Company Profile

Company Focus

Summary

University Research Park 455 Science Drive, Suite 120

Madison, Wisconsin 53711

Fax: 608-233-9139 www.quincybioscience.com

Quincy Bioscience LLC

Quincy Bioscience is a biotechnology company whose mission is to fight health challenges that result from neuronal calcium imbalance. Quincy Bioscience began in 2004 with the development of proprietary calcium-binding protein technology based on a protein called “apoaequorin” originally discovered in a certain species of jellyfish. Extensive research has described an important role for unregulated calcium levels in the etiology of cognitive declines seen in aging individuals. One suggestion for the disruption of calcium homeostasis is decreased levels of calcium binding proteins (CaBPs). Preclinical studies at the University of Wisconsin-Milwaukee demonstrated that following addition of apoaequorin, 50% more brain cells survived in a model of ischemic stroke. Quincy Bioscience developed Prevagen® and Prevagen Professional™, brand brain health supplements, containing the active ingredient apoaequorin, for brain cell protection. Human studies demonstrated Prevagen® improved memory for those reporting memory difficulties over the course of three months.

Quincy Bioscience, located in the University Research Park in Madison Wisconsin, was established in 2004 and is focused on the discovery, development and commercializa- tion of novel approaches to the challenges associated with aging and calcium dysregula-tion.

Quincy Bioscience has partnered with academic research laboratories in areas of scientific or commercial interest, related to calcium homeostasis. Quincy Bioscience has a research relationship with the laboratory of James R. Moyer, Jr., Ph.D. of the University of Wisconsin-Milwaukee. Dr. Moyer is an expert in the field of calcium-mediated cellular death. Quincy Bioscience is dedicated to fighting the

effects of calcium dysregulation on several fronts. In addition to the development of a novel dietary supplement, we are developing therapeutics from our calcium binding protein technology. Quincy Bioscience’s first product, Prevagen® brand dietary supplement, is now available in health food and chain drug stores nationwide.

Prevagen Professional™, twice the potency of Prevagen®, is offered exclusively to health-care professionals for distribution to their patients. Prevagen® is the first dietary supple-ment to restore calcium-binding proteins and address the effects of aging.

Quincy Bioscience’s technology has led to patent filings for both nutraceutical and pharmaceutical applications of the calcium-binding protein apoaequorin.

While apoaequorin has been used in laboratory research for over forty years, it had never been examined for human therapeutic use prior to Quincy Bioscience's research efforts. Apoaequorin is from a family of molecules called calcium-binding proteins (CaBPs).

Calcium-binding proteins are vital in regula-tion of calcium levels in certain cells types and

become depleted during in the aging process.It is the company’s hypothesis that both cellu-lar dysfunction and cellular death can be averted or ameliorated when intracellular calcium levels are better controlled. Manage-ment of calcium levels during or after acute or chronic insults to the cell can forestall thecytotoxic affects of excess calcium.

By assisting the body in the management of the intracellular calcium ions, problems associated with aging can be addressed, enhancing the quality of human life.

QUINCY BIOSCIENCE

QUINCY BIOSCIENCE

Phone: 888-895-MIND (6463)

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Calcium Regulation and Brain Health

Prevagen® is a patent-pending die-tary supplement designed to fight aging and replenish the calcium-binding pro-teins you lose in the natural aging proc-ess. Prevagen® is the only dietary sup-plement to use the age-fighting proteins contained within the jellyfish. Pre-vagen® is formulated for the retail con-sumer market.*

Prevagen Brands

●function in aging*● Formulated for Health Care Practitioners ● Once daily dosing in capsule form ● Available only through Health Care Practitioners ● 20 mg apoaequorin: twice regular Prevagen

●brain function* ● Once daily dosing in capsule form

● Available in Health Food and Retail stores ● 10 mg apoaequorin

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

Patent Pending

Intended for patients concerned with slowing brain

Intended for adults over 40 interested in preserving

Importance of intracellular calcium Calcium is an essential second messenger that plays an important role in a variety of neuronal functions, includ-ing synaptic plasticity, activation of kinases and phosphatases, regulation of gene expression, and excito-toxic cell death (Williams and Johnston, 1989; Bröcher et al., 1992; Uchitel et al., 1992; Choi, 1994; Yeckel et al., 1999). The latter is particularly important because, while vital to normal neuronal function, calcium levels are tightly regulated and excess calcium is harmful. Unregulated calcium influx is particularly troublesome for aging neurons because they are less able to handle excessive calcium, in part, due to decreases in expres-sion of calcium binding proteins, which help to buffer intra-cellular calcium.

Calcium Hypothesis of AgingOver the last fifteen years, a hypothesis has emerged which attempts to explain the cognitive deficits seen in aging populations. The calcium hypothesis of aging (Khachaturian, 1987; Landfield, 1987; Khachaturian, 1994) posits that dysregulation of calcium homeostasis is a primary factor contributing to age-related learning and memory impairments observed in many species, includ-ing humans. In healthy people, the levels of calcium ions are well controlled. However, in aging, the body gradu-ally loses its ability to manage the levels of calcium ions (Squier et al., 2000).

There is a loss of calcium homeostasis and the unregulated calcium levels begin to wreak havoc on neuronal tissue. Eventually, elevated calcium triggers excito- toxic events that will kill the neurons. Currently, there are no approaches that address the problem of excess calcium ions (Ripova et al., 2004).

Relevance of Calcium Binding Proteins Calcium-binding proteins (CaBPs) are recognized as protective factors in susceptible neuronal populations. CaBPs are important for regulating the intracellular calcium concentration of neurons (Baimbridge et al., 1992). Studies have shown that neurons lacking CaBPs are less able to handle ionic insults (Mattson et al., 1991).

A number of studies suggest that there is a selective decrease in certain CaBPs in the brains of aged animals, including humans (Ichimiya et al., 1988; Iacopino and Christakos, 1990; Hof and Morrison, 1991; Amenta et al., 1994; Selden et al., 1994; Villa et al., 1994; De Jong et al., 1996; Zettel et al., 1997; Moyer et al., 2001). Loss of CaBPs with advancing age may leave populations of neurons vulnerable to insults that result in even moderate increases in intracellular calcium concentrations.

The jellyfish-derived protein “apoaequorin” is from the EF-hand family of calcium-binding proteins and is similar in DNA sequence to CaBPs expressed in human neurons.

QUINCY BIOSCIENCE

Prevagen Professional™ was developed exclusively for Healthcare Practitioners and their patients. Prevagen Professional™ is a patent-pending brain health supplement designed to fight aging and replenish the calcium-binding proteins lost in the natural aging process. Prevagen Professional™ has twice the potency of consumer strength Prevagen®.*

For wholesale orders call: 888-895-MIND (6463)

www.prevagenpro.com

www.prevagen.com

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Prevagen® Research

Prevagen® helps memory

sllec detaertnU

Apoaequorin neuroprotection increases with age

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

Patent Pending

In repeated preclinical studies conducted at the University of Wisconsin-Milwaukee apoae-quorin prevented cell death as shown in these slides. Utilizing an established model of ischemic insult to assess neuroprotection, a significantly greater number of untreated nerve cells died compared to the apoaequorin treated cells. Dead cells from brain slices are shown stained trypan blue.

Apoaequorin increases cell survival

Models of ischemic insult are used to establish a compound’s neuroprotective ability due to the close biochemical similarities between an ischemic insult and neurodegeneration over time.

In additional studies when comparing the neuroprotective effect of apoaequorin in adult versus aged subjects, 55% more neurons survived in the aged subjects compared to approximately 30% in the younger group. The amount of protective calcium-binding proteins expressed by neurons diminish with age. This data shows that apoaequorin has a greater neuroprotective effect in aging.

The Prevagen® Quality of Life Study was an open-label study of 56 generally healthy participants over a 90 day period measuring changes in overall cognition, quality of sleep, energy, mood, pain, and general health. Changes in performance were measured via a standardized battery of questions. The results of the study showed improvement across all parameters.

Prevagen® provides a clear benefit in the area of memory especially for those who reported having poor memory at Day 0 (baseline) of the trial. No participants discontinued the study due to an adverse event. The two graphs illustrate questions from the memory portion of the study where participants reported a decrease in overall forget-fulness and a reduction in the amount of reminders needed to complete tasks as a part of their daily life.

QUINCY BIOSCIENCE

% R

epor

ting

a ch

ange

in f

orge

tful

ness

Change in Level of Forgetfulness100%

90%

80%

70%

60%

50%

40%

30%

20%

10%

0%

Day 8 Day 30 Day 60

23%

57%63%

34%42%

68%

8%0%

3%

% Feeling Less Forgetful

% Feeling More Forgetful

% No Change

% R

epor

ting

a ch

ange

Change in Number of Reminders Needed 100%

90%

80%

70%

60%

50%

40%

30%

20%

10%

0%

Day 30Day 8 Day 60 Day 90

69% 69%

69% 80%

19%26%

19% 11%

61%

30%

7%3% 0%

% Feeling Less Forgetful

% Feeling More Forgetful

% No Change

Apoaequorin treated cells

Num

ber o

f dea

d ce

lls

Apoaequorin reduces cell death with age100

80

60

40

20

apoaequorincontrol

Day 90

68%

29%

3%

55% less cell death30% less cell death

Adults Aged Adults

Quincy Bioscience LLC

Aequorin is a naturally occurring substance; discovered in 1962 in a species of jellyfish in the Puget Sound, WA.

Brooks, Susan. “The discovery of aequorin and green fluorescent protein.” Journal of Microscopy Vol. 217, Pt 1 (Jan 2005): pp.1-2.

Aequorin is non-toxic. Blinks, John. “Use of photoproteins as Intracellular Calcium Indicators.” Environmental Health PerspectivesVol. 84 (1990): pp. 75-81.

Aequorin does not interfere with other internal cellular function.Miller, Al, et al. “Imaging CA2+ with aequorin using a photon imaging detector.” Methods in Cell Biology(1994): 40:305-338.

Aequorin is a protein which binds calcium ions. Inouye, Satoshi, et al. “Cloning and sequence analysis of cDNA for the luminescent protein aequorin.” Proceedings of the National Academy of Sciences, USA. Vol. 82 (May 1985): pp. 3154-3158.

Aequorin is similar in DNA sequence to other calcium-binding proteins produced in the human body.

Moncrief, N.D. “Evolution of EF-hand calcium-modulated proteins.” Journal of Molecular Evolution. Vol. 30, Issue 6 (1990): pp. 522-562.

Aequorin has demonstrated a neuroprotective effect. Moyer, James. “Neuroprotective Effects of aequorin on hippocampal CA1 neurons following ischemia.” Society for Neuroscience (2006) Scientific Abstract.

Aequorin (apoaequorin) Research

References

Amenta F, et al. (1994) Calbindin D-28k immunoreactivity in the rat cerebellar cortex: age-related changes. Neurosci Lett 178:131-134.

Baimbridge KG, Celio MR, Rogers JH (1992) Calcium-binding proteins in the nervous system. Trends in Neuroscience 15:303-308. Bröcher S, Artola A, Singer W (1992) Intracellular injection of Ca2+ chelators blocks induction of long-term depression in rat visual cortex. Proc Natl Acad Sci USA 89:123-127.

Choi DW (1994) Calcium and excitotoxic neuronal injury. Ann N Y Acad Sci 747:162-171.

Cobbold PH, Rink TJ (1987) Fluorescence and bioluminescence measurement of cytoplasmic free calcium. Biochemical Journal 248:31 3-328. De Jong GI, Naber PA, Van der Zee EA, Thompson LT, Disterhoft JF, Luiten PGM (1996) Age-related loss of calcium binding protein s in rabbit hippocampus. Neurobiol Aging 17:459-465. Hof PR, Morrison JH (1991) Neocortical neuronal subpopulations labeled by a monoclonal antibody to calbindin exhibit differenti al vulnerability in Alzheimer's disease. Exp Neurol 111:293-301. Iacopino, AM and Christakos, S. (1989). Specific alterations in calcium-binding protein gene expression in neurodegenerative di seases. Abstract- UCLA Symp. Neurodegen. Diseases. Iacopino AM, Christakos S (1990) Specific reduction of calcium-binding protein (28-kilodalton calbindin-D) gene expression in a ging and neurodegenerative diseases. Proc Natl Acad Sci USA 87:4078-4082. Ichimiya Y, Emson PC, Mountjoy CQ, Lawson DEm, Heizmann CW (1988) Loss of calbindin-28K immunoreactive neurones from the cortex in Alzheimer-type dementia. Brain Res 475:156-159.

Khachaturian ZS (1987) Hypothesis on the regulation of cytosolic calcium concentration and the aging brain. Neurobiol Aging 8:3 45-346.

Khachaturian ZS (1994) Calcium hypothesis of Alzheimer's disease and brain aging. Ann N Y Acad Sci 747:1-11.

Landfield PW (1987) 'Increased calcium current' hypothesis of brain aging. Neurobiol Aging 8:346-347. Mattson MP, Rychlik B, Chu C, Christakos S (1991) Evidence for calcium-reducing and excito-protective roles for the calcium-bin ding protein calbindin-D28k in cultured hippocampal neurons. Neuron 6:41-51. Moyer JR, Jr., Brown TH (2002) Patch-clamp techniques applied to brain slices. In: Advanced Techniques for Patch-Clamp Analysis (Walz W, Boulton AA, Baker GB, eds), pp 135-194. Totowa, NJ: Humana Press.

Moyer JR, Jr., Disterhoft JF (1994) Nimodipine decreases calcium action potentials in an age- and concentration-dependent manne r. Hippocampus 4:11-18. Moyer JR, Jr., Brown TH (1998) Methods for whole-cell recording from visually preselected neurons of perirhinal cortex in brain slices from young and aging rats. J Neurosci Meth 86:35-54. Moyer JR, Jr., Thompson LT, Black JP, Disterhoft JF (1992) Nimodipine increases excitability of rabbit CA1 pyramidal neurons in an age- and concentration-dependent manner. J Neurophysiol 68:2100-2109. Moyer JR, Jr., Power JM, Thompson LT, Disterhoft JF (2000) Increased excitability of aged rabbit CA1 neurons after trace eyebli nk conditioning. J Neurosci 20:5476-5482. Moyer JR, Jr., Kelsey SM, McGann JP, Brown TH (2001) Morphology and distribution of calbindin-D28k in adult and aged rat perirhinal cortex. Soc Neurosci Abstr 27: Program No. 327.7. Pascale and Etcheberrigaray (1999). Calcium alterations in Alzheimer’s disease: pathophysiology, models and therapeutic opportu nities. Pharmacol Res, 39(2), 81-8. Ripova D, Platilova V, Strunecka A, Jirak R, Hoscchl C (2004) Alterations in calcium homeostasis as biological marker for Alzhe imer's disease? Physiol Res 53(4):449-52. Selden N, Geula C, Hersh L, Mesulam M-M (1994) Human striatum: chemoarchitecture of the caudate nucleus, putamen and ventral striatum in health and Alzheimer's disease. Neurosci 60:621-636.

Squier, T. et al. (2000). Protein oxidation and age-dependent alterations in calcium homeostasis. Frontiers in Bioscience, 5, D 504-D526. Uchitel OD, Protti DA, Sanchez V, Cherksey BD, Sugimori M, Llinas R (1992) P-type voltage-dependent calcium channel mediates pr esynaptic calcium influx and transmitter release in mammalian synapses. Proc Natl Acad Sci USA 89:3330-3333.

Verkhratsky and Toescu. (1998). Calcium and neuronal aging. Trends Neurosci, 21(1), 2-7. Villa A, Podini P, Panzeri MC, Racchetti G, Meldolesi J (1994) Cytosolic Ca2+ binding proteins during rat brain ageing: loss of calbindin and calretinin in the hippocampus, with no change in the cerebellum. Eur J Neurosci 6:1491-1499. Visser PJ, Verhey FR, Hofman PA, Scheltens P, Jolles J (2002) Medial temporal lobe atrophy predicts Alzheimer's disease in patients with minor cognitive impair-ment. J Neurol Neurosurg Psychiatry 72:491-497. Williams S, Johnston D (1989) Long-term potentiation of hippocampal mossy fiber synapses is blocked by postsynaptic injection of calcium chelators. Neuron 3:583-588. Yeckel MF, Kapur A, Johnston D (1999) Multiple forms of LTP in hippocampal CA3 neurons use a common postsynaptic mechanism. Nature Neuroscience 2:625-633. Zettel ML, Frisina RD, Haider S-E-A, O'Neill WE (1997) Age-related changes in calbindin D-28k and calretinin immunoreactivity in the inferior colliculus of CBA/CaJ and C57B1/6 mice. J Comp Neurol 386:92-110.

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease. Patent Pending

QUINCY BIOSCIENCE

University Research Park 455 Science Drive, Suite 120

Madison, Wisconsin 53711

Fax: 608-233-9139 www.quincybioscience.com

Phone: 888-895-MIND (6463)