Biochem Solutions, “INC”, has developed an entirely new medicinal agent, Trioxolane, designated Alphamir™. This agent was developed in response to the increasingly urgent need to treat the worldwide threat of viral epidemics, as well as to the increasing occurrence of antibiotic-resistant organisms. We believe Alphamir™ is a major breakthrough in therapeutic medicine and its broad efficacy brings a new understanding of the human immune system and our natural disease fighting mechanisms.

The most broadly successful therapy for human disease is provided by our own immune system. This includes all infectious, neoplastic, and autoimmune diseases. An intact and functioning immune system maintains a disease-free state, while a suppressed or dysfunctional immune system leaves us susceptible to a wide spectrum of maladies, almost without restriction.

The process by which Alphamir™ acts as a microbicidal agent is best explained through the understanding of the Respiratory Burst; the natural way our bodies fight microbes and tumor cells. White blood cells produce high-energy bio-oxidants, to kill viruses, fungi, and bacteria and to modulate immune function. Through significant in-vitro, pre-clinical and clinical research studies, BioChem Solutions has demonstrated that Alphamir™ augments this natural process.

Phagocytes employ, as antimicrobial agents, a number of compounds generated by partial reduction of oxygen. Oxygen is initially reduced to superoxide (O2-) by a membrane-associated flavoprotein. This process occurs in a respiratory burst via glucose oxidation in the hexose monophosphate shunt. Oxidized NADPH participates as follows: (O2 + NADPH yields 2O2- + NADP- + H-) subsequently by dismutation (superoxide dismutase) 2O2- + 2H+2 yields O2 + H2O2. Present theory suggests that microbicidal action by phagocytes is mediated by myeloperoxidase that catalyzes the conversion of H2O2 and Cl- to hypochlorous acid (HOCl). In support of the effectiveness of this mechanism it is interesting to note that 2X10-7 M of HOCl generated by 106 neutrophils will destroy 15x107 e.coli in milliseconds. In short, neutrophils purposely generate large quantities of reactive oxidants for microbicidal purposes. Interestingly, HOCl is the sole active ingredient in bleach. HOCl quickly reacts with primary or secondary amines to form an additional family of microbicidal agents called chloramines. The term “respiratory burst” refers to a coordinated series of metabolic events that take place when phagocytes are exposed to appropriate stimuli. This group of events underlies all oxygen-dependent killings by phagocytes.

Alphamir incorporates Trioxolane derivates that, upon introduction to the body’s aqueous ambience, reduce and produce high-energy oxygen metabolites within the blood stream as well as activate certain receptor cells in the pharyngeal cavity. These receptor cells cause the body to produce cells that are the precursor cells to the evolvement of lymphocytes, and thereby modulate the natural immune process of the human body. More specifically, AlphamirTM acts in vivo through the production of free radicals. Neutrophils and other phagocyte leukocytes can utilize these free radicals to produce multiple pathogenic toxins thus materially increasing the efficiency of the immune system to kill invading microorganisms. In addition, these free radicals exert a strong direct microbiocidal effect even in the absence of leukocytes. Free radicals also exert both an immunomodulatory and immunostimulatory effect by chemotactically signaling the immune system that a pathogen/leukocyte interaction is occurring. Little is known as to how AlphamirTM works on a molecular level. Effects can be divided into long-term and short-term actions. Short-term effects include such things as lysis of pathogenic organisms, abnormal cells, and toxins. AlphamirTM may have activity by destroying or blocking the activity of inflammatory agents such as prostaglandins. Long-term effects are mediated via immune system modulation and stimulation as well as enzyme system modulation. It has been shown that uptake of these radicals in infected cells is preferential in a ratio of 4 to 1 with uninfected cells. It appears that AlphamirTM also plays a role in cell membrane stabilization.

Alphamir is a safe and non-toxic substance. The safety profile was performed over a period of 6 years between 1988 and 1994 in four laboratories located in the United States, Cuba, and Kenya. Three of the facilities were medical academic institutions (University of California Irvine, Kenya Medical Research Institute, and University of Cuba, La Habana ) and the fourth was a professional contract research organization located in California. 19 different safety and toxicity studies were performed including: Minimum Inhibition Concentration assays, Minimum Bacterial Concentration assays, acute systemic toxicity, dermal toxicity, oral toxicity, ocular irritation, primary skin irritation, vaginal and rectal irritation, AMES Mutagenesis assays, Micronuclei in Mouse Bone Marrow, and other topical studies were performed in order to substantiate the effectiveness, safety, and tolerability of AlphamirTM. Of these 19 studies, a total of 312 mice, 65 rats, and 70 rabbits were used in order to substantiate the safety of the product. The following includes a summary of important results:

AlphamirTM was considered non-irritant to ocular tissue in the rabbit.

The product would be considered dermally non-toxic to the rabbit; the LD50 was greater than 2.3 ml/kg of body weight of a 1% (w/v) solution of the test article in the solvent.

The product would be considered a slight irritant to the skin.

The oral, single dose, LD50 of AlphamirTM was determined to be greater than 5,010 mg/kg body weight in the rat.

The results show that the rats can tolerate daily I.P. of AlphamirTM at a dose of 214 mg/kg that is almost 25 times higher than that proposed for AIDS patients (8.7 mg/kg).

Female rats given AlphamirTM I.P. doses up to 63 mg (586 mg/kg) in 0.5 cc tolerate a higher dose level [63 mg (586 mg/kg)] than male rats. The AlphamirTM level tolerated by rats is at least 380 mg/kg.

The result was an LD50 of AlphamirTM in mice has been calculated to be 700 mg/kg. The minimum tolerable dose is 600 mg/kg.

Medium lethal dose was not obtained because only one male rat died in 4 hours after a single oral dose larger than 5 g/kg. Substances with a LD50 larger than 5 g/kg orally administered to rodents are considered as non-toxic or moderately toxic substances. Thus, this pharmaceutical preparation of AlphamirTM is practically non-toxic when orally administered.

AlphamirTM does not show a mutagenic effect at any of the studied concentration for all strains included in AMES Test. Because of the phenotypic characteristics of Salmonella stocks selected in the AMES Test, AlphamirTM does not present a mutagenic effect of the kind of mutations due to a frame shift running nor to changes of base pairs.

Toxic concentration values found in some strains do not correspond to the reported inhibitory concentrations for AlphamirTM in several pathogenic bacteria.

No toxicity sign was observed during a period of 15 days in mice of both sexes, after being topically administered with a larger dose of 5000 mg/kg. There was no sign of dermic irritation during the time of observation. AlphamirTM does not show any toxicity sign due to its topical administration in single doses to mice of both sexes.

Davy Kiprotich Koech BSc, MS, PhD, Cbiol, MIBiol, FinstPM, SS, CuD (Hon.), OGW: Since 1989, Dr. Davy Koech has served as Chief Research Officer and Director of the Kenya Medical Research Institute. He is the author of 161 refereed journal publications in the fields of Leishmaniasis, Schistosomiasis, Malaria, AIDS, and numerous other diseases. He has performed research under numerous grants and programs with the World Health Organization’s Immunology Research and Training Centre, served as a Fulbright-Hays Scholar/Pharmacologist at Duquesne University, Montefiore Hospital (Department of Neurosurgery), and Harvard University Medical School (Departments of Medicine and Biological Chemistry). Since 1988 Dr. Koech has served as a member of the World Health Organization’s Regional Panel of Experts on AIDS and as a member of the International Council for Infectious Diseases. He was honored to receive the Presidential Award (State Investiture) of the Decoration of the Silver Star of Kenya (S.S.) in 1984 and the Presidential Award (State Investiture) of the Decoration of the Order of the Grand Warrior of Kenya in 1989 both in recognition of distinguished service rendered to his nation. Dr. Koech is a member of Who’s Who in Science and a member of the International Who’s Who in Medicine. Dr. Koech was also honored to receive the Medal of Honor commemorating distinguished lifelong achievements from the American Biographical Institute in 1987.

Dr. Koech received his BSc (Chemistry & Zoology) from the University of Nairobi in 1974, his MS (Pharmacology – Majored in Clinical Pharmacology) from Duquesne University in Pittsburgh, PA in 1977, and his Ph.D. (Medical Pathology, Immunology) from the University of Nairobi. Dr. Koech is a member of the East African Society of Parasitologists, British Society for Immunology, British Transplantation Society, Institute of Biology (U.K.), Institute of Professional Managers and Administrators (Fellow), Britain, International Society of Infectious Diseases, Association of Physicians of East and Central Africa, and Kenya Association of Clinical Pathologists.

After sufficient safety and toxicity studies were performed, a Phase I study protocol was developed and deployed at the Kenya Medical Research Institute by physicians under the direction of its Chief Research Officer, Dr. Davy Koech. This Phase I double blind 12 week clinical trial in consenting individuals infected with HIV-1 using AlphamirTM was performed to evaluate the clinical efficacy and safety of AlphamirTM in the management of symptoms associated with HIV infections and to assess the changes in immunological profiles in patients receiving the drug.

Patients of either sex were included in the study who had symptoms of ARC or AIDS with laboratory confirmation of HIV seropositivity by both ELISA and Western Blot or the equivalent tests, were between the ages of 12-60 years old, had a Karnofsky performance score (KPS) of between 40-90, and gave informed consent to participate. Patients under the age of 12, pregnant woman and lactating mothers, patients on specific anti-HIV medication such as AZT and interferon’s, those on systemic or local steroids, and patients with renal impairment were excluded from the study.

The study divided the 30 patients into three groups of 10 patients each selected as described by the criteria above. The Pharyngeal and Suppository Groups each received 125mg daily while the control received a placebo. The results of the trial demonstrate a significant decline in clinical complaints with a substantial increase in CD4+ lymphocyte levels as compared to the controls where HIV related clinical complaints and CD4+ lymphocyte levels remained consistent or marginally depressed.

Dose Range Determination of Trioxolane (AlphamirTM) for Efficacy, Safety and Tolerance in Individuals with HIV/AIDS – Performed at Kenya Medical Research Institute. (Note: for a more complete description with data, please see Appendix B)

The most recent study was an open label, randomized dose ranging clinical trial for efficacy, safety and tolerability of Trioxolane (AlphamirTM) in asymptomatic HIV-1 individuals with CD4 counts of 100-500 cells/ul of whole blood. In this study, 48 patients with proven HIV-1 status were recruited.

The study consisted of three arms at buccal dose levels of 100mg (Group 1), 200 mg (Group 2), and 400 mg (Group 3) daily for a period of 4 months. The patients CD4+ T cell counts were divided into low and medium, 100-250 cell/ul and 251-500 cell/ul of whole blood respectively before random allocation to the 3-treatment dose levels. Efficacy was determined largely on the basis of changes in the levels of CD4+ T cells as well as those of viral loads. Toxicity was assessed by monitoring liver, renal, and bone marrow functions. Follow-up was done every two weeks. At each follow-up, all toxicity and efficacy assessments were done. Because of costs and the known slow pace of change, samples for the analysis of viral loads were taken every month, but those of two monthly intervals were analyzed. CD4+ T cell levels were determined every two weeks.

A total of 48 individuals were recruited into the formal study. Six of them could not complete the study for reasons not related to the medication. Three were due to relocation of their work place following posting by their employers; two were due to the frequent travels in and out of the country that could not offer sufficient time for regular follow-up and visits. One simply indicated that he was too busy to adhere to follow-up timetable. However, they still insisted that they wanted to continue with the medication. They were then given medication, but were withdrawn from the study. A total of 43 out of 48 subjects had complete examinations (clinical) and full laboratory results for various measurements completed and assessed at baseline and at each of the eight follow-up visits up to 16 weeks. There were 17 patients in Group 1 of whom 14 completed the study, 16 in Group 2 of whom 15 completed and 15 in Group 3 of whom 14 completed the study.

CD4+ T cell levels showed better increase over the base line in those on daily doses of 100 mg. The levels tended to plateau during the third month of treatment at an average of 30% increase over the baseline. Some had increases of more than 60 percent over the baseline. On the average, 50 percent of the patients on 100 mg had significant increase in CD4+ T cells while it was 47 percent in those on 200 mg daily dose and 14 percent in those on 400 mg daily dose. A reduction of 50 percent or more of the baseline in viral load was considered significant while an increase of 100 percent or more was considered significant in the other direction.

AlphamirTM at 100 mg/day given in 4 divided doses had a good effect on the viral load reduction of 66.7% at 2 months. This degree in viral load reduction dropped by 33.3% by 16 weeks. Similarly, the observed significant reduction in log viral load dropped by over 50% at 16 weeks. At 200 mg, given in 4 divided doses, AlphamirTM showed a reduction in viral load of 46% at 2 months. This degree of reduction dropped by 29% by 16 weeks. At 400 mg similarly administered, the viral load drop was only 30% at 2 months, but this drop was insignificant.

At 16 weeks the number of patients with this minimal drop in viral loads rose to 64%. But only one person showed any significant drop in the log viral load drop at both 4 weeks and 16 weeks follow-ups.

18 out of 43 registered a significant reduction in their viral load. Ten of them were on 100 mg daily dose while 5 were on 200 mg daily dose and the remaining 3 were on 400 mg daily dose. None of those on 100 mg daily dose registered any significant increase in their viral load.

The drug, AlphamirTM when given in four equal doses at a daily dose of 100 mg, is able to significantly increase the levels of CD4+ T cells. From the foregoing, the data suggest that the lower dose appears to cause a better drop in viral loads than the higher dose.

However, even this lower dose showed a better effect at 2 months than at 16 weeks. This suggests that a much lower dose than 100 mg per day might be what is required for a possible sustained viral load reduction. The drug is able to cause significant viral load reduction. The 100 mg daily dose was found to be better than 200 mg or 400 mg daily dose. Further follow-up led to the conclusion that a daily dose of 100 mg gave better results and hence, all follow-up as well as subsequent patients were put on 100 mg daily dose beginning August 2000. Those with previous weight loss gained an average of 1.2k (2.6 lb) by the fourth week and this has been maintained. Because of the known slow pace of change, the viral loads are being done every month. Additional data have so far not been analyzed but no adverse effects have been encountered. The results obtained so far justify the need for facilitating wider use of this drug in the clinical management of HIV/AIDS.

It is expected that in the coming year at least three other diseases’ clinical trials will be undertaken and completed. The Company intends to proceed with clinical trials of Prophamir™, the use of Trioxolane as a prophylactic for women against sexually transmitted diseases including HIV/AIDS.

The Company expects that the results of the studies on HIV/AIDS and the resultant approval by the Kenyan authorities will embrace Alphamir™ as the drug of choice for Africa. Two factors will influence that decision: the efficacy of Trioxolane in treatment of the symptoms of HIV and the product’s low cost. Whereas the present cost of drugs to maintain an HIV patient in the United States is some $3,000 to $10,000 annually, the generic version cost $ 316 annually from HAART. It will be possible with appropriate funding to achieve better results, with minimal side effects, and reduce the cost to approximately $205 per patient per year or less in Africa. In addition, the use of Alphamir™ requires minimal patient monitoring and training.

In the near future, the Company will commence with the requirements to obtain approvals in the U.S., Europe, Asia and South America. At this time, it is not clear how long it will take to fulfill those requirements; however, it is anticipated that the results achieved in Africa will highly impact that time span. Funding is being sought now to increase the number of patients for Phase III of the clinical trials.

We are taking an integrated approach with a cost effective treatment program, as the spread of HIV/AIDS will soon reach catastrophic proportions. Our non-toxic, efficacious, low cost treatment is part of our treatment strategy to reduce the proliferation of HIV/AIDS.

Biochem Solutions recommends that the only viable and effective approach to contain HIV/AIDS must include a comprehensive program to:

1) administer a low cost self-testing procedure which we will co-market;

2) treat the infected HIV/AIDS population with Alphamir; and

3) administer a vaginal gel for the prevention of transmission which we are developing.

The demand for the use of this treatment strategy is great enough to support incrementally larger requirements of funding. It should be noted that the best scientific evidence supports the fact that viral strains cannot develop resistance to Alphamir™ and this represents a major ingredient in the ability to effectively control the AIDS pandemic.

The Company has received approval for sale and distribution of its products for HIV/AIDS and Rheumatoid Arthritis. The Company is continuing clinical trials as required by the Kenya Pharmacy & Poisons Board. BioChem Solutions has contracted with a nationally recognized law firm for life sciences intellectual property to review our current patents and work with the Company on future patents we intend to file. BioChem Solutions will also be working with the law firm’s FDA regulatory experts on making sure we are in compliance with all state regulations and Title 21 Code of Federal Regulations/Food and Drugs as well as all other federal regulations.

BioChem Solutions plans on working with a contract research organization that coordinates clinical trials in order to be sure that data being documented in the ongoing trial in Kenya will comply with FDA or FDA equivalent requirements. This data will be used when we are ready to submit an Investigational New Drug (IND) application to the United States Food and Drug Administration. In addition, BioChem Solutions plans on expanding registration and/or licensing our products for uses outside of HIV/AIDS and Rheumatoid Arthritis.

Once we have adequate funding from investors, BioChem Solutions plans on leasing a 12,500 square foot facility to meet the expected production requirements. Product will then be sent to pharmaceutical facilities for final formulation and packaging. BioChem Solutions plans on recruiting experienced individuals, some of which have been identified, who have managed pharmaceutical companies, preferably with HIV/AIDS experience. They will work with the Company to present our data to the US FDA.