Products & Research

At Archer Pharmaceuticals, Inc. (Archer), we have established a leading-edge pharmaceutical facility in Sarasota, Florida, with in-house expertise in the following areas:

• Target discovery
• Drug discovery
• Target validation
• Pre-clinical efficacy
• Small-scale manufacturing
• Phase I clinical trials
• Drug development
• Global marketing and licensing

Code	Phase	Mechanism
ARC029	1	SARC
ARC031	1	SARC
ARC031 SR	1	SARC
ARC050	PC	BACE Inhibitor
ARC069	PC	Gamma Secretase Inhibitor
SARC = Soluble Amyloid Reducing/Clearing Agent PC = Pre-Clinical

ARC029 is Archer’s first compound to be selected for clinical development. With Archer’s worldwide rights pending to ARC029 for its use in Alzheimer’s disease, it is our intention to fast track its development to deliver a first-in-class drug.

ARC029 – Timeline
Phase I Clinical – Fourth Quarter – 2008
Phase II Clinical – Third Quarter – 2009
Phase III Clinical – Third Quarter – 2012
Product Launch – 2015

ARC029 – A Cure in Sight
ARC029 was selected from approximately 2,000 chemicals in the same class as our first-line treatment of 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. Other drugs in the class do not cross the blood brain barrier.

Importantly, ARC029 acts to lower the soluble forms of amyloid before they become deposits in the brain. We believe that the soluble forms (rather than the deposited forms) are the real culprit in the disease, and so reducing them is our goal with ARC029.

ARC029 – Current Findings in Mild Cognitive Impairment
Based on current studies, Archer has extensive safety data and a well-defined theory on how ARC029 works in the brain. It has been suggested that the parent molecule of ARC029, nilvadipine, may prevent cognitive decline in patients with mild cognitive impairment (MCI) and act as a disease modifying agent(Hanyu et al., 2007).

Since posteromedial hypoperfusion suggests the presence of underlying Alzheimer’s disease pathology and predicts conversion to Alzheimer’s disease (Hirao et al., 2005), most patients with MCI in this study (Hanyu et al., 2007) were at high risk of progression to Alzheimer’s disease and may also have included a portion of patients with prodromal Alzheimer’s disease. This study then suggests that ARC029 may stabilize cognitive function over time.

Although the mechanism of this effect is not known, nilvadipine has been shown to have beneficial effects, such as counteracting dysregulation of calcium homeostasis, vasoconstriction and neuronal apoptosis associated with amyloid peptide, and moreover is a more efficient free-radical scavenger than other calcium channel blockers (Iwasaki et al., 2003;Paris et al., 2004). In addition, Archer has data suggesting that nilvadipine and related compounds can have direct effect on lowering soluble amyloid levels independently of their impact on calcium channels.  Critically, this has allowed the development of non-calcium channel blocking derivatives of nilvadipine, including ARC031, which is anticipated to enter clinical trials in 2009.

Although these findings suggest that ARC029 may be associated with a lower rate of conversion to Alzheimer’s disease, larger randomized controlled studies are needed to confirm these results.

ARC031 – Follow-up Compound
ARC031 is not a calcium channel blocker but works in the same way as ARC029 to lower soluble amyloid levels. This compound has the advantage of not having antihypertensive effects in comparable doses to ARC029, which may be an additional advantage in Alzheimer’s disease.

ARC050 – BACE Inhibitors
Archer possesses patent pending approaches that are targeted at the inhibition of BACE. This target is felt by many experts to be critical in the course of developing Alzheimer’s disease.

ARC069 – Gamma Secretase Inhibitors
Another approach being pursued by Archer, is to target gamma secretase that do not dysregulate the notch pathway.