Drug Development Program

Drug Development Program

  • Neuropathic Pain
  • Osteoarthritis
  • Mechanism of Action (MOA)
  • Backup Program

Lateral Pharma is repurposing LAT8881 for treatment of neuropathic pain, osteoarthritis and other painful chronic diseases.  Lateral has worked with external CROs and collaborators using different approaches to investigate analgesic properties of LAT8881 and other backup LAT peptides:

  • Prof David Spanswick at Pacific Discovery Services (PDS)/Neurosolutions and Charles River Labs have been key collaborators for the pain studies in the following model systems :
  • Ex vivo spinal cord slice model (DRG) preparations from rats subject to chronic nerve constriction (Chung model) directly monitoring neuronal activity with electrophysiology
  • In vivo behavioural models of pain monitoring mechanical or thermal hyperalgesia or other pain responses mostly conducted by Pacific Discovery Services (PDS):
    • Chung model of chronic nerve constriction injury – studies conducted by PDS
    • Chemotherapy-induced neuropathic pain model – two studies, one conducted by PDS and one by Charles River Laboratories
    • Streptozotocin Diabetic neuropathy – one study conducted by PDS
    • Reserpine model of fibromyalgia – one study conducted by PDS
    • Post operative surgical pain – one study conducted by PDS
    • Models of osteoarthritis, (1) Intra-articular Collagenase – one study conducted by Prof Kwon of Daegu Catholic University Medical Center and (2) Mono-iodo acetate – two studies, one conducted by PDS and one by Charles River Laboratories

Lateral has obtained positive results with IA delivery of LAT8881 in the rabbit collagenase model of OA

    • LAT8881 alone was as effective as Hyaluronic acid (HA)
    • LAT8881 plus HA resulted in additive effects on lameness and joint architecture
    • Published by Kwon et al in Ann Clin Lab Sci 2015

Charles River Labs have completed a model of OA in the rat in which joint pathology is induced by local injection of mono-iodoacetate (MIA)

    • LAT8881 given orally improved weight bearing on affected limb in rats at 3 and 21 days after disease induction

PDS also confirmed efficacy of oral LAT8881 in their MIA model

    • LAT8881 at 5mg/kg given orally improved weight bearing in rats on the affected limb at 14 days

Conclusion LAT8881 has effects on the painful symptoms in some models of OA and may also improve the repair of damaged joint tissue

Lateral Pharma has been conducting an extensive program of work with various external contract research laboratories and academic collaborators to understand how LAT8881 achieves its analgesic effects in neuropathic pain (both its Mode of Action & Mechanism of Action).

Lateral is currently conducting external research projects at Evotec to identify the molecular target for LAT peptides (France & Germany), Pacific Discovery Services to characterise their biological effects in nerve slices and animal models (Australia/UK) and Metrion to investigate effects on cell lines expressing candidate ion channels (UK). Electrophysiology conclusions from research projects are:

  • LAT8881 when dosed to animals or when applied directly to spinal cord slice DRG preparations from chronic nerve constriction models has an inhibitory effect on pain signal transmission
  • LAT8881 reduced post-synaptic excitation following stimulation of dorsal root afferents within 8 minutes
    • The effect was reversible on wash out
    • GH had no effect
  • LAT8881 reduced wind-up and spontaneous activity of spinal cord dorsal horn neurons
  • Effects consistent with an ultimate effect on ion channels

LAT8881 is our lead compound and has entered clinical development for the treatment of neuropathic pain. We have identified several other orally active peptides derived from LAT8881 that could have cost of goods or formulation advantages over LAT8881. We have also identified other compounds derived from different proteins with activity in spinal cord slice assays which provide additional IP. Once the LAT8881 target is identified we aim to perform HTS to identify new peptide and non-peptide leads as potential follow on compounds.

The potential for enhanced tissue repair suggested by the Mesenchymal Stem Cell differentiation and rabbit OA studies presents a potential additional opportunity for development of a treatment for Osteoarthritis.

Newly filed patents around backup compounds also provide the potential for Lateral Pharma to revisit the treatment of obesity.