The Company’s Projects
Plant Growth Hormones
- Actinogen completed initial pot trials in 2011 on a series of actinomycetes that produce plant growth hormones
- The pot trials, which were conducted in 2010 and 2011 showed significant increased root growth and leaf and stem growth (Actinogen AGM Presentations 2011 and 2012).
- Independent pot trials have been set up to begin tomorrow and will test the ability of the growth hormones to increase the root, leaf and stem growth of wheat and peas.
- The independent trials are being run for approximately six to seven weeks and results should be available at that time.
Actinogen Limited (“Actinogen”, ASX:ACW), has discovered actinomycetes that produce plant growth hormones. Actinogen tested the growth hormones in pot trials and recorded significant extra root and leaf growth in broad bean plants (Actinogen Annual Report 2012 page 9 and Actinogen AGM Presentation 2012).
Actinogen is pleased to announce that independent trials have been set up in order to further test the performance of the growth hormones. Pot trials at an independent laboratory have been set up for the trials to begin tomorrow.
The trials will test the effectiveness of the growth hormones on wheat and peas. The trials will be conducted in controlled greenhouses and measure the amount of root, leaf and stem growth. The results of the trials will be available in approximately six to seven weeks.
Actinogen will keep the market fully informed of all developments in relation to the growth hormone trials.
Actinogen Limited (“Actinogen”, ASX:ACW), has discovered a series of actinomycetes that can produce Shikimic acid. Shikimic acid is a main component used in the production of Tamiflu that has on occasion been in short supply globally.The production of Tamiflu is complex and one of the most expensive components is Shikimic acid.
Tamiflu is an oral antiviral treatment that can significantly reduce an influenza virus from spreading inside the human body, if taken within 48 hours of the onset of influenza symptoms. In the event of a pandemic, Tamiflu will be in major demand and will continue to be so globally for use in treating influenza and will be in particular demand in the foreseeable future. In 2006 and 2007, the H1N1 avian influenza became a global concern. The World Health Organization recommends treatment with antiviral drugs within the first 48 hours of symptoms appearing, however at the time, there was a shortage of Tamiflu as governments around the world attempted to stockpile the drug. The H1N1 virus remains a global concern, as do other strains of the influenza virus.
Currently, Shikimic acid is mainly produced from the star anise fruit and from a fermentation process using an Escherichia-coli bacterium. The star anise tree only grows under certain climate conditions (humid, hot weather and high altitude) and takes 6 years to mature.The Shikimic acid is then extracted from the pods of the star anise. Thirty kilograms of star anise is required to produce approximately one kilogram of Shikimic acid.
Actinogen is producing Shikimic acid from actinomycetes grown at room temperature in aerobic conditions. As the threat of a global influenza pandemic continues to be a real possibility, Actinogen is focusing on developing their process in order to produce Shikimic acid in commercial quantities for use in antiviral drugs.
Actinogen is now looking for partners to help develop this process and will keep the market fully informed of all developments as they occur.
On 9 November 2011, the Company announced that it can produce cellulase(s) from actinomycetes that can break down cellulose from plant materials, newspaper or industrial waste glycerol. Cellulase(s) are an important step in the production of second generation bio-ethanols. Second generation bio-ethanols use waste or plantation plant material (such as sedge grass), straw or paper wastes to make motor fuel. Unlike some other methods that use oils, sugars and costly foodstuffs as a feedstock. Thus Actinogen’s process can be potentially much cheaper and not use dwindling food stocks that populations can need. This traditional method of producing cellulase(s) is usually performed in an anaerobic environment at high temperatures, which is usually costly. The Company can produce cellulase(s) in an aerobic environment at room temperature, which can potentially be lower cost.
Actinogen has received samples of waste glycerol from a biodiesel plant and has begun testing these samples to produce cellulase(s). After this, the Company plans to construct a test pilot plant to produce glucose and other sugars. Glucose and some other sugars are used to make bio-ethanol in a simple distillation process. Once the Company can produce glucose and other sugars from waste glycerol and waste plant material then it is relatively simple to convert the sugars into bioethanol.
Reasons why we expect that Actinogen will soon have the ability to make motor fuel (bio-ethanol) cheaper at the pump and produce profits for the Company (subject to final feasibility studies, provisional patent lodged):
- Actinogen’s ability to produce cellulase(s) has been confirmed in scale at fermentation trials by CSIRO. Samples of the cellulases produced during the CSIRO proving have been compared to two commercially available preparations and all Actinogen’s preparations have been shown to be more active using a well diffusion assay.
- CSIRO has completed independent tests on Actinogen’s method of producing cellulase(s) and has confirmed that Actinogen can produce cellulase(s) in volumes of up to at least 10 litres.
- Actinogen is now doing tests with an actinomycetes that produces lignase that can break down the woody stems of plants similar to cellulase that breaks down cellulose materials in plants, material or paper.
- Some industrial plants around the world have a problem with excess waste glycerol. Actinogen’s process can use this waste glycerol and other cheap materials to produce cellulase(s) which are usually costly to produce. Cellulase(s) are enzymes that break down cellulose materials. The have traditionally been a very large fraction of the cost of bio-ethanol production from cheap forest waste and grassy materials. Cellulase(s) which are produced from Actinogen’s method are potentially much cheaper to produce and can potentially cut the cost of commercial bio-ethanol production by a great deal.
This “green” industry will not be required to pay carbon tax and Actinogen may be able to apply for the current government subsidy of 38.14 cents per litre of bio-ethanol produced. (As well as other government grants and subsidies that are or become available).
The government subsidy is a grant from the Federal Government. They are currently offering a grant under the Ethanol Production Grants program where grants are payable to ethanol producers at a rate of 38.143 cents per litre for eligible ethanol. The Company is currently investigating other possible government grants.
Actinogen has engaged Dr Karne De Boer, a renewable energy engineer, to produce an independent report which outlines recommendations for developing Actinogen’s research into a commercial bioethanol plant. Dr De Boer has recommended that the Company conduct further bench top trials to optimize the plans for construction of a test pilot plant. The Company intends to use funds from the rights issue to implement these recommendations with the end goal of producing bio-ethanol in large scale commercial quantities.
Recently Actinogen has acquired Celgenics, a company advanced in the research on Cancer Stem Cells. Current theory suggests that Cancer tumours may contain a tiny proportion of Cancer Stem Cells and that they may be resistant to current chemotherapy. Cancer Stem Cells may remain after primary chemotherapy and subsequently replicate to give rise to fatal secondary cancer development.
Actinogen plans to search its extensive Actinomycetes libraries and elsewhere for new agents that may specifically kill or inhibit Cancer Stem Cells that may remain inside the human body and could develop into secondary cancer tumours, after chemotherapy has killed the cancer cells
Actinogen has an ongoing series of screening programmes designed to discover new bioactive anti cancer molecules produced by actinomycetes isolated, mainly, from soil in Western Australia.
The basic programme screens the supernatants from liquid cultures of the actinomycetes for the presence of bioactive molecules that are either cytotoxic or cytostatic for a series of cell lines derived from various human and animal cancers.
The cell lines used are representative of human epithelial adenocarcinoma of the cervix, human epithelial carcinoma of the lung, murine melanoma (to be replaced over 2012 by a human derived melanoma cell line), murine neoplastic subcutaneous fibroblast (to be replaced over 2012 with a human fibroblast cell line.
Secondary screening begins to determine the mode of action of positive supernatants that can induce cell death by simple cell necrosis or via apoptosis, or cell suicide. Concurrently HPLC analyses of the active supernatants are compared to Actinogen’s chemical compound library to determine whether or not the preparations contain previously discovered or currently used anti cancer molecules as well as other compounds.
Recently Actinogen has acquired Celgenics, a company dedicated to search for bioactive molecules directed towards a specialized group of cancer cells thought to be derived from adult stem cells and known as Cancer Stem Cells (CSC). Actinogen’s cancer screening programme is to be expanded to incorporate cancer cell lines( a human epithelial glioblastoma and a human glioblastoma- astrocytoma) believed to express on their surface the CD 133 stem cell epitope. The CSC cells are detected using tests that locate the so called CD 133 marker which is considered to be a definitive marker for the CSC.
Current dogma suggests that human tumours may contain a small proportion of CSC (2%) and that these cells may be resistant to currently used chemotherapeutic agents. It is these cells that may remain after primary chemotherapy and subsequently replicate to give rise to often fatal secondary cancer development.
There is a need to find new agents that can specifically kill these CSC thus providing another step forward for the control through bioactive molecules that may be specifically directed towards the killing of the CSC and also to pin-point the stage of the cell cycle that the bioactive molecules are directed against.
Furthermore through an agreement with Celgenics and the Human Ethics Committee of the Sir Charles Gairdner Hospital, Actinogen now has access to human tumour material, if it wishes.
There has been a recent development in fluorescent based equipment that is geared to powerful integrative automated image cytometry. This equipment performs rapid cell analyses for up to four channels simultaneously and provides a wide range of information on cell viabilities, cell cycle analyses, modes of cell death including detailed analyses of apoptosis or suicidal cell death.
Using computer based integrative software detailed analyses of cell cycles can determine at which stage of the cycle a bioactive molecule, such as that found in actinomycetes, has induced cell death or a cytostatic response.
The machine performs the tests very rapidly often down to a few seconds, thus it should increase Actinogen’s throughput for all its cell lines.
The equipment can also be used to detect the CSC- CD 133 marker. This will allow studies to be carried out specifically on these cells in a mixed culture by gating processes to favour these cells.
It will also allow Actinogen to study the dynamics of the presentation of the CD 133 marker at the cell surface during the course of the cell cycle under normal circumstances and under chemotoxic stress.
It is anticipated that results forthcoming from this major development in the R&D capabilities of Actinogen’s cancer screening programe, will enable it to not only rapidly gain information in its general screening programme but will also provide a major input to the discovery of actinomycete bio-active molecules directed specifically to the CSC.
Actinogen intends to use part of the funds raised in the rights issue for the purchase of this machine which it considers will provide a major boost to its anti cancer screening programme.
Actinogen runs a major screening program designed to discover new soil actinomycetes that synthesize bacterial antibiotics. Actinogen is advanced in its research of antibiotics directed against the Methicillin resistant Staphloccus aureus (golden Staph) [MRSA] and new antibiotics directed against the anaerobic gut pathogen, Clostridium difficile. Actinogen has discovered a small number of actinomycetes that produce antibiotic activity directed against Clostridium difficile but which do not kill normal gut flora in vitro. There is believed to be a pressing world shortage of such new antibiotics.
The details of the Offer of New Shares are described in this Prospectus. You should have received a personalised Entitlement and Acceptance Application Form with this Prospectus, but if you are in any doubt, please contact the Company’s Share Registry.
Please note that the Closing Date for acceptances is 5.00 pm WST on 24 April 2012. If you wish to participate in this Rights Issue of New Shares and New Options it is essential that your Completed Entitlement and Acceptance Application Form reaches the Company’s Share Registry by this time.
If you have any questions or queries regarding the details contained in this document, please contact your financial adviser or our Company Secretary, Mr Suraj Sanghani, on (08) 9225 4815.
Actinogen has recently discovered a completely new way to produce pure Anacardic Acid, currently offered by others for sale at around $1,000.00 per gram!
Anacardic Acid has many varied uses such as in anti-corrosives and new potential growing uses in the nanotechnology area.
The company has lodged provisional patents and/or had significant results for new anti-fungals, antibiotics and bio-degradation of plastic and paper, as well as research in the areas of new organic dyes and extracting metals from ores.
Equally exciting is that we are also now moving to commercialise a range of biodegradable nappies and other products, containing actinomycetes that should biodegrade much faster than current products. THE GLOBAL MARKET FOR DISPOSABLE NAPPIES ALONE IS ESTIMATED IN EXCESS OF $25 BILLION. CURRENT DISPOSABLE NAPPIES REPRESENT A LANDFILL AND ENVIRONMENTAL PROBLEM. They are believed to sometimes take centuries TO BREAK DOWN IN LAND FILL. Even current biodegradable plastic bags, paper and packaging products without bioactives added, may still take centuries to break down. We believe this has inhibited the widespread take up of biodegradable products. With Actinogen eco-friendly actinomycetes included in products in the future this could change very dramatically.
The Company has commenced research into the detection and isolation of soil actinomycetes found in the Western Australian environment and the Company intends to become a forerunner in this field in Australia. The Company believes that this is an exciting concept in the field of biotechnology in Australia. The Company is directing its efforts to the isolation of actinomycetes by selection techniques developed by the Company and using the isolates to locate, through selective screening processes, those producing biologically active compounds of potential medical, agricultural and industrial significance. The isolates are then broadly classified and catalogued. Site histories from soil sampling are also maintained in order that repeat sampling can be easily carried out if apparently unique bioactive compounds are identified from a particular site.
The Company intends to partially characterize bioactive compounds that have the potential for use as antibiotics directed specifically against the clinically important Methicillin Resistant Staphylococci Aureus (MRSA) and the Vancomycin Resistant Enterococci (VRE) bacteria and/or as antifungal agents specifically directed against clinically important Candida yeasts and Taphrina deformans. DNA sequencing techniques will provide more precise information on the genera and/or speciation of the selected organisms. These compounds and their source actinomycetes will then either be offered for sale or the Company will seek to enter into joint venture programs with other companies for the proving and seeking of commercial applications.
The company has identified a series of isolates that are capable of tolerating saline solutions that may have application for the rehabilitation of salt affected soils.
The Company also intends to actively seek specific cooperative programs by approaching companies with industrial and environmental problems which might be suited for rectification by actinomycetes from the Australian environment.
Several of the Company’s screening techniques have widespread application. For example, the Company has developed a “Bench Manual” for the detection and isolation of unique bioactive compounds. This manual provides for the practical requirements for the detection and isolation of unique bioactive compounds which includes initial soil sampling techniques, isolation procedures and specific screening tests to locate actinomycetes with the required characteristics.
The Company has established an arrangement with the PathWest laboratories at the QE II Medical Centre, Sir Charles Gardiner Hospital, Shenton Park, Perth, Western Australia, to utilise laboratories and equipment for carrying out its research into the detection and isolation of the desired actinomycetes and their bioactive compounds.
The bench protocols are now well established and the Company has isolated 2 actinomycetes [streptomycetes] that are producing significant antibiotic activity against the Methicillin Resistant Staphylococcus Aureus (MRSA) and the Vancomycin Resistant Enterococci (VRE) bacteria.
The Company has also identified a series of isolates which produce bioactive compounds that are active against clinically important fungal infections and some common agricultural diseases.
Currently the Company’s initial screening assays are simple and rapid to perform. Using these techniques the Company’s laboratories can screen between 100-200 actinomycete isolates a day as required.
Any actinomycetes that appear to be producing antibiotic and/or antifungal activity against the Company’s target organisms are then screened against a panel of 10 further MRSA bacteria with a wide range of antibiotic resistance patterns and also against a panel of 10 Candida yeasts of clinical importance, some of which are resistant to currently used antifungal chemicals.
Actinomycetes that prove to be active against these panels are then moved to the second level of the Company’s screening program. In the second level of the Company’s screening program the identified active actinomycetes are grown in liquid cultures and their supernatants tested for the excretion of antibiotic activity. The stability of the bioactive compounds produced are tested at room temperature, +4C, -18C and -80C over time.
The Company has commenced research into the detection and isolation of soil actinomycetes found in the Western Australian environment.
The supernatants are also screened for bacteriostatic and fungiostatic properties as well as bactericidal and fungicidal properties.
The Company intends to conduct further tests using liquid chromatography and centrifugal analysis to determine if more than one bioactive compound is present in the supernatants. Preliminary molecular weight analyses of the identified bioactive compounds will also be determined.
In the future the Company intends to conduct in vitro and in vivo tests to obtain information on toxicity and intestinal absorption of the identified bioactive compounds. Any compounds that successfully pass these tests will then be reproduced in quantities large enough for
chromatographic purification and structural analysis.
Concurrently with these tests a more detailed analysis of the actinomycetes producing the bioactive compounds will be carried out. A wide range of biochemical substrate analyses will be conducted along with DNA sequencing to better delineate the classification of the actinomycetes under test.
The Company also has the capacity to test for the ability of actinomycetes isolated from West Australian soils to digest 3 types of plastic currently in use in the domestic market and to screen for the capacity of the actinomycetes to tolerate different concentrations of saline. Salt tolerant actinomycetes form a separate sub library of microorganisms which may be of use in the rehabilitation of salt affected soils.
In addition to the specific activities described above there are numerous potential commercial applications for the bioactive compounds that may be identified by the Company through selective screening techniques.
Those applications include other antibiotics and anti– fungal, anti-viral and anti-cancer agents.
It is anticipated that the Company’s screening techniques may be extended to identifying micro-organisms that have application for bio-remedial control of environmental and mining pollutants. Examples include microorganisms that may digest various sources of cellulose, domestic wastes, toxic chemicals in polluted ground or water, plastics and the treatment of salt affected soils.
The Company intends to partially characterize bioactive compounds that have the potential for use as antibiotics.
Other potential applications for actinomycetes and the compounds which they produce may include the concentration and extraction of various metals in the mining industry, the discovery of new fluorescent dyes for paints and colour directed pH indicators, the discovery of new methods of production of amino acids and the discovery of new sunscreens.
Recent developments by other researchers unrelated to the Company have led to the discovery of bioactive compounds produced by actinomycetes which are capable of alleviating clinical conditions such as blood clots and obesity in humans.