Samaritan Updates Alzheimer's and HIV Drug Development.

LAS VEGAS -- Samaritan Pharmaceuticals Inc. (AMEX:LIV) a developer of innovative drugs announced today it has updated its Alzheimer's and HIV drug development programs.

Overview of Samaritan's Research Pipeline

Samaritan's proprietary HIV drug SP-01A headlines the Company's pipeline. SP-01A is an oral HIV entry-inhibitor that works by blocking the HIV viruses' ability to infect CD4+ cells. In Phase I/II clinical trials, SP-01A demonstrated "proof of concept" with significance in two crucial areas, viral load and improvement in quality of life. The drug was also observed to have a favorable safety profile and was well tolerated. The data suggests that SP-01A is a promising drug for patients experiencing "drug resistance." The innovative concept underlying the mechanism of action of SP-01A was the basis used to develop two new HIV drug candidates, SP-10 and SP-03, both with robust HIV entry inhibitor properties.

Samaritan's Alzheimer's technology features: four promising therapeutics, SP-04, SP-04m, SP-08, and SP-233; two neural stem cell differentiation therapies, SP-sc4 and SP-sc7; a predictive diagnostic; and an animal model. The stem cell therapy drugs have been shown, in cells cultures and in animal, to awaken brain dormant stem cells and to transform them (differentiate) into new neurons. The Alzheimer's diagnostic is a simple blood test that has proven superior to the invasive spinal taps and MRIs currently used. Finally, the Alzheimer's animal model offers a model to rapidly screen and develop innovative drugs for Alzheimer's disease 

A promising cancer drug, SP-C007, and a breast cancer diagnostic highlight Samaritan's cancer program. The diagnostic provides a predictive prognosis of cancerous tumor aggressiveness with a more than twice accuracy rate than that of current technologies.

Samaritan's pipeline rounds out nicely with its cholesterol recognition peptide. This technology plays a role in binding and taking out cholesterol from LDL, thus offering an immediate response to hypercholesterolemia.

Samaritan's Drug Development Programs

AIDS/HIV Program

--SP-01A for HIV Resistance (Oral Entry Inhibitor); PII/III Clinical trials 2005-2006

--SP-10 for HIV Resistance (Oral Entry Inhibitor); Preclinicals being readied to apply for Investigational New Drug (IND) application with the FDA 

Alzheimer's Program

--SP-233 for Alzheimer's, Preclinicals being readied to apply for Investigational New Drug (IND) application with the FDA

--SP-004 and SP-04m for Alzheimer's; Preclinicals being readied to apply for Investigational New Drug (IND) application with the FDA

AIDS/HIV Drug Development Program

SP-01A as an Oral HIV Entry Inhibitor

In pursuing hypothesis, we discovered that the modulatory effect of SP-01A on the stress-induced corticosteroid increase may be related to a reduction of the expression of the cholesterol synthesis key enzyme HMG-CoA reductase mRNA leading to a reduction in cholesterol synthesis. Several observations have also established that inhibitors of cholesterol synthesis inhibit cell fusion formation induced by HIV-l and that drugs extracting cholesterol from the cellular membrane exert an anti-HIV-1 effect in-vitro.

Taken together, Samaritan's preclinical data appears to suggest that the effect of SP-01A on cholesterol synthesis leads to a modification of the cholesterol content of the host cell membrane, which, in turn, reduces the HIV-1 virus replication by rendering it much more difficult for the virus to enter and infect the cell.

SP-10 Second HIV Drug Development in Conjunction with SP-01A

SP-10 was discovered in Samaritan Laboratories, Georgetown University. After its discovery, continuous HIV preclinical studies demonstrated that SP-10 exhibited antiviral properties by blocking the entry of HIV and multi drug-resistant HIV viruses into the cells. Moreover, SP-10 has shown very low toxicity, suggesting that it lacks serious side effects. Toxicity is a major problem with most current antivirals, along with the development of drug resistance. So far, all of the current antivirals on the market are demonstrating drug resistance.

Since SP-01A is intended to be administered in combination with current antiviral therapy for the indication of HIV drug resistance; Samaritan decided to pursue SP-10 as overall antiviral for HIV that could be administered alone or in combination with the normally administered triple therapy for both HIV in general and drug resistance.

In pursuing the preclinical development of SP-01A as an antiviral for drug resistance, we decided, at the same time, to accomplish the same preclinical data required by the FDA for SP-01A for SP-10 although we intend to study SP-10 as a stand alone antiviral.

So far, preclinical data taken together for SP-01A and SP-10, suggest that theses compounds reduce HIV virus replication, by modifying the structure of the host cell membrane thus rendering it impossible for the HIV virus to enter and infect the cell. They both can be classified as oral entry inhibitors and could prove more effective than today's antiretroviral therapy because they would prevent HIV from invading healthy cells, rather than going after the virus when it might be too late as it has already inserted itself into these cells.

SP-01A Development

Proof of Concept/Phase I/II study

The safety and dose response of orally administered SP-01A in HIV-infected patients was assessed in a Phase I/II study. The study was an 8-week non-randomized, open-label study conducted at a single investigational site (AIDS Research Alliance, West Hollywood, CA) with 29 patients infected with HIV-1 who were being treated with concomitant triple combination antiretroviral therapy for at least 8 weeks prior to study initiation.

Upon submitting PI/II clinical study efficacy data, and upon evaluation by the FDA, Samaritan's IND/protocol was transferred to the Anti-Viral Division of FDA, which in turn requested further supporting antiviral preclinical studies, such as demonstration of anti-HIV-1 drug resistance and numerous other studies where SP-01A confirmed its results as an antiretroviral therapy. In addition, the inhibitory effect of SP-01A on the entry of HIV and multi drug resistant HIV viral strains reinforced our conviction of a new mechanism of action which targets the host cell, rather than the virus itself, rendering therefore SP-01A less susceptible, than any other drug on the market, to emerging resistances. Studies to investigate whether SP-01A induces resistance are underway.

SP-01 A Phase II/III Development

Samaritan expects to commence "A Multi-Center Double-Blind, Randomized, Placebo-Controlled Study of Orally Administered SP-01A as Monotherapy Treatment of HIV-Infected Patients" trial to demonstrate efficacy as an antiviral and gather dosage data in preparation for later stage PIII clinical trials, assuming positive outcome data.

Drug Development Alzheimer's Program

Samaritan has a long-term commitment to developing innovative and unique treatments for Alzheimer's disease. It is widely recognized that new approaches are vitally needed to help suffering patients and their families in the fight against Alzheimer's disease.

Alzheimer's Diagnostic

In Samaritan's quest to find an accurate diagnostic, inventors have surprisingly found that central nervous system DHEA is increased in patients having Alzheimer's, in contrast to decreased levels of DHEA found in the periphery (blood). Samaritan inventors have identified a distinct mechanism for DHEA formation in brain from precursors that they are able to follow in the blood; using a chemical reaction, that allows the prediction of DHEA levels in brain. This research has been the basis of Samaritan's Alzheimer's diagnostic test and granting of research funds from the National Institute of Health (NIH).

SP-233 Alzheimer's Drug

Excessive accumulation in the brain of the beta-amyloid peptide, due either to overproduction and/or decreased clearance and the formation of senile plaques, is one of the hallmarks of Alzheimer disease.

SP-233 was identified based on its ability to protect neurons against beta-amyloid-induced toxicity. SP233 was shown to bind to beta-amyloid peptide, prevent its oligomerization and entry into neurons, protect neuronal mitochondria from beta-amyloid-induced damage, and maintain neuronal cell energy levels. Samaritan's preclinical data is suggesting SP-233 as a new unique approach for Alzheimer's disease therapy.

SP-223 Development

Detailed studies on the mechanism of action of SP-233, in rodent and human neurons, have been performed and the toxicity of the compound in "in vitro" studies has been studied. Samaritan has performed the majority of the preclinical studies required to apply to the FDA for an IND and is currently performing toxicology studies.

SP-004/SP-04m Alzheimer's drug

Alzheimer's disease is characterized by multifaceted pathology involving a number of dysregulated molecular mechanisms that include, at least, changes in (i) cholinergic transmission, (ii) sigma-1 receptor-mediated pathways, and (iii) increased free radical production. Even though the improvement of the cholinergic transmission of the patients suffering from Alzheimer's is necessary (the basis of most of today's therapies), targeting acetyl cholinesterase solely is certainly not sufficient, in relationship to the numerous pathways involved in Alzheimer's disease pathology. A number of compounds were developed with the goal to express multiple properties allowing them to act simultaneously at two distinct targets, important in neuronal function, i.e., enzyme acetyl cholinesterase, and the sigma 1 receptor SP-004 and SP-04m efficacy has been validated in vitro, and in animal models, in vivo.

SP-004/SP-04m Development

Detailed studies on the mechanism of action of SP-004 and SP-04m have been performed and the toxicity of the compound in vitro has been studied. Preclinical toxicology studies will be now undertaken required to apply to the FDA for an IND.

Alzheimer's Stem Cell Drugs

Samaritan is fast tracking its development of its neuronal stem cell therapy drugs (SP-sc4 and SP-sc7) that can induce dormant brain neuronal stem cells to differentiate rapidly into adult neuron cells as a novel treatment for Alzheimer's disease and other neurodegenerative disorders. Repairing brain damage by replacing the lost neurons and restoring neuronal function is certainly the most ambitious and exciting challenge physicians and scientists are currently facing. In that aspect, the concept of stem cell therapy is extremely promising. Hence, the access to the differentiation of stem cells into neurons may serve as a database of specialized cells for regenerative medicine as a treatment for neurodegenerative diseases and brain stroke.

SP-sc4 and SP-sc7 Development

Screening a database/collection of naturally occurring compounds, identified compounds that were efficacious, in inducing "in vitro" and in rats' "in vivo" neural stem cell differentiation, and neurogenesis. Further, "in vivo" studies in animal models of neurodegenerative disease are in progress, in order to validate the use of these compounds in regenerating the neuronal network from pre-existing stem cells in the adult.

Alzheimer's Rat Model

Our animal rat model provides us with the means to rapidly screen, and develop therapeutics; coupled with an approach to unveil the mechanisms underlying the onset, and progression of Alzheimer's. Its development is in the expectation of validation by other academic scientists specializing in this area of research in the near future.

NIH Grants

1. 1R41 NS048688 STTR ($188,000) entitled "Plasma Diagnostic for Alzheimer's disease".

2. 1R41 AG024684 STTR ($100,000) entitled "SP004, a sigma-1 ligand with AchE inhibition properties".

Samaritan Pharmaceuticals: "A Cure Is Closer Than You Think."

Samaritan, a small Biopharmaceutical company is committed to winning the race to approval for its life-saving affordable drugs. Samaritan, in collaboration with Georgetown University, is advancing its proprietary compounds for AIDS, Alzheimer's, Cancer and Cardiovascular disease.

Visit our Web site at www.samaritanpharma.com.

Disclaimer

The company disclaims any information that is created by an outside party and endorses only information that is communicated by its press releases, filings and Web site. This news release contains forward-looking statements that reflect management's current beliefs about the potential for its drug candidates, science and technology. However, as with any biopharmaceutical under development, there are significant risks and uncertainties in the process of development and regulatory review. There are no guarantees that products will prove to be commercially successful. For additional information about the factors that affect the company's business, please read the company's latest Form 10-K filed April 14, 2004. The company undertakes no duty to update forward-looking statements.