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Amarillo Biosciences Issues Progress Report
Amarillo Biosciences, Inc. (OTC BB: AMAR) today issued the following progress report:
In October 2005, patients will start enrolling in our study of bone marrow disorders at M.D. Anderson Cancer Center. The investigational new drug (IND) application and protocol have passed FDA review. The protocol has passed the Institutional Review Board (IRB) and clinical supplies of interferon lozenges have been prepared, tested, shipped and are ready to be dispensed to patients.
The interferon lozenges will be tested in patients with one of two stem cell disorders of the bone marrow, polycythemia vera (PV) and essential thrombocythemia (ET). A pilot study, previously conducted in PV and ET patients at the Mayo Clinic, provided enough positive data to justify a second study at the M.D. Anderson Cancer Center. Carried to its conclusion, 20 PV and 20 ET patients will be enrolled to take interferon lozenges. The study is expected to take approximately one year to complete.
October 18, 2005 is the date that the Turkish Ministry of Health (MOH) is expected to rule on the adequacy of our planned study of patients with Behçet's disease in Turkey. The IND and protocol have passed FDA review. The Turkish IRB will meet after the MOH approves the study and then clinical supplies will be packaged. The clinical supplies have been prepared, tested and shipped to the Company for coding and randomization.
In October, a term sheet for funding of our clinical trial on oral warts in HIV+ patients is expected from an investment bank with which ABI has executed an engagement letter. The IND and protocol for a phase II clinical trial in patients with oral warts has passed review by the FDA. Ten clinical sites have been identified and the study awaits funding. It is our goal to acquire funding and start the study in the first quarter of 2006.
The clinical data on 17 patients with idiopathic pulmonary fibrosis (IPF) analyzed last week is extremely encouraging. Four out of 5 IPF patients with coughing at night have experienced significant relief of coughing resulting in more sleep for themselves and for household members. This "quality of life" measure will form the basis of future studies on IPF patients.
On September 21, 2005, the Company filed a grant application with the Texas Emerging Technology Fund seeking $5 million in funding. We expect to hear shortly whether our grant application will pass local review and be submitted to the governor's office for consideration.
The Company continues to view the future influenza pandemic -- which has resulted in the death of 150 million birds and 65 humans to date in 11 countries -- with alarm. The Company has contacted international, state and federal authorities on what the Company believes is an inadequate response plan. Vaccine is not available and the expense, inadequate supply and modest benefits of antiviral drugs leave most people completely vulnerable to influenza. Data generated in the former Soviet Union, China, Japan and Bulgaria indicate that low doses of oral or nasal interferon reduce the severity and duration of influenza. In 2006, we are expecting to work with scientists and/or companies in Southeast Asia to test oral interferon in influenza.
BioVet, Inc., a Tokyo based animal health company was granted approval in July 2004 by the Ministry of Agriculture, Forestry and Fisheries of Japan for production and marketing of oral IFNa (interferon alpha) treatment of rotavirus in cattle. Rotavirus diarrhea is a major cause of disease and death in animals and humans. The animal health approval in Japan is for low-dose oral administration of human IFNa supplied by Hayashibara Biochemical Laboratories (HBL). The approved oral dosage is 0.5 IU (international units) of human IFNa per kilogram of body weight, once daily for 5 days to treat rotavirus diarrhea in calves not more than 30 days old. The product was launched in Japan in August 2004. Amarillo Biosciences receives a royalty on sales in Japan and is negotiating with BioVet regarding expanding animal health development outside of Japan.
AMAR has already invested nearly $37 million in R&D, clinical studies, regulatory affairs, a patent portfolio, etc. and is seeking $5 million funding to complete the FDA approval process for multiple human diseases.
How will AMAR be able to achieve FDA approval for low-dose, oral interferon at such a low cost?
Fortunately, interferon given by injection in high doses is already FDA approved so AMAR's interferon is not a new chemical entity unknown to FDA, subject to extensive and expensive safety testing. AMAR is developing interferon to be delivered: (1) by a less hazardous route of administration (oral is safer than injectable), (2) at a much lower dose with 90% fewer side effects (injectable interferon is typically given at a concentration at least 10,000 times greater than AMAR's oral dose), and (3) at a lower cost. AMAR is seeking approval of oral interferon for treatment of diseases for which injectable interferon is not approved.
What is the market size for injectable interferon?
The annual world market for human use of injectable interferon in 2004 was greater than $5.0 billion (Med Ad News, May 2005). The market would probably be larger except treatment with injectable interferon often causes moderate to serious side effects, including fever, depression, nausea, flu-like syndrome and changes in blood cells. Approximately 60% of hepatitis C patients given injectable interferon and Ribavirin consider suicide in the first 30 days of therapy.
Why is injectable interferon so toxic?
Interferon is a protein. Scientists assumed that if interferon were swallowed, its medicinal effects would be damaged in the digestion process. Moreover, scientists thought interferon must have a blood level to be effective and could only achieve blood levels by intramuscular, intravenous, or subcutaneous injection. To counteract the kidney's clearance of interferon from the blood injectable interferon must be given in doses much higher than what occurs naturally. The high doses of injected interferon cause moderate to severe side effects in at least 50% of treated patients (Physician's Desk Reference, 2005).
How is AMAR's interferon different?
Low-dose, oral interferon is human interferon alpha administered in a small tablet (lozenge) to humans or in powder to animals. Low-dose, oral interferon binds to surface (mucosal) cells in the mouth and throat causing mucosal lymphocytes (a type of white blood cell in the mucosa) to interact with cells in the peripheral blood to activate hundreds of genes affecting immune function. Orally delivered interferon has been shown to turn on genes in man, cattle, and mice. Studies in humans and animals show that oral interferon is effective against disorders such as cancer, viral diseases and autoimmunity. Since oral interferon is administered in doses 10 thousand times less concentrated than injectable interferon, side effects are dramatically reduced.
Once FDA approval is granted, oral interferon will likely to be used more than injectable interferon. The oral route of administration of interferon in low doses is an effective treatment with virtually no side effects. Data from over 4,000 patients in 70 human clinical studies show that side effects are generally experienced by less than 5% of patients. Interferon in lozenge formulation is stable without refrigeration for two years, whereas injectable interferon requires refrigeration. Patients given oral interferon need fewer doctor visits to manage the side effects of treatment. Patients may administer the lozenges orally themselves without a needle or syringe.
How far along is Amarillo Biosciences in the FDA approval process?
Oral Interferon-alpha Development Progress and FDA Approval Timetable:
Human Health-USA Preclinical Phase Phase Phase Commercial
I II III Opportunity
Oral Warts in HIV+ ---------------------- 2010
Pts
Sjögren's Syndrome ----------------------------- 2011
Behçet's Disease* ---------------------- 2010
Pulmonary Fibrosis ---------------------- 2010
Polycythemia Vera ----------------------
Essential ----------------------
Thrombocythemia
Animal Health
Products
Rotavirus in ------------------------------- Approved
Cattle Japan - 2004
*Study to be conducted in Turkey
How long does it take to get FDA approval for oral interferon?
It took 30 years from discovery to the first FDA approval for interferon. According to the Tufts Center for the Study of Drug Development, it takes 10-15 years on average for an experimental drug to travel from lab to patients. Preclinical testing involves laboratory and animal testing to determine effectiveness and safety. Then, an Investigational New Drug (IND) Application must be filed with the FDA to begin Phase I, II and III clinical trials. After successful clinical trials in humans are completed, a New Drug Application (NDA) is submitted to the FDA for drug approval. It takes the FDA approximately 1-1.5 years for review of an NDA and approval. Diseases that affect fewer than 200,000 patients in the US and receive the FDA "orphan drug designation" require fewer patients in clinical studies and generally take less time to achieve FDA approval.
AMAR owns 15 patents relating to the manufacture or the oral delivery of interferon. The most important patent owned is "Interferon Dosage Form and Method Therefor." This patent issued on April 16, 2002 and will expire on April 16, 2019. It provides market protection for low dose interferon given by oral administration in humans and animals. It is possible to extend the life of a patent (Patent Term Restoration) for 1-1.5 years to make up for FDA review time.
Our goal has been to create layers of patent protection. For example, if Sjögren's syndrome is treated by low-dose oral interferon using our lozenges, then 3 patents apply:
1) Treatment of Autoimmune Disorders with Oral Interferon, US Patent No. 5,846,526, expires December 2015.
2) Interferon Alpha Medicated Upregulation of Aquaporin Expression, US Patent No. 6,506,377, expires December 2021.
3) Interferon Dosage Form and Method Therefore, US Patent No. 6,372,218 B1, expires April 2019.
Injectable interferons (alpha, beta or gamma) are approved by the FDA for treatment of leukemia, myeloma, renal cell carcinoma, Kaposi's sarcoma, melanoma, hepatitis, papillomas, multiple sclerosis and chronic granulomatous disease. The injectable interferon market for human use in 2004 worldwide was greater than $5.0 billion (Med Ad News, May 2005).
AMAR believes that FDA approval for oral interferon will allow AMAR to compete favorably in this $5 billion market. Patients will prefer our low-dose oral formulation of interferon to the current high dose injectable forms on the market.
AMAR sold our building in 2003 with the intention of relocating the Company. We have made visits to other cities in Texas and cities in Pennsylvania, Ohio and West Virginia to seek incentives for relocation. We are actively working with one site in Ohio to craft a package of incentives for relocation.
We are not pleased with the fact that our stock price has been less than $1.00 for months. In 2005 we will try to enhance shareholder value through advancement of the various projects outlined above. We are seeking more development partners.
In summary, AMAR possesses several cytokines that hold the promise of treating significant human and animal diseases. There is reason for optimism for the Company's future. My staff and I at AMAR will be working diligently to make this promise a reality.
Amarillo Biosciences to Provide Oral Interferon for MD Anderson Clinical Trial in Patients With Bone Marrow Disorders
Enrollment at MD Anderson Cancer Center Open
Amarillo Biosciences, Inc. (ABI) (OTC BB: AMAR) today announced that a study to test low dose oral interferon alpha in forty patients with rare bone marrow proliferative disorders is now open to enrollment. Amarillo Biosciences filed the Investigational New Drug Application with the FDA, and, in conjunction with principal investigator Srdan Verstovsek, MD, PhD, Assistant Professor, Myeloproliferative Disorders Program Leader, University of Texas, MD Anderson Cancer Center, Houston, Texas, helped to develop the protocol for the clinical trial. In addition, Amarillo Biosciences will provide the low dose oral interferon that will be used in the study. Twenty patients, each with either polycythemia vera (PV) or primary thrombocythemia (ET), will be given low dose oral interferon alpha daily as a treatment to relieve the signs and symptoms associated with these disorders. This study is open to patients not previously exposed to interferon preparations. Potential participants should not be currently taking other medications to control their blood cell count.
PV and ET are stem cell disorders considered to be incurable. Treatment is directed at reducing morbidity and preventing life-threatening complications. The clinical course of both ET and PV are characterized by vasomotor disturbances (headaches, dizziness), acral dysesthesia (impaired sensations in limbs, fingers, ears), erythromelalgia (diffused redness and atrophy of skin on legs), visual symptoms, thrombohemorrahagic (inappropriate clotting) events, and the risk of transformation into acute myeloid leukemia (AML) or fibrosis of the bone marrow (myelofibrosis).
Treatment efforts in ET strive to reduce clotting events in patients at high-risk for thrombosis without increasing the intrinsically low risk of developing leukemia. All patients with PV require phlebotomy (drawing blood), with the goal of reducing hematocrit levels (the concentration of red blood cells). This maneuver prolongs survival by decreasing the risk of thrombosis. The goal of therapy in PV is not only to prevent thrombosis, but also to reduce the risk of transformation into AML or myelofibrosis.
PV and ET patients interested in enrollment should contact Srdan Verstovsek, MD, PhD, Assistant Professor, Myeloproliferative Disorders Program Leader, University of Texas, MD Anderson Cancer Center, Houston, Texas at (713) 792-7305.
Amarillo Biosciences Low-Dose Oral Interferon Study With NOBEL to Treat Behcet's Disease Clears FDA Review Process
Study Expected to Commence in October 2005
Amarillo Biosciences, Inc. (ABI) (OTC BB: AMAR) today announced that it has resolved all clinical and safety issues with the U.S. Food and Drug Administration (FDA) and is ready to initiate a study with a leading Turkish pharmaceutical company, NOBEL ILAC SANAYII VE TICARET A.S. The study is expected to commence in October 2005 and to be completed within a year from that date. ABI's oral low-dose interferon-alpha will be tested as a treatment for Behcet's Disease in 90 Turkish patients. NOBEL has a license to ABI's oral interferon in Azerbaijan, Bosnia & Herzegovina, Bulgaria, Croatia, Georgia, Kazakhstan, Kyrgyzstan, Macedonia, Romania, Russia, Saudi Arabia, Slovenia, Tajikistan, Turkmenistan, Turkey, Uzbekistan, and Federal Republic of Yugoslavia.
In Turkey, the incidence of Behcet's Disease -- as a percentage of the population -- is 600 times more common than in the United States. The availability of a large patient population and worldly renowned clinical experts in Istanbul were leading factors in choosing to conduct the study in Turkey. Behcet's Disease is an autoimmune disorder that is characterized by mouth ulcers and generally two additional "hallmark" symptoms such as recurrent genital ulceration, eye or skin lesions or a positive pathergy (skin) test. Currently, this severe, chronic, and debilitating condition is incurable with no existing satisfactory treatment.
Low-dose orally administered interferon-alpha is administered as a lozenge, which is allowed to dissolve slowly in the mouth. Oral dosing with interferon-alpha has a number of advantages over the injectable form; in addition to substantially fewer side effects, the lozenge is more convenient, cost effective and does not require refrigerated storage.
The FDA has granted Orphan Drug Designation for this product for the clinical indication of Behcet's Disease to Amarillo Biosciences. The Orphan Drug Designation is designed to promote the development of treatments for diseases that are rare in the United States and provides certain marketing exclusivity incentives outlined under the Orphan Drug Act.
"We are excited to partner with NOBEL to take oral low-dose interferon-alpha to the next level in clinical trials. They have the expertise to make this an excellent near-term revenue generating opportunity," said Dr. Joseph M. Cummins, President and CEO of Amarillo Biosciences. "In Turkey alone, the market could be more than 100 million interferon doses annually, which represents an enormous potential for Amarillo Biosciences and NOBEL."
Under the terms of the agreement, Amarillo Biosciences and NOBEL will conduct Behcet's Disease studies in Turkey. U.S. FDA approval will be sought and this FDA approval will be owned by Amarillo Biosciences, but will be used by NOBEL to seek regulatory approval in each country of the Territory.
In addition to its NOBEL study on Behcet's Disease, Amarillo Biosciences is engaged in three other human studies involving low-dose interferon alpha. The company is participating in studies of two myeloproliferative diseases at a major cancer center in Texas and an Idiopathic Pulmonary Fibrosis study at Texas Tech University Health Science Center. Amarillo Biosciences is also working on an Helicobacter pylori study funded by National Institute of Health at The Ohio State University.
Separately, Amarillo Biosciences announced that it has been receiving royalty revenues from sales of human interferon alpha to BioVet, Inc., a Tokyo based animal health company. Manufactured by Amarillo Biosciences' longtime strategic partner Hayashibara Biochemical Laboratories (HBL), this interferon, known as Bimuron, is used to treat rotavirus in cattle. BioVet has been selling the Bimuron to veterinarians in Japan since September 2004 following Japanese regulatory approval that was announced July 16, 2004. Amarillo Biosciences owns the worldwide distribution rights outside of Japan to orally administered HBL interferon and receives a royalty on animal health sales in Japan.
Amarillo Biosciences, Inc. Receives Another SBIR Grant to Develop Vaccine and Oral Cytokine Therapy for Helicobacter Pylori
Helicobacter Pylori Is a Major Cause of Gastric Cancer
Amarillo Biosciences, Inc. (ABI) (OTC BB: AMAR) today announced that the Company has received a Small Business Innovative Research (SBIR) grant from the National Institutes of Health (NIH). The SBIR grant is for $104,372 and will be used by Amarillo Biosciences to further develop a vaccine to combat Helicobacter pylori (H. pylori), a major cause of gastritis and gastroduodenal ulcer disease in humans. Amarillo Biosciences will collaborate with Steven Krakowka, DVM, PhD of The Ohio State University.
H. pylori is a spiral-shaped bacterium that is found in the stomach of humans in which it causes more than 90% of duodenal ulcers and up to 80% of gastric ulcers. In developing countries, infection is frequently symptomatic and is thought to be responsible for the high incidence of gastric cancer in those areas. The cost and expense of pharmacological intervention is beyond the means of most of the world's population. A safe and effective vaccine, or affordable therapy could provide significant relief to the infected population.
Dr. Joseph M. Cummins, President and CEO of Amarillo Biosciences, Inc., said, "Data generated from our vaccine trials in swine will provide the basis for future studies in humans. We are excited to partner with Dr. Krakowka who has the expertise to make this a successful vaccine for a major disease worldwide."
"Preliminary data in the gnotobiotic piglet model of H. pylori are very encouraging," says Dr. Krakowka. "The piglet model was the first non-primate animal developed for this disease and is widely used in drug screening and efficacy trials. In this regard, the piglet, unlike rodents, is physiologically similar to humans. In a previous SBIR grant, we demonstrated that parenteral vaccinations with a nonliving and nontoxic H. pylori vaccine preparation prevented gastric colonization in 80% of challenged swine. In this application, we will extend these studies to explore the feasibility of using this vaccine for the prevention of recrudescence of the infection in swine treated with antimicrobial agents. In the developed world, medicinal treatment failures and re-appearance of the infection and gastritis after completion of therapeutic regimens are major complications of antimicrobial therapy. We have good preliminary evidence which suggests that orally administered interferons will prevent gastric colonization by this microbe. We are very excited about this opportunity to explore this phenomenon in greater detail," said Krakowka.
Under the terms of the SBIR grant, ABI will fund the research and development of a vaccine and an oral interferon cocktail formulation for use as an adjunct to antimicrobial therapies. If the Phase I work goes as expected, ABI will request a larger Phase II SBIR grant in 2006 to fund human trials.
Amarillo Biosciences, Inc. Announces Progress Report to Shareholders and Annual Meeting Agenda
Amarillo Biosciences, Inc. (ABI) (OTC BB: AMAR) announces that proxy material is being mailed to its approximately 1,400 shareholders of record as of April 7, 2005, regarding a shareholders' meeting to be held at 10 am CDT in the Colorado room at the Ambassador Hotel in Amarillo, Texas, on May 27, 2005. At that meeting, the Director of Clinical and Regulatory Affairs, Martin Cummins will discuss clinical trials to be conducted in 1) Southeast Asia on humans with influenza, 2) Texas on myeloproliferative diseases, and 3) Turkey on Behcet's disease. President and CEO, Joseph M. Cummins, will discuss relocation plans, license/partnership progress, funding strategy, personnel additions, and collaboration on agroterrorism, among other topics. Lorenz Lutherer, MD will review clinical data from the Company's study of patients with idiopathic pulmonary fibrosis.
Southeast Asia Avian Flu Study
The recent outbreak of the avian influenza, known as the H5N1 virus, has already killed millions of birds and more than 50 people in Southeast Asia. The World Health Organization (WHO) has warned that the epidemic in birds could spread to people causing a deadly flu pandemic. WHO predicts many millions of people could die from the next flu pandemic.
With associates from the state of Washington and an influenza expert from Australia, the Company plans to participate in a study of its interferon lozenges in humans with influenza caused by the deadly H5N1 virus in Southeast Asia. Previous clinical studies published by others from 1967-1987 indicated that low doses of interferon given intranasally or orally significantly reduced the illness rate and mortality due to influenza. Amarillo Biosciences intends to renew the study of interferon's safety and efficacy against influenza by testing oral interferon against the H5N1 virus.
Myeloproliferative Disease Study
The myeloproliferative disease study at a major cancer center in Texas is anticipated to launch in the Summer of 2005. The cancer center's Clinical Research Committee meets April 27, 2005, and the Institutional Review Board meets May 4, 2005. The myeloproliferative diseases to be studied are polycythemia vera and essential thrombocythemia, 20 patients each.
Behcet's Disease Study
Documents will be submitted to the Turkish government this quarter seeking permission to conduct a study on 90 patients with Behcet's disease. The Company will provide details about the study at the meeting. Nobel ILAC and the Company have agreed on a 12-week study design that will allow for evaluation of both initial response to interferon treatment as well as the durability of response.
Idiopathic Pulmonary Fibrosis Study
Clinical data from the Company's ongoing study of oral interferon therapy of idiopathic pulmonary fibrosis, a deadly lung disease, will be reviewed and plans for future studies will be discussed. The principal investigator, Lorenz Lutherer, MD from Texas Tech University Health Science Center, has been invited to the Company's annual shareholders' meeting to present the results of the study that has been underway for 3 years.
Foot-and-Mouth Disease
A study of oral interferon planned in Africa will be discussed. This study is expected to produce data that the Company believes will motivate the government to reconsider slaughter as a control measure for Foot-and-Mouth Disease (FMD). The virus that causes FMD is considered the number one threat to the nation's livestock industry.
BioVet Sales Royalties
Amarillo Biosciences has begun recognizing royalty revenues from sales of human interferon alpha to BioVet, Inc., a Tokyo based animal health company. Manufactured by Amarillo Biosciences' longtime strategic partner Hayashibara Biochemical Laboratories (HBL), this interferon, known as Bimuron, is used to treat rotavirus in cattle. BioVet has been selling the Bimuron to veterinarians in Japan since September 2004 following Japanese regulatory approval that was announced July 16, 2004. Amarillo Biosciences owns the worldwide distribution rights outside of Japan to orally administered HBL interferon and receives a royalty on Japanese sales.
Licensing Discussions
The Company expects to announce the results of ongoing license/partnership discussions. These discussions include Southeast Asia and other regions.
Amarillo Biosciences to Explore Financing Options to Fund Clinical Trials
At its Annual Meeting, Amarillo Biosciences will propose a financing strategy that would be used to fund clinical trials for human use. As a result, shareholders are being asked to increase the authorized number of shares of common stock from the current 20 million to 50 million. The Company has approximately 16 million shares currently outstanding and issued. The Company will remain vigilant about avoiding excessive dilution.
Management Changes
The Company's choice for CFO and another management position will be introduced. The Company's Board of Directors stands for re-election and shareholder approval is being sought.
About Amarillo Biosciences, Inc.
Amarillo Biosciences, Inc., is a U.S. biotechnology firm operating in global partnership with the Hayashibara Group, which also holds 20.5% of Amarillo Biosciences shares and has provided over $16.5 million in loans, grants and equity investments. The Company's primary focus is extensive and ongoing R&D into the use of low-dose, orally administered interferon as a treatment for a variety of conditions, including Sjogren's syndrome, Behçet's disease, and opportunistic infections in patients who are HIV positive. In its 20-year history, ABI has invested $37 million to establish oral interferon as a therapeutic agent. The overwhelming majority of those funds were invested in clinical trials in an effort to achieve FDA approval for interferon. Additional information is available on the ABI web site at http://www.amarbio.com/.
Except for the historical information contained herein, the matters discussed in this news release are forward-looking statements that involve risks and uncertainties, including uncertainties related to product development, uncertainties related to the need for regulatory and other government approvals, dependence on proprietary technology, uncertainty of market acceptance of oral interferon or the Company's other product candidates and other risks detailed from time to time in the Company's filings with the Securities and Exchange Commission. In particular, see "Item 1. Description of Business" of the Company's Form 10-KSB for the year ended December 31, 2003.
