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Safe Harbor & Data Presented Statements about the Company's future expectations, including statements about the potential use and scientific results for the Company's drug candidates, science and technology, and all other statements in this presentation other than historical facts, are "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934, and as that term is defined in the Private Securities Litigation Reform Act of 1995. The Company intends that such forward-looking statements be subject to the safe harbors created thereby. These future events may not occur as and when expected, if at all, and, together with the Company's business, are subject to various risks and uncertainties. The Company's actual results could differ materially from expected results as a result of a number of factors, including the uncertainties inherent in research and development collaborations, pre-clinical and clinical trials and product development programs (including, but not limited to the fact that future results or research and development efforts may prove less encouraging than current results or cause side effects not observed in current pre-clinical trials), the evaluation of potential opportunities, the level of corporate expenditures and monies available for further studies, capital market conditions, and others set forth in the Company's periodic report on Form 10-Q for the three months ended September 30, 2009 as filed with the Securities and Exchange Commission and report on Form 10-K for the year ended December 31, 2008 as filed with the Securities and Exchange Commission. There are no guarantees that any of the Company's proposed products will prove to be commercially successful. The Company undertakes no duty to update forward-looking statements. Data presented in this presentation may not be comprehensive; please contact ImmuneRegen for additional information.
Mission We are a biotechnology company, focused on advancing products that regenerate or strengthen the human immune system, in part, through stimulation of adult stem cells. We are working to capitalize on our drug candidates by continuing our own development programs and simultaneously seeking to license product use for specific indications to Industry partners. “ To be recognized for developing safe and effective therapeutics and for driving value through drug development programs that attract licensing and collaborative partnerships.”
Idiopathic Pulmonary Fibrosis Influenza Therapeutic Cancer Therapeutic Vaccine Adjuvant Biological and Chemical Agents Radiation Damage (Neutropenia) Wound Healing Oral Administration
Solid dosage form provides compounding flexibility
No additional devices needed for administration
Ships formulated for maximum stability, no liquid additions
Solid may preclude need for cold chain
May enable remote stockpiling
May provide environment-insensitive stability
Oral Bioavailability Study shows oral or intra-duodenal Homspera administration results in measurable and pharmacologically relevant plasma and pulmonary drug concentrations. Indications – Oral administration Potential Benefits of Oral Administration
(Arg Pro Lys Pro Gln Gln Phe Phe Sar Leu Met(O 2 ) -NH 2 ) Homspera ® vs. Substance P Homspera – NK-1 Receptor Specific Homspera NK-1R (neurokinin-1 receptor) Substance P NK-1R NK-3R NK-2R (Arg Pro Lys Pro Gln Gln Phe Phe Gly Leu Met -NH 2 )
Alberts, B. et al. (2002) Molecular Biology of the Cell (4 th ed.); Koon, H. et al. (2007) PNAS. 104:2013-2018; Koon, H. et al. (2006) J Immunology. 176:5050-5059; Yang, C et al. (2002) Cellular Signaling. 14:913-923; Koon, H. et al. (2005) J Pharmacology & Experimental Therapeutics. 314:1393-1400. Mechanism of Action Homspera®
Homspera - Resistant to enzymatic degradation Homspera ® vs. Substance P Homspera modifications Arg – Pro – Lys – Pro – Gln – Gln – Phe – Phe – Gly – Leu – Met – NH 2 1 2 3 4 5 6 7 8 9 10 11 Dipeptidyl peptidase IV Angiotensin converting enzyme Neprilysin Substance P endopeptidase Endothelin-converting enzyme - 1 Prolyl endopeptidase (E.C. 126.96.36.199) (E.C. 188.8.131.52) (E.C. 184.108.40.206) (E.C. 220.127.116.11) (E.C. 18.104.22.168)
Roosterman D et al. PNAS 2007;104:11838-11843 ECE-1 regulates NK1 recycling Homspera – Resistant to ECE-1 degradation
NK1-R links to MAPK and ERK1/2 (1) SP binding to the NK1R leads to recruitment of β -arrestin to the receptor, assembly of a MAPK signalosome, and ERK1/2 activation. (2) Degradation of SP by ECE-1 in acidified endosomes disrupts the SP/NK1R/arr/MAPK signalosome. (3) NK1R recycles to the plasma membrane for resensitization. (4) Inhibiting ECE-1 activity causes sustained ERK1/2 activation and SP-induced cell death. From Murphy JE, Padilla BE, Hasdemira B, Cottrell GS and Bunnett NW (2009) PNAS 106(42) 17615-17622 Endosomal ECE-1 regulates SP-induced ERK activation and cell death NK1-R internalization coupled to beta-arrestin scaffolding triggers kinase cascade. Substance P degradation recycles receptor/terminates signal. Homspera resistance to ECE-1 alters intracellular signal for discordant membrane / intra-cellular signals (published by others)
Mechanism of Action Summary of Underlying NK1-R Mechanisms
Increased hematopoietic progenitor cells from both the myeloid and lymphoid lineages
Direct stimulation of immune cells including macrophages and neutrophils AND antigen presenting cells
Augmentation of the innate immune response dependent upon the status of the local microenvironment
Direct stimulation of dermal fibroblasts, keratinocytes and epidermal cells
Distinct antagonist and intracellular activity profiles compared to SP
Image adapted from http://www.isscr.org/public/images/blood_fig_sm.jpg Cell Differentiation Primitive Stem Cell Specialized Cells Hematopoietic Stem Cell CFU-GEMM Common Lymphoid Progenitor Common Myeloid Progenitor Granulocytes Megakaryocyte Erythrocyte CFU-GM Platelets NK cell T cell B cell Macrophage Monocyte Adult Hematopoietic Stem Cells (HSCs)
Data collected by ImmuneRegen under contract with HemoGenix HSCs - Homspera stimulates progenitors Methodology: Colony forming assays were performed under both optimal and sub-optimal cytokine/growth factor conditions. The sub-optimal conditions were 1/50th the concentration of those considered optimal and were concentrations known to support stem cell growth and differentiation. Culturing the cells under sub-optimal growth conditions is an important control often used to examine a compound’s stimulatory effect on HSCs. If the cells in culture are already maximally stimulated (as they could be under optimal conditions), there is a reduced chance of detecting a compound’s stimulatory activity. Likewise, if an experimental compound merely substitutes for a deficient growth factor, it would only be effective under sub-optimal conditions. Therefore, it is useful to compare results under both conditions.
Data collected by ImmuneRegen under contract with University of Medicine and Dentistry of New Jersey Colony forming assays were performed under optimal cytokine/growth factor conditions. HSCs - Homspera stimulates progenitors
Increases stem cell differentiation into cells that are required to regenerate or strengthen the human immune system
Enhances production of the following precursors:
White blood cells
Red blood cells
Data collected by ImmuneRegen under contract with the University of Medicine and Dentistry, New Jersey (UMDNJ) and HemoGenix Adult Hematopoietic Stem Cells Homspera – Summary of effects
Radiation & Neutropenia Homspera Findings
Increased survival of small animals exposed to lethal radiation levels
Treatment is more effective after exposure to radiation
WBC numbers increase in treated animals
Data suggest Homspera could resolve the neutropenia often associated with chemotherapy drugs
Radiation studies performed by TD2 (dose-rate study and pre vs. post-exposure efficacy) and University of Arizona (survival)
Performed at the University of Arizona Radiation - Homspera findings Homspera promotes survival of lethally-irradiated animals Methodology: Sixteen male C57BL/6 mice (N=8 Homspera-treated and N=8 radiation-only controls) were given a single 7.75 Gy whole body dose of gamma radiation. The control group was administered saline daily via nebulizer for 15 min/day with treatment beginning within 2 hours of radiation exposure. The treatment group was administered Homspera, 50 µM solution, 15 min/day under the same conditions. Irradiated + Homspera Irradiated Control
Performed by TD2 Radiation - Homspera findings Homspera increases WBC counts following radiation Methodology: 72 Balb/c mice of age 5-6 weeks and normal physiological state (Taconic) were separated into 4 groups: Non-irradiated control (n=12), Irradiated control (n=20), Irradiated / Treated pre-exposure (n=20), and Irradiated / Treated post-exposure (n=20). On Day 1, animals were placed into the X-ray irradiator (RadSource 2000) for 4 minutes. Non-irradiated controls received no radiation exposure while the irradiated controls were exposed to radiation at the level of 1 Gy/minute. Animals were either treated with vehicle control or Homspera in vehicle control solution. The Non-irradiated control group and Irradiated control group were administered 25 μL of sterile saline intranasally daily for 7 days following radiation exposure. Animals treated with Homspera pre-radiation exposure were administered 25 μL of 300 μM solution intranasally 1-day prior to radiation exposure and daily thereafter for 7 days. Animals treated with Homspera post-radiation exposure were administered 25 μL of 300 μM solution intranasally daily for 7 days following radiation exposure.
Immune Activity - Mechanisms
Increases DC trafficking to skin-draining lymph nodes
Dramatic mobilization of Langerhans’ cells observed 24-hours post-treatment
Administration in conjunction with antigen results in the increased expression of CCL21/SLC, a DC chemoattractant, in lymphatic vessels
Rescues DC from undergoing apoptosis
DC apoptosis is an immuno-compromising effect often observed during viral infection such as infection with H5N1 influenza 1
Homspera-stimulated BMDCs found to have increased survival (95% compared to 63% in untreated animals) in vivo
Bone marrow-derived stem cells express NK1 receptors
NK1 receptor expression is upregulated by TLR agonists
Enhances humoral antibody responses
Increased antigen-specific antibody titers approximately 10-fold when administered prior to gene gun-delivered DNA antigen (Figure 1)
In another study intranasally-administered Homspera and antigen revealed a nearly 10-fold increase of serum antigen-specific antibodies compared to antigen-only controls
When administered intranasally while Ag was administered via IP, a 3-fold increase in serum antigen-specific antibody titers AND a 2.5-fold increase in heterotypic antibodies (H5N1-derived protein compared to H1N1-derived protein) was observed when compared to non-Homspera treated controls
Immune Activity Ag + Homspera Ag Control Figure 1
Survival determined 14 days after intranasal challenge with 1 x 10 6 EID50 of H5N1 virus. Increased antibodies correlate with increased survival Immune Activity
Survival correlates to 3-fold increases in both homotypic and heterotypic antibody levels observed in mice treated with Homspera intranasally and antigen intraperitoneally.
100 75 H5N1 Ag + H1N1 Ag 0 0 PBS 100 100 H5N1 Ag + H1N1 Ag + Homspera 100 100 H1N1 Ag + Homspera 33.3 100 H1N1 Ag 0 0 PBS + Homspera 100 100 H5N1 Ag + Homspera 100 100 H5N1 Ag H5N1 A/Indo/5/05 H5N1 A/VN/1203/04 Vaccine Group
Elevates CD4+ memory T-helper cell function
Enhanced delayed-type hypersensitivity (DTH) composed of statistically elevated numbers of CD4 + , CD8 + lymphocytes and macrophages to the vaccination site following epidermal application of vaccine antigen along with Homspera (Figure 2).
By augmenting both innate and humoral immunity, Homspera may also increase the antibody-dependent cell-mediated cytotoxicity effect, which limits and contains infection and controls tumor growth.
Figure 2 * indicates a p < 0.05 compared with the non-sensitized animals (naive). ** indicates p < 0.05 compared with immunizations alone at each time point. Immune Activity Control Ag Ag + Homspera Ag + NK1 antagonist
Increase the antigen-specific cytotoxic function on T-cells by in vivo killing assays (Figure 3).
Induction of a robust CTL response was also observed using a more aggressive immunization course, which involved one priming dose, and two booster doses. When this immunization scheme was employed Homspera was observed to increase specific cell killing to 92%.
P < 0.05 Immune Activity Figure 3 Ag Ag + Homspera
Augments innate immunity and cytokine expression
NK1R activation by Homspera signals through the NF-κB pathway.
Th1-biased immune response.
IFN- γ (Figure 4) , TNF- α, IL-1, IL-2, and GM-CSF production predominately influenced. NF- κ B also regulates the genes encoding the chemokines Interleukin-8 (IL-8) and macrophage inflammatory protein-1 α ( MIP-1 α) .
Splenic CD4+ T-cells Splenic CD8+ T-Cells Immune Activity Ag + Homspera Ag Control Ag + Homspera Ag Control
Reduction of virus particles in the lung and nose
Reduction of illness-related symptoms
Reduction of pathology
Increased survival of infected animals
Head-to-head greater efficacy than Tamiflu ®
Homspera reduces lung inflammation observed in mock-treated and Tamiflu-treated animals
Unlike Tamiflu®, Homspera reduces weight loss associated with influenza infection
Approximately 90% reduction of viral titers Influenza studies using a cotton rat model of seasonal influenza (Influenza A/Wuhan/359/95) were performed by Virion Systems, Inc. Influenza – Homspera findings Methodology: Young adult (6-8 weeks old) cotton rats ( Sigmodon Hispidus ) of both genders were obtained from an inbred colony maintained at Virion Systems, Inc. (Rockville, MD). A stock of Influenza/A/Wuhan/359/95 was prepared by Novavax, Inc. Animals were either treated intranasally with Homspera or vehicle 1 day before influenza infection OR given Homspera beginning 1 hour following influenza infection. Homspera treatment was continued daily for 10 days following infection. Homspera doses were equivalent 0.023mg/kg (10uM x 0.1mL), 0.23mg/kg (100uM x 0.1mL), Homspera 1.16mg/kg (500uM x 0.1mL).
Reduction of viral particles and abnormal cilia Influenza studies using a mouse model performed at University of Arizona Influenza – Homspera findings Infected control lungs show Influenza virions inside infected cells (left picture, arrow) and the lack of airway cilia in infected lung (right picture. single arrow) and stressed airway epithelial cell with numerous mitochondria (right picture, double arrows). Homspera treated lungs show normal ciliated epithelial cell (single arrow) and normal mitochondrial complement (double arrows).
Reduction of pulmonary inflammation Influenza studies using a cotton rat model of seasonal influenza (Influenza A/Wuhan/359/95) were performed by Virion Systems, Inc. Influenza – Homspera findings Methodology: Young adult (6-8 weeks old) cotton rats ( Sigmodon Hispidus ) of both genders were obtained from an inbred colony maintained at Virion Systems, Inc. A stock of Influenza/A/Wuhan/359/95 was prepared by Novavax, Inc. Animals were grouped into mock-treated / infected, oseltamivir (Tamiflu®) 10 mg/kg / infected, Homspera 0.23 mg/kg / infected, oseltamivir (Tamiflu®) 10 mg/kg + Homspera 0.23mg/kg / infected. Homspera was administered intranasally and oseltamivir solution was administered orally. Treatments commenced 1-day prior to infection. Lung were dissected and inflated, then assessed histologically. Parameters quantified on 0-4 severity scale: interstitial pneumonia (inflammatory cell infiltration and thickening of alveolar walls), and alveolitis (cells within the alveolar spaces), peribronchiolitis (inflammatory cells clustered around the periphery of small airways), perivasculitis (inflammatory cells clustered around the vesicles).
More significant reduction of weight loss than Tamiflu® Influenza studies using a cotton rat model of seasonal influenza (Influenza A/Wuhan/359/95) were performed by Virion Systems, Inc. Influenza – Homspera findings Methodology: Young adult (6-8 weeks old) cotton rats ( Sigmodon Hispidus ) of both genders were obtained from an inbred colony maintained at Virion Systems, Inc. A stock of Influenza/A/Wuhan/359/95 was prepared by Novavax, Inc. Animals were grouped into mock-treated / infected, oseltamivir (Tamiflu®) 10 mg/kg / infected, Homspera 0.23 mg/kg / infected. Homspera was administered intranasally and oseltamivir solution was administered orally. Treatments commenced 1-day prior to infection. Weights were measured daily.
More significant reduction of weight loss than Tamiflu® Influenza studies using a cotton rat model of seasonal influenza (Influenza A/Wuhan/359/95) were performed by Virion Systems, Inc. Influenza – Homspera findings Methodology: Young adult (6-8 weeks old) cotton rats (Sigmodon Hispidus) of both genders were obtained from an inbred colony maintained at Virion Systems, Inc. A stock of Influenza/A/Wuhan/359/95 was prepared by Novavax, Inc. Tamiflu® (oseltamivir, Roche Inc.) was obtained commercially. Animals were grouped into mock-treated / infected, oseltamivir (Tamiflu®) 2mg/kg / infected, Homspera 0.23mg/kg / infected, oseltamivir (Tamiflu®) 2mg/kg + Homspera 0.23mg/kg / infected. Homspera was administered intranasally and oseltamivir solution was administered orally. All treatments began approximately 1-hour following infection with Influenza/A/Wuhan/359/95. Homspera was administered once daily, whereas oseltamivir was administered twice daily, once in the morning and once in the evening. Treatment was continued daily for three days. Weights were measured daily.
Reduction of Tamiflu®-associated mortality Influenza studies using a cotton rat model of seasonal influenza (Influenza A/Wuhan/359/95) were performed by Virion Systems, Inc. Influenza – Homspera findings Methodology: Young adult (6-8 weeks old) cotton rats (Sigmodon Hispidus) of both genders were obtained from an inbred colony maintained at Virion Systems, Inc. A stock of Influenza/A/Wuhan/359/95 was prepared by Novavax, Inc. from supernatants of MDCK cells that had been inoculated 3 days previously at a low multiplicity of infection (m.o.i). Tamiflu® (oseltamivir, Roche Inc.) was obtained commercially. Animals were grouped into mock-treated / infected, oseltamivir (Tamiflu®) 2mg/kg / infected, oseltamivir (Tamiflu®) 2mg/kg + Homspera 0.23mg/kg / infected, Homspera 0.23mg/kg / infected. Homspera was administered intranasally and oseltamivir solution was administered orally. All treatments began approximately 1-hour following infection with Influenza/A/Wuhan/359/95. Homspera was administered once daily, whereas oseltamivir was administered twice daily, once in the morning and once in the evening. Treatment was continued daily for three days. p = 0.012 (Fisher’s Exact Test)
Influenza – H5N1 findings Increased survival – 60% greater than controls Influenza studies in Ferrets infected with H5N1 (A/Whooperswan/Mongolia/244/2005) were performed under contract with the University of Pittsburgh. Methodology: 20 young adult (20 weeks old) Fitch ferrets of both genders were inoculated with Influenza A/Whooperswan/Mongolia/244/2005 (H5N1) with 0, 10 3 or 10 5 plaque-forming units (PFU) on Day 0. Uninfected controls were treated with 2 mg/kg Homspera via intranasal administration beginning on Day 1 and continued daily thru Day 5. Animals infected with 10 3 PFU were split into 2 groups – 1 group received vehicle control treatment daily for 5 days, the other received 2 mg/kg Homspera treatment intranasally commencing 1 day after infection and continuing thru Day 5. Similarly, animals infected with 10 5 PFU were split into 2 groups – 1 group received vehicle control treatment daily for 5 days, the other received 2 mg/kg Homspera treatment intranasally commencing 1 day after infection and continuing thru Day 5. Homspera Homspera Homspera
Reduction in tumor metastases using well-established B16-lung metastasis model
63% reduction in metastases and 24% increase in survival in animals treated with Homspera for 7 days immediately following cancer cell injection.
97% reduction in metastases in animals treated with Homspera for 7 days beginning 7 days after cancer cell injection.
Human melanoma cells are not stimulated
A375 and A2058 cell lines were not stimulated following Homspera exposure.
Chemotherapeutic sensitivity is not affected
OVCAR-3 (human ovarian adenocarcinoma), SK-OV-3 (human ovarian adenocarcinoma), and MDA-MD-231 (human breast adenocarcinoma) sensitivity to chemotherapeutics was not affected by Homspera exposure.
Oncology - Homspera findings
Oncology - Homspera findings Figure 1: Homspera increases cellular immune responses, and reduces and delays the growth of melanoma in mice genetically immunized with GG encoding the melanoma self antigen, TRP2. Control groups include non-immunized mice and mice immunized with irrelevant transgenic Ag (luc-luciferase) and injected with B16/F0 malignant melanoma cells. Animals receiving Homspera and TRP2 antigen received either 1 or 2 doses. Naive WO 2009/129498 A2 (patent application) Picture of mice treated and sacrificed 22d after injection of B16 melanoma cells. Mice were genetically immunized with GG encoding the melanoma self-Ag TRP2 in the presence or absence of Homspera or the NK1R antagonist L733060 and injected with B16/F0 malignant melanoma cells. Data represents means 1SE of tumor area (mm 2 ) of 6 mice per experimental group. Both GG TRP2 plus Homspera treatments (1 or 2 doses) significantly inhibit tumor growth compared to GG encoding irrelevant Ag or TRP2 antigen in mice injected with B16/F0 cells (**p<0.0001). There was a significant inhibition on the tumor growth in mice treated with GG pCMV-TRP2 plus Homspera 2-times compared to 1-times (*p<0.01). No Vaccine GG - Luc GG – TRP2 GG – TRP2 + Homspera 2 doses GG – TRP2 + Homspera 1 dose GG – TRP2 + NK1 antagonist GG-Luc GG-TRP2 GG-TRP2 + Homspera (2 doses) Survival curve of mice genetically immunized as described. An indefinite survival of 45% and of 50% of mice injected either with one dose or with two doses of Homspera respectively. Data represents number of mice that survived out of 6 mice treated per experimental group. GG-TRP2 plus one or two doses of Homspera prolonged significantly the survival of mice compared to GG-TRP2 alone or with GG encoding irrelevant Ag and non-immunized mice injected with B16/F0 cells. Naïve Homspera GG-Luc GG-TRP2 GG-TRP2 + Homspera (1 dose) GG-TRP2 + Homspera (2 doses)
Accelerates wound healing in vivo
Increases proliferation of fibroblasts in vitro
Stimulates hematopoietic stem cell activity
Activates Dendritic cells and improves T-cell responses
Data collected by ImmuneRegen under contract with the following laboratories: MIR, HemoGenix, Bio-Quant Wound Healing – Homspera Findings
Methodology: Fibroblasts were seeded in a 96 well plate using IMDM (media) containing 0.5% FBS. Next day, these serum starved cells were treated with various amounts of Homspera or Homspera + antagonist-(Spantide I) for a period of 1 or 3 days. Cells were pretreated with Homspera in serum free media (0.5%FBS) for 3 hrs. Cells were then re-stimulated with serum (5%FBS) or not (0.5%FBS) while maintaining the presence of Homspera. MTT assays were performed after 1 and 3 days of treatment with test article. These results are indicative of two independent experiments. Results are represented as % growth where mean OD of each sample is normalized to its control. Wound Healing – Homspera Findings Homspera increases the proliferation of human dermal fibroblasts in vitro Performed at Johns Hopkins University
Performed at Bio-Quant Methodology: Two normal, female Yorkshire pigs three months in age, weighing 15-20 kg, were anesthetized and wounded. A total of 20 full-thickness wounds each with a 3 cm diameter were created on each pig using a scalper, 2 cm apart and 10 per side of the animal. 8 tattoo labels were made around surrounding the wound for measuring purposes. Pigs were observed daily for morbidity and toxic signs for 21 days after wound induction. Homspera (at 10 -4 M, 10 -6 M, 10 -8 M and 10 -10 M) and control (DPBS) articles were applied topically intra-wound. On each pig, 2 ml of Homspera at the test concentration or control solution was applied to fill the wound and covered it with saline-moistened (not wet) non-adherent Telfa gauze. Sterile techniques were performed as much as possible during the surgery to minimize the risk of infection on wound area. Dressings were changed every 5 days and Homspera was re-applied at each dressing change. Wound healing was evaluated by measuring the diameters of wound closure in 4 different directions on designated time point at Days 7, 10, 14, 17, 21, and 24 post-wounding. Wound Healing – Homspera Findings Homspera reduces healing wound area – pig model
Phases of Wound Healing Witte, M.B., Barbul, A. (1997) Surg Clin North Am . 77:509-528. Wound Healing Coagulation Inflammation Cell Migration / Proliferation Re-vascularization Epithelial growth Wound contraction Fibrous tissue growth Maturation
Substance P induces the proliferation of smooth muscle cells and dermal fibroblasts
Substance P stimulates keratinocyte proliferation and migration
Substance P stimulates, via NK1, endothelial cell mitogenesis and neovascularization, and the formation of vascular-like tubules in vivo
Topical application of Substance P significantly decreased wound areas on wound days 1, 2, 6, and 8
Exogenous administration of substance P enhances wound healing in a genetic diabetic mouse model
Substance P administration elicited a doubling in the rate of wound healing and was accompanied by vasodilation in aged rats
Exogenous administration of substance P increased the rate of healing in bisected rat medial collateral ligaments AND promoted an increase (nearly 3-fold) in the force-to-failure strength of healed ligaments
Literature references available upon request
Idiopathic Pulmonary Fibrosis (IPF)
Estimated 218,000 patients with IPF globally
Only 60% (or about 125,000) have been diagnosed
Enhanced diagnostics will lead to more diagnoses soon
Estimated $2B global market
Five-year survival rate of 20%
No FDA-approved therapies on market
InterMune has submitted NDA for Pirfenidone – March FDA review
Orphan Drug and Fast Track designation available
50% tax credit on clinical trials and 7 years market exclusivity
Idiopathic Pulmonary Fibrosis
Co-Principal Investigator: Center for Biophysical Assessment and Risk Management Following Irradiation (CBARMFI) – 1 of 8 national Centers for Medical Countermeasures Against Radiation (CMCRs) funded by NIAID
Expertise and publications:
Pulmonary effects of radiation exposure
Biomarkers of radiation exposure
Development of therapeutics to treat post-radiation exposure sequelae
Eight NIH funded
CBARMFI (U-19) funding
Professor of Pediatrics and Environmental Medicine and Radiation Oncology (University of Rochester) Development work supported by Dr. Jacob Finkelstein
Idiopathic Pulmonary Fibrosis
Homspera® prevents pulmonary injury in chemical-induction models
Biomarkers of IPF are critical
Animal models of pulmonary fibrosis are poor correlates of clinical efficacy
IPF Observations Homspera ® / NK1R effect Basal Substance P levels reduced NK1-agonist, like Substance P, may ameliorate fibrogenesis TGF-beta levels elevated and plays critical role in fibrogenesis Diminished TGF-beta production and potentially inhibition of TGF-beta Interleukin-1-alpha (IL-1a) levels elevated Diminished IL-1a production p53 levels elevated Diminished p53 production PARP levels elevated Diminished PARP production NO elevated and plays critical role in fibrogenesis Decreased secretion of iNOS Interleukin-4 (Th2 cytokine; increases TGF-beta) levels elevated Th1-biasing activity
The stimulatory effects observed on adult hematopoietic stem cells lead Management to believe Homspera regenerates and strengthens the immune system, thereby contributing to the effectiveness of treatment in the following indications: Hematopoietic stem cells Homspera stimulation Immune cell activation Increased survival and enhanced immune system
Idiopathic Pulmonary Fibrosis
Immune / Stem Cell Stimulant
Biological / Chemical Agents
Comparator Compounds and Companies Company Overview Recent Financial Data Drug Company Application Target / Relationship Stage / Value Neupogen Amgen Stem Cell Cytokines, G-CSF Approved Mozobil Genzyme Stem Cell CXCR4 NDA submitted QS-21 Antigenics Adjuvant Partnerships GSK: $2MM initial Elan: $1MM initial Acambis: $0.2MM initial Pirfenidone InterMune Idiopathic Pulmonary Fibrosis Anti-fibrotic mechanisms Pending Approval TLR agonists Coley Adjuvant Buyout Pfizer: $164MM Provenge Dendreon Cancer Vaccine Prostate Annual sales: $1B (est.) Ticker Symbol (OTCBB) IRBS Recent Price (Feb. 9, 2010) $0.35 52-Week Range $1.18 - $0.02 Shares Outstanding 13.1 million Market Capitalization $4.65 million Average Volume 33,000 (90-day) 17,500 (200-day) Public Market Float 6.6 million Insiders +5% Owners ~22% Institutional Ownership ~20%
Management Team Michael K. Wilhelm, Chief Executive Officer and Board Member Michael K. Wilhelm has been our President and Chief Executive Officer and a member of our Board of Directors since July 2003. Mr. Wilhelm has been President and Chief Executive Officer and a member of the Board of Directors since co-founding ImmuneRegen BioSciences, Inc., our wholly-owned subsidiary, in December 2002. Mr. Wilhelm has served as Managing Director of Foresight Capital Corporation since July 1996, a company he founded to consult and assist early-stage companies in furthering their growth and development. Mr. Wilhelm holds a Bachelors of Finance degree from SUNY Buffalo. John N. Fermanis, Chief Financial Officer Mr. Fermanis has served as our Chief Financial Officer since December 2004. From May 2001 to October 2004 Mr. Fermanis served as Chief Financial Officer of AMPS Wireless Data, Inc., a privately held Arizona corporation which he co-founded in 1998. From 1997 to 2001, Mr. Fermanis held the position of Treasury Manager for Peter Piper, Inc., a national restaurant chain headquartered in Scottsdale, Arizona. Mr. Fermanis has over 18 years of financial management experience with both the American Express Corporation and Citigroup in New York City. Mr. Fermanis holds a Bachelor of Arts degree from the S.U.N.Y. at Stony Brook and attended Pace University's Graduate School of Management in New York City. Hal Siegel, Ph.D., Chief Scientific Officer and Board Member Dr. Siegel has served on the Board of Directors since June 2006. Dr. Siegel was appointed as Chief Scientific Officer and Vice President in January 2008 after serving as our Senior Director of Product Development and Regulatory Affairs since June 2006. Prior to joining the company, Dr. Siegel served as Acting General Manager and Vice President Regulatory and Scientific Affairs for Zila Biotechnology, Inc. from 2004 to October 2006. In addition, since 2001, Dr. Siegel has provided consulting services for Siegel Consultancy LLC, which has been providing strategic and tactical expertise to life science companies, helping them meet FDA requirements from pre-clinical studies through the regulatory submission process and into the post-approval marketplace. Dr. Siegel holds degrees from Rensselaer Polytechnic Institute and SUNY Buffalo, where he earned his Ph.D., in Biochemical Pharmacology.
Theodore E. Staahl, M.D. Dr. Staahl has served on our Board of Directors since April 2003. Dr. Staahl is employed at the Cosmetic, Plastic and Reconstructive Surgery Center, a company which he founded in 1978. Dr. Staahl's professional training was received at the University of Illinois and the University of Wisconsin and is board certified by the American Board of Facial, Plastic and Reconstruction Surgeons, the Board of Cosmetic Surgeons and the American Board of Head and Neck Surgeons. Dr. Staahl has presented papers at national and international meetings on hair transplant, rhinoplasty and cleft lip deformities. Robert J. Hariri, M.D., Ph.D. Dr. Hariri, M.D. has served on our Board of Directors since April 2007. Dr. Hariri has been CEO of Celgene Cellular Therapeutics, a division of Celgene, since 2005. Previously, he had been President of the division from 2002 to 2005. The division focuses on human stem and biomaterial solutions for a range of clinical indications. From 1998 to 2002, prior to joining Celgene Cellular Therapeutics, Dr. Hariri was Founder, Chairman and Chief Scientific Officer for Anthrogenesis Corp./LIFEBANK, Inc., a New Jersey-based privately held biomedical technology and service corporation involved in umbilical cord blood banking and its supporting technology platform. From 1987 to 1994, he was Co-founder, Vice Chairman and Chief Scientific Officer of Neurodynamics, a privately held medical device and technology corporation. Dr. Hariri has held academic positions at Cornell University Medical College Cornell University Graduate School of Medical Sciences. He has also played a prominent medical role at Cornell University Medical College, The New York Hospital-Cornell Medical Center and The Jamaica Hospital-Cornell Trauma Center. While at Cornell, he was the Director of The Center for Trauma Research. He received his Medical Degree and Ph.D. from Cornell University and was awarded a Bachelor of Arts Degree from Columbia College. Jerome B. Zeldis, M.D., Ph.D. Dr. Zeldis has served on our Board of Directors since November 2007. Dr. Zeldis currently serves as Chief Medical Officer of Celgene Corporation, Warren N.J., a position he has held since 1997. He is also currently, and since 2003, Professor of Clinical Medicine at the Robert Wood Johnson Medical School in New Brunswick, N.J. Prior to working at Celgene, Dr. Zeldis worked at Sandoz Research Institute from 1994 to 1995 and Janssen Research Institute from 1995 to 1997 in both clinical research and medical development. He has been a Board member of a few start-up biotechnology companies and is currently on the Board of the Semorex Corporation, the N.J. Chapter of the Arthritis Foundation, and the Castleman’s Disease Organization. Outside Board Members Lance K. Gordon, Ph.D. Dr. Gordon has served on our Board of Directors since May 2007. He currently serves as President and CEO of ImmunoBiologics Corporation, a formative biotechnology company that he founded in 2007. Prior to his work at ImmunoBiologics Corporation Dr. Gordon served as President, Chief Executive Officer and as a Director of VaxGen, Inc. from 2001 to 2007. Prior to joining VaxGen, Dr. Gordon was Executive Director of North America for Acambis plc. and a member of the Company’s Board of Directors from 1999 to 2001. Previously, he served as President and CEO of OraVax, Inc. from 1990 to 1999, prior to its acquisition by Peptide Therapeutics to form Acambis. Before joining OraVax, he served as the CEO of North American Vaccine from 1988 to 1990, prior to its acquisition by Baxter International. Dr. Gordon received his Ph.D. in Biomedical Science, Immunology from the University of Connecticut and completed his postdoctoral fellowship as an NIH fellow at the Division of Allergy and Immunology, Washington University Medical School, St. Louis. He currently serves on the DHHS National Vaccines Advisory Committee and on the Board of Trustees of the Sabin Vaccine Institute.
Scientific Advisory Board John Dann, M.D., D.D.S., Graduate of Harvard University Dental School and Washington University Medical School, Board Certified maxillofacial and craniofacial surgeon. Jacob Finkelstein, Ph.D., a professor in the departments of Pediatrics, Radiation Oncology and Environmental Medicine at the University of Rochester Medical School, recognized for investigations into the effects of radiation on cells and functions of the lung. Jeffrey Friedman, M.D., Diplomat, American Board of Cosmetic Surgery, American Board of Otolaryngology Head and Neck Surgery, Fellow of the American Academy of Cosmetic Surgery. Adriana T. Larregina, M.D., Ph.D., University of Pittsburgh School of Medicine faculty member of the Dermatology and Immunology departments and director of Cutaneous Biology Laboratories and Education, published extensively on the role dendritic cells and their precursors play in stimulating immune responses. Susan E. Leeman, Ph.D, Professor in the Department of Pharmacology and Experimental Therapeutics at the Boston University School of Medicine. One of the first scientists to isolate substance P in the central nervous and gastrointestinal systems. She was elected to the National Academy of Sciences in 1991. K.A. Kelly McQueen, M.D., M.P.H., Anesthesiologist and Public Health Consultant; Infectious Disease and Disaster Planning for U.S. Army and US Northern Combatant Command. Pranela Rameshwar, Ph.D., Professor in the Department of Medicine, Division of Hematology/Oncology at the University of Medicine and Dentistry of New Jersey; research areas include Substance P, stem cells and cancer. Ivan Rich, Ph.D., CEO and founder of HemoGenix, a biotechnology company focused on the development of 21 st century stem cell assays.
Eight issued U.S. and foreign patents
At least 67 pending patent applications including:
16 pending U.S. utility patent applications
2 pending U.S. provisional applications
7 pending international patent applications
41 pending foreign patent applications
Recent Events January 27, 2010 - National Cancer Institute Initiates Studies on ImmuneRegen BioSciences' Vaccine Adjuvant Candidate January 5, 2010 - ImmuneRegen BioSciences(R) Reports Additional Positive Results From Study of Homspera(R) in Treating Highly Pathogenic Influenza December 14, 2009 - ImmuneRegen BioSciences'(R) Drug Candidate Homspera Confirms Efficacy as Cancer Vaccine Adjuvant November 10, 2009 - ImmuneRegen reports Homspera improves survival and reduces symptoms of highly lethal influenza virus infection without any additional treatment October 22, 2009 - ImmuneRegen to further Homspera research in U.S. Government funded study on reducing the detrimental effects of radiation on lung immune system function October 12, 2009 - ImmuneRegen initiates Homspera studies against global influenza threat by performing studies for efficacy against highly lethal H5N1 Avian Influenza and to further define the adjuvant efficacy when coupled with a novel vaccine for H5N1 September 22, 2009 - ImmuneRegen enters into a partnership with Bachem, Inc., for manufacturing of Homspera