The World Leader in Oral Interferon Company Overview December 2012

Transcription

1 OTCBB:AMAR The World Leader in Oral Interferon Company Overview December 2012 Phone: Web: 1

2 Company Overview Specialty Pharmaceutical & Nutraceutical Company Low-dose interferon-alpha (IFNα) with patented oral delivery Systemic benefits without the side effects Strategic focus on treating thrombocytopenia Partner funding hepatitis C and influenza research in Taiwan Maxisal - dietary supplement for dry mouth symptoms Dry mouth affects 25 million Americans. 2

3 Product Overview Pharmaceutical and Nutraceutical Products Pharmaceutical Product: Low-dose interferon-alpha (IFNα) Convenient, low-cost, stable formulation: orally dissolving lozenges Systemic benefits of IFNα without side effects Mechanism of action: upregulation of IFN-stimulated genes Strategic focus on treating thrombocytopenia Proof-of-concept study planned for launch in 2013 Product has application in drug-related causes of thrombocytopenia, like chemotherapy and high-dose injectable IFN-alpha. Provisional US patent application filed in March 2012 Partner company funding hepatitis C and influenza research in Taiwan Completed Phase 2 study showed reduction in relapse rate in HCV patients with mild fibrosis and improvement in peg-ifn-induced thrombocytopenia Results from a Phase 2 study of oral IFN plus Tamiflu vs. Tamiflu alone are expected in early 2013 Dietary Supplement: Maxisal tablets - Relief of dry mouth symptoms 3

4 Product Overview Patented Oral Delivery of Interferon-alpha* VELDONA (Very Low Dose Oral Natural Alpha) IFNα lozenges are stable at room temperature for 2 years & for 5+ years under refrigeration. *US patent number 6,372,218 B1 issued to ABI covers solid oral dose forms of IFNα up to 1500 IU per dose. This patent will remain in effect until April 16,

5 Product Overview Comparison of Oral IFN to Injectable Competitors Comparison Oral Injectable Dose Up to 500 units Up to 10,000,000 units Side Effects Rare/Mild Common/severe Treatment Cost Cost Effective Expensive Administration Lozenges Needle/syringe Stability Stable room temp Refrigeration Required Production Natural Recombinant 5

6 Product Overview What is Interferon? Frequently Asked Questions A group of small proteins induced in vertebrate cells in response to viruses, bacteria & protozoa What is an international unit (IU) of interferon? One IU of interferon inhibits 50% of the virus in test system. What is the specific activity of interferon alpha? At least 2x10 8 IU/mg of protein How much interferon is produced naturally in people? Nanograms, or IU, not millions of IU Is Interferon effective when given orally? Yes, receptors for interferon exist in the oral cavity. Yes, systemic biological effects (gene up-regulation) can be demonstrated after oral administration. 6

7 Product Overview Mechanism of Action of Low Dose Oral IFNα Activation of Humoral Immunity (Antibody) Tonsil Mandibular Lymph Nodes Virus Oral Epithelial Cells Activation of Perioral Lymphoid Cells and Peripheral Lymphoid Tissues IFNα Activation of Cell Mediated Immunity Interferon placed in the mouth binds to receptors in the mucosal lining and initiates systemic effects on the immune system in animals and man. These immunomodulatory effects are safe and effective in helping control viral and autoimmune diseases as well as cancer. Low-dose oral IFNα has been shown to induce significant systemic immunologic effects: upregulation of IFN-gamma induction of Th1 cytokines modulation of mature T and B cell activities increases in NK cell activity clonal expansion and survival of CD8+ T cells upregulation of hundreds of IFN-stimulated genes 7

8 Oral Interferon Recent Clinical Findings Hepatitis C Virus (HCV) Infection Phase 2 study of 169 HCV patients completed in Taiwan. Double-blind, placebo-controlled trial: 2 active doses vs. placebo All subjects treated with peg-ifn plus Ribavirin, and were HCV negative at study start. Aim was prevention of relapse at 1 year post-treatment. Study treatment was given daily for 24 weeks, followed by 24 weeks of untreated observation to check for relapse through week 48. Significant clinical findings announced June 2012 Trend toward a reduced relapse rate was seen in the once daily IFN group, compared to placebo, among HCV patients with mild fibrosis (14% vs. 32%). Greater rate of platelet count normalization in the once daily IFN group, compared to placebo, among HCV patients with peg-ifn-induced thrombocytopenia (81% vs. 42%, P<0.005). ABI filed a provisional US patent on treatment of thrombocytopenia in May

9 Oral Interferon for Thrombocytopenia Treatment of Thrombocytopenia in HCV Patients Normalization of Platelets 90.0% 80.0% 70.0% 60.0% 50.0% 40.0% 30.0% 20.0% 10.0% 0.0% * placebo (n=31) 500 IU (n=21) 1500 IU (n=24) Percentage of subjects in the normal range at study end. All subjects had a low baseline platelet count. *Significantly greater than placebo at P<

10 Oral Interferon for Thrombocytopenia Development Plan and Market Phase 2 study of 200 patients completing chemotherapy Cancer patients with chemotherapy-induced thrombocytopenia Double-blind, randomized treatment trial: 500 IU/day vs. placebo Aim is normalization of suppressed platelet counts. Treatment time is 12 weeks; total study duration = 12 months. Positive results will allow ABI to raise money or attract a big Pharma partner to fund Phase 3 clinical development. Chemotherapy-Induced Thrombocytopenia (CIT) CIT affects up to 80% of cancer patients given certain treatment regimens. Overall, 20% of newly treated cancer patients experience CIT. At it s peak, CIT represents an annual market in excess of $400 million. 10

11 Clinical Indication: Influenza Evidence that Oral Interferon can Prevent Influenza Oral or intra-nasal delivery of low-dose IFN reduced the incidence of infection and/or the severity of human flu in studies conducted in Japan, Bulgaria, China and Russia. Oral interferon protected mice from a fatal infection of mouseadapted flu virus. It has been reported that intra-nasal interferon suppresses flu in ferrets & guinea pigs. A Phase 2 study in Australia demonstrated safety and efficacy of ABI s IFN-alpha lozenges when administered prophylactically in reducing the severity of respiratory illness (colds and flu) in healthy volunteers. 11

12 Oral Interferon Reduces the Severity of Influenza 14,000 people participated in controlled studies of placebo versus interferon treatment during a natural outbreak of Hong Kong influenza. Interferon (about 128 units) or placebo was dripped into the nose daily for 5 days starting about the time of the first reported influenza cases. Interferon significantly (P<0.01) reduced the number of influenza cases. 25 Efficacy of Human Leukocyte Interferon as Prophylaxis Against Influenza Percent of Patients Sick Interferon Placebo 0 Adults Children 7-12 yr Children 2-6 yr Population (14,000 subjects total) Soloviev, Bull. WHO 41: ,

13 Oral Interferon Protects Mice from Influenza Body weight of C57BL/6J mice treated with IFN α A daily and infected with mouse adapted influenza A/PR/8/34 H1N1 at day weight (g) * p< IU IFN/dose 1 IU IFN/dose 10 IU IFN/dose 100 IU/dose 15 p< p< days post infection Mice given oral IFN at 100 IU/day had significantly less weight loss, compared to lower IFN doses and placebo. Mice in the 100 IU group all survived, while mice in the other groups were euthanized due to extreme weight loss. Beliharz M et al., Biochem Biophys Res Commun 335:740-44,

14 Clinical Indication: Influenza Phase 2 Prophylaxis Study Completed in Australia Results to be published in Influenza and Other Respiratory Viruses in volunteers in double-blind, placebo-controlled study Once/day treatment for 16 weeks during cold/flu season Subjects reported severity of 13 cold/flu symptoms weekly IFN prophylaxis was effective at: reducing influenza-like illness (ILI) rate, particularly in older subjects and those vaccinated against influenza reducing symptom severity in IFN subjects with a confirmed respiratory virus infection reducing mod/severe febrile acute respiratory illness IFN treatment was safe with no increase in side effect incidence or severity, compared to placebo. 14

15 Influenza Phase 2 Study Results Influenza-like Illness (ILL) Rates in Age/Vaccination Sub-groups Percentage of Subjects Reporting ILI During Treatment 80% 70% 60% 50% 40% 30% 20% 10% 0% p=0.83 p=0.15 p=0.50 p=0.002 age 50/none age 50/Fluvax age <50/none age <50/Fluvax Subject Age/Vaccine Status placebo (n=26/20/22/17) IFN (n=27/20/35/17) Older, vaccinated subjects in the IFN group reported ILL significantly less often than such subjects in the placebo group. 15

16 Influenza Phase 2 Study Results Symptom Incidence in Subjects with a Confirmed Viral Infection Percentage of Subjects Reporting Moderate/Severe Symptoms 70% 60% 50% 40% 30% 20% 10% 0% body ache chest congestion chills p<0.05 p<0.10 p<0.05 p<0.10 p<0.05 p<0.10 cough feverishness headache head congestion hoarseness plugged nose runny nose scratchy throat p<0.10 sneezing sore throat placebo (n=12) IFN (n=15) Subjects in the IFN group with a confirmed viral respiratory infection reported many cold/flu symptoms with lower frequency, compared to such subjects in the placebo group. 16

17 Influenza Phase 2 Study Results Febrile vs. Non-febrile Acute Respiratory Illness The incidence of moderate to severe acute febrile respiratory illness was significantly reduced in the IFN group, compared to the placebo group. 17

18 Clinical Indication: Influenza Phase 2 Treatment Study Ongoing in Taiwan Study funded/conducted by ABI licensee CytoPharm, Inc. 40 subjects during 2011/12 flu season in Taiwan Subjects with fever and at least one respiratory and one constitutional symptom of influenza infection 150 IU IFNα lozenges vs. placebo (bid for 5 days) All subjects will also receive Tamiflu. Does Tamiflu + oral IFN reduce duration of fever and symptoms compared to Tamiflu alone? Study results expected in early

19 Hepatitis C: a Global Pandemic 19

20 Oral Interferon for Hepatitis C Oral Interferon for Prevention of Relapse in HCV High-dose injectable interferon plus oral ribavirin is the standard of care for HCV infection, but the regimen has significant side effects and relapse is common. Oral interferon treatment is free from side effects and has been shown to up-regulate many genes that are important for host control of the hepatitis C virus. Oral interferon was found to eliminate HCV replication in 50% of treated patients, compared to 0% of the controls in a preliminary dose-ranging study. (Vitapharm Research, internal report) 20

21 Oral Interferon for Hepatitis C Dose-Ranging Pilot Study of Oral IFN for Hepatitis C 60 50% % Sero-conversion % 11% 19% 20% 10% HCV-RNA Anti-HCV 0 0% 0% 100 IU 200 IU 400 IU placebo HCV RNA became undetectable in the serum of 5/10 HCV patients given oral interferon at 400 IU per day, compared to 0/9 HCV patients given placebo. 21

22 Oral Interferon for Hepatitis C Hepatitis C Virus (HCV) Infection Phase 2 study of 169 HCV patients completed in Taiwan. Double-blind, placebo-controlled trial: 2 active doses vs. placebo Aim was prevention of relapse in HCV patients. All subjects previously treated with peg-ifn and Ribavirin and were free from detectable HCV at study start. Treatment was given daily for 24 weeks, followed by 24 weeks of untreated observation to check for relapse. Funding by ABI s Taiwanese licensee CytoPharm. Significant clinical findings announced in June 2012 Trend toward a reduced relapse rate was seen in the once daily IFN group, compared to placebo, among HCV patients with mild fibrosis (14% vs. 32%). Greater rate of platelet count normalization in the once daily IFN group, compared to placebo, among the 60% of study subjects with peg-ifn-induced thrombocytopenia at baseline (81% vs. 42%, P<0.005). 22

23 Maxisal Maxisal is a dietary supplement, which: Promotes oral comfort Helps promote normal salivary function Enhances salivary function Helps relieve dry mouth associated with aging, and Increases oral comfort of fluid restricted individuals. 23

24 Maxisal Dry mouth represents a substantial medical problem: Reports indicate that 20% of people over the age of 50 suffer from dry mouth. At least 25 million people in the U.S. experience some form of dry mouth. Dry mouth can cause serious health problems such as: Oral infections Tooth decay Bad breath Altered taste sensation Difficulty in chewing, swallowing, and speaking 24

25 Maxisal Maxisal Clinical Research: Maxisal lozenges were given three times daily for 24 weeks to 97 patients with primary Sjögren s syndrome in one study and 100 Sjögren s syndrome patients in a second study. (J Altern Complement Med 2001 & 2002) Mouth comfort was significantly increased and symptoms of dry mouth and dry throat were significantly improved after just 6 weeks of Maxisal. Nearly 40% of the patients who finished the study had a clinically important (>50%) increase in salivary output after taking Maxisal. 25

26 Maxisal Average Mouth Dryness Scores (mm) Combined Results from 2 Sjogren's Studies * Week 0 Week 6 Week 12 Week 18 Week 24 *p<0.001 **p< ** ** ** 26