Phase 2a
Phase 2a
Topline Phase 2a data
(1H 2022)
Topline Phase 2a data
(1H 2022)
ETX-155
(GABAA receptor PAM)
Major depressive
disorder (MDD)
Perimenopausal
depression (PMD)
Focal onset seizure
(FOS)
Phase 1 MAD
Phase 1 MAD
Phase 1 MAD
Topline Phase 2a data
(1H 2023)
Topline Phase 2a data
(1H 2023)
Topline Phase 1b
photosensitive epilepsy data
(1H 2022)
Preclinical Pipeline
Kv7 Program
(Kv7.2/3 potassium channel opener)
Next Generation Anxiolytic
(2,3-benzo)
Pain
Epilepsy
Generalized
anxiety
Clinical Candidate Nomination
(2H 2021)
Clinical Candidate Nomination
(2022)
Product Candidates (Mechanism of Action) ETX-810
(PEA prodrug)
ETX-155
(GABAA receptor PAM)
Preclinical
Pipeline
Target Indications
Diabetic
neuropathic
pain
Lumbosacral
radicular
pain
(sciatica)
Major depressive disorder (MDD)
Perimenopausal depression (PMD)
Focal onset seizure (FOS)
Kv7 Program (Kv7.2/3 potassium channel opener)
Pain
Epilepsy
Next Generation Anxiolytic (2,3-benzo)
Generali-
zed anxiety
Preclinical
Phase 2a
Phase 2a
Phase 1 MAD
Phase 1 MAD
Phase 1
Phase 2
Phase 3
Anticipated Milestones
Topline Phase 2a data (1H 2022)
Topline Phase 2a data (1H 2022)
Topline Phase 2a data (1H 2023)
Topline Phase 1b photosensitive epilepsy data (1H 2022)
Clinical Candidate 2H 2021
Clinical Candidate 1H 2022

ETX-810

Our most advanced program is ETX-810 for chronic pain conditions. ETX-810 is an investigational first-in-class, non-opioid, new chemical entity (NCE) designed for enhanced efficacy, limited drug-to-drug interactions and a favorable safety and tolerability profile. We believe it has the potential to address the shortfalls of current therapies across a range of chronic pain conditions.

Unmet Clinical Need
There is significant unmet need for the treatment of chronic pain. Despite a massive global chronic pain therapeutics market that is expected to pass $29 billion in the next decade1, currently approved therapies have demonstrated inadequate efficacy, with less than half of patients achieving a 50 percent reduction in their pain in multiple pain indications2. In addition to limited efficacy, the current standard of care is hindered by dose-limiting side effects, including dizziness, sedation, gastrointestinal disturbances, as well as concerns over abuse liability.

The Science of ETX-810
ETX-810 is a non-opioid prodrug of palmitoylethanolamide (PEA), which is an endogenous bioactive lipid that is known to broadly modulate neuroinflammation and pain signaling, representing a promising potential mechanism to treat multiple conditions of chronic pain3,4,5. PEA has been evaluated as a treatment for various pain conditions in more than 30 clinical studies, with over 2,500 patients treated with PEA in these studies6-13. Fifteen of these studies were randomized, controlled trials (RCTs) in a total of approximately 1,500 patients, where PEA consistently demonstrated statistically significant reductions in pain with favorable safety and tolerability. Despite this promising precedent clinical data, there are no approved PEA-based therapeutics. Rather, PEA is only currently available as a dietary supplement (nutraceutical), which has shown low bioavailability and overall poor drug-like properties.

As a prodrug of PEA, ETX-810 was designed to significantly improve the absorption and systemic exposure of PEA to maximize the therapeutic effect. In addition to its potential as a novel approach to significantly reduce chronic pain, ETX-810 has no known drug-to-drug interactions or abuse liability, and in clinical testing to date has demonstrated a very encouraging safety and tolerability profile.

In chronic pain (center panel), synthesis of PEA decreases and metabolism increases, leading to a net decrease in PEA beyond the level needed to maintain its anti-inflammatory and analgesic activity in healthy physiology (left panel). ETX-810 is an investigational novel, small molecule prodrug with the ability to supplement endogenous PEA, ensuring sufficient PEA levels are reached to exert its therapeutic effect (right panel).

PEA is a broad modulator of inflammatory processes which also affect pain sensation and neuroprotection. Its mode of action has multiple effects (i.e., pleiotropic), as it involves many pathways and targets in both the peripheral and central nervous systems.

Clinical Trials for ETX-810

Phase 2a clinical trials for ETX-810 are underway in lumbosacral radicular pain (chronic sciatica) and in diabetic peripheral neuropathic pain. 

ETX-155

Our other clinical program is ETX-155 for use in multiple disorders of high unmet need, including major depressive disorder (MDD), perimenopausal depression (PMD) and focal onset seizures (FOS). ETX-155 is an investigational oral, next generation, neuroactive steroid NCE that acts as a GABAA positive allosteric modulator (PAM) designed to address the shortcomings of other molecules targeting the GABAA channel. We believe it has the potential to be a best-in-class treatment.

Unmet Clinical Need

There is significant unmet need for new treatments for mood disorders and epilepsy.

MDD affects approximately 35 million adults globally, causing significant impairment to daily life14. While there are effective therapies available for individuals suffering from MDD, there is considerable variability in patient responsiveness. There is a pressing need for safe, well tolerated, and rapidly acting antidepressants that reliably provide clinical improvement faster than the up to 6 weeks associated with standard of care SSRIs/SNRIs.

Epilepsy affects approximately 4.7 million people globally, with approximately 1 million of these patients experiencing uncontrolled focal onset seizures (FOS) that are refractory to multiple anti-seizure medications (ASMs)15,16,17. FOS patients have a high prevalence of psychiatric co-morbidities like depression, and for many patients, their current ASMs have a negative impact on mood. There is a pressing need for new ASMs that not only reduce the number of seizures but also provide a positive effect on mood.

The Science of ETX-155

ETX-155 is an investigational novel, oral, next generation, neurosteroid GABAA PAM that demonstrates dual synaptic and extrasynaptic receptor activity with an approximate 24-hour half-life and no clinically meaningful food effect. Preclinical and Phase 1 clinical data demonstrate the potential for ETX-155 to be a best-in-class treatment for multiple neuronal excitability disorders.

ETX-155 is an investigational oral neuroactive steroid GABAA receptor positive allosteric modulator (PAM) that binds at the neurosteroid site on extrasynaptic and synaptic receptors. Binding at the extrasynaptic and synaptic receptors causes enhanced GABAergic tone and GABAergic synaptic transmission, respectively, leading to decreased neuron excitability and firing.

Clinical Trials for ETX-155

ETX-155 is being evaluated in Phase 1 studies with plans to initiate proof of concept trials targeting multiple disorders, including major depressive disorder, hormone-related mood disorders (e.g., perimenopausal mood disorders or post-partum depression) and focal onset seizures. Phase 1b and Phase 2 clinical trials across multiple indications are planned to begin in the second half of 2021.

Preclinical Pipeline

Eliem is progressing a pipeline of preclinical candidates for other neuronal excitability disorders, with two programs currently in advanced discovery stage.  Our lead preclinical program is a Kv7.2/3 channel opener. The Kv7.2/3 mechanism has been validated through regulatory approvals of multiple first generation Kv7.2/3 channel openers, which showed powerful efficacy but subsequently had to be withdrawn from the market due to significant safety issues. Eliem is focused on harnessing the efficacy of the Kv7.2/3 channel approach while significantly enhancing its safety and tolerability profile.  Eliem is also developing a next generation non-sedating anxiolytic based upon a clinically validated mechanism.

References

  1. DRG, Chronic Pain Disease Landscape & Forecast. Jan 2021
  2. Lyrica Prescribing Information; Cymbalta Prescribing Information
  3. Petrosino S., Di Marzo V. The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations. Br. J. Pharmacol. 2017;174:1349–1365
  4. Petrosino and Moriello. Palmitoylethanolamide: A Nutritional Approach to Keep Neuroinflammation within Physiological Boundaries – A Systematic Review. Int. J Mol Sci. 2020;21(24):9526.
  5. D’Amico et al. Palmitoylethanolamide and Its Formulations on Management of Peripheral Neuropathic Pain. Int J Mol Sci. 2020;21(15):5330
  6. Artukoglu et al. Efficacy of Palmitoylethanolamide for Pain: A Meta-Analysis. Pain Physician. 2017 Jul;20(5):353-362
  7. Paladini et al. Palmitoylethanolamide, a Special Food for Medical Purposes, in the Treatment of Chronic Pain: A Pooled Data Meta-analysis. Pain Physician. 2016 Feb;19(2):11-24
  8. Cruccu et al. Micronized Palmitoylethanolamide: A Post Hoc Analysis of a Controlled Study in Patients with Low Back Pain – Sciatica. CNS & Neurological Disorders – Drug Targets, 2019,18:491-495.
  9. Guida et al. Palmitoylethanolamide (Normast) in chronic neuropathic pain caused by compressive-type lumbar sciatica: a multicenter clinical trial. DOLOR. 2010;25:35-42.
  10. Steels et al. A double-blind randomized placebo controlled study assessing safety, tolerability and efficacy of palmitoylethanolamide for symptoms of knee osteoarthritis. Inflammopharmacology. 2019;27(3):475-485.
  11. Cocito et al. Short-term efficacy of ultramicronized palmitoylethanolamide in peripheral neuropathic pain. Pain Res Treat. 2014;2014:854560.
  12. Schifilliti et al. Micronized Palmitoylethanolamide Reduces the Symptoms of Neuropathic Pain in Diabetic Patients. Pain Res Treat. 2014;2014:849623.
  13. Gatti et al. Palmitoylethanolamide in the treatment of chronic pain caused by different etiopathogenesis. Pain Med. 2012;13(9):1121-30.
  14. DRG, Unipolar Depression Disease Landscape & Forecast. Sept 2020
  15. DRG, Epilepsy Disease Landscape & Forecast. Jan 2021
  16. Epilepsy Foundation
  17. Picot MC et al. The prevalence of epilepsy and pharmacoresistant epilepsy in adults: A population-based study in a Western European country. Epilepsia 2008;49(7):1230-1238

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Eliem Therapeutics, Inc.
23515 NE Novelty Hill Road, Suite B221 #125
Redmond, WA 98053

Eliem Therapeutics (UK) Ltd: Reg. 11893311
3rd Floor, 1 Ashley Road
Altrincham, Cheshire WA14 2DT