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Sweden: Neuropathic Pain Alzecure Develops Novel Pain Killer Based on Nobel Prize-Winning Discoveries

Editor: MA Alexander Stark

A novel clinical candidate analgesic drug for peripheral neuropathic pain developed by Alzecure, is based on the seminal discoveries of TRPV1 by Prof. David Julius, and for which he was awarded the Nobel Prize in Medicine 2021.

Martin Jönsson CEO And Johan Sandin CSO Alzecure Pharma
Martin Jönsson CEO And Johan Sandin CSO Alzecure Pharma
(Source: Jenny Lagerqvist)

Huddinge/Swden — David Julius, PhD, professor and chair of the Department of Physiology and Morris Herzstein Chair in Molecular Biology and Medicine at UC San Francisco, has been awarded the 2021 Nobel Prize in Physiology or Medicine. His work has focused on how we can sense heat, cold, and chemical irritants, leading to new insights about the fundamental nature of pain and new targets for pain therapy. His fundamental research led to the identification and cloning of the specific protein responsible for the sensation of burning pain, TRPV1, in 1997.

ACD440 is a clinical-stage TRPV1 antagonist that is being developed as a new topical, local treatment for neuropathic pain. The candidate drug, which was incorporated via an important strategic in-licensing arrangement carried out in January 2020, has its origins in Big Pharma and is based on strong scientific grounds. The compound is being developed as a topical gel for local use, thereby keeping the systemic exposure very low, while the local concentration of the compound can be kept high for maximum analgesic effect.

“It is fantastic news that these seminal findings by professor Julius receive the appropriate attention. The discovery of TRPV1 and its link to pain perception is something that we have made use of in our ACD440 program,” said Johan Sandin, CSO at Alzecure.

In December 2020, Alzecure initiated a phase Ib clinical trial with ACD440 to assess both tolerability and early signals of efficacy. The positive study results were communicated according to plan in April 2021. The company is currently preparing for a phase II study with the candidate drug.

“About 50 percent of patients do not respond to current first-line treatment and there is a need to identify analgesics with improved efficacy as well as with a better risk-benefit ratio, said Martin Jönsson, CEO at AlzeCure. A potent topical compound acting by inhibiting the TRPV1 channel would be a novel non-opioid mechanism to obtain an analgesic effect without the associated side-effects observed with the existing therapies.”

TRPV1 are specialized cation channels, primarily expressed in sensory neurons. TRPV1 are activated by e.g. heat, acidic pH and capsaicin in “hot” peppers, and play a crucial role in heat sensation and nociception. They are sensitized from noxious stimuli, leading to inflammatory conditions and pain. In chronic pain states, TRPV1 are up-regulated on neurons, have reduced activation thresholds, and cause an increased perception of pain. Interestingly, it is also upregulated in the skin of individuals with many types of neuropathic pain.

“Neuropathic pain is an area with major medical need and associated with impaired quality of life and current treatments rarely provide adequate pain relief,” said Märta Segerdahl, CMO at Alzecure. “In all, an estimated 7–8 percent of the adult population worldwide suffers from pain with neuropathic elements.”