ACD440

ACD440 is a TRPV1 antagonist that is in the clinical development phase, and the company’s aim is to develop a new topical local treatment for neuropathic pain. The drug candidate, which was an important strategic in-licensing carried out in January 2020, fits well into the company’s existing pipeline and strengthens the clinical portfolio.

The project has its origins in Big Pharma and is based on strong scientific grounds. The 2021 Nobel Prize in Physiology or Medicine was awarded to Professor David Julius at UCSF, USA for the discovery of and insights into TRPV1, the biological system that serves as the basis for ACD440 and is central to temperature regulation and pain (https://www.nobelprize.org/prizes/medicine/2021/press-release/). The compound has previously undergone Phase I clinical trials, in which both good tolerability and early positive signals of efficacy were observed. The mechanism of action of the project is via TRPV1 receptors, which have a key role in pain signaling, and ACD440 has been shown in preclinical trials to have an effect on both nociceptive and neuropathic pain. The compound has previously undergone extensive preclinical safety studies and since the compound is being developed for local use, systemic exposure can be kept very low, while the concentration of the compound locally can be kept high for maximum analgesic effect.

Nociceptors are stimulated by heat, acid and strong food, which can lead to feelings of pain. Despite the differences in these stimuli, a single target protein expressed in these pain-sensing nerve cells responds to them all. The molecular target is the TRPV1 receptor, which is expressed in sensory neurons and is upregulated in the skin of individuals with certain types of neuropathic pain. Consequently, there is strong scientific support for local treatment with this type of target mechanism. Neuropathic pain is associated with impaired quality of life and current treatments rarely provide adequate pain relief. In all, an estimated 7–8 percent of the adult population worldwide suffers from pain with neuropathic elements, corresponding to about 80 million individuals in the US, Europe and Japan alone. Over half of these patients do not respond to current first-line treatment and it is specifically toward this group of individuals that AlzeCure is aiming its new intended treatment.

As planned, AlzeCure initiated a Phase Ib clinical trial of the drug candidate in late 2020, which was presented in April 2021 and showed positive proof-of-mechanism data, i.e. an analgesic effect in humans. The efficacy of ACD440 was clearly significant compared with placebo. It was also well tolerated as a topical gel on the skin, indicating good suitability for further clinical development as topical treatment for neuropathic pain conditions. As part of the preparations, an application was submitted to the FDA for a pre-IND meeting in the fourth quarter, and the response received provided good guidance for the project moving forward. The company is now planning further Phase II trials.