ARC029 is Archer’s first compound to be selected for clinical development. Archer has worldwide rights to ARC029 for use in Alzheimer’s disease and related disorders. ARC029 was selected from approximately 1,800 chemicals in the same class to be advanced to clinical trials in Alzheimer’s for several reasons:

• The compound was one of the most proficient at lowering amyloid levels in the pre-clinical tests and models of Alzheimer’s disease.
• Very importantly, ARC029 easily crosses the blood brain barrier, and there is evidence that it accumulates in the brain, which is important for targeting Alzheimer’s disease.
• ARC029 lowers the soluble forms of toxic amyloid before they become deposits in the brain.
• ARC029 also has a beneficial impact on tau pathology (the other main aberration in Alzheimer’s) in preclinical models of the disease.
• A novel mechanism of action supports the use of ARC029 and its derivatives in early-stage Alzheimer's disease.

Background studies relevant to ARC029:

Nilvadipine has been shown to have beneficial effects in preclinical studies, such as inhibiting amyloid production, increasing amyloid clearance across the blood brain barrier, decreasing neuroinflammation and reducing tau pathology (Paris et al., 2010; Bachmeier et al., 2011; Paris et al., 2014).

In human subjects, independent research has shown that Nilvadipine may prevent cognitive decline in patients with mild cognitive impairment (MCI) and reduces the rate of conversion to full blown Alzheimer’s disease (Hanyu et al., 2007).

Archer’s open label Phase I/IIa trial of Nilvadipine in Alzheimer’s patients demonstrated its safety and tolerability, and also showed APOE-genotype dependent stabilization of cognition and improvement in executive function over the 6 week duration (Kennelly et al., 2011a & b).

These promising findings led to the creation of the NILVAD consortium to evaluate the effects of 18 months of treatment with Nilvadipine in Alzheimer’s patients in a double-blind placebo controlled Phase III trial study conducted in nine European countries, which was completed in 2017.

ARC031 is a derivative of ARC029 which has beneficial effects on Alzheimer pathology in preclinical studies but which, in contrast to ARC029, does not dilate blood vessels and is therefore predicted not to lower blood pressure. Consequently, we anticipate being able to use higher doses of ARC031 in human studies without blood pressure related adverse events. Archer is currently planning regulatory strategies to advance ARC031 into human clinical trials.