King cobra venom peptide is believed to operate via antinociceptive mechanism that activates enkephalin system.

Theralpha has been awarded €2.55 million in French agency grants to support preclinical and early clinical development of the firm’s lead snake venom-derived candidate THA903 for the management of acute pain. The award will support the three-year SubAlgic program, through which Theralpha will work alongside collaborators at peptides firm Synprosis, the CNRS Institut de Pharmacologie Moleculaire (IPMC) in Sophia Antipolis, and the Clermont Ferrand Center of Clinical Investigation. SubAlgic has been accredited by the Eurobiomed cluster as part of the 12th FUI (Fond Unique Interministeriel) and is also supported by the regional agency Conseil Général 06, Région PACA.

THA903 is a sublingually administered, nonopioid, and water-soluble 11-amino acid peptide derived from hannalgesin, a neurotoxin isolated from King Cobra (Ophiophagus hannah) venom. Studies in preclinical models have demonstrated the drug to be safe and have analgesic properties, and while the mechanism of action of THA903 has not been fully worked out, it is thought to operate via a nNOS-dependent mechanism that results in activation of the endogenous enkephalin system, Theralpha notes.

Established in 2009, the firm is focused on the development of venom-derived pain control drugs, and in particular those that target acid-sensing ion channel (ASICs) pathways implicated in pain signal transmission. Its primary ASIC-targeting venom-based technology platform was developed by researchers at the IPMC, although the firm also has worldwide rights to the analgesic venom-derived peptide THA903 from the National University of Singapore spin-out, Protherapeutics.  

In addition to lead product THA903, Theralpha has three candidates that originate from IPMC research in preclinical development. THA901 is an ASIC1a antagonist in development as a treatment for neuropathic pain, cancer pain, and postoperative pain. The drug is a 40-amino acid peptide derived from the venom of the South American tarantula Psalmopoeus cambridgei.

THA902 is a 42-amino acid ASIC3 antagonist isolated from the sea anemone Anthopleura elegantissima, which is in development as a subcutaneous patch for treating inflammatory pain, fibromyalgia, postoperative pain, and osteoarthritis pain. Theralpha’s fourth candidate, THA904, is an ASIC 1a and 1b antagonist in development for the treatment of neuropathic pain. 

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